37 results on '"Manhal, Habib"'
Search Results
2. Prognostic Utility of Intermediate-signal-intensity Late Gadolinium Enhancement in Patients with Hypertrophic Cardiomyopathy
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Raymond Ho Ming Chan, MD, MPH, Ali Pedarzadeh, MD, Ali Sakhnini, MD, Chiara Zocchi, MD, Cindy Chow, BSc, Manhal Habib, MD, PhD, Deacon Lee, MD, Beata Bruchal Garbicz, Arnon Adler, MD, Iacopo Olivotto, MD, and Harry Radowski, MD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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3. Cardio-Oncology Rehabilitation—Present and Future Perspectives
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Boaz Elad, Manhal Habib, and Oren Caspi
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cardiac rehabilitation ,cardiotoxicity ,cardiomyopathy ,exercise ,Science - Abstract
Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and deconditioning. In the general population, regular exercise can reduce the risk of cardiovascular morbidity, mortality, and cancer. Exercise-induced modifications of gene expression result in improvements of cardiovascular parameters and an increased general fitness, influencing telomere shortening, oxidative stress, vascular function, and DNA repair mechanisms. In cancer patients, exercise training is generally safe and well-tolerated; it is associated with a 10–15% improvement in cardiorespiratory fitness and can potentially counteract the adverse effects of anti-cancer therapy. It is well known that exercise programs can benefit patients with heart disease and cancer, but little research has been conducted with cardio-oncology patients. To date, there are a limited number of effective protective treatments for preventing or reversing cardiotoxicity caused by cancer therapy. Cardiac rehabilitation has the potential to mitigate cardiotoxicity based on the benefits already proven in populations suffering from either cancer or heart diseases. Additionally, the fact that cardiotoxic harm mechanisms coincide with similar mechanisms positively affected by cardiac rehabilitation makes cardiac rehabilitation an even more plausible option for cardio-oncology patients. Due to unstable functional capacity and fluctuating immunocompetence, these patients require specially tailored exercise programs designed collaboratively by cardiologists and oncologists. As the digital era is here, with the digital world and the medical world continuously intertwining, a remote, home-based cardio-oncology rehabilitation program may be a solution for this population.
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- 2022
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4. The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure
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Leor Perl, David Meerkin, Domenico D'amario, Binyamin Ben Avraham, Tuvia Ben Gal, Tatyana Weitsman, Tal Hasin, Hüseyin Ince, Sebastian Feickert, Giuseppe D'ancona, Ulrich Schaefer, Horst Sievert, Francisco Leyva, Zachary I. Whinnett, Carlo Di Mario, Michael Jonas, Michael Glikson, Manhal Habib, Oren Caspi, Oran Koren, William T. Abraham, Ran Kornowski, and Filippo Crea
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Cardiology and Cardiovascular Medicine - Published
- 2022
5. Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis
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John R. Power, Joachim Alexandre, Arrush Choudhary, Benay Ozbay, Salim S. Hayek, Aarti Asnani, Yuichi Tamura, Mandar Aras, Jennifer Cautela, Franck Thuny, Lauren Gilstrap, Dimitri Arangalage, Steven Ewer, Shi Huang, Anita Deswal, Nicolas L. Palaskas, Daniel Finke, Lorenz H. Lehmann, Stephane Ederhy, Javid Moslehi, Joe-Elie Salem, Charlotte Fenioux, Baptiste Abbar, Yves Allenbach, Shanthini M. Crusz, Arjun K. Ghosh, Tyler Moran, Tyler Mehegan, Lawrence Piro, Wei-Ting Chang, Johnny Chahine, Danette Flint, Ben Stringer, Valérie Gounant, Martin Nicol, Barouyr Baroudjian, Marie-Claire Zimmer, Elvire Mervoyer, Darryl Leong, Ryota Morimoto, Nicolas Piriou, Cecilia Monge, Amy Copeland, Kambiz Ghafourian, Avirup Guha, Sergey Brodsky, Osnat Itzhaki Ben Zadok, Manhal Habib, Grace Dy, Ellen Warner, Michal Laufer-Perl, Lily Koo Lin, Ana Narezkina, Alan Baik, Carrie Lenneman, Pankit Vachhani, Tariq U. Azam, Daniel Perry, Pennelope Blakely, Kazuko Tajiri, Matthew Martini, Joseph Nowatzke, Olusola Ayodeji Orimoloye, Andrew Hughes, Lauren A. Baldassarre, and Milan Patel
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Male ,Myocarditis ,Heart Block ,Humans ,Arrhythmias, Cardiac ,Female ,General Medicine ,Cardiology and Cardiovascular Medicine ,Immune Checkpoint Inhibitors ,Aged ,Retrospective Studies - Abstract
Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown.To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia.A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated.The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004).Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.
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- 2022
6. Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial
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D'Amario, Domenico, Meerkin, David, Restivo, Attilio, Ince, Hüseyin, Sievert, Horst, Wiese, Andrea, Schaefer, Ulrich, Trani, Carlo, Bayes-Genis, Antoni, Leyva, Francisco, Whinnett, Zachary I, Di Mario, Carlo, Jonas, Michael, Manhal, Habib, Amat-Santos, Ignacio J, Del Trigo, Maria, Gal, Tuvia Ben, Ben Avraham, Binyamin, Hasin, Tal, Feickert, Sebastian, D'Ancona, Giuseppe, Altisent, Omar Abdul-Jawad, Koren, Oran, Caspi, Oren, Abraham, William T, Crea, Filippo, Anker, Stefan D, Kornowski, Ran, and Perl, Leor
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Heart Failure ,Device in Heart Failure ,Remote Care ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,Digital Health ,Haemodynamic Remote Monitoring - Published
- 2023
7. IV Sodium Ferric Gluconate Complex in Patients With Iron Deficiency Hospitalized due to Acute Heart Failure—Investigator Initiated, Randomized Controlled Trial
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Erez Marcusohn, Itay Borreda, Yaron Hellman, Manhal Habib, Fadel Bahouth, Danny Epstein, and Robert Zukermann
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Heart Failure ,Pharmacology ,Iron ,Sodium ,COVID-19 ,Stroke Volume ,Iron Deficiencies ,Ferric Compounds ,Ventricular Function, Left ,Hospitalization ,Treatment Outcome ,Humans ,Single-Blind Method ,Prospective Studies ,Cardiology and Cardiovascular Medicine - Abstract
Patients with heart failure (HF) with iron deficiency (ID) have worse New York Heart Association class and are at a higher risk of recurrent hospitalizations. Intravenous (IV) iron has been shown to improve exercise ability and reduce hospitalizations. IV sodium ferric gluconate complex (SFGC) has been found to be safe and affordable but has not been studied in this population in a randomized trial. This was a prospective, single-blind, investigator-initiated, randomized controlled trial. Patients admitted for acute heart failure with ID were randomly assigned 1:1 to receive IV SFGC on top of optimal medical treatment. The primary outcome was the change in the 6-minute walk test (6MWT) from baseline to 3 and 6 months. Between September 2019 and May 2021, 34 patients were randomized. 19 patients (55%) were randomized to the treatment arm receiving 125 mg of IV SFGC per day for 3-5 days. COVID-19 was a major barrier to the implementation of the study follow-up protocol, which caused the study to end early. Both groups of patients had similar clinical characteristics, comorbidities, median left ventricular ejection fraction, and rate of death and readmissions due to HF. A higher level of NT-proBNP was observed in patients treated with IV iron (7902 pg/mL vs. 3158, P = 0.04). There was no difference in 6MWT change between groups at 3 months (improvement of 21.6 vs. 24.1 meters) or 6 months (-5 meters vs. 46 meters). In conclusion, IV SFGC-treated patients had a comparable 6-minute walk at 3 and 6 months despite suffering from more severe HF with higher baseline NT-proBNP (NCT04063033).
