Skeletal muscle, adipose tissue and cardiac metabolism in advanced heart failure
We are analyzing markers of systemic and local metabolism in patients with advanced heart failure. We perform a detailed functional assessment of patients with heart failure through functional testing, analysis of body composition and clinical performance. Molecular markers of local metabolism and their relation with circulating biomarkers are collected. We perform a histologic quantification of muscle fiber type distribution (oxidative vs. glycolytic), candidate gene analysis in muscle, myocardium and adipose tissue, protein expression analysis and a systematic biomarker analysis. Our hypothesis is that common transcriptional changes occur in a multitude of peripheral tissues in advanced heart failure and that these changes are reversible after hemodynamic correction through implantation of ventricular assist devices and after cardiac transplantation.
These studies are performed in collaboration with the Department of Surgery and the Irving Institute for Clinical and Translational Research - Biomarker Core Unit and Statistical Core Unit at Columbia University.
Relevant Publications:
Khan RS, Kato TS, Chokshi A, Chew M, Yu S, Wu C, Singh P, Cheema FH, Takayama H, Harris C, Reyes-Soffer G, Knöll R, Milting H, Naka Y, Mancini D, Schulze PC. Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation. Circ Heart Fail. 2012;5(3):340-8
Chokshi A, Drosatos K, Cheema FH, Ji R, Khawaja T, Yu S, Kato T, Khan R, Takayama H, Knöll R, Milting H, Chung CS, Jorde U, Naka Y, Mancini DM, Goldberg IJ, Schulze PC. Ventricular Assist Device Implantation Corrects Myocardial Lipotoxicity, Reverses Insulin Resistance and Normalizes Cardiac Metabolism in Patients with Advanced Heart Failure. Circulation. 2012;125(23):2844-53
Akat KM, Moore-McGriff D, Morozov P, Brown M, Gogakos T, Correa Da Rosa J, Mihailovic A, Sauer M, Ji R, Ramarathnam A, Totary-Jain H, Williams Z, Tuschl T, Schulze PC. Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. Proc Natl Acad Sci U S A. 2014;111(30):11151-6
These studies are performed in collaboration with the Department of Surgery and the Irving Institute for Clinical and Translational Research - Biomarker Core Unit and Statistical Core Unit at Columbia University.
Relevant Publications:
Khan RS, Kato TS, Chokshi A, Chew M, Yu S, Wu C, Singh P, Cheema FH, Takayama H, Harris C, Reyes-Soffer G, Knöll R, Milting H, Naka Y, Mancini D, Schulze PC. Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation. Circ Heart Fail. 2012;5(3):340-8
Chokshi A, Drosatos K, Cheema FH, Ji R, Khawaja T, Yu S, Kato T, Khan R, Takayama H, Knöll R, Milting H, Chung CS, Jorde U, Naka Y, Mancini DM, Goldberg IJ, Schulze PC. Ventricular Assist Device Implantation Corrects Myocardial Lipotoxicity, Reverses Insulin Resistance and Normalizes Cardiac Metabolism in Patients with Advanced Heart Failure. Circulation. 2012;125(23):2844-53
Akat KM, Moore-McGriff D, Morozov P, Brown M, Gogakos T, Correa Da Rosa J, Mihailovic A, Sauer M, Ji R, Ramarathnam A, Totary-Jain H, Williams Z, Tuschl T, Schulze PC. Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. Proc Natl Acad Sci U S A. 2014;111(30):11151-6
Glucose and lipid metabolism of skeletal muscle in cardiac disease states
Skeletal muscle is the primary target of insulin for glucose uptake and metabolism. Insulin resistance is a hallmark of inflammation and has been linked to increased morbidity and mortality in patients with cardiovascular disease such as heart failure and coronary artery disease. This translational research project focuses on the role of abnormal glucose and lipid metabolism and its relation to function parameters of muscle function (strength and fatigability). We systematically test muscle function in patients with heart failure (BIODEX) and analyze structural, molecular and metabolic changes in skeletal muscle biopsies. Using animal models of cardiac disease such as myocardial infarction and genetic cardiomyopathies, we test the role of metabolic and pharmacologic interventions in vivo. Cell culture models using C2C12 myoblasts and cardiomyocytes are used for the analysis of specific signaling events. We hypothesize a role of abnormal lipid metabolism in heart failure leading to accumulation of toxic lipid intermediates in skeletal muscle and myocardium.
