Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 29 appraisals
Heart (British Cardiac Society)
Impact of diabetes on outcomes in hypertrophic cardiomyopathy: a GRADE meta-analysis
BACKGROUND: Diabetes mellitus (DM) is a common comorbidity in hypertrophic cardiomyopathy (HCM) and may exacerbate arrhythmic risk, promote structural remodelling and worsen heart failure outcomes. Its overall prognostic impact and effect on cardiac structure and function in adults with HCM remain uncertain. METHOD: We systematically searched PubMed, Scopus, Web of Science and Cochrane to January 2025 for observational studies comparing adults with HCM-DM versus HCM without DM. Random-effects meta-analyses were performed to pool ORs for clinical outcomes and standardised mean differences (SMDs) for echocardiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework after Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) evaluation. Subgroup, sensitivity and heterogeneity analyses were undertaken. RESULT: Eight studies encompassing approximately 47 592 patients met inclusion criteria. DM was associated with higher odds of all-cause mortality (OR 1.43, 95% CI 1.29 to 1.58; high certainty), heart failure (OR 1.34, 95% CI 1.25 to 1.43; moderate certainty) and atrial fibrillation (OR 1.41, 95% CI 1.18 to 1.68; high certainty). The association with atrial fibrillation was most pronounced in patients younger than 50 years (OR 2.55) and attenuated in those with body mass index ≥30 kg/m². HCM-DM was also linked to smaller left ventricular end-diastolic volumes (SMD -0.26) and impaired global longitudinal strain (SMD 0.58), consistent with subclinical systolic dysfunction, although heterogeneity was high and certainty low to moderate. Evidence for left ventricular ejection fraction, mass and septal thickness was inconclusive. Results were robust across sensitivity analyses. CONCLUSIONS: DM is a clinically important risk marker in HCM, associated with excess mortality, heart failure and atrial fibrillation, as well as adverse structural-functional changes. These findings support closer rhythm and function monitoring in HCM-DM and highlight the need for prospective studies to determine whether targeted metabolic interventions can improve outcomes. PROSPERO REGISTRATION NUMBER: CRD420250650799.
26 July 2026
Read appraisal →European journal of clinical pharmacology
Impact of carvedilol versus metoprolol on ventricular arrhythmia burden and ICD therapies: a systematic review and meta-analysis
BACKGROUND: Ventricular arrhythmias (VA) are major causes of morbidity and mortality in patients with cardiovascular disease. Implantable cardioverter-defibrillators (ICDs) are commonly used to prevent sudden cardiac death. However, patients with ICDs frequently experience recurrent arrhythmias and inappropriate shocks, which impact quality of life. Beta-blockers, specifically carvedilol and metoprolol, are commonly prescribed in this context. This meta-analysis aims to compare the impact of both medications in this patient population. METHODS: Comprehensive literature search was conducted to identify relevant studies comparing carvedilol to metoprolol in patients with VA or ICDs. Study outcomes included all-cause mortality, recurrent VA, and inappropriate ICD shocks. Effect estimates are presented as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Five independent study populations, reported across six publications, including 7,777 patients (5,138 on carvedilol, 2,639 on metoprolol) were analyzed. Carvedilol was associated with a significantly lower risk of inappropriate ICD shocks (HR = 0.66, 95% CI: 0.48-0.90, P = 0.009) and inappropriate anti-tachycardia pacing (HR = 0.67, 95% CI: 0.49-0.91, P = 0.01) compared with metoprolol. There were no significant differences between the two beta-blockers in recurrent ventricular tachyarrhythmias or all-cause mortality. CONCLUSION: Carvedilol may provide additional benefit over metoprolol in reducing inappropriate ICD therapies and anti-tachycardia pacing, while no significant differences were found in recurrent ventricular arrhythmias or all-cause mortality. These findings support consideration of carvedilol in patients with ICDs, but further research is warranted to guide optimal beta-blocker selection.