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- 2022
8. Acute Kidney Injury After Primary Angioplasty: Is Contrast‐Induced Nephropathy the Culprit?
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Oren Caspi, Manhal Habib, Yuval Cohen, Arthur Kerner, Ariel Roguin, Eitan Abergel, Monther Boulos, Michael R. Kapeliovich, Rafael Beyar, Eugenia Nikolsky, and Doron Aronson
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contrast media ,contrast‐induced nephropathy ,myocardial infarction ,primary percutaneous coronary intervention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundAcute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI) is frequently interpreted as contrast‐induced AKI but may result from other insults. We aimed to determine the causal association of contrast material exposure and the incidence of AKI following pPCI using a control group of propensity score–matched patients with ST‐segment–elevation myocardial infarction who were not exposed to contrast material. Methods and ResultsWe studied 2025 patients with ST‐segment–elevation myocardial infarction who underwent pPCI and 1025 patients receiving fibrinolysis or no reperfusion who were not exposed to contrast material during the first 72 hours of hospital stay (control group). AKI was defined as creatinine of ≥0.5 mg/dL or >25% rise within 72 hours. AKI rates were similar in the pPCI and control groups (10.3% versus 12.1%, respectively; P=0.38). Propensity score matching resulted in 931 matched pairs with PCI and no PCI, with balanced baseline covariates (standardized difference
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- 2017
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9. Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry
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Joseph Nowatzke, Paul Guedeney, Nicholas Palaskas, Lorenz Lehmann, Stephane Ederhy, Han Zhu, Jennifer Cautela, Sanjeev Francis, Pierre-Yves Courand, Anita Deswal, Steven M. Ewer, Mandar Aras, Dimitri Arangalage, Kambiz Ghafourian, Charlotte Fenioux, Daniel Finke, Giovanni Peretto, Vlad Zaha, Osnat Itzhaki Ben Zadok, Kazuko Tajiri, Nausheen Akhter, Joshua Levenson, Lauren Baldassarre, John Power, Shi Huang, Jean-Philippe Collet, Javid Moslehi, Joe-Elie Salem, Nazanin Aghel, Joachim Alexandre, Kazutaka Aonuma, Aarti H. Asnani, Juliane Behling, Mehmet Bilen, Wendy Bottinor, Eve Cariou, Johnny Chahine, Weiting Chan, Aman Chauhan, Max Cohen, Shanthini Crusz, Suran Fernando, Roberta Florido, Mauro Frigeri, Satoshi Fukushima, Elizabeth Gaughan, Benjamin P. Geisler, Lauren Gilstrap, Christian Grohe, Avirup Guha, Manhal Habib, Eva Haegler-Laube, Andrew Haydon, Salim Hayek, Andrew Hughes, Rysk Imai, Yumi Katsume, Hideki Kimura, Lily Koo Lin, Carrie Lenneman, Daryl Leong, Vicky Makker, Nicolas Martinez-Calle, Melissa Moey, Masahiro Mohri, Ryota Morimoto, Yoshinobu Moritoki, Anna Narezkina, Martin Nicol, Ajay Nooka, Olusola Orimoloye, Milan Patel, Michal Perl, Nicolas Piriou, Jayant K. Raikhelkar, Yasmin Raza, Anjali Rao, Sunil Reddy, Nobuhiko Seki, Karl Stangl, Andrew Stewart, Bryan Stringer, Balaji K. Tamarappoo, Yuichi Tamura, Frank Thuny, Sean Tierney, Romain Tresorier, Waqas Ullah, Jean-Jacques Von Hunolstein, Ellen Warner, Allison Weppler, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Heidelberg [Heidelberg] = Heidelberg University, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), CHU Saint-Antoine [AP-HP], Groupe de REcherche en Cardio Oncologie (GRC 27 - GRECO), Sorbonne Université (SU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The University of Texas Medical School at Houston, University of Wisconsin-Madison, University of California [San Francisco] (UC San Francisco), University of California (UC), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Heidelberg, Medical Faculty, Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Universität Heidelberg [Heidelberg], Service de Cardiologie [CHU Saint-Antoine], Groupe de REcherche en Cardio Oncologie [CHU Saint-Antoine] (GRC 27 GRECO), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Service de Pharmacologie médicale [CHU Pitié-Salpêtrière]
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Cancer Research ,Coronary Artery Disease ,Prognosis ,Coronary revascularization ,Myocarditis ,Oncology ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Risk Factors ,Immune-related adverse events ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,Humans ,Registries ,Immune checkpoint blockers ,Acute coronary syndrome ,[PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph] ,Immune Checkpoint Inhibitors ,Retrospective Studies - Abstract
International audience; Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocar-ditis) may present similarly and/or overlap with other cardiac pathology including acute cor-onary syndrome presenting a challenge for prompt clinical diagnosis.Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery steno-sis >70% in patients undergoing coronary angiogram.Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coro-nary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coro-nary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revas-cularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was margin-ally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057).Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diag-nosis and treatment or more severe presentation of ICB-myocarditis.
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- 2022
10. Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy
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Raymond H. Chan, Barry J. Maron, Harry Rakowski, Kimia Fardfini, Arnon Adler, Manhal Habib, Kate Hanneman, Martin S. Maron, Sara Hoss, and Ethan J. Rowin
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medicine.medical_specialty ,business.industry ,Hypertrophic cardiomyopathy ,Patient characteristics ,030204 cardiovascular system & hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,Heart failure ,cardiovascular system ,Cardiology ,Medicine ,Late gadolinium enhancement ,Radiology, Nuclear Medicine and imaging ,Myocardial fibrosis ,In patient ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Cardiac magnetic resonance - Abstract
Objectives This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making. Background Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM. Methods A total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years. Results At the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p 8% of LV mass, indexed LV mass >100 g/m2, maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p Conclusions Myocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.
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- 2021
11. Temporal Changes in Cardiac Morphology and Its Relationship with Clinical Characteristics and Outcomes in Patients with Hypertrophic Cardiomyopathy
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Manhal Habib, Arnon Adler, Sara Hoss, Kate Hanneman, Olga Katz, Hadeel Halloun Habib, Kimia Fardfini, Harry Rakowski, and Raymond H. Chan
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Cohort Studies ,Heart Failure ,Ventricular Dysfunction, Left ,Humans ,Cardiomyopathy, Hypertrophic ,Cardiology and Cardiovascular Medicine ,Magnetic Resonance Imaging - Abstract
In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8 ± 2.1 years. Progression of indexed left ventricular mass (LVMI) was correlated with lower LVMI at baseline (p 0.00001) and older age50 years. In terms of maximal wall thickness (MWT), progression was associated with lower baseline MWT and with the presence of LV outflow tract obstruction. No association was demonstrated between the degree of progression of LVMI or MWT and baseline LV volumes, the severity of mitral regurgitation, gender, or the presence of pathogenic HC variants. Progression of left atrial size was significantly associated with the development of atrial fibrillation (p = 0.014; odds ratio 1.18, confidence interval 1.03 to 1.35) and admission for heart failure (p = 0.018; odds ratio 1.18, confidence interval 1.03 to 1.36). No correlation was demonstrated between changes in LV mass or MWT and clinical outcomes of admission for heart failure, progression to New York Heart Association 2/3, progression to end-stage HC, or implantable cardioverter-defibrillator implantation. In conclusion, our study provides novel insights into the natural history of HC from a morphological perspective. It shows that HC is a dynamic disease in which LV morphology and hypertrophy extent change over time, with the presence of risk factors associated with disease progression.
