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Ravi Karra

Associate Professor of Medicine
Medicine, Cardiology
Box 102152 Med Ctr, Durham, NC 27710
247A CARL Building, Durham, NC 27710

Selected Publications


Cardioprotective effects of the angiocrine CRELD2 after ischemic injury

Journal Article Nature Cardiovascular Research · February 1, 2024 In acute myocardial infarction treated with reperfusion, functional preservation of myocardium requires an angiogenic response. A new study shows that CRELD2, an endoplasmic reticulum (ER)-resident protein induced in response to ER stress, acts as an angio ... Full text Cite

LMNA Cardiomyopathy: Important Considerations for the Heart Failure Clinician.

Journal Article J Card Fail · December 2023 BACKGROUND: A diagnosis of Lamin proteins A and C cardiomyopathy (LMNA-CM) not only impacts disease prognosis, but also leads to specific guideline-recommended treatment options for these patients. This etiology is fundamentally different from other geneti ... Full text Link to item Cite

Incidence and Predictors of Relapse After Weaning Immune Suppressive Therapy in Cardiac Sarcoidosis.

Journal Article Am J Cardiol · October 1, 2023 Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients ... Full text Link to item Cite

Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure.

Journal Article J Card Fail · June 2023 BACKGROUND: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We measured 25 proteins rel ... Full text Link to item Cite

From mechanisms of heart failure to clinical heart success.

Journal Article Disease models & mechanisms · May 2023 Full text Cite

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article Cell Stem Cell · January 5, 2023 The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ... Full text Link to item Cite

MIMICKING THE GREAT MIMICKER: LMNA CARDIOMYOPATHY PRESENTING AS ISOLATED CARDIAC SARCOIDOSIS

Conference JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY · 2023 Cite

Toward improved understanding of cardiac development and congenital heart disease: The advent of cardiac organoids.

Journal Article J Thorac Cardiovasc Surg · December 2022 Human cardiac organoid systems hold significant promise for mechanistic studies of early heart morphogenesis and an improved understanding of congenital cardiac disease. ... Full text Link to item Cite

Cardiac Sarcoidosis: Current Approaches to Diagnosis and Management.

Journal Article Curr Allergy Asthma Rep · December 2022 PURPOSE OF REVIEW: Cardiac sarcoidosis (CS) is an important cause of non-ischemic cardiomyopathy and has specific diagnostic and therapeutic considerations. With advances in imaging techniques and treatment approaches, the approach to monitoring disease pr ... Full text Link to item Cite

Coupled myovascular expansion directs cardiac growth and regeneration.

Journal Article Development · September 15, 2022 Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mou ... Full text Link to item Cite

Recovery of left ventricular function is associated with improved outcomes in LVAD recipients.

Journal Article J Heart Lung Transplant · August 2022 BACKGROUND: The significance of recovered left ventricular ejection fraction (LVEF) in LVAD recipients, outside of pump explantation, is unclear. METHODS: Patients undergoing first LVAD implantation at Duke University Hospital between 2006 and 2017 were ev ... Full text Link to item Cite

Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization.

Journal Article Circulation · April 19, 2022 BACKGROUND: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. M ... Full text Link to item Cite

Heart Sound Analysis in Individuals Supported With Left Ventricular Assist Devices.

Journal Article IEEE Trans Biomed Eng · October 2021 OBJECTIVE: LVADs are surgically implanted mechanical pumps that improve survival rates of individuals with advanced heart failure. LVAD therapy is associated with high morbidity, which can be partially attributed to challenges with detecting LVAD complicat ... Full text Link to item Cite

Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial.

Journal Article Eur J Heart Fail · July 2021 AIMS: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on ca ... Full text Link to item Cite

Cardioprotective effects of the angiocrine CRELD2 after ischemic injury

Journal Article Nature Cardiovascular Research · February 1, 2024 In acute myocardial infarction treated with reperfusion, functional preservation of myocardium requires an angiogenic response. A new study shows that CRELD2, an endoplasmic reticulum (ER)-resident protein induced in response to ER stress, acts as an angio ... Full text Cite

LMNA Cardiomyopathy: Important Considerations for the Heart Failure Clinician.

Journal Article J Card Fail · December 2023 BACKGROUND: A diagnosis of Lamin proteins A and C cardiomyopathy (LMNA-CM) not only impacts disease prognosis, but also leads to specific guideline-recommended treatment options for these patients. This etiology is fundamentally different from other geneti ... Full text Link to item Cite

Incidence and Predictors of Relapse After Weaning Immune Suppressive Therapy in Cardiac Sarcoidosis.