This project is a collaboration with Dr. Ira Goldberg's group at Columbia University.
Relevant Publications:
Shin JY, Mendez-Lopez I, Wang Y, Hays AP, Tanji K, Lefkowitch JH, Schulze PC, Worman HJ, Dauer WT. Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance. Dev Cell. 2013;26:591-603
Chung CJ, Wu C, Jones M, Kato TS, Dam TT, Givens R, Templeton DL, Maurer MS, Naka Y, Takayama H, Mancini DM, Schulze PC. Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement. J Cardiac Fail. 2014;20(5):310-5
Khawaja T, Chokshi A, Ji R, Kato TS, Xu K, Zizola C, Wu C, Forman DE, Ota T, Takayama H, Naka Y, George I, Mancini DM, Schulze PC. Ventricular Assist Device Implantation Improves Skeletal Muscle Function, Oxidative Capacity and Growth Hormone/Insulin-like Growth Factor-1 Axis Signaling in Patients with Advanced Heart Failure. J Cachexia Sarcopenia Muscle. In Press.
This project is a collaboration with Dr. Ira Goldberg's group at Columbia University.
Relevant Publications:
Shin JY, Mendez-Lopez I, Wang Y, Hays AP, Tanji K, Lefkowitch JH, Schulze PC, Worman HJ, Dauer WT. Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance. Dev Cell. 2013;26:591-603
Chung CJ, Wu C, Jones M, Kato TS, Dam TT, Givens R, Templeton DL, Maurer MS, Naka Y, Takayama H, Mancini DM, Schulze PC. Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement. J Cardiac Fail. 2014;20(5):310-5
Khawaja T, Chokshi A, Ji R, Kato TS, Xu K, Zizola C, Wu C, Forman DE, Ota T, Takayama H, Naka Y, George I, Mancini DM, Schulze PC. Ventricular Assist Device Implantation Improves Skeletal Muscle Function, Oxidative Capacity and Growth Hormone/Insulin-like Growth Factor-1 Axis Signaling in Patients with Advanced Heart Failure. J Cachexia Sarcopenia Muscle. In Press.
Endocannabinoid signaling in normal and failing myocardium
The endocannabinoid system consists of the two known receptors CB1 and CB2 and its endogenous ligands anandamide and 2-arachidonoylglycerol. This system is involved in the control of pain, central and peripheral metabolism and regulates food uptake and satiety. Its most prominent role is in obesity. We study the myocardial and skeletal muscle regulation of the endocannabinoid system. This project analyzes the signaling cascades controlled by the receptors CB1 and CB2 in cardiomyocytes and myoblasts and the role of its endogenous ligands in normal and failing myocardium.
These studies are performed in collaboration with Dr. William Blaner's group at Columbia University.
These studies are performed in collaboration with Dr. William Blaner's group at Columbia University.
Blood pressure variability in patients with heart failure and ventricular assist devices
The physiologic regulation of vascular tone and subsequently blood pressure is impaired in heart failure. The recent advent of ventricular assist device systems allows the mechanical support of the failing heart. The last generation of assist devices employs non-pulsatile, continuous flow which leads to the inherent difficulty to reliably measure and follow the peripheral blood pressure regulation. This project studies the low-frequency blood pressure oscillation in patients with heart failure, patients with ventricular assist devices and controls using a NEXFIN system.
This project is a collaboration with Dr. Richard Sloan and Dr. Daichi Shimbo, Columbia University.
This project is a collaboration with Dr. Richard Sloan and Dr. Daichi Shimbo, Columbia University.
