Benefit In Heart Failure Research Articles

Survival benefit of ICD implantation for primary prevention in dilated cardiomyopathy

Objectives: Dilated cardiomyopathy (DCM) represents a significant cause of heart failure unrelated to ischemic heart disease, posing a high risk of sudden cardiac death (SCD) due to low left ventricular ejection fraction (LVEF). This study evaluates the survival benefits of implantable cardiac defibrillators (ICDs) for primary prevention in DCM patients. Methods: We enrolled 52 symptomatic non-ischemic cardiomyopathy patients (LVEF ≤ 35%, NYHA class II-III) eligible for ICD implantation in Afshar Hospital, Yazd, Iran, from 2014 to 2015. Exclusion criteria included those with ischemic indications or requiring cardiac resynchronization therapy. We divided patients into ICD recipients and those on a waiting list, collected the baseline data (age, functional class, LVEF), then followed up with patients to assess mortality rates. Results: Among 45 patients, 64.5% received ICDs while 35.5% were on the waiting list. The mean age was 57±13 years, predominantly male (67.3%). The ICD group had a significantly lower mortality rate (17.3%) than the waiting list group (42.7%, p = 0.54). Although age and functional class did not significantly predict outcomes, lower LVEF was a crucial factor for long-term survival. Despite some studies suggesting no survival benefit in non-ischemic heart failure, our findings highlight the efficacy of ICDs in reducing mortality among DCM patients. Conclusions: ICD implantation in DCM patients substantially reduces all-cause mortality compared to those awaiting the procedure, underscoring the importance of timely ICD deployment for primary prevention in this population.

Science of left ventricular unloading.

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Update on the clinical applications of SGLTis: Insight to benefits beyond hypoglycemic and cardiorenal protection.

Sodium glucose cotransporter inhibitor (SGLTi) drugs have been widely used in clinical practice. In addition to their benefits in hyperglycemia, heart failure (HF), and kidney disease, their effects on obesity, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly named nonalcoholic fatty liver disease [NAFLD]), polycystic ovarian syndrome (PCOS), abnormal lipid metabolism, hyperuricemia, obstructive sleep apnea syndrome (OSAS), anemia, and syndrome of inappropriate antidiuresis (SIAD, formerly named syndrome of inappropriate antidiuretic hormone [SIADH]) have been explored. In this review, we searched the data of clinical randomized controlled trials (RCTs) and meta-analyses of SGLTis in patients with diabetes from the PubMed library between January 1, 2020, and February 1, 2024. According to our review, certain SGLTis exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can provide additional medication options for patients with different disease scenarios. However, studies of SGLTis in these diseases are relatively rare, with shortcomings such as small sample sizes and short intervention periods. Therefore, further large-scale, long-term, well-designed studies are needed to clarify the findings.

Mechanisms of heart failure and chronic kidney disease protection by SGLT2 inhibitors in nondiabetic conditions.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: 1) the impact on renal hemodynamics and tubuloglomerular feedback; 2) the natriuretic effects via proximal tubule Na+/H+ exchanger NHE3 inhibition; 3) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; 4) the impact on erythropoiesis, not only in the context of local hypoxia but also systemic inflammation and iron regulation; 5) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; 6) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance, and stimulation of lipolysis and ketogenesis; 7) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and 8) the direct cardiac effects. The intricate interplay between renal, neurohumoral, metabolic, and cardiac effects underscores the complexity of SGLT2i actions and provides valuable insights into their therapeutic implications for HF and CKD. Furthermore, this review sets the stage for future research to evaluate the individual contributions of these mechanisms in diverse clinical settings.

A potential novel treatment for cirrhosis-related ascites: Empagliflozin is safe and tolerable in advanced chronic liver disease.

