Recurrent Heart Failure Hospitalizations Research Articles

Prediction of recurrent heart failure hospitalizations and mortality using the echocardiographic Killip score.

Examine the performance of a simple echocardiographic "Killip score" (eKillip) in predicting heart failure (HF) hospitalizations and mortality after index event of decompensated HF hospitalization. HF patients hospitalized at our facility between 03/2019-03/2021 who underwent an echocardiography during their index admission were included in this retrospective analysis. The cohort was divided into 4 classes of eKillip according to: stroke volume index (SVI) < 35ml/m2 > and E/E' ratio < 15 > . An eKillip Class I was defined as SVI ≥ 35ml/m2 and E/E' ≤ 15 and was used as reference. Included 751 patients, median age 78.1 (IQR 69.3-86) years, 59% men, left ventricular ejection fraction 45 (IQR 30-60)%, brain natriuretic peptide levels 634 (IQR 331-1222)pg/ml. Compared with eKillip Class I, a graded increase in the combined endpoint of 30-day mortality and rehospitalizations rates was noted: (Class II: HR 1.77, CI 0.95-3.33, p = 0.07; Class III: HR 1.94, CI 1.05-3.6, p = 0.034; Class IV: HR 2.9, CI 1.64-5.13, p < 0.001 respectively), which overall persisted after correction for clinical (Class II: HR 1.682, CI 0.9-3.15, p = 0.105; Class III: HR 2.104, CI 1.13-3.9, p = 0.019; Class IV: HR 2.74, CI 1.54-4.85, p = 0.001 respectively) or echocardiographic parameters (Class II: HR 1.92, CI 1.02-3.63, p = 0.045; Class III: HR 1.54, CI 0.81-2.95, p = 0.189; Class IV: HR 2.04, CI 1.1-3.76, p = 0.023 respectively). Specifically, the eKillip Class IV group comprised one-third of the patient population and persistently showed increased risk of 30-day HF hospitalizations or mortality following multivariate analysis. A simple echocardiographic score can assist identifying high-risk decompensated HF patients for recurrent hospitalizations and mortality.

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

Transition from asymptomatic to symptomatic systolic chronic heart failure: rationale and design of TransitionCHF.

Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials. TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

Daprodustat and Heart Failure in CKD.

Patients with chronic kidney disease (CKD) are at higher risk for heart failure. The hypoxia inducible factor prolyl hydroxylase inhibitor daprodustat is an orally acting alternative to conventional injectable erythropoietin-stimulating agents (ESA) for the treatment of anemia in patients with CKD. Whether daprodustat affects the risk of heart failure hospitalization is unknown. The ASCEND-D (n=2,964) and ASCEND-ND (n=3,872) trials compared daprodustat to conventional ESA in patients with anemia of CKD who did or did not require dialysis, respectively. We identified risk factors for heart failure hospitalization and assessed the effect of daprodustat compared to conventional ESA on heart failure hospitalizations. History of heart failure, diabetes, and higher systolic blood pressure were independently associated with heart failure hospitalization in both trials, irrespective of treatment assignment. The number of first heart failure hospitalizations was greater in the daprodustat arm in patients not receiving dialysis (hazard ratio [HR] 1.22 [0.95-1.56], p=0.12] and in patients receiving dialysis (HR 1.10 [0.84-1.45], p=0.47), though these differences were not statistically significant. HRs in patients with and without history of heart failure were 1.37 (0.89-2.11) vs 1.08 (0.79-1.46) (p-interaction=0.36) in ASCEND-ND, and 1.52 (0.97-2.38) vs 0.93 (0.66-1.30) (p-interaction=0.09) in ASCEND-D, respectively. In post hoc analyses, daprodustat increased total (first and recurrent) heart failure hospitalizations in participants not receiving dialysis (rate ratio 1.46 [1.11-1.92], p=0.007) ) but not in participants receiving dialysis (rate ratio 1.01 [0.74-1.39], p=0.93). Daprodustat did not significantly affect the risk of a composite outcome of first heart failure hospitalization or death. A greater number of first heart failure hospitalization events occurred in patients treated with daprodustat compared with conventional ESA, but this difference did not reach statistical significance. Differences in the number of heart failure hospitalization events were most apparent in patients not receiving dialysis and in patients with history of heart failure.

Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON-HF study.

Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population. We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS <16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02-1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction >0.1). In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF.

Effect of sacubitril valsartan on heart failure with mid-range or preserved ejection fraction in patients on maintenance hemodialysis: real-world experience in a single-center, prospective study

BackgroundThis study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF).MethodsThis single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day.ResultsTwenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e’) improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF.ConclusionsSV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.

Psychological Distress and the Risk of Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease

BackgroundPsychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear. ObjectivesThe purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction. MethodsPooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years. ResultsIn both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved. ConclusionsAmong patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

Recurrent heart failure hospitalizations in heart failure with preserved ejection fraction: an analysis of TOPCAT trial.

Recurrent heart failure hospitalization (HFH) is an important feature of the progression of heart failure (HF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, we analysed risk factors for recurrent HFH events in HF patients with preserved ejection fraction (HFpEF) and developed a risk prediction model for recurrent HFH. This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n=1767). Recurrent HFH was defined as two or more hospitalizations for HF during the follow-up period. Lasso regression and multivariate logistic regression were used to screen the risk factors, and the risk prediction model of recurrent HFH was established. During a median follow-up period of 3.4 (95% confidence interval: 3.3-3.6) years, 72.2% (542 of 751 total hospitalizations) of HFH events occurred in 9.4% (n=163) of patients with recurrent HFHs. Patients in the recurrent HFH group had higher cardiovascular mortality rate [6.2 per 100 patient-years (PY) vs. 3.8 per 100 PY, P=0.016] and all-cause mortality rate (10.0 per 100 PY vs. 6.8 per 100 PY, P=0.015) than those in the non-recurrent HFH group. The model consisting of nine predictors has moderate predictive power for recurrent HFH events in patients with HFpEF (AUC=0.75, Brier score=0.08). Decision curve analysis showed a net clinical benefit from the application of the prediction model. In patients with HFpEF, the majority of HFHs occur in a small proportion of patients with repeated hospitalizations, who typically have more comorbidities and are at higher risk of death. The predictive model developed in this study helps to identify patients at high risk of recurrent HFH.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF)<40%, development of heart failure within the last month of pregnancy or 5months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4±6.8years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP≥30mmHg. After a median follow-up of 3.4years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P=0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP≥30mmHg had a lower probability of survival free from adverse events (log-rank P=0.04). African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Prognostic role of mitral regurgitation in patients with advanced heart failure

AimThe impact of mitral regurgitation (MR) in patients with advanced heart failure (HF) is poorly known. We aimed to evaluate the impact of MR on clinical outcomes of a real-world, contemporary, multicentre population with advanced HF. MethodsThe HELP-HF registry enrolled patients with HF and at least one “I NEED HELP” criterion, at four Italian centres between January 2020 and November 2021. The population was stratified by none/mild MR vs. moderate MR vs. severe MR. Outcomes of interest were all-cause, cardiovascular (CV) death, the composite of all-cause death or first HF hospitalization, first HF hospitalization and recurrent HF hospitalizations. ResultsAmong 1079 patients, 429 (39.8%) had none/mild MR, 443 (41.1%) had moderate MR and 207 (19.2%) had severe MR. Patients with severe MR were most likely to be inpatients, present with cardiogenic shock, need intravenous loop diuretics and inotropes/vasopressors, have lower ejection fraction and higher natriuretic peptides. Estimated rates of all-cause death, CV death, and the composite of all-cause death or first HF hospitalization at 1 year increased with increasing MR severity. Compared with no/mild MR, severe MR was independently associated with an increased risk of CV death (adjusted HR 1.61, 95% CI 1.04–2.51, p = 0.033) and recurrent HF hospitalizations (adjusted HR 1.49, 95% CI 1.08–2.06, p = 0.015), but not with and increased risk of all-cause death, first HF hospitalization and composite outcome. ConclusionsIn unselected patients with advanced HF, severe MR was common and independently associated with an increased risk of CV death and of recurrent HF hospitalizations.

Impact of qualified nursing education on self-care and disease knowledge in heart failure patients

Abstract Purpose Guidelines on management of heart failure patients support intensive patient education on self-care. To evaluate the short and long-term impact of a structured education by a qualified heart failure nurse on patient´s self-care and disease knowledge. Methods 131 patients (66±12 years) hospitalized for heart failure participated in a structured one hour education program by a heart failure nurse. Patients completed a questionnaire consisting of 15 questions, nine of the European Heart Failure Self-Care Behaviour Scale (EHFScB-9) and additionally six questions on the patient´s disease knowledge 1 day before, 6 months and 12 months after the education course. Possible responses ranged from 1 (complete agreement) to 5 (complete disagreement). Clinical events during the 12 months follow-up period were determined. Factors predicting with potential impact on the teaching effect were evaluated. Seven patients refused further participation during follow-up, 13 patients were lost during follow-up, and one patient was excluded from the study due to progressive dementia. Results Nine patients died during the study and 33 patients had recurrent hospitalization for heart failure. EHFScB-9 scale improved from 24.0±7.2 at baseline to 17.0±7.4 (p&amp;lt;0.001) at 6 months, and 17.2±6.1 (p&amp;lt;0.001 vs. baseline) after 12 months. Concerning the disease knowledge score, it improved from 17.9±5.3 at baseline to 12.1±4.3 (p&amp;lt;0.05) at 6 months follow-up, and to 12.0±5.5 (p&amp;lt;0.05) at 12 months after education. Scores to individual questions prior to education ranged from 1.2±0.8 on adherence to the medication protocol to 2.7±1.4 on everyday weighting habits. Greatest improvement after education were obtained on reaction to weight gains (-1.9±1.3), daily weight control (-1.6±1.4) and knowledge on the reason of patient’s heart failure (-1.6±1.2). The NYHA-classification improved from 2.8±0.8 before teaching to 2.2±0.7 (p&amp;lt;0.001) at 12-months follow-up. No predictor of an insufficient teaching effect could be defined. Patients with a clinical event (death, recurrent hospitalization) had a combined EHFScB-9 and disease knowledge score of 32.6±8.1vs. 28.9±9.9 in those patients without a clinical event. Patients with more than one hospitalization due to acute decompensated heart failure during the follow-up period express insignificant improvement of the combined EHFScB-9 and disease knowledge score immediately after the education session. Conclusions A qualified nurse education program improves self-care behaviour and patient´s disease knowledge with a persisting effect at 6 and 12 months follow-up. There are no patient characteristics which preclude the implementation of an educational session.

Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis

Abstract Introduction AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) by using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. Material and methods We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. Results FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3,258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2&amp;gt;50%) between the trials for any of the analyzed outcomes. Conclusions Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD without benefit on CVD. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.Summary

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy

Abstract Background Peripartum cardiomyopathy (PPCM) is a type of pregnancy associated heart failure with reduced ejection of unknown etiology that is associated with significant morbidity and mortality in young women. It is a leading cause of peripartum maternal death in the United States, with mortality as high as 25% in some cohorts, and accounts for approximately 50% of cases of maternal cardiogenic shock. Purpose We sought to identify factors associated with right ventricular (RV) dysfunction and elevated RV systolic pressure (RVSP) and association with adverse outcomes in PPCM. Methods We conducted a multi-center cohort study to identify subjects with PPCM with the following criteria: LVEF &amp;lt; 40%, development of heart failure within the last month of pregnancy or 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of 1) major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) or 2) recurrent heart failure hospitalization. Results In all, 229 women (1993 to 2017) met criteria. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had RVSP &amp;gt; = 30mmHg. After a median follow-up of 3.4 years (IQR 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and RVSP were significant predictors of RV dysfunction (Table 1). Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: HR 3.21 (95% CI: 1.11-9.28), p = 0.03 in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease and LVEF. Women with RVSP &amp;gt;= 30mmHg had a lower probability of survival free from adverse events (log rank p = 0.04) (Figure 1). Conclusion African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated RVSP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring, genetic testing, or early referral for advanced therapies.Table of predictorsSurvival curves

Effects of blood pressure lowering according to baseline cardiovascular disease: systematic review and meta-analysis of randomized trials

Abstract Background Blood pressure (BP)-lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. There are no data on the effect of BP lowering in patients with a history of CV disease [i.e., coronary heart disease (CHD), stroke, or heart failure with preserved ejection fraction (HFpEF)]. Purpose To demonstrate the effect of BP-lowering treatment on CV events in patients with different types of baseline CV disease. Methods A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, search from 1966 to 11/2022) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on fatal or nonfatal cardiovascular outcomes and all-cause death. Trials or subgroups of trials were identified, including patients with a history of CV disease. We excluded heart failure studies with reduced ejection fraction, acute myocardial infarction, or acute stroke. Risk ratios (RR) were calculated with their 95% confidence interval (CI) under the random-effects model. Results We included 18 BP-lowering treatment trials with 52,359 CHD patients (mean follow-up, 4.2 years; achieved systolic/diastolic BP, 129.2/76.1 mmHg). Despite the fact that mortality outcomes, stroke, and recurrent CHD were not decreased as a result of BP-lowering therapy, the risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was reduced by 11% (95% CI, 3-18%) and the risk of recurrent heart failure hospitalization by 28% (95% CI, 18-38%). In addition, we examined 8 trials with 37,866 patients with a history of stroke (mean follow-up, 2.7 years; achieved systolic/diastolic BP, 136.5/79.8 mmHg), in which BP-lowering treatment reduced recurrent stroke by 18% (95% CI, 7-27%) and CV death by 12% (95% CI, 3-21%). Among 5 heart failure trials with 11,597 patients (mean follow-up, 3.4 years; achieved systolic/diastolic BP, 130.8/76.7 mmHg), the combined outcome of major CV events was decreased by 10% (95% CI, 4-16%), and recurrent heart failure hospitalization by 12% (95% CI, 4-19%). Conclusions Maximum CV protection is offered when systolic BP is reduced to levels &amp;lt; 130 mmHg in patients with CHD, to 130-140 mmHg levels in patients with a history of stroke, and to levels of approximately 130 mmHg in patients with heart failure. These findings support the recommendation for more aggressive BP lowering in patients with a history of CHD or optimally treated patients with HFpEF, and for less aggressive BP reduction in post-stroke patients.

Abstract 16776: Recurrent Admission of Acute Decompensated Heart Failure Among Patients With and Without PAD and Its Significance in the CKD Population: The ARIC Cohort Study

Introduction: Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF). Methods: Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m 2 . Results: From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m 2 ). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD ( Figure 1 ). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 - 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15). Conclusion: Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.

The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction

BackgroundIn some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial. Method and ResultsIRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men). Patients were randomized, open label, to FDI (n = 397) or usual care (n = 374) and followed for a median of 2.6 years. The primary end point, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78, 95% confidence interval 0.61–1.01; P = .063). First event analysis for cardiovascular death or hospitalization for heart failure, less affected by the coronavirus disease 2019 pandemic, gave similar results (hazard ratio 0.77, 95% confidence interval 0.62–0.96; P = .022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality of life, for overall (P = .013) and physical domain (P = .00093) scores at 4 months. ConclusionsIn patients with iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, intravenous FDI improves quality of life and may decrease cardiovascular events.

Use of Win Statistics to Analyze Outcomes in the DAPA-HF and DELIVER Trials

BackgroundThe primary end point in most heart failure (HF) trials is a composite of time to a first worsening HF event or cardiovascular death. Prevention of recurrent events and improvements in symptoms/quality of life are also important for patients but are usually analyzed separately. Win statistics can integrate all these outcomes into a single composite end point, which is analyzed in hierarchical order, reflecting the clinical importance of each component.MethodsThe Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF, n=4744) and Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER, n=6263) trials enrolled patients with New York Heart Association class II, III, or IV HF, elevated natriuretic peptides, and either an ejection fraction of 40% or less (DAPA-HF) or greater than 40% and left atrial enlargement/left ventricular hypertrophy (DELIVER). We examined the effects of dapagliflozin compared with placebo on a hierarchical composite outcome, including cardiovascular death, total (first and recurrent) HF hospitalizations, total urgent HF visits, and improvement/deterioration in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS; range from 0 to 100, with a higher score indicating fewer symptoms and physical limitations) at 8 months.ResultsFor this composite outcome, the win ratio was 1.30 (95% confidence interval [CI], 1.23 to 1.36) in the pooled cohort, 1.33 (95% CI, 1.23 to 1.43) in the DAPA-HF trial, and 1.27 (95% CI, 1.18 to 1.36) in the DELIVER trial. Win odds and net benefit in overall patients were 1.19 (95% CI, 1.14 to 1.24) and 8.7% (95% CI, 6.6 to 10.9%), respectively. In the overall pooled cohort, the majority of wins and losses were accounted for by KCCQ-TSS; 52.4% were settled by the KCCQ-TSS tier in the pooled cohort.ConclusionsIn both the DAPA-HF and DELIVER trials, dapagliflozin led to a significant improvement in composite outcomes that incorporated patient-reported outcomes along with total HF events, as well as cardiovascular deaths. These analyses provided a comprehensive presentation of win statistics and illustrated the utility and flexibility of win statistics in describing the effects of dapagliflozin in two recent clinical trials in patients with HF. (Funded by British Heart Foundation Centre of Research Excellence and others; clinical trial registration numbers, NCT03036124 and NCT03619213.)

Neighbourhood-level social deprivation and the risk of recurrent heart failure hospitalizations in type 2 diabetes.

The importance of type 2 diabetes mellitus (T2D) in heart failure hospitalizations (HFH) is acknowledged. As information on the prevalence and influence of social deprivation on HFH is limited, we studied this issue in a racially diverse cohort. Linking data from US Veterans with stable T2D (without prevalent HF) with a zip-code derived population-level social deprivation index (SDI), we grouped them according to increasing SDI as follows: SDI: group I: ≤20; II: 21-40; III: 41-60; IV: 61-80; and V (most deprived) 81-100. Over a 10-year follow-up period, we identified the total (first and recurrent) number of HFH episodes for each patient and calculated the age-adjusted HFH rate [per 1000 patient-years (PY)]. We analysed the incident rate ratio between SDI groups and HFH using adjusted analyses. In 1 012 351 patients with T2D (mean age 67.5 years, 75.7% White), the cumulative incidence of first HFH was 9.4% and 14.2% in SDI groups I and V respectively. The 10-year total HFH rate was 54.8 (95% CI: 54.5, 55.2)/1000 PY. Total HFH increased incrementally from SDI group I [43.3 (95% CI: 42.4, 44.2)/1000 PY] to group V [68.6 (95% CI: 67.8, 69.9)/1000 PY]. Compared with group I, group V patients had a 53% higher relative risk of HFH. The negative association between SDI and HFH was stronger in Black patients (SDI × Race pinteraction < .001). Social deprivation is associated with increased HFH in T2D with a disproportionate influence in Black patients. Strategies to reduce social disparity and equalize racial differences may help to bridge this gap.

Effects of dapagliflozin on heart failure hospitalizations according to severity of inpatient course: Insights from DELIVER and DAPA-HF.

Dapagliflozin resulted in significant and sustained reductions in first and recurrent heart failure (HF) hospitalizations among patients with HF across the spectrum of ejection fraction. How treatment with dapagliflozin differentially impacts hospitalization for HF of varying complexity is not well studied. In the DELIVER and DAPA-HF trials, we examined the effects of dapagliflozin on adjudicated HF hospitalizations of varying complexity and hospital length of stay (LOS). HF hospitalizations requiring intensive care unit stay, intravenous vasoactive therapies, invasive/non-invasive ventilation, mechanical fluid removal or mechanical circulatory support were categorized as complicated. The balance was classified as uncomplicated. Of the total 1209 HF hospitalizations reported in DELIVER, 854 (71%) were uncomplicated and 355 (29%) were complicated. Of the total 799 HF hospitalizations reported in DAPA-HF, 453 (57%) were uncomplicated and 346 (43%) were complicated. Relative to patients experiencing a first uncomplicated HF hospitalization, those with complicated HF hospitalizations had a significantly higher in-hospital mortality both in DELIVER (16.7% vs. 2.3%, p < 0.001) and DAPA-HF (15.1% vs. 3.8%, p < 0.001). Dapagliflozin similarly reduced total 'uncomplicated' (DELIVER: rate ratio [RR] 0.67, 95% confidence interval [CI] 0.55-0.82 and DAPA-HF: RR 0.69, 95% CI 0.54-0.87) and 'complicated' HF hospitalizations (DELIVER: RR 0.82, 95% CI 0.63-1.06 and DAPA-HF: RR 0.75, 95% CI 0.58-0.97). Dapagliflozin consistently reduced hospitalizations irrespective of their LOS: <5 days (DELIVER: RR 0.76, 95% CI 0.58-0.99 and DAPA-HF: RR 0.58, 95% CI 0.42-0.80) or ≥5 days (DELIVER: RR 0.71, 95% CI 0.58-0.86 and DAPA-HF: RR 0.77, 95% CI 0.62-0.94). A substantial proportion of hospitalizations (∼30-40%) among patients with HF irrespective of ejection fraction required intensification of treatment beyond standard intravenous diuretics. Such patients experienced significantly higher in-hospital mortality. Treatment with dapagliflozin consistently reduced HF hospitalizations regardless of severity of inpatient course or LOS. ClinicalTrials.gov, DELIVER (NCT03619213) and DAPA-HF (NCT03036124).