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Oleg F Sharifov,1 Thomas S Denney Jr,2 J Michael Wells,1,3,4 Gregory A Payne,1,4 Swati Gulati,1,3 Himanshu Gupta,5 Mark T Dransfield,1,3,4 Steven G Lloyd1,4 1Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; 2Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA; 3UAB Lung Health Center, Birmingham, AL, USA; 4Birmingham VA Medical Center, Birmingham, AL, USA; 5Advanced Cardiovascular Imaging, Valley Medical Group, Paramus, NJ, USACorrespondence: Steven G LloydDepartment of Medicine, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 201, Birmingham, AL 35294-0012, USATel +1 205 934 9736Fax +1 205 934 9730Email slloyd@uabmc.eduPulmonary hypertension (PH) is an important prognostic indicator in patients with chronic obstructive pulmonary disease (COPD); however, PH in these patients is typically mild-to-moderate severity and invasive testing is not typically utilized.1 Though echocardiography can be used to screen for PH, it has limited accuracy in measuring pulmonary artery (PA) pressure and often hindered by window limitations in COPD patients.2 Cardiovascular magnetic resonance (CMR) does not have window limitations and can accurately evaluate the right ventricular (RV) and PA function. Therefore, there is a growing interest in the use of CMR for the diagnosis and management of PH, including patients with lung diseases. Recently, we have validated a novel non-invasive CMR-derived parameter that, similar to impedance, reflects pulsatile and resistive properties of the PA.3 This approach relies on the principle that compliant PA vessel walls cause changes in the velocity profile as it travels through the PA over the cardiac cycle. The frequency-dependent relationship between the input and output velocity profiles is described by a velocity transfer function (VTF), which is the relationship between the frequency spectra of input and output velocity.3 In suspected PH patients who underwent right heart catheterization, we found that VTF correlates with invasive PA impedance and the mean high-frequency modulus (MHFM) of VTF correlates with the pulmonary vascular resistance (PVR) and RV remodeling.3 Moreover, MHFM >1 accurately predicted an increased PVR.3 We hypothesized that elevated MHFM of VTF, reflecting increased PVR and pulmonary vascular disease, would be associated with reduced exercise capacity measured by 6-mins walk distance (6MWD) in a COPD cohort.

Objectives: The purpose of the study was to evaluate the effect of long-term β(1)-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR).Background: Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function.Methods: Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or β(1)-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate.Results: Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the β(1)-AR blockade group required mitral valve surgery (p = 0.23).Conclusions: β(1)-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428). [ABSTRACT FROM AUTHOR]

Objectives: This study assessed myocardial damage in patients with chronic isolated mitral regurgitation (MR) and left ventricular ejection fraction (LVEF) >60%.Background: Typically, MR patients have decreased LVEF after mitral valve (MV) repair despite normal pre-operative LVEF.Methods: Twenty-seven patients with isolated MR had left ventricular (LV) biopsies taken at time of MV repair. Magnetic resonance imaging with tissue tagging was performed in 40 normal subjects and in MR patients before and 6 months after MV repair.Results: LVEF (66 +/- 5% to 54 +/- 9%, p < 0.0001) and LV end-diastolic volume index (108 +/- 28 ml/m(2) to 78 +/- 24 ml/m(2), p < 0.0001) decreased, whereas left ventricular end-systolic (LVES) volume index was 60% above normal pre- and post-MV repair (p < 0.05). The LV circumferential and longitudinal strain rates decreased below normal following MV repair (6.38 +/- 1.38 vs. 5.11 +/- 1.28, p = 0.0009, and 7.51 +/- 2.58 vs. 5.31 +/- 1.61, percentage of R to R interval, p < 0.0001), as LVES stress/LVES volume index ratio was depressed at baseline and following MV repair versus normal subjects (0.25 +/- 0.10 and 0.28 +/- 0.05 vs. 0.33 +/- 0.12, p < 0.01). LV biopsies demonstrated cardiomyocyte myofibrillar degeneration versus normal subjects (p = 0.035). Immunostaining and immunoblotting demonstrated increased xanthine oxidase in MR versus normal subjects (p < 0.05). Lipofuscin deposition was increased in cardiomyocytes of MR versus normal subjects (0.62 +/- 0.20 vs. 0.33 +/- 0.11, percentage of area: p < 0.01).Conclusions: Decreased LV strain rates and LVES wall stress/LVES volume index following MV repair indicate contractile dysfunction, despite pre-surgical LVEF >60%. Increased oxidative stress could cause myofibrillar degeneration and lipofuscin accumulation resulting in LV contractile dysfunction in MR. [ABSTRACT FROM AUTHOR]

