Outcomes In Heart Failure With Preserved Ejection Fraction Research Articles

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction.

AimsInsulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF).Methods and resultsWe examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM‐Preserved (left ventricular ejection fraction ≥ 45%), I‐Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N‐terminal pro‐B‐type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end‐diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient‐years in patients without diabetes, and 10.2 and 17.1 per 100 patient‐years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin‐treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23–1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20–2.32, p = 0.002) for sudden death (insulin‐treated diabetes vs. other diabetes).ConclusionsInsulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose‐lowering treatments in HF needs to be evaluated in clinical trials.

Characteristics and outcomes of HFpEF with declining ejection fraction.

Some patients with heart failure with preserved ejection fraction (HFpEF) experience declining of left-ventricular ejection fraction (LVEF) during follow-up. We aim to investigate the characteristics and outcomes of patients with HF with declining ejection fraction (HFdEF). We analyzed a prospective, nationwide multicenter cohort with consecutive patients with acute HF enrolled from March 2011 to December 2014. HFpEF was defined as LVEF ≥ 50% at index admission. After 1year, HFpEF patients were further classified as HFdEF (LVEF ≥ 50% at admission and < 50% at 1year), and persistent HFpEF (LVEF ≥ 50% both at admission and 1year). Primary outcome was 4-year all-cause mortality according to HF type from HFdEF diagnosis. Of patients with HFpEF, 426 (90.4%) were diagnosed as having persistent HFpEF and 45 (9.6%) as having HFdEF. Natriuretic peptide level was an independent predictor of HFdEF (natriuretic peptide level > median: odds ratio: 3.20, 95% confidence interval [CI]: 1.42-7.25, P = 0.005). During 4-year follow-up, patients with HFdEF had higher mortality than those with persistent HFpEF (Log-rank P < 0.001). After adjustment, HFdEF was associated with an almost twofold increased risk for mortality (hazard ratio 1.82, 95% CI 1.13-2.96, P = 0.015). The use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was not associated with improved prognosis of patients with HFdEF. HFdEF is a distinct HF type with grave outcomes. Further investigations that focus on HFdEF are warranted to better understand and develop treatment strategies for these high-risk patients. ClinicalTrial.gov identifier: NCT01389843. URL: https://clinicaltrials.gov/ct2/show/NCT01389843.

Prognostic significance of polyvascular disease in heart failure with preserved left ventricular ejection fraction.

The prognostic significance of systemic atherothrombosis in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the relation between the presence of polyvascular disease (PVD) and cardiovascular outcomes in HFpEF patients.A total of 510 consecutive HFpEF patients were prospectively observed for up to 1500 days or until occurrence of cardiovascular events. PVD was defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, and cerebrovascular disease.Overall, 124 cardiovascular events were observed during follow-up (median: 1430 days). Kaplan–Meier curve showed HFpEF with PVD (n = 84) experienced more cardiovascular events than did those without PVD patients (44.0% vs 20.4%, log-rank: P < .001). Multivariable Cox proportional hazards analysis with significant factors from univariate analysis showed the presence of PVD (hazard ratio [HR]: 2.875, 95% [CI]: 1.894–4.365, P < .001), previous HF hospitalization (HR: 1.578, 95% CI: 1.031–2.414, P = .036), hemoglobin (HR: 0.889, 95% CI: 0.805–0.983, P = .021), serum sodium (HR: 0.946, 95% CI 0.896–1.000, P = .048), ln-BNP (per 1.0, HR: 1.255, 95% CI: 1.055–1.494, P = .010), and E/e’ (HR: 1.047, 95% CI: 1.020–1.075, P < .001) significantly predicted future cardiovascular events. Multivariable Cox hazard analysis with 4 established factors (age, BNP, diabetes mellitus, and previous HF hospitalization) from the I-PRESERVE (Irbesartan in HFpEF) study showed PVD was independently associated with cardiovascular events in HFpEF patients (HR: 2.562, 95% CI: 1.715–3.827, P < .001).The presence of PVD is significantly associated with cardiovascular events in HFpEF, suggesting the importance of screening PVD in HFpEF.

Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThis study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). BackgroundConventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown. MethodsPatient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i.e., sudden death and pump failure death), and all-cause death in unadjusted and adjusted analyses. ResultsOf the 8,466 patients included, 682 patients (8%) had a pacemaker. Pacemaker patients were older and more often men and had lower body mass indexes, estimated glomerular filtration rates, and blood pressures but higher concentrations of N-terminal pro–B-type natriuretic peptide than those without a pacemaker. The rate of the primary composite outcome in pacemaker patients was almost twice that in patients without a pacemaker (13.6 vs. 7.6 per 100 patient-years of follow up, respectively), with a similar finding for HF hospitalizations (10.8 vs. 5.1 per 100 patient-years, respectively). This risk rate persisted after adjusting for other prognostic variables (hazard ratio [HR] for the composite outcome: 1.17; 95% confidence interval [CI]: 1.02 to 1.33; p = 0.026), driven mainly by HF hospitalization (HR: 1.37; 95% CI: 1.17 to 1.60; p < 0.001). The risk of death was not significantly higher in pacemaker patients in the adjusted analyses. ConclusionsThese findings raise the possibility that right ventricular pacing-induced left ventricular dyssynchrony may be detrimental in HFpEF patients.

Relationships between maintenance of sinus rhythm and clinical outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation

BackgroundAlthough atrial fibrillation (AF) is associated with exacerbation of heart failure with preserved ejection fraction (HFpEF), the relationships between maintenance of sinus rhythm (SR) and clinical outcomes in HFpEF is unknown. We investigated whether maintenance of SR was associated with better prognosis compared with rate control in patients with concomitant HFpEF and AF. MethodsWe conducted a retrospective, observational study of 283 patients with HFpEF and AF. Of these, 107 patients achieved maintenance of SR by catheter ablation and/or antiarrhythmic drugs (rhythm control) and 176 were treated with rate control. The propensity score (PS) for each patient in both treatment groups was estimated, resulting in selectively matched subgroups of 79 patients each. All-cause death and a composite of cardiovascular death or hospitalization for heart failure (HF) were analyzed. ResultsDuring a median follow-up period of 24 months, all-cause mortality was comparable between groups; however, maintenance of SR was significantly associated with a lower incidence of the composite endpoint [adjusted hazard ratio (HR), 0.30; 95% confidence interval, 0.18–0.98; p=0.04] in the PS-matched cohort. The PS-adjusted multivariable analysis based on 283 pre-matched patients also revealed that rhythm control was associated with a lower rate of the composite endpoint (adjusted HR, 0.27; 95% CI, 0.12–0.61; p=0.002). Subgroup analyses suggested that rhythm control was consistently related to the composite endpoint across a wide spectrum of HFpEF patients. ConclusionsMaintenance of SR was associated with a lower risk of composite of cardiovascular death or hospitalization for HF in patients with HFpEF and AF. A randomized trial is necessary to confirm this result.

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction

The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF. Patients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome. Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, P = .04). PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.

Prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction: insights from TOPCAT

Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF. We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P < 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001-1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS-risk relationship for any endpoint (P > 0.1 for all). Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization.

Imaging and Management of Heart Failure and Preserved Ejection Fraction.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising and in some places, it is already the most prevalent form of heart failure. The usual treatments of HF do not improve mortality or outcomes in HFpEF, suggesting a distinct pathophysiology that remains poorly characterized. The neutrality of clinical trial results is also attributable to the heterogeneity of patient profiles, and by poor characterization offered by classical echocardiography parameters. Emerging imaging modalities may overcome this problem. We therefore aimed to summarize recent advances offered by cardiovascular imaging in disease characterization, and the implication of findings to new phenotype-specific treatment options. Novel cardiovascular imaging techniques such as LV global longitudinal strain, left atrial strain, tissue characterization by magnetic resonance T1 time, as well as incorporation of systolic and diastolic stress testing offer greatly improved characterization, diagnosis, and stratification of disease pathogenesis. These techniques offer insight into identification of HFpEF sub-phenotypes that are resistant to, or responsive to therapies. There is a growing body of evidence that novel cardiovascular imaging modalities are able to characterize HFpEF patients with much greater accuracy than current guideline-driven parameters. Whether this information can be synthesized to adequately stratify patients into sub-phenotypes with clearer disease pathogenesis amenable to targeted intervention will be of particular future interest.

Heart failure with preserved ejection fraction in Asia

Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia. We prospectively studied clinical characteristics, echocardiographic parameters and outcomes in 1204 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n = 252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines, n = 409). Mean age was 68 ±12 years (37% were < 65 years) and 50% were women. Seventy per cent of patients had ≥2 co-morbidities, most commonly hypertension (71%), followed by anaemia (57%), chronic kidney disease (50%), diabetes (45%), coronary artery disease (29%), atrial fibrillation (29%) and obesity (26%). Southeast Asian patients had the highest prevalence of all co-morbidities except atrial fibrillation, South Asians had the lowest prevalence of all co-morbidities except anaemia and obesity, and Northeast Asians had more atrial fibrillation. Left ventricular hypertrophy and concentric remodelling were most prominent among Southeast and South Asians, respectively (P < 0.001). Overall, 12.1% of patients died or were hospitalized for heart failure within 1 year. Southeast Asians were at higher risk for adverse outcomes, independent of co-morbidity burden and cardiac geometry. These first prospective multinational data from Asia show that HFpEF affects relatively young patients with a high burden of co-morbidities. Regional differences in types of co-morbidities, cardiac remodelling and outcomes of HFpEF across Asia have important implications for public health measures and global HFpEF trial design.

Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial.

To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

Correlation with invasive left ventricular filling pressures and prognostic relevance of the echocardiographic diastolic parameters used in the 2016 ESC heart failure guidelines and in the 2016 ASE/EACVI recommendations: a systematic review in patients with heart failure with preserved ejection fraction.

Five echocardiographic parameters-left atrial volume index, left ventricular mass index, tricuspid regurgitation velocity, myocardial tissue velocity, and the ratio of early mitral inflow to tissue velocity of the mitral annulus (E/e')-are recommended in both the current European Society of Cardiology heart failure guidelines and the American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations for the evaluation of left ventricular diastolic function. We aimed to perform a systematic review of these echocardiographic parameters at resting conditions for their correlation with left ventricular filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). In addition, the prognostic value of these parameters was assessed. Nine studies reported the correlation between echocardiography and invasive haemodynamics, and 18 papers reported on the prognostic value of echocardiography in HFpEF. Among the parameters, most data were reported for E/e'. The pooled correlation coefficient r was 0.56 for the relation between E/e' and invasively measured filling pressures. Combined weighted-mean meta-analysis of prognostic studies resulted in a hazard ratio of 1.05 (95% confidence interval 1.03-1.06) per unit increase in E/e' for the combined outcome of all-cause mortality and cardiovascular hospitalization. The other echocardiographic parameters, when taken individually, had similar or lower association with prognosis. Only a small number of studies validated the use of echocardiographic parameters at rest in patients with HFpEF. The best established parameter appears to be E/e', but the existing data only show modest correlations of E/e' with invasive filling pressures and outcomes in HFpEF.

Left atrial rather than left ventricular impaired mechanics are associated with the pro-fibrotic ST2 marker and outcomes in heart failure with preserved ejection fraction.

Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r=-0.30, P=0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P>0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P=0.023). Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF.

Pharmacological treatments for heart failure with preserved ejection fraction-a systematic review and indirect comparison.

Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), β-adrenoceptor blockers (β-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017. The study outcomes were mortality, hospitalization, changes in indexes of cardiac structure and function, biomarkers, and indexes of functional capacity-quality of life (QoL) assessment and 6-min walk distance test (6-MWD). The random-effects models were used to estimate pooled relative risks (RRs) for the binary outcomes and standardized mean differences for continuous outcomes, with 95% CI. A network meta-analysis using a random-effects model was employed to estimate the comparative efficacy of treatments. We included data from 15 RCTs comprising 5930 patients. There was no significant effect seen with all treatments compared with placebo and comparative efficacy of any two treatments on all outcomes assessed. However, mineralocorticoid antagonist spironolactone demonstrated a trend towards reducing mortality compared with placebo (RR 0.92; 95% CI 0.79-1.08), sildenafil (0.14; 0.01-2.78), perindopril (0.87; 0.59-1.28), and eplerenone (0.91; 0.25-3.33). Similar trends in treatment effect were observed with spironolactone on surrogate outcomes while eplerenone demonstrated a trend of superior effect in reduction of hospitalizations compared with all other drug treatment. No drug treatment demonstrated statistically significant improvement in clinical and surrogate outcomes in HFpEF diagnosed according to the ESC 2016 guideline. Spironolactone and eplerenone showed clinically relevant reduction in mortality and hospitalization respectively compared with other drug treatments. Further trials with MRAs are warranted to confirm treatment effects in HFpEF.

Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is a clinical syndrome of diverse etiologies and can be associated with preserved, reduced, or mid-range ejection fraction (EF). In the community, heart failure with preserved ejection fraction (HFpEF) is emerging as the most common form of HF. There remains considerable uncertainty regarding its pathogenesis, diagnosis, and optimal therapeutic approach. Hypotheses have been advanced to explain the underlying pathophysiology responsible for HFpEF, but to date, no specific therapy based on these hypotheses has been proven to improve outcomes in HFpEF. We provide a clinically focused review of the epidemiology, clinical presentation, diagnostic approach, pathophysiology, and treatment of HFpEF.

Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic problem affecting more than half of the patients with heart failure (HF). HFpEF has a significant morbidity and mortality and so far no treatment has been clearly demonstrated to improve the outcomes in HFpEF, in contrast to the efficacy of treatment in heart failure with reduced ejection fraction (HFrEF).The failure of proven beneficial drugs in HFrEF to influence the outcome of patients with HFpEF could be related to the heterogeneity of the disease, its various phenotypes and multifactorial pathophysiology, incompletely elucidated yet. The diagnosis of HFpEF could be demanding or even inaccurate. Moreover, the therapeutic strategies were influenced by different cut-offs used to define preserved ejection fraction (EF). From this perspective, the current guidelines have classified HFpEF by an EF≥50%, together with a distinct entity, heart failure with mid-range ejection fraction (HFmrEF), defined by an EF ranging from 41-49%.New therapies have been developed to interfere with the mediator pathways of HFpEF at the cellular and molecular level, including mineralocorticoid receptor antagonists, soluble guanylate cyclase stimulators, or angiotensin receptor-neprilysin inhibitors. A number of antidiabetic drugs, such as sodium/glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors are promising options, being under research in large clinical trials. Until the results of ongoing trials shed light on these therapies, guidelines recommend empirical treatment for established HFpEF, and emphasize the crucial role of addressing cardiovascular comorbidities leading to HFpEF, in particular arterial hypertension.

Association of Abnormal Left Ventricular Functional Reserve With Outcome in Heart Failure With Preserved Ejection Fraction

ObjectivesThis study sought to determine the prognostic value of abnormal diastolic and systolic responses to exercise (on the basis of exertional E/e′ and global longitudinal strain rate [GSR]) in a well-characterized population of patients with heart failure with preserved ejection fraction (HFpEF). BackgroundImpaired cardiovascular functional reserve is believed to contribute to adverse outcomes in HFpEF. However, the exact characteristics of pathophysiological profiles associated with increased clinical risk are still poorly defined. MethodsA complete echocardiogram (including assessment of myocardial deformation) was performed at rest in 205 patients (64 ± 8 years of age) with symptomatic HFpEF. Echocardiography following maximal exercise was undertaken to assess abnormal diastolic reserve (AbnDR) (exertional E/e′ >14) and exercise GSR. Patients were followed over 26 ± 5 months for death and cardiovascular or heart failure (HF) hospitalization. ResultsCardiovascular hospitalization or death occurred in 64 patients (31%), including 51 (25%) with HF hospitalization. The composite endpoint was associated with AbnDR (hazard ratio: 2.69; 95% confidence interval: 1.44 to 5.04; p = 0.002) and reduced exercise GSR (hazard ratio: 0.14; 95% confidence interval: 0.04 to 0.49; p = 0.002). Both exercise parameters showed prognostic value, independent from and incremental to clinical data and B-type natriuretic peptide. The ability of E/e′ and GSR measurements to predict outcomes on exertion exceeded their prognostic value at rest, and the presence of reduced exertional GSR in patients with AbnDR was associated with worse prognosis (p = 0.03 for the composite endpoint and p = 0.01 for HF hospitalization). ConclusionsBoth left ventricular systolic and diastolic reserves contribute to risk prediction in HFpEF. The inclusion of the exertional assessment of left ventricular function to diagnostic algorithms may improve the prognostication process in this disease condition.

Abstract 21000: Interaction Between Mineralocorticoid Receptor Antagonist and Soluble ST2 in Heart Failure With Preserved Ejection Fraction

Background: Mineralocorticoid receptor antagonist (MRA) has a potential to improve clinical outcomes in heart failure with preserved ejection fraction (HFpEF), since MRA inhibits progression of myocardial hypertrophy and fibrosis. Soluble ST2 (sST2) is a novel biomarker reflecting myocardial stress and fibrosis. MRA plays a role in the interleukin-33/ST2 signaling modulation. Hypothesis: We hypothesized that the effect of MRA on clinical outcomes in HFpEF differed by sST2 level. This study aimed to evaluate the relationship between sST2 and clinical outcomes and to test for an interaction between the effect of MRA and sST2 level. Methods: 191 patients with acute decompensated HF and EF ≥50% were prospectively enrolled. The primary endpoint was major adverse cardiovascular events (MACE), which included death from cardiovascular disease, unplanned hospitalization for heart failure, acute coronary syndrome and stroke. Results: During follow-up (421±258days), 53 patients (27.7%) met endpoints. In a multivariable analysis, use of MRA and sST2 level were significantly associated with the endpoint (HR 0.48, 95%CI 0.26-0.86, P=0.01, HR 1.02, 1.01-1.03, P=0.01). Patients were divided into 4 groups according to use of MRA and a cutoff value of sST2 (18.5 ng/ml) determined by ROC analysis. Estimated event rate for MACE were significantly higher in patients without MRA compared with those in patients with MRA regardless of category of sST2 level. In a multivariable analysis, MRA was not a significant predictor of outcome in high sST2 group (HR 0.62, 0.28-1.30, P=0.21), whereas MRA was significantly associated with improved outcome in low sST2 group (HR 0.37, 0.13-0.91, P=0.03). Conclusion: The present study showed that higher sST2 level was associated with worse prognosis and predictive of less response to MRA treatment in patients with HFpEF, which suggests that sST2 may be used to predict response to MRA treatment.

The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVEThis study examined the prognostic significance of diabetes and microvascular complications in patients with heart failure with preserved ejection fraction (HFpEF).RESEARCH DESIGN AND METHODSThis analysis included 3,385 patients (mean age 69 ± 9.6 years; 49% male; 89% white) with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Diabetes and microvascular complications were ascertained by self-reported history and medical record review. Microvascular complications included neuropathy, nephropathy, and retinopathy. Outcomes included hospitalization, hospitalization for heart failure, death, and cardiovascular death. Cox regression was used to examine the risk of each outcome associated with diabetes and microvascular complications.RESULTSOf the 1,109 subjects (32%) with diabetes, 352 (32%) had at least one microvascular complication. Patients with diabetes and microvascular complications had an increased risk for hospitalization (no diabetes: referent; diabetes + no microvascular complication: hazard ratio [HR] 1.18, 95% CI 1.01, 1.37; diabetes + microvascular complications: HR 1.54, 95% CI 1.25, 1.89; P-trend <0.001), hospitalization for heart failure (no diabetes: referent; diabetes + no microvascular complication: HR 1.51, 95% CI 1.14, 1.99; diabetes + microvascular complications: HR 1.97, 95% CI 1.38, 2.80; P-trend <0.001), death (no diabetes: referent; diabetes + no microvascular complication: HR 1.35, 95% CI 1.04, 1.75; diabetes + microvascular complications: HR 1.73, 95% CI 1.22, 2.45; P-trend = 0.0017), and cardiovascular death (no diabetes: referent; diabetes + no microvascular complication: HR 1.34, 95% CI 0.96, 1.86; diabetes + microvascular complications: HR 1.70, 95% CI 1.09, 2.65; P-trend = 0.018). When the analysis was limited to participants who reported prior hospitalization for heart failure (n = 2,449), a higher risk of rehospitalization for heart failure was observed across diabetes categories (no diabetes: referent; diabetes + no microvascular complication: HR 1.40, 95% CI 1.01, 1.96; diabetes + microvascular complications: HR 1.78, 95% CI 1.18, 2.70; P-trend = 0.0036).CONCLUSIONSDiabetes is associated with adverse cardiovascular outcomes in HFpEF, and the inherent risk of adverse outcomes in HFpEF patients with diabetes varies by the presence of microvascular complications.

Pulmonary vascular indices and survival in left heart disease: illusion of conclusion?

Pulmonary vascular indices and survival in left heart disease: illusion of conclusion?

Wedge Pressure Rather Than Left Ventricular End-Diastolic Pressure Predicts Outcome in Heart Failure With Preserved Ejection Fraction

ObjectivesThis study sought to compare the prognostic power of left ventricular end-diastolic pressure (LVEDP) and pulmonary arterial wedge pressure (PAWP) in heart failure with preserved ejection fraction (HFpEF). BackgroundIt is broadly accepted that direct measurement of LVEDP in HFpEF more robustly reflects left ventricular hemodynamics than PAWP. MethodsA total of 173 consecutive HFpEF patients were prospectively enrolled. Of these, 152 patients fulfilled registry inclusion criteria. Study participants underwent clinical evaluation, lung function tests, echocardiography, cardiac magnetic resonance, coronary angiography, and invasive hemodynamic assessments with PAWP and LVEDP measurements in 1 procedure. The study endpoint was defined as hospitalization for heart failure or cardiac death. ResultsA modest pressure difference (2.0 ± 4.4 mm Hg) was observed between PAWP (21.5 ± 5.6 mm Hg) and LVEDP (19.5 ± 5.2 mm Hg) at baseline. After a mean follow-up of 23.5 ± 21.3 months, PAWP was predictive of outcome (p = 0.010), whereas LVEDP was not (p = 0.261) by Kaplan-Meier curves. By multivariate regression analysis, diffusion capacity of carbon monoxide (DLCO) was the only parameter that was independently related to the pressure difference between PAWP and LVEDP. When patients were stratified according to DLCO between ≤45% and >45%, those in the low DLCO group were found to have a more pronounced pressure drop between PAWP and LVEDP (3.1 ± 4.8 mm Hg vs. 0.8 ± 3.8 mm Hg, respectively; p = 0.031) and to be in more advanced disease stages. ConclusionsOur data indicate that PAWP but not LVEDP is associated with outcome in HFpEF. A more pronounced difference between PAWP and LVEDP and more advanced disease is found in patients with low DLCO.