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Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction.

ABSTRACT: INTRODUCTION:Cardiopulmonary exercise testing (CPET) plays an important role in properly phenotyping signs and symptoms of heart failure with preserved ejection fraction (HFpEF). The prognostic value of CPET is strengthened when accompanied by cardiac hemodynamic measurements. Although recognized as the "gold" standard, cardiac catheterization is impractical for routine CPET. Thus, advancing the scientific/methodologic understanding of noninvasive techniques for exercise cardiac hemodynamic assessment is clinically impactful in HFpEF. This study tested the concurrent validity of noninvasive acetylene gas (C2H2) uptake, echocardiography (ECHO), and oxygen pulse (O2pulse) for measuring/predicting exercise stroke volume (SV) in HFpEF. METHODS:Eighteen white HFpEF and 18 age-/sex-matched healthy controls participated in upright CPET (ages, 69 ± 9 yr vs 63 ± 9 yr). At rest, 20 W, and peak exercise, SV was measured at steady-state via C2H2 rebreathe (SVACET) and ECHO (SVECHO), whereas O2pulse was derived (=V?O2/HR). RESULTS:Resting relationships between SVACET and SVECHO, SVECHO and O2pulse, or SVACET and O2pulse were significant in HFpEF (R = 0.30, 0.36, 0.67), but not controls (R = 0.07, 0.01, 0.09), respectively. Resting relationships persisted to 20 W in HFpEF (R = 0.70, 0.53, 0.70) and controls (R = 0.05, 0.07, 0.21), respectively. Peak exercise relationships were significant in HFpEF (R = 0.62, 0.24, 0.64), but only for SVACET versus O2pulse in controls (R = 0.07, 0.04, 0.33), respectively. Standardized standard error of estimate between techniques was strongest in HFpEF at 20 W: SVACET versus SVECHO = 0.57 ± 0.22; SVECHO versus O2pulse = 0.71 ± 0.28; SVACET versus O2pulse = 0.56 ± 0.22. CONCLUSIONS:Constituting a clinically impactful step towards construct validation testing, these data suggest SVACET, SVECHO, and O2pulse demonstrate moderate-to-strong concurrent validity for measuring/predicting exercise SV in HFpEF.

SUBMITTER: Van Iterson EH

PROVIDER: S-EPMC5561476 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction.

Van Iterson Erik H EH Olson Thomas P TP Borlaug Barry A BA Johnson Bruce D BD Snyder Eric M EM

Medicine and science in sports and exercise 20170901 9

<h4>Introduction</h4>Cardiopulmonary exercise testing (CPET) plays an important role in properly phenotyping signs and symptoms of heart failure with preserved ejection fraction (HFpEF). The prognostic value of CPET is strengthened when accompanied by cardiac hemodynamic measurements. Although recognized as the "gold" standard, cardiac catheterization is impractical for routine CPET. Thus, advancing the scientific/methodologic understanding of noninvasive techniques for exercise cardiac hemodyna ...[more]

PMID: 28471812

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Project description:BACKGROUND:Aortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). OBJECTIVES:This study compared indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive control subjects to examine their relationships to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite. METHODS:A total of 22 hypertensive control subjects and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis to measure oxygen consumption. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection. RESULTS:Arterial load and wave reflections in HFpEF were similar to those in control subjects at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures in control subjects. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p < 0.0001). With peak exercise, increased wave reflections, impaired compliance, and increased resistance and elastance were observed in subjects with HFpEF. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo therapy in a 1:1 double-blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance and elastance and central hemodynamics during exercise. CONCLUSIONS:Abnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF. (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease [EXEC]; NCT01418248. Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction; NCT01932606. Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction; NCT02262078).

Project description:Background Maximal left atrial (LA) volume is reported by most echocardiography laboratories and is associated with clinical outcomes in patients with heart failure (HF). Recent studies suggest that minimal LA volume may better reflect left ventricular filling pressure and may be more prognostic than maximal LA volume. This study assessed the prognostic value of indexed minimal LA volume (LAVImin) in patients with HF with preserved ejection fraction. Methods and Results We assessed the relationship of LAVImin with a primary composite end point of cardiovascular death, aborted cardiac death, or HF hospitalization in 347 patients with HF with preserved ejection fraction enrolled from the Americas region in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We compared LAVImin with indexed maximal LA volume with respect to their prognostic values. In addition, we assessed if LA functional parameters provide additional prognostic information over LAVImin. During a median follow-up of 2.5 years, 107 patients (31%) experienced a primary composite end point. LAVImin was associated with increased risk of a primary composite outcome (hazard ratio [HR], 1.35; 95% CI, 1.12-1.61) and HF hospitalization alone (HR, 1.42; 95% CI, 1.17-1.71) after adjusting for clinical confounders and ejection fraction. In contrast, indexed maximal LA volume was not related to the primary composite outcome, but related to HF alone (HR, 1.25; 95% CI, 1.02-1.54). In comparison with indexed maximal LA volume, LAVImin was significantly more prognostic for primary composite outcome (P for comparison=0.032). Both LA emptying fraction and LA strain were prognostic of primary outcome independent of LAVImin (all P<0.05). Conclusions In patients with HF with preserved ejection fraction, LAVImin was more predictive of cardiovascular outcome than indexed maximal LA volume, suggesting this measure may be more physiologically relevant and might better identify patients at high risk for cardiovascular events. LA functional parameters provide prognostic information independent of LAVImin. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00094302.

Project description: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.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 VO2, 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 ?mol/L; P=0.0003), peak VO2 (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.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 VO2. NO3(-) increased exercise vasodilatory and cardiac output reserves. NO3(-) also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.www.clinicaltrials.gov. Unique identifier: NCT01919177.

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Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction.

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Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction.

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