Heart Failure With Preserved Left Ventricular Ejection Fraction Research Articles

P2609H2FPEF score as a prognostic value in HFpEF patients

Abstract Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). Purpose We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.

P786Plasma volume status is associated with the change in nutritional status during hospitalization in acute decompensated heart failure patients with preserved left ventricular ejection fraction

Abstract Introduction Plasma volume (PV) expansion has an essential role in heart failure (HF). PV can be estimated by a simple formula using hematocrit and body weight, and PV status (PVS) provides prognostic information in patients (pts) with chronic HF. Nutritional status (NS) based on the prognostic nutritional index (PNI) and NS change during hospitalization have been shown to predict prognosis in pts admitted with acute decompensated HF (ADHF). Purpose We sought to assess the hypothesis that PVS is associated with NS change during hospitalization in pts with HF with preserved LVEF (HFpEF) who are admitted with ADHF. Methods We prospectively studied 411 pts who were admitted for ADHF with LVEF ≥50% and survived to discharge. Body weight measurement and venous blood sampling were performed on admission and at discharge. PVS was defined as follows: actual PV = (1 − hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females); and PVS = [(actual PV − ideal PV)/ideal PV] × 100 (%). PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). The pts were divided into 3 groups by PNI: normal (>38), moderate malnutrition (35–38), and severe malnutrition (<35). During admission, pts who remained in the moderate or severe malnutrition group or whose NS worsened were defined as no improvement in NS. Follow-up data was obtained in 203 cases. They were followed for up to 18 months, and the incidence of all-cause death was evaluated. Results On admission, PVS in the moderate (n=71, 13.3±13.9%) or severe malnutrition group (n=69, 14.8±10.8%) was significantly higher than in the normal PNI group (n=271, 5.4±10.8%, p<0.001). During hospitalization, 123 pts had no NS improvement. Admission PVS was significantly higher in pts with no NS improvement than in pts with improved NS (13.9±11.2% vs 5.9±12.8%, p<0.0001). In multivariate logistic regression analysis, admission PVS was independently associated with no NS improvement during hospitalization (OR 1.06, 95% CI 1.03–1.08, p<0.0001). Receiver operating characteristics curve analysis revealed that the optimal cut-off value of admission PVS for predicting no NS improvement was 9.4% (sensitivity: 72%, specificity: 63%). The area under the curve for predicting no NS improvement using admission PVS was significantly greater than for other independent factors (Figure 1A). During the follow-up period (median 12.4 months), 68 of 203 patients had all-cause death. Kaplan-Meier analysis showed that the patients with no NS improvement had a significantly higher risk of all-cause death (Figure 1B). Figure 1 Conclusions In this multicenter study, admission PVS was shown to be associated with poor improvement in NS during hospitalization in HFpEF pts admitted for ADHF. Acknowledgement/Funding Roche diagnostics, FUJIFILM Toyama Chemical

H2FPEF Score as a Prognostic Value in HFpEF Patients.

The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0-3), intermediate- (4-6), and high-score (7-9) groups and followed for 50 months. The primary and secondary endpoints were composite cardiovascular/cerebrovascular events (cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation, and nonfatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50 months, respectively. Kaplan-Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events among those with a higher H2FPEF score (log-rank test, P = 0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P < 0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (hazard ratio [HR], 1.179; 95% confidence interval [CI], 1.066-1.305; P = 0.001 and HR, 1.288; 95% CI, 1.134-1.463; P = 0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (area under the curve [AUC], 0.626; 95% CI, 0.557-0.693; P < 0.001) and HF-related events (AUC, 0.680; 95% CI, 0.600-0.759; P < 0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. The H2FPEF score might be a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients. Trail Number UMIN000029600.

Zalety stosowania spironolaktonu w niewydolności serca u pacjentów z zachowaną frakcją wyrzutową lewej komory

