One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction

Abstract

Background: Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. Methods: Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V–V 0 )}–1], where “P” is transmural pressure (pulmonary capillary wedge pressure – right atrial pressure), “S” is the pressure asymptote of the curve, “V” is the LV end-diastolic volume index, “V 0 ” is equilibrium volume, and “a” is the constant that characterizes LV myocardial stiffness. Results: Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min –1 ·kg –1 , P <0.0001, interaction P =0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min –1 ·kg –1 , P =0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P =0.001). Conclusions: In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03476785.

Identification of patients with preclinical heart failure with preserved ejection fraction using the H2FPEF score

“…While many preventive measures are already broadly indicated (such as recommendation of regular exercise, weight loss, or control of blood pressure), others may be more optimally applied to patients at greater risk due to cost, risk, or patient burden. Examples include high intensity exercise training, pharmacologic or surgical weight loss interventions, catheter ablation for atrial fibrillation, or drug therapies, each of which could potentially reduce risk for new-onset HFpEF based upon preliminary studies, 11 , 28 – 30 but would ideally be applied only to high risk patients. Such strategies will require testing in future preventive trials, but the present data show that the H2FPEF score can be used to stratify risk to identify patients to enroll in such trials.…”

Late Fontan Circulatory Failure. What Drives Systemic Venous Congestion and Low Cardiac Output in Adult Fontan Patients?

“…This, in combination with aging of the ventricle in older Fontan patients, will render ventricular dysfunction (systolic and diastolic) a more important issue in the years to come ( 26 ). Aging may even be accelerated in Fontan patients similarly to what has been observed in sedentary people where the left ventricle becomes stiffer (due to lack of exercise induced ventricular stretching) and evolves toward heart failure with preserved ejection fraction phenotype ( 48 , 49 ). Increased afterload (which could contribute to systolic and diastolic deterioration) has been reported, but may be secondary to decreased output in order to maintain blood pressure ( 50 ).…”

Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

“…In fact, multiple studies including randomized controlled clinical trials such as the HF-ACTION trial, systematic reviews and meta-analyses have shown that exercise is safe and improves symptoms in HF patients, both HFrEF and HFpEF patients. 5,6,[129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144] Exercise training is therefore recommended in HF patients. 5,16 Unfortunately, exercise is initially accompanied by increases in discomfort and many HF patients are apprehensive or physically challenged by non-cardiac comorbidities.…”

“…Clinical data also suggest that exercise is beneficial for HF patients. In fact, multiple studies including randomized controlled clinical trials such as the HF‐ACTION trial, systematic reviews and meta‐analyses have shown that exercise is safe and improves symptoms in HF patients, both HFrEF and HFpEF patients 5,6,129–144 . Exercise training is therefore recommended in HF patients 5,16 .…”