To determine the blood pressure independent effects of spironolactone on left atrial (LA) size and function in patients with resistant hypertension (RHTN). Patients with RHTN (n = 36, mean age 55 ± 7) were prospectively recruited. Spironolactone was initiated at 25 mg/day and increased to 50 mg/day after 4 weeks. Other antihypertensives were withdrawn to maintain constant blood pressure. Cardiac magnetic resonance imaging was performed at baseline and after 6 months of spironolactone treatment and changes in LA functional metrics were assessed. LA size and function parameters were improved (p < 0.05) from baseline to month-6: LA volumes indexed to body surface area (LAVI) were reduced (LAVI maximum 41.4 ± 12 vs. 33.2±9.7 mL/m 2 ; LAVI pre-A 32.6 ± 9.8 vs. 25.6 ± 8.1 mL/m 2 ; median LAVI minimum 18.5 [13.9-24.8] vs. 14.1 [10.9-19.2] mL/m 2 ); left atrioventricular coupling index was reduced (28.2 ± 11.5 vs. 22.7 ± 9.2%); LA emptying fractions (LAEF) were increased (median total LAEF 52.4 [48.7-60.3] vs. 55.9 [50.3-61.1] %; active LAEF 40.2 ± 8.6 vs. 43.1 ± 7.8%). LA global longitudinal strain in the active phase was increased (16.3 ± 4.1 vs. 17.8 ± 4.2%). The effect of spironolactone was similar in patients with high (N = 18) and normal (N = 18) aldosterone status (defined by plasma renin activity and 24-h urine aldosterone). Treatment of RHTN with spironolactone is associated with improvements in LA size and function, and atrioventricular coupling, regardless of whether aldosterone levels were normal or high at baseline. This study suggests the need for larger prospective studies examining effects of mineralocorticoid receptor antagonists on atrial function and atrioventricular coupling., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Left atrial (LA) strain is impaired in left ventricular (LV) diastolic dysfunction, associated with increased LV end diastolic pressure (LVEDP). In patients with preserved LV ejection fraction (LVEF), coronary artery disease (CAD) is known to impair LV diastolic function. The relationship of LVEDP with CAD and impact on LA strain is not well studied., Methods and Results: Patients with LVEF >50% (n = 37, age 61 ± 7 years) underwent coronary angiography, high-fidelity LV pressure measurements and cardiac magnetic resonance imaging. LA volumes, LA emptying fraction (LAEF), LA reservoir strain (LARS) and LA long-axis shortening (LALAS) were measured. By coronary angiography, patients were assigned into 3 groups: severe-CAD (n = 19, with obstruction of major coronary arteries >70% and/or history of coronary revascularization), mild-to-moderate-CAD (n = 10, obstruction of major coronary arteries 30-60%), and no-CAD (n = 8, obstruction of major coronary arteries and branches <30%). Overall, LVEF was 65 ± 8% and LVEDP was 14.4 ± 5.6 mmHg. Clinical characteristics, LVEDP and LV function measurements were similar in 3 groups. Severe-CAD group had lower LAEF, LALAS and LARS than those in no-CAD group (P < 0.05 all). In regression analysis, LARS and LALAS were associated with CAD severity and treatment with Nitrates, whereas LAEF and LAEF active were associated with CAD severity, treatment with Nitrates and LA minimum volume (P < 0.05 all). LAEF passive was associated with LVED volume (P < 0.05)., Conclusions: LA functional impairment may be affected by coexistent CAD severity, medications, in particular, Nitrates, and loading conditions, which should be considered when assessing LA function and LA-LV interaction. Our findings inspire exploration in a larger cohort., Competing Interests: Declaration of Competing Interest Authors declare no potential conflicts of interest related to this study., (Published by Elsevier B.V.)

Purpose: Knowledge of the timing of cardiac valve opening and closing is important in cardiac physiology. The relationship between valve motion and electrocardiogram (ECG) is often assumed, however is not clearly defined. Here we investigate the accuracy of cardiac valve timing estimated using only the ECG, compared to Doppler echocardiography (DE) flow imaging as the gold standard., Methods: DE was obtained in 37 patients with simultaneous ECG recording. ECG was digitally processed and identifiable features (QRS, T, P waves) were examined as potential reference points to determine opening and closure of aortic and mitral valves, as compared to DE outflow and inflow measurement. Timing offset of the cardiac valves opening and closure between ECG features and DE was measured from derivation set (n = 19). The obtained mean offset in combination with the ECG features model was then evaluated on a validation set (n = 18). Using the same approach, additional measurement was also done for the right sided valves., Results: From the derivation set, we found a fixed offset of 22 ± 9 ms, 2 ± 13 ms, 90 ± 26 ms, and - 2 ± - 27 ms when comparing S to aortic valve opening, T end to aortic valve closure, T end to mitral valve opening, and R to mitral valve closure respectively. Application of this model to the validation set showed good estimation of aortic and mitral valve opening and closure timing value, with low model absolute error (median of the mean absolute error of the four events = 19 ms compared to the gold standard DE measurement). For the right-sided (tricuspid and pulmonic) valves in our patient set, there was considerably higher median of the mean absolute error of 42 ms for the model., Conclusion: ECG features can be used to estimate aortic and mitral valve timings with good accuracy as compared to DE, allowing useful hemodynamic information to be derived from this easily available test., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Resistant hypertension (RHTN), defined as blood pressure (BP) that is uncontrolled with ≥3 medications, including a long-acting thiazide diuretic, also includes a subset with BP that is controlled with ≥4 medications, so-called controlled RHTN. This resistance is attributed to intravascular volume excess. Patients with RHTN overall have a higher prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction compared to patients with non-RHTN. We tested the hypothesis that patients with controlled RHTN due to the intravascular volume excess have higher left ventricular mass index (LVMI), higher prevalence of LVH, larger intracardiac volumes, and more diastolic dysfunction compared to patients with controlled non-resistant hypertension (CHTN), defined as BP controlled with ≤3 anti-hypertensive medications. Patients with controlled RHTN (n = 69) or CHTN (n = 63) who were treated at the University of Alabama at Birmingham were offered enrollment and underwent cardiac magnetic resonance imaging. Diastolic function was assessed by peak filling rate, time needed in diastole to recover 80% of stroke volume, E:A ratios and left atrial volume. LVMI was higher in patients with controlled RHTN (64.4 ± 22.5 vs 56.9 ± 11.5; P = .017). Intracardiac volumes were similar in both groups. Diastolic function parameters were not significantly different between groups. There were no significant differences in age, gender, race, body mass index, dyslipidemia between the two groups. The findings show that patients with controlled RHTN have higher LVMI, but comparable diastolic function to those of patients with CHTN., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background Virtual interviewing for cardiology fellowship was instituted in the 2021 fellowship application cycle because of the COVID-19 pandemic and restricted travel. The impact on geographic patterns of fellow-training program matching is unknown. This study sought to determine if there was a difference in geographic placement of matched fellows for cardiology fellowship match after initiation of virtual interviews compared with in-person interviewing. Methods and Results All US-based accredited cardiovascular disease fellowship programs that participated in the 2019 to 2021 fellowship match cycles and had publicly available data with fellowship and residency training locations and training year were included. Each fellow was categorized based on whether their fellowship and residency programs were in the same institution, same state, same US census region, or different census region. Categories were mutually exclusive. Of 236 eligible programs, 118 (50%) programs were identified, composed of 1787 matched fellows. Compared with the previrtual cohort (n=1178 matched fellows), there was no difference in the geographic placement during the 2021 virtual cycle (n=609 matched fellows) ( P =0.19), including the proportion matched at the same program (30.6% versus 31.5%), same state but different program (13% versus 13.8%), same region but different state (24.2% versus 19.7%), or different region (35% versus 33.1%). There was also no difference when stratified by program size or geographic region. Conclusions The use of virtual interviewing in the 2021 cardiology fellowship application cycle showed no significant difference in the geographic placement of matched fellows compared with in-person interviewing. Further study is needed to evaluate the impact of virtual interviewing and optimize its use in fellowship recruitment.