Advanced chronic liver disease and advanced chronic liver disease-related ascites have a high mortality. The pharmacological treatment of ascites and fluid overload has changed little over time. Empagliflozin, a sodium-glucose cotransporter type 2 inhibitor is an untested potential novel treatment in cirrhosis, as it has survival benefits in heart failure, which has similar pathophysiological fluid overload mechanisms. Before investigating empagliflozin's potential benefit in cirrhosis, its safety must be addressed. Ten participants (five each with compensated or decompensated advanced chronic liver disease, based on Child-Pugh class) received empagliflozin 10 mg orally daily for 4 weeks with 2 weeks follow-up. Empagliflozin safety, pharmacokinetics and pharmacodynamics were investigated. In total, eight patients (80%) reported an adverse event, and three patients (30%) experienced a serious adverse event, one of which was attributed to empagliflozin. Overall, the frequency of adverse events was similar to previous phase 3 trials of gliflozins. Higher plasma empagliflozin concentrations did not significantly increase the risk of adverse events. Four-week treatment with empagliflozin was safe and well tolerated in patients with advanced chronic liver disease. These preliminary data support assessment of long-term treatment on disease-related and mortality outcomes in patients with cirrhosis through randomized control trials.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30days, 1year, and 3years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). BB showed lower all-cause mortality at 30days, 1year, and 3years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Revisiting nitrates use in pre-shock state of contemporary cardiogenic shock classification.

Patients at each shock stage may behave and present differently with a spectrum of shock severity and adverse outcomes. Shock severity, shock aetiology, and several factors should be integrated in management decision-making. Although the contemporary shock stages classification provided a standardized shock severity assessment, individual agents or management strategy has not yet been studied in the context of each shock stage. The pre-shock state may comprise a wide range of presentations. Nitrate therapy has potential benefit in myocardial infarction and acute heart failure. Herein, this review aims to discuss the potential use of nitrate therapy in the context of the pre-shock state or stage B of the contemporary shock classification given its various presentations.

Sodium-glucose co-transporter 2 inhibitors in acute heart failure: real-world prescription trends and outcomes analysis.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited. We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n=289) and a non-SGLT2i group (n=819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P<0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n=413), HF with mildly reduced EF (n=226), and HF with preserved EF (n=466) (log-rank test; P=0.044, P=0.013, and P=0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P<0.001). This association was also significant in the LVEF subgroups (P=0.005, P=0.032, and P=0.004, respectively). The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF.

Iterative Causal Forest: A Novel Algorithm for Subgroup Identification.

Precisely and efficiently identifying subgroups with heterogeneous treatment effects (HTEs) in real-world evidence studies remains a challenge. Based on the causal forest (CF) method, we developed an iterative CF (iCF) algorithm to identify HTEs in subgroups defined by important variables. Our method iteratively grows different depths of the CF with important effect modifiers, performs plurality votes to obtain decision trees (subgroup decisions) for a family of CFs with different depths, and then finds the cross-validated subgroup decision that best predicts the treatment effect as a final subgroup decision. We simulated 12 different scenarios and showed that the iCF outperformed other machine learning methods for interaction/subgroup identification in the majority of scenarios assessed. Using a 20% random sample of fee-for-service Medicare beneficiaries initiating sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, we implemented the iCF to identify subgroups with HTEs for hospitalized heart failure. Consistent with previous studies suggesting patients with heart failure benefit more from sodium-glucose cotransporter-2 inhibitors, iCF successfully identified such a subpopulation with HTEs and additive interactions. The iCF is a promising method for identifying subgroups with HTEs in real-world data where the potential for unmeasured confounding can be limited by study design.

Abstract 15007: Time to SGLT2i Initiation in Patients With Heart Failure

Introduction: SGLT2i, initially introduced as antidiabetic agents, have shown cardiovascular benefits for heart failure (HF) patients, irrespective of their diabetes status. Given the growing evidence from post-hoc analyses of landmark trials advocating for early initiation, this study aims to investigate the temporal trends in the timing of SGLT2i initiation after HF hospitalization. Methods: A cross-sectional study was conducted using administrative health data from Ontario, Canada. Our cohort included patients aged ≥65 years who filled an SGLT2i prescription after their HF hospitalization in Ontario, Canada between 4/2016-3/2021. We computed the median number of days to the first SGLT2i prescription after the HF discharge date, exclusively for patients who started SGLT2i. Patients were further stratified based on their diabetes status. Results: We identified 64,183 HF patients, of which 5,257 filled an SGLT2i prescription after discharge (mean age was 82.49; 46.9% men; 49.6% had diabetes). The number of patients starting an SGLT2i increased from 889 (16.9%) in 2016/17 to 1,206 (22.9%) by 2020/21. The median time from discharge following the index HF admission to first dispensation of an SGLT2i prescription decreased 7-fold over this period, from 1,082 days to 156 days (Figure 1). In 2016/17, patients with diabetes started an SGLT2i at a median of 930 days, and patients without diabetes at 1,640 days. However, by 2020/21, the median initiation times were closer at 143 and 189 days, respectively. Conclusions: Our findings demonstrate a substantial reduction in the time to SGLT2i initiation for patients after HF admission, suggesting increased clinician recognition of their cardiovascular benefits. However, initiation remains delayed, especially for patients without diabetes. To optimize patient outcomes, it is crucial to encourage early initiation of SGLT2i therapy in hospitalized HF patients and address potential barriers to SGLT2i initiation.

