Citations

Background The utility of longitudinal, circumferential, and radial strain and strain rate in determining prognosis in chronic heart failure is not well established. Methods and Results In 416 patients with chronic systolic heart failure, we performed speckle‐tracking analyses of left ventricular longitudinal, circumferential, and radial strain and strain rate on archived echocardiography images (30 frames per second). Cox regression models were used to determine the associations between strain and strain rate and risk of all‐cause mortality, cardiac transplantation, and ventricular‐assist device placement. The area under the time‐dependent ROC curve ( AUC ) was also calculated at 1 year and 5 years. Over a maximum follow‐up of 8.9 years, there were 138 events (33.2%). In unadjusted models, all strain and strain rate parameters were associated with adverse outcomes ( P <0.001). In multivariable models, all parameters with the exception of radial strain rate ( P =0.11) remained independently associated, with patients in the lowest tertile of strain or strain rate parameter having a ≈2‐fold increased risk of adverse outcomes compared with the reference group ( P <0.05). Addition of strain to ejection fraction ( EF ) led to a significantly improved AUC at 1 year (0.697 versus 0.633, P =0.032) and 5 years (0.700 versus 0.638, P =0.001). In contrast, strain rate did not provide incremental prognostic value to EF alone. Conclusions Longitudinal and circumferential strain and strain rate, and radial strain are associated with chronic heart failure prognosis. Strain provides incremental value to EF in the prediction of adverse outcomes, and with additional study may be a clinically relevant prognostic tool.

Background— Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak V O 2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF. Methods and Results— RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. β-blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak V O 2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and V E /V CO 2 was higher. Conclusions— AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867.

Background— Low-gradient severe aortic stenosis with preserved ejection fraction is an increasingly recognized entity, and symptomatic patients may benefit from aortic valve replacement. However, systemic hypertension frequently coexists with low-gradient severe aortic stenosis, which itself may cause elevated left ventricular (LV) filling pressures with resultant symptoms of dyspnea. Methods and Results— Symptomatic patients with hypertension (aortic systolic pressure >140 mm Hg) and low-gradient (mean gradient <40 mm Hg) severe aortic stenosis (aortic valve area <1 cm 2 ) with preserved ejection fraction (ejection fraction >50%) who underwent invasive hemodynamic catheterization of the left and right sides of the heart received infusion of intravenous sodium nitroprusside to reduce blood pressure and arterial afterload. At baseline, patients had severe hypertension (aortic systolic pressure, 176±26 mm Hg), pulmonary hypertension (mean pressure, 39±12 mm Hg), elevated LV end-diastolic pressure (19±5 mm Hg), and reduced stroke volume (33±8 mL/m 2 ). All measures of afterload were reduced with nitroprusside ( P <0.001 for all). Nitroprusside reduced mean pulmonary artery pressure (25±10 mm Hg) and LV end-diastolic pressure (11±5 mm Hg; P <0.001 for both compared with baseline). Aortic valve area (0.86±0.11 to 1.02±0.16 cm 2 ; P =0.001) and mean gradient (27±5 to 29±6 mm Hg; P =0.02) increased with nitroprusside. Conclusions— Systemic hypertension in low-gradient severe aortic stenosis with preserved ejection fraction is associated with elevated LV filling pressures and pulmonary hypertension. Treatment of hypertension with vasodilator therapy results in a lowering of the total LV afterload, with a decrease in LV filling pressures and pulmonary artery pressures. These findings have important implications for the management of patients with low-gradient severe aortic stenosis with preserved ejection fraction and hypertension.

Background— Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes. Methods and Results— Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67–2.26±0.70 mm Hg/mL; P <0.0001) and Eed increased by 8% (0.13±0.03–0.14±0.04 mm Hg/mL; P <0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed ( r =0.5; P <0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function. Conclusions— Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.

Background— The pathophysiology of low flow, low gradient severe aortic stenosis (LGSAS) with preserved ejection fraction is poorly understood. It has been proposed that abnormalities of arterial circulation are a major contributor to this syndrome. Methods and Results— We invasively examined systemic arterial afterload (effective arterial elastance, Ea; total arterial compliance, Ca; and systemic vascular resistance index) in patients with LGSAS (mean gradient, <40 mm Hg; aortic valve area, <1.0 cm 2 ) and preserved ejection fraction (≥50%), and compared these findings with patients with high gradient (≥40 mm Hg) severe aortic stenosis (HGSAS) and moderate AS (mean gradient, <40 mm Hg; aortic valve area, >1.0 cm 2 ). Patients with LGSAS (n=36), HGSAS (n=31), and moderate AS (n=19) were similar with respect to age, sex, body size, symptoms, comorbidities, and ejection fraction. Aortic valve area was similar between groups with LGSAS and HGSAS, but the patients with LGSAS had reduced stroke volume index and cardiac index ( P =0.003 for both). In comparison with patients with HGSAS and moderate AS, measures of afterload, including Ea (4.02±0.98 versus 3.13±0.81 and 3.06±0.79 mm Hg·m 2 /mL; P <0.0001) and systemic vascular resistance index (3116±799 versus 2515±645 and 2380±546 dyn·s·m 2 /cm 5 ; P =0.001), were significantly higher in LGSAS, whereas Ca was lower (0.46±0.16 versus 0.57±0.13 and 0.59±0.19 mL/m 2 per mm Hg; P =0.002). All invasive measures of arterial afterload were related to stroke volume index. Conclusions— Patients with LGSAS and preserved ejection fraction display elevated arterial afterload compared with patients with HGSAS and moderate AS. These findings identify systemic arterial effects that contribute to the hemodynamic presentation in patients with LGSAS and help to further define this entity.

Abstract Aims Exercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF), yet its mechanisms remain unclear. The current study sought to determine whether increases in cardiac output (CO) during exercise are appropriately matched to metabolic demands in HFpEF. Methods and results Patients with HFpEF (n = 109) and controls (n = 73) exercised to volitional fatigue with simultaneous invasive (n = 96) or non-invasive (n = 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO2) during upright or supine exercise. At rest, HFpEF patients had higher LV filling pressures but similar heart rate, stroke volume, EF, and CO. During supine and upright exercise, HFpEF patients displayed lower peak VO2 coupled with blunted increases in heart rate, stroke volume, EF, and CO compared with controls. LV filling pressures increased dramatically in HFpEF patients, with secondary elevation in pulmonary artery pressures. Reduced peak VO2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO2 was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O2, P = 0.0005). While absolute increases in arterial–venous O2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial–venous O2 difference relative to VO2 was greater in HFpEF patients (8.9 ± 3.4 vs. 5.5 ± 2.0 min/dL, P &lt; 0.0001). These differences were observed in the total cohort and when upright and supine exercise modalities were examined individually. Conclusion While diastolic dysfunction promotes congestion and pulmonary hypertension with stress in HFpEF, reduction in exercise capacity is predominantly related to inadequate CO relative to metabolic needs.