scholarly journals Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction

2020 ◽  
Author(s):  
Li Shen ◽  
Pardeep S. Jhund ◽  
Inder S. Anand ◽  
Peter E. Carson ◽  
Akshay S. Desai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Sudden Death ◽  
Ejection Fraction ◽  
External Validation ◽  
Model Performance ◽  
Preserved Ejection Fraction ◽  
Clinical Model ◽  
Pump Failure ◽  
History Of

Abstract Background Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF. Methods Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials. Results The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell’s C of 0.71 (95% CI 0.68–0.75) and 0.78 (95% CI 0.75–0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination. Conclusions The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials. Clinical trial registration I-Preserve: ClinicalTrials.gov NCT00095238; TOPCAT: ClinicalTrials.gov NCT00094302; CHARM-Preserved: ClinicalTrials.gov NCT00634712. Graphic abstract

Factors predicting adverse cardiovascular outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
S Saksena ◽  
APRIL Slee ◽  
D Lakkireddy ◽  
DIPEN Shah ◽  
LUIGI Di Biase ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Cox Model ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
P Value ◽  
Preserved Ejection Fraction ◽  
Pump Failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Electrophysiology Research Foundation Introduction Atrial fibrillation (AF) is known to impact cardiovascular(CV) mortality in heart failure (HF) patients (pts) with preserved ejection fraction (pEF) but its exact causes are unknown. Methods  We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD) in HFpEF pts in the TOPCAT AMERICAS trial. We analyzed two AF presentations 1. Pts in sinus rhythm (SR, n = 1319) compared to AF  on ECG (n = 446) at entry or 2. Pts with no AF event by history or ECG ( n = 1007 ) to those with any AF event (n = 760 ). Results (Table): 5 year (yr) CV mortality was higher in pts with AF on ECG (30%) than SR (18%, p = 0.014) but 5 yr SCD was (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p = ns). 5 yr PFD was higher in AF on ECG  (13%) than SR (5%, p = 0.007)  Conclusions : 1. CV death risk in HFpEF pts increased with AF on ECG.. 2. SCD was not more frequent with both AF presentations 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate. 4. The recording of AF on ECG was more strongly associated with CV death & PFD, possibly due to greater AF burden . Predictors of adverse outcomes in HFpEF AF on ECG* Any AF* Endpoint Covariate HR (95% CI) p-value HR (95% CI) p-value Time to cardiovascular death Atrial Fibrillation* 1.44 (1.08, 1.92) 0.014 1.15 (0.87, 1.51) 0.338 Age (years) 1.03 (1.02, 1.05) <.001 1.03 (1.02, 1.05) <.001 Black/AA (vs. White) 0.97 (0.65, 1.46) 0.002 0.96 (0.64, 1.44) 0.004 Other race (vs. White) 2.41 (1.46, 3.99) 2.32 (1.41, 3.83) Smoking 2.62 (1.63, 4.20) <.001 2.60 (1.62, 4.17) <.001 Diabetes 1.47 (1.12, 1.94) 0.006 1.45 (1.10, 1.91) 0.009 Systolic BP (mmHg) 0.99 (0.98, 1.00) 0.022 0.99 (0.98, 1.00) 0.014 Heart rate (bpm) 1.02 (1.00, 1.03) 0.012 1.02 (1.01, 1.03) 0.006 Time to Any sudden cardiac death Atrial Fibrillation* 1.17 (0.69, 1.96) 0.563 0.85 (0.53, 1.35) 0.484 Female (vs. Male) 0.46 (0.28, 0.75) 0.002 0.46 (0.28, 0.74) 0.002 Black/AA (vs. White) 1.57 (0.87, 2.82) 0.194 1.49 (0.83, 2.69) <.001 Other race (vs. White) 1.76 (0.70, 4.41) 1.70 (0.68, 4.25) Diabetes 1.70 (1.07, 2.70) 0.024 1.65 (1.04, 2.62) 0.033 Time to pump failure death Atrial Fibrillation* 2.04 (1.22, 3.42) 0.007 1.62 (0.96, 2.75) 0.074 Age (years) 1.06 (1.03, 1.10) <.001 1.06 (1.03, 1.10) <.001 Heart rate (bpm) 1.03 (1.00, 1.05) 0.034 1.03 (1.01, 1.05) 0.015 Cox model of covariates associated with outcomes adjusted for baseline imbalances

Long-term systolic blood pressure and all-cause mortality in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Huang ◽  
C Liu
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Risk Of Mortality ◽  
All Cause Mortality ◽  
History Of

Abstract Background Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear. Purpose To examine the association of long-term SBP and all-cause mortality among patients with HFpEF. Methods We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: <120mmHg, ≥120mmHg and <130mmHg, ≥130mmHg and <140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%. Results The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of <120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of <120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis. Conclusions Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)

scholarly journals Heart Rate–Induced Myocardial Ca 2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Daniel N. Silverman ◽  
Mehdi Rambod ◽  
Daniel L. Lustgarten ◽  
Robert Lobel ◽  
Martin M. LeWinter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Sinus Rhythm ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Preserved Ejection Fraction ◽  
Volume Loss ◽  
Heart Rates ◽  
Patients With Heart Failure

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca 2+ overload caused by increased myocardial Na + levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg, P =0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%, P =0.009). Coronary venous [Ca 2+ ] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na + ] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca 2+ retention.

scholarly journals Heart rate in heart failure with preserved ejection fraction: target or marker?

2017 ◽  
Vol 19 (11) ◽  
pp. 1504-1506 ◽  
Author(s):  
Andreas P. Kalogeropoulos ◽  
Javed Butler
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction

Role of High-Dose Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction and Elevated Heart Rate

2018 ◽  
Vol 131 (12) ◽  
pp. 1473-1481 ◽  
Author(s):  
Phillip H. Lam ◽  
Neha Gupta ◽  
Daniel J. Dooley ◽  
Steven Singh ◽  
Prakash Deedwania ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Beta Blockers ◽  
High Dose ◽  
Preserved Ejection Fraction ◽  
Patients With Heart Failure ◽  
Elevated Heart Rate

P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stavrakis ◽  
K Elkholey ◽  
L Morris ◽  
Y Li ◽  
S S Po
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Female Rats ◽  
Autonomic Modulation ◽  
Preserved Ejection Fraction ◽  
Qtc Prolongation ◽  
Male And Female ◽  
Male And Female Rats

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic. Purpose To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes. Methods Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality. Results A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner. Conclusions Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.

scholarly journals Ventricular Arrhythmias Underlie Sudden Death in Rats With Heart Failure and Preserved Ejection Fraction

2018 ◽  
Vol 11 (8) ◽  
Author(s):  
Jae Hyung Cho ◽  
Rui Zhang ◽  
Stephan Aynaszyan ◽  
Kevin Holm ◽  
Joshua I. Goldhaber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Ventricular Arrhythmias ◽  
Preserved Ejection Fraction

Lower Heart Rate Associated With Improved Outcomes in Heart Failure With Preserved Ejection Fraction

2012 ◽  
Vol 18 (8) ◽  
pp. S87
Author(s):  
Luke Cunningham ◽  
Anita Deswal ◽  
Wenyaw Chan ◽  
David Augilar ◽  
Biykem Bozkurt ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Lower Heart Rate ◽  
Improved Outcomes

scholarly journals How to Estimate the Optimal Heart Rate in Patients with Heart Failure with Preserved Ejection Fraction

2021 ◽  
Author(s):  
Toshihide Izumida ◽  
Teruhiko Imamura ◽  
Takuya Fukui ◽  
Takatoshi Koi ◽  
Yohei Ueno ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Patients With Heart Failure
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