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- 2022
12. Markers of responsiveness to disopyramide in patients with hypertrophic cardiomyopathy
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Manhal Habib, Beata Bruchal-Garbicz, Lynne Williams, Arnon Adler, Harry Rakowski, Raymond H. Chan, and Sara Hoss
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Male ,Alcohol septal ablation ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Ventricular Outflow Obstruction ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Left atrial ,Internal medicine ,Humans ,Medicine ,In patient ,030212 general & internal medicine ,Aged ,Voltage-Gated Sodium Channel Blockers ,Mitral regurgitation ,Ejection fraction ,business.industry ,Hypertrophic cardiomyopathy ,Stroke Volume ,Cardiomyopathy, Hypertrophic ,Middle Aged ,Atrial Function ,medicine.disease ,Treatment Outcome ,Echocardiography ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Wall thickness ,Disopyramide ,medicine.drug - Abstract
Background Significant left-ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients, nearly 30% of HCM patients do not respond. We sought to study the clinical and echocardiographic variables associated with disopyramide-induced LVOT-gradient reduction. Methods Forty-one disopyramide-treated HCM patients (average daily-dose 305 mg) were subdivided into two groups: (1) nineteen responders, with a reduction of LVOT-gradients of at least 30% from baseline, and (2) twenty-two non-responders, in whom LVOT-gradients did not change or increased following treatment. All patients had a thorough clinical and echocardiographic assessment pre- and post-treatment initiation. Results Patients who responded to disopyramide had better pretreatment left ventricular (LV) systolic function (LV ejection fraction of 67.9 ± 5.6% vs. 59.7 ± 5.8%, p = 0.0001), better LV global longitudinal strain (−17.9 ± 2.3% vs. −16.1 ± 2.5%, p = 0.048), less mitral regurgitation, smaller LV size (indexed LV end-systolic volume of 16.2 ± 5.1 ml/m2 vs. 23.2 ± 6.8 ml/m2, p = 0.001), and lower LV maximal wall thickness (17.2±3 mm vs.19.2 ± 3.4 mm, p = 0.046). Baseline left atrial (LA) volumes were significantly lower in the responders, with higher indices of LA ejection fraction (62 ± 11.2% vs. 50.5 ± 12.2%, p = 0.005), systolic LA strain (34 ± 12.4% vs. 25.8 ± 10.6%, p = 0.04), and LA strain-rate (1.34 ± 0.49%/sec vs. 0.99 ± 0.24%/sec, p = 0.012). In multivariable analysis, the presence of reduced LV systolic function and systolic LA strain-rate remained independently associated with poor response to disopyramide. Conclusions Obstructive HCM patients with more severe disease at baseline tend to respond less to disopyramide treatment. In those patients, early referral for alcohol septal ablation or myectomy surgery should be considered.
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- 2019
13. The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring
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Leor, Perl, David, Meerkin, Domenico, D'amario, Binyamin Ben, Avraham, Tuvia Ben, Gal, Tatyana, Weitsman, Tal, Hasin, Hüseyin, Ince, Sebastian, Feickert, Giuseppe, D'ancona, Ulrich, Schaefer, Horst, Sievert, Francisco, Leyva, Zachary I, Whinnett, Carlo, Di Mario, Michael, Jonas, Michael, Glikson, Manhal, Habib, Oren, Caspi, Oran, Koren, William T, Abraham, Ran, Kornowski, and Filippo, Crea
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Heart Failure ,Cardiac Catheterization ,Atrial Pressure ,Humans ,Stroke Volume ,Prospective Studies - Abstract
Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF.The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlicDiastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes.To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076).The V-LAP left atrium monitoring system appears to be safe and accurate.
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- 2021
14. Hypertrophic Cardiomyopathy
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Shemy Carasso, Lynne Williams, Manhal Habib, and Harry Rakowski
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- 2021
15. Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study
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Manhal, Habib, Arnon, Adler, Kimia, Fardfini, Sara, Hoss, Kate, Hanneman, Ethan J, Rowin, Martin S, Maron, Barry J, Maron, Harry, Rakowski, and Raymond H, Chan
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Magnetic Resonance Spectroscopy ,Predictive Value of Tests ,Myocardium ,Contrast Media ,Humans ,Gadolinium ,Cardiomyopathy, Hypertrophic ,Fibrosis - Abstract
This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.A total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.At the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p 0.0001), greater LV maximal wall thickness (p 0.0001), apical aneurysm at CMR-1 (p 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent8% of LV mass, indexed LV mass100 g/mMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.
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- 2020
16. Genetic Testing for Diagnosis of Hypertrophic Cardiomyopathy Mimics
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Kate Hanneman, Harry Rakowski, Robert M. Iwanochko, Sara Hoss, Melanie Care, Raymond H. Chan, Michael H. Gollob, Josh Silver, Arnon Adler, Manhal Habib, and Chantal F Morel
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Male ,0301 basic medicine ,Multifactorial Inheritance ,medicine.medical_specialty ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Clinical significance ,Genetic Testing ,cardiovascular diseases ,Aged ,Retrospective Studies ,Genetic testing ,Amyloid Neuropathies, Familial ,medicine.diagnostic_test ,business.industry ,Noonan Syndrome ,Hypertrophic cardiomyopathy ,General Medicine ,Enzyme replacement therapy ,Cardiomyopathy, Hypertrophic ,Middle Aged ,Prognosis ,medicine.disease ,Fabry disease ,Glycogen Storage Disease Type IIb ,PTPN11 ,030104 developmental biology ,Mutation ,Fabry Disease ,Noonan syndrome ,Female ,business ,Biomarkers ,Follow-Up Studies - Abstract
Background Genetic testing is helpful for diagnosis of hypertrophic cardiomyopathy (HCM) mimics. Little data are available regarding the yield of such testing and its clinical impact. Methods The HCM genetic database at our center was used for identification of patients who underwent HCM-directed genetic testing including at least 1 gene associated with an HCM mimic ( GLA , TTR , PRKAG2 , LAMP2 , PTPN11 , RAF1 , and DES ). Charts were retrospectively reviewed and genetic and clinical data extracted. Results There were 1731 unrelated HCM patients who underwent genetic testing for at least 1 gene related to an HCM mimic. In 1.45% of cases, a pathogenic or likely pathogenic variant in one of these genes was identified. This included a yield of 1% for Fabry disease, 0.3% for familial amyloidosis, 0.15% for PRKAG2 -related cardiomyopathy, and 1 patient with Noonan syndrome. In the majority of patients, diagnosis of the HCM mimic based on clinical findings alone would have been challenging. Accurate diagnosis of an HCM mimic led to change in management (eg, enzyme replacement therapy) or family screening in all cases. Conclusions Genetic testing is helpful in the diagnosis of HCM mimics in patients with no or few extracardiac manifestations. Adding these genes to all HCM genetic panels should be considered.
