Hospitalization For Heart Failure Events Research Articles

#2766 Impact of CKD screening in high-risk populations and guideline-directed therapy on CV event occurrence and costs in Europe: an IMPACT CKD analysis

Abstract Background and Aims Chronic kidney disease (CKD) is a growing health problem in Europe exacerbated by aging and the rise of comorbidities such as diabetes mellitus (DM) and hypertension (HTN). Patients with CKD are often multi-morbid and commonly present with cardiovascular (CV) complications. While CV events including myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF) occur more often in patients with advanced CKD, patients with early-stage CKD are also at increased risk. Patients with CKD also experience an increased risk of CV-related mortality, with many patients dying from CV events prior to kidney failure and renal replacement therapy. CV events also present a significant burden to clinicians and healthcare systems due to the high costs and resource use required to manage and treat them. Despite this multidimensional burden, CKD is currently underdiagnosed in Europe, and CKD screening and treatment are rarely included in public health strategies to improve mortality and health outcomes. This study aims to explore the impact of targeted CKD screening followed by guideline-directed therapy in high-risk populations on CV event occurrence and associated treatment costs across Europe. Method The IMPACT CKD microsimulation model simulates CKD progression, CV events, and comorbidities. CKD status is assigned based on estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio levels (UACR), and CKD progression is predicted by an annual eGFR decline rate. The model was used to compare two scenarios in four country populations (Germany, Netherlands, Spain, United Kingdom [UK]): 1) targeted screening for people with DM and/or HTN followed by optimal compliance to guideline-directed therapy and 2) current practice (no screening, underdiagnosis, low treatment rates). Annual targeted screening assumed both eGFR and UACR testing. Treatment initiation for people diagnosed with CKD was based on Kidney Disease Improving Global Outcomes guidelines with a 90% compliance assumed to approximate maximum clinical benefit. Therapies were assumed to have a multiplicative treatment effect on eGFR decline and CV events. Current practice assumed observed diagnosis rates without screening and observed treatment rates in each country. For both scenarios, the model projected incidence of CV events and associated management costs in year 10 (2032) and cumulatively over the 10 simulated years (2023-2032). Results Results compare the targeted screening followed by guideline-directed treatment scenario to continuation of current practices for Germany, Netherlands, Spain, and UK (Table 1). The timely diagnosis of patients with CKD and effective treatment was associated with a reduction of 46.7-53.3%, 38.9-41.6%, and 42.1-50.5% in the number of MI, stroke, and HHF events, respectively in 2032 across the four countries. These decreases in the number of CV events were accompanied by proportional reductions in costs to treat the events. Additionally, this policy approach resulted in declines in the cumulative 10-year CV event development and associated healthcare costs, with MI having the largest reductions (40.6-47.2%), followed by HHF (37.4-43.0%), and stroke (29.8-36.1%) across the four countries. Conclusion This study illustrated that early identification of high-risk patients with CKD coupled with guideline-directed treatment would yield substantial clinical and economic benefits from reducing CV events across all four European countries. Fewer MI, stroke, and HHF events were projected in patients with CKD in both 2032 and cumulatively from 2023 to 2032 due to delayed disease progression following effective interventions. Driven by the reduced clinical burden, lower healthcare costs for CV event management were also predicted. These findings support the need for the adoption of policies for early diagnosis and treatment of CKD to slow disease progression and mitigate the growing CV disease burden among patients with CKD and for health systems. Future studies should explore the costs associated with targeted CKD screening and the guideline-directed pharmacological therapies for CKD.

Association Between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure: A Population-Based Study.

The relation between age at diagnosis of type 2 diabetes (T2D) and hospitalization for heart failure (HHF) is unclear. We assessed the association between age at diagnosis of T2D and HHF. We conducted a population-based cohort study using administrative health databases from the Canadian province of Ontario, including participants without prior heart failure. We identified people with new-onset T2D between April 1, 2005 and March 31, 2015, and matched each person with 3 diabetes-free adults, according to birth year and sex. We estimated adjusted hazard ratios (HRs) and rate ratios (RRs) for the association between age at T2D diagnosis and incident HHF, which was assessed until March 31, 2020. Among 743 053 individuals with T2D and 2 199 539 matched individuals without T2D, 126 241 incident HHF events occurred over 8.9 years. T2D was associated with a greater adjusted hazard of HHF at younger ages (eg, HR at age 30 years: 6.94 [95% CI, 6.54-7.36]) than at older ages (eg, HR at age 60 years: 2.50 [95% CI, 2.45-2.56]) relative to matched individuals. Additional adjustment for mediators (hypertension, coronary artery disease, and chronic kidney disease) marginally attenuated this relationship. Age at T2D diagnosis was associated with a greater number of HHF events relative to matched individuals at younger ages (eg, RR at age 30 years: 6.39 [95% CI, 5.76-7.08]) than at older ages (eg, RR at age 60 years: 2.65 [95% CI, 2.54-2.76]). Younger age at T2D diagnosis is associated with a disproportionately elevated HHF risk relative to age-matched individuals without T2D.

