99 results on '"Masliza Mahmod"'
Search Results
2. Improving Sex-based Differences in ECG Diagnostic Performance for CMR Abnormalities Post Severe COVID-19 Infections
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Azlan Helmy Abd Samat, MD, Masliza Mahmod, MD, PhD, Adam Lewandowski, PhD, Celeste McCracken, PhD, MSc, Mark P Cassar, MD, Abid M Akhtar, MD, Zakariye Ashkir, MD, Alastair J Moss, MD, PhD, Charlotte Manisty, MD, PhD, Thomas A Treibel, MD, PhD, Elena Lukaschuk, MSc, Stefan Piechnik, PhD, FSCMR, Vanessa Ferreira, DMD, MD, FSCMR, Chrysovalantou Nikolaidou, MD, PhD, Christopher Miller, PhD, Amedeo Chiribiri, PhD, MB, FSCMR, Declan O'Regan, PhD, Richard P Steeds, Jonathan R Weir-McCall, MD, PhD, Sven Plein, MD, PhD, Gerry McCann, Rachael A Evans, MD, PhD, Christopher E. Brightling, MD, PhD, Stefan Neubauer, MD, PhD, and Betty Raman, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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3. Right ventricular function declines prior to left ventricular ejection fraction in hypertrophic cardiomyopathy
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Masliza Mahmod, Betty Raman, Kenneth Chan, Sanjay Sivalokanathan, Robert W. Smillie, Azlan H. Abd Samat, Rina Ariga, Sairia Dass, Elizabeth Ormondroyd, Hugh Watkins, and Stefan Neubauer
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Hypertrophic cardiomyopathy ,Cardiac magnetic resonance ,Right ventricular function ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background The right ventricle (RV) in hypertrophic cardiomyopathy (HCM) tends to be neglected, as previous efforts have predominantly focused on examining the prognostic value of left ventricular (LV) abnormalities. The objectives of this study were to assess RV function in HCM, changes over time, and association with clinical outcomes. Methods Two hundred and ninety HCM patients with preserved LV ejection fraction (LVEF ≥ 55%) and 30 age- and sex-matched controls underwent cardiovascular magnetic resonance (CMR). All patients were followed up for clinical events for a median duration of 4.4 years. Sixty-three patients had a follow-up CMR undertaken at a median interval of 5.4 years. Main study measures and outcomes were RV function (RV ejection fraction (RVEF) and RV strain) at baseline, temporal changes in RV function over time and prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM. Results When compared to controls, HCM patients exhibited lower RV and LV peak global longitudinal systolic strains on feature-tracking analysis of cine images, while RVEF and LVEF were within the normal range. On follow-up CMR, both RV and LV strain parameters decreased over time. RVEF decreased at follow-up (65 ± 7% to 62 ± 7%, P
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- 2022
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4. Incremental value of left atrial booster and reservoir strain in predicting atrial fibrillation in patients with hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study
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Betty Raman, Robert W. Smillie, Masliza Mahmod, Kenneth Chan, Rina Ariga, Chrysovalantou Nikolaidou, Elizabeth Ormondroyd, Kate Thomson, Andrew R. Harper, Gifford Tan, Adam J. Lewandowski, Fernando Rodriguez Bajo, Eleanor C. Wicks, Barbara Casadei, Hugh Watkins, and Stefan Neubauer
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Hypertrophic cardiomyopathy ,Atrial fibrillation ,Cardiovascular magnetic resonance imaging ,Left atrial strain ,Booster strain ,Reservoir strain ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.
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- 2021
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5. Design and rationale of the EMPA‐VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
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Moritz J. Hundertmark, Olorunsola F. Agbaje, Ruth Coleman, Jyothis T. George, Rolf Grempler, Rury R. Holman, Hanan Lamlum, Jisoo Lee, Joanne E. Milton, Heiko G. Niessen, Oliver Rider, Christopher T. Rodgers, Ladislav Valkovič, Eleanor Wicks, Masliza Mahmod, and Stefan Neubauer
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Heart failure ,Diabetes ,SGLT2 inhibitors ,31P‐MRS ,Trial design ,Empagliflozin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium‐glucose co‐transporter‐2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR‐Reduced trial and cardiovascular mortality in the EMPA‐REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results The EMPA‐VISION trial is a double‐blind, randomized, placebo‐controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine‐to‐adenosine triphosphate ratio, as measured by 31Phosphorus‐MRS. Conclusions EMPA‐VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR‐Reduced and EMPEROR‐Preserved).
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- 2021
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6. Editorial Expression of Concern: Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance
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Alexander Liu, Rohan S. Wijesurendra, Rina Ariga, Masliza Mahmod, Eylem Levelt, Andreas Greiser, Mario Petrou, George Krasopoulos, John C. Forfar, Rajesh K. Kharbanda, Keith M. Channon, Stefan Neubauer, Stefan K. Piechnik, and Vanessa M. Ferreira
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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7. Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects
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Fitri Fareez Ramli, Syed Alhafiz Syed Hashim, Betty Raman, Masliza Mahmod, and Yusof Kamisah
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cardiomyopathy ,diabetes ,hypertensive ,TETA ,triethylenetetramine ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Abnormality in myocardial copper homeostasis is believed to contribute to the development of cardiomyopathy. Trientine, a copper-chelating drug used in the management of patients with Wilson’s disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy. This review aims to present the updated development of the roles of trientine in hypertrophic cardiomyopathy. The drug has been demonstrated in animal studies to restore myocardial intracellular copper content. However, its mechanisms for improving the medical condition remain unclear. Thus, comprehending its mechanistic aspects in cardiomyopathy is crucial and could help to expedite future research.
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- 2022
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8. The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study
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Masliza Mahmod, Nikhil Pal, Jennifer Rayner, Cameron Holloway, Betty Raman, Sairia Dass, Eylem Levelt, Rina Ariga, Vanessa Ferreira, Rajarshi Banerjee, Jurgen E. Schneider, Christopher Rodgers, Jane M. Francis, Theodoros D. Karamitsos, Michael Frenneaux, Houman Ashrafian, Stefan Neubauer, and Oliver Rider
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Cardiovascular magnetic resonance ,Spectroscopy ,Diastolic strain rate ,Heart failure ,Steatosis ,Maximal oxygen consumption ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. Methods Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate. Results When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. Conclusions Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
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- 2018
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9. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge
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Betty Raman, Mark Philip Cassar, Elizabeth M. Tunnicliffe, Nicola Filippini, Ludovica Griffanti, Fidel Alfaro-Almagro, Thomas Okell, Fintan Sheerin, Cheng Xie, Masliza Mahmod, Ferenc E. Mózes, Adam J. Lewandowski, Eric O. Ohuma, David Holdsworth, Hanan Lamlum, Myles J. Woodman, Catherine Krasopoulos, Rebecca Mills, Flora A. Kennedy McConnell, Chaoyue Wang, Christoph Arthofer, Frederik J. Lange, Jesper Andersson, Mark Jenkinson, Charalambos Antoniades, Keith M. Channon, Mayooran Shanmuganathan, Vanessa M. Ferreira, Stefan K. Piechnik, Paul Klenerman, Christopher Brightling, Nick P. Talbot, Nayia Petousi, Najib M. Rahman, Ling-Pei Ho, Kate Saunders, John R. Geddes, Paul J. Harrison, Kyle Pattinson, Matthew J. Rowland, Brian J. Angus, Fergus Gleeson, Michael Pavlides, Ivan Koychev, Karla L. Miller, Clare Mackay, Peter Jezzard, Stephen M. Smith, and Stefan Neubauer
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Coronavirus ,SARS-CoV-2 infection ,COVID-19 ,Survivors ,Medium term ,Follow up ,Medicine (General) ,R5-920 - Abstract
Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. Findings: At 2–3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p
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- 2021
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10. Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease
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Eylem Levelt, Stefan K. Piechnik, Alexander Liu, Rohan S. Wijesurendra, Masliza Mahmod, Rina Ariga, Jane M. Francis, Andreas Greiser, Kieran Clarke, Stefan Neubauer, Vanessa M. Ferreira, and Theodoros D. Karamitsos
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Cardiovascular magnetic resonance ,Diabetes mellitus ,Myocardial perfusion ,ShMOLLI T1-mapping ,Microvascular obstruction ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Methods Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. Results All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p
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- 2017
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11. Distinct ECG Phenotypes Identified in Hypertrophic Cardiomyopathy Using Machine Learning Associate With Arrhythmic Risk Markers
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Aurore Lyon, Rina Ariga, Ana Mincholé, Masliza Mahmod, Elizabeth Ormondroyd, Pablo Laguna, Nando de Freitas, Stefan Neubauer, Hugh Watkins, and Blanca Rodriguez
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hypertrophic cardiomyopathy ,electrocardiography ,e-cardiology ,phenotyping ,computational clustering ,Physiology ,QP1-981 - Abstract
Aims: Ventricular arrhythmia triggers sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), yet electrophysiological biomarkers are not used for risk stratification. Our aim was to identify distinct HCM phenotypes based on ECG computational analysis, and characterize differences in clinical risk factors and anatomical differences using cardiac magnetic resonance (CMR) imaging.Methods: High-fidelity 12-lead Holter ECGs from 85 HCM patients and 38 healthy volunteers were analyzed using mathematical modeling and computational clustering to identify phenotypic subgroups. Clinical features and the extent and distribution of hypertrophy assessed by CMR were evaluated in the subgroups.Results: QRS morphology alone was crucial to identify three HCM phenotypes with very distinct QRS patterns. Group 1 (n = 44) showed normal QRS morphology, Group 2 (n = 19) showed short R and deep S waves in V4, and Group 3 (n = 22) exhibited short R and long S waves in V4-6, and left QRS axis deviation. However, no differences in arrhythmic risk or distribution of hypertrophy were observed between these groups. Including T wave biomarkers in the clustering, four HCM phenotypes were identified: Group 1A (n = 20), with primary repolarization abnormalities showing normal QRS yet inverted T waves, Group 1B (n = 24), with normal QRS morphology and upright T waves, and Group 2 and Group 3 remaining as before, with upright T waves. Group 1A patients, with normal QRS and inverted T wave, showed increased HCM Risk-SCD scores (1A: 4.0%, 1B: 1.8%, 2: 2.1%, 3: 2.5%, p = 0.0001), and a predominance of coexisting septal and apical hypertrophy (p < 0.0001). HCM patients in Groups 2 and 3 exhibited predominantly septal hypertrophy (85 and 90%, respectively).Conclusion: HCM patients were classified in four subgroups with distinct ECG features. Patients with primary T wave inversion not secondary to QRS abnormalities had increased HCM Risk-SCD scores and coexisting septal and apical hypertrophy, suggesting that primary T wave inversion may increase SCD risk in HCM, rather than T wave inversion secondary to depolarization abnormalities. Computational ECG phenotyping provides insight into the underlying processes captured by the ECG and has the potential to be a novel and independent factor for risk stratification.