Abstract 13696: Sotagliflozin is Associated With Early Clinical Benefit for Heart Failure and Atherosclerotic Events

Background: SGLT inhibitors reduce cardiovascular (CV) death and heart failure (HF)-related outcomes in HF patients, with benefits observed within 1 month. Less data exist for the time to clinical benefit for reducing HF or major cardiovascular events (MACE; CV death, myocardial infarction, and stroke) with SGLT inhibitors in patients with chronic kidney disease at high CV risk. Objective: This analysis evaluates the time to clinical benefit for HF-related events and MACE with sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, in SCORED. Methods: SCORED was a randomized, double-blind study of 10,584 patients with type 2 diabetes, chronic kidney disease, and other CV risk factors, where patients were randomized 1:1 to sotagliflozin or placebo. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. A prespecified secondary endpoint was total MACE. The present post hoc analysis calculated the sotagliflozin:placebo hazard ratios (HR) and 95% confidence intervals (CI) for each of these outcomes and determined the day after randomization where the treatment effect reached statistical significance (p&lt;0.05) and remained statistically significant for the duration of follow-up. Results: The overall risk of the primary endpoint was reduced by 26% (HR (95% CI) = 0.74 (0.63, 0.88); p&lt;0.001) with sotagliflozin, with a sustained significant reduction 95 days after randomization (HR (95% CI) = 0.70 (0.50, 0.98) at 95 days; Figure A). For MACE, the overall risk reduction with sotagliflozin was 23% (HR (95% CI) = 0.77 (0.65, 0.91); p&lt;0.001), with a sustained significant reduction 94 days after randomization (HR (95% CI) = 0.69 (0.47, 0.99) at 94 days; Figure B). Conclusion: In this stable, outpatient population at high risk for CV events, the time to clinical benefit with sotagliflozin was very early at approximately three months for both HF- and MACE-related outcomes.

Optimization of guideline-directed medical treatment for heart failure patients with reduced ejection fraction.

With the increasing number of medications demonstrating mortality benefits in heart failure with reduced ejection fraction (HFrEF), the pharmacological treatment of HFrEF is entering a new phase. To enhance outcomes in heart failure patients through medical treatment, the choice of appropriate medications and simultaneous and rapid uptitration are critical. However, there are several challenges encountered during this medication uptitration, including issues like hypotension, fatigue, worsening renal function, and hyperkalemia. This paper addresses strategies for effectively managing these challenges to successfully reach the maximum tolerated dose in patients. Additionally, it will discuss the management of comorbidities often associated with heart failure, the importance of exercise and rehabilitation, and the significance of proper nutrition intake, in addition to guideline-directed medical therapy.

Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY-747 designed for the treatment of resistant hypertension.

First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required. We report the high-throughput screening (HTS)-based discovery of a second generation of sGC stimulators from a novel imidazo[1,2-a]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY-747). The pharmacokinetic profile of BAY-747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension. BAY-747 is a highly potent sGC stimulator in vitro. In addition, BAY-747 showed an excellent pharmacokinetic profile with long half-life and low peak-to-trough ratio. BAY-747 was investigated in experimental in vivo models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY-747 caused a dose-related and long-lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12 days resulted in a persistent decrease. BAY-747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY-747 caused a dose-related and long-lasting (>6 h) MAP decrease. BAY-747 is a potent, orally available sGC stimulator. BAY-747 shows long-acting pharmacodynamic effects with a very low peak-to-trough ratio. BAY-747 could be a treatment alternative for patients with hypertension, especially those not responding to standard-of-care therapy.