Background: We previously reported increased plasma XO (xanthine oxidase) activity in patients with resistant hypertension. Increased XO can cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Here, we report racial differences in XO activity and mtDNA DAMPs in Black and White adults with resistant hypertension., Methods: This retrospective study includes 91 resistant hypertension patients (44% Black, 47% female) with blood pressure >140/90 mm Hg on ≥4 medications and 37 normotensive controls (30% Black, 54% female) with plasma XO activity, mtDNA DAMPs, and magnetic resonance imaging of left ventricular morphology and function., Results: Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; P =0.001), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion (mg/24 hour per kg) was positively related to left ventricular end-diastolic volume ( r =0.527, P =0.001) and left ventricular mass ( r =0.394, P =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( P <0.001), with Black mtDNA DAMPS greater than Whites ( P <0.001). Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrates mitochondria cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation., Conclusions: These data warrant a large study to examine the role of XO and mitochondrial mtDNA DAMPs in cardiac remodeling and heart failure in Black adults with resistant hypertension.

Objective. We developed a method using cardiovascular magnetic resonance imaging to model the untwisting of the left ventricle (LV) as a damped torsional harmonic oscillator to estimate shear modulus (intrinsic myocardial stiffness) and frictional damping, then applied this method to evaluate the torsional stiffness of patients with resistant hypertension (RHTN) compared to a control group. Approach. The angular displacement of the LV during diastole was measured. Myocardial shear modulus and damping constant were determined by solving a system of equations modeling the diastolic untwisting as a damped, unforced harmonic oscillator, in 100 subjects with RHTN and 36 control subjects. Main Results. Though overall torsional stiffness was increased in RHTN (41.7 (27.1-60.7) versus 29.6 (17.3-35.7) kdyn*cm; p  = 0.001), myocardial shear modulus was not different between RHTN and control subjects (0.34 (0.23-0.50) versus 0.33 (0.22-0.46) kPa; p = 0.758). RHTN demonstrated an increase in overall diastolic frictional damping (6.13 ± 3.77 versus 3.35 ± 1.70 kdyn*cm*s; p < 0.001), but no difference in damping when corrected for the overlap factor (74.3 ± 25.9 versus 68.0 ± 24.0 dyn*s/cm 3 ; p  = 0.201). There was an increase in the polar moment (geometric component of stiffness; 11.47 ± 6.95 versus 7.58 ± 3.28 cm 4 ; p <0.001). Significance. We have developed a phenomenological method, estimating the intrinsic stiffness and relaxation properties of the LV based on restorative diastolic untwisting. This model finds increased overall stiffness in RHTN and points to hypertrophy, rather than tissue- level changes, as the major factor leading to increased stiffness., (© 2022 Institute of Physics and Engineering in Medicine.)