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- 2018
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12. Correction to: Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease
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Eylem Levelt, Stefan K. Piechnik, Alexander Liu, Rohan S. Wijesurendra, Masliza Mahmod, Rina Ariga, Jane M. Francis, Andreas Greiser, Kieran Clarke, Stefan Neubauer, Vanessa M. Ferreira, and Theodoros D. Karamitsos
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract In the original publication of this article [1] Fig. 1 was incorrect due to the use of a colour bar with wrong range in error.
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- 2017
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13. 3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy
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Bobak Heydari, Alessandro Satriano, Michael Jerosch-Herold, Paul Kolm, Dong-Yun Kim, Kathleen Cheng, Yuna L. Choi, Panagiotis Antiochos, James A. White, Masliza Mahmod, Kenneth Chan, Betty Raman, Milind Y. Desai, Carolyn Y. Ho, Sarahfaye F. Dolman, Patrice Desvigne-Nickens, Martin S. Maron, Matthias G. Friedrich, Jeanette Schulz-Menger, Stefan K. Piechnik, Evan Appelbaum, William S. Weintraub, Stefan Neubauer, Christopher M. Kramer, and Raymond Y. Kwong
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Published
- 2023
14. Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging
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Shveta Monga, Ladislav Valkovič, Damian Tyler, Craig A. Lygate, Oliver Rider, Saul G. Myerson, Stefan Neubauer, and Masliza Mahmod
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Predictive Value of Tests ,Humans ,Radiology, Nuclear Medicine and imaging ,Aortic Valve Stenosis ,Cardiology and Cardiovascular Medicine ,Magnetic Resonance Imaging - Abstract
Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.
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- 2022
15. Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin:The Randomized, Controlled EMPA-VISION Trial
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Moritz J. Hundertmark, Amanda Adler, Charalambos Antoniades, Ruth Coleman, Julian L. Griffin, Rury R. Holman, Hanan Lamlum, Jisoo Lee, Daniel Massey, Jack J.J.J. Miller, Joanne E. Milton, Shveta Monga, Ferenc E. Mózes, Areesha Nazeer, Betty Raman, Oliver Rider, Christopher T. Rodgers, Ladislav Valkovič, Eleanor Wicks, Masliza Mahmod, and Stefan Neubauer
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sodium-glucose transporter proteins ,Physiology (medical) ,empagliflozin ,heart failure ,Cardiology and Cardiovascular Medicine ,magnetic resonance spectroscopy - Abstract
BACKGROUND: Sodium–glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness. METHODS: EMPA-VISION is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr:ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated. RESULTS: Empagliflozin treatment did not change cardiac energetics (ie, PCr:ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin – placebo], –0.25 [95% CI, –0.58 to 0.09]; P =0.14) or HFpEF (adjusted mean treatment difference, –0.16 [95% CI, –0.60 to 0.29]; P =0.47]. Likewise, there were no changes in PCr:ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, –0.13 [95% CI, –0.35 to 0.09]; P =0.23) or HFpEF (adjusted mean treatment difference, –0.22 [95% CI, –0.66 to 0.23]; P =0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed. CONCLUSIONS: In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03332212.
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- 2023
16. 29 Role of cardiac energetics in aortic stenosis disease progression: identifying the high-risk metabolic phenotype
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Shveta Monga, Ladislav Valkovič, Masliza Mahmod, Saul G Myerson, Stefan Neubauer, and Oliver J Rider
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- 2023
17. 30 A randomised double-blind placebo-controlled study of fenofibrate as a metabolic modulator to augment cardiac physiology in moderate-severe aortic stenosis
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Shveta Monga, Ladislav Valkovič, Saul G Myerson, Stefan Neubauer, Masliza Mahmod, and Oliver J Rider
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- 2023
18. 10 Impaired stress myocardial oxygenation precedes contractile abnormalities in three models of cardiac hypertrophy: insights from a novel oxygen sensitive cardiac magnetic resonance approach
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Mohammed Abid Akhtar, Hasan Mohiaddin, Boon-Seng Yeoh, Eylem Levelt, Hugh Watkins, Masliza Mahmod, Stefan Neubauer, and Betty Raman
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- 2023
19. Predictors of Major Atrial Fibrillation Endpoints in the National Heart, Lung, and Blood Institute HCMR
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Matthias G. Friedrich, Michelle Michels, Stefan K. Piechnik, Dana Dawson, Daniel Jacoby, Patrice Desvigne-Nickens, John P. DiMarco, William Bradlow, Christopher M. Kramer, Carolyn Y. Ho, Jeanette Schulz-Menger, Chiara Buccarelli-Ducci, Adam S. Helms, Michael Salerno, Hugh Watkins, Barbara Casadei, Lubna Choudhury, James A. White, Martin S. Maron, Jonathan W. Weinsaft, Paul Kolm, Amedeo Chiribiri, Anjali T. Owens, Sarahfaye Dolman, Evan Appelbaum, Hcmr Investigators, Raymond Y. Kwong, William S. Weintraub, Sherif F. Nagueh, Dong-Yun Kim, Milind Y. Desai, Stefan Neubauer, Michael Jerosch-Herold, Nancy L. Geller, Masliza Mahmod, and Colin Berry
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medicine.medical_specialty ,medicine.medical_treatment ,Catheter ablation ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Heart Atria ,Prospective Studies ,030212 general & internal medicine ,Risk factor ,Aged ,Framingham Risk Score ,Proportional hazards model ,business.industry ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,Middle Aged ,medicine.disease ,United States ,Catheter Ablation ,Cardiology ,National Heart, Lung, and Blood Institute (U.S.) ,business ,Body mass index ,Natural history study - Abstract
Objectives This study sought to identify predictors of major clinically important atrial fibrillation endpoints in hypertrophic cardiomyopathy. Background Atrial fibrillation (AF) is a common morbidity associated with hypertrophic cardiomyopathy (HCM). The HCMR (Hypertrophic Cardiomyopathy Registry) trial is a prospective natural history study of 2,755 patients with HCM with comprehensive phenotyping. Methods All patients received yearly telephone follow-up. Major AF endpoints were defined as requiring electrical cardioversion, catheter ablation, hospitalization for >24 h, or clinical decisions to accept permanent AF. Penalized regression via elastic-net methodology identified the most important predictors of major AF endpoints from 46 variables. This was applied to 10 datasets, and the variables were ranked. Predictors that appeared in all 10 sets were then used in a Cox model for competing risks and analyzed as time to first event. Results Data from 2,631 (95.5%) patients were available for analysis after exclusions. A total of 127 major AF endpoints events occurred in 96 patients over 33.3 ± 12.4 months. In the final model, age, body mass index (BMI), left atrial (LA) volume index, LA contractile percent (active contraction), moderate or severe mitral regurgitation (MR), and history of arrhythmia the most important. BMI, LA volume index, and LA contractile percent were age-dependent. Obesity was a stronger risk factor in younger patients. Increased LA volume, reduced LA contractile percent, and moderate or severe MR put middle-aged and older adult patients at increased risk. Conclusions The major predictors of major AF endpoints in HCM include older age, high BMI, moderate or severe MR, history of arrhythmia, increased LA volume, and reduced LA contractile percent. Prospective testing of a risk score based on these parameters may be warranted.
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- 2021
20. Design and rationale of the EMPA‐VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
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Eleanor Wicks, Hanan Lamlum, Jyothis T. George, Olorunsola F. Agbaje, Christopher T. Rodgers, Rury R. Holman, Oliver J Rider, Ladislav Valkovič, Heiko G. Niessen, Rolf Grempler, Stefan Neubauer, Moritz Hundertmark, Joanne E. Milton, Jisoo Lee, Ruth L. Coleman, Masliza Mahmod, Rodgers, Christopher [0000-0003-1275-1197], and Apollo - University of Cambridge Repository
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31P-MRS ,Trial design ,medicine.medical_specialty ,Study Designs ,Empagliflozin ,Heart failure ,Placebo ,31P‐MRS ,Glucosides ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Benzhydryl Compounds ,Study Design ,Ejection fraction ,business.industry ,Diabetes ,Type 2 Diabetes Mellitus ,medicine.disease ,Clinical trial ,Diabetes Mellitus, Type 2 ,RC666-701 ,Cohort ,Cardiology ,Quality of Life ,Cardiology and Cardiovascular Medicine ,business ,SGLT2 inhibitors - Abstract
Aims Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium-glucose co-transporter-2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR-Reduced trial and cardiovascular mortality in the EMPA-REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results The EMPA-VISION trial is a double-blind, randomized, placebo-controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine-to-adenosine triphosphate ratio, as measured by 31Phosphorus-MRS. Conclusions EMPA-VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR-Reduced and EMPEROR-Preserved).