The main goal of treatment in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) is to improve left ventricular (LV) diastolic function and reduce the symptoms of heart failure (HF), and thereby improve their quality of life. An additional goal of treatment should be normalization of blood pressure and/or prevention of atrial fibrillation (AF). In patients with HFpEF, spironolactone therapy had beneficial effect on anatomical changes and improved LV systolic and diastolic function. The STRUCTURE study showed that regression of LV remodeling along with the improvement of LV systolic and diastolic function following administration of spironolactone resulted in a significantly improved exercise capacity of these patients, assessed by spiroergometry. In the subpopulation analysis of North and South American participants of the TOPCAT study, spironolactone therapy was associated with a significant reduction in the primary composite endpoint (time to cardiovascular death + hospitalization due to HF + cardiac arrest), cardiovascular mortality, hospitalization due to HF, and re-hospitalization due to HF. In AF patients with structural heart disease, spironolactone added to standard therapy, including amiodarone, significantly increased the time to hospitalization or cardioversion due to another AF episode. In the ASCOT-BPLA study, spironolactone, administered as the 4th antihypertensive agent, caused a significant decrease in systolic and diastolic blood pressure in patients with resistant hypertension. When assessing the results of the studies with spironolactone, it can be noticed that the therapy with this drug was relatively safe in patients with HFpEF, considering the age of these patients and their comorbidities. The results of previous studies assessing the efficacy of mineralocorticoid receptor antagonists in HFpEF do not indicate a class effect of these drugs.

Effective blood hemoglobin level to predict prognosis in heart failure with preserved left ventricular ejection fraction: results of the Japanese heart failure syndrome with preserved ejection fraction registry.

High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan-Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.

The clinical application value of the plasma copeptin level in the assessment of heart failure with reduced left ventricular ejection fraction: A cross-sectional study.

This study aimed to evaluate the clinical applicability of the plasma copeptin level to assess heart failure with reduced left ventricular ejection fraction (HFrEF).One hundred thirty-one patients with HFrEF, 127 patients with heart failure with preserved left ventricular ejection fraction (HFpEF), and 119 healthy candidates were involved. The basic data and examination results of patients were collected. The heart function of the patients with HFrEF and HFpEF were graded on the basis of the criteria of New York Heart Association (NYHA) classification. The plasma copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were tested using enzyme-linked immunosorbent assays (ELISAs).The copeptin and NT-proBNP levels were higher in the HFrEF group than in the HFpEF group. The copeptin and NT-proBNP values increased as the NYHA grade increased in the patients with HFrEF. However, for the patients with HFpEF, the copeptin levels did not change markedly as the NYHA grade increased. The copeptin levels were positively correlated with the NT-proBNP levels in the patients with HFrEF; however, there was no correlation between the copeptin and NT-proBNP values in the patients with HFpEF.Copeptin is involved in the process of progression in patients with HFrEF and the copeptin values might be useful for HFrEF prediction and assessment in the clinic.

A novel predictor of clinical outcomes in patients with heart failure with preserved left-ventricular ejection fraction: a pilot study.

Predictors of outcomes in patients with heart failure with preserved left-ventricular ejection fraction (HFpEF) remain unclear. The ratio of early diastolic transmitral flow velocity to early diastolic myocardial velocity (E/e') has been proposed, but the predictive accuracy remains unsatisfactory. We hypothesized that E/e' normalized by the stroke volume (SV), E/e'/SV, could be a good predictor of outcome in HFpEF patients by reflecting the terminal slope of the end-diastolic pressure-volume relation, i.e., stiffness of the left ventricle. This pilot study was conducted to propose a novel echocardiographic index for predicting the outcomes of patients with HFpEF. Echocardiography including E/e'/SV measurement was performed in consecutive 80 HFpEF patients at discharge in index hospitalization due to HF. The end points included the readmission for heart failure and cardiovascular death at 1 year after discharge. 19 patients (24%) met the end points. Receiver-operating characteristic analysis showed that E/e''/SV was a strong predictive factor (AUC = 0.78) compared to E/e' (AUC = 0.74). Kaplan-Meier analysis showed that patients with E/e'/SV > 0.40 had a poorer prognosis than those with E/e'/SV < 0.40 (p < 0.01). By Cox regression multi-variate analysis, a high E/e'/SV was an independent predictor of event-free survival [adjusted hazard ratio (95% CI) 14.26 (3.18, 63.93) (p = 0.01)]. E/e'/SV has potential to predict clinical outcomes in patients with HFpEF.

Hypertrophic cardiomyopathy in glycogen storage disease type III: Clinical features and long-term outcome

Glycogen storage disease type III (GSD III) is an autosomal recessive disease, due to deficiency of glycogen debranching enzyme (GDE), a key enzyme involved in glycogen degradation. Hypertrophic cardiomyopathy is a classical complication in this disease. We performed a longitudinal study in order to describe the natural history of heart involvement, relationship with genotype and to determine long term follow up related to hypertrophic cardiomyopathy in patients with GSD III. We included all consecutive patients with GSD III followed in Pitié-Salpêtrière and Antoine Beclere centers and collected clinical, genetic, electrocardiogram and echocardiography data and cardiac events. 37 patients were included in this study (12 males/25 females). Mean age was 22.4 years [1–52]. All patients were in sinus rhythm expect one patient (atrial fibrillation). Electrical left ventricular hypertrophy was found in 16 (43%) patients. Symptomatic heart failure was found in 8 (22%) patients and 1 (3%) patient disclosed left ventricular dysfunction. Left ventricular hypertrophy (LVH) was found in 16 (43%) patients, mostly symmetric and 4 (11%) patients disclosed obstructive hypertrophic cardiomyopathy. Patients essentially developed heart failure with preserved LVEF (HFpEF) which prevalence increased with age. In univariate analysis, nonsense mutations were associated with more LVH than other type of mutations but not in multivariate analysis. Hypertrophic cardiomyopathy is frequent in patients with GSD3 and is associated with cardiac clinical events, especially HFpEF.

Clinical significance of brachial-ankle pulse-wave velocity in patients with heart failure with preserved left ventricular ejection fraction.

Although pulse-wave velocity (PWV) is a recognized risk predictor for cardiovascular diseases, its association with cardiovascular outcomes in heart failure with preserved left ventricular ejection fraction (HFpEF) is unclear. The 502 patients with HFpEF finally enrolled in this study (mean follow-up duration: 1017 days) were divided into those with or without peripheral artery disease (PAD). The latter were further grouped according to brachial-ankle PWV (baPWV) quintiles using an ankle-brachial pressure index device. Kaplan-Meier analysis revealed a significantly higher risk of all-cause mortality and total cardiovascular events (both P = 0.01) in HFpEF patients with than without PAD. Multivariate Cox hazard analysis, including predictors identified as significant by simple Cox hazard analysis, identified PAD as a significant and independent predictor of cardiovascular events (hazard ratio: 1.85; 95% confidence interval: 1.01-3.39; P = 0.04). In an analysis of HFpEF patients without PAD grouped according to baPWV quintiles, estimated glomerular filtration rate (r = 0.21, P < 0.01) and hemoglobin (r = 0.18, P = 0.01) levels correlated negatively with baPWV. In the Kaplan-Meier analysis, patients with a baPWV more than 1900 cm/s and those with the lowest baPWV (<1300 cm/s) had a significantly higher frequency of total cardiovascular events than patients with 1300 baPWV or less which is less than 1900, indicating a J-shaped association between baPWV and total cardiovascular events as well as similarities to HFpEF patients with PAD. By contrast, the lowest baPWV group had the highest risk of heart failure-related events, accompanied by the highest brain natriuretic peptide levels. Identifying complications of PAD and measuring baPWV values in HFpEF patients can improve risk stratification.

Teasing Apart Heart Failure With Preserved Ejection Fraction Phenotypes With Echocardiographic Imaging: Potential Approach to Research and Clinical Practice.

Phenotyping heart failure represents a major challenge for both research studies and clinical practice. Large-scale clinical trials have failed to achieve meaningful improvement in clinical outcomes with different pharmacological agents in patients with heart failure and preserved left ventricular ejection fraction. Therefore, an alternative scheme for phenotyping heart failure is needed, which is both pathophysiologically distinct and practical for routine clinical application. Heart failure is a syndromic diagnosis broadly based on clinical features, physical findings, and serum biomarkers. Although the assessment of exercise hemodynamics and invasive estimation of filling pressures may be necessary, it is typically confirmed and phenotyped by the imaging data. Phenotyping heart failure represents a major challenge despite decades of ongoing research, vast clinical experience in the field, and multiple iterations of published guidelines. Left ventricular ejection fraction (LVEF) remains the major phenotyping tool endorsed by multiple cardiology societies. However, it has multiple limitations especially in patients with heart failure with preserved LVEF (HFpEF), and many have questioned the current approach to phenotyping of heart failure but no alternative, widely accepted, scheme (which is both clinically relevant and practical) has been offered.1 The existing phenotyping approach to heart failure is based on the premise of LVEF as a surrogate marker for left ventricular systolic performance and, in turn, prognosis. Heart failure patients with reduced LVEF (HFrEF) are assumed to have systolic heart failure, whereas many heart failure patients have preservation of LVEF and are commonly labeled as HFpEF. This assumption makes LVEF the primary marker of heart failure and excludes other important abnormalities that can create the heart failure syndrome. Furthermore, LVEF is an imperfect marker even for assessment of systolic function: it has high interobserver variability, it mainly reflects radial shortening, it is load dependent, and it does not reflect the remodeling pattern of the …

Сердечная недостаточность с сохраненной фракцией выброса левого желудочка: эпидемиология, «портрет» больного, клиника, диагностика

The article focuses on current aspects of epidemiology, clinical picture, and diagnostics of patients with chronic heart failure (CHF) associated with preserved left ventricular (LV) systolic function. Heart failure with preserved LV ejection fraction (HFpEF) is shown to be prevalent in a population that accounts for more than a half of all CHF cases. The group at risk for HFpEF consists primarily of older women with arterial hypertension, type 2 diabetes mellitus, obesity, and atrial fibrillation. The article presents algorithms for diagnosis of HFpEF based on classic and tissue Doppler echocardiography and measurement of natriuretic peptides.

Heart rate as a prognostic marker and therapeutic target in acute and chronic heart failure

Since increased heart rate (HR) is associated with higher mortality in several cardiac disorders, HR is considered not only a physiological indicator but also a prognostic and biological marker. In heart failure (HF), it represents a therapeutic target in chronic phase. The use or up-titration of beta-blockers, a milestone in HF with reduced left ventricular ejection fraction (LVEF) treatment, is at times limited by patients' hemodynamic profile or intolerance. Ivabradine, a HR-lowering drug inhibiting the f-current in pacemaker cells, has been shown to improve outcome in patients with chronic HF, in sinus rhythm with increased HR beyond beta-blocker therapy. The rationale for this review is to update the role of HR as a prognostic biomarker and a potential therapeutic target in other scenarios than chronic HF; namely, in patients with coexisting atrial fibrillation (AF), in HF with preserved LVEF (HFpEF), in acute HF, and in patients discharged after an episode of acute HF. Preliminary studies and case reports that evaluated the use of ivabradine in the setting of acute HF will be summarized. Recent results of HR reduction in the setting of HFpEF with ivabradine will be presented. Finally, data from large registries and trials that evaluated the prognostic impact of HR in patients with acute HF and sinus rhythm or AF will be reviewed, showing that only patients in sinus rhythm may benefit from HR reduction.

YIA-CS1-6 - Importance of Left Ventricular End-systolic Volume Index as a Prognostic Indicator in Heart Failure with Preserved Left Ventricular Ejection Fraction

Background: A prognostic efficacy of Left ventricular ejection fraction (LVEF) in heart failure with preserved LVEF (HFpEF) is unclear. Methods: We enrolled 471 patients (LVEF>&=50%) who received a catheterization study and obtained baseline characteristics including LVEF, LV end-diastolic and end-systolic volume indices (LVEDVI, LVESVI) which were measured by left ventriculography. Pressure parameters such as tau, and inertia force of late systolic aortic flow (IFLAF) were also obtained using a catheter-tipped micro-manometer. Cardiovascular death or hospitalization for HF were defined as adverse events, and prognostic values of parameters were estimated using a Cox proportional-hazard model. In addition, we compared the prognostic efficacy and correlations with pressure parameters between LVEF, LVESVI, and LVEDVI. Results: During 6.61 ± 4.08 year-follow-up, 39 adverse events were documented. The Cox model after adjustments for age, gender, and hemoglobin level demonstrated that 3 parameters had a significant prognostic value for adverse events (LVEF: HR: 0.951, 95%CI: 0.916–0.987, P = .008; LVEDVI: HR: 1.033, 95%CI: 1.017–1.049, P < .001; LVESVI: HR: 1.049, 95%CI: 1.025–1.074, P < .001) According to the comparison of AUC in the 3 parameters, the LVESVI was most accurate (AUC: 0.694, 0.351 (LVEF), 0.661 (LVEDVI)). Furthermore, the LVESVI demonstrated the strongest correlations with tau (r = 0.364, -0.284 (LVEF), 0.330 (LVEDVI)) and IFLAF (r=-0.358, 0.320 (LVEF), -0.277 (LVEDVI)) in the 3 parameters. Conclusion: Enlargement of LVESVI could be a reliable prognostic indicator in HFpEF.

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study.

This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by 11C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). Included in the study were 34 patients (age 63±15years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). 11C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a 11C-HED retention index (RI, %/min). To identify predictors of regional 11C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix. Global 11C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P<0.01 for all). Regional 11C-HED RI was correlated positively with systolic wall thickening (r=0.42, P<0.001) and negatively with the extent of LGE (r=-0.43, P<0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional 11C-HED RI among all segments (P<0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional 11C-HED RI in HFpEF patients (both P≤0.001). Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.

CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.

Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic substudy of patients randomized to sildenafil (n = 85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0.045 for repeated measures analysis), although this P value did not meet our corrected significance threshold of 0.0167. In the more homogeneous Caucasian subgroup, this association was significant (adjusted P=0.0165 for repeated measures). Hence, CYP3A4 inferred phenotype is associated with peak sildenafil dose-adjusted concentrations in patients with HFpEF receiving high doses of sildenafil. The clinical impact of this association requires further investigation.

Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study.

The new category of heart failure (HF), HF with mid-range left ventricular ejection fraction (LVEF) (HFmrEF), has recently been proposed. However, the clinical features of HFmrEF, with reference to HF with preserved LVEF (HFpEF) and HF with reduced LVEF (HFrEF) in the same HF cohort, remain to be fully examined. In the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study, we examined 3480 consecutive HF patients with echocardiography data consisting of 2154 HFpEF (LVEF ≥50%), 596 HFmrEF (LVEF 40-49%) and 730 HFrEF (LVEF <40%). While clinical characteristics and prognostic factors of HFmrEF were intermediate between HFpEF and HFrEF, prognosis of HFmrEF resembled HFpEF and the prognostic impact of cardiovascular medications in HFmrEF resembled that of HFrEF. Analysis of LVEF transition among the three groups revealed that HFmrEF and HFrEF dynamically transitioned to other categories, especially within 1 year, whereas HFpEF did not; HFmrEF at registration transitioned to HFpEF and HFrEF by 44% and 16% at 1 year, and 45% and 21% at 3 years, respectively. Landmark analysis demonstrated that, regardless of HF stages at registration, HFmrEF patients at 1 year had mortality comparable to that of HFpEF patients, which was better than HFrEF patients, but HFmrEF patients at registration had increased mortality when transitioned to HFrEF at 1 year. These results indicate that clinical characteristics of HFmrEF are intermediate between HFpEF and HFrEF and that HFmrEF dynamically transitions to HFpEF or HFrEF, especially within 1 year, suggesting that HFmrEF represents a transitional status or an overlap zone between HFpEF and HFrEF, rather than an independent entity of HF.

Mitral systolic velocity at peak exercise predicts impaired exercise capacity in patients with heart failure with preserved ejection fraction.

Nearly half of patients with heart failure have normal left ventricular ejection fraction (LVEF), but their prognosis is no better than those with reduced LVEF. Although peak oxygen consumption (VO2 ) is an independent predictor of mortality in heart failure, it is unclear how cardiac function during exercise contributes to peak VO2 . Therefore, we explored the useful parameters measured by exercise stress echocardiography to predict peak VO2 in patients with heart failure with preserved LVEF (HFpEF). We assessed 80 patients being investigated for effort intolerance or dyspnea and finally analyzed 50 patients who satisfied the HFpEF criteria. Mean peak VO2 was 16.4±2.8mL/kg/min. Twenty-three patients (46.0%) achieved a peak VO2 <16.0mL/kg/min (Weber class C or D). There was a significant relationship between mitral systolic velocity (S') and cardiac output (CO) at rest (R=.55, P<.0001) and peak exercise (R=.64, P<.0001). The absolute increase in S' from rest to peak exercise also correlated with the absolute increase in CO (R=.32, P=.02). Multivariate logistic regression analysis showed that S' at peak exercise independently predicted peak VO2 . Receiver-operator characteristic curve analysis identified that an S' at peak exercise of ≤8.13cm/s predicted a peak VO2 <16.0mL/kg/min (sensitivity 95.7%, specificity 44.4%, area under curve 0.70, 95% confidence interval 0.55-0.84, P=.004). Mitral systolic velocity at peak exercise accurately reflects peak VO2 and may facilitate stratification of risk in patients with HFpEF.

BNP and obesity in acute decompensated heart failure with preserved vs. reduced ejection fraction: The Atherosclerosis Risk in Communities Surveillance Study

BackgroundLevels of B-type natriuretic peptide (BNP), a prognostic marker in patients with heart failure (HF), are lower among HF patients with obesity or preserved Left Ventricular Ejection Fraction (LVEF). We examined the distribution and prognostic value of BNP across BMI categories in acute decompensated heart failure (ADHF) patients with preserved vs. reduced LVEF. MethodsWe analyzed data from the Atherosclerosis Risk in Communities (ARIC) HF surveillance study which sampled and adjudicated ADHF hospitalizations in patients aged ≥55years from 4 US communities (2005–2009). We examined 5 BMI categories: underweight (<18.5kg/m2), normal weight (18.5–<25), overweight (25–<30), obese (30–<40) and morbidly obese (≥40) in HF with preserved LVEF (HFpEF) and reduced LVEF (HFrEF). The outcome was 1-year mortality from admission. We used ANCOVA to model log BNP and logistic regression for 1-year mortality, both adjusted for demographics and clinical characteristics. ResultsThe cohort included 9820 weighted ADHF hospitalizations (58% HFrEF; 42% HFpEF). BNP levels were lower in HFpEF compared to HFrEF (p<0.001) and decreased as BMI increased within the LVEF groups (p<0.001). After adjustment for covariates, log10 BNP independently predicted 1-year mortality (adjusted OR 1.62 (95% CI 1.17–2.24)) with no significant interaction by BMI or LVEF groups. ConclusionsBNP levels correlated inversely with BMI, and were higher in HFrEF compared to HFpEF. Obese patients with HFpEF and ADHF had a significant proportion with BNP levels below clinically accepted thresholds. Nevertheless, BNP was a predictor of mortality in ADHF across groups of BMI in HFpEF and HFrEF.

The Impact Exerted on Clinical Outcomes of Patients With Chronic Heart Failure by Aldosterone Receptor Antagonists: A Meta-Analysis of Randomized Controlled Trials.

BackgroundAldosterone receptor antagonists (ARAs) have been associated with improved clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with heart failure with preserved left ventricular ejection fraction (HFpEF). With the aim to study this topic more deeply, we carried out a meta-analysis of selective and non-selective ARAs in HFREF and HFpEF.MethodsWe searched PubMed and Scopus databases. We decided to incorporate in the meta-analysis only randomized controlled trials (RCTs) of ARAs in patients with chronic heart failure (CHF) if they met the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause death, hospitalizations from cardiovascular cause, hyperkalemia, or gynecomastia.ResultsWe detected 15 studies representing 15,671 patients. ARAs were associated with a reduced odds of all-cause death (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.73 - 0.87) and hospitalizations from cardiovascular cause (OR: 0.73; 95% CI: 0.61 - 0.89). However, subgroup analysis showed that these advantages were limited to HFREF (all-cause death: OR: 0.77, 95% CI: 0.69 - 0.84; hospitalizations from cardiovascular cause: OR: 0.66, 95% CI: 0.51 - 0.85), but they did not affect the HFpEF group (all-cause death: OR: 0.91, 95% CI: 0.76 - 1.1; hospitalizations from cardiovascular cause: OR: 0.85, 95% CI: 0.7 - 1.09). ARAs increased the risk of hyperkalemia (OR: 2.17; 95% CI: 1.88 - 2.5). Non-selective ARAs, but not selective ARAs, increased the risk of gynecomastia (OR: 8.22, 95% CI: 4.9 - 13.81 vs. OR: 0.74, 95% CI: 0.43 - 1.27).ConclusionsARAs reduced the risk of adverse cardiac events in HFREF but not HFpEF. In particular, ARA use in HFpEF patients is questionable, since in this CHF type, no significant improvement in all-cause death and cardiovascular hospitalizations was demonstrated with ARA treatment, in the face of the well-known risks of hyperkalemia and/or gynecomastia that chronic ARA therapy entails. Selective ARAs were equally effective as non-selective ARAs, without the risk of gynecomastia.

Molecular Approaches in HFpEF: MicroRNAs and iPSC-Derived Cardiomyocytes.

Heart failure with preserved left ventricular ejection fraction (HFpEF) has emerged as one of the largest unmet needs in cardiovascular medicine. HFpEF is increasing in prevalence and causes significant morbidity, mortality, and health care resource utilization. Patients have multiple co-morbidities which contribute to the disease complexity. To date, no effective treatment for HFpEF has been identified. The paucity of cardiac biopsies from this patient population and the absence of well-accepted animal models limit our understanding of the underlying molecular mechanisms of HFpEF. In this review, we discuss combining state-of-the-art technologies of microRNA profiling and human induced pluripotent cell-derived cardiomyocytes (iPSC-CMs) in order to uncover novel molecular pathways that may contribute to the development of HFpEF. Here, we focus the advantages and limitations of microRNA profiling and iPSC-CMs as a disease model system to discover molecular mechanisms in HFpEF.