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase-contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P <0.001) and pulsatility and distensibility increased (15.9%±5.3% to 22.1%±7.9%, P <0.001; and 0.28%±0.10%/mm Hg to 0.40%±0.14%/mm Hg, P <0.001, respectively) following 6 months of spironolactone. Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Background: Anomalous coronary arteries (ACAs) may present increased risk for adverse cardiac events. We sought to evaluate the accuracy of conventional coronary angiography (CCA), as it is currently used in clinical practice, compared with expert interpretation and cardiac magnetic resonance imaging (CMR) in determining the site of origin and proximal course of ACAs., Methods: Fifty consecutive patients without concomitant congenital heart disease, who were referred for CMR to diagnose the course of an ACA, were retrospectively evaluated. Original CCA reports were reviewed. Angiography images were available in all patients and were interpreted by 2 experts blinded to the prior interpretation and CMR results. The accuracy of interpretation in each group was then compared to the current gold standard of CMR., Results: Identification of the site of origin (ie, aortic sinus) by referring angiographers was similar to that of expert angiographers (sensitivity, 89% vs 98%, respectively; P=.10). However, referring angiographers were less likely to correctly identify the proximal course as compared with expert angiographers (sensitivity, 27% vs 98%, respectively; P<.001)., Conclusions: As it is used in current practice, CCA does not provide sufficient diagnostic accuracy for identifying the proximal course of an ACA. Review by expert angiographers added sensitivity, improving the accuracy to nearly 100%. Expert consultation may be nearly as accurate as advanced imaging, and should be considered in cases of ACA in which there is diagnostic uncertainty.

Background: Half of U.S. adults have received at least one dose of the COVID-19 vaccines produced by either Pfizer, Moderna, or Johnson and Johnson, which represents a major milestone in the ongoing pandemic. Given the emergency use authorizations for these vaccines, their side effects and safety were assessed over a compressed time period. Hence, ongoing monitoring for vaccine-related adverse events is imperative for a full understanding and delineation of their safety profile., Case Presentation: An 22-year-old Caucasian male presented to our hospital center complaining of pleuritic chest pain. Six months prior he had a mild case of COVID-19, but was otherwise healthy. He had received his first dose of the Moderna vaccine three days prior to developing symptoms. Laboratory analysis revealed a markedly elevated troponin and multiple imaging modalities during his hospitalization found evidence of wall motion abnormalities consistent with a diagnosis of perimyocarditis. He was started on aspirin and colchicine with marked improvement of his symptoms prior to discharge., Conclusions: We present a case of perimyocarditis that was temporally related to COVID-19 mRNA vaccination in an young male with prior COVID-19 infection but otherwise healthy. Our case report highlights an albeit rare but important adverse event for clinicians to be aware of. It also suggests a possible mechanism for the development of myocardial injury in our patient., (© 2021. The Author(s).)

Background: In 2016, the American Society of Echocardiography (ASE) released guidelines for identifying left ventricular (LV) diastolic dysfunction (DD), but its ability to detect early hemodynamic abnormalities is not well established, especially in the setting of subclinical coronary artery disease (CAD). We hypothesize that the accuracy of ASE categorization of early LVDD is affected by knowledge of whether CAD history is present., Methods: We studied 34 patients (age 62 ± 7 years) with NYHA class I to II symptoms and with transthoracic echocardiography without findings suggesting myocardial disease (all with preserved LV ejection fraction), who underwent cardiac catheterization with high-fidelity LV pressure measurement. Echocardiographic images were evaluated for LVDD using ASE algorithm without and with knowledge of CAD history and angiography findings. CAD was considered as having DD for the algorithm., Results: CAD was identified in 22 patients at catheterization (65%). Using ASE guidelines without including history of CAD or angiographic results, 29 patients were DD-, 3 were DD+ (all grade II), and 2 were indeterminate. Inclusion of CAD history recategorized 59% (n = 20) patients to DD+ (all grade I) from DD- (P < .0001). Nineteen of the recategorized patients (95%) had increased isovolumetric relaxation time (IVRT). The addition of echocardiographic IVRT improved discrimination between DD- and DD+, when the presence of CAD is unknown., Conclusions: 2016-ASE algorithm reasonably accurately identifies early LVDD at rest as reflected by LV catheterization when CAD is disclosed, but without knowledge of the presence of CAD, it underdiagnoses DD+ grade I. The addition of IVRT may improve early LVDD diagnostics., (© 2020 Wiley Periodicals LLC.)

Aims: Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored., Methods and Results: The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P < 0.05)., Conclusions: Leucocyte count >7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Pulmonary hypertension (PH) is a clinical condition characterised by elevation of pulmonary arterial pressure (PAP) above normal range due to various aetiologies. While cardiac right-heart catheterisation (RHC) remains the gold standard and mandatory for establishing the diagnosis of PH, noninvasive imaging of the heart plays a central role in the diagnosis and management of all forms of PH. Although Doppler echocardiography (ECHO) can measure a range of haemodynamic and anatomical variables, it has limited utility for visualisation of the pulmonary artery and, oftentimes, the right ventricle. Cardiovascular magnetic resonance (CMR) provides comprehensive information about the anatomical and functional aspects of the pulmonary artery and right ventricle that are of prognostic significance for assessment of long-term outcomes in disease progression. CMR is suited for serial follow-up of patients with PH due to its noninvasive nature, high sensitivity to changes in anatomical and functional parameters, and high reproducibility. In recent years, there has been growing interest in the use of CMR derived parameters as surrogate endpoints for early-phase PH clinical trials. This review will discuss the role of CMR in the diagnosis and management of PH, including current applications and future developments, in comparison to other existing major imaging modalities., Competing Interests: Conflict of interest: S.R. Aryal has nothing to disclose. Conflict of interest: O.F. Sharifov has nothing to disclose. Conflict of interest: S.G. Lloyd has nothing to disclose., (Copyright ©ERS 2020.)