Assessment of epicardial fat accumulation in patients with advanced coronary artery disease and heart failure
Epicardial fat has recently been linked to severity and progression of coronary artery disease. It has been suggested to play a role in cardiac metabolism and might contribute to mechanisms of remodeling and failure. Using computed tomography and nuclear perfusion imaging, we study the interaction of epicardial fat accumulation with markers of cardiac function and structure in a large patient cohort established at Columbia University. These findings are linked to baseline and follow-up laboratory markers and clinical outcome.
This project is a collaboration with Dr. Andrew Einstein, Division of Cardiology, Columbia University.
Relevant Publications:
Khawaja T, Greer C, Chokshi A, Chavarria N, Thadani S, Jones M, Schaefle K, Bhatia K, Collado JE, Shimbo D, Einstein AJ, Schulze PC. Epicardial fat volume in patients with left ventricular systolic dysfunction. Am J Cardiol. 2011;108(3):397-401Bokhari S, Raina A, Rosenzweig EB, Schulze PC, Bokhari J, Einstein AJ, Barst RJ, Johnson LL. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging. 2011;4(6):641-7
This project is a collaboration with Dr. Andrew Einstein, Division of Cardiology, Columbia University.
Relevant Publications:
Khawaja T, Greer C, Chokshi A, Chavarria N, Thadani S, Jones M, Schaefle K, Bhatia K, Collado JE, Shimbo D, Einstein AJ, Schulze PC. Epicardial fat volume in patients with left ventricular systolic dysfunction. Am J Cardiol. 2011;108(3):397-401Bokhari S, Raina A, Rosenzweig EB, Schulze PC, Bokhari J, Einstein AJ, Barst RJ, Johnson LL. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging. 2011;4(6):641-7
Osteoclastogenesis and bone metabolism in heart failure
Abnormal bone metabolism in patients with advanced heart failure leads to reduced bone density and increased fracture risk. We study the regulation of osteoclastogenesis in animal models of heart failure and the specific role of glucose and lipid metabolism genes for the control of osteoclast function and metabolism.
This project is a collaboration with the group of Dr. Schulze-Spate, Columbia University College of Dental Medicine.
Relevant Publications:
Drosatos-Tampakaki Z, Drosatos K, Siegelin Y, Gong S, Khan S, Van Dyke T, Goldberg IJ, Schulze PC, Schulze-Spate U. Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis while oleic acid-induced triglyceride formation prevents it. J Bone Miner Res. 2014;29:1183-95
Wu C, Kato TS, Pronschinske K, Qiu S, Naka Y, Takayama H, Schulze-Spate U, Cremers S, Shane E, Mancini D, Schulze PC. Dynamics of bone turnover markers in patients with heart failure and following haemodynamic improvement through ventricular assist device implantation. Eur J Heart Fail. 2012;14:1356-1365
This project is a collaboration with the group of Dr. Schulze-Spate, Columbia University College of Dental Medicine.
Relevant Publications:
Drosatos-Tampakaki Z, Drosatos K, Siegelin Y, Gong S, Khan S, Van Dyke T, Goldberg IJ, Schulze PC, Schulze-Spate U. Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis while oleic acid-induced triglyceride formation prevents it. J Bone Miner Res. 2014;29:1183-95
Wu C, Kato TS, Pronschinske K, Qiu S, Naka Y, Takayama H, Schulze-Spate U, Cremers S, Shane E, Mancini D, Schulze PC. Dynamics of bone turnover markers in patients with heart failure and following haemodynamic improvement through ventricular assist device implantation. Eur J Heart Fail. 2012;14:1356-1365
Analysis of clinical outcome factors in patients with heart failure before and after ventricular assist device placement and cardiac transplantation
Heart failure is defined by the inability of the heart to provide sufficient cardiac output for the metabolic needs of the body. Exercise performance in patients with advanced heart failure has been linked to overall survival and the need for cardiac transplantation or ventricular assist device placement. We study in a large patient cohort (>450 patients) exercise performance and its relation to central and peripheral metabolism, biomarker profiles and clinical events in patients with heart failure. Further, we study the acute and long-term outcome of patients undergoing ventricular assist device placement in a large cohort of patients undergoing ventricular assist device placement (>250 patients) with a special emphasis on changes in glucose and lipid metabolism after hemodynamic correction in advanced heart failure and post-operative survival. Finally, we aim to define groups of patients who might benefit from alternative listing criteria and an expanded donor selection pool. Further, we analyze the specific dynamics in metabolism in patients undergoing cardiac transplantation and the association of changes in metabolic parameters and clinical outcome after cardiac transplantation in large cohort of >1500 individuals.
