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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.

ABSTRACT: BACKGROUND: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. HYPOTHESIS:RPP and its components are associated with HFpEF outcomes. METHODS:We performed an analysis of Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF; http://www.clinicaltrials.gov NCT00475852), which studied 7141 patients with acute HF. HFpEF was defined as left ventricular ejection fraction ?40%. Outcomes were assessed by baseline heart rate, SBP, and RPP, as well as the change of these variables using adjusted Cox models. RESULTS:After multivariable adjustment, in-hospital change but not baseline heart rate, SBP, and RPP were associated with 30-day mortality/HF hospitalization (hazard ratio [HR]: 1.17 per 5-bpm heart rate, HR: 1.20 per 10-mm Hg SBP, and HR: 1.02 per 100?bpm?×?mm Hg RPP; all P?

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]

PMID: 29781109

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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.

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).

Project description:ObjectivesThis study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF).BackgroundAlthough diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined.MethodsWe 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.ResultsThe 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).ConclusionsStrain 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).

Project description:BackgroundHeart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin.MethodsWe performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure).ResultsA total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P=0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant).ConclusionsCompared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: PRESERVED-HF NCT03030235.

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.

Dataset Information

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.

Publications

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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