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- 2021
21. OP2 A randomised double-blind placebo-controlled study of fenofibrate as a metabolic modulator to augment cardiac physiology in moderate-severe aortic stenosis
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Shveta Monga, Ladislav Valkovič, Saul G Myerson, Stefan Neubauer, Masliza Mahmod, and Oliver J Rider
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- 2022
22. Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy
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John Farrant, Susanna Dodd, Carly Vaughan, Anna Reid, Matthias Schmitt, Clifford Garratt, Mohammed Akhtar, Masliza Mahmod, Stefan Neubauer, Robert M Cooper, Sanjay K Prasad, Anvesha Singh, Ladislav Valkovič, Betty Raman, Zakariye Ashkir, Dannii Clayton, Olatz Baroja, Beatriz Duran, Catherine Spowart, Emma Bedson, Josephine H Naish, Chris Harrington, and Christopher A Miller
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Cardiology and Cardiovascular Medicine - Abstract
AimsHypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.MethodsThe Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I–III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.ConclusionTEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.Trial registration numbersNCT04706429andISRCTN57145331.
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- 2023
23. Symptom persistence despite improvement in cardiopulmonary health -- Insights from longitudinal CMR, CPET and lung function testing post-COVID-19
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Cheng Xie, Masliza Mahmod, Vanessa M Ferreira, David A. Holdsworth, Rachael A. Evans, Ling-Pei Ho, Christopher E. Brightling, Mark Philip Cassar, Nick P. Talbot, Azlan Helmy Abd Samat, Nayia Petousi, Stefan K. Piechnik, Betty Raman, Elizabeth M. Tunnicliffe, Adam J. Lewandowski, and Stefan Neubauer
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Spirometry ,medicine.medical_specialty ,Lung ,Ejection fraction ,medicine.diagnostic_test ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,COVID-19 ,Magnetic resonance imaging ,General Medicine ,Disease ,Natural history ,medicine.anatomical_structure ,CPET ,Internal medicine ,Symptom persistence ,Cardiology ,medicine ,CMR ,long COVID ,business ,Lung function ,Research Paper - Abstract
Background The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Methods Fifty-eight patients and thirty matched controls (single visit), recruited between 14th March - 25th May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. • View related content for this article Findings At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m2, P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. Interpretation In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. Funding The authors’ work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107.
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- 2022
24. Association Between Sarcomeric Variants in Hypertrophic Cardiomyopathy and Myocardial Oxygenation: Insights From a Novel Oxygen-Sensitive Cardiovascular Magnetic Resonance Approach
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Hugh Watkins, Rina Ariga, Joseph B. Selvanayagam, Yi Jie Gifford Tan, Aaron T. Hess, Masliza Mahmod, Michael Jerosch-Herold, Sanjay Sivalokanathan, Moritz Hundertmark, Betty Raman, Elizabeth M. Tunnicliffe, Eric O Ohuma, Stefan Neubauer, Theodoros D. Karamitsos, and Kenneth H. Chan
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Sarcomeres ,medicine.medical_specialty ,chemistry.chemical_element ,Contrast Media ,Gadolinium ,Oxygen ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Myocardial oxygenation ,Myocardium ,Hypertrophic cardiomyopathy ,Magnetic resonance imaging ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Image Enhancement ,Magnetic Resonance Imaging ,Molecular Imaging ,BOLD protocol ,chemistry ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Perfusion ,Oxidation-Reduction - Published
- 2021
25. Longitudinal trajectory of cardiac magnetic resonance and cardiopulmonary exercise testing findings in moderate to severe COVID-19 and association with symptoms
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David A. Holdsworth, Mark Philip Cassar, Elizabeth M. Tunnicliffe, Cheng Xie, S Neubauer, Nick P. Talbot, Adam J. Lewandowski, Nayia Petousi, Betty Raman, and Masliza Mahmod
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Moderate to severe ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Internal medicine ,Cardiology ,medicine ,Cardiopulmonary exercise testing ,Cardiology and Cardiovascular Medicine ,Cardiac magnetic resonance ,Association (psychology) ,business - Abstract
Background Cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET) have provided important insights into the prevalence of early cardiopulmonary abnormalities in COVID-19 patients. It is currently unknown whether such abnormalities persist over time and relate to ongoing symptoms. Purpose To describe the longitudinal trajectory of cardiopulmonary abnormalities on CMR and CPET in moderate to severe COVID-19 patients and assess their relationship with ongoing symptoms. Methods Fifty-eight previously hospitalised COVID-19 patients and 30 age, sex, body mass index, comorbidity-matched controls underwent CMR, CPET and a symptom-based questionnaire at 2–3 months (2–3m). Repeat assessments (including gas transfer) were performed in 46 patients at 6 months (6m). Results During admission, 1/3rd of patients needed ventilation or intensive care (Table 1) and three (5%) had a raised troponin. On CMR, patients had preserved left (LV) and right ventricular (RV) volumes and function at 2–3m from infection. By 6m, LV function did not change but RV end diastolic volume decreased (mean difference −4.3 mls/m2, p=0.005) and RV function increased (mean difference +3.2%, p Patients had higher native T1 (a marker of fibroinflammation) at 2–3m compared to controls (Table 1, Fig. 1B), which normalised by 6m. Extracellular volume was normal and improved by 6m. Native T2, a marker of myocardial oedema, did not differ between patients and controls on serial CMR. At 2–3m, late gadolinium enhancement (LGE) was higher in patients (p=0.023) but became comparable to controls by 6m (p=0.62). Six (12%) patients had LGE in a myocarditis pattern and one (2%) had myocardial infarction. None had active myocarditis using the Modified Lake Louise Criteria. Lung imaging (T2-weighted) revealed parenchymal abnormalities in 2/3rds of patients at 2–3 and 6 months. The extent of abnormalities improved on serial imaging (Table 1). Gas transfer (DLco) was worse in those with lung abnormalities (77% vs 91% of predicted, p=0.009). CPET revealed reduced peak oxygen consumption (pVO2) in patients at 2–3m, which normalised by 6m (80.5% to 93.3% of predicted, p=0.001) (Table 1, Fig. 1C). At 2–3m, 49% of patients had submaximal tests (respiratory exchange ratio Cardiac symptoms (chest pain, dyspnoea, palpitations, dizziness or syncope) were present in 83% of patients at 2–3m, reducing to 52% by 6m (p Conclusions Cardiopulmonary parameters (on CMR and CPET) improved in moderate-severe COVID-19 patients from 2–3 to 6 months post infection. Despite this, patients continued to experience cardiac symptoms which had no relationship with measured parameters. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): 1. NIHR Oxford and Oxford Health Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust2. Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107 Table 1Figure 1
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- 2021
26. Late Breaking Abstract - Breathlessness post COVID-19 despite improvement in cardiopulmonary health
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Mark Philip Cassar, Nick P. Talbot, Masliza Mahmod, Adam J. Lewandowski, Stefan K. Piechnik, Vanessa M Ferreira, Stefan Neubauer, Nayia Petousi, Betty Raman, Elizabeth M. Tunnicliffe, Ling-Pei Ho, David A. Holdsworth, and Cheng Xie
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Spirometry ,medicine.medical_specialty ,Lung ,Myocarditis ,medicine.diagnostic_test ,Coronavirus disease 2019 (COVID-19) ,business.industry ,respiratory system ,medicine.disease ,Natural history ,FEV1/FVC ratio ,medicine.anatomical_structure ,Gas transfer ,Internal medicine ,Cardiology ,medicine ,business ,Lung function - Abstract
Background: Breathlessness is common in patients post-COVID-19, yet its association with objective measures of cardiopulmonary health is unknown. We sought to 1) describe the natural history of breathlessness and cardiopulmonary abnormalities & 2) evaluate their relationship post-COVID-19. Methods: Fifty-eight previously hospitalised COVID-19 patients & 30 controls underwent cardiopulmonary MRI (CMR), lung function testing & CPET at 2-3 & 6 months (m) from symptom-onset. Results: At 2-3m persistent breathlessness (MRC grade>1) was reported by 64% of patients, reducing to 57% by 6m, vs 10% of controls. On CMR, patients had preserved cardiac volumes & function at both 2-3m & 6m. Myocardial native T1, a marker of inflammation, was raised in 26% at 2-3m, but normalised by 6m, with no signs of active myocarditis (Fig1A). 60% of patients had lung parenchymal abnormalities at 2-3m, improving in extent by 6m. Patients had reduced FEV1 & FVC on spirometry at 2-3m. At 6m, FEV1 normalised, FVC remained slightly reduced & gas transfer was impaired in 52%. CPET revealed reduced peak VO2 & abnormal VE/VCO2 slope (marker of lung efficiency) in patients at 2-3m, which improved by 6m (Fig1B). There was no relationship between persistent breathlessness & CMR, CPET or spirometry measures at 6m (Fig1C). Conclusions: Despite improvement in objective measures of cardiopulmonary health, over half the patients post-COVID-19 continue to experience breathlessness at 6m.