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- 2020
17. Effect of adding Eruca Sativa Seeds and Vit.E.on the diet of mal Awassi lambs on same production traits
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Manhal Habib Salman Al-Fityin
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Veterinary medicine ,SF600-1100 - Abstract
The aim of this study was to find out the effect of adding Eruca Sativa seed in concentrate diet alone or with Vit.E administration on productivity of male Awassi lambs.This study was conducted on Veterinary College,Baghdad University.Fifteen Awassi ram lambs at age of 5-6 months ,were divided equally in to three groups accordingly and treated as followed :The frist group A(G)was fed on concentrate diet containing Eruca Sativa seeds (5%)at a rate of 400g/day /haed,The second group B(G+E) was fed on the same ration mentioned above with Vit.E with a dose of 400mg/head was given orally bimonthly ,The animals in the third group C (control)were fed on a concentrate diet free of Eruca Sativa at a rate of 400g/day.All animals offered 0.5kg alfalfa/day/head and freely grazing for 3-6 h daily. The results revealed the followings:Body weight was increased in all animal progressively. Animals in group (G)and (G+E)were significantly (p
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- 2009
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18. Evaluation of Hypertrophic Cardiomyopathy: Newer Echo and MRI Approaches
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Sara Hoss, Harry Rakowski, and Manhal Habib
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medicine.medical_specialty ,Contrast Media ,Magnetic Resonance Imaging, Cine ,Gadolinium ,macromolecular substances ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Left atrial ,Internal medicine ,medicine ,Late gadolinium enhancement ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Cardiac imaging ,business.industry ,Myocardium ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,Heart ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Ventricle ,Echocardiography ,cardiovascular system ,Cardiology ,Cardiology and Cardiovascular Medicine ,Cardiac magnetic resonance ,business - Abstract
This review discusses the basic and evolving echocardiographic and cardiac magnetic resonance (CMR) approaches in the diagnosis and management of patients with hypertrophic cardiomyopathy (HCM). Newer imaging technologies and techniques in both echocardiography and CMR have proved to add incremental value to our understanding of HCM. 3D reconstruction in echocardiography and CMR allows for more accurate morphological and volumetric assessment of the left ventricle. Echocardiographic and CMR-based left atrial assessment, including for its mechanical properties, has been shown to be correlated to outcomes and development of atrial fibrillation. Tissue characterization and scar burden quantification by late gadolinium enhancement on CMR has revolutionized our understanding of fibrotic processes in HCM and their contribution to disease severity and clinical outcomes. Cardiac imaging plays a crucial role in HCM patients. Using echocardiography and CMR as complementary modalities allows for improved diagnostics, optimization of treatment, and better prognostication.
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- 2019
19. Pulmonary arterial capacitance in patients with heart failure and reactive pulmonary hypertension
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Nazzareno Galiè, Manhal Habib, Haitham Sholy, Robert Dragu, Shmuel Rispler, Haim Hammerman, and Doron Aronson
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medicine.medical_specialty ,business.industry ,Hazard ratio ,Hemodynamics ,medicine.disease ,Pulmonary hypertension ,Confidence interval ,Pulse pressure ,medicine.anatomical_structure ,medicine.artery ,Heart failure ,Internal medicine ,Pulmonary artery ,Vascular resistance ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Reactive pulmonary hypertension (PH) is a severe form of PH secondary to left-sided heart failure (HF). Given the structural and functional abnormalities in the pulmonary vasculature that occur in reactive PH, we hypothesized that pulmonary artery capacitance (PAC) may be profoundly affected, with implications for clinical outcome. Methods and results We studied 393 HF patients of whom 124 (32%) were classified as having passive PH and 140 (36%) as having reactive PH, and 91 patients with pulmonary arterial hypertension (PAH). Mean PAC was highest in patients without PH (4.5 ± 2.1 mL/mmHg), followed by the passive PH group (2.8 ± 1.4 mL/mmHg) and was lowest in those with reactive PH (1.8 ± 0.7 mL/mmHg) (P = 0.0001). PAC and pulmonary vascular resistance (PVR) fitted well to a hyperbolic inverse relationship (PAC = 0.25/PVR, R2 = 0.70), with reactive PH patients dispersed almost predominantly on the flat part of the curve where a reduction in PVR is associated with a small improvement in PAC. Elevated PCWP was associated with a significant lowering of PAC for any PVR (P = 0.036). During a median follow-up of 31 months, both reactive PH [hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.14–4.46, P = 0.02] and reduced PAC (HR 0.72 per 1 mL/mmHg increase, 95% CI 0.59–0.88, P = 0.001) were independent predictors of mortality. Conclusions The development of reactive PH is associated with a marked reduction in PAC. PAC is a strong independent haemodynamic marker of mortality in HF and may contribute to the increased mortality associated with reactive PH.
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- 2014
20. Acute Kidney Injury After Primary Angioplasty: Is Contrast-Induced Nephropathy the Culprit?
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Manhal Habib, Eitan Abergel, Michael Kapeliovich, Eugenia Nikolsky, Ariel Roguin, Yuval Cohen, Rafael Beyar, Oren Caspi, Doron Aronson, Arthur Kerner, and Monther Boulos
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Male ,Time Factors ,Databases, Factual ,Nephrology and Kidney ,medicine.medical_treatment ,Contrast Media ,Kaplan-Meier Estimate ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Kidney ,0302 clinical medicine ,contrast‐induced nephropathy ,Risk Factors ,Odds Ratio ,030212 general & internal medicine ,Myocardial infarction ,Israel ,Original Research ,Incidence ,Acute kidney injury ,Age Factors ,Acute Kidney Injury ,Middle Aged ,primary percutaneous coronary intervention ,Treatment Outcome ,myocardial infarction ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Glomerular Filtration Rate ,medicine.medical_specialty ,Primary angioplasty ,Contrast-induced nephropathy ,Culprit ,Risk Assessment ,Disease-Free Survival ,03 medical and health sciences ,Percutaneous Coronary Intervention ,Internal medicine ,medicine ,Kidney injury ,Humans ,Intensive care medicine ,Propensity Score ,Aged ,Proportional Hazards Models ,Heart Failure ,Chi-Square Distribution ,Kidney in Cardiovascular Disease ,business.industry ,Hemodynamics ,Percutaneous coronary intervention ,medicine.disease ,Logistic Models ,Case-Control Studies ,Multivariate Analysis ,Linear Models ,ST Elevation Myocardial Infarction ,business - Abstract
Background Acute kidney injury ( AKI ) following primary percutaneous coronary intervention ( pPCI ) is frequently interpreted as contrast‐induced AKI but may result from other insults. We aimed to determine the causal association of contrast material exposure and the incidence of AKI following p PCI using a control group of propensity score–matched patients with ST‐segment–elevation myocardial infarction who were not exposed to contrast material. Methods and Results We studied 2025 patients with ST‐segment–elevation myocardial infarction who underwent pPCI and 1025 patients receiving fibrinolysis or no reperfusion who were not exposed to contrast material during the first 72 hours of hospital stay (control group). AKI was defined as creatinine of ≥0.5 mg/dL or >25% rise within 72 hours. AKI rates were similar in the pPCI and control groups (10.3% versus 12.1%, respectively; P =0.38). Propensity score matching resulted in 931 matched pairs with PCI and no PCI, with balanced baseline covariates (standardized difference AKI rates were not significantly different with and without PCI (8.6% versus 10.9%, P =0.12). In the pPCI cohort, independent predictors of AKI included age ≥70 years, insulin‐treated diabetes mellitus, diuretic therapy, anterior infarction, baseline estimated glomerular filtration rate, and variables related to the presence of pump failure (higher Killip class, intra‐aortic balloon pump use) and reduced left ventricular ejection fraction but not contrast material dose. A risk score based on the PCI cohort had similar discriminatory capacity for AKI in the control group (C statistic 0.81±0.02 and 0.78±0.02, respectively; P =0.26). Conclusions The development of AKI in patients with ST‐segment–elevation myocardial infarction undergoing pPCI is mainly related to older age, baseline estimated glomerular filtration rate, heart failure, and hemodynamic instability. Risk for AKI is similar among ST‐segment–elevation myocardial infarction patients with and without contrast material exposure.