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.

Prognostic significance of growth differentiation factor-15 across the BMI spectrum in patients with chronic heart failure: Insights from the SUPPORT trial

Abstract Background Obesity is a risk factor for cardiovascular diseases including heart failure (HF), yet patients with obesity have better outcomes than their leaner counterparts in HF (i.e. the obesity paradox). We sought to investigate whether growth differentiation factor-15 (GDF15), an emerging biomarker in HF reflecting inflammation and oxidative stress, is a prognostic indicator across the body mass index (BMI) spectrum in chronic heart failure (CHF). Methods Serum levels of GDF15 and its prognostic significance across BMI were examined in a total of 1,040 Japanese patients with CHF enrolled in a randomized clinical trial of the SUPPORT trial (supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan) (mean age 66.0±9.9 years, 26% female). Patients were categorized into four groups: underweight (BMI <18.5 kg/m2; n = 56), normal (BMI 18.5-22.9; n = 304), overweight (BMI 23-24.9; n = 257), and obese (BMI ≥25; n = 423) defined based on the WHO recommendation for Asian-Pacific population. Results The underweight group consisted of older patients with a higher prevalence of NYHA class III and reduced left ventricular ejection fraction (LVEF) compared to obese patients (mean age 69.0 vs 64.7 years, NYHA class III 17.9 vs 5.9%, and mean LVEF 49.3 vs 55.5%; all p<0.05). Median GDF15 level in the underweight group was higher (1,864 pg/mL [IQR 1,070-2,626]) but was similar in overweight and obese groups (1,285 [953, 1772] and 1,220 [888-1,789], respectively) compared to normal BMI group (1,276 [879-2,018]). During follow-up (median 10.3 years), 540 composite events of HF hospitalization or all-cause death occurred. The risk was higher in the underweight group (adjusted HR 1.8, 95%CI [1.3-2.5]) and lower in the obesity group (adjusted HR 0.8 [95% CI 0.6-0.9]) compared to the normal BMI group. An increased GDF15 incurred a consistently higher risk from underweight to obese groups; per unit increase in logGDF15 (pg/mL) was associated with 4.1, 2.4, 1.7 and 2.4 times higher risk, respectively. The optimal cut-off point for discriminating those with and without the composite events was 1,343 pg/mL in overall patients. This cut-off value performed well as a prognostic indicator across the continuous BMI spectrum including those with higher BMI (Figure). Conclusions The prognostic significance of GDF15 persisted across the BMI spectrum in patients with CHF. GDF15 may be useful for providing prognostic information across patients with a diverse range of BMI even in those with modest outcomes.HF events in high GDF15 across BMI

Role of fragmented QRS complex in the prognosis of patients undergoing cardiac resynchronization therapy. A new red flag to look for?

Abstract Introduction Cardiac resynchronization therapy (CRT) has demonstrated to reduce mortality and hospitalization for heart failure in selected patients with heart failure with reduced ejection fraction (HFrEF). However, there is a significant percentage of readmissions for heart failure (HF) after implantation. In the recent years, several biomarkers and electrocardiographic findings possibly related with prognosis in this group of patients have been identified. Fragmentation of QRS complex (fQRS) has been related with worse prognosis in various cardiac diseases, but the evidence in patients undergoing CRT is limited. Purpose The objective of this study is to evaluate if the presence of pre-implantation fragmented QRS complex has a prognostic role in patients undergoing cardiac resynchronization therapy in terms of hospitalization for HF. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. Fragmentation of the QRS complex was defined by the presence of different RSR′ patterns including an additional R-wave (R′), notching of the R-wave and S-wave or the presence of more than 1R′ in two contiguous leads corresponding to a main coronary artery territory. Results 244 patients were included. Mean age at the implantation of the device was 71.8 years (standard deviation, SD ±9.8 years), 79.5% were male and 40.2% were diabetic. Mean LVEF was 24.9% (SD ±8.9) and the aetiology was non-ischaemic in 50.8% of the patients and ischaemic in 49.2%. 40.2% had prior history of acute myocardial infarction. Pre-implantation fragmented QRS complex was found in 58.6% of the patients and mostly in inferior leads of the surface ECG. Mean QRS duration was 157.9ms and 82.0% had left-bundle branch block morphology. CRT with defibrillator implantation was performed in 71.4% of the patients. The median follow-up time was 27.4 month. After device implantation, mean LVEF was 33.2% and 76.6% presented NYHA class I-II. During this period, 28.7% of the patients died. Additionally, 29.1% of the patients presented at least one hospitalization for heart failure (HF), 22.5% with fQRS and 6.6% without fQRS. A multivariate survival study using Cox regression showed that the presence of pre-implantation fQRS was an independent predictor of HF hospitalization events (HR 2.24; 95% CI 1.20-4.18). Figure 1 presents Kaplan-Meier curves for hospitalization for HF. Conclusions According to our results, pre-implantation fQRS is a strong independent predictor of hospitalization for HF after CRT implantation. Thus, patients with fQRS could benefit from a more rigorous follow-up as they present higher risk of decompensation. Further research is needed to confirm our findings.Figure 1.Kaplan-Meier curves

