Rate pressure product and the components of heart rate and systolic blood pressure in hospitalized heart failure patients with preserved ejection fraction: Insights from ASCEND-HF.
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SUBMITTER: Verma AK
PROVIDER: S-EPMC6103846 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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Rate pressure product and the components of heart rate and systolic blood pressure in hospitalized heart failure patients with preserved ejection fraction: Insights from ASCEND-HF.
Verma Amanda K AK Sun Jie-Lena JL Hernandez Adrian A Teerlink John R JR Schulte Phillip J PJ Ezekowitz Justin J Voors Adriaan A Starling Randall R Armstrong Paul P O'Conner Christopher M CM Mentz Robert J RJ
Clinical cardiology 20180717 7
<h4>Background</h4>Heart rate and systolic blood pressure (SBP) are prognostic markers in heart failure (HF) with reduced ejection fraction (HFrEF). Their combination in rate pressure product (RPP) as well as their role in heart failure with preserved ejection fraction (HFpEF) remains unclear.<h4>Hypothesis</h4>RPP and its components are associated with HFpEF outcomes.<h4>Methods</h4>We performed an analysis of Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated He ...[more]
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Project description:BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
| S-EPMC8109279 | biostudies-literature
Project description:Importance:Lower systolic blood pressure (SBP) levels are associated with poor outcomes in patients with heart failure. Less is known about this association in heart failure with preserved ejection fraction (HFpEF). Objective:To determine the associations of SBP levels with mortality and other outcomes in HFpEF. Design, Setting, and Participants:A propensity score-matched observational study of the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 25 354 patients who were discharged alive; 8873 (35.0%) had an ejection fraction of at least 50%, and of these, 3915 (44.1%) had stable SBP levels (≤20 mm Hg admission to discharge variation). Data were collected from 259 hospitals in 48 states between March 1, 2003, and December 31, 2004. Data were analyzed from March 1, 2003, to December 31, 2008. Exposure:Discharge SBP levels less than 120 mm Hg. A total of 1076 of 3915 (27.5%) had SBP levels less than 120 mm Hg, of whom 901 (83.7%) were matched by propensity scores with 901 patients with SBP levels of 120 mm Hg or greater who were balanced on 58 baseline characteristics. Main Outcomes and Measures:Thirty-day, 1-year, and overall all-cause mortality and heart failure readmission through December 31, 2008. Results:The 1802 matched patients had a mean (SD) age of 79 (10) years; 1147 (63.7%) were women, and 134 (7.4%) were African American. Thirty-day all-cause mortality occurred in 91 (10%) and 45 (5%) of matched patients with discharge SBP of less than 120 mm Hg vs 120 mm Hg or greater, respectively (hazard ratio [HR], 2.07; 95% CI, 1.45-2.95; P < .001). Systolic blood pressure level less than 120 mm Hg was also associated with a higher risk of mortality at 1 year (39% vs 31%; HR, 1.36; 95% CI, 1.16-1.59; P < .001) and during a median follow-up of 2.1 (overall 6) years (HR, 1.17; 95% CI, 1.05-1.30; P = .005). Systolic blood pressure level less than 120 mm Hg was associated with a higher risk of heart failure readmission at 30 days (HR, 1.47; 95% CI, 1.08-2.01; P = .02) but not at 1 or 6 years. Hazard ratios for the combined end point of heart failure readmission or all-cause mortality associated with SBP level less than 120 mm at 30 days, 1 year, and overall were 1.71 (95% CI, 1.34-2.18; P < .001), 1.21 (95% CI, 1.07-1.38; P = .004), and 1.12 (95% CI, 1.01-1.24; P = .03), respectively. Conclusions and Relevance:Among hospitalized patients with HFpEF, an SBP level less than 120 mm Hg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in patients with HFpEF.
| S-EPMC5875342 | biostudies-literature
Project description:OBJECTIVES:This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). BACKGROUND:Although diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. METHODS:We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined. RESULTS:The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (-20.0 ± 2.1 and -17.07 ± 2.04 vs. -14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (-27.1 ± 3.1 and -30.1 ± 3.5 vs. -22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = -0.46; p < 0.0001; CS, R = -0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001). CONCLUSIONS:Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588).
| S-EPMC7195816 | biostudies-literature
Project description:Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril-valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97?mg of sacubitril with 103?mg of valsartan twice daily) or valsartan (target dose, 160?mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.
| S-EPMC7944492 | biostudies-literature
Project description:BackgroundLow flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition.MethodsA cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years.ResultsRVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not.ConclusionParadoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.
| S-EPMC7262439 | biostudies-literature
Project description:Background:Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF). Methods:Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization. Results:1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p?<?0.05), multivariate COX model confirmed that anemia was not independently associated with all-cause mortality [hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.85-1.52, p?=?0.386] and all-cause re-hospitalization (HR 1.13, 95% CI 0.96-1.33, p?=?0.152). Similarly, RD was not an independent predictor of all-cause mortality (HR 1.18, 95% CI 0.88-1.57, p?=?0.269) and all-cause re-hospitalization (HR 0.94, 95% CI 0.79-1.12, p?=?0.488) as assessed in the adjusted COX regression model. The interaction between RD and anemia on end-points events was also not statistically significant. However, anemia was associated with increased all-cause re-hospitalization in patients with New York Heart Association (NYHA) class III-IV. Conclusions:In patients with HFpEF from CN-HF registry, anemia was common, but was not an independent predictor of all-cause mortality and all-cause re-hospitalization, except for the all-cause re-hospitalization in patients with NYHA class III-IV.Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/home; ID: NCT02079428.