15 July 2026
Read appraisal →Journal of the American Heart Association
Diagnostic and Prognostic Utility of Mitral Annular Plane Systolic Excursion: A Systematic Review and Meta-Analysis
BACKGROUND: Movement of the mitral annulus toward the left ventricular (LV) apex during systole, termed atrioventricular plane displacement or mitral annular plane systolic excursion (MAPSE), was first observed by Leonardo da Vinci in the 15th century. MAPSE, a measure of longitudinal movement, shows good agreement between transthoracic echocardiography and cardiovascular magnetic resonance imaging and can also be measured by transesophageal echocardiography and cardiac computed tomography. Measurement is fast, simple, and easily automated. However, no major imaging guidelines advise routine measurement. METHODS: We present a systematic review of studies appraising the diagnostic and prognostic performance of MAPSE from PubMed, Medline, Google Scholar, and Embase until September 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies assessing MAPSE in adult populations were included, and non-English publications, abstracts, and studies of congenital heart disease were excluded. Newcastle-Ottawa Scale assessed study quality. Correlation coefficients between MAPSE and markers of systolic function were pooled using Hunter-Schmidt meta-analysis. Heterogeneous diagnostic and prognostic outcomes were synthesized narratively. RESULTS: The review included 92 studies. MAPSE correlated with LV ejection fraction (r=0.64 [95% CI, 0.54-0.74]) and global longitudinal strain (r=0.53 [95% CI, 0.45-0.63]), showing a modest association with systolic function, particularly useful in patients with poor echocardiographic windows. MAPSE was frequently reduced despite preserved LV ejection fraction across multiple pathologies, enabling earlier detection of systolic impairment. MAPSE also demonstrated strong prognostic value, outperforming LVEF and global longitudinal strain in predicting adverse events in several studies. CONCLUSIONS: Overall, MAPSE has a clinically important role meriting integration into routine cardiac imaging and care.
9 July 2026
Read appraisal →The American journal of cardiology
Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials
Chemotherapy-related cardiac dysfunction (CTRCD) is a major limitation of cardiotoxic cancer therapies. Although global longitudinal strain (GLS) allows early detection of myocardial injury, preventive strategies remain scarce. Angiotensin receptor-neprilysin inhibitors (ARNIs) may offer cardioprotection, but current evidence is limited. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating Sacubitril/Valsartan versus control in patients undergoing chemotherapy. PubMed, Embase, and Cochrane databases were searched. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for binary and continuous outcomes. Four randomized controlled trials comprising 412 participants were included; 42.7% received ARNI therapy, with follow-up ranging from 6 to 18 months. Compared with control, ARNI significantly preserved left ventricular systolic function (MD 1.47%, 95% CI 0.59-2.34) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38). However, ARNI did not significantly reduce the incidence of CTRCD (RR 0.40, 95% CI 0.08-1.97) or all-cause mortality (RR 0.63, 95% CI 0.08-5.01). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. In conclusion, ARNI therapy improves GLS and left ventricular ejection fraction during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.
16 June 2026
Read appraisal →Annals of medicine
Predicting major adverse cardiovascular and cerebrovascular events in chronic heart failure: a machine learning study
BACKGROUND: Heart failure (HF) is a clinical syndrome characterized by impaired cardiac diastolic and systolic function due to structural or functional damage to the myocardium. HF represents the end-stage manifestation of many cardiac diseases. Therefore, early identification of high-risk patients is crucial. This study aims to utilize machine learning (ML) methods to develop and validate a model to predict major adverse cardiovascular and cerebrovascular events (MACCE) in patients with HF and identify its key predictive features. METHODS: This study is a retrospective cohort study. We enrolled a total of 271 patients, who were divided into training and testing sets. Baseline data, including cardiopulmonary exercise testing (CPET) parameters and laboratory tests, were collected for all participants. Based on the presence or absence of MACCE during follow-up, they were categorized into a No-event group and MACCE group. We developed seven ML models to predict the incidence of MACCE in patients with chronic heart failure (CHF) using CPET parameters. The predictive performance of these models was systematically compared, and model interpretability was evaluated using Shapley Additive exPlanations (SHAP). Subsequently, retaining only those with HF with preserved ejection fraction (HFpEF) for a sensitivity analysis. Additionally, a subgroup analysis was conducted between No-event group and Worsening HF (WHF) group. RESULTS: We used Boruta feature selection, four important predictive features were identified. Among the ML models constructed with these features, the Categorical Boosting (CatBoost) model demonstrated the best performance. SHAP analysis was applied to interpret the optimal model, revealing that lower values of heart rate recovery at 1 min (HRR1), as well as a higher carbon dioxide ventilation equivalent slope (VE/VCO2 slope), were associated with higher SHAP values-indicating greater importance in predicting adverse outcomes. CONCLUSION: HRR1 and VE/VCO2 slope can serve as independent predictors for the incidence of MACCE in patients with CHF. Both impaired HRR1 and an elevated VE/VCO2 slope serve as significant independent predictors of MACCE in the CHF population.HRR1 is an independent predictor of WHF in patients with CHF.