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- 2017
21. DETERMINANTS OF RESPONSIVENESS TO DISOPYRAMIDE IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
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Raymond H. Chan, Lynne Williams, Harry Rakowski, Manhal Habib, Arnon Adler, Sara Hoss, and Bruchal-Garbicz Beata
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Inotrope ,medicine.medical_specialty ,Adverse outcomes ,business.industry ,Hypertrophic cardiomyopathy ,Ventricular outflow tract obstruction ,macromolecular substances ,medicine.disease ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,In patient ,cardiovascular diseases ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Disopyramide ,medicine.drug - Abstract
Significant left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients through its negative inotropic properties, nearly one third of HCM patients with
- Published
- 2019
22. A combined cell therapy and in-situ tissue-engineering approach for myocardial repair
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Oren Caspi, Manhal Habib, Amira Gepstein, Doron Aronson, Keren Shapira-Schweitzer, Lior Gepstein, Gil Arbel, and Dror Seliktar
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Materials science ,medicine.medical_treatment ,Cell- and Tissue-Based Therapy ,Myocardial Infarction ,Biophysics ,Bioengineering ,Matrix (biology) ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Polyethylene Glycols ,Biomaterials ,Andrology ,Cell therapy ,Tissue engineering ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,Saline ,Cells, Cultured ,Embryonic Stem Cells ,Tissue Engineering ,Myocardium ,Fibrinogen ,Embryonic stem cell ,Rats, Inbred F344 ,Rats ,Transplantation ,Echocardiography ,Mechanics of Materials ,Ceramics and Composites ,Stem cell ,Ligation ,Biomedical engineering - Abstract
Myocardial cell-replacement strategies are hampered by limited sources for human cardiomyocytes and by significant cell loss following transplantation. We tested the hypothesis that a combined delivery of cardiomyocytes with an in-situ polymerizable hydrogel into a post-MI rat heart will result in better functional outcomes than each intervention alone. A photopolymerizable, biodegradable, PEGylated-fibrinogen (PF) hydrogel matrix was used as the carrier for the cardiomyocytes [neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)]. Infarcted rat hearts (LAD ligation) were randomized to injection of saline, NRVCMs, biopolymer, or combined biopolymer-cell delivery. Echocardiography revealed typical post-infarction remodeling after 30 days in the saline-injected control group [deterioration of fractional shortening (FS) by 31.0 ± 3.6%]. Injection of NRVCMs or PF alone significantly (p
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- 2011
23. A photopolymerizable hydrogel for 3-D culture of human embryonic stem cell-derived cardiomyocytes and rat neonatal cardiac cells
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Dror Seliktar, Manhal Habib, Lior Gepstein, and Keren Shapira-Schweitzer
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Cell type ,Photochemistry ,Fluorescent Antibody Technique ,Actinin ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Microscopy, Electron, Transmission ,Animals ,Humans ,Myocyte ,Myocytes, Cardiac ,Molecular Biology ,Cells, Cultured ,Embryonic Stem Cells ,Actin ,Syncytium ,Tissue Engineering ,Chemistry ,Anatomy ,Immunohistochemistry ,Embryonic stem cell ,Rats ,Cell biology ,Animals, Newborn ,Self-healing hydrogels ,Stem cell ,Cardiology and Cardiovascular Medicine ,Heptanol - Abstract
The purpose of this study was to assess the in vitro ability of two types of cardiomyocytes (cardiomyocytes derived from human embryonic stem cells (hESC-CM) and rat neonatal cardiomyocytes (rN-CM)) to survive and generate a functional cardiac syncytium in a three-dimensional in situ polymerizable hydrogel environment. Each cell type was cultured in a PEGylated fibrinogen (PF) hydrogel for up to two weeks while maturation and cardiac function were documented in terms of spontaneous contractile behavior and biomolecular organization. Quantitative contractile parameters including contraction amplitude and synchronization were measured by non-invasive image analysis. The rN-CM demonstrated the fastest maturation and the most significant spontaneous contraction. The hESC-CM maturation occurred between 10-14 days in culture, and exhibited less contraction amplitude and synchronization in comparison to the rN-CMs. The maturation of both cell types within the hydrogels was confirmed by cardiac-specific biomolecular markers, including alpha-sarcomeric actin, actinin, and connexin-43. Cellular responsiveness to isoproterenol, carbamylcholine and heptanol provided further evidence of the cardiac maturation in the 3-D PF hydrogel as well as identified a potential to use this system for in vitro drug screening. These findings indicate that the PF hydrogel biomaterial can be used as an in situ polymerizable biomaterial for stem cells and their cardiomyocyte derivatives.
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- 2009
24. Human embryonic stem cells for cardiomyogenesis
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Manhal Habib, Lior Gepstein, and Oren Caspi
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Pluripotent Stem Cells ,Tissue Engineering ,Myogenesis ,Cell ,Anatomy ,Germ layer ,Biology ,Embryonic stem cell ,Cell biology ,Cell therapy ,Blastocyst ,medicine.anatomical_structure ,Tissue engineering ,medicine ,Humans ,Myocyte ,Myocytes, Cardiac ,Cardiology and Cardiovascular Medicine ,Induced pluripotent stem cell ,Molecular Biology ,Embryonic Stem Cells - Abstract
Myocardial cell replacement strategies are emerging as novel therapeutic paradigms for heart failure but are hampered by the paucity of sources for human cardiomyocytes. Human embryonic stem cells (hESC) are pluripotent stem cell lines derived from human blastocysts that can be propagated, in culture, in the undifferentiated state under special conditions and coaxed to differentiate into cell derivatives of all three germ layers, including cardiomyocytes. The current review describes the derivation and properties of the hESC lines and the different cardiomyocyte differentiation system established so far using these cells. Data regarding the structural, molecular, and functional properties of the hESC-derived cardiomyocytes is provided as well as description of the methods used to achieve cardiomyocyte enrichment and purification in this system. The possible applications of this unique differentiation system in several cardiovascular research and applied areas are discussed. Specific emphasis is put on the descriptions of the efforts performed to date to assess the feasibility of this emerging technology in the fields of cardiac cell replacement therapy and tissue engineering. Finally, the obstacles remaining on the road to clinical translation are described as well as the steps required to fully harness the potential of this new technology.