The 2019 American College of Cardiology Scientific Sessions displayed innovation in many areas for the evaluation and management of cardiovascular disease from preventive evaluation and care to advanced interventions. Imaging played a central role in these developments with a highlight of the conference being the imaging research presented. This review will summarize key imaging studies which were presented at this scientific meeting which will lead to innovation in the evaluation and management of cardiovascular disease. Experts in nuclear imaging (DW/MA), echocardiography (MS), cardiac magnetic resonance (SL), and cardiac computed tomography (RB) selected abstracts which they found to be of particular interest to the multimodality imaging audience and were integrated into this review (LP).

Increasing left atrial (LA) size predicts outcomes in patients with isolated mitral regurgitation (MR). Chymase is plentiful in the human heart and affects extracellular matrix remodeling. Chymase activation correlates to LA fibrosis, LA enlargement, and a decreased total LA emptying fraction in addition to having a potential intracellular role in mediating myofibrillar breakdown in LA myocytes. Because of the unreliability of the left ventricular ejection fraction in predicting outcomes in MR, LA size and the total LA emptying fraction may be more suitable indicators for timing of surgical intervention.

Purpose: Phase-contrast cardiovascular magnetic resonance (PC-CMR) quantification of intracardiac shunt (measuring the pulmonary to systemic flow ratio, Qp/Qs) is typically determined by measuring flow through planes perpendicular the pulmonary trunk (PA) and ascending aorta (Ao). This method is subject to error from presence of background velocity offsets and requires two scan acquisitions. We evaluated an alternate PC-CMR technique for quantifying Qp/Qs using a single modified plane that encompasses both the PA and Ao., Material and Methods: In 53 patients evaluated for intracardiac shunting, PC-CMR measurement in the individual Ao and PA planes and also in a single-acquisition plane was obtained and Qp/Qs calculated by each method. Bland-Altman analysis was performed to evaluate the agreement between the two methods., Results: The 95% confidence limits of agreement ranged from -0.52 to +0.34 indicating good agreement between the two methods. There was excellent agreement on the clinically relevant threshold value of Qp/Qs ratio of 1.5 (representing criteria for surgical correction of shunt)., Conclusions: Qp/Qs determined from the single-acquisition approach agrees well with that of the individual PA and Ao method and offers potential improved accuracy (due to background velocity offset)., (© 2019 Wiley Periodicals, Inc.)

Background: We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD)., Methods: Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated., Results: In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively., Conclusions: Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone., (© 2019 Wiley Periodicals, Inc.)

Background: Left ventricular (LV) remodeling and diastolic properties are affected by both underlying cardiovascular disease/cardiovascular disease risk factors (CVDRFs) and corresponding medication therapy. However, these effects may not be apparent in patients with multiple CVDRFs. We evaluated the effect of medication classes on hemodynamics in a patient cohort with normal LV dimensions and systolic function., Methods: In 38 participants (61 ± 7 years, 64 ± 9% LV ejection fraction) undergoing coronary angiography, LV pressure measurement and cardiac magnetic resonance imaging was performed. The effects of coronary artery disease (CAD), CVDRFs and their corresponding medication therapy on LV parameters were analyzed considering the number of CAD/CVDRFs and 'adequacy' of medication therapy to address each existing condition with specific indication-based medication classes., Results: Of the patients studied, 68% had CAD, 87% had hypertension, 87% had dyslipidemia, and 45% had diabetes. Neither individual or total number of CAD/CVDRFs were associated with overall differences in LV diastolic parameters. However, those without (n = 20) and with (n = 18) 'adequate' medication therapy for underlying CAD/CVDRFs differed in values of LV end diastolic pressure (17 ± 4 vs. 11 ± 5 mm Hg, P < 0.001), wall stress (3.9 ± 1.6 vs. 2.2 ± 1.2 x1000 N/m 2 , P < 0.001), pressure/volume ratio (0.13 ± 0.04 vs. 0.08 ± 0.03 mm Hg/ml, P < 0.01), and mass/volume ratio (0.77 ± 0.20 vs. 0.92 ± 0.24 g/ml, P < 0.05), but not in systolic blood pressure or LV mass index., Conclusions: Our results suggest an association between the degree of LV diastolic impairment and LV remodeling with the intensity of treatment for CAD/CVDRFs. Comprehensive treatment of all identified CAD/CVDRFs may be an important factor for the preservation of diastolic function.

