[show abstract][hide abstract] ABSTRACT: -Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF) but its clinical profile and impact on exercise capacity remains unclear. RELAX was a multicenter randomized trial testing the impact of sildenafil on peak VO2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among HFpEF patients who were in sinus rhythm (SR) or AF.
-RELAX enrolled 216 HFpEF patients with 79 (37%) in AF, 124 (57%) in SR and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing (CPXT), echocardiogram, biomarker and rhythm status assessment prior to randomization. AF patients were older than those in SR but had similar symptom severity, co-morbidities and renal function. Betablocker use and chronotropic indices were also similar. Despite comparable LV 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 to SR. Pulmonary artery systolic pressure was higher in AF. AF patients had higher NT-proBNP, aldosterone, endothelin-1, troponin I and CITP levels suggesting more severe neurohumoral activation, myocyte necrosis and fibrosis. Peak VO2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and VE/VCO2 was higher.
-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 HFpEF patients with AF is warranted. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
[show abstract][hide abstract] ABSTRACT: Low gradient (LG) severe aortic stenosis (AS) with preserved ejection fraction (EF) is an increasingly recognized entity, and symptomatic patients may benefit from aortic valve replacement. However, systemic hypertension frequently coexists with LG severe AS, which itself may cause elevated left ventricular (LV) filling pressures with resultant symptoms of dyspnea.
Symptomatic patients with hypertension (aortic systolic pressure>140 mmHg) and LG (mean gradient<40 mmHg) severe AS (aortic valve area<1 cm(2)) with preserved EF (EF>50%) who underwent invasive hemodynamic left and right heart catheterization received infusion of intravenous sodium nitroprusside to reduce blood pressure and arterial afterload. At baseline, patients had severe hypertension (aortic systolic pressure 176±26 mmHg), pulmonary hypertension (mean pressure 39±12 mmHg), elevated LV end diastolic pressure (19±5 mmHg) 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 mmHg) and LV end diastolic pressure (11±5 mmHg) (p<0.001 for both as compared to 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 mmHg, p=0.02) increased with nitroprusside.
Systemic hypertension in LG severe AS with preserved EF 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 LG severe AS with preserved EF and hypertension.
[show abstract][hide abstract] ABSTRACT: To examine the relationships between right ventricular (RV) function, body composition and prognosis in patients with advanced heart failure (HF).
Previous studies investigating HF-related cachexia have not examined the impact of RV function on body composition. We hypothesized that RV dysfunction is linked to weight loss, abnormal body composition and worsened prognosis in advanced HF.
Subjects with advanced HF (n=408) underwent prospective assessment of body composition (skinfold thickness, DEXA), comprehensive echocardiography and blood testing. Subjects were followed for adverse events defined as death, transplantation or circulatory assist device.
Subjects with RV dysfunction (51%) had lower body mass index (BMI), lower fat mass index and were more likely to display cachexia (19%). The extent of RV dysfunction correlated with greater antecedent weight loss and lower fat/lean body mass ratio. Over a median follow-up of 541 days, there were 150 events (37%). Risk of event was greater in subjects with RV dysfunction (HR 3.09, 2.18-4.45) and cachexia (HR 2.90, 2.00-4.12) in both univariate and multivariate analysis. Increased BMI was associated with lower event rate (HR per kg.m(-2): 0.92, 0.88-0.96) and this protection was mediated by higher fat mass (0.91, 0.87-0.96) but not fat-free mass index (0.97, 0.92-1.03).
RV dysfunction and cardiac cachexia often coexist, have additive adverse impact and might be mechanistically interrelated. Wasting of fat but not of lean mass was predictive of adverse outcome, suggesting that fat loss is either a surrogate of enhanced catabolism or adipose tissue is cardioprotective in the context of HF.
Journal of the American College of Cardiology 07/2013; · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: -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. Additionally it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes.
-Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly-selected community-based study at two 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 (Ea). Over 4 years, blood pressure, Ea 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 to 2.26±0.70 mmHg/ml, p<0.0001) and Eed increased by 8% (0.13±0.03 to 0.14±0.04 mmHg/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.
-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.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: The objective of this study was to compare the physiologic determinants of ejection fraction (EF) - ventricular size, contractile function, and ventricular-arterial (VA) interaction - and their associations with clinical outcomes in chronic heart failure (HF). BACKGROUND: EF is a potent predictor of HF outcomes, but represents a complex summary measure that integrates several components including left ventricular (LV) size, contractile function, and VA coupling. The relative importance of each of these parameters in determining prognosis is unknown. METHODS: In 466 participants with chronic systolic HF, we derived quantitative echocardiographic measures of EF; cardiac size (end-diastolic volume [EDV]); contractile function (the end systolic pressure volume relation slope [Eessb] and intercept [V0]); and VA coupling (Ea/Eessb). We determined the association between these parameters and the following adverse outcomes: 1) the combined endpoint of death, cardiac transplantation, or ventricular assist device (VAD) placement and 2) cardiac hospitalization. RESULTS: Over a median followup of 3.4 years, there were 76 deaths, 52 transplants, 14 VAD placements, and 684 cardiac hospitalizations. EF was independently associated with death, transplantation, and VAD placement (adjusted Hazard Ratio [HR] 3.0, 95%CI 1.8-5.0 comparing 3(rd) versus 1(st) tertile), as were EDV (HR 2.6, 95%CI 1.5-4.2); V0 (HR 3.6, 95% CI 2.1-6.1); and Ea/Eessb (HR 2.1, 95%CI 1.3-3.3). EDV, V0, and Ea/Eessb were also associated with risk of cardiac hospitalization. Eessb was not significantly associated with any adverse outcomes in adjusted analyses. CONCLUSIONS: LV size, V0, and VA coupling are associated with prognosis in systolic HF, but end-systolic elastance (Eessb) is not. Assessment of VA coupling via Ea/Eessb is an additional noninvasively derived metric that can be used to gauge prognosis in human HF.