Functional tricuspid regurgitation associated with left-side valvulopathy: clinical profile and long term evolution based on pulmonary pressure

Abstract Introduction Tricuspid regurgitation (TR) is an entity with multiple etiologies, with functional TR associated with left-sided valvulopathy being the most frequent group in clinical practice, accounting for approximately 50%. This group has traditionally been considered a consequence of pulmonary hypertension (PH) secondary to left-sided valvulopathy, although this dogma has hardly been evaluated despite new clinical and pathophysiological knowledge of TR. In this study we aimed to evaluate the clinical profile and evolution of a large series of patients with significant TR based on pulmonary pressure. Methods Multicenter and retrospective study that included a series of consecutive patients with significant TR (moderate to severe or greater) diagnosed between 2002 and 2017. After excluding patients with organic TR (congenital or acquired), those with TR associated with left-sided valvular disease were included, defined by the presence of mild mitral stenosis, previous left-sided surgery, left-sided valvular prosthesis or other left-sided valvular disease of at least moderate grade. Patients were classified according to the absence or presence of PH which was estimated by echocardiography, defining a systolic pulmonary arterial pressure (PASP) ≥ 50 mmHg. Subsequently, the baseline clinical characteristics of the sample were compared and a follow-up was carried out to evaluate long-term mortality and hospitalization events due to heart failure (HF). Results A total of 422 patients were were included (160 with PASP <50 and 262 with PASP ≥50). The attached table shows the baseline characteristics of both groups. Patients with PASP <50 were younger, had a higher percentage of previous valvular surgery, AF, HTN, and DM, along with a lower percentage of pulmonary disease and right HF. After follow-up (median 42.6 months), significant differences were observed between the two groups (Figures 1 and 2) with higher overall long-term survival (p<0.001) and higher freedom from HF hospitalization (p 0.013) in the group without PH. Cox regression analysis showed that female sex was a predictor of higher survival (p<0.001) while age and previous diagnosis of RHF were predictors of mortality (p<0.001). Similarly, the presence of previous RHF and previous hospitalizations for HF were predictors of the HF hospitalization event (p<0.001). Conclusions In a large series of patients with left-sided valvular heart disease and TR, cases with estimated absence of significant PH were frequent (37.9%). Furthermore, it was observed that pulmonary disease (a possible concomitant cause of PH) was more frequent in the group with significant PH. The group without PH had a different clinical profile and a better long-term prognosis. All of this suggests that there are different factors that determine the development of significant TR associated with left-sided valvular heart disease, beyond secondary PH itself. These factors could influence the patient's prognosis.Baseline clinical characteristics.Kaplan Meier survival curves.

Abstract 17225: Association Between Moderate and Vigorous Physical Activity on Long-Term Heart Failure Risk: The Cooper Center Longitudinal Study

Introduction: Regular physical activity (PA) is associated with a lower risk of heart failure (HF). However, the relative contributions of moderate and vigorous intensity exercise on HF risk is still unclear. We characterized the association between moderate (MPA) and vigorous physical activity (VPA) on the long-term risk for HF. Methods: We included participants free from baseline coronary disease in the Cooper Center Longitudinal Study (CCLS) who were Medicare eligible at age 65 years. PA was measured from a self-report instrument that included duration (minutes/week) and intensity of exercise (METs), with moderate intensity as 3-6 METs and vigorous intensity as 6 METs. Incident HF was defined as a HF hospitalization event (primary diagnosis) from Medicare claims files. MPA and VPA were considered separately as continuous variables. The association between baseline PA and incident HF was evaluated by Cox proportional hazards models adjusted for standard HF risk factors. Results: Of 32,322 individuals (mean age 50.9, 74.2% men), the mean number of hours/week of MPA and VPA was 1.2 and 1.4, respectively. 56.42% reported zero MPA and 42.6% reported zero VPA. Higher levels of VPA, but not MPA, were associated with a lower burden of HF risk factors. After 275,373 person-years of follow-up, we observed 954 incident HF hospitalizations. MPA was not significantly associated with HF risk in either model. VPA was inversely associated with HF risk in age-adjusted models. After multivariable adjustment, VPA was not associated with HF risk (see table). Conclusions: Midlife VPA, but not MPA, was associated with a lower risk for HF. However, after additional adjustment for traditional HF risk factors, the association between higher VPA and HF risk was no longer significant. These findings suggest that the inverse association between midlife VPA and long-term HF risk may be mediated by a more favorable risk factor profile.