Background: The extra-renal effects of aldosterone on left ventricular (LV) structure and function are exacerbated by increased dietary sodium in persons with hypertension. Previous studies demonstrated endothelial dysfunction and increased oxidative stress with high salt diet in normotensive salt-resistant subjects. We hypothesized that increased xanthine oxidase (XO), a product of endothelial cells, is related to 24-h urinary sodium and to LV hypertrophy and function in patients with resistant hypertension (RHTN)., Methods: The study group included persons with RHTN (n = 91), defined as a blood pressure > 140/90 mmHg on ≥ 3 medications at pharmacologically effective doses. Plasma XO activity and 24-h urine were collected, and cardiac magnetic resonance imaging (MRI) was performed to assess LV function and morphology. Sixty-seven normotensive persons on no cardiovascular medications served as controls. A subset of RHTN (n = 19) received spironolactone without salt restriction for six months with follow-up XO activity measurements and MRI analyses., Results: XO activity was increased two-fold in RHTN vs. normal and was positively correlated with LV mass, LV diastolic function, and 24-h urinary sodium. In RHTN patients receiving spironolactone without salt restriction, LV mass decreased, but LV diastolic function and XO activity did not improve. Baseline urinary sodium was positively associated with rate of change of LV mass to volume ratio and the LV E/A ratio., Conclusions: These results demonstrate a potential role of endothelium-derived oxidative stress and excess dietary salt in the pathophysiology of LV hypertrophy and diastolic dysfunction in persons with RHTN unaffected by the addition of spironolactone., (Copyright © 2019. Published by Elsevier Inc.)

This review summarizes key imaging studies that were presented at the American Heart Association Scientific Sessions 2018 in Chicago related to the fields of nuclear cardiology (including single photon emission computed tomography and positron emission tomography), cardiac computed tomography, cardiac magnetic resonance, and echocardiography. The aim of this bird's eye view is to inform readers of the various studies discussed at the meeting from these imaging modalities. While this review is directed to the benefit of those of us who were not able to attend the conference, we find that a general overview may also be useful to those that did since it is often difficult to get exposure to all abstracts at large meetings. Further, we hope that the presentation of multiple imaging studies in a single synthesized review will stimulate new ideas for future research in imaging.

Background Pulmonary artery ( PA ) stiffness is associated with increased pulmonary vascular resistance ( PVR ). PA stiffness is accurately described by invasive PA impedance because it considers pulsatile blood flow through elastic PA s. We hypothesized that PA stiffness and impedance could be evaluated noninvasively by PA velocity transfer function ( VTF ), calculated as a ratio of the frequency spectra of output/input mean velocity profiles in PA s. Methods and Results In 20 participants (55±19 years, 14 women) undergoing clinically indicated right-sided heart catheterization, comprehensive phase-contrast and cine-cardiac magnetic resonance imaging was performed to calculate PA VTF , along with right ventricular mass and function. PA impedance was measured as a ratio of frequency spectra of invasive PA pressure and echocardiographically derived PA flow waveforms. Mean PA pressure was 29.5±13.6 mm Hg, and PVR was 3.5±2.8 Wood units. A mixed-effects model showed VTF was significantly associated with PA impedance independent of elevation in pulmonary capillary wedge pressure ( P=0.005). The mean of higher frequency moduli of VTF correlated with PVR (ρ=0.63; P=0.003) and discriminated subjects with low (n=10) versus elevated PVR (≥2.5 Wood units, n=10), with an area under the curve of 0.95, similar to discrimination by impedance (area under the curve=0.93). VTF had a strong inverse association with right ventricular ejection fraction (ρ=-0.73; P<0.001) and a significant positive correlation with right ventricular mass index (ρ=0.51; P=0.02). Conclusions VTF , a novel right ventricular- PA axis coupling parameter, is a surrogate for PA impedance with the potential to assess PA stiffness and elevation in PVR noninvasively and reliably using cardiac magnetic resonance imaging.

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P =0.003) and had a greater proportion of women (75.0% versus 43%; P =0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m 2 ; P <0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P =0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P <0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention., (© 2018 American Heart Association, Inc.)

Background: Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform., Methods: In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch., Results: The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival., Conclusions: We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity., (© 2017 American Heart Association, Inc.)

This review summarizes key imaging studies that were presented in the American Heart Association Scientific Sessions 2017 related to the fields of nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. The aim of this bird's eye view is to inform readers about multiple studies reported at the meeting from these different imaging modalities. While such a review is most useful for those that did not attend the conference, we find that a general overview may also be useful to those that did since it is often difficult to get exposure to many abstracts at large meetings. The review, therefore, aims to help readers stay updated on the newest imaging studies presented at the meeting and will hopefully stimulate new ideas for future research in imaging.

Background: Accurate noninvasive diagnostic tools for evaluating left ventricular (LV) diastolic dysfunction (LVDD) are limited in preserved LV ejection fraction. We previously proposed the relationship of normalized rate of change in LV torsion shear angle (φ') to corresponding rate of change in LV volume (V') during early diastole (represented as -dφ'/dV') as a measure of LV diastolic function. We prospectively evaluated diagnostic accuracy of -dφ'/dV' in respect to invasive LV parameters., Methods and Results: Participants (n=36, age 61±7 years) with LV ejection fraction ≥50% and no acute myocardial infarction undergoing coronary angiography for chest pain and/or dyspnea evaluation were studied. High-fidelity invasive LV pressure measurements and cardiac magnetic resonance imaging with tissue tagging were performed. τ, the time constant of LV diastolic relaxation, was 58±10 milliseconds (mean±SD), and LV end-diastolic pressure was 14.5±5.5 mm Hg. Cardiac magnetic resonance imaging-derived -dφ'/dV' was 5.6±3.7. The value of -dφ'/dV' correlated with both τ and LV end-diastolic pressure ( r =0.39 and 0.36, respectively, P <0.05). LVDD was defined as τ>48 milliseconds and LV end-diastolic pressure >12 mm Hg (LVDD1), or, alternatively, τ>48 milliseconds and LV end-diastolic pressure >16 mm Hg (LVDD2). Area under the curve (AUC) of -dφ'/dV' for identifying LVDD1 was 0.83 (0.67-0.98, P =0.001), with sensitivity/specificity of 72%/100% for -dφ'/dV' ≥6.2. AUC of -dφ'/dV' for identifying LVDD&#95;2 was 0.82 (0.64-1.00, P =0.006), with sensitivity/specificity of 76%/85% for -dφ'/dV' ≥6.9. There were good limits of agreement between pre- and post-nitroglycerin -dφ'/dV'., Conclusions: The -dφ'/dV' obtained from the LV torsion volume loop is a promising parameter for assessing global LVDD with preserved LV ejection fraction and requires further evaluation., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