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- 2021
27. Incremental value of left atrial booster and reservoir strain in predicting atrial fibrillation in patients with hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study
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K Thomson, Stefan Neubauer, Robert Smillie, Betty Raman, Gifford Tan, Masliza Mahmod, Eleanor C. Wicks, Kenneth H. Chan, Rina Ariga, Andrew R. Harper, Barbara Casadei, Adam J. Lewandowski, Elizabeth Ormondroyd, Hugh Watkins, Chrysovalantou Nikolaidou, and Fernando Rodriguez Bajo
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medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Left atrial strain ,Sudden death ,Booster strain ,Predictive Value of Tests ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Humans ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Heart Atria ,Angiology ,Cardiovascular magnetic resonance imaging ,Ejection fraction ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Research ,Hypertrophic cardiomyopathy ,Magnetic resonance imaging ,Atrial fibrillation ,Reservoir strain ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Blood pressure ,RC666-701 ,cardiovascular system ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Body mass index - Abstract
Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.
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- 2021
28. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge
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Michael Pavlides, Peter Jezzard, Masliza Mahmod, Charalambos Antoniades, H Lamlum, Matthew J. Rowland, Stefan K. Piechnik, Fergus V. Gleeson, Frederik J Lange, Mayooran Shanmuganathan, Cheng Xie, Thomas W. Okell, Paul Klenerman, Mark Philip Cassar, Rebecca J. Mills, Chaoyue Wang, Nick P. Talbot, Kathryn J Saunders, David A. Holdsworth, Eric O Ohuma, Nicola Filippini, Ferenc E. Mózes, Karla L. Miller, Ivan Koychev, Ludovica Griffanti, McConnell Fak., Najib M. Rahman, Vanessa M Ferreira, Mark Jenkinson, Ho L-P., Christoph Arthofer, Stephen M. Smith, Stefan Neubauer, Elizabeth M. Tunnicliffe, Clare E. Mackay, M J Woodman, C Krasopoulos, Paul Harrison, Keith M. Channon, Fidel Alfaro-Almagro, Nayia Petousi, Fintan Sheerin, Christopher E. Brightling, Betty Raman, Adam J. Lewandowski, Kyle T.S. Pattinson, Jesper L. R. Andersson, John R. Geddes, and Brian Angus
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Spirometry ,medicine.medical_specialty ,Research paper ,Exercise intolerance ,Disease ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,medicine ,030212 general & internal medicine ,Effects of sleep deprivation on cognitive performance ,Post-hospital discharge ,Survivors ,0101 mathematics ,Depression (differential diagnoses) ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,SARS-CoV-2 infection ,010102 general mathematics ,VO2 max ,COVID-19 ,General Medicine ,Follow up ,Medium term ,Magnetic Resonance Imaging ,Multiorgan effects ,Coronavirus ,Mental health ,medicine.symptom ,business ,lcsh:Medicine (General) ,Body mass index - Abstract
Background The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. Methods Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. Findings At 2–3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p Interpretation A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. Funding NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.
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- 2021
29. Abstract 16702: Myocardial Deformation Analysis in Hypertrophic Cardiomyopathy With Sarcomere Mutations: Insights From 2,221 Patients Within the NHLBI-HCM Registry
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Naeem Merchant, Betty Raman, Milind Y. Desai, William S. Weintraub, Carolyn Y. Ho, Alessandro Satriano, Dong-Yun Kim, James A. White, John P. DiMarco, Christopher M. Kramer, Michael Jerosch-Herold, Sarahfaye Dolman, Panagiotis Antiochos, Nancy L. Geller, Masliza Mahmod, Hugh Watkins, Bobak Heydari, Raymond Y. Kwong, Paul Kolm, Stefan Neubauer, Patrice Desvigne-Nickens, and Kenneth H. Chan
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medicine.medical_specialty ,business.industry ,Hypertrophic cardiomyopathy ,Deformation (meteorology) ,Gene mutation ,medicine.disease ,Sarcomere ,Contractility ,Physiology (medical) ,Internal medicine ,Cardiology ,Medicine ,Relaxation (physics) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes that alter myocardial contractility and relaxation. Three-dimensional myocardial deformation analysis (3D-MDA) may elucidate left ventricular (LV) abnormalities associated with sarcomere genotype status. Hypothesis: We hypothesize that HCM patients with sarcomere mutations have changes in myocardial contractility profiles that are associated with adverse LV architectural changes. Methods: 3D-MDA was measured using validated feature-tracking software applied to 2D cine cardiac MRI studies in 2,221 genotyped patients within the NHLBI HCM Registry. Results: Baseline, cardiac MRI, and 3D MDA-derived strain characteristics stratified by sarcomere status are shown in Table 1. Sarcomere positive patients were younger, had less LV outflow tract obstruction and lower indexed LV mass, but similar LVEF and trend towards higher serum NT-proBNP levels. Maximal wall thickness, measures of diffuse myocardial fibrosis (native T1, extracellular volume fraction) were elevated with corresponding reduction in global radial strain. Global minimum principal and epicardial layer conventional strain values were higher in sarcomere positive patients. Epicardial minimum principal strain was highly correlated with indexed LV mass (r=0.42, P Conclusions: Sarcomere positive HCM patients had differences in myocardial deformation strain profiles that were correlated to LV architectural changes and NT-proBNP levels despite lower indexed LV mass. More sensitive measures of contractile dysfunction may help elucidate pathophysiological mechanisms by which sarcomere mutations cause disease progression and adverse clinical outcomes in HCM.
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- 2020
30. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge
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Hanan Lamlum, Elizabeth M. Tunnicliffe, Rebecca J. Mills, Myles J Woodman, Chaoyue Wang, Peter Jezzard, Paul Harrison, Matthew J. Rowland, Michael Pavlides, Kate E. A. Saunders, Karla L. Miller, Masliza Mahmod, Charalambos Antoniades, Fergus V. Gleeson, Thomas W. Okell, Kyle T.S. Pattinson, Ivan Koychev, Mark Philip Cassar, Ferenc E. Mózes, Fidel Alfaro-Almagro, Stefan Neubauer, Stefan K. Piechnik, Ludovica Griffanti, Frederik J Lange, Fintan Sheerin, Christopher E. Brightling, Eric O Ohuma, Stephen M. Smith, Vanessa M Ferreira, Adam J. Lewandowski, Clare E. Mackay, Christoph Arthofer, Brian Angus, Paul Klenerman, Nicola Filippini, Keith M. Channon, Najib M. Rahman, LP Ho, Jesper L. R. Andersson, Nick P. Talbot, Catherine Krasopoulos, Mayooran Shanmuganathan, Cheng Xie, David A. Holdsworth, Flora A. Kennedy McConnell, John R. Geddes, Mark Jenkinson, Nayia Petousi, and Betty Raman
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Spirometry ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,VO2 max ,Magnetic resonance imaging ,Disease ,Quality of life ,Internal medicine ,Medicine ,Anxiety ,Effects of sleep deprivation on cognitive performance ,medicine.symptom ,business ,Depression (differential diagnoses) - Abstract
BackgroundThe medium-term effects of Coronavirus disease (COVID-19) on multiple organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.MethodsFifty-eight COVID-19 patients post-hospital discharge and 30 comorbidity-matched controls were prospectively enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments.FindingsAt 2-3 months from disease-onset, 64% of patients experienced persistent breathlessness and 55% complained of significant fatigue. On MRI, tissue signal abnormalities were seen in the lungs (60%), heart (26%), liver (10%) and kidneys (29%) of patients. COVID-19 patients also exhibited tissue changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domain relative to controls. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance (405±118m vs 517±106m in controls, pInterpretationA significant proportion of COVID-19 patients discharged from hospital experience ongoing symptoms of breathlessness, fatigue, anxiety, depression and exercise limitation at 2-3 months from disease-onset. Persistent lung and extra-pulmonary organ MRI findings are common. In COVID-19 survivors, chronic inflammation may underlie multiorgan abnormalities and contribute to impaired quality of life.FundingNIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.
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- 2020
31. Rationale and design of the African Cardiomyopathy and Myocarditis Registry Program: The IMHOTEP study
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Sarah M. Kraus, Gasnat Shaboodien, Veronica Francis, Nakita Laing, Jacqui Cirota, Ashley Chin, Shahiemah Pandie, John Lawrenson, George A.M. Comitis, Barend Fourie, Liesl Zühlke, Ambroise Wonkam, Helen Wainwright, Albertino Damasceno, Ana Olga Mocumbi, Lungile Pepeta, Khulile Moeketsi, Baby M. Thomas, Kandathil Thomas, Makoali Makotoko, Stephen Brown, Mpiko Ntsekhe, Karen Sliwa, Motasim Badri, Freedom Gumedze, Heather J. Cordell, Bernard Keavney, Vanessa Ferreira, Masliza Mahmod, Leslie T. Cooper, Magdi Yacoub, Stefan Neubauer, Hugh Watkins, Bongani M. Mayosi, Ntobeko A.B. Ntusi, Julius Mwita, Ahmed El-Guindy, Sir Magdi Yacoub, Tolno Sandy Kola, F. Ayub Barasa, Okechukwu Ogah, James Russell, Sarah Kraus, Bongani Mayosi, Ntobeko Ntusi, Shaheen Pandie, Blanche Cupido, George Comitis, Rik De Decker, Paul Brink, Marshall Heradien, Nomlindo Makubalo, Mahlubandile Nxele, Benjamin Longo-Mbenza, Baby Thomas, Kandithalal Thomas, Ahmed Suliman, Sulafa Ali, Kemilembe Tibazarwa, Charles Mondo, Michael Mungoma, Heather Cordell, and Ellise Tapiwa Gambahaya
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Adult ,Pediatrics ,medicine.medical_specialty ,Myocarditis ,Heart disease ,Cardiomyopathy ,Disease ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Registries ,Prospective cohort study ,Child ,Retrospective Studies ,business.industry ,medicine.disease ,Cohort ,Africa ,Etiology ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies ,Cohort study - Abstract
Background Heart failure (HF), the dominant form of cardiovascular disease in Africans, is mainly due to hypertension, rheumatic heart disease and cardiomyopathy. Cardiomyopathies pose a great challenge because of poor prognosis and high prevalence in low- and middle-income countries (LMICs). Little is known about the etiology and outcome of cardiomyopathy in Africa. Specifically, the role of myocarditis and the genetic causes of cardiomyopathy are largely unidentified in Africans. Method The Afr i can Cardio m yopat h y and My o cardi t is R e gistry P rogram (the IMHOTEP study) is a pan-African multi-centre, hospital-based cohort study, designed with the primary aim of describing the clinical characteristics, genetic causes, prevalence, management and outcome of cardiomyopathy and myocarditis in children and adults. The secondary aim is to identify barriers to the implementation of evidence-based care and provide a platform for trials and other intervention studies to reduce morbidity and mortality in cardiomyopathy. The registry consists of a prospective cohort of newly diagnosed (i.e., incident) cases and a retrospective (i.e., prevalent) cohort of existing cases from participating centres. Patients with cardiomyopathy and myocarditis will be subjected to a standardized 3-stage diagnostic process. To date, 750 patients have been recruited into the multi-centre pilot phase of the study. Conclusion The IMHOTEP study will provide comprehensive and novel data on clinical features, genetic causes, prevalence and outcome of African children and adults with all forms of cardiomyopathy and myocarditis in Africa. Based on these findings, appropriate strategies for management and prevention of the cardiomyopathies in LMICs are likely to emerge.