Clinical outcomes with the use of sodium-glucose cotransporter-2 inhibitors in patients with atrial fibrillation and type 2 diabetes mellitus: a multi-centre, real-world cohort study.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular outcomes and reduce the incidence of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We investigated the clinical outcomes with and without the use of SGLT2is in patients with T2DM and concomitant AF. We derived patient data from a clinical data warehouse constructed from the electronic medical records of seven medical centres. Data for 11 012 patients diagnosed with both AF and T2DM were analysed. New SGLT2i users were classified into the SGLT2i group and those who were not prescribed SGLT2is were classified into the control group. We performed a 1:2 propensity score (PS)-matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure (HF) events in 3 years. The PS-matched population consisted of 1115 patients in the SGLT2i group and 2050 patients in the control group. Incidence of the primary endpoint was significantly lower in the SGLT2i group [8.4 vs. 14.6%, hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.55-0.87]. Sodium-glucose cotransporter-2 inhibitors use was associated with significantly lower all-cause mortality (HR 0.43, 95% CI 0.29-0.67) and HF hospitalization (HR 0.77, 95% CI 0.59-0.99). Adverse renal events, defined as >50% increase in serum creatinine level or initiation of dialysis, occurred less often in the SGLT2i group (HR 0.50, 95% CI 0.38-0.66, P < 0.001). Use of SGLT2is in patients with T2DM and concomitant AF was associated with reduced mortality or HF hospitalization events.

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P<0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12months (P=0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P=0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n=6, 20%) and 3years (n=10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600pg/mL, or estimated glomerular filtration rate (eGFR) <30mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

Sex differences in long-term outcomes following acute heart failure hospitalization: Findings from the Get With The Guidelines-Heart Failure registry.

Sex differences in long-term outcomes following hospitalization for heart failure (HF) across ejection fraction (EF) subtypes are not well described. In this study, we evaluated the risk of mortality and rehospitalization among males and females across the spectrum of EF over 5 years of follow-up following an index HF hospitalization event. Patients hospitalized with HF between 1 January 2006 and 31 December 2014 from the American Heart Association's Get With The Guidelines-Heart Failure registry with available 5-year follow-up using Medicare Part A claims data were included. The association between sex and risk of mortality and readmission over a 5-year follow-up period for each HF subtype (HF with reduced EF [HFrEF, EF ≤40%], HF with mildly reduced EF [HFmrEF, EF 41-49%], and HF with preserved EF [HFpEF, EF >50%]) was assessed using adjusted Cox models. The effect modification by the HF subtype for the association between sex and outcomes was assessed by including multiplicative interaction terms in the models. A total of 155 670 patients (median age: 81 years, 53.4% female) were included. Over 5-year follow-up, males and females had comparably poor survival post-discharge; however, females (vs. males) had greater years of survival lost to HF compared with the median age- and sex-matched US population (HFpEF: 17.0 vs. 14.6 years; HFrEF: 17.3 vs. 15.1 years; HFmrEF: 17.7 vs. 14.6 years for age group 65-69 years). In adjusted analysis, females (vs. males) had a lower risk of 5-year mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.87-0.90, p < 0.0001), and the risk difference was most pronounced among patients with HFrEF (aHR 0.87, 95% CI 0.85-0.89; pinteraction [sex*HF subtype] = 0.04). Females (vs. males) had a higher adjusted risk of HF readmission over 5-year follow-up (aHR 1.06, 95% CI 1.04-1.08, p < 0.0001), with the risk difference most pronounced among patients with HFpEF (aHR 1.11, 95% CI 1.07-1.14; pinteraction [sex*HF subtype] = 0.001). While females (vs. males) had lower adjusted mortality, females experienced a significantly greater loss in survival time than the median age- and sex-matched US population and had a greater risk of rehospitalization over 5 years following HF hospitalization.

Heart failure management guided by remote multiparameter monitoring: A meta-analysis

BackgroundSeveral implant-based remote monitoring strategies are currently tested to optimize heart failure (HF) management by anticipating clinical decompensation and preventing hospitalization. Among these solutions, the modern implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been equipped with sensors allowing continuous monitoring of multiple preclinical markers of worsening HF, including factors of autonomic adaptation, patient activity, and intrathoracic impedance. ObjectivesWe aimed to assess whether implant-based multiparameter remote monitoring strategy for guided HF management improves clinical outcomes when compared to standard clinical care. MethodsA systematic literature research for randomized controlled trials (RCTs) comparing multiparameter-guided HF management versus standard of care was performed on PubMed, Embase, and CENTRAL databases. Incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) were calculated using the Poisson regression model with random study effects. The primary outcome was a composite of all-cause death and HF hospitalization events, whereas secondary endpoints included the individual components of the primary outcome. ResultsOur meta-analysis included 6 RCTs, amounting to a total of 4869 patients with an average follow-up time of 18 months. Compared with standard clinical management, the multiparameter-guided strategy reduced the risk of the primary composite outcome (IRR 0.83, 95%CI 0.71–0.99), driven by statistically significant effect on both HF hospitalization events (IRR 0.75, 95%CI 0.61–0.93) and all-cause death (IRR 0.80, 95%CI 0.66–0.96). ConclusionImplant-based multiparameter remote monitoring strategy for guided HF management is associated with significant benefit on clinical outcomes compared to standard clinical care, providing a benefit on both hospitalization events and all-cause death.

188-LB: Association between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure (HHF)

Background: The relation between age at T2D diagnosis and HHF is unclear. We conducted a population-based cohort study to examine the association between age at diagnosis of T2D and incident HHF in Ontario, Canada. Methods: Using administrative health databases, we identified people with new-onset T2D between April 1, 2005 and March 31, 2015. We matched each person to 3 other people without diabetes according to birth year and sex. We excluded any people with prior HHF. We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) for the association between age at T2D diagnosis and incident HHF (followed up until March 31, 2020). Results: Among 743,053 individuals with T2D and 2,199,539 matches, 126,241 incident HHF events occurred (median follow-up 8.9 years). T2D was associated with a greater adjusted hazard of HHF at younger ages (e.g., HR at age 30 years: 5.71, 95% CI: 5.46-5.96; Figure: Model 1) than at older ages (e.g., HR at age 60 years: 2.51, 2.46-2.55). Additional adjustment for recognized mediators (hypertension, coronary artery disease, chronic kidney disease) marginally attenuated this relation (Figure: Model 2). Conclusion: Younger age at T2D diagnosis is independently associated with a disproportionately elevated risk of HHF relative to age-matched individuals without T2D. This relation may be substantially mediated by novel mechanisms that are inadequately understood. Disclosure C. Ke: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Abbott. B. R. Shah: None. J. Echouffo tcheugui: None. Funding National Heart, Lung, and Blood Institute (K23HL153774 to J.E.T.); University of Toronto (to B.R.S.)

Scientific evidence of sodium-glucose cotransporter-2 inhibitors for heart failure with preserved ejection fraction: an umbrella review of systematic reviews and meta-analyses.

It remains controversial whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are effective in treating heart failure with preserved ejection fraction (HFpEF). The objective of this umbrella review is to provide a summary of the available evidence regarding the efficacy and safety of SGLT-2is for the treatment of HFpEF. We extracted pertinent systematic reviews and meta-analyses (SRs/MAs) from PubMed, EMBASE, and the Cochrane Library that were published between the inception of the database and December 31, 2022. Two independent investigators assessed the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs in randomized controlled trials (RCTs). We further evaluated the overlap of the included RCTs by calculating the corrected covered area (CCA) and assessed the reliability of the effect size by performing excess significance tests. Additionally, the effect sizes of the outcomes were repooled to obtain objective and updated conclusions. Egger's test and sensitivity analysis were used to clarify the stability and reliability of the updated conclusion. This umbrella review included 15 SRs/MAs, and their methodological quality, risk of bias, report quality, and evidence quality were unsatisfactory. The total CCA for 15 SRs/MAs was 23.53%, indicating a very high level of overlap. The excess significance tests did not reveal any significant results. Our updated MA demonstrated that the incidence of the composite of hospitalization for heart failure (HHF) or cardiovascular death (CVD), first HHF, total HHF, and adverse events as well as the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and 6 min-walk distance (6MWD) were all substantially improved in the SGLT-2i intervention group compared to the control group. However, there was limited evidence that SGLT-2is could improve CVD, all-cause death, plasma B-type natriuretic peptide (BNP) level, or plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. Egger's test and sensitivity analysis proved that the conclusion was stable and reliable. SGLT-2 is a potential treatment for HFpEF with favourable safety. Given the dubious methodological quality, reporting quality, evidence quality, and high risk of bias for certain included SRs/MAs, this conclusion must be drawn with caution. https://inplasy.com/, doi: 10.37766/inplasy2022.12.0083, identifier INPLASY2022120083.