This review summarizes key imaging studies that were presented in the American Heart Association Scientific Sessions 2016 related to the fields of nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. This bird's eye view will inform readers about multiple studies from these different modalities. We hope that this general overview will be useful for those that did not attend the conference as well as to those that did since it is often difficult to get exposure to many abstracts at large meetings. The review, therefore, aims to help readers stay updated on the newest imaging studies presented at the meeting.

Tagged magnetic resonance imaging (tMRI) is a well-established method for evaluating regional mechanical function of the heart. Many techniques have been developed to compute 2D or 3D cardiac deformation and strain from tMRI images. In this paper, we present a new method for measuring 3D plus time biventricular myocardial strain from tMRI data. The method is composed of two parts. First, we use a Gabor filter bank to extract tag points along tag lines. Second, each tag point is classified to one of a set of indexed reference tag lines using a point classification with graph cuts (PCGC) algorithm and a motion compensation technique. 3D biventricular deformation and strain is computed at each image time frame from the classified tag points using a previously published finite difference method. The strain computation is fully automatic after myocardial contours are defined near end-diastole and end-systole. An in-vivo dataset composed of 30 human imaging studies with a range of pathologies was used for validation. Strains computed with the PCGC method with no manual corrections were compared to strains computed from both manually placed tag points and a manually-corrected unwrapped phase method. A typical cardiac imaging study with 10 short-axis slices and 6 long-axis slices required 30 min for contouring followed by 44 min of automated processing. The results demonstrate that the proposed method can reconstruct accurate 3D plus time cardiac strain maps with minimal user intervention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation., Materials and Methods: We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy., Results: Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last., Conclusions: Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies., Competing Interests: The authors have declared that no competing interests exist.

Objective: Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited., Methods: Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for American Heart Association class I indications was evaluated for desmin, the voltage-dependent anion channel, α-B-crystallin, and α, β-unsaturated aldehyde 4-hydroxynonenal by fluorescence microscopy. The same was evaluated in 6 normal control LV autopsy specimens. Cardiomyocyte ultrastructure was examined by transmission electron microscopy. Magnetic resonance imaging with tissue tagging was performed in 55 normal subjects and 22 MR patients before and 6 months after mitral valve repair., Results: LV end-diastolic volume was 1.5-fold (P < .0001) higher and LV mass-to-volume ratio was lower in MR (P = .004) hearts versus normal hearts and showed improvement 6 months after mitral valve surgery. However, LV ejection fraction decreased from 65% ± 7% to 52% ± 9% (P < .0001) and LV circumferential (P < .0001) and longitudinal strain decreased significantly below normal values (P = .002) after surgery. Hearts with MR had a 53% decrease in desmin (P < .0001) and a 2.6-fold increase in desmin aggregates (P < .0001) versus normal, along with substantial, intense perinuclear staining of α, β-unsaturated aldehyde 4-hydroxynonenal in areas of mitochondrial breakdown and clustering. Transmission electron microscopy demonstrated numerous electron-dense deposits, myofibrillar loss, Z-disc abnormalities, and extensive granulofilamentous debris identified as desmin-positive by immunogold transmission electron microscopy., Conclusions: Despite well-preserved preoperative LV ejection fraction, severe oxidative stress and disruption of cardiomyocyte desmin-mitochondrial sarcomeric architecture may explain postoperative LV functional decline and further supports the move toward earlier surgical intervention., (Published by Elsevier Inc.)

High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.

Multiple novel studies were presented at the 2015 American Heart Association Scientific Sessions which was considered a successful conference at many levels. In this review, we will summarize key studies in nuclear cardiology, cardiac magnetic resonance, echocardiography, and cardiac computed tomography that were presented at the Sessions. We hope that this bird's eye view will keep readers updated on the newest imaging studies presented at the meeting whether or not they were able to attend the meeting.