14 June 2026
Read appraisal →Medicine
The clinical efficacy of Astragalus-containing Chinese patent medicines in the effective treatment of heart failure: A systematic review and network meta-analysis
BACKGROUND: The incidence of cardiovascular diseases, particularly heart failure, has been rising year by year. Traditional Chinese medicines containing Astragalus have been widely used in clinical research. However, there is no definitive research on the efficacy of proprietary Chinese medicines containing Astragalus. A network meta-analysis was conducted to investigate the efficacy and safety of oral traditional Chinese medicines containing Astragalus for the treatment of heart failure. METHODS: This study searched 6 databases for clinical randomized controlled trials involving the use of traditional Chinese herbal medicines containing Astragalus alone or in combination with other drugs, with a search period from the establishment of the databases to May 27, 2025. Using the Cochrane Quality Assessment Manual, we conducted a bias analysis of the included studies, and the extracted data were analyzed using network meta-analysis in Stata 18. RESULTS: A total of 18 studies were included, involving 1584 patients with heart failure, with 16 types of traditional Chinese medicines containing Astragalus. The network meta-analysis via Surface Under the Cumulative Ranking Curve analysis indicated that: Compared to using Western medicine (WM) alone, Astragalus Granule + WM ranked best for improving overall clinical efficacy rate; Qiangxin Capsule + WM was optimal for improving six-minute walk test; Astragalus Granule + WM showed the best efficacy for reducing B-type natriuretic peptide levels; Yanxing Decoction + WM ranked first for lowering N-terminal pro-B-type natriuretic peptide levels; Xinlishen Compound + WM was the optimal combination for improving left ventricular ejection fraction; Qili Qiangxin Capsule + WM performed best for reducing left ventricular end-diastolic diameter; Yangxin Tongmai II Prescription + WM exhibited the highest efficacy for decreasing Minnesota Heart Failure Quality of Life Questionnaire scores. CONCLUSIONS: Adding oral traditional Chinese medicine containing Astragalus to WM treatment can further improve the clinical efficacy of heart failure. However, due to the limited number and quality of the included studies in this research, the above conclusions still require further validation through well-designed randomized double-blind controlled trials.
31 May 2026
Read appraisal →The New England journal of medicine
Stem-Cell-Derived Biologic Ventricular Assist Tissue in Heart Failure
BACKGROUND: Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction. METHODS: We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS). RESULTS: A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event. CONCLUSIONS: In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).
30 May 2026
Read appraisal →Heart (British Cardiac Society)
Natural history of asymptomatic moderate or severe aortic regurgitation: a systematic review and meta-analysis
BACKGROUND: The natural history of asymptomatic moderate or severe aortic regurgitation (AR) remains uncertain, with conflicting reports about its progression and surgical timing. We aimed to quantify adverse outcomes under conservative management and evaluate the association of aortic valve replacement/repair (AVR) with mortality. METHODS: Systematic searches (inception-July 2025) identified cohort studies of asymptomatic moderate/severe AR. Random-effects models estimated pooled incidence rates of adverse events; fixed-effects models were used for hazard ratios (HRs) of AVR vs conservative management. RESULTS: Twenty-seven studies (4720 patients; mean age 49 years; mean follow-up 3.9 years) were included. Pooled incidence rates per 100 person-years were 1.75 (95% CI 1.27 to 2.41) for all-cause mortality, 1.29 for cardiac death, 0.29 for sudden death, 4.30 for new symptoms and 7.01 for AVR. Asymptomatic low left ventricular ejection fraction occurred in only 0.9 per 100 person-years. Mortality rates were more than double those of the general population across age groups-2.45 (1.90 to 3.18) per 100 person-years for cohorts with mean age ≥50 years versus 0.59 (0.29 to 1.21) for younger cohorts. Early AVR was associated with lower mortality (pooled HR 0.33; 95% CI 0.30 to 0.37). CONCLUSION: Asymptomatic moderate/severe AR carries significant excess mortality irrespective of age, contradicting its historically benign reputation. Given the rarity of asymptomatic LV dysfunction, earlier intervention guided by more sensitive markers of LV damage may improve outcomes, although heterogeneity and study quality warrant cautious interpretation. PROSPERO REGISTRATION NUMBER: CRD42024522683.