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- 2008
25. Transplantation of Human Embryonic Stem Cell-Derived Cardiomyocytes Improves Myocardial Performance in Infarcted Rat Hearts
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Lior Yankelson, Gil Arbel, Rafael Beyar, Lior Gepstein, Oren Caspi, Doron Aronson, Izhak Kehat, Amira Gepstein, Irit Huber, and Manhal Habib
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Male ,medicine.medical_specialty ,Cell Survival ,Myocardial Infarction ,Infarction ,Cell therapy ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Myocyte ,Animals ,Humans ,Myocytes, Cardiac ,Myocardial infarction ,reproductive and urinary physiology ,Embryonic Stem Cells ,Heart Failure ,Microscopy, Confocal ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Myocardium ,Cell Differentiation ,equipment and supplies ,medicine.disease ,Embryonic stem cell ,Myocardial Contraction ,Surgery ,Rats ,Transplantation ,embryonic structures ,Cardiology ,biological phenomena, cell phenomena, and immunity ,Stem cell ,business ,Cardiology and Cardiovascular Medicine ,Ex vivo ,Cell Division - Abstract
Objectives We evaluated the ability of human embryonic stem cells (hESCs) and their cardiomyocyte derivatives (hESC-CMs) to engraft and improve myocardial performance in the rat chronic infarction model. Background Cell therapy is emerging as a novel therapy for myocardial repair but is hampered by the lack of sources for human cardiomyocytes. Methods Immunosuppressed healthy and infarcted (7 to 10 days after coronary ligation) rat hearts were randomized to injection of undifferentiated hESCs, hESC-CMs, noncardiomyocyte hESC derivatives, or saline. Detailed histological analysis and sequential echocardiography were used to determine the structural and functional consequences of cell grafting. Results Transplantation of undifferentiated hESCs resulted in the formation of teratoma-like structures. This phenomenon was prevented by grafting of ex vivo pre-differentiated hESC-CMs. The grafted cardiomyocytes survived, proliferated, matured, aligned, and formed gap junctions with host cardiac tissue. Functionally, animals injected with saline or nonmyocyte hESC derivatives demonstrated significant left ventricular (LV) dilatation and functional deterioration, whereas grafting of hESC-CMs attenuated this remodeling process. Hence, post-injury baseline fractional shortening deteriorated by 50% (from 20 ± 2% to 10 ± 2%) and by 30% (20 ± 2% to 14 ± 2%) in the saline and nonmyocyte groups while improving by 22% (21 ± 2% to 25 ± 3%) in the hESC-CM group. Similarly, wall motion score index and LV diastolic dimensions were significantly lower in the hESC-CM animals. Conclusions Transplantation of hESC-CMs after extensive myocardial infarction in rats results in the formation of stable cardiomyocyte grafts, attenuation of the remodeling process, and functional benefit. These findings highlight the potential of hESCs for myocardial cell therapy strategies.
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- 2007
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26. Identification and selection of cardiomyocytes during human embryonic stem cell differentiation
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Amira Gepstein, Manhal Habib, Irit Huber, Izhak Kehat, Lior Yankelson, Ilanit Itzhaki, Gil Arbel, Oren Caspi, Lior Gepstein, and Maty Tzukerman
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Cellular differentiation ,Green Fluorescent Proteins ,Population ,Embryoid body ,Biology ,Transfection ,Biochemistry ,Regenerative medicine ,Cell Line ,Genes, Reporter ,Genetics ,Humans ,education ,Molecular Biology ,Embryonic Stem Cells ,DNA Primers ,Muscle Cells ,education.field_of_study ,Reporter gene ,Myocardium ,Cell Differentiation ,Heart ,Embryonic stem cell ,Molecular biology ,Clone Cells ,P19 cell ,Stem cell ,Biotechnology - Abstract
Human embryonic stem cells (hESC) are pluripotent lines that can differentiate in vitro into cell derivatives of all three germ layers, including cardiomyocytes. Successful application of these unique cells in the areas of cardiovascular research and regenerative medicine has been hampered by difficulties in identifying and selecting specific cardiac progenitor cells from the mixed population of differentiating cells. We report the generation of stable transgenic hESC lines, using lentiviral vectors, and single-cell clones that express a reporter gene (eGFP) under the transcriptional control of a cardiac-specific promoter (the human myosin light chain-2V promoter). Our results demonstrate the appearance of eGFP-expressing cells during the differentiation of the hESC as embryoid bodies (EBs) that can be identified and sorted using FACS (purity95%, viability85%). The eGFP-expressing cells were stained positively for cardiac-specific proteins (93%), expressed cardiac-specific genes, displayed cardiac-specific action-potentials, and could form stable myocardial cell grafts following in vivo cell transplantation. The generation of these transgenic hESC lines may be used to identify and study early cardiac precursors for developmental studies, to robustly quantify the extent of cardiomyocyte differentiation, to label the cells for in vivo grafting, and to allow derivation of purified cell populations of cardiomyocytes for future myocardial cell therapy strategies.
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- 2007
27. Tissue Engineering of Vascularized Cardiac Muscle From Human Embryonic Stem Cells
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Lior Gepstein, Amira Gepstein, Oren Caspi, Yaara Basevitch, Shulamit Levenberg, Ayelet Lesman, Gil Arbel, and Irit Huber Manhal Habib
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Muscle tissue ,Pathology ,medicine.medical_specialty ,Physiology ,Angiogenesis ,Cell Culture Techniques ,Neovascularization, Physiologic ,Biology ,Mural cell ,Tissue engineering ,medicine ,Humans ,Myocytes, Cardiac ,Cells, Cultured ,Embryonic Stem Cells ,Cell Proliferation ,Microscopy, Confocal ,Tissue Engineering ,Myocardium ,Cardiac muscle ,Coronary Vessels ,Embryonic stem cell ,Transplantation ,medicine.anatomical_structure ,Stem cell ,Cardiology and Cardiovascular Medicine - Abstract
Transplantation of a tissue-engineered heart muscle represents a novel experimental therapeutic paradigm for myocardial diseases. However, this strategy has been hampered by the lack of sources for human cardiomyocytes and by the scarce vasculature in the ischemic area limiting the engraftment and survival of the transplanted muscle. Beyond the necessity of endothelial capillaries for the delivery of oxygen and nutrients to the grafted muscle tissue, interactions between endothelial and cardiomyocyte cells may also play a key role in promoting cell survival and proliferation. In the present study, we describe the formation of synchronously contracting engineered human cardiac tissue derived from human embryonic stem cells containing endothelial vessel networks. The 3D muscle consisted of cardiomyocytes, endothelial cells (ECs), and embryonic fibroblasts (EmFs). The formed vessels were further stabilized by the presence of mural cells originating from the EmFs. The presence of EmFs decreased EC death and increased EC proliferation. Moreover, the presence of endothelial capillaries augmented cardiomyocyte proliferation and did not hamper cardiomyocyte orientation and alignment. Immunostaining, ultrastructural analysis (using transmission electron microscopy), RT-PCR, pharmacological, and confocal laser calcium imaging studies demonstrated the presence of cardiac-specific molecular, ultrastructural, and functional properties of the generated tissue constructs with synchronous activity mediated by action potential propagation through gap junctions. In summary, this is the first report of the construction of 3D vascularized human cardiac tissue that may have unique applications for studies of cardiac development, function, and tissue replacement therapy.
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- 2007
28. Pulmonary arterial capacitance in patients with heart failure and reactive pulmonary hypertension
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Robert, Dragu, Shmuel, Rispler, Manhal, Habib, Haitham, Sholy, Haim, Hammerman, Nazzareno, Galie, Doron, Aronson, Dragu, Robert, Rispler, Shmuel, Habib, Manhal, Sholy, Haitham, Hammerman, Haim, Galie, Nazzareno, and Aronson, Doron
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Heart Failure ,Male ,Cardiac Catheterization ,Hypertension, Pulmonary ,Medicine (all) ,Middle Aged ,Pulmonary Artery ,Pulmonary hypertension ,Pulse pressure ,Case-Control Studies ,Vascular Capacitance ,Humans ,Female ,Pulmonary arterial capacitance ,Case-Control Studie ,Cardiology and Cardiovascular Medicine ,Aged ,Human - Abstract
AIMS: Reactive pulmonary hypertension (PH) is a severe form of PH secondary to left-sided heart failure (HF). Given the structural and functional abnormalities in the pulmonary vasculature that occur in reactive PH, we hypothesized that pulmonary artery capacitance (PAC) may be profoundly affected, with implications for clinical outcome. METHODS AND RESULTS: We studied 393 HF patients of whom 124 (32%) were classified as having passive PH and 140 (36%) as having reactive PH, and 91 patients with pulmonary arterial hypertension (PAH). Mean PAC was highest in patients without PH (4.5 ± 2.1 mL/mmHg), followed by the passive PH group (2.8 ± 1.4 mL/mmHg) and was lowest in those with reactive PH (1.8 ± 0.7 mL/mmHg) (P = 0.0001). PAC and pulmonary vascular resistance (PVR) fitted well to a hyperbolic inverse relationship (PAC = 0.25/PVR, R(2) = 0.70), with reactive PH patients dispersed almost predominantly on the flat part of the curve where a reduction in PVR is associated with a small improvement in PAC. Elevated PCWP was associated with a significant lowering of PAC for any PVR (P = 0.036). During a median follow-up of 31 months, both reactive PH [hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.14-4.46, P = 0.02] and reduced PAC (HR 0.72 per 1 mL/mmHg increase, 95% CI 0.59-0.88, P = 0.001) were independent predictors of mortality. CONCLUSIONS: The development of reactive PH is associated with a marked reduction in PAC. PAC is a strong independent haemodynamic marker of mortality in HF and may contribute to the increased mortality associated with reactive PH.
- Published
- 2015
29. Ethnic differences in population approach and experience regarding complementary-alternative medicine (CAM)
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Manhal Habib, Norberto Krivoy, and Zaher S. Azzam
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Adult ,Complementary Therapies ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Epidemiology ,Judaism ,Population ,Alternative medicine ,Ethnic group ,Sex Factors ,medicine ,Humans ,Outpatient clinic ,Pharmacology (medical) ,education ,Aged ,education.field_of_study ,Traditional medicine ,business.industry ,Patient Visit ,Middle Aged ,humanities ,Arabs ,Jews ,Family medicine ,Arab population ,Female ,Complementary medicine ,business - Abstract
Purpose The aim of this survey was to characterize one urban Arab population who turns to complementary-alternative medicine (CAM). Methods Outpatient participants were selected randomly by their ethnical affiliation. The questionnaire was filled during patient visit to their assigned urban outpatient clinic. The answers to the first two questions determined whether the questionnaire was to be completed or not (if at least one answer was Yes, the questionnaire was completed). Results More males (19%) seek for CAM in the Arab group in comparison to more females in the Jewish population (27%). Fifteen per cent and 7% of the individuals in the Jewish and Arab groups who used CAM have academic education. Fifty-two per cent and 27% of the Jewish and Arab populations declared themselves seculars, 72% of the Arab individuals declared to be traditionalists-religious-orthodox in their believes in comparison to 47% in the Jewish population. Twenty-eight per cent and 0% in the Jewish and Arab populations, respectively, preferred a conventional doctor (MD) in CAM practice. More than 30% in both populations preferred CAM to be delivered in medical and nursing schools. Conclusions Forty per cent and 31% in the Jewish and Arab groups experienced complementary medicine intervention at least once. When comparing people who used complementary medicine to those who did not, it is observed that the percentage of individuals holding academic degrees in the Jewish group is higher than in the Arab interviewed in the group utilizing complementary medicine. Traditionalist-religious-orthodox individuals seek more complementary medicine in the Arab population (72%) in comparison to 47% in the Jewish individuals. Only 17% of the Arab individuals and 19% in the Jewish group knew about the adverse reactions caused by CAM therapies. More than 30% in both ethnic groups were in favor of ‘legalizing’ complementary medicine. Copyright © 2005 John Wiley & Sons, Ltd.
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- 2006
30. Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients
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Aaron Winterstern, Manhal Habib, Lior Gepstein, Amira Gepstein, Limor Zwi-Dantsis, Irit Huber, and Gil Arbel
- Subjects
medicine.medical_specialty ,Cell Survival ,Cellular differentiation ,Genetic Vectors ,Induced Pluripotent Stem Cells ,Karyotype ,Transplantation, Heterologous ,Kruppel-Like Transcription Factors ,030204 cardiovascular system & hematology ,Regenerative medicine ,Cell therapy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Kruppel-Like Factor 4 ,0302 clinical medicine ,SOX2 ,Internal medicine ,Medicine ,Animals ,Humans ,Myocytes, Cardiac ,Transgenes ,Induced pluripotent stem cell ,030304 developmental biology ,Heart Failure ,0303 health sciences ,business.industry ,SOXB1 Transcription Factors ,Cell Differentiation ,medicine.disease ,Cellular Reprogramming ,3. Good health ,Cell biology ,Rats ,Transplantation ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Reprogramming ,Octamer Transcription Factor-3 - Abstract
Aims Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges. We aimed to derive hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte differentiation, to characterize the generated hiPSC-derived cardiomyocytes (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac tissue. Methods and results Dermal fibroblasts from two HF patients were reprogrammed by retroviral delivery of Oct4 , Sox2 , and Klf4 or by using an excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed adequate reprogramming properties and could be induced to differentiate into cardiomyocytes with the same efficiency as control hiPSCs (derived from human foreskin fibroblasts). Gene expression and immunostaining studies confirmed the cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation. Next, functional integration and synchronized electrical activities were demonstrated between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally, in vivo transplantation studies in the rat heart revealed the ability of the HF-hiPSC-CMs to engraft, survive, and structurally integrate with host cardiomyocytes. Conclusions Human-induced pluripotent stem cells can be established from patients with advanced heart failure and coaxed to differentiate into cardiomyocytes, which can integrate with host cardiac tissue. This novel source for patient-specific heart cells may bring a unique value to the emerging field of cardiac regenerative medicine.
- Published
- 2012
31. Transplantation of a tissue-engineered human vascularized cardiac muscle
- Author
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Shulamit Levenberg, Oren Caspi, Manhal Habib, Ayelet Lesman, Gil Arbel, Lior Gepstein, and Amira Gepstein
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Biomedical Engineering ,Bioengineering ,Biochemistry ,Umbilical vein ,Cell Line ,Biomaterials ,Rats, Sprague-Dawley ,Mice ,Tissue engineering ,In vivo ,Absorbable Implants ,medicine ,Animals ,Humans ,Embryonic Stem Cells ,Tissue Engineering ,Chemistry ,Regeneration (biology) ,Myocardium ,Cardiac muscle ,Fibroblasts ,Tissue Graft ,Coronary Vessels ,Coculture Techniques ,Rats ,Transplantation ,medicine.anatomical_structure ,Ex vivo ,Biomedical engineering - Abstract
Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human-specific CD31 and alpha-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3 +/- 8/mm(3), p < 0.05) when compared with scaffolds containing only CMs (39.0 +/- 14.4/mm(3)). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion.
- Published
- 2009
32. Hydrogels for cardiac tissue regeneration
- Author
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Manhal Habib, Dror Seliktar, Lior Gepstein, Keren Shapira, and Daniel Dikovsky
- Subjects
chemistry.chemical_classification ,Materials science ,Guided Tissue Regeneration ,Regeneration (biology) ,Myocardium ,Biomedical Engineering ,Cardiac muscle ,Biomaterial ,Biocompatible Materials ,Hydrogels ,General Medicine ,Polymer ,Biomaterials ,medicine.anatomical_structure ,Photopolymer ,Polymerization ,chemistry ,Tissue engineering ,Biomimetic Materials ,Self-healing hydrogels ,medicine ,Animals ,Humans ,Biomedical engineering - Abstract
Our research is focused on the design of engineered biomaterials that can harness natural cellular and molecular healing pathways to enhance functional tissue regeneration. Two important considerations for tissue regeneration are induction and remodeling. Although the healing process that leads to functional regeneration relies on numerous biological events, it can often be catalyzed and sustained by a single inductive biological factor. Ideally, one can engineer a synthetic biomaterial to possess inductive healing properties using protein immobilization techniques and also to be susceptible to cell-mediated remodeling. Toward this goal, we developed a novel biomimetic material that can harness the inductive properties of the natural blood clot protein fibrinogen. Using synthetic polymer conjugation chemistry, we modify the fibrinogen molecule with poly(ethylene glycol) (PEG) to create a biosynthetic precursor with tunable physicochemical properties based on the molecular relationship between the two constituents [1]. A hydrogel matrix is formed from the biocompatible liquid precursor by non-toxic free-radical polymerization using light activation (photopolymerization). The susceptibility of this hydrogel biomaterial to protease degradation and consequent cell-mediated remodeling is precisely controlled by the amount and size of the PEG constituent in the polymer network [4]. The protein-based material also conveys inductive signals to cells through bioactive sites on the fibrinogen backbone. This biomimetic material has been tested in cell-based tissue engineering applications and in acellular in vivo tissue regeneration applications with bone [7], cartilage [2,9], and cardiac tissues [11,12]. In cardiac cell therapy for example, the inability to locally deliver and retain cell grafts in the damaged cardiac muscle has limited the effectiveness of this important treatment option. As cardiac stem cell research addresses the issue of cell sourcing, there is still a need for biomaterials that can effectively deliver the cell grafts into the infarct region and promote structural and functional integration with the native myocardium, without damaging the cells or the heart muscle [3]. Injectable hydrogel biomaterials based on hydrophilic, biocompatible polymers are an optimal delivery system for cardiac tissue engineering [6]; the high water content of these polymers creates a tissue-like environment, and in situ polymerization provides a means of injection and gelation of a cell suspension polymer mixture directly in the site of the infarct [8]. In the current investigation, we explore the use PEGylated fibrinogen polymer hydrogels for myocardial tissue engineering. The optimization of hydrogel composition and cell seeding density were assessed
- Published
- 2008
33. Abstract 2877: A Combined Cell Therapy and In Situ Tissue Engineering Approach for Myocardial Repair
- Author
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Manhal Habib, Keren Shapira, Oren Caspi, Gil Arbel, Amira Gepstein, Dror Seliktar, and Lior Gepstein
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Cell replacement and tissue engineering strategies are emerging as novel therapeutic paradigms for myocardial repair. Here we tested the hypothesis that a combined in situ tissue engineering and cell delivery strategy utilizing transplantable hydrogel-embedded cardiomyocytes [either neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)] will improve functional performance in the rat infarction model. Methods and results : A novel liquid biodegradable PEGylated fibrinogen was developed, which was proved to be compatible with cardiomyocyte survival and maturation in vitro . Photopolymerization using UV beam results in a rapid liquid to hydrogel transformation. Animals were randomized to injection of saline, NRVCMs alone, the biopolymer alone, or the combined delivery of the biopolymer and the NRVCMs. Histological studies demonstrated the presence of the hydrogel-embedded cardiomyocytes within the scar tissue. The biopolymer was fully absorbed one month following delivery. Echocardiography revealed typical post-infarction remodeling in the control group (saline injection) as manifested by the deterioration of ejection fraction (EF) by 28±3% (from 43±2% at post-injury baseline to 30±2% at 4 weeks). Injection of the biopolymer or NRVCMs alone prevented this remodeling process (39±2% to 39±2% and 43±3% to 43±2% respectively; p Conclusions: We describe a novel injectable in-situ-forming hydrogel that functions as an efficient cardiomyocyte carrier for both NRVCM and hESC-CMs and acts synergistically with the grafted cells to prevent the unfavorable post-infarction cardiac remodeling and improve ventricular function in rats.
- Published
- 2008
34. Myocardial Regeneration via Embryonic Stem Cell-Derived Cardiomyocytes
- Author
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Manhal Habib and Lior Gepstein
- Subjects
Regeneration (biology) ,Biology ,Embryonic stem cell ,Cell biology - Published
- 2007
35. Effect of adding Eruca Sativa Seeds and Vit.E.on the diet of mal Awassi lambs on same production traits
- Author
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Al-Fityin, Manhal Habib Salman, primary
- Published
- 2009
- Full Text
- View/download PDF
36. Application of Nanotechnology and Chemical Sensors for Diagnosis of Decompensated Heart Failure by Respiratory Samples
- Author
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Manhal Habib MD, PhD, Principal investigator
- Published
- 2017
37. Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial.
- Author
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D'Amario D, Meerkin D, Restivo A, Ince H, Sievert H, Wiese A, Schaefer U, Trani C, Bayes-Genis A, Leyva F, Whinnett ZI, Di Mario C, Jonas M, Manhal H, Amat-Santos IJ, Del Trigo M, Gal TB, Avraham BB, Hasin T, Feickert S, D'Ancona G, Altisent OA, Koren O, Caspi O, Abraham WT, Crea F, Anker SD, Kornowski R, and Perl L
- Subjects
- Humans, Cardiac Catheterization methods, Prospective Studies, Pulmonary Wedge Pressure, Atrial Pressure, Heart Failure
- Abstract
Aims: In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients., Methods and Results: The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05)., Conclusion: The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2023
- Full Text
- View/download PDF
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