Subsequent Heart Failure Events Research Articles

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

High-sensitivity troponin-i and risk of heart failure in individuals with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity cardiac troponin-I (hsTnI) concentrations are associated with short- and long-term mortality and recurrent ischemic events in individuals with suspected acute coronary syndrome. However, the relation to subsequent heart failure events is less well established. Purpose To examine the association between single and serial hsTnI concentrations and subsequent hospitalization or outpatient contact for heart failure in subjects with suspected acute coronary syndrome. Methods Using Danish national registries, we identified persons without known heart failure who underwent two hsTnI measurements (Siemens TnI Flex® Reagent, 99th percentile upper reference limit, 45 ng/l) separated by 1-7 hours, during hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019. Individuals were stratified according to their hsTnI concentration pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (secondary groups: <20%, >20 to 50%, or >50% in either direction). Finally, they were grouped into quantiles based on the first hsTnI measurement (< = 15 ng/l, 16-30 ng/l, 31-44 ng/l, > = 45 ng/l) to explore whether the risk of heart failure was greater with higher hsTnI concentrations. We calculated standardized risks of hospitalization or outpatient contact for heart failure using multivariable logistic regression with average treatment effect modeling. Results A total of 18,939 individuals were included of whom 21.9% were discharged with a diagnosis of myocardial infarction, 4.8% with unstable angina, and 73.3% with observation for suspected myocardial infarction or chest pain. Median age was 61.9 years, and 52.5% were male. With respect to known cardiovascular disease, 17.6% had coronary artery disease, 5.4% had undergone prior coronary revascularization, and 8.0% had atrial fibrillation or flutter. A total of 429 individuals received a diagnosis of heart failure within the first 30 days while an additional 526 were diagnosed from days 31-365. The standardized absolute risk was lowest in subjects with two normal hsTnI values (days 0-30: 0.45%; days 31-365: <0.01%) and highest in those with persistently elevated concentrations (days 0-30: 8.56%; days 31-365: 9.50%) (Figure). The degree of hsTnI within each main group did not appear to affect the risk of heart failure. Conversely, the risk of heart failure was positively associated with hsTnI concentrations measured on the first sample. Conclusions Among individuals with suspected acute coronary syndrome, those with a persistently elevated hsTnI concentration consistently had the highest risk of a subsequent hospitalization or outpatient contact for heart failure. In addition, there appeared to be a dose-response relationship between hsTnI concentrations and the risk of heart failure.Figure

Clinical significance of ST-segment depression during atrial fibrillation rhythm for subsequent heart failure events.

The clinical significance of ST-segment depression during atrial fibrillation (AF) rhythm has not been fully evaluated. The aim of the present study was to explore the association of ST-segment depression during AF rhythm with subsequent heart failure (HF) events. The study enrolled 2718 AF patients whose baseline electrocardiography (ECG) was available from a Japanese community-based prospective survey. We assessed the association of ST-segment depression in baseline ECG during AF rhythm with clinical outcomes. The primary ednpoint was a composite HF endpoint: cardiac death or hospitalization due to HF. The prevalence of ST-segment depression was 25.4% (upsloping 6.6%, horizontal 18.8%, downsloping 10.1%). Patients with ST-segment depression were older and had more comorbidities than those without. During the median follow-up of 6.0 years, the incidence rate of the composite HF endpoint was significantly higher in patients with ST-segment depression than those without (5.3% vs. 3.6% per patient-year, log-rank P < 0.01). The higher risk was present in horizontal or downsloping ST-segment depression, but not in upsloping one. By multivariable analysis, ST-segment depression was an independent predictor for the composite HF endpoint (hazard ratio 1.23, 95% confidence interval 1.03-1.49, P = 0.03). In addition, ST-segment depression at anterior leads, unlike inferior or lateral leads, was not associated with higher risk for the composite HF endpoint. ST-segment depression during AF rhythm was associated with subsequent HF risk; however, the association was affected by type and distribution of ST-segment depression.

Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study

BackgroundPatients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known.MethodsThe phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied.ResultsPatients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04).ConclusionApabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.

Predictive value of early cardiac mri functional and geometric indexes on adverse left ventricular remodelling in anterior STEMI patients. A report from the CIRCUS study

Post-infarction adverse left ventricular (LV) remodelling is strongly associated with subsequent heart failure events. The conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR). The aim of our study was to assess their predictive value on one-year adverse LV remodelling in patients with anterior myocardial infarction. CMR studies were performed in 129 anterior ST-elevated myocardial infarction (STEMI) patients (58 ± 12 years, 78%men) from the randomized CIRCUS trial (CMR sub-study) treated with the primary percutaneous coronary intervention (PCI) and were followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). The conicity index, sphericity index, LVGFI, infarct size (IS) and microvascular obstruction (MVO) were assessed by CMR performed 5 ± 2 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 15% by transthoracic echocardiography at 1 year. Adverse LV remodeling occurred in 27% of patients in one year. IS and MVO were significantly predictive of adverse LV remodelling (OR = 1.03, CI 95% [1.02–1.05], P < 0.001 and OR = 1.12, CI 95% [1.05–1.22] P < 0.001, respectively). Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR = 1.10, CI 95% [1.03–1.16], P = 0.001). In multivariate analysis, only IS remained an independent predictor of adverse LV remodeling at 1 year (OR = 1.05, CI 95% [1.02–1.08], P < 0.001). LVGFI and IS were associated with the occurrence of MACE (OR = 1.21; CI 95% [1.08–1.37], P < 0.001 and OR = 1.02; CI 95% [1.00–1.04], P = 0.018 respectively). However, the conicity and sphericity indexes were not associated with MACE ( Fig. 1 ). LVGFI was associated with adverse LV remodelling and MACE at one year after anterior STEMI. However, this relationship and its predictive value in on top of infarct size remain hypothesis-generating at this stage. Further studies are needed to explore the relationship of all these remodelling indices with adverse outcomes in larger populations of MI patients.

Atrial fibrillation burden and subsequent heart failure events in patients with cardiac resynchronization therapy devices.

Atrial fibrillation (AF) and heart failure (HF) often coexist but little is known on how AF burden associates with subsequent episodes of HF. The aim of this study was to quantitatively assess the short- and long-term association of AF burden with subsequent episodes of HF events in patients with reduced ejection fraction. Patients with cardiac resynchronization therapy (CRT) devices with at least 90 days of device data were included in the study. Time-dependent Cox regression with a 7-day window was used to evaluate the association of short- and long-term AF burden with subsequent HF events. Each patient with HF was matched to two control patients without an HF event based on age, gender, year of implant and CRT defibrillation capability. In our cohort with 2:1 matching (N = 549), 183 patients developed HF events and 275 (50.1%) had AF over an average follow-up of 24 ± 11 months. A 1-hour increase in short-term AF burden was associated with a 3% increased risk of HF events (HR, 1.034; 95% confidence interval [CI], 1.012-1.056; P = .01; HR for 24-hour = 2.23). In contrast, the association between long-term AF burden and subsequent HF events was not statistically significant (HR, 1.009; 95% CI, 0.992-1.026; P = .373). A 24-hour increase in AF burden is associated with a more than two-fold increased risk of HF events over the subsequent week while the long-term AF burden is not significantly associated with HF events.

Myocardial Extracellular Volume Fraction Adds Prognostic Information Beyond Myocardial Replacement Fibrosis.

Cardiac magnetic resonance techniques permit quantification of the myocardial extracellular volume fraction (ECV), representing a surrogate marker of reactive interstitial fibrosis, and late gadolinium enhancement (LGE), representing replacement fibrosis or scar. ECV and LGE have been independently linked with heart failure (HF) events. In deriving ECV, coronary artery disease type LGE, but not non-coronary artery disease type LGE, has been consistently excluded. We examined the associations between LGE, global ECV derived from myocardial tissue segments free of any detectable scar, and subsequent HF events. Mid short-axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from only segments without LGE. ECV was considered elevated if >30%, the upper 95% bounds of a reference group without known cardiac disease (n=28). Patients were divided into 4 groups by presence of elevated ECV and of any LGE. Subsequent HF hospitalization and any death were ascertained. Their relationship with ECV was examined separately and as a composite with Cox proportional hazard models. Of 1604 serial patients with T1 maps, 1255 were eligible after exclusions and followed over a median 26.3 (interquartile range, 15.9-37.5) months. Patients with elevated ECV had increased risk for death (hazard ratio [HR] 2.45 [95% CI, 1.76-3.41]), HF hospitalization (HR, 2.45 [95% CI, 1.77-3.40]), and a combined end point of both outcomes (HR, 2.46 [95% CI, 1.94-3.14]). After adjustments for covariates including LGE, the relationship persisted for death (HR, 1.82 [95% CI, 1.28-2.59]), hospitalization (HR, 1.60 [95% CI, 1.12-2.27]), and combined end points (HR, 1.73 [95% CI, 1.34-2.24]). ECV measures of diffuse myocardial fibrosis were associated with HF outcomes, despite exclusion of replacement fibrosis segments from their derivation and even among patients without any scar. ECV may have a synergistic role with LGE in HF risk assessment.