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- 2020
32. 2378Blunted stress myocardial oxygenation and not myocardial perfusion reserve is associated with arrhythmic risk in hypertrophic cardiomyopathy
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Theodoros D. Karamitsos, Joseph B. Selvanayagam, Elizabeth M. Tunnicliffe, Sanjay Sivalokanathan, Rina Ariga, Aaron T. Hess, Masliza Mahmod, Stefan Neubauer, Betty Raman, Ka Hung Chan, and Hugh Watkins
- Subjects
medicine.medical_specialty ,business.industry ,Myocardial oxygenation ,Hypertrophic cardiomyopathy ,Vasodilation ,Perfusion reserve ,Left ventricular hypertrophy ,medicine.disease ,Sudden cardiac death ,Fibrosis ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Perfusion - Abstract
Background In hypertrophic cardiomyopathy (HCM), myocardial ischaemia is believed to play a role in fatal life-threatening ventricular arrhythmias and caused by microvascular dysfunction manifesting as impaired myocardial perfusion. However, previous studies suggest that myocardial oxygenation during vasodilator stress may also be blunted when perfusion is normal, due to increased metabolic demands conferred by energy-costly sarcomeric mutations, left ventricular hypertrophy and outflow obstruction. Whether or not impaired myocardial perfusion reserve or blunted stress oxygenation on cardiac magnetic resonance (CMR) predict the risk of ventricular arrhythmia in HCM is unknown. Purpose We sought to investigate if impaired myocardial perfusion reserve or stress oxygenation is associated with an increased risk of ventricular arrhythmia in HCM. Methods 103 genotyped HCM patients (mean age 47±15 years) and 32 age- and sex-matched healthy controls underwent adenosine stress blood oxygen level dependent (BOLD) imaging, first pass perfusion and late gadolinium imaging (LGE) on CMR to assess stress oxygenation (BOLD ΔSI), myocardial perfusion reserve index (MPRI), and fibrosis respectively. All HCM patients were monitored for ventricular tachycardia (≥3 beats, ≥120 beats per minute) on a 24-hour Holter. Results As expected, MPRI was significantly reduced in HCM (1.5±0.4 vs 2.0±0.3, p Figure 1 Conclusion In HCM, blunted stress-induced oxygenation is associated with an increased risk of ventricular arrhythmia and may represent a novel biomarker of arrhythmic risk. Sarcomeric mutation status is an important determinant of stress oxygenation response. Acknowledgement/Funding National Institute for Health Research Oxford Biomedical Centre and British Heart Foundation.
- Published
- 2019
33. Metabolic Profiling of Aortic Stenosis and Hypertrophic Cardiomyopathy Identifies Mechanistic Contrasts in Substrate Utilisation
- Author
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Julian L. Griffin, John French, Nikhil Pal, Parisa Yavari, Rina Ariga, William T.E. Briggs, Tim Dent, Masliza Mahmod, Arash Yavari, Houman Ashrafian, Mark Cassar, John D. Horowitz, Jeremy S Dwight, Zsuzsanna Ament, James A. West, Bernard D. Prendergast, David L Hare, Anthony C Keech, Animesh Acharjee, Hugh Watkins, Kate S. Elliott, Helen Lockstone, Rajesh K. Kharbanda, Violetta Steeples, Michael P. Frenneaux, Neil J. Howell, Mark Richards, Thanh H Nguyen, and Steven Unger
- Subjects
0303 health sciences ,Fatty acid metabolism ,business.industry ,Hypertrophic cardiomyopathy ,macromolecular substances ,030204 cardiovascular system & hematology ,medicine.disease ,Bioinformatics ,3. Good health ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolic pathway ,0302 clinical medicine ,Metabolomics ,chemistry ,Perhexiline ,cardiovascular system ,Metabolome ,Medicine ,cardiovascular diseases ,business ,Coronary sinus ,030304 developmental biology ,medicine.drug - Abstract
Background Aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM) are highly distinct disorders leading to LVH, but whether cardiac metabolism substantially differs between these in humans remains to be elucidated. Method We undertook a detailed invasive (aortic root and coronary sinus) metabolic profiling in patients with severe AS and HCM in comparison to non-LVH controls, to investigate cardiac fuel selection and metabolic remodelling. These patients were assessed under different physiological states (at rest and during stress induced by pacing). The identified changes in the metabolome were further validated by metabolomic and orthogonal transcriptomic analysis, in separately recruited patient cohorts. We then present findings from the clinical trial using perhexiline, a metabolic modulator of long-chain fatty acid β-oxidation, in patients with severe AS, and contextualise these with the up-stream metabolomic findings. Results We identified a highly discriminant metabolomic signature in severe AS characterised by striking accumulation of long-chain acylcarnitines, intermediates of long-chain transport and fatty acid metabolism, and validated this in a separate cohort. Mechanistically, we identify a down-regulation in the PPAR-α transcriptional network, including expression of genes regulating FAO. Evaluation of the symptomatic impact of perhexiline in severe AS, in contrast to HCM, revealed no significant beneficial effect, suggesting the underlying metabolic changes are attempts at metabolic adaptation. Conclusions We present a comprehensive analysis of changes in the metabolic pathways (transcriptome to metabolome) in severe AS, and its comparison to HCM. Our results demonstrate fundamental distinctions in substrate preference between AS and HCM, highlighting insufficient long-chain FAO, and the PPAR-α signalling network as a specific metabolic therapeutic target in AS.
- Published
- 2019
34. Letter to the Editor
- Author
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Joseph Westaby, Mario Petrou, Theodoros D. Karamitsos, Stefan Neubauer, Saul G. Myerson, Houman Ashrafian, Kenneth H. Chan, Mary N. Sheppard, Rana Sayeed, Masliza Mahmod, Sairia Dass, and Betty Raman
- Subjects
Male ,medicine.medical_specialty ,Biopsy ,Coronary stenosis ,030204 cardiovascular system & hematology ,Severity of Illness Index ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Coronary Circulation ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Endothelial dysfunction ,Aged ,business.industry ,Myocardium ,Myocardial Perfusion Imaging ,Endothelial Cells ,Aortic Valve Stenosis ,Middle Aged ,Perfusion reserve ,medicine.disease ,Coronary Vessels ,Magnetic Resonance Imaging ,Capillaries ,Stenosis ,Capillary density ,Case-Control Studies ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Myocardial perfusion reserve is impaired in aortic stenosis (AS) even in the absence of epicardial coronary stenosis [(1)][1], which may be due to reduced capillary density and endothelial dysfunction [(2,3)][2]. However, the relationship between histopathological abnormalities of the vasculature
- Published
- 2019
35. 122 Endothelial loss as a cause of impaired myocardial perfusion reserve in severe aortic stenosis
- Author
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Kenneth Chan, Betty Raman, Joseph Westaby, Sairia Dass, Mairo Petrou, Rana Sayeed, Houman Ashrafian, Saul Myerson, Theodoros Karamitsos, Mary Sheppard, Stefan Neubauer, and Masliza Mahmod
- Published
- 2019
36. 20 Reappraising remodelling pattern of left ventricle in aortic stenosis: axis orientation as a unique signature of positive remodelling
- Author
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Ernesto Zacur, Masliza Mahmod, Sairia Dass, Marzia Rigolli, Theodoros D. Karamitsos, Rina Ariga, Stefan Neubauer, Pablo Lamata, Betty Raman, Saul G. Myerson, Kenneth H. Chan, Michelle D’Souza, and Jane M Francis
- Subjects
medicine.medical_specialty ,Orientation (computer vision) ,business.industry ,medicine.disease ,Apex (geometry) ,Sphericity ,Stenosis ,medicine.anatomical_structure ,Aortic valve replacement ,Ventricle ,Internal medicine ,Healthy control ,cardiovascular system ,medicine ,Cardiology ,Cardiac magnetic resonance ,business - Abstract
Introduction In aortic stenosis (AS), characterisation of ventricular (LV) remodelling beyond left ventricular mass measurements is lacking. We sought to study the 3-dimensional (3D) geometric LV remodelling pattern in severe AS pre- and post-surgical aortic valve replacement (AVR), and compared it with hypertensive and healthy controls. Methods Ninety-one subjects (36 severe AS, 19 hypertension and 36 healthy controls) underwent cardiac magnetic resonance (CMR). 18 AS patients had a repeat CMR eight-month post-AVR. 3D meshes were reconstructed from the myocardial contours of the CMR cine images. Principle component analysis and linear discrimination analysis were used to derive shape coefficients. Results AS patients had a significant shift in LV axis and apex orientation towards the septum, and more spherical LV shape which were not seen in the hypertensive and healthy control groups. As expected severe AS was associated with thicker and larger LV compared to the other two groups. Post AVR, despite significant reduction in LV thickness and sphericity, interestingly the shift in the LV axis/orientation was unchanged/irreversible (Figure 1). Conclusion Severe AS is characterised by unique remodelling pattern which is not reversible post AVR. The novel shape metrics that comprehensively quantify the LV morphology may be a potential marker for risk stratification in the management of AS. Conflict of Interest none
- Published
- 2019
37. D Stress myocardial oxygenation and not perfusion reserve determines arrhythmic risk in hypertrophic cardiomyopathy: insights from a novel oxygen-sensitive CMR approach
- Author
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Masliza Mahmod, Aaron T. Hess, Joseph B. Selvanayagam, Stefan Neubauer, Theodoros D. Karamitsos, Rina Ariga, Hugh Watkins, Kenneth H. Chan, Moritz Hundertmark, Betty Raman, Elizabeth M. Tunnicliffe, and Sanjay Sivalokanathan
- Subjects
medicine.medical_specialty ,Univariate analysis ,Blood-oxygen-level dependent ,business.industry ,Ischemia ,Hypertrophic cardiomyopathy ,Oxygenation ,medicine.disease ,Ventricular tachycardia ,Sudden cardiac death ,Muscle hypertrophy ,Internal medicine ,cardiovascular system ,Cardiology ,medicine ,cardiovascular diseases ,business - Abstract
Myocardial ischemia has long been implicated in promoting arrhythmic events and triggering sudden cardiac death in hypertrophic cardiomyopathy (HCM). However, the evidence for this is scarce due to challenges presented in direct ischemia assessment which generally requires an invasive approach. Blood oxygen level dependent cardiac magnetic resonance (BOLD CMR) permits the non-invasive assessment of tissue oxygenation, without gadolinium contrast, overcoming many limitations suffered by traditional methods. From a clinical perspective, T2-prepared steady-state free precession (T2-SSFP) BOLD is promising, but suffers from reduced diagnostic accuracy, owing to imprecisions in BOLD measurements secondary to heart-rate (HR) dependence. To resolve this, we developed a novel oxygen-sensitive CMR approach, Fast Low Angle Shot (FLASH) interleaved T2-SSFP BOLD, which was designed to eliminate both HR dependence and spatial variations seen with standard T2-SSFP BOLD. A comparison of both standard and novel approaches in 20 healthy subjects confirmed that FLASH-normalised T2-SSFP BOLD is highly reproducible, HR independent and more precise than standard T2-SSFP BOLD. In addition, the mean BOLD effect did not differ between the two methods. Importantly, using this novel approach, one could visualise changes in oxygen-sensitive signal from rest to stress qualitatively, making it feasible for direct incorporation into a clinical work flow. We then set out to test the hypothesis that stress oxygenation (as assessed on FLASH normalised T2-SSFP BOLD) is more powerful that myocardial perfusion reserve (MPRI) at determining arrhythmic risk in HCM patients. Adenosine stress BOLD, first pass perfusion imaging and late gadolinium enhancement CMR were undertaken in 103 genotyped-HCM patients. All patients underwent 24-hour Holter to monitor for evidence of ventricular tachycardia (≥3 beats, ≥120 beats per minute). Thirty-two age- and sex-matched healthy subjects served as controls. Although both stress oxygenation and MPRI were impaired in HCM, only stress oxygenation, but not MPRI, associated with ventricular tachycardia on univariate analysis. There was a step-wise increase in ventricular tachycardia prevalence with decreasing quartiles of stress oxygenation. HCM patients with the lowest quartile of oxygenation were at a three-fold increased risk of ventricular tachycardia (OR 3.04, p=0.04) after adjusting for LGE mass, age and baseline risk of sudden cardiac death. Sarcomeric mutation status was an independent determinant of stress oxygenation, irrespective of the extent of hypertrophy, MPRI or LGE burden (univariate predictors). In conclusion, we have successfully developed and implemented a novel oxygen-sensitive CMR method which has provided important insights into the role of stress oxygenation as a promising biomarker of arrythmic risk and potential therapeutic target for drug discovery in HCM.
- Published
- 2019
38. 20 Endothelial loss as a cause of impaired myocardial perfusion reserve on CMR in severe aortic stenosis
- Author
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Rana Sayeed, Mario Petrou, Kenneth H. Chan, Joseph Westaby, Stefan Neubauer, Theodoros D. Karamitsos, Houman Ashrafian, Betty Raman, Masliza Mahmod, Sairia Dass, Mary Sheppard, and Saul G. Myerson
- Subjects
Pressure overload ,Aortic valve ,medicine.medical_specialty ,Endothelium ,business.industry ,medicine.disease ,Muscle hypertrophy ,Stenosis ,medicine.anatomical_structure ,Aortic valve replacement ,Fibrosis ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,business ,Perfusion - Abstract
Background Impaired myocardial perfusion reserve occurs in pressure overload hypertrophy such as in severe aortic stenosis (AS) despite unobstructed epicardial coronaries. However the pathological mechanisms underlying this are poorly understood. We sought to assess myocardial perfusion reserve in severe AS by stress perfusion cardiovascular magnetic resonance (CMR), and examine the findings in relation to the histological evidence of vascular changes in the myocardium. Methods Fourteen patients with severe AS and unobstructed epicardial coronaries underwent adenosine stress perfusion CMR before and 6 months after surgical aortic valve replacement (AVR). Myocardial biopsies were obtained during AVR and stained using CD31 +for endothelium, smooth muscle actin (SMA) for smooth muscle, and picrosirius red for fibrosis. Nine age- and sex- matched post-mortem myocardial samples served as histological controls. Results When compared to controls, the myocardium of patients with severe AS had reduced vessel density, total quantity of SMA +ve and CD31 +ve, in addition to the expected increase in fibrosis. There was absence of CD31 +ve endothelium in SMA +ve arterioles, indicating endothelial loss. (Figure 1) Importantly, patients with an aortic valve area (AVA) ≤0.8cm2 had greater endothelial loss compared to those with an AVA >0.8 and≤1.0cm2 (1.34%±0.44% vs 2.84±1.03%, p=0.006), and endothelial loss also correlated with myocardial perfusion reserve index (MPRI), r=0.66, p=0.019. MPRI improved significantly post AVR (from 0.95±0.17 to 1.50±0.43, p=0.018). Conclusion In severe AS, there is microvascular rarefaction and loss of endothelium, which is more pronounced in patients with the most severe aortic valve narrowing. This appears to be an underlying mechanism for reduced myocardial perfusion reserve, which may be reversible post AVR.
- Published
- 2019
39. 22 Impaired stress-induced oxygenation in hypertrophic cardiomyopathy is associated with an increased risk of ventricular arrhythmia
- Author
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Theodoros D. Karamitsos, Hugh Watkins, Kenneth H. Chan, Sanjay Sivalokanathan, Joseph B. Selvanayagam, Betty Raman, Stefan Neubauer, Elizabeth M. Tunnicliffe, Masliza Mahmod, Aaron T. Hess, and Rina Ariga
- Subjects
medicine.medical_specialty ,Blood-oxygen-level dependent ,business.industry ,Hypertrophic cardiomyopathy ,Oxygenation ,medicine.disease ,Ventricular tachycardia ,Intensity (physics) ,Fibrosis ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,Biomarker (medicine) ,cardiovascular diseases ,business ,Body mass index - Abstract
Background Myocardial ischaemia is believed to promote fatal life-threatening ventricular arrhythmias in hypertrophic cardiomyopathy (HCM). Oxygen sensitive cardiac magnetic resonance (CMR) or blood oxygen level dependent (BOLD) imaging can detect blunted myocardial oxygenation during vasodilator stress in HCM. Whether or not impairment in stress oxygenation is associated with ventricular arrythmia risk is unknown. Objectives To investigate the relationship between blunted stress oxygenation and ventricular arrhythmia in HCM and examine the determinants of stress oxygenation in HCM. Methods 103 genotyped HCM patients and 32 (age, gender and body mass index matched) healthy controls underwent adenosine stress BOLD, stress first pass perfusion imaging and late gadolinium imaging (LGE) to assess stress oxygenation, myocardial perfusion reserve index (MPRI), and fibrosis burden respectively. Stress oxygenation response (BOLD ΔSI) was estimated as a relative increase in oxygen sensitive BOLD signal intensity from rest to peak vasodilator stress. All HCM patients had 24-holter monitoring to assess for ventricular tachycardia (≥3 beats,≥120 beats per minute). Results As expected, both MPRI (1.5±0.4 v 2.0±0.3, p Conclusion In HCM, impaired stress-induced oxygenation is associated with an increased risk of ventricular arrhythmia and may represent a novel biomarker of arrhythmic risk. Sarcomeric mutation status independently predicts a blunted stress oxygenation response in HCM.