27 May 2026
Read appraisal →Circulation journal : official journal of the Japanese Circulation Society
High Human Epididymis Protein 4 Levels Are Associated With Lower Systolic Function and Poor Prognosis in Heart Failure With Reduced Ejection Fraction
BACKGROUND: Human epididymis protein 4 (HE4) is a novel fibrosis marker expressed in activated myofibroblasts. Although we previously demonstrated its prognostic value in dilated cardiomyopathy, its significance in general heart failure with reduced ejection fraction (HFrEF) remains unclear. METHODS AND RESULTS: Serum HE4 concentrations were measured in 140 patients with HFrEF (left ventricular ejection fraction <40%) and followed for up to 3 years to assess cardiovascular (CV) death and heart failure hospitalization. Kaplan-Meier analysis revealed significantly higher CV event rates in the high HE4 group (above the median) than in the low HE4 group (log-rank P<0.001). Multivariate Cox regression analysis identified HE4 (ln[HE4]) as an independent predictor of adverse outcomes (hazard ratio 3.99; 95% confidence interval [CI] 2.05-7.75; P<0.001). In multivariate linear regression, HE4 was significantly associated with age, serum creatinine, plasma B-type natriuretic peptide, E/e', and global longitudinal strain (GLS; β=-0.083; 95% CI -0.111, -0.054; P<0.001). Combining HE4 and GLS demonstrated that patients with high HE4 and low GLS had the highest CV event rate (log-rank P<0.001). CONCLUSIONS: HE4 is an independent prognostic biomarker in HFrEF, and its association with GLS may reflect underlying myocardial dysfunction and fibrotic remodeling leading to adverse outcomes.
26 May 2026
Read appraisal →Open heart
Predictors of high-grade atrioventricular block recovery in Takotsubo cardiomyopathy: a systematic review of case reports
BACKGROUND: Atrioventricular block (AVB) in Takotsubo cardiomyopathy (TCM) is a rarely reported complication. Due to its low incidence and lack of randomised trials, there remain significant gaps in the evidence regarding its underlying mechanisms, the probability of conduction recovery and the optimal timing for permanent pacemaker implantation. METHODS: A systematic review was conducted on published case reports on TCM associated with high-grade AVB, diagnosed simultaneously or within the same hospital admission. Cases with low-grade AVB, sole sinus node disease or TCM induced by pacemaker implantation were excluded. RESULTS: A total of 50 cases were included in the final analysis; stratified into two groups based on AVB recovery. Fifteen patients (30%) developed complete AVB recovery. Compared with persistent AVB, those who experienced recovery were younger (median (IQR): 66 (61-73) vs 77 (65-82), p=0.02), more frequently reported identifiable emotional or physical stressors (93% vs 49%, p=0.004) and demonstrated earlier recovery of left ventricular ejection fraction (LVEF) within 1 week (60% vs 24%, p=0.02). No significant differences were observed in terms of comorbidities (hypertension in 27% vs 47%, p=0.22), presenting symptoms (chest pain in 40% vs 14%, syncope or presyncope in 27% vs 46%, p=0.22), ST elevation (27% vs 14%, p=0.28) or regional wall motion abnormalities (apical akinesia in 47% vs 46%, p=0.93). On multivariate analysis, the presence of an identifiable stressor was an independent predictor of AVB recovery (HR 8.27; 95% CI 1.07 to 63.73, p=0.04). CONCLUSION: In patients with TCM and high-grade AVB, the absence of a clear stressor highlights the possibility of baseline conduction disorder, with a higher risk of persistent AVB. Earlier LVEF recovery and younger age may help to predict AVB recovery and guide patient selection for PPM implantation. PROSPERO REGISTRATION NUMBER: CRD420251173831.
