Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective

Area of Science:

• Cardiovascular Physiology
• Transplantation Medicine
• Computational Biology

Background:

• Cardiac denervation after heart transplantation (HTx) leads to resting tachycardia and chronotropic incompetence.
• Hemodynamic changes post-HTx, particularly early after surgery, are not fully understood.
• Understanding these changes is crucial for improving patient quality of life and clinical outcomes.

Purpose of the Study:

• To develop a model-based description of hemodynamic changes in heart transplant recipients (HTxRs) at rest and during exercise.
• To elucidate the contributions of intrinsic and autonomic control to heart rate regulation post-HTx.
• To quantify the impact of cardiac denervation on cardiovascular function.

Main Methods:

• A lumped-parameter cardiovascular system model was developed for early HTxRs.
• The model integrated intrinsic sinoatrial (SA) node function and autonomic control (aortic baroreflex, pulmonary stretch reflex).
• Model parameters were tuned using data from 15 clinical studies, followed by rest and exercise simulations.

Main Results:

• Simulations predicted increased resting heart rate (93.8 vs. 69.5 bpm) due to vagal denervation, with reduced stroke volume maintaining normal cardiac output.
• Exercise simulations showed markedly reduced peak cardiac output (13 vs. 19.8 L/min) due to diminished peak heart rates and contractility.
• HTxRs maintained normal cardiac output during low-to-medium intensity exercise via increased stroke volume augmentation (Frank-Starling mechanism).

Conclusions:

• Increased resting heart rate post-HTx is primarily due to the loss of vagal tone.
• Chronotropic incompetence is the main determinant of reduced exercise capacity, with peripheral factors playing a lesser role.
• HTxRs can compensate for diminished exercise capacity by increasing stroke volume, thus maintaining adequate cardiac output during submaximal exercise.