| S-EPMC6726881 | biostudies-literature
Project description:Background The association between blood pressure control and clinical outcomes is unclear among patients with heart failure with preserved ejection fraction. Both too high and too low of systolic blood pressure (SBP) have been reported to be related to poor clinical prognosis. This study aimed to assess the association between time in SBP target range and adverse clinical events among patients with heart failure with preserved ejection fraction. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, a randomized clinical trial that compared the efficacy and safety of spironolactone in patients with heart failure with preserved ejection fraction. Time in target range (TTR) was calculated using linear interpolation, with the target range of SBP defined as 110 to 130 mm Hg. The association between TTR with adverse outcomes was estimated using multivariable Cox regression to adjust for multiple confounders. Participants with greater TTR were younger, more likely to be White, had less comorbidities, and lower body mass index. After adjusting for multiple covariates including mean SBP, 1-SD increment (38.3%) of TTR was significantly associated with a decreased risk of primary composite end point (hazard ratio [HR], 0.81 [0.73-0.90]), as well as a lower risk of all-cause mortality (HR, 0.81 [0.73-0.90]), cardiovascular death (HR, 0.78 [0.68-0.90]), and heart failure hospitalization (HR, 0.85 [0.74-0.97]). Results were similar when participants were categorized by TTR groups. Subgroup analyses showed that the associations were more significant in young people than in the old (Pinteraction=0.028). Conclusions In patients with heart failure with preserved ejection fraction, greater time in SBP target range was statistically associated with a decreased risk of cardiovascular outcomes and mortality events beyond blood pressure level, especially among younger patients.
| S-EPMC9075464 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ?50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
| S-EPMC6334030 | biostudies-literature
Project description:BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Some patients develop elevated filling pressures exclusively during exercise and never require hospitalization, whereas others periodically develop congestion that requires inpatient treatment. The features differentiating these cohorts are unclear.MethodsWe performed a secondary analysis of 7 National Institutes of Health-sponsored multicenter trials of HFpEF (EF ≥ 50%, N = 727). Patients were stratified by history of hospitalization because of HF, comparing patients never hospitalized (HFpEFNH) to those with a prior hospitalization (HFpEFPH). Currently hospitalized (HFpEFCH) patients were included to fill the spectrum. Clinical characteristics, cardiac structure, biomarkers, quality of life, functional capacity, activity levels, and outcomes were compared.ResultsAs expected, HFpEFCH (n = 338) displayed the greatest severity of congestion, as assessed by N-terminal pro B-type natriuretic peptide levels, edema and orthopnea. As compared to HFpEFNH (n = 109), HFpEFPH (n = 280) displayed greater comorbidity burden, with more lung disease, renal dysfunction and anemia, along with lower activity levels (accelerometry), poorer exercise capacity (6-minute walk distance and peak exercise capacity), and more orthopnea. Patients with current or prior hospitalization displayed higher rates of future HF hospitalization, but quality of life was similarly impaired in all patients with HFpEF, regardless of hospitalization history.ConclusionsA greater burden of noncardiac organ dysfunction, sedentariness, functional impairment, and higher event rates distinguish patients with HFpEF and prior HF hospitalization from those never hospitalized. Despite lower event rates, quality of life is severely and similarly limited in patients with no history of hospitalization. These data suggest that the 2 clinical profiles of HFpEF may require different treatment strategies.
| S-EPMC7704788 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence as the general population ages. Poorly managed heart failure symptoms of decompensated HFpEF is one of the most common reasons for prolonged hospital admission. The high rate of morbidity and mortality associated with HFpEF is compounded by a poor understanding of the underpinning pathophysiology. Randomized controlled trials have so far been unable to identify an evidence base for reducing morbidity and mortality in patients with HFpEF, although there is some evidence to support quality of life (QOL) improvement. In this review, we described the recent advances on the pathophysiological understanding of HFpEF, the current and emerging treatment strategies, and what this may mean for individual patients. Potential treatments for HFpEF were divided into their relative management strategies and the current evidence assessed for effect on HFpEF mortality, hospital admission frequency, and QOL improvement. Overall, the understanding of HFpEF pathophysiology is improving and has been made a priority in identifying potential therapeutic targets. There is growing evidence that patients with ejection fractions (EF) of less than 60% may obtain a mortality benefit from ACE-inhibitors, angiotensin-neprilysin inhibitors, Angiotensin Receptor Blockers, and Mineralocorticoid Receptor Antagonists. However, this covers only a small proportion of the HFpEF spectrum. Therefore, currently there are no universal treatment strategies recommended for HFpEF, and management should focus on an individualised approach and this should take into account the comorbidities of each patient.
| S-EPMC7186731 | biostudies-literature