- Published
- 2019
40. 6 RV function deteriorates earlier than LV function and predicts adverse cardiovascular outcomes
- Author
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Betty Raman, Rina Ariga, Elizabeth Ormondroyd, Sanjay Sivalokanathan, Kenneth H. Chan, Stefan Neubauer, Robert Smillie, Hugh Watkins, and Masliza Mahmod
- Subjects
Lv function ,medicine.medical_specialty ,Ejection fraction ,Longitudinal strain ,business.industry ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,medicine.disease ,Internal medicine ,Heart failure ,Rv function ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,business ,Cardiovascular outcomes - Abstract
Background The current assessment of hypertrophic cardiomyopathy (HCM) places emphasis on left ventricular (LV) function which is usually preserved in early disease. There are limited data on right ventricular (RV) assessment in HCM, progressive functional changes, and impact of RV dysfunction on clinical outcomes. Objectives To examine the natural history of RV functional changes (ejection fraction and strain) and investigate its prognostic role in HCM. Methods 311 patients (mean age 52±15 years) with HCM and preserved LV function (ejection fraction; EF ≥50%) underwent cardiac magnetic resonance (CMR) imaging and were compared to age- and sex- matched healthy controls (n=30). In 71 patients, follow-up CMR imaging was further undertaken at a median interval of 5.3 years. All patients were followed up for a composite endpoint of adverse cardiovascular outcomes, including new-onset atrial fibrillation, ventricular arrhythmia, hospitalisation due to heart failure or embolic events, or cardiovascular death. Results HCM patients exhibited lower RV ejection fraction (RVEF) and global peak systolic strains (radial/circumferential/longitudinal) on feature-tracking analysis of cine images than healthy controls. On follow up CMR imaging, RVEF, peak RV circumferential and longitudinal strains decreased over time while LVEF remained preserved. All patients were followed up clinically for a median duration of 4.4 years. Both reduced RVEF and RV longitudinal strain were independent predictors of ventricular arrhythmias and composite cardiovascular endpoint (arrhythmia, cardiac hospitalisation and cardiovascular death), after adjusting for baseline NYHA class, medication use, maximal LV wall thickness, and late gadolinium enhancement. Patients with RVEF −16.3%) demonstrated a higher risk of ventricular arrhythmias (HR 2.20, 95% CI 1.20 to 4.01, figure 1C) and composite cardiac events (HR 2.49, 95% CI 1.61 to 3.84, figure 1D) compared to others. Conclusions Despite preserved LVEF, RVEF and strain decline over time in HCM. RVEF and strain predict the occurrence of adverse cardiovascular outcomes and may have a role in prognostic risk stratification in HCM.
- Published
- 2019
41. The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study
- Author
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Jürgen E. Schneider, Jane M. Francis, Rina Ariga, Betty Raman, Houman Ashrafian, Nikhil Pal, Rajarshi Banerjee, Vanessa M Ferreira, Masliza Mahmod, Michael P. Frenneaux, Jennifer J Rayner, Stefan Neubauer, Eylem Levelt, Christopher T. Rodgers, Oliver J Rider, Sairia Dass, Cameron J. Holloway, Theodoros D. Karamitsos, Apollo - University of Cambridge Repository, and Mahmod, Masliza [0000-0002-0601-3510]
- Subjects
Male ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Steatosis ,Phosphocreatine ,Proton Magnetic Resonance Spectroscopy ,Myocardial steatosis ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Ventricular Function, Left ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Adenosine Triphosphate ,Prospective Studies ,Diastolic strain rate ,Spectroscopy ,Ejection fraction ,Exercise Tolerance ,Radiological and Ultrasound Technology ,VO2 max ,Middle Aged ,Biomechanical Phenomena ,Lipotoxicity ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Diastole ,Magnetic Resonance Imaging, Cine ,Heart failure ,03 medical and health sciences ,Oxygen Consumption ,Predictive Value of Tests ,Internal medicine ,Maximal oxygen consumption ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Triglycerides ,Aged ,business.industry ,Research ,Myocardium ,medicine.disease ,Myocardial Contraction ,lcsh:RC666-701 ,Case-Control Studies ,Exercise Test ,Cardiovascular magnetic resonance ,Heart failure with preserved ejection fraction ,business ,Energy Metabolism ,Biomarkers - Abstract
Background Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. Methods Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate. Results When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. Conclusions Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
- Published
- 2018
42. Discrepancy between pathological progression and clinical stability in a young patient with hypertrophic cardiomyopathy
- Author
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Stefan Neubauer, Masliza Mahmod, Betty Raman, Kenneth H. Chan, Hugh Watkins, and David Wen
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Heart Ventricles ,Cardiomyopathy ,Magnetic Resonance Imaging, Cine ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Fibrosis ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Young adult ,Pathological ,medicine.diagnostic_test ,business.industry ,Myocardium ,Disease progression ,Hypertrophic cardiomyopathy ,Follow up studies ,Magnetic resonance imaging ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Myocardial Contraction ,Echocardiography ,Cardiology ,Disease Progression ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Published
- 2018
43. COVID-19 and Major Organ Thromboembolism: Manifestations in Neurovascular and Cardiovascular Systems
- Author
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Joyce Pauline Joseph, Masliza Mahmod, Presaad Pillai, and Nurul Huda Mohamad Fadzillah
- Subjects
medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Clinical Neurology ,Arterial Occlusive Diseases ,Review Article ,Disease ,Risk Assessment ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Fibrinolytic Agents ,Risk Factors ,Thromboembolism ,Pandemic ,medicine ,Humans ,Intensive care medicine ,Venous Thrombosis ,business.industry ,Rehabilitation ,COVID-19 ,Venous Thromboembolism ,Cardiovascular disease ,Prognosis ,Neurovascular bundle ,medicine.disease ,Thrombosis ,COVID-19 Drug Treatment ,Cerebrovascular Disorders ,Systematic review ,Neurovascular disease ,D-dimer ,Surgery ,Neurology (clinical) ,Immunothrombosis ,Pulmonary Embolism ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause multisystemic damage. We undertook a systematic literature review and comprehensive analysis of a total of 55 articles on arterial and venous thromboembolism in COVID-19 and articles on previous pandemics with respect to thromboembolism and compared the similarities and differences between them. The presence of thrombosis in multiple organ systems points to thromboembolism being an integral component in the pathogenesis of this disease. Thromboembolism is likely to be the main player in the morbidity and mortality of COVID -19 in which the pulmonary system is most severely affected. We also hypothesize that D-dimer values could be used as an early marker for prognostication of disease as it has been seen to be raised even in the pre-symptomatic stage. This further strengthens the notion that thromboembolism prevention is necessary. We also examined literature on the neurovascular and cardiovascular systems, as the manifestation of thromboembolic phenomenon in these two systems varied, suggesting different pathophysiology of damage. Further research into the role of thromboembolism in COVID-19 is important to advance the understanding of the virus, its effects and to tailor treatment accordingly to prevent further casualties from this pandemic.
- Published
- 2021
44. Reevaluation of the South Asian MYBPC3Δ25bp Intronic Deletion in Hypertrophic Cardiomyopathy
- Author
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Andrew R. Harper, Michael Bowman, Jesse B.G. Hayesmoore, Helen Sage, Silvia Salatino, Edward Blair, Carolyn Campbell, Bethany Currie, Anuj Goel, Karen McGuire, Elizabeth Ormondroyd, Kate Sergeant, Adam Waring, Jessica Woodley, Christopher M. Kramer, Stefan Neubauer, Martin Farrall, Hugh Watkins, Kate L. Thomson, Theodore Abraham, Lisa Anderson, Evan Appelbaum, Camillo Autore, Colin Berry, Elena Biagini, William Bradlow, Chiara Bucciarelli-Ducci, Amedeo Chiribiri, Lubna Choudhury, Andrew Crean, Dana Dawson, Milind Y. Desai, Eleanor Elstein, Andrew Flett, Matthias Friedrich, Stephen Heitner, Adam Helms, Carolyn Ho, Daniel L. Jacoby, Han Kim, Bette Kim, Eric Larose, Masliza Mahmod, Heiko Mahrholdt, Martin Maron, Gerry McCann, Michelle Michaels, Saidi Mohiddin, Sherif Nagueh, David Newby, Iacopo Olivotto, Anjali Owens, F. Pierre-Mongeon, Sanjay Prasad, Ornella Rimoldi, Michael Salerno, Jeanette Schulz-Menger, Mark Sherrid, Peter Swoboda, Albert van Rossum, Jonathan Weinsaft, James White, and Eric Williamson
- Subjects
Adult ,Male ,0301 basic medicine ,haplotypes ,Asia ,South asia ,genotype ,introns ,Cardiomyopathy ,Disease ,030204 cardiovascular system & hematology ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Risk Factors ,Genotype ,medicine ,Humans ,Exome ,Aged ,Sequence Deletion ,Genetics ,Heart Failure ,Base Sequence ,Haplotype ,Hypertrophic cardiomyopathy ,General Medicine ,Original Articles ,Middle Aged ,Cardiomyopathy, Hypertrophic ,medicine.disease ,030104 developmental biology ,Increased risk ,Case-Control Studies ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Female ,Carrier Proteins ,Cardiomyopathies ,exome - Abstract
Supplemental Digital Content is available in the text., Background: The common intronic deletion, MYBPC3Δ25, detected in 4% to 8% of South Asian populations, is reported to be associated with cardiomyopathy, with ≈7-fold increased risk of disease in variant carriers. Here, we examine the contribution of MYBPC3Δ25 to hypertrophic cardiomyopathy (HCM) in a large patient cohort. Methods: Sequence data from 2 HCM cohorts (n=5393) was analyzed to determine MYBPC3Δ25 frequency and co-occurrence of pathogenic variants in HCM genes. Case-control and haplotype analyses were performed to compare variant frequencies and assess disease association. Analyses were also undertaken to investigate the pathogenicity of a candidate variant MYBPC3 c.1224-52G>A. Results: Our data suggest that the risk of HCM, previously attributed to MYBPC3Δ25, can be explained by enrichment of a derived haplotype, MYBPC3Δ25/−52, whereby a small subset of individuals bear both MYBPC3Δ25 and a rare pathogenic variant, MYBPC3 c.1224-52G>A. The intronic MYBPC3 c.1224-52G>A variant, which is not routinely evaluated by gene panel or exome sequencing, was detected in ≈1% of our HCM cohort. Conclusions: The MYBPC3 c.1224-52G>A variant explains the disease risk previously associated with MYBPC3Δ25 in the South Asian population and is one of the most frequent pathogenic variants in HCM in all populations; genotyping services should ensure coverage of this deep intronic mutation. Individuals carrying MYBPC3Δ25 alone are not at increased risk of HCM, and this variant should not be tested in isolation; this is important for the large majority of the 100 million individuals of South Asian ancestry who carry MYBPC3Δ25 and would previously have been declared at increased risk of HCM.