Background: Implantable cardioverter-defibrillators (ICDs) are generally considered a contraindication to magnetic resonance imaging (MRI)., Objective: The purpose of the ProMRI Phase C study, a multicenter, prospective, single-arm, nonrandomized study, was to evaluate the clinical safety of the Biotronik ProMRI Iforia ICD system during MRI., Methods: Patients were enrolled after ICD implantation, with either a dual-chamber DR-T or single-lead VR-T DX system. Study-defined, nondiagnostic cardiac or thoracic spine MRI was performed at least 1 week after enrollment. ICDs were placed into MRI mode with ventricular fibrillation (VF) detection/therapy programmed "off" before scan and restored to non-MRI mode after scan. Interrogation was performed before, immediately after, and 1 month post-MRI. The primary end-points were (1) ventricular pacing threshold increase >0.5 V from pre-MRI to 1 month post-MRI; (2) R-wave amplitude decrease >50% from pre-MRI to 1 month post-MRI or R-wave amplitude <5 mV at 1 month post-MRI; and (3) MRI and ICD system-related serious adverse device effects., Results: One hundred seventy patients were enrolled at 39 US centers. One hundred fifty-three patients underwent MRI (25.7% cardiac, 74.3% thoracic spine) and completed follow-up. Freedom from the primary end-points was met in all but 1 subject, in whom reduced R-wave amplitude was detected 1 month post-MRI. No serious adverse device effects occurred during the course of the study., Conclusion: These results demonstrate the clinical safety and efficacy of the ProMRI ICD system in patients subjected to thoracic spine and cardiac MRI imaging in 1.5-T scanners., (Copyright © 2015 Heart Rhythm Society. All rights reserved.)

Objective: The relationship of mitral annular (MA) kinetics to left ventricular (LV) and left atrial (LA) function before and after mitral valve (MV) repair has not been well studied. Here we sought to provide comprehensive analysis that relates to MA motions, and LA and LV diastolic function post MV repair., Methods: Three-dimensional analyses of mitral annular motion, LA function, and LV volumetric and diastolic strain rates were performed on 35 degenerative mitral regurgitation (MR) patients at baseline and 1-year post MV repair, and 51 normal controls, utilizing cardiac magnetic resonance imaging with tissue tagging., Results: All had normal LV ejection fraction (EF) at baseline. LV and LA EFs decreased 1-year post-surgery vs. controls. LV early diastolic myocardial strain rates decreased post-surgery along with decreases in normalized early diastolic filling rate, E/A ratio, and early diastolic MA relaxation rates. Post-surgical LA late active kick remained higher in MR patients vs. control. LV and LA EFs were significantly associated with peak MA centroid to apex shortening. Furthermore, during LV systolic phase, peak LV ejection and LA filling rates were significantly correlated with peak MA centroid to apex shortening rate, respectively. While during LV diastolic phase, both peak early diastolic MA centroid to apex relaxation rate and LA ejection rate were positively significantly associated with LV peak early diastolic filling rate., Conclusion: MA motion is significantly associated with LA and LV function. Mitral annular motion, left atrial function, and LV diastolic strain rates are still impaired 1 year post MV repair. Long-term effects of these impairments should be prospectively evaluated.

Purpose: To evaluate the relationship between left ventricular (LV) twist, shear, and twist-per-volume and the severity of mitral regurgitation (MR). Primary MR is a valvular disorder that induces LV dysfunction. There exist several measures of LV rotational mechanics, but it remains unclear which measure of LV dysfunction best accords with the severity of MR. We hypothesized that LV systolic twist-per-volume slope would decrease with increasing severity of MR because of both decreases in rotational mechanics and increases in stroke volumes., Materials and Methods: Normal subjects (n = 54), moderate MR patients (n = 29), and severe MR patients (n = 54) were studied. Magnetic resonance imaging (MRI) was performed on a 1.5T scanner and grid-tagged LV images were collected at the LV base and LV apex. Measures of LV rotational mechanics were derived from tagged images using Fourier Analysis of STimulated echoes (FAST)., Results: Peak systolic twist-per-volume slope was significantly different for all pairwise comparisons (P < 0.0001) and compared to normal subjects (-0.14 ± 0.05°/mL) was decreased in moderate MR (-0.12 ± 0.04°/mL) and further decreased in severe MR (-0.07 ± 0.03°/mL)., Conclusion: Peak systolic twist-per-volume slope significantly decreased with increasing severity of MR and is therefore a suitable quantitative imaging biomarker for LV dysfunction in patients with MR., (© 2014 Wiley Periodicals, Inc.)

Background: Marathon runners (MTH) and patients with mitral regurgitation (MR) exhibit left ventricular (LV) overload, and LV geometric changes in these groups have been reported. In this study, right ventricular (RV) adaptation to chronic volume overload was evaluated in MTH and MR and normal controls together with interventricular septal remodeling and tricuspid annulus (TA) motion., Methods: A total of 60 age-matched subjects (including 19 MTH, 17 isolated chronic compensated MR patients, and 24 normal subjects) underwent conventional cine and tagged cardiac magnetic resonance imaging. Myocardial strain and curvature were computed on the interventricular septum and RV free wall. A dual-propagation technique was applied to construct RV volume-time curves for a single cardiac cycle. Similarly, the TA was tracked throughout the cardiac cycle to create displacement over time curve., Results: Septal curvature was significantly lower in MTH and MR compared to controls. No significant differences in RV free-wall strain or RV ejection fraction were noted among the three groups. However, longitudinal TA excursion was significantly higher in MTH compared to controls (p = 0.0061). The peak late diastolic TA velocity in MR was significantly faster than MTH (p = 0.0031) and controls (p = 0.020)., Conclusion: Increased TA kinetics allows for improved RV performance in MTH. Septal remodeling was observed in both MR and MTH, therefore a direct relationship of septal remodeling to TA kinetics in athlete's heart could not be elucidated in this study.

We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH.