Early Cardiopulmonary Fitness after Heart Transplantation as a Determinant of Post-Transplant Survival

Background: Decreased peak oxygen consumption during exercise (peak Vo2) is a well-established prognostic marker for mortality in ambulatory heart failure. After heart transplantation, the utility of peak Vo2 as a marker of post-transplant survival is not well established. Methods and Results: We performed a retrospective analysis of adult heart transplant recipients at the Hospital of the University of Pennsylvania who underwent cardiopulmonary exercise testing within a year of transplant between the years 2000 to 2011. Using time-to-event models, we analyzed the hazard of mortality over nearly two decades of follow-up as a function of post-transplant percent predicted peak Vo2 (%Vo2). A total of 235 patients met inclusion criteria. The median post-transplant %Vo2 was 49% (IQR 42 to 60). Each standard deviation (±14%) increase in %Vo2 was associated with a 32% decrease in mortality in adjusted models (HR 0.68, 95% CI 0.53 to 0.87, p = 0.002). A %Vo2 below 29%, 64% and 88% predicted less than 80% survival at 5, 10, and 15 years, respectively. Conclusions: Post-transplant peak Vo2 is a highly significant prognostic marker for long-term post-transplant survival. It remains to be seen whether decreased peak Vo2 post-transplant is modifiable as a target to improve post-transplant longevity.

[1]  E. Bouhlel,et al.  Relationship between oxygen pulse and arteriovenous oxygen difference in healthy subjects: Effect of exercise intensity , 2019 .

[2]  D. O. Dahle,et al.  Effect of High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia: One-Year Follow-Up of the HITTS Randomized, Controlled Study , 2019, Circulation.

[3]  J. Wald,et al.  Cardiopulmonary Exercise Testing—A Valuable Tool, Not Gatekeeper When Referring Patients With Adult Congenital Heart Disease for Transplant Evaluation , 2019, World journal for pediatric & congenital heart surgery.

[4]  E. Rimm,et al.  Development and validation of anthropometric prediction equations for lean body mass, fat mass and percent fat in adults using the National Health and Nutrition Examination Survey (NHANES) 1999-2006. , 2017 .

[5]  N. Houstis,et al.  Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O2 Pathway Analysis , 2017, Circulation.

[6]  E. Ashley,et al.  A Reference Equation for Normal Standards for VO2 Max: Analysis from the Fitness Registry and the Importance of Exercise National Database (FRIEND Registry). , 2017, Progress in cardiovascular diseases.

[7]  S. Russell,et al.  Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in Heart Failure , 2017, Circulation. Heart failure.

[8]  Rajeev Malhotra,et al.  Cardiopulmonary Exercise Testing in Heart Failure. , 2016, JACC. Heart failure.

[9]  O. Havik,et al.  Peak oxygen uptake and self‐reported physical health are strong predictors of long‐term survival after heart transplantation , 2016, Clinical transplantation.

[10]  M. McKenna,et al.  Exercise limitation following transplantation. , 2012, Comprehensive Physiology.

[11]  M. Allen,et al.  The effects of race on peak oxygen consumption and survival in patients with systolic dysfunction. , 2010, Journal of cardiac failure.

[12]  W. Kraus,et al.  Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. , 2009, JAMA.

[13]  Michael Böhm,et al.  Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology , 2007, European journal of heart failure.

[14]  W. Kraus,et al.  Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale. , 2007, American heart journal.

[15]  O. al-Rawas,et al.  Exercise Responses Following Heart Transplantation: 5 Year Follow-Up , 2006, Scottish medical journal.

[16]  M. Allen,et al.  Effects of gender on peak oxygen consumption and the timing of cardiac transplantation. , 2005, Journal of the American College of Cardiology.

[17]  B. Grassi,et al.  Serial assessment of peak VO2 and VO2 kinetics early after heart transplantation. , 2003, Medicine and science in sports and exercise.

[18]  Andrea Giordano,et al.  Contribution of peak respiratory exchange ratio to peak VO2 prognostic reliability in patients with chronic heart failure and severely reduced exercise capacity. , 2003, American heart journal.

[19]  P. Royston,et al.  Flexible parametric proportional‐hazards and proportional‐odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects , 2002, Statistics in medicine.

[20]  Victor F. Froelicher,et al.  Exercise capacity and mortality among men referred for exercise testing. , 2002, The New England journal of medicine.

[21]  M C Limacher,et al.  Assessment of functional capacity in clinical and research applications: An advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association. , 2000, Circulation.

[22]  A. Coats,et al.  The "muscle hypothesis" of chronic heart failure. , 1996, Journal of molecular and cellular cardiology.

[23]  J. Wilson,et al.  Dissociation between peak exercise oxygen consumption and hemodynamic dysfunction in potential heart transplant candidates. , 1995, Journal of the American College of Cardiology.

[24]  J R Wilson,et al.  Value of Peak Exercise Oxygen Consumption for Optimal Timing of Cardiac Transplantation in Ambulatory Patients With Heart Failure , 1991, Circulation.

[25]  A. Fishman,et al.  Oxygen Utilization and Ventilation During Exercise in Patients with Chronic Cardiac Failure , 1982, Circulation.

[26]  David A. Schoenfeld,et al.  Partial residuals for the proportional hazards regression model , 1982 .

[27]  Svetlana Borovkova,et al.  Analysis of survival data , 2002 .