#4406 INCREASE IN HOSPITALIZED DAYS AFTER HYPERKALEMIA-RELATED REDUCTION IN RAASI USE: AN OBSERVATIONAL STUDY ON CARDIORENAL PATIENTS IN SWEDEN AND JAPAN

Abstract Background and Aims Guidelines recommend renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at the maximum tolerated dose to achieve optimal treatment benefits in chronic kidney disease (CKD) and heart failure (HF). However, hyperkalemia (HK) is a barrier to achieving guideline-directed target dosing, with RAASi treatment often down-titrated or discontinued in patients who experience HK. Current international guidelines recommend novel oral anti-HK treatments to manage HK and facilitate optimization of RAASi therapy. The aim of this study was to describe the extent of RAASi reduction (down-titration or discontinuation) following an HK episode, and the associated change in inpatient days, in patients with cardiorenal disease in Sweden and Japan. Methods This observational study used data from health registers and hospital records in Sweden (national registers linked with health records from two large regions) and Japan (Medical Data Vision). Patients with an index HK episode, defined as ICD-10 code E87.5 (Japan and Sweden) or potassium &amp;gt;5.0 mmol/L (Sweden only), during March 2018 to July 2020 (Sweden) or May 2020 to February 2022 (Japan), with a prior diagnosis of CKD and/or HF, and RAASi use at index were included. RAASi classes included angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and an angiotensin receptor-neprilysin inhibitor (ARNi). Patients were defined as having reduced or maintained their pre-HK RAASi treatment based on filled prescriptions, or lack thereof, within 90 (Japan) or 120 (Sweden) days before versus after the index HK episode. Propensity score matching (1:1) was applied to balance the cohorts who reduced versus maintained their pre-HK RAASi treatment on demographics, comorbidities, baseline medications (including RAASi), and inpatient days prior to index. The change in number of all-cause, CKD-, and HF-related inpatient days (per person-years of follow-up) was described from 6 months before to 6 months after the index HK episode. Results In total, 20,824 patients from Sweden and 7789 from Japan were included. The mean age was 76 (Sweden) and 74 (Japan) years; 57% and 65%, respectively, were male. In Sweden, 86% had CKD and 57% had HF; in Japan, 49% had CKD and 75% had HF. The most common RAASi classes in Sweden were ACEi (used by 49%), ARB (44%), and MRA (30%). In Japan, ARB was the most common class (73%), followed by MRA (28%), and ACEi (17%). Overall, 42% (n = 8716) of patients in Sweden and 38% (n = 2976) in Japan reduced their RAASi treatment after the HK episode. In the propensity score matched cohorts, the increase in number of all-cause inpatient days following an HK episode in those with reduced RAASi treatment was 18.2 days in Sweden (n = 6998) and 17.9 days in Japan (n = 2092) (Figure A and B). For reference, the increase in those who maintained their RAASi treatment was 9.4 and 8.5 days in Sweden and Japan, respectively. Similar patterns were observed for CKD- and HF-related inpatient days. Conclusion In clinical practice, an episode of hyperkalemia was often followed by reduced RAASi treatment. Reduced RAASi treatment was associated with a greater increase in the number of inpatient days, compared with maintained RAASi treatment. A better understanding of how guideline adherence can be increased to maintain RAASi treatment in patients experiencing HK is needed to achieve optimal treatment benefits in chronic kidney disease (CKD) and heart failure (HF).