Relevant Publications:
Kato TS, Jiang J, Schulze PC, Jorde U, Uriel N, Kitada S, Takayama H, Naka Y, Mancini D, Gillam L, Homma S, Farr M. Serial echocardiography using tissue Doppler and speckle tracking imaging to monitor right ventricular failure before and after left ventricular assist device surgery. JACC Heart Fail. 2013 Jun;1(3):216-22.
Kato TS, Cheema FH, Yang J, Kawano Y, Takayama H, Naka Y, Farr M, Lederer DJ, Baldwin MR, Jin Z, Homma S, Mancini DM, Schulze PC. Preoperative serum albumin levels predict 1-year postoperative survival of patients undergoing heart transplantation. Circ Heart Fail. 2013;6:785-791
Kato TS, Collado E, Khawaja T, Kawano Y, Kim M, Farr M, Mancini DM, Schulze PC. Value of peak exercise oxygen consumption combined with b-type natriuretic peptide levels for optimal timing of cardiac transplantation. Circ Heart Fail. 2013;6:6-14
Kato TS, Stevens GR, Jiang J, Schulze PC, Gukasyan N, Lippel M, Levin A, Homma S, Mancini D, Farr M. Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation. J Heart Lung Transplant. 2013;32:333-340
Kato TS, Kitada S, Yang J, Wu C, Takayama H, Naka Y, Farr M, Mancini DM, Schulze PC. Relation of preoperative serum albumin levels to survival in patients undergoing left ventricular assist device implantation. Am J Cardiol. 2013;112:1484-1488
Schulze PC, Jiang J, Yang J, Cheema FH, Schaeffle K, Kato TS, Farr M, Restaino S, Deng M, Maurer M, Horn E, Latif F, Colombo PC, Jorde U, Uriel N, Haythe J, Bijou R, Drusin R, Lee SH, Takayama H, Naka Y, Mancini DM. Preoperative assessment of high-risk candidates to predict survival after heart transplantation. Circ HF. 2013;6:527-534
Kim MS, Kato TS, Farr MJ, Wu C, Givens RC, Collado E, Mancini DM, Schulze PC. Hepatic Dysfunction in Ambulatory Patients with Heart Failure – Application of the MELD Scoring System for Outcome Prediction. J Am Coll Cardiol. 2013; 61(22):2253-61
Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN. Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Respirology. 2014 Jul;19(5):675-82Schulze PC, Kitada S, Clerkin K, Jin Z, Mancini DM. Regional Differences in Recipient Waitlist Time and Pre- and Post-Transplant Mortality After the 2006 United Network for Organ Sharing Policy Changes in the Donor Heart Allocation Algorithm. JACC Heart Fail. 2014;2:166-77
Kato TS, Lippel M, Naka Y, Mancini DM, Schulze PC. Post-transplant survival estimation using pre-operative albumin levels. J Heart Lung Transplant. 2014;33(5):547-8
Pronschinske K, Qiu S, Wu C, Kato TS, Khawaja T, Takayama H, Naka Y, Templeton D, George I, Farr MA, Mancini DM, Schulze PC. Neutrophil gelatinase-associated lipocalin and cystatin C for the prediction of clinical events in patients with advanced heart failure and after ventricular assist device placement. J Heart Lung Transplant. In Press.