Association of Nondihydropyridine Calcium Channel Blockers Versus β-Adrenergic Receptor Blockers With Risk of Heart Failure Hospitalization

Heart failure (HF) with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are interrelated and often coexisting conditions in older adults. Although equally recommended, nondihydropyridine calcium channel blockers (non-DHP CCBs), such as diltiazem and verapamil, are less often used than β blockers. Because recent studies suggested that β-blocker use in both HFpEF and AF may increase the risk for HF, we tested whether non-DHP CCBs were associated with lower HF hospitalization risk than β blockers. We examined fee-for-service Medicare beneficiaries who were aged ≥66years, had HFpEF or AF, and newly initiated a β blocker (n=83,458) or non-DHP CCB (n=18,924) from 2014 to 2018. The outcomes of HF hospitalization and all-cause mortality were analyzed using multivariable-adjusted Cox regression in the full cohort and, separately, in the subset without a recent hospital or skilled nursing discharge. Follow-up was analyzed using 2 frameworks: intention-to-treat and censored-at-drug-switch-or-discontinuation. There was a modestly protective association of non-DHP CCBs for the risk of HF hospitalization. Before drug switch or discontinuation, the use of diltiazem or verapamil was associated with decreased risk of HF hospitalization in the full cohort (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.81 to 1.00, p=0.05) and in the subgroup (HR 0.70, 95% CI 0.56 to 0.89, p=0.003). However, the association with all-cause mortality tended to favor β blockers, including in the intention-to-treat analysis (HR 1.21, 95% CI 1.17 to 1.25, p <0.001). In conclusion, compared with β blockers, the initiation of diltiazem or verapamil in patients with HFpEF or AF may be associated with fewer HF hospitalization events but also with more all-cause deaths.

PO-03-076 MACHINE LEARNING METHODS IDENTIFYING RISK FOR 30-DAY HEART FAILURE READMISSION USING DIAGNOSTICS PARAMETERS FROM IMPLANTED CARDIOVASCULAR DEVICES

Heart failure (HF) related diagnostics parameters measured daily from implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRTD) have shown to change before, during and after HF hospitalization events. We assessed the ability to identify patients at risk of a recurrent HF admission with different machine learning techniques leveraging statistical and temporal behavior of the cardiac compass parameters prior and during HF hospitalization events. We linked Optum® deidentified Electronic Health Record dataset during the period from 2007-2021 to the Medtronic CareLinkTM data warehouse with device based continuous diagnostic monitoring data. Patients with ICD/CRTD implants with intra-thoracic impedance diagnostic feature were included for this study. Retrospective analysis was completed identifying HF admissions with diagnostic parameters from 30-days prior admission day ending on discharge day. Analyzed events included such HF admissions within the 2 to 30 days for length of stay. Admission day parameters were evaluated with the following criteria: 7-days to 30-days activity, night heart rate and day heart rate ratios, plus 3-day impedance change. In addition, diagnostic data during hospitalization was summarized into range, median, mean, and standard deviation. Length of stay was also used as an input for the models. Two groups were created based on hospitalization events with or without 30-day readmission. Dataset was split into training and validation subsets. Multiple machine learning models were trained to classify events indicating those followed by a close HF readmission. Models’ results were compared in terms of sensitivity, specificity, and false positive rates on validation set. 1745 HF hospitalization events were assessed in this study, including 486 preceding a re-admission event within 30-days post discharge. The average length of stay on this cohort was 6.2 days. Seven machine learning models were trained using 28 features derived from diagnostic data and length of stay as input. Models’ sensitivity and specificity ranged from 0.11 to 0.84 and 0.89 to 0.93 respectively. Table 1 depicts area under the curve (AUC) for each trained model. Mean model accuracy on validation data was 0.84. A machine learning derived HF diagnostic criteria evaluating diagnostic parameters on HF admission day plus while in hospital may be useful to identify patients at higher risk of 30-days HF readmission at time of discharge.Tabled 1Table 1. AUC for each Classification ModelMODEL NAMEAUCLogistic Regression0.92Decision Tree0.82RUSBoosted Trees0.94Support Vector Machine0.83Bi-layered Neural Network0.86Three-layered Neural Network0.86Optimizable Neural Network0.94 Open table in a new tab

CI-452766-4 LONG-TERM CLINICAL OUTCOMES OF LEFT BUNDLE BRANCH AREA PACING VERSUS BIVENTRICULAR PACING FOR HEART FAILURE TREATMENT: REAL-WORLD EXPERIENCE

Left bundle branch area pacing (LBBAP) has shown potential to be an alternative to biventricular pacing (BiVP) in patients with indications for cardiac resynchronization therapy (CRT). However, few studies focused on the long-term clinical outcomes of LBBAP versus BiVP. This prospective observational study aimed to compare long-term clinical outcomes and complications between LBBAP and BiVP. Consecutive patients with left ventricular ejection fraction (LVEF) <50% and CRT indications were enrolled and prospectively followed up at device clinic if they received successful LBBAP or BiVP from Jan. 2019 to Dec. 2020 at two centers. The primary endpoint was the composite outcomes of all-cause death or heart failure hospitalization (HFH). Secondary endpoints included the occurrence of death, or HFH, or malignant ventricular arrhythmias (VAs). The safety endpoints were device-related complications. Pacing parameters and cardiac function were routinely tracked. A total of 259 patients (mean age 63 ± 11 years, male 65.6%, LVEF 30.4% ± 6.9%) were enrolled, including 106 cases with LBBAP and 153 with BiVP. The paced QRS duration of LBBAP was significantly shorter than that of BiVP (137.3 ± 27.8 ms vs. 148.8 ± 22.1 ms, p<0.001). During the median follow-up of 27 months, LBBAP achieved a higher LVEF improvement from baseline (12.8 ± 12.3% vs. 9.81 ± 12.7%, p=0.043) and similar echo response or super response as compared with BiVP. The risk of the primary endpoint was significantly decreased by 42% in patients with LBBAP than those with BiVP [21.7% vs. 41.2%, adjusted hazard ratio (aHR) 0.58; 95% confidence interval (CI) 0.35–0.98; p=0.041], which was primarily driven by significantly reduced events of HFH after LBBAP treatment [16.0% vs. 36.6%, aHR (95%CI): 0.49 (0.28, 0.85), p=0.012]. The events of all-cause death or malignant VAs were comparable between two groups. Subgroup analysis revealed that patients with left bundle branch block (LBBB) benefited more from LBBAP [aHR (95%CI): 0.35 (0.17, 0.73), p=0.005] than those with non-LBBB or narrow QRS (p for interaction=0.005). The device-related complications were lower in the LBBAP than BiVP group (3.8% vs. 13.1%, p=0.005), mainly due to lead-related complications (1.9% vs. 11.1%, p<0.001). The long-term clinical outcomes of LBBAP for HF treatment might be superior to BiVP with reduced HFH events and lead-related complications in patients with indications for CRT.

Native T1 is predictive of cardiovascular death/heart failure events and all-cause mortality irrespective of the patient's volume status.

Native T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis. Patients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim's formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality. A total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52-72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (β = 0.11, p < 0.0001). Patients with volume expansion (PVS > -13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ -13%; median (IQR); native T1 1,130 (1,095-1,170) vs. 1,123 (1,086-1,166) ms, p < 0.003; and T2 39 (37-40) vs. 38 (36-40) ms, p < 0.0001]. In Cox regression analysis both native T1 and PVS were independently predictive of the primary endpoint and all-cause mortality. Despite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort.

The cardiovascular effects of SGLT2 inhibitors, RAS inhibitors, and ARN inhibitors in heart failure.

No studies have comprehensively compared the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, renin-angiotensin system (RAS) inhibitors, and angiotensin receptor neprilysin (ARN) inhibitors based on different type of heart failure, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The aim of this network meta-analysis was to evaluate the relative efficacy of SGLT2 inhibitor (SGLT2i), RAS inhibitor (RASi) and ARN inhibitor (ARNI) in different types of heart failure. A systemic literature search was performed from inception to 19 November 2022 for randomized control trials assessing the risk of cardiovascular (CV) death or hospitalization for heart failure (HHF) of these drugs in HF. A network meta-analysis was performed. Risk ratio (RR) with 95% confidence intervals (CI) were synthesized. Seventeen studies were selected with a total of 61 489 patients. In patients with HFrEF, ARNI led to a reduced risk of a composite outcome of CV death or HHF when compared with placebo (RR=0.83, 95% CI 0.77-0.89). Similar trends were observed when focusing on the outcome of CV death or HHF alone. In patients with HFpEF, SGLT2i showed the beneficial effects on the CV death or HHF events when compared with placebo and RASi (RR=0.82, 95% CI 0.74-0.92; RR=1.16, 95% CI 1.02-1.31). For CV death, all these three drugs could not show beneficial effects in HFpEF. For the incidence of HHF in HFpEF, both SGLT2i and ARNI demonstrated the beneficial effects but SGLT2i was superior to ARNI. There were no differences in the events of discontinuation under these drugs when compared with placebo or each other in either HFrEF or HFpEF patients. SGLT2i showed the least renal injury among these interventions in HFrEF and there were no differences in the incidence of renal injury of these interventions in HFpEF. Among these drugs, ARNI showed the greatest ability to lower the incidence of CV death or HHF and SGLT2i exerted the least renal injury in patients with HFrEF. In patients with HFpEF, SGLT2i was associated with a reduction in the risk of CV death or HHF. There were no differences in the incidence of renal injury of these interventions in HFpEF. The intolerance of these drugs were comparable in both HFrEF and HFpEF.

Machine Learning Models Predicting Cardiovascular and Renal Outcomes and Mortality in Patients with Hyperkalemia.

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition. We developed risk prediction models using extreme gradient boosting (XGB), multiple logistic regression (LR), and deep neural network. Models were derived from a retrospective cohort of hyperkalemic patients with either heart failure or chronic kidney disease stage ≥3a from a Japanese nationwide database (1 April 2008-30 September 2018). Studied outcomes included all-cause death, renal replacement therapy introduction (RRT), hospitalization for heart failure (HHF), and cardiovascular events within three years after hyperkalemic episodes. The best performing model was further validated using an external cohort. A total of 24,949 adult hyperkalemic patients were selected for model derivation and internal validation. A total of 1452 deaths (16.6%), 887 RRT (10.1%), 1,345 HHF (15.4%), and 621 cardiovascular events (7.1%) were observed. XGB outperformed other models. The area under receiver operator characteristic curves (AUROCs) of XGB vs. LR (95% CIs) for death, RRT, HHF, and cardiovascular events were 0.823 (0.805-0.841) vs. 0.809 (0.791-0.828), 0.957 (0.947-0.967) vs. 0.947 (0.936-0.959), 0.863 (0.846-0.880) vs. 0.838 (0.820-0.856), and 0.809 (0.784-0.834) vs. 0.798 (0.772-0.823), respectively. In the external dataset including 86,279 patients, AUROCs (95% CIs) for XGB were: death, 0.747 (0.742-0.753); RRT, 0.888 (0.882-0.894); HHF, 0.673 (0.666-0.679); and cardiovascular events, 0.585 (0.578-0.591). Kaplan-Meier curves of the high-risk predicted group showed a statistically significant difference from that of the low-risk predicted groups for all outcomes (p &lt; 0.005; log-rank test). These findings suggest possible use of machine learning models for real-world risk assessment as a guide for observation and/or treatment decision making that may potentially lead to improved outcomes in hyperkalemic patients while retaining the benefit of life-saving therapies.

Effects of sodium-glucose cotransporter-2 inhibitors and aldosterone antagonists, in addition to renin-angiotensin system antagonists, on major adverse kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A systematic review and network meta-analysis.

To compare the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (MRAs), selective aldosterone antagonists and nonselective aldosterone antagonists, on top of renin-angiotensin-aldosterone system (RAAS) blockade, in reducing kidney-specific composite events, cardiovascular outcomes, and other events of special interest in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD). PubMed, EMBASE and CENTRAL were searched for studies published up to January 20, 2022. Randomized clinical trials enrolling participants with T2D and CKD were included, in which SGLT2 inhibitors, nonsteroidal MRAs, selective aldosterone antagonists and nonselective aldosterone antagonists were compared with either each other, or with placebo or no treatment. A network meta-analysis using a Bayesian approach was performed. The primary outcome was a kidney-specific composite event. Secondary outcomes included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and all-cause mortality. We also examined blood pressure and safety outcomes of interest, including acute kidney injury, hyperkalaemia, hyponatraemia, and volume reduction events. All research was conducted according to a protocol registered in the PROSPERO database (CRD42022307113). This meta-analysis of 17 trials randomizing 22 981 participants found SGLT2 inhibitors (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52 to 0.73) and nonsteroidal MRAs (OR 0.76, 95% CI 0.66 to 0.88) were associated with significantly lower kidney-specific composite events than the control groups. Nonsteroidal MRAs (OR 0.78, 95% CI 0.66 to 0.92) and SGLT2 inhibitors (OR 0.57, 95% CI 0.45 to 0.72) were associated with greater reductions in hospitalization for heart failure than the control groups. SGLT2 inhibitors were associated with a lower risk of hospitalization for heart failure events compared with nonsteroidal MRAs (OR 0.73, 95% CI 0.55-0.97). SGLT2 inhibitors were associated with a reduction in cardiovascular death (OR 0.80, 95% CI 0.65 to 0.98) and all-cause mortality (OR 0.79, 95% CI 0.66 to 0.93) compared with the control groups. When compared to the control groups, both nonsteroidal MRAs (weighted mean difference [WMD] -10.96, 95% CI -20.49 to -1.46) and SGLT2 inhibitors (WMD -3.50, 95% CI -6.01 to -1.013) were linked with lower systolic blood pressure, nonsteroidal MRAs (OR 2.27, 95% CI 2.02 to 2.56) and nonselective aldosterone antagonists (OR 3.22, 95% CI 1.43 to 7.66) were associated with an increased risk of hyperkalaemia, nonsteroidal MRAs were linked with an increased risk of hyponatraemia (OR 16.56, 95% CI 2.78 to 455.19), and SGLT2 inhibitors were associated with an increased risk of volume reduction events (OR 1.28, 95% CI 1.06 to 1.56). SGLT2 inhibitors were ranked the best for our primary and secondary outcomes. Confidence in the evidence was often high or moderate. In this network meta-analysis, the use of SGLT2 inhibitors or nonsteroidal MRAs, combined with RAAS blockade, was associated with a reduction in kidney-specific composite events and hospitalization for heart failure events in patients with T2D and CKD compared to placebo or no treatment. SGLT2 inhibitors were associated with a lower risk of hospitalization for heart failure events compared with nonsteroidal MRAs. Use of SGLT2 inhibitors was associated with lower mortality than placebo or no treatment.