Journal of the American College of Cardiology 06/2013; · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objectives
The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients.
The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood.
In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers.
Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = −0.33; norepinephrine: r = −0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information.
Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: -The pathophysiology of low flow, low gradient severe aortic stenosis (LGSAS) with preserved ejection fraction (EF) is poorly understood. It has been proposed that abnormalities of the 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, SVRI) in patients with LGSAS (mean gradient <40mmHg; aortic valve area <1.0 cm(2)) and preserved EF (≥50%), and compared these findings to patients with high gradient (≥40 mmHg) severe aortic stenosis (HGSAS) and moderate AS (mean gradient < 40mmHg; 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, co-morbidities, and EF. Aortic valve area was similar between LGSAS and HGSAS groups, but the LGSAS patients had reduced stroke volume index and cardiac index (p=0.003 for both). In comparison to HGSAS and moderate AS patients, measures of afterload including Ea (4.02 ± 0.98 vs. 3.13 ± 0.81 and 3.06 ± 0.79 mmHg*m(2)/mL; p<0.0001) and SVRI (3116 ± 799 vs. 2515 ± 645 and 2380 ± 546 dyn•s•m(2)/cm(5); p=0.001) were significantly higher in LGSAS, while Ca was lower (0.46 ± 0.16 vs. 0.57 ± 0.13 and 0.59 ± 0.19 mL/m(2)/mmHg; p=0.002). All invasive measures of arterial afterload were related to stroke volume index. CONCLUSIONS: -Patients with LGSAS and preserved EF display elevated arterial afterload compared to 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.
[show abstract][hide abstract] ABSTRACT: IMPORTANCE Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF). OBJECTIVE To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. DESIGN Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction ≥50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012. INTERVENTIONS Sildenafil (n = 113) or placebo (n = 103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. MAIN OUTCOME MEASURES Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks. RESULTS Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e' (16), left atrial volume index (44 mL/m2), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (-0.20 [IQR, -0.70 to 1.00]) or sildenafil (-0.20 [IQR, -1.70 to 1.11]) were not significantly different (P = .90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, -0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P = .85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P = .92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). CONCLUSION AND RELEVANCE Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00763867.
JAMA The Journal of the American Medical Association 03/2013; · 29.98 Impact Factor
[show abstract][hide abstract] 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 (VO(2)) 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 VO(2) 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 VO(2) in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO(2) was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O(2), P = 0.0005). While absolute increases in arterial-venous O(2) difference with exercise were similar in HFpEF patients and controls, augmentation in arterial-venous O(2) difference relative to VO(2) was greater in HFpEF patients (8.9 ± 3.4 vs. 5.5 ± 2.0 min/dL, P < 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.
European Journal of Heart Failure 02/2013; · 5.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Diastolic dysfunction is frequently seen after myocardial infarction (MI) 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 MI. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular (LV) 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 endpoint was pulmonary capillary wedge pressure (PCWP), secondary endpoints comprised cardiac index (CI) and pulmonary arterial pressure (PAP) at rest and during exercise after 9 weeks. After 9 weeks there were no differences in PCWP at rest (13±4 vs. 13±3 mmHg, p=0.25) or at peak exercise (35±8 mmHg vs. 31±7 mmHg, p=0.07). However with treatment CI increased at rest (p=0.006) and peak exercise (p=0.02) in the sildenafil group, 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 LV end-diastolic volume index (LVEDVI) 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-MI patients with diastolic dysfunction. However, there were effects on secondary endpoints which require further studies. CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/show/NCT01046838. Identifier: NCT01046838.
[show abstract][hide abstract] ABSTRACT: Objectives
The purpose of this study was to assess the clinical, functional, and hemodynamic characteristics of passive and mixed pulmonary hypertension (PH), compare outcomes, and contrast conventional and novel hemodynamic partition values in patients with chronic heart failure of reduced left ventricular ejection fraction (HFREF).
PH in HFREF may develop from left-sided venous congestion (passive PH) or the combination of pulmonary arterial disease and venous congestion (mixed PH). Subgroup outcomes are not well defined, and the partition values used to define risk are based largely on consensus opinion rather than outcome data.
