Heart Failure And A Preserved Ejection Fraction Research Articles

Impact of Sex in Left Atrial Indices for Prognosis of Heart Failure with Preserved Ejection Fraction.

Objective: We aim to clarify the differences in the association between re-admission for heart failure (HF) and left atrial (LA) overload indices by sex in heart failure and a preserved ejection fraction (HFpEF). Methods: We analyzed 898 HFpEF patients hospitalized for acute decompensated HF. Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re-admission for HF during the first year. Results: The ratio of diastolic elastance to arterial elastance (p = 0.014), a relative index of LA pressure overload, in men and LA volume index (LAVI, p = 0.020) in women were significant for re-admission for HF during the first year in the multivariable Fine–Gray analysis. Stroke volume (SV)/LA volume (LAV), another index for LAV overload, was not a significant prognostic factor of re-admission for HF during this time. Conclusion: LA overload was an important prognostic factor for HF re-readmission during the first year after enrolment in patients with HFpEF, but the indices relating to LA overload differed by sex.

Outpatient diuretic intensification as endpoint in heart failure with preserved ejection fraction trials: an analysis from TOPCAT.

Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas. Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p< 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p< 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p= 0.044). Using win ratio provided similar estimates. In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.

Abstract 12357: Discordant Mechanisms in Hypertrophy and Heart Failure

Introduction: Patients with heart failure and a preserved ejection fraction (HFpEF) present heart function abnormalities that remain poorly understood. Defining proteomic signature of HF that is independent of left ventricular hypertrophy (LVH) should allow for stratification of its subtypes and potential mechanism that contributes to the disease. Hypothesis: We hypothesized that HFpEF proteomic signature would be comprised of the hypertrophy and contractile protein phenotype. Methods: Intraoperative left ventricular (LV) myocardial biopsies were obtained from patients (n=21) recruited to undergo coronary artery bypass grafting (CABG). Patients were categorized to: control non-hypertensive (n=9), LVH (n=5), and HFpEF (n=7). Myocardial tissue was subfractionated: cytoplasmic- (neutral pH), myofilament- (acidic pH), and membrane-enriched extract (SDS-soluble). Samples were assessed for protein quantity and Lys/Arg modifications using liquid chromatography mass spectrometry (LC-MS). Results: In HFpEF, 13% of the cardiac LV proteome changed compared to control heart, with a substantial proportion (77%) decreasing in quantity across all three cardiac fractions, while with LVH, 61% of the proteomic LV changes were increased. Although glycolysis and gluconeogenesis increased in both cardiopathies with respect to control, in HFpEF more subtly than in LVH. Modified proteome of the HFpEF was dominated by decreases in protein succinylation (e.g. ATP5L, THIM, IDHP, APOB, GSH1, KNTC1) and to a lesser degree in methylation (ROA3, HSP7C) or acetylation compared to control group. This general trend of down-regulation of succinylation can be attributed to depletion in the levels of succinyl-CoA, the cofactor of enzymatic Lys succinylation. Importantly, there was a striking discordant activation/inhibition of cell death and proliferation pathways between the HFpEF and LVH. Two major upstream regulator clusters linked the proteome changes in cell growth and proliferation to RICTOR and Myc that showed completely opposite trends in LVH and HFpEF groups. Conclusions: HFpEF has a unique proteome signature compared to LV hypertrophy profile which does not arise from sub-proteome involved in contraction but rather is involved in overall cell death.

Abstract 16928: Discordant Mechanisms in Heart Failure and Hypertrophy

Introduction: Patients with heart failure and a preserved ejection fraction (HFpEF) present heart function abnormalities that remain poorly understood. Defining proteomic signature of HF that is independent of left ventricular hypertrophy (LVH) should allow for stratification of its subtypes and potential mechanism that contributes to the disease. Hypothesis: We hypothesized that HFpEF proteomic signature would be comprised of the hypertrophy and contractile protein phenotype. Methods: Intraoperative left ventricular (LV) myocardial biopsies were obtained from patients (n=21) recruited to undergo coronary artery bypass grafting (CABG). Patients were categorized to: control non-hypertensive (n=9), LVH (n=5), and HFpEF (n=7). Myocardial tissue was subfractionated: cytoplasmic- (neutral pH), myofilament- (acidic pH), and membrane-enriched extract (SDS-soluble). All fractions were assessed for protein quantity and Lys/Arg modifications using liquid chromatography mass spectrometry (LC-MS). Results: In HFpEF, 13% of the cardiac LV proteome changed compared to control heart, with a substantial proportion (77%) decreasing in quantity across all three cardiac fractions, while with LVH, 61% of the proteomic LV changes were increased. Although glycolysis and gluconeogenesis increased in both cardiopathies with respect to control, in HFpEF more subtly than in LVH. Modified proteome of the HFpEF was dominated by decreases in protein succinylation (e.g. ATP5L, THIM, IDHP, APOB, GSH1, KNTC1) and to a lesser degree in methylation (ROA3, HSP7C) or acetylation compared to control. This general trend of down-regulation of succinylation can be attributed to depletion in the levels of succinyl-CoA, the cofactor of enzymatic Lys succinylation. Importantly, there was a striking discordant activation/inhibition of cell death and proliferation pathways between the HFpEF and LVH. Two major upstream regulator clusters linked the proteome changes in cell growth and proliferation to RICTOR and Myc that showed completely opposite trends in LVH and HFpEF groups. Conclusions: HFpEF has a unique proteome signature compared to LV hypertrophy profile which does not arise from sub-proteome involved in contraction but rather is involved in overall cell death.

Sodium-glucose cotransporter2 inhibitors: A drug with antidiabetic and cardioprotective properties.

Recently, two large double-blind randomized controlled trials testing the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure with and without diabetes have led to a paradigm shift for the indication of this class of drugs. Key clinical features and main results in these two studies are summarized in Table 1 and 2. The dapagliflozin and prevention of adverse outcomes in heart failure (DAPA-HF) trial included 4744 patients with heart failure and a reduced ejection fraction (HFrEF).

Determinants of Diastolic Dysfunction in Swine with HFpEF Arising From Transient Repetitive Left Ventricular Pressure Overload

ObjectiveWe recently demonstrated that swine subjected to 2‐weeks of repetitive pressure overload (RPO) exhibit adaptive myocardial remodeling in the absence of left ventricular (LV) hypertrophy. This remodeling is similar to that arising in many patients with heart failure and a preserved ejection fraction (HFpEF). While LV compliance is markedly reduced, the relative contribution of altered myocardial relaxation vs. passive myocardial properties to this is unclear. Accordingly, the objective of the present study was to determine how RPO affects passive myocardial stiffness and active myocardial relaxation, two key components of LV diastolic function.MethodsSwine (n=14) were subjected to 2‐weeks of RPO via daily infusions of phenylephrine (300 ug/min, 2 hours/day). Invasive measurements of LV performance were collected before and after RPO at rest and during alterations in loading conditions elicited by transient manipulation of venous return. To assess reversibility, a subset of animals (n=6) underwent repeat studies 2‐weeks after cessation of RPO. After the final study, myocardial tissue was collected from the LV free wall for post‐mortem assessment of calcium handling protein expression (western blot; n=8), passive myocardial stiffness (uniaxial tensile testing; n=3), and quantification of interstitial fibrosis (picrosirius red staining).ResultsCompared with baseline measurements, 2‐weeks of RPO did not significantly affect the LV relaxation time constant (Tau) or the rate of LV pressure change during isovolumic relaxation (dP/dtmin; Table ). Consistent with this observation, myocardial expression of calcium handling proteins SERCA (from 0.58±0.24 to 0.52±0.25, p=0.62), ryanodine receptor (from 0.37±0.17 to 0.36±0.14, p=0.99), and phospholamban (from 0.46±0.21 to 0.33±0.15, p=0.17) was not different following RPO vs. normal controls (n=8). However, assessment of LV performance under altered loading conditions revealed a significant increase in the LV stiffness coefficient (β) during IVC occlusion as well as the ΔEDP/ΔEDV ratio during rapid saline loading. These functional changes persisted for 2‐weeks following cessation of RPO and were accompanied by a significant increase in passive myocardial stiffness and interstitial fibrosis.ConclusionsThese results demonstrate that the reduction in LV compliance arising after RPO is not related to delayed active myocardial relaxation at rest or altered expression of sarcoplasmic reticulum calcium handling proteins. However, RPO elicits a persistent increase in passive myocardial stiffness that is likely mediated by interstitial collagen deposition. These passive diastolic properties may explain exercise intolerance in HFpEF patients despite normal resting hemodynamics and the absence of anatomic LV hypertrophy.Support or Funding InformationFunding Sources: The National Heart Lung and Blood Institute (HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), the Community Foundation for Greater Buffalo, and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine. Baseline/Control RPO Cessation of RPO Tau (ms) 36.5 ± 1.6 35.9 ± 1.6 34.3 ± 1.7 dP/dtmin (mmHg/s) −2116 ± 369 −2301 ± 133 −2464 ± 272 Diastolic Stiffness Coefficient (β) 0.025 ± 0.003 0.054 ± 0.007 * 0.043 ± 0.009 * ΔEDP/ΔEDV During Saline Loading (mmHg/mL) 0.09 ± 0.02 0.21 ± 0.04 * 0.23 ± 0.03 * Ex Vivo Passive Stiffness (kPa) 77.8 ± 11.0 ‐‐‐ 131.0 ± 6.1 * Interstitial Fibrosis (%) 6.6 ± 0.7 12.9 ± 1.8 * 16.3 ± 1.1 * Values are mean ± SEM. *p&lt;0.05 vs. Baseline/Control

Transthyretin Cardiac Amyloidosis as Diagnosed by 99mTc-PYP Scanning in Patients with Acute Heart Failure and Preserved Ejection Fraction.

Transthyretin amyloid deposition is present in 17% of autopsies of patients with heart failure and a preserved ejection fraction (HFpEF). Technetium-pyrophosphate scintigraphy (Tc-PYP) is sensitive and specific to diagnose cardiac transthyretin amyloid deposition (ATTR). The prevalence of ATTR by Tc-PYP was evaluated along with echocardiographic parameters in patients with HFpEF. One-hundred consecutive patients with HFpEF, who had Tc-PYP, were retrospectively evaluated. Echocardiographic variables were analyzed to compare patients with positive versus negative ATTR infiltration. Myocardial ATTR was present in 19% of patients. Individuals with ATTR were older with a mean age of 82 ± 7 versus 75 ± 13 years (P = 0.03), had increased left ventricular hypertrophy with the interventricular septum measuring 1.6 (IQR, 1.4-2.0) versus 1.4 (IQR, 1.3-1.6) cm (P = 0.002), had a greater mean left ventricular mass index of 160 ± 50 g/m versus 131 ± 44 g/m (P = 0.01), and a reduced global longitudinal strain measuring -11% (IQR, -9 to -12) versus -12% (IQR, -10 to -16), P = 0.04. The prevalence of ATTR myocardial deposition demonstrated by Tc-PYP in patients with HFpEF is comparable to that of autopsy studies. It is more common in older patients, with increased left ventricular hypertrophy and reduced global longitudinal strain.

Measurement of Dyspnea in Ambulatory African Americans With Heart Failure and a Preserved or Reduced Ejection Fraction.

Dyspnea is a burdensome and disabling heart failure (HF) symptom. Few studies examining dyspnea in HF have included African Americans (AAs), despite their developing HF at a younger age and having the highest mortality rates. The purpose of this cross-sectional study was to examine dyspnea in AA patients with HF and a preserved ejection fraction (HFpEF) compared with those with a reduced ejection fraction (HFrEF), before and after the 6-minute walk test (6MWT). A convenience sample of ambulatory AA patients (HFrEF, n = 26; HFpEF, n = 19) 50 years or older was recruited from an urban HF clinic. The Borg Scale and a visual analog scale (VAS) were used to measure dyspnea intensity before and after the 6MWT. Activity limitations related to dyspnea were described using the modified Medical Research Council Dyspnea Scale. Group comparisons were analyzed using repeated-measures analysis of variance and χ 2tests. Convergent validity was determined between the Borg and VAS using Bland-Altman plots. No significant differences were found in age, gender, and comorbidities between HF groups. Most HFpEF patients reported dyspnea at baseline (Borg, 63%; VAS, 73%) and after the 6MWT (Borg, 78%; VAS, 79%). In the HFrEF group, the prevalence of baseline dyspnea was greater when measured with the VAS (Borg, 34%; VAS, 80%) but was similar between instruments after the 6MWT (Borg, 64%; VAS, 77%). Both groups reported a similar change in dyspnea intensity during and after the 6MWT. The Bland-Altman plots indicated moderate agreement at each time point. Most patients described walking hurriedly or uphill as dyspnea-provoking on the Modified Respiratory Council Dyspnea Scale. The prevalence of dyspnea at baseline and after the 6MWT was high for both groups, but intensity varied with the dyspnea instrument used.

New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study.

To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study. KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF). We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure. Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012. The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF.

Differences in Blood Volume Components Between Hyporesponders and Responders to Erythropoietin Alfa: The Heart Failure With Preserved Ejection Fraction (HFPEF) Anemia Trial

BackgroundHyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy. MethodsAs part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with 131iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls. ResultsNine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (−96.2 ± 126 vs −402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P < .0001) as well as a decline in plasma volume (r = −0.55; P = .06). ConclusionsAmong older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.

Heart Failure in Patients With Atrial Fibrillation Is Associated With a High Symptom and Hospitalization Burden: The RealiseAF Survey

Atrial fibrillation (AF) and heart failure (HF) often coexist; the consequences of such coexistence are unclear. HF in patients with AF is associated with poor outcomes. This post hoc analysis of RealiseAF, a survey of AF patients, compared symptoms, hospitalizations, management, and AF control in patients with vs without HF. A total of 10,523 AF patients were analyzed according to presence/absence of HF. History of HF was present in 45.8%, and in more patients with permanent vs persistent, paroxysmal, or first-episode AF (55.6%, 44.3%, 32.9%, and 29.8%, respectively; P < 0.0001). Patients with vs those without history of HF, and patients with HF and reduced ejection fraction (HF-REF) vs those with HF and a preserved ejection fraction (HF-PEF), had more frequent cardiovascular (CV) risk factors and more severe symptoms. Presence vs absence of HF, and HF-REF vs HF-PEF, were associated with lower rates of AF control (54.6% vs 62.8% and 49.3% vs 60.3%, respectively; both P < 0.0001). The rate-control strategy was used more frequently in HF patients, particularly those with HF-REF, than the rhythm-control strategy. CV hospitalizations occurred more frequently in patients with HF than those without (41.8% vs 17.5%; P < 0.001) and more frequently in patients with HF-REF than in those with HF-PEF (51.6% vs 35.6%; P < 0.0001). AF patients with HF, particularly HF-REF, experience heavy symptom and hospitalization burdens, and have relatively low rates of AF control. Further studies are needed to identify ways to improve the management and treatment outcomes of this very high-risk patient population.

Biomarkers of Diastolic Dysfunction and Myocardial Fibrosis: Application to Heart Failure with a Preserved Ejection Fraction

Comprehensive diagnostic criteria, accurate prognostic indicators, and effective treatment for patients with heart failure and a preserved ejection fraction (HFpEF) represent a critically important unmet need in cardiovascular medicine. Novel approaches to fill this unmet need are likely to be facilitated by targeting the underlying and unique pathophysiologic mechanisms that characterize patients with HFpEF. Two possible targets include hemodynamic overload evidenced by increased LV diastolic pressure (LVDP) and myocardial fibrosis evidenced by increased extracellular matrix fibrillar collagen. The measurement of LVDP and fibrosis generally requires either invasive procedures and/or complex and sophisticated imaging techniques. However, biomarkers measured in the plasma have been shown to accurately reflect changes in hemodynamic load and myocardial fibrosis and may have important application to the management of patients with HFpEF. The purpose of this review is to describe current and future applications of biomarkers in the management of patients with HFpEF.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction

The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality. The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B-type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all P<0.05). Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF.

A Dosing Algorithm for Erythropoietin Alpha in Older Adults with Heart Failure and a Preserved Ejection Fraction

Erythropoietin stimulating agents (ESAs) is an active area of clinical investigation in heart failure (HF) but can cause hypertension and higher hemoglobin concentrations (Hb) that have been associated with adverse outcomes. We evaluated a dosing algorithm and potential confounders' effect on Hb and blood pressure (BP) in a clinical trial. In an ongoing randomized, placebo controlled, single blind clinical trial of ESA (epoetin alfa) in anemic patients with HF and a preserved ejection fraction (HFPEF), Hb was measured weekly as was BP, weight and concomitant medical therapy. A repeated measure mixed model evaluated determinants of weekly changes in Hb and BP. Among 45 subjects (78 ± 11 years, 67% women, EF = 57 ± 9%) with a total of 780 repeated weekly Hb measures, Hb significantly increased over time in those assigned to ESA (β = 0.933, P < 0.0001), compared to placebo. Dose (β = -0.108, P < 0.0001), patient weight (β = -0.016, P = 0.0037), diuretic use (β = -0.124, P = 0.0389), and time (β = 0.003, P = 0.0331), were all significantly associated with Hb change. Increased diuretic dose and weight change were significantly inversely associated with changes in Hb. ESA administration and dose were not significant determinants of absolute BP or changes in BP from baseline. In addition to ESA dose and duration of therapy, factors indicative of volume status including weight and diuretic use are determinants of hemoglobin levels in HF subjects. The currently employed dosing algorithm, which adjusts the administration of ESA based on the absolute hemoglobin and weekly change in hemoglobin increases Hb with relatively a low weekly dose of ESA without significant effects on BP.

The Impact of Extra Cardiac Comorbidities on Pressure Volume Relations in Heart Failure and Preserved Ejection Fraction

Background Extracardiac comorbidities are common in patients with heart failure and a preserved ejection fraction (HFPEF). We sought to evaluate the relationship between comorbidities and ventricular structure and function in patients with HFPEF through evaluation of pressure-volume analysis. Methods and Results Two hundred twenty Chinese patients with a preserved ejection fraction who were either healthy (n = 75), hypertensive without heart failure (HTN; n = 89), or hypertensive with HFPEF (HFPEF; n = 56) were studied. Using echocardiographic measures, estimated end-systolic and end-diastolic pressure-volume relationships, and the area between them as a function of EDP, the isovolumic pressure-volume areas (PVA iso), were calculated. Ventricular capacitance, as measured by V 30, was larger in patients with HFPEF compared with normal control subjects and tended to be larger compared with hypertensive control subjects. The presence of diabetes and renal insufficiency was independently associated with greater ventricular capacitance in patients with HFPEF. The PVA iso was increased in patients with HFPEF compared with HTN and normal control subjects, and in particular, it was increased in HFPEF patients with multiple comorbidities. Conclusions The presence of comorbid conditions is associated with altered pressure-volume relations and enhanced pump function in subjects with HFPEF, supporting an important role for extracardiac comorbidities in the pathophysiology of patients with this condition.

Racial Differences in Blood Volumes in Patients With Heart Failure and a Preserved Ejection Fraction (HFPEF): Implications for Diagnosing Anemia

Background: Anemia is common in subjects with HFPEF but the diagnosis can be confounded by the concomitant expansion of plasma volume (PV) that occurs in volume overloaded states such as heart failure. The contracted red blood cell volume (RBCV) that characterizes anemia often induces a compensatory expansion of PV in order to maintain the overall blood volume (BV) at a constant level. We analyzed blood volume in subjects with HFPEF to determine if racial differences were present. Methods: 62 patients (70 ± 13 years, 61% female, 34% White, 40% Latino, 26% African-American) with HFPEF (EF = 55 ± 6%) underwent measurement of blood volume by a radiolabeled albumin technique (Daxor Inc, New York, USA) in a stable outpatient state.

Clinical Summaries

Clinical Summaries

Mode of Death in Patients With Heart Failure and a Preserved Ejection Fraction

The mode of death has been well characterized in patients with heart failure and a reduced ejection fraction; however, less is known about the mode of death in patients with heart failure and a preserved ejection fraction (HFPEF). The purpose of this study was to examine the mode of death in patients with HFPEF enrolled in the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-Preserve) trial and to determine whether irbesartan altered the distribution of mode of death in HFPEF. All deaths were reviewed by a clinical end-point committee, and the mode of death was assigned by consensus of the members. The annual mortality rate was 5.2% in the I-Preserve trial. There were no significant differences in mortality rate between the placebo and irbesartan groups. The mode of death was cardiovascular in 60% (including 26% sudden, 14% heart failure, 5% myocardial infarction, and 9% stroke), noncardiovascular in 30%, and unknown in 10%. There were no differences in the distribution of mode-specific mortality rates between placebo and irbesartan. Sixty percent of the deaths in patients with HFPEF were cardiovascular, with sudden death and heart failure death being the most common. Treatment with irbesartan did not affect overall mortality or the distribution of mode-specific mortality rates. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.