Journal Article Am J Cardiol · October 1, 2023 Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients ... Full text Link to item Cite

Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure.

Journal Article J Card Fail · June 2023 BACKGROUND: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We measured 25 proteins rel ... Full text Link to item Cite

From mechanisms of heart failure to clinical heart success.

Journal Article Disease models & mechanisms · May 2023 Full text Cite

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article Cell Stem Cell · January 5, 2023 The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ... Full text Link to item Cite

MIMICKING THE GREAT MIMICKER: LMNA CARDIOMYOPATHY PRESENTING AS ISOLATED CARDIAC SARCOIDOSIS

Conference JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY · 2023 Cite

Toward improved understanding of cardiac development and congenital heart disease: The advent of cardiac organoids.

Journal Article J Thorac Cardiovasc Surg · December 2022 Human cardiac organoid systems hold significant promise for mechanistic studies of early heart morphogenesis and an improved understanding of congenital cardiac disease. ... Full text Link to item Cite

Cardiac Sarcoidosis: Current Approaches to Diagnosis and Management.

Journal Article Curr Allergy Asthma Rep · December 2022 PURPOSE OF REVIEW: Cardiac sarcoidosis (CS) is an important cause of non-ischemic cardiomyopathy and has specific diagnostic and therapeutic considerations. With advances in imaging techniques and treatment approaches, the approach to monitoring disease pr ... Full text Link to item Cite

Coupled myovascular expansion directs cardiac growth and regeneration.

Journal Article Development · September 15, 2022 Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mou ... Full text Link to item Cite

Recovery of left ventricular function is associated with improved outcomes in LVAD recipients.

Journal Article J Heart Lung Transplant · August 2022 BACKGROUND: The significance of recovered left ventricular ejection fraction (LVEF) in LVAD recipients, outside of pump explantation, is unclear. METHODS: Patients undergoing first LVAD implantation at Duke University Hospital between 2006 and 2017 were ev ... Full text Link to item Cite

Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization.

Journal Article Circulation · April 19, 2022 BACKGROUND: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. M ... Full text Link to item Cite

Heart Sound Analysis in Individuals Supported With Left Ventricular Assist Devices.

Journal Article IEEE Trans Biomed Eng · October 2021 OBJECTIVE: LVADs are surgically implanted mechanical pumps that improve survival rates of individuals with advanced heart failure. LVAD therapy is associated with high morbidity, which can be partially attributed to challenges with detecting LVAD complicat ... Full text Link to item Cite

Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial.

Journal Article Eur J Heart Fail · July 2021 AIMS: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on ca ... Full text Link to item Cite

Novel Acoustic Biomarker of Quality of Life in Left Ventricular Assist Device Recipients.

Journal Article J Am Heart Assoc · March 16, 2021 Background Although technological advances to pump design have improved survival, left ventricular assist device (LVAD) recipients experience variable improvements in quality of life. Methods for optimizing LVAD support to improve quality of life are neede ... Full text Link to item Cite

A Roadmap to Heart Regeneration Through Conserved Mechanisms in Zebrafish and Mammals.

Journal Article Curr Cardiol Rep · March 2, 2021 PURPOSE OF REVIEW: The replenishment of lost or damaged myocardium has the potential to reverse heart failure, making heart regeneration a goal for cardiovascular medicine. Unlike adult mammals, injury to the zebrafish or neonatal mouse heart induces a rob ... Full text Link to item Cite

Coupled myovascular expansion directs cardiac growth and regeneration

Journal Article · January 21, 2021 ABSTRACTBackgroundHeart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile p ... Full text Cite

Differentiation of Human Induced Pluripotent Stem Cells into Epicardial-Like Cells.

Chapter · 2021 The epicardium is a multipotent cell layer that is vital to myocardial development and regeneration. Epicardial cells contribute to cardiac fibroblast and smooth muscle populations of the heart and secrete paracrine factors that promote cardiomyocyte proli ... Full text Link to item Cite

Evaluating the effect of longitudinal dose and INR data on maintenance warfarin dose predictions

Conference BHI 2021 - 2021 IEEE EMBS International Conference on Biomedical and Health Informatics, Proceedings · January 1, 2021 Warfarin, a commonly prescribed drug to prevent blood clots, has a highly variable individual response. Determining a maintenance warfarin dose that achieves a therapeutic blood clotting time, as measured by the international normalized ratio (INR), is cru ... Full text Cite

Heart Sound Analysis in Individuals Supported with Left Ventricular Assist Device: A First Look

Conference Computing in Cardiology · September 13, 2020 The left ventricular assist device (LVAD) has emerged as a bridge or alternative to heart transplant in individuals with advanced heart failure. However, the LVAD recipient population currently faces high rehospitalization rates. Remote analysis of precord ... Full text Cite

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial.

Journal Article Eur J Heart Fail · September 2020 AIMS: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contractio ... Full text Link to item Cite

Cardiac Implantable Electronic Devices: A Window Into the Evolution of Conduction Disease in Cardiac Amyloidosis.

Journal Article JACC Clin Electrophysiol · September 2020 OBJECTIVES: This study characterized the relationship between conduction disease and cardiac amyloidosis (CA) through longitudinal analysis of cardiac implantable electronic device (CIED) data. BACKGROUND: Bradyarrhythmias and tachyarrhythmias are commonly ... Full text Link to item Cite

Clonal Analysis of the Neonatal Mouse Heart using Nearest Neighbor Modeling.

Journal Article J Vis Exp · August 22, 2020 By replacing lost or dysfunctional myocardium, tissue regeneration is a promising approach to treat heart failure. However, the challenge of detecting bona fide heart regeneration limits the validation of potential regenerative factors. One method to detec ... Full text Link to item Cite

Heterogeneous Outcomes of Heart Failure with Better Ejection Fraction.

Journal Article J Cardiovasc Transl Res · April 2020 We evaluated the heterogeneity of outcomes among heart failure patients with ventricular recovery. The BEST trial studied patients with left ventricular ejection fraction (LVEF) ≤ 35%. Serial LVEF assessment was performed at baseline, 3 months, and 12 mont ... Full text Link to item Cite

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration.

Journal Article Elife · November 8, 2019 In recent years, there has been increasing interest in the role of lymphatics in organ repair and regeneration, due to their importance in immune surveillance and fluid homeostasis. Experimental approaches aimed at boosting lymphangiogenesis following myoc ... Full text Link to item Cite

Epigenome-Wide Association Study for All-Cause Mortality in a Cardiovascular Cohort Identifies Differential Methylation in Castor Zinc Finger 1 (CASZ1).

Journal Article J Am Heart Assoc · November 5, 2019 Background DNA methylation is implicated in many chronic diseases and may contribute to mortality. Therefore, we conducted an epigenome-wide association study (EWAS) for all-cause mortality with whole-transcriptome data in a cardiovascular cohort (CATHGEN ... Full text Link to item Cite

Acoustic Signatures of Left Ventricular Assist Device Thrombosis.

Journal Article J Eng Sci Med Diagn Ther · May 2019 Left ventricular assist devices (LVADs) are life-saving, surgically implanted mechanical heart pumps used to treat patients with advanced heart failure (HF). While life-saving, LVAD support is associated with a high incidence of complications, making early ... Full text Link to item Cite

Endothelial Contributions to Zebrafish Heart Regeneration.

Journal Article J Cardiovasc Dev Dis · December 11, 2018 Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. In particular, recent work has identified revascularization of the wound to be a sentinel event during heart regener ... Full text Link to item Cite

Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.

Journal Article Proc Natl Acad Sci U S A · August 28, 2018 During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not know ... Full text Link to item Cite

The relationship between cardiac endothelium and fibroblasts: it's complicated.

Journal Article J Clin Invest · August 1, 2017 Coronary revascularization is an effective means of treating ischemic heart disease; however, current therapeutic revascularization strategies are limited to large caliber vessels. Because the mammalian heart scars following cardiac injury, recent work sho ... Full text Link to item Cite

Resolving Heart Regeneration by Replacement Histone Profiling.

Journal Article Dev Cell · February 27, 2017 Chromatin regulation is a principal mechanism governing animal development, yet it is unclear to what extent structural changes in chromatin underlie tissue regeneration. Non-mammalian vertebrates such as zebrafish activate cardiomyocyte (CM) division afte ... Full text Link to item Cite

Redirecting cardiac growth mechanisms for therapeutic regeneration.

Journal Article J Clin Invest · February 1, 2017 Heart failure is a major source of morbidity and mortality. Replacing lost myocardium with new tissue is a major goal of regenerative medicine. Unlike adult mammals, zebrafish and neonatal mice are capable of heart regeneration following cardiac injury. In ... Full text Link to item Cite

Deciphering Heart Regeneration by Histone Exchange Profiling.

Conference MOLECULAR BIOLOGY OF THE CELL · January 1, 2017 Link to item Cite

Modulation of tissue repair by regeneration enhancer elements.

Journal Article Nature · April 14, 2016 How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lep ... Full text Link to item Cite

Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.

Journal Article Development · January 15, 2016 In contrast to mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of cardiomyocytes spared from damage. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration th ... Full text Link to item Cite

Myocardial NF-κB activation is essential for zebrafish heart regeneration.

Journal Article Proc Natl Acad Sci U S A · October 27, 2015 Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferati ... Full text Link to item Cite

Back in Black.

Journal Article Dev Cell · June 22, 2015 In this issue of Developmental Cell, Iyengar and colleagues (2015) employ live imaging of melanocyte regeneration in adult zebrafish to define a bias in progenitor cell fates that enables both rapid pigment cell renewal and maintenance of regenerative capa ... Full text Link to item Cite

Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish.

Journal Article Elife · April 1, 2015 Featured Publication Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to st ... Full text Open Access Link to item Cite

Mediastinitis

Chapter · January 1, 2015 The mediastinum is the space in the thorax between the lungs; it houses the heart, great vessels, esophagus, trachea, thymus, and lymph nodes. The connective tissues of the mediastinum are continuous with the long fascial planes of the head and neck, one r ... Full text Cite

Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration.

Journal Article Dev Biol · October 15, 2013 Unlike adult mammals, adult zebrafish vigorously regenerate lost heart muscle in response to injury. The epicardium, a mesothelial cell layer enveloping the myocardium, is activated to proliferate after cardiac injury and can contribute vascular support ce ... Full text Link to item Cite

Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration.

Journal Article Proc Natl Acad Sci U S A · August 13, 2013 Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes ... Full text Link to item Cite

An injury-responsive gata4 program shapes the zebrafish cardiac ventricle.

Journal Article Curr Biol · July 8, 2013 A common principle of tissue regeneration is the reactivation of previously employed developmental programs. During zebrafish heart regeneration, cardiomyocytes in the cortical layer of the ventricle induce the transcription factor gene gata4 and prolifera ... Full text Link to item Cite

Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation.

Journal Article Circ Res · March 15, 2013 RATIONALE: Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). OBJECTIVE: To identify ... Full text Link to item Cite

Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5.

Journal Article Circ Res · June 22, 2012 RATIONALE: Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. OBJECTIVE: To assess the efficiency of direct fibroblast reprogramming via ... Full text Link to item Cite

Mediastinitis

Journal Article · January 1, 2010 The mediastinum is defined as the space in the thorax between the lungs; it houses the heart, great vessels, esophagus, trachea, thymus, and lymph nodes. The connective tissues of the mediastinum are continuous with the long fascial planes of the head and ... Full text Cite

Multipotent stem cells in cardiac regenerative therapy.

Journal Article Regen Med · March 2008 The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a 'first-in-man' approach using autologous stem cells from a variety of tissues. However, recent clinic ... Full text Link to item Cite

Cardiovascular Stem Cells in Regenerative Medicine: Ready for Prime Time?

Journal Article Drug Discov Today Ther Strateg · 2008 Restoration of cardiovascular function is the ultimate goal of stem cell-based therapy. In principle, cardiovascular stem cells can improve cardiac function via de novo cardiomyogenesis, enhanced myocardial neovascularization, and prevention of post-infarc ... Full text Link to item Cite

Risk factors for 1-year mortality after postoperative mediastinitis.

Journal Article J Thorac Cardiovasc Surg · September 2006 OBJECTIVE: Postoperative mediastinitis after median sternotomy is associated with disability and mortality. The aim of this study was to identify risk factors for mortality 1 year after postoperative mediastinitis diagnosis. METHODS: Postoperative mediasti ... Full text Link to item Cite

Molecular evidence for arterial repair in atherosclerosis.

Journal Article Proc Natl Acad Sci U S A · November 15, 2005 Atherosclerosis is a chronic inflammatory process and progresses through characteristic morphologic stages. We have shown previously that chronically injecting bone-marrow-derived vascular progenitor cells can effect arterial repair. This repair capacity d ... Full text Link to item Cite