Gregory Lewis

Since arriving at MGH in 1999 I have had the privilege of training in internal medicine and cardiology, teaching as a chief resident and as a cardiology attending, providing clinical care to patients with a broad range of cardiovascular diseases, and conducting research. I current serve as Section Head of Heart Failure, Medical Director of the Heart Transplant Program, and Director of the Cardiopulmonary Exercise Testing Laboratory.

As an investigator at MGH I have published over 100 manuscripts in fields ranging from the evaluation of novel therapies for heart failure to mechanisms of exercise intolerance in cardiovascular disease and metabolic response patterns to exercise. I am particularly interested in the role of the lung circulation and other extra-cardiac organs in mediating exercise intolerance in patients with heart failure. Through metabolic profiling of human plasma at rest and during exercise, in collaboration with the Broad Institute, our group has established metabolic signatures of cardiovascular disease states that may help to refine current phenotyping approaches.

Our cardiopulmonary exercise laboratory focuses on clinical evaluation of patients with shortness of breath of unclear etiology through comprehensive evaluations of each organ system's contribution to reduced functional capacity. Our laboratory also focuses on risk stratification in heart failure patients and serial assessments of exercise performance before and after medical interventions.

As Medical Director of the MGH Heart Transplant Program it has been an honor to work in close collaboration with my medical and surgical colleagues and the Transplant Center to help bring innovative approaches to heart transplantation with a particular focus on organ pool expansion.

Clinical Interests:

• Exercise physiology
• Heart failure
• Heart transplant
• Pulmonary hypertension

Medical Education

• MD, University of Rochester School of Medicine and Dentistry
• Residency, Massachusetts General Hospital
• Fellowship, Massachusetts General Hospital

Research Summary

My background is in biochemistry and cardiopulmonary physiology, and I have formal training in trial design, clinical investigation, and mass spectrometry-based metabolic profiling . A major objective of my current research is to understand mechanisms of exercise intolerance in patients with heart failure and to define physiologic and biochemical signatures of heart failure subphenotypes.

One area of focus has been on defining physiologic and metabolomic signatures of right ventricular-pulmonary vascular (RV-PV) interactions during exercise in heart failure. Through a unique exercise protocol that integrates hemodynamic measurements, ventriculography, gas exchange measurement, and plasma sampling we have found that the periodic breathign and kinetics of oxygen uptake and efficiency of ventilation provide complementary gas exchange signatures of RV-PV dysfunction during exercise. This physiologic data is complemented by measurements of circulating small molecules that serve as metabolomic signatures of RV-PV dysfunction. Taken together, these easily acquired parameters promote recognition of impaired RV-PV function in HF and may also may inform targeted interventions for RV-PV dysfunction.

A second area of focus is the periphery in heart failure, which constitutes the vasculature and skeletal muscle systems. Although these systems are outside of the heart they play a critical role in determining functional capacity in patients with heart failure. My group recently reported that peripheral oxygen extraction is abnormal in patients with heart failure. To improve peripheral oxygen utilization we are currently investigating iron homeostasis in heart failure and whether or not oral iron repletion improves exercise capacity in heart failure through an NIH-sponsored multicenter trial (IRONOUT-HF, PI=Lewis).

Publications

• Lewis GD, Shah R, Shahzad K, et al. Sildenafil Improves Exercise Capacity and Quality of Life in Patients with Systolic Heart Failure and Secondary Pulmonary Hypertension. Circulation. 2007.116:1555-1562.
• Lewis GD, Gona P, Benjamin EJ, et al. Exercise Blood Pressure and the Risk of Incident Cardiovascular Disease: The Framingham Heart Study. Am J Cardiol 2008, Jun 1;101(11):1614-20
• Lewis GD, Farrell L, Wood MJ, et al. Metabolic Signatures of Exercise in Human Plasma. Science Translational Medicine. 2010;2(33)
• Lewis GD et al. Metabolic Signatures of Right Ventricular-Pulmonary Vascular Dysfunction. Journal of the American College of Cardiology, 2016.
• Malhotra R, Bakken K, Lewis GD. Cardiopulmonary Exercise Testing in Heart Failure. JACC Heart Faillure, 2016
• Malhotra R et al. Pullmonary Vascular Distensibility Predicts PH Severity and Outcomes in Heart Failure. Circulation Heart Failure. June 2016