#3303 SUBOPTIMAL EXTENT OF RAASI RE-INITIATION AFTER DISCONTINUATION FOLLOWING HYPERKALEMIA: AN OBSERVATIONAL STUDY OF CARDIORENAL PATIENTS IN THE US AND JAPAN

Abstract Background and Aims Guidelines recommend renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at the maximal tolerated dose to achieve optimal treatment benefits in chronic kidney disease (CKD) and heart failure (HF). However, hyperkalemia (HK) is a barrier to achieving guideline-directed target dosing and RAASi treatment is often compromised in patients who experience HK. Current international guidelines recommend novel oral anti-HK treatments to manage HK and facilitate RAASi therapy. This study assessed the extent of both temporary and longer-term discontinuation of RAASi following an HK episode, and the magnitude of RAASi re-initiation, in cardiorenal patients in the US and Japan. Method This observational study used data from hospital records and claims from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Patients with an index HK event (ICD-10 code E87.5) during July 2019–September 2021 (US) or May 2020–February 2022 (Japan) with a prior diagnosis of CKD and/or HF and use of RAASi in the preceding 6 months were included. RAASi classes included angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor neprilysin inhibitors (ARNi). In patients who discontinued RAASi treatment following their index HK episode, duration of discontinuation was described within a time frame of 6 months from the date of discontinuation (those with &amp;lt;6 months follow-up time were excluded). The RAASi dose prior to discontinuation versus at re-initiation was also assessed. Results In total, 25,963 patients from the US and 8,722 from Japan were included. The mean age was 68.3 (US) and 74.8 (Japan) years; 53% and 65% were male; and 30% and 12% of patients had a recorded history of HK prior to their index event. In the US, 85% filled a RAASi prescription in the 3 months prior to HK episode; the most common RAASi classes were ACEi (used by 46% of the overall cohort), ARB (27%), and MRA (19%). In Japan, 91% filled a RAASi prescription in the 3 months prior to HK episode; ARB was the most common (67%), followed by MRA (25%), and ACEi (16%). ARNi was used by &amp;lt;5% of patients in the US and &amp;lt;2% in Japan; it was not assessed further due to low patient numbers. Following the HK episode, ACEi/ARB were discontinued in 23–26% of patients, while MRA was discontinued in 33–46% (Table 1). In those who discontinued, re-initiation within 6 months occurred among 10–15% of patients in the US and among 6–8% of patients in Japan. In those who re-initiated, 17–37% of patients in the US and Japan had their dose reduced by &amp;gt;25%. Conclusion In clinical practice, HK leads to discontinuation of RAASi treatment despite guidelines recommending maintained treatment. Re-challenge of RAASi treatment is uncommon and, when re-introduced, the dose is commonly reduced. These findings emphasize the need for improved guideline adherence in managing HK to facilitate continued RAASi therapy.

Sacubitril-valsartan shows benefit in heart failure with ejection fraction of >40.

Sacubitril-valsartan shows benefit in heart failure with ejection fraction of >40.

Prevention of Cancer Therapy-Related Cardiac Dysfunction With Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blocker: A Systematic Review of Randomised Controlled Trials

Cancer therapy-related cardiac dysfunction (CTRCD) is an important complication of selected chemotherapy agents associated with decline in left ventricular ejection fraction (LVEF) or clinical heart failure. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing and treating CTRCD remains controversial. This systematic review aimed to assess the efficacy of ACEI and ARB in the prevention of CTRCD. PubMed, Embase, and Cochrane were systematically searched. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving chemotherapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome of interest was the change in LVEF from baseline. Death, clinical heart failure, and adverse drug reactions were also recorded. A total of 3,731 search records were screened and 12 studies were included, comprising a total of 1,645 participants. Nine studies assessed the prevention of anthracycline-induced CTRCD, of which five studies showed a beneficial effect (1%–14% higher LVEF in treated groups), while four studies showed no beneficial effect. Three studies assessed the prevention of trastuzumab-induced CTRCD, of which one study showed a beneficial effect (4% higher LVEF) in a subset of participants. There is mixed evidence regarding the efficacy of ACEI or ARB in preventing the decline in LVEF in patients undergoing chemotherapy with either anthracyclines or trastuzumab, with a small but clinically meaningful benefit observed in some studies.

The Role of SGLT2 Inhibitors in Cardiovascular Management.

Cardiovascular disease is a major cause of morbidity and mortality worldwide in patients with type 2 diabetes. Type 2 diabetes confers an elevated risk of developing heart failure and atherosclerotic cardiovascular disease. Until recently, there have been limited options to prevent and reduce the cardiovascular complications of type 2 diabetes. However, recent therapeutic advances have led to the adoption of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in cardiovascular management. Though SGLT2i were originally used for antihyperglycemic treatment, a series of landmark trials found that SGLT2i may confer cardio-protective effects in patients with heart failure and atherosclerotic cardiovascular disease, particularly a reduction in cardiovascular mortality and hospitalizations for heart failure. The cardiovascular benefits of SGLT2i were similarly demonstrated in patients with and without type 2 diabetes. Though previous trials found SGLT2i to be cardio-protective in heart failure with reduced ejection fraction, recent trials demonstrated that SGLT2i may also provide cardiovascular benefits in heart failure with mildly reduced and preserved ejection fraction. These advances have led SGLT2i to become an instrumental component of cardiovascular therapy.

Effectiveness of home-based cardiac telerehabilitation in patients with heart failure: A systematic review and meta-analysis of randomised controlled trials.

To evaluate the effectiveness of home-based cardiac telerehabilitation in patients with heart failure. This systematic review and meta-analysis of randomised controlled trials were designed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two researchers independently screened eligible studies. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias within the included studies. A fixed- or random-effects meta-analysis model was used to determine the mean difference, based on the results of the heterogeneity test. A librarian-designed search of the Cochrane Library, PubMed, Web of Science, EMBASE, CINAHL, CBM, CNKI and Wanfang databases was conducted to identify studies in English or Chinese on randomised controlled trials up to 15 August 2022. A total of 2291 studies were screened. The meta-analysis included data from 16 studies representing 4557 participants. The results indicated that home-based cardiac telerehabilitation could improve heart rate, VO2 peak, 6-minute walk distance, quality of life and reduce readmission rates. No significant differences were observed in the left ventricular ejection fraction percentages between the home-based cardiac telerehabilitation and usual care groups. Compared with centre-based cardiac rehabilitation, home-based cardiac telerehabilitation showed no significant improvement in outcome indicators. Patients with heart failure benefit from home-based cardiac telerehabilitation intervention. With the rapid development of information and communication technology, home-based cardiac telerehabilitation has great potential and may be used as an adjunct or substitute for centre-based cardiac rehabilitation. This systematic review and meta-analysis found that patients with heart failure would benefit from home-based cardiac telerehabilitation intervention in terms of cardiac function, functional capacity, quality-of-life management and readmission rate. Future clinical interventions should consider home-based cardiac telerehabilitation as an alternative to conventional cardiac rehabilitation in patients with heart failure to improve their quality of life. Our paper is a systematic review and meta-analysis, and such details do not apply to our work.

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor Ameliorate Metabolic Disorder and Obesity Induced Cardiomyocyte Injury and Mitochondrial Remodeling.

Sodium-glucose transporter 2 inhibitors (SGLT2is) exert significant cardiovascular and heart failure benefits in type 2 diabetes mellitus (DM) patients and can help reduce cardiac arrhythmia incidence in clinical practice. However, its effect on regulating cardiomyocyte mitochondria remain unclear. To evaluate its effect on myocardial mitochondria, C57BL/6J mice were divided into four groups, including: (1) control, (2) high fat diet (HFD)-induced metabolic disorder and obesity (MDO), (3) MDO with empagliflozin (EMPA) treatment, and (4) MDO with glibenclamide (GLI) treatment. All mice were sacrificed after 16 weeks of feeding and the epicardial fat secretome was collected. H9c2 cells were treated with the different secretomes for 18 h. ROS production, Ca2+ distribution, and associated proteins expression in mitochondria were investigated to reveal the underlying mechanisms of SGLT2is on cardiomyocytes. We found that lipotoxicity, mitochondrial ROS production, mitochondrial Ca2+ overload, and the levels of the associated protein, SOD1, were significantly lower in the EMPA group than in the MDO group, accompanied with increased ATP production in the EMPA-treated group. The expression of mfn2, SIRT1, and SERCA were also found to be lower after EMPA-secretome treatment. EMPA-induced epicardial fat secretome in mice preserved a better cardiomyocyte mitochondrial biogenesis function than the MDO group. In addition to reducing ROS production in mitochondria, it also ameliorated mitochondrial Ca2+ overload caused by MDO-secretome. These findings provide evidence and potential mechanisms for the benefit of SGLT2i in heart failure and arrhythmias.