24 May 2026
Read appraisal →The AAPS journal
A Mechanistic Framework Integrating Renal QSP-PK-PD and Machine Learning for Baseline-Informed Stratification of Diuretic Resistance
Diuretic resistance represents a major source of heterogeneity in loop diuretic response and remains a key barrier to effective decongestion in heart failure. A key clinical challenge is the early identification of patients at high risk of an inadequate response to standard-dose furosemide in order to inform timely treatment intensification or alternative decongestive strategies. However, current approaches remain reactive and rely on post-treatment response, limiting prospective risk stratification and treatment decision-making. To address this problem, we integrated a mechanistic renal quantitative systems pharmacology (QSP) model with furosemide pharmacokinetics and pharmacodynamics to enable baseline-informed risk stratification of diuretic resistance. The model was calibrated using published clinical pharmacokinetic and renal response data and applied to generate a physiologically constrained virtual patient population capturing heterogeneity in renal function, tubular sodium handling, and neurohormonal activation. Machine learning methods were incorporated as complementary analytical tools to identify and validate baseline physiological determinants that define risk categories of diuretic response within the mechanistic simulation framework. Model-based analyses indicated that diuretic resistance arises from the combined effects of reduced filtration capacity, enhanced tubular sodium avidity, diminished pharmacodynamic sensitivity and sustained neurohormonal activation. Across analytical approaches, baseline fractional excretion of sodium and glomerular filtration rate emerged as integrative biomarkers that stratify patients into distinct risk categories of diuretic response, reflecting a mechanism-informed reduction of underlying physiological variability. These findings provide a mechanistically grounded framework for baseline-informed risk stratification and may inform earlier identification of patients at risk of inadequate response, supporting model-informed evaluation of treatment intensification or alternative decongestive strategies.
24 May 2026
Read appraisal →European heart journal
Mitral transcatheter edge-to-edge repair and outcomes according to baseline health status: the RESHAPE-HF2 trial
BACKGROUND AND AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) using the MitraClip device improves clinical outcomes in patients with moderate-to-severe ventricular secondary mitral regurgitation (vSMR) and heart failure (HF). This study evaluated whether the effects of M-TEER on clinical outcomes vary by baseline health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), and assessed the impact of M-TEER on health status post-randomization. METHODS: The RESHAPE-HF2 trial included patients with symptomatic HF and moderate-to-severe vSMR (mean effective regurgitant orifice area .25 cm2; 14% >.40 cm2, 23% <.20 cm2). The impact of baseline KCCQ-clinical summary score (CSS) on the effect of M-TEER on clinical outcomes was assessed using Cox proportional hazards models. Changes post-randomization in health status and responder analyses were performed to assess the odds ratio (OR) of improvement and deterioration in KCCQ scores. RESULTS: Among 505 patients, M-TEER reduced cardiovascular death or HF hospitalization risk [hazard ratio (HR): .71 (.48-1.05), .50 (.29-.85), and .73 (.38-1.41)] across KCCQ-CSS tertiles of <38.9, 38.9-66.1, and >66.1, respectively (P-trend = .53). Similar results were seen for total HF hospitalization (P-trend = .48). M-TEER improved KCCQ-CSS, total symptom score, and overall summary score at 1, 6, 12, and 24 months compared to medical therapy alone (P < .05 at all time points). More patients in the M-TEER arm experienced a ≥5-point [OR 3.38 (2.09-5.45)], ≥10-point [OR 3.12 (1.93-5.02)], and ≥15-point [OR 3.25 (1.94-5.45)] improvement, and less patients had a ≥5-point deterioration [OR .34 (.19-.57)] in KCCQ-CSS at 6 months. Similar results were seen across other KCCQ domains and all time points. CONCLUSIONS: In patients with HF and moderate-to-severe vSMR, M-TEER showed a consistent trend towards a lower risk of HF hospitalization, with or without cardiovascular death, across all KCCQ-CSS tertiles and improved health status over time.
19 May 2026
Read appraisal →European heart journal
Wearable devices and cardiovascular health: revolutionizing remote monitoring and disease prevention
Wearable devices are transforming cardiovascular medicine by enabling continuous monitoring of physiologic and behavioural measures outside of traditional clinical settings. Smartwatches and activity trackers, the most widely used wearables, employ motion and biometric sensors to measure physical activity, sleep quality, heart rate, and rhythm. By converting health goals into objective, quantifiable measures, wearable devices empower patients to assume a more active role in their health while providing clinicians with novel opportunities for longitudinal, real-world assessment. Clinical applications span the cardiovascular continuum from lifestyle interventions targeting physical activity and sleep to the remote management of chronic conditions such as heart failure. Widespread clinical adoption of wearables remains limited by challenges, such as variability in device methodology, data outputs, validation, and intended use; incompatