Prasad Konda

Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Background— Inorganic nitrate (NO3−), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3− supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise. Methods and Results— Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3−, 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak O2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 &mgr;mol/L; P=0.0003), peak O2 (12.6±3.7 versus 11.6±3.1 mL O2·min−1·kg−1; P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3− led to greater reductions in systemic vascular resistance (−42.4±16.6% versus −31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3− reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function. Conclusions— NO3− increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and O2. NO3− increased exercise vasodilatory and cardiac output reserves. NO3− also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01919177.

Effective Arterial Elastance Is Insensitive to Pulsatile Arterial Load

Effective arterial elastance (EA) was proposed as a lumped parameter that incorporates pulsatile and resistive afterload and is increasingly being used in clinical studies. Theoretical modeling studies suggest that EA is minimally affected by pulsatile load, but little human data are available. We assessed the relationship between EA and arterial load determined noninvasively from central pressure–flow analyses among middle-aged adults in the general population (n=2367) and a diverse clinical population of older adults (n=193). In a separate study, we investigated the sensitivity of EA to changes in pulsatile load induced by isometric exercise (n=73). The combination of systemic vascular resistance and heart rate predicted 95.6% and 97.8% of the variability in EA among middle-aged and older adults, respectively. EA demonstrated a quasi-perfect linear relationship with the ratio of systemic vascular resistance/heart period (middle-aged adults, R=0.972; older adults, R=0.99; P<0.0001). Aortic characteristic impedance, total arterial compliance, reflection magnitude, and timing accounted together for <1% of the variability in EA in either middle-aged or older adults. Despite pronounced changes in pulsatile load induced by isometric exercise, changes in EA were not independently associated with changes pulsatile load but were rather a nearly perfect linear function of the ratio of systemic vascular resistance/heart period (R=0.99; P<0.0001). Our findings demonstrate that EA is simply a function of systemic vascular resistance and heart rate and is negligibly influenced by (and insensitive to) changes in pulsatile afterload in humans. Its current interpretation as a lumped parameter of pulsatile and resistive afterload should thus be reassessed.

IMPACT OF TOTAL ARTERIAL COMPLIANCE, ASCENDING AND DESCENDING AORTIC WALL STIFFNESS ON LEFT VENTRICULAR MASS AND GEOMETRY

Impact of Total Arterial Compliance, Ascending and Descending Aortic Wall Stiffness on Left Ventricular Mass and Geometry The compliance of the arterial tree and aortic wall stiffness influence the pulsatile load of the left ventricle (LV). Limited data are available regarding the relationships

OBESITY, SLEEP APNEA, LV REMODELING AND MYOCARDIAL FIBROSIS ASSESSED WITH CARDIAC MRI

Obesity, Sleep Apnea, LV Remodeling and Myocardial Fibrosis Assessed with Cardiac MRI Both obesity and sleep apnea (SA) are predictive of heart failure (HF). Limited data are available regarding the independent effects of SA and obesity on left ventricular (LV) remodeling. We recruited 280