Abstract 216: Left Ventricular Enlargement and Heart Failure Events: Is Bigger Better?

Background: Since stroke volume (SV) is a function of ejection fraction (EF) and end-diastolic volume (EDV) (SV = EF x EDV), we hypothesized that increased EDV may be advantageous in systolic heart failure (HF), allowing the left ventricle to supply increased cardiac output. Methods: Echocardiograms from 968 consecutive patients seen in our hospital’s HF clinic were reviewed. Left ventricular volumes were measured both at end systole and end diastole using the bi-plane Simpson’s method and were indexed to body surface area. EF was calculated using (EDV-ESV)/EDV. Dates of subsequent HF events (death or admission for HF exacerbation) were obtained from our database. Results: Systolic HF (EF &lt; 50%) was found in 649 of the study subjects. Increased SV index was associated with increased EDV index. The strength of this association varied with EF, Figure. In a bivariate Cox regression model, lower SV index and higher EDV index were each independent predictors of HF events. Increase in EDV by 50 cc was associated with a 20% increase in HF events, p&lt;0.001. Decrease in SVI by 5 cc was associated with 5% increase in HF events, p&lt;0.001. These associations were limited to those with systolic HF. The associations between both EDVI and SVI and HF events were not confounded by patient age, sex and New York Heart Association Class. Conclusion: Increased EDV index was independently associated with increased HF events, indicating that LV enlargement in HF is not favorable. These findings underscore the individual contributions of the components of EF (SV and EDV) in predicting HF outcomes.

Reduction of the Risk of Recurring Heart Failure Events With Cardiac Resynchronization Therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy)

The evaluation of the risk of recurring heart failure events (HFEs) was a pre-specified substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the occurrence of recurring heart failure episodes after a first post-implantation HFE.Data with regard to recurring HFEs were prospectively collected for all 1,820 MADIT-CRT participants. The CRT-D versus defibrillator-only risk for nonfatal first- and subsequent-HFEs was assessed by Cox proportional hazards and Andersen-Gill proportional intensity regression modeling, respectively, in efficacy analyses recognizing active device-type during follow-up.Multivariate analysis showed that CRT-D was associated with a significant reduction in the risk of a first HFE (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44 to 0.67, p < 0.001) and with a similar magnitude of reduction in the risk of HFEs subsequent to a first post-enrollment event (HR: 0.62, 95% CI: 0.45 to 0.85, p = 0.003). The benefit of CRT-D for the prevention of first and subsequent HFEs was pronounced among patients with left bundle branch block (HR: 0.38, 95% CI: 0.29 to 0.49, p < 0.001; and HR: 0.50, 95% CI: 0.33 to 0.76, p = 0.001, respectively) and nonsignificant in non-left bundle branch block patients (HR: 1.12, 95% CI: 0.77 to 1.64, p = 0.55; and HR: 0.99, 95% CI: 0.58 to 1.69, p = 0.96, respectively; p values for interaction: p < 0.001 and p = 0.06, respectively). The occurrences of first and second HFEs were associated with 7- and nearly 19-fold respective increases in the risk of subsequent mortality.In the MADIT-CRT trial, the benefit of cardiac resynchronization therapy for the reduction in recurring HFEs was maintained after the occurrence of a first post-enrollment event. The occurrence of HFEs greatly increased the risk of death. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).

Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations: Results From PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) Study

We sought to determine the utility of combined heart failure (HF) device diagnostic information to predict clinical deterioration of HF in patients with systolic left ventricular dysfunction. Some implantable devices continuously monitor HF device diagnostic information, but data are limited on the ability of combined HF device diagnostics to predict HF events. The PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) was a prospective, multicenter observational study in patients receiving cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillators. HF events were independently adjudicated. A combined HF device diagnostic algorithm was developed on an independent dataset. The algorithm was considered positive if a patient had 2 of the following abnormal criteria during a 1-month period: long atrial fibrillation duration, rapid ventricular rate during atrial fibrillation, high (≥60) fluid index, low patient activity, abnormal autonomics (high night heart rate or low heart rate variability), or notable device therapy (low CRT pacing or implantable cardioverter-defibrillator shocks), or if they only had a very high (≥100) fluid index. We used univariate and multivariable analyses to determine predictors of subsequent HF events within a month. We analyzed data from 694 CRT defibrillator patients who were followed for 11.7 ± 2 months. Ninety patients had 141 adjudicated HF hospitalizations with pulmonary congestion at least 60 days after implantation. Patients with a positive combined HF device diagnostics had a 5.5-fold increased risk of HF hospitalization with pulmonary signs or symptoms within the next month (hazard ratio: 5.5, 95% confidence interval: 3.4 to 8.8, p < 0.0001), and the risk remained high after adjusting for clinical variables (hazard ratio: 4.8, 95% confidence interval: 2.9 to 8.1, p < 0.0001). Monthly review of HF device diagnostic data identifies patients at a higher risk of HF hospitalizations within the subsequent month. (PARTNERS HF: Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure; NCT00279955).

B-Type Natriuretic Peptide and Impedance Cardiography at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events

Background Detection of heart failure (HF) in stable outpatients can be difficult until an overt event occurs. This study sought to determine whether the combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG) could be used in a nonacute clinical setting to risk stratify and predict HF-related events in stable outpatients. Methods and Results Patients undergoing routine outpatient echocardiography underwent ICG and BNP testing and were followed for one year for HF-related events (Emergency Department [ED] visit or hospitalization due to HF or all-cause death). A total of 524 patients were analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations, and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time ratio index (STRI) by ICG proved to be the strongest predictors of future HF-related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec -1 had a significantly lower event-free survival rate than those with a high BNP and low STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP and STRI values were high, the relative risk of a HF-related event increased by 12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low STRI (P<.001). Conclusions In a nonacute clinical setting, both BNP and ICG testing can provide unique predictive power of long-term HF-related events in a stable cohort of patients with and without LV dysfunction.

The Association Between High-Dose Diuretics and Clinical Stability in Ambulatory Chronic Heart Failure Patients

Objective In chronic heart failure (HF), diuretic doses increase as the disease progresses, often after hospitalization for instability, and have been associated with worsening renal function and increased mortality. Methods and Results A prospective observational analysis of 183 patients in an advanced HF clinic stratified at baseline by diuretic dose (low dose ≤ 80 mg, high dose > 80 mg furosemide equivalent) was performed. All patients were followed for 1 year, and the primary outcome was a combined HF event of admission for HF, cardiac transplant, mechanical cardiac support, or death. Compared with patients taking low-dose diuretics (n = 113), patients taking high-dose diuretics (n = 70) had more markers of increased cardiovascular risk and were more likely to have a history of recent instability (33% vs 4.4% in low dose, P < .001). High doses of diuretics were a strong univariate predictor of subsequent HF events (hazard ratio 3.83, 95% confidence interval 1.82–8.54); however, after adjustment for clinical stability, diuretic dose no longer remained significant (hazard ratio 1.53, 95% confidence interval 0.58–4.03). Conclusion High-dose diuretics may be more of a marker than a cause of instability. A history of HF stability during the past 6 months is associated with an 80% lower risk of an HF event during the next year, independently of baseline diuretic dose.

N-terminal pro B-Type Natriuretic Peptide (Nt proBNP) and Prediction of Subsequent Heart Failure Events in Class A and B Heart Failure Patients

N-terminal pro B-Type Natriuretic Peptide (Nt proBNP) and Prediction of Subsequent Heart Failure Events in Class A and B Heart Failure Patients

B-Type Natriuretic Peptide Levels and Prediction of Subsequent Heart Failure Events in Class A and B Heart Failure Patients

B-Type Natriuretic Peptide Levels and Prediction of Subsequent Heart Failure Events in Class A and B Heart Failure Patients

B-Type Natriuretic Peptide and Impedance Cardiography Testing at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events

B-Type Natriuretic Peptide and Impedance Cardiography Testing at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events