Cardiomyopathy Research
The Inherited Cardiomyopathy Program has active research investigations in three core areas:
- Genotype-Phenotype Correlation: the goal of these projects is to advance our understanding of the relationship between putative disease causing mutations and disease expression within and between families. Improved understanding of this relationship is critical to the provision of outstanding clinical care and to development of novel therapies.
- Prevalence and Disease Outcome: because recognition of inherited disease is often limited by practice patterns which are in turn heavily influenced by the urgent demands of caring for sick patients, an important proportion of inherited disease is misdiagnosed. As an example, we discovered that nearly 25% of patients undergoing heart transplant for end stage cardiomyopathy have inherited disease, whereas current recognition of inherited disease in this population is limited to 4% of patients. This research was presented at the International Society of Heart and Lung Transplant in Prague (2012).
- Novel Gene Discovery: collaborating with Dr. Arya Mani and the Yale Department of Genetics, and the National Institutes of Health, we helping families with clear inherited disease uncover the pathogenic gene mutation responsible for their family’s disease. Discoveries in this arena open disease treatment to novel therapeutics and improved prognostication.
PubMed List
2022
- Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond.Morelli C, Ingrasciotta G, Jacoby D, Masri A, Olivotto I. Eur J Intern Med. 2022 May 6; 2022 May 6. PMID: 35534374.
- Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Circulation. 2022 Apr 19; 2022 Apr 6. PMID: 35384713.
- Risk and predictors of mortality after implantable cardioverter-defibrillator implantation in patients with sarcoid cardiomyopathy.Higgins AY, Annapureddy AR, Wang Y, Minges KE, Bellumkonda L, Lampert R, Rosenfeld LE, Jacoby DL, Curtis JP, Miller EJ, Freeman JV. Am Heart J. 2022 Apr; 2021 Dec 27. PMID: 34968442.
2021
- Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy.Hegde SM, Lester SJ, Solomon SD, Michels M, Elliott PM, Nagueh SF, Choudhury L, Zemanek D, Zwas DR, Jacoby D, Wang A, Ho CY, Li W, Sehnert AJ, Olivotto I, Abraham TP. J Am Coll Cardiol. 2021 Dec 21. PMID: 34915982.
- Predictors of Major Atrial Fibrillation Endpoints in the National Heart, Lung, and Blood Institute HCMR.Kramer CM, DiMarco JP, Kolm P, Ho CY, Desai MY, Kwong RY, Dolman SF, Desvigne-Nickens P, Geller N, Kim DY, Maron MS, Appelbaum E, Jerosch-Herold M, Friedrich MG, Schulz-Menger J, Piechnik SK, Mahmod M, Jacoby D, White J, Chiribiri A, Helms A, Choudhury L, Michels M, Bradlow W, Salerno M, Dawson DK, Weinsaft JW, Berry C, Nagueh SF, Buccarelli-Ducci C, Owens A, Casadei B, Watkins H, Weintraub WS, Neubauer S. JACC Clin Electrophysiol. 2021 Nov; 2021 Jun 30. PMID: 34217663.
- Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy.Nauffal V, Marstrand P, Han L, Parikh VN, Helms AS, Ingles J, Jacoby D, Lakdawala NK, Kapur S, Michels M, Owens AT, Ashley EA, Pereira AC, Rossano JW, Saberi S, Semsarian C, Ware JS, Wittekind SG, Day S, Olivotto I, Ho CY. Eur Heart J. 2021 Oct 7. PMID: 34491319.
- Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction.Abou Ziki MD, Bhat N, Neogi A, Driscoll TP, Ugwu N, Liu Y, Smith E, Abboud JM, Chouairi S, Schwartz MA, Akar JG, Mani A. Hum Mutat. 2021 Oct; 2021 Jul 29. PMID: 34289528.
- Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation.Sewanan LR, Park J, Rynkiewicz MJ, Racca AW, Papoutsidakis N, Schwan J, Jacoby DL, Moore JR, Lehman W, Qyang Y, Campbell SG. J Gen Physiol. 2021 Sep 6; 2021 Jul 28. PMID: 34319370.
- Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation.Thompson AD, Helms AS, Kannan A, Yob J, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Mazzarotto F, Olivotto I, Ho CY, Day SM. Genet Med. 2021 Jul; 2021 Mar 29. PMID: 33782553.
- Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.Spertus JA, Fine JT, Elliott P, Ho CY, Olivotto I, Saberi S, Li W, Dolan C, Reaney M, Sehnert AJ, Jacoby D. Lancet. 2021 Jun 26; 2021 May 15. PMID: 34004177.
- Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, Pereira AC, Ingles J, Semsarian C, Jacoby D, Colan SD, Rossano JW, Wittekind SG, Ware JS, Saberi S, Helms AS, Ho CY. Eur Heart J. 2021 May 21. PMID: 33769460.
- Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.Goli R, Li J, Brandimarto J, Levine LD, Riis V, McAfee Q, DePalma S, Haghighi A, Seidman JG, Seidman CE, Jacoby D, Macones G, Judge DP, Rana S, Margulies KB, Cappola TP, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Alexis JD, Boehmer J, Kamiya C, Gustafsson F, Damm P, Ersbøll AS, Goland S, Hilfiker-Kleiner D, McNamara DM, Arany Z. Circulation. 2021 May 11; 2021 Apr 20. PMID: 33874732.
- Impact of the new heart allocation policy on patients with restrictive, hypertrophic, or congenital cardiomyopathies.Chouairi F, Mullan CW, Sen S, Mori M, Fuery M, Elder RW, Lesse J, Norton K, Clark KA, Miller PE, Mulligan D, Formica R, Rogers JG, Jacoby D, Maulion C, Anwer M, Geirsson A, Desai NR, Ahmad T. PLoS One. 2021; 2021 Mar 2. PMID: 33651802.
- Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM Cardiac Magnetic Resonance Substudy Analysis.Saberi S, Cardim N, Yamani M, Schulz-Menger J, Li W, Florea V, Sehnert AJ, Kwong RY, Jerosch-Herold M, Masri A, Owens A, Lakdawala NK, Kramer CM, Sherrid M, Seidler T, Wang A, Sedaghat-Hamedani F, Meder B, Havakuk O, Jacoby D. Circulation. 2021 Feb 9; 2020 Nov 15. PMID: 33190524.
- Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy.Lakdawala NK, Olivotto I, Day SM, Han L, Ashley EA, Michels M, Ingles J, Semsarian C, Jacoby D, Jefferies JL, Colan SD, Pereira AC, Rossano JW, Wittekind S, Ware JS, Saberi S, Helms AS, Cirino AL, Leinwand LA, Seidman CE, Ho CY. Circ Genom Precis Med. 2021 Feb; 2020 Dec 7. PMID: 33284039.
- Mavacamten for hypertrophic obstructive cardiomyopathy - Authors' reply.Jacoby D, Ho CY, Lester SJ, Wang A, Olivotto I. Lancet. 2021 Jan 30. PMID: 33516332.
- Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions.Zhang X, Walsh R, Whiffin N, Buchan R, Midwinter W, Wilk A, Govind R, Li N, Ahmad M, Mazzarotto F, Roberts A, Theotokis PI, Mazaika E, Allouba M, de Marvao A, Pua CJ, Day SM, Ashley E, Colan SD, Michels M, Pereira AC, Jacoby D, Ho CY, Olivotto I, Gunnarsson GT, Jefferies JL, Semsarian C, Ingles J, O'Regan DP, Aguib Y, Yacoub MH, Cook SA, Barton PJR, Bottolo L, Ware JS. Genet Med. 2021 Jan; 2020 Oct 13. PMID: 33046849.
2020
- Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.Helms AS, Thompson AD, Glazier AA, Hafeez N, Kabani S, Rodriguez J, Yob JM, Woolcock H, Mazzarotto F, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Olivotto I, Ho CY, Day SM. Circ Genom Precis Med. 2020 Oct; 2020 Aug 25. PMID: 32841044.
- Survival Following Implantable Cardioverter-Defibrillator Implantation in Patients With Amyloid Cardiomyopathy.Higgins AY, Annapureddy AR, Wang Y, Minges KE, Lampert R, Rosenfeld LE, Jacoby DL, Curtis JP, Miller EJ, Freeman JV. J Am Heart Assoc. 2020 Sep 15; 2020 Sep 1. PMID: 32867553.
- Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial.Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D. Lancet. 2020 Sep 12; 2020 Aug 29. PMID: 32871100.