Ambulatory patients referred for hemodynamic catheterization were analyzed retrospectively (N = 463).
Comparing patients with no PH to those with passive PH and mixed PH, a progressive gradient of more severely deranged hemodynamics, diastolic dysfunction, and mitral regurgitation was observed. In multivariate analysis, the presence of any PH or mixed PH was associated with older age, diuretic use, atrial fibrillation, and lower pulmonary artery compliance (PAC). Over a median follow-up of 2.1 years, patients with PH displayed greater risk of death (hazard ratio [HR]: 2.24; confidence limits [95% CL]: 1.39, 3.98; p < 0.001) with mixed PH demonstrating greater risk than passive PH (HR: 1.55; 95% CL: 1.11, 2.20; p < 0.001). Partition values identifying highest risk were pulmonary vascular resistance >4 Wood units, systolic pulmonary artery pressure >35 mm Hg, pulmonary wedge pressure >25 mm Hg, and PAC <2.0 ml/mm Hg.
Among stable HFREF outpatients, PH was associated with markers of greater disease severity and risk of death. However, the presence of pulmonary arterial disease (mixed PH) carries incremental risk. Abnormalities in pulmonary vascular resistance and compliance may serve as novel therapeutic targets.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction (HFpEF). However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remains unknown. METHODS AND RESULTS: Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (MPAP) to volume loading with rapid saline infusion (100-200 ml/min). Hemodynamic responses to saline infusion in HFpEF (n=11) were then compared to healthy young (<50yrs) and older-aged (≥50yrs) subjects. In healthy subjects, PCWP increased from 10±2 to 16±3 mmHg after ~1L and to 20±3 mmHg after ~2L of saline infusion. Older women displayed a steeper increase in PCWP relative to volume infused (16±4mmHg·L(-1)·m(2)) than the other 3 groups (p≤0.019). Saline infusion resulted in a greater increase in MPAP relative to cardiac output in women compared to men, irrespective of age. Subjects with HFpEF exhibited a steeper increase in PCWP relative to infused volume (25±12 mmHg·L(-17)·m(2)) than healthy young and older subjects (p≤0.005). CONCLUSIONS: Filling pressures rise significantly with volume loading, even in normal volunteers. Older women and patients with HFpEF exhibit the largest increases in PCWP and MPAP.
[show abstract][hide abstract] ABSTRACT: Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] ≥50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis.
In this prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic Optimization Strategies Evaluation study, clinical features and N-terminal pro-B-type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric acid), and procollagen type III N-terminal peptide were compared in HFpEF and HFrEF at enrollment and 60-day follow-up.
Compared with HFrEF (n = 219), HFpEF (n = 81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar New York Heart Association class, jugular venous pressure, and edema severity. N-terminal pro-B-type NP was lower, and systolic blood pressure and cystatin C were higher in HFpEF. Despite higher systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and procollagen type III N-terminal peptide levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n = 50).
Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress, and collagen synthesis as in HFrEF.
American heart journal 11/2012; 164(5):763-770.e3. · 4.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: This study sought to assess sex differences in ventricular-arterial interactions. BACKGROUND: Heart failure with preserved ejection fraction is more prevalent in women than in men, but the basis for this difference remains unclear. METHODS: Echocardiography and arterial tonometry were performed to quantify arterial and ventricular stiffening and interaction in 461 participants without heart failure (189 men, age 67 ± 9 years; 272 women, age 65 ± 10 years). Aortic characteristic impedance (Z(c)), total arterial compliance (pulsatile load), and systemic vascular resistance index (steady load) were compared between men and women, and sex-specific multivariable regression analyses were performed to assess associations of these arterial parameters with diastolic dysfunction and ventricular-arterial coupling (effective arterial elastance/left ventricular end-systolic elastance [Ea/Ees]) after adjustment for potential confounders. RESULTS: Z(c) was higher and total arterial compliance was lower in women, whereas systemic vascular resistance index was similar between sexes. In women but not men, higher log Z(c) was associated with mitral inflow E/A ratio (β ± SE: -0.17 ± 0.07), diastolic dysfunction (odds ratio: 7.8; 95% confidence interval: 2.0 to 30.2) and Ea/Ees (β ± SE: 0.13 ± 0.04) (p ≤ 0.01 for all). Similarly, total arterial compliance was associated with E/A ratio (β ± SE: 0.12 ± 0.04), diastolic dysfunction (odds ratio: 0.33; 95% confidence interval: 0.12 to 0.89), and Ea/Ees (β ± SE: -0.09 ± 0.03) in women only (p ≤ 0.03 for all). Systemic vascular resistance index was not associated with diastolic dysfunction or Ea/Ees. CONCLUSIONS: Proximal aortic stiffness (Z(c)) is greater in women than men, and women may be more susceptible to the deleterious effects of greater pulsatile and early arterial load on diastolic function and ventricular-arterial interaction. This may contribute to the greater risk of heart failure with preserved ejection fraction in women.
Journal of the American College of Cardiology 10/2012; · 14.09 Impact Factor