Relevant Publications:
Kato TS, Jiang J, Schulze PC, Jorde U, Uriel N, Kitada S, Takayama H, Naka Y, Mancini D, Gillam L, Homma S, Farr M. Serial echocardiography using tissue Doppler and speckle tracking imaging to monitor right ventricular failure before and after left ventricular assist device surgery. JACC Heart Fail. 2013 Jun;1(3):216-22.
Kato TS, Cheema FH, Yang J, Kawano Y, Takayama H, Naka Y, Farr M, Lederer DJ, Baldwin MR, Jin Z, Homma S, Mancini DM, Schulze PC. Preoperative serum albumin levels predict 1-year postoperative survival of patients undergoing heart transplantation. Circ Heart Fail. 2013;6:785-791
Kato TS, Collado E, Khawaja T, Kawano Y, Kim M, Farr M, Mancini DM, Schulze PC. Value of peak exercise oxygen consumption combined with b-type natriuretic peptide levels for optimal timing of cardiac transplantation. Circ Heart Fail. 2013;6:6-14
Kato TS, Stevens GR, Jiang J, Schulze PC, Gukasyan N, Lippel M, Levin A, Homma S, Mancini D, Farr M. Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation. J Heart Lung Transplant. 2013;32:333-340
Kato TS, Kitada S, Yang J, Wu C, Takayama H, Naka Y, Farr M, Mancini DM, Schulze PC. Relation of preoperative serum albumin levels to survival in patients undergoing left ventricular assist device implantation. Am J Cardiol. 2013;112:1484-1488
Schulze PC, Jiang J, Yang J, Cheema FH, Schaeffle K, Kato TS, Farr M, Restaino S, Deng M, Maurer M, Horn E, Latif F, Colombo PC, Jorde U, Uriel N, Haythe J, Bijou R, Drusin R, Lee SH, Takayama H, Naka Y, Mancini DM. Preoperative assessment of high-risk candidates to predict survival after heart transplantation. Circ HF. 2013;6:527-534
Kim MS, Kato TS, Farr MJ, Wu C, Givens RC, Collado E, Mancini DM, Schulze PC. Hepatic Dysfunction in Ambulatory Patients with Heart Failure – Application of the MELD Scoring System for Outcome Prediction. J Am Coll Cardiol. 2013; 61(22):2253-61
Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN. Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Respirology. 2014 Jul;19(5):675-82Schulze PC, Kitada S, Clerkin K, Jin Z, Mancini DM. Regional Differences in Recipient Waitlist Time and Pre- and Post-Transplant Mortality After the 2006 United Network for Organ Sharing Policy Changes in the Donor Heart Allocation Algorithm. JACC Heart Fail. 2014;2:166-77
Kato TS, Lippel M, Naka Y, Mancini DM, Schulze PC. Post-transplant survival estimation using pre-operative albumin levels. J Heart Lung Transplant. 2014;33(5):547-8
Pronschinske K, Qiu S, Wu C, Kato TS, Khawaja T, Takayama H, Naka Y, Templeton D, George I, Farr MA, Mancini DM, Schulze PC. Neutrophil gelatinase-associated lipocalin and cystatin C for the prediction of clinical events in patients with advanced heart failure and after ventricular assist device placement. J Heart Lung Transplant. In Press.
Periodontal disease in patients with advanced heart failure and after cardiac transplantation
Patients with advanced heart failure develop abnormalities in bone metabolism and increased levels of inflammatory cytokines. While various studies have investigated the prevalence of periodontal disease in patients with coronary artery disease, no study has been performed in patients with heart failure. We analyze the prevalence and severity of periodontal disease in patients listed for cardiac transplantation and after cardiac transplantation. Periodontal status will be correlated to circulating biomarkers and markers of bone metabolism.
This study is a collaboration with the Division of Periodontics at Columbia University College of Dental Medicine.
This study is a collaboration with the Division of Periodontics at Columbia University College of Dental Medicine.