- Published
- 2020
45. P1808Patients with heart failure with mid-range and reduced left ventricular ejection fraction show similar derangement of cardiac energy and lipid metabolism
- Author
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Christopher T. Rodgers, S Neubauer, Victoria Stoll, T D Karamitsos, Moritz Hundertmark, Betty Raman, Masliza Mahmod, Sairia Dass, Oliver J Rider, C Holloway, and Rina Ariga
- Subjects
medicine.medical_specialty ,Derangement ,Ejection fraction ,business.industry ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Lipid metabolism ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2018
46. Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias
- Author
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Rina, Ariga, Elizabeth M, Tunnicliffe, Sanjay G, Manohar, Masliza, Mahmod, Betty, Raman, Stefan K, Piechnik, Jane M, Francis, Matthew D, Robson, Stefan, Neubauer, and Hugh, Watkins
- Subjects
Male ,Time Factors ,Heart Ventricles ,Myocardium ,Magnetic Resonance Imaging, Cine ,Reproducibility of Results ,Cardiomyopathy, Hypertrophic ,Middle Aged ,Ventricular Function, Left ,Imaging, Three-Dimensional ,Diastole ,Electrocardiography, Ambulatory ,Tachycardia, Ventricular ,Humans ,Female ,Prospective Studies ,Follow-Up Studies - Abstract
Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia.This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia.A total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T.Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036).DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.
- Published
- 2018
47. 6 Diffusion tensor magnetic resonance imaging of myocardial disarray in hypertrophic cardiomyopathy
- Author
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Stefan Neubauer, Sanjay G. Manohar, Rina Ariga, Jane M Francis, Elizabeth M. Tunnicliffe, Stefan K. Piechnik, Hugh Watkins, Masliza Mahmod, Matthew D. Robson, and Betty Raman
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medicine.medical_specialty ,business.industry ,Diastole ,Hypertrophic cardiomyopathy ,Diffusion tensor magnetic resonance imaging ,medicine.disease ,Arrhythmogenic substrate ,Myocardial disarray ,Fibrosis ,Internal medicine ,Fractional anisotropy ,cardiovascular system ,Cardiology ,Medicine ,cardiovascular diseases ,business ,Diffusion MRI - Abstract
Introduction Disarray and fibrosis are a likely nidus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). These microstructural changes can be inferred by mapping the diffusion of water using diffusion tensor cardiac magnetic resonance (DT-CMR). Fractional anisotropy (FA) quantifies directionality of diffusion. We hypothesised that diastolic FA will be reduced in HCM and represents the arrhythmogenic substrate. Methods 50 HCM patients (47±14 y, 74% male) and 30 controls (46±16 y, 70% male) underwent DT-CMR of the mid-ventricular slice in diastole, cine, late gadolinium enhancement (LGE) and extracellular volume (ECV) imaging at 3 T. Results FA was reduced in HCM (slice mean 0.49±0.05 v 0.52±0.03, p Conclusion DT-CMR allowed in vivo assessment of HCM microstructure which matched patterns of disarray and fibrosis found at histology. Low FA was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. We propose that diastolic FA is the first in vivo marker of disarray and a potential independent risk factor in HCM.
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- 2018
48. P21 Cardiac metabolism in patients with heart failure with mid-range ejection fraction
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Christopher T. Rodgers, Stefan Neubauer, Oliver J Rider, Moritz Hundertmark, and Masliza Mahmod
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Energy metabolism ,Cardiac metabolism ,In patient ,business ,medicine.disease - Abstract
Rationale Disturbance in cardiac energy metabolism is a key feature of heart failure (HF). It is unknown whether HF with mid-range left ventricular (LV) ejection fraction (HFmrEF), defined by LVEF 40%–49%, represents a separate clinical entity and whether there are distinct cardio-metabolic changes compared with HF patients with more severely reduced EF (HFrEF – LVEF Methods 53 subjects (13 HFmrEF, 13 HFrEF and 25 age, sex and BMI-matched controls) underwent cardiovascular magnetic (MR) resonance at 3 Tesla (3T) to assess left ventricular (LV) volumes and function, 31P-MR spectroscopy (MRS) to measure myocardial PCr/ATP, and 1H-MRS to measure MTG content. Results There were no significant differences in PCr/ATP ratios between the two HF groups (HFmrEF 1.69±0.39 vs HFrEF 1.64±0.41 HFrEF, p Conclusion Our results indicate no differences in energetic and lipid derangement between HFmrEF and HFrEF. This emphasises the need for a new phenotyping model for HF patients based on factors other than LVEF.
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- 2018
49. A Hyperdynamic RV Is an Early Marker of Clinical Decompensation and Cardiac Recovery in Aortic Stenosis With Normal LV Ejection Fraction
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Rohan S. Wijesurendra, Rina Ariga, Theodoros D. Karamitsos, Marzia Rigolli, Stefan Neubauer, Saul G. Myerson, Margaret Loudon, Sacha Bull, Jane M Francis, Masliza Mahmod, and Sanjay Sivalokanathan
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medicine.medical_specialty ,Time Factors ,Hypertension, Pulmonary ,Ventricular Dysfunction, Right ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Ventricular Function, Left ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Afterload ,Internal medicine ,Severity of illness ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Decompensation ,Prospective Studies ,Heart Valve Prosthesis Implantation ,Ejection fraction ,business.industry ,Stroke Volume ,Stroke volume ,Aortic Valve Stenosis ,Recovery of Function ,medicine.disease ,Pulmonary hypertension ,Stenosis ,medicine.anatomical_structure ,Treatment Outcome ,Ventricle ,Case-Control Studies ,cardiovascular system ,Cardiology ,Ventricular Function, Right ,Cardiology and Cardiovascular Medicine ,business - Abstract
The right ventricle (RV) has been poorly studied in patients with aortic stenosis (AS) and normal left ventricular (LV) function, due to the belief that it is only affected by pulmonary hypertension (PH) secondary to advanced LV dysfunction. Despite this, increased RV afterload is frequent in AS [(1
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- 2018
50. A multicentre, randomized, placebo-controlled trial of mirabegron
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Renaud Lhommel, Alexandre Persu, Piotr Ponikowski, Elisabeth Pieske-Kraigher, Damien Gruson, Nancy Van Overstraeten, Ignatios Ikonomidis, Jean Noël Trochu, Fausto J. Pinto, Gerasimos Filippatos, Michele Senni, Oana Brosteanu, A.C. Pouleur, Bernhard Gerber, Stefan D. Anker, Dulce Brito, Frank Edelmann, Barbara Casadei, Rolf Wachter, Dirk Hasenclever, Jean-Luc Balligand, Masliza Mahmod, Burkert Pieske, Stefan K. Piechnik, Stefan Neubauer, Repositório da Universidade de Lisboa, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Département de médecine interne et services associés, Pouleur, A, Anker, S, Brito, D, Brosteanu, O, Hasenclever, D, Casadei, B, Edelmann, F, Filippatos, G, Gruson, D, Ikonomidis, I, Lhommel, R, Mahmod, M, Neubauer, S, Persu, A, Gerber, B, Piechnik, S, Pieske, B, Pieske-Kraigher, E, Pinto, F, Ponikowski, P, Senni, M, Trochu, J, Van Overstraeten, N, Wachter, R, and Balligand, J
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medicine.medical_specialty ,Heart disease ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,Muscle hypertrophy ,03 medical and health sciences ,0302 clinical medicine ,Cardiac magnetic resonance imaging ,Original Research Articles ,Internal medicine ,Medicine ,Original Research Article ,030212 general & internal medicine ,Mirabegron ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Hypertensive structural heart disease ,medicine.disease ,3. Good health ,Heart failure with preserved ejection fraction ,Heart failure ,Cardiology ,β3 adrenergic receptor ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution‐Non Commercial‐No Derivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made., Aims: Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3‐LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Methods and results: Beta3‐LVH is a randomized, placebo‐controlled, double‐blind, two‐armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co‐primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F‐fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Conclusions: Beta3‐LVH is the first large‐scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3‐LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients., This work was funded by the European Union Horizon 2020 grant (UE LSHM‐CT‐05‐018833) to J.‐L.B. B.C. is supported by the British Heart Foundation (RG/11/15/29375), the National Institute for Health Research Biomedical Research Centre, Oxford, the European Union's Horizon 2020 research and innovation programme (grant number 633196[CATCH ME]), and the British Heart Foundation Centre of Research Excellence, Oxford (grant number RE/08/004). S.P. and S.N. are supported by the NIHR Biomedical Research Centre, Oxford. They also acknowledge the support from the British Heart Foundation Centre of Research Excellence, Oxford, UK (RE/08/004 to R.W.). A.‐C.P. is sponsored by a Post‐doctorate Clinical Master Specialist of the Fondation Nationale de la Recherche Scientifique of the Belgian Government (FRSM: SPD 10844948).
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- 2018
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