Citations

Background— Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction. Methods and Results— Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P =0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P =0.07). However, with treatment cardiac index increased at rest ( P =0.006) and peak exercise ( P =0.02) in the sildenafil group, and systemic vascular resistance index (resting, P =0.0002; peak exercise, P =0.007) and diastolic blood pressure (resting, P =0.005; peak exercise, P =0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased ( P =0.001) within the sildenafil group but was unchanged in the placebo group. Conclusions— Sildenafil did not decrease filling pressure at rest or during exercise in post–myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov/ct2/show/NCT01046838 . Unique identifier: NCT01046838.

Background— Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown. Methods and Results— Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100–200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (<50 years of age) and older (≥50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10±2 to 16±3 mm Hg after ~1 L and to 20±3 mm Hg after ~2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16±4 mm Hg·L −1 ·m 2 ) than the other 3 groups ( P ≤0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25±12 mm Hg·L −1 ·m 2 ) than healthy young and older subjects ( P ≤0.005). Conclusions— Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure.

Background— Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Methods and Results— Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Conclusions— Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

Background— Left ventricular diastolic dysfunction (DD) is common after myocardial infarction (MI) despite preservation of left ventricular ejection fraction, yet it remains unclear how or whether DD affects cardiac hemodynamics with stress. Methods and Results— Invasive hemodynamic exercise testing was performed in 46 patients with a recent MI and left ventricular ejection fraction >45% and in 10 healthy volunteers. MI patients were enrolled prospectively and divided into those with DD (MI+DD; left atrial volume index >34 mL/m 2 and diastolic E/e′ ratio>8; n=35) and those without DD (MI–DD; left atrial volume index <34 mL/m 2 and E/e′ ratio<8; n=11). All underwent a supine cycle ergometer test with simultaneous right heart catheterization and echocardiography. At rest, 10 patients in MI+DD (29%) had pulmonary capillary wedge pressure >15 (14±4 mm Hg), whereas none of the MI−DD (10±2 mm Hg) or controls (9±2 mm Hg) displayed pulmonary capillary wedge pressure elevation ( P =0.03). During exercise, an abnormal rise in pulmonary capillary wedge pressure (>25 mm Hg) was observed in 94% of MI+DD (36±6 mm Hg) compared with 36% of MI−DD (24±6 mm Hg) and none of the controls (16±6 mm Hg; P <0.0001). Exercise right atrial pressure was the highest in MI+DD followed by MI−DD and control (15±5 versus 9±4 versus 7±5 mm Hg; P <0.001), whereas no difference in cardiac index was found between groups. Conclusions— In post-MI patients with preserved ejection fraction and left ventricular DD, cardiac output with exercise is maintained at the expense of substantially increased filling pressure. DD and loss of diastolic reserve may promote progression from stage B to stage C heart failure after MI. (Circ Heart Fail. 2012;5:-451.)

Background— Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R PA ) and compliance (C PA ) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Methods and Results— Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R PA -C PA relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R PA -C PA hyperbolic (inverse) dependence, C PA =0.564/(0.047+R PA ), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R PA -C PA relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C PA for any R PA and negatively correlating with the resistance-compliance product ( P <0.0001). Conclusions— Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R PA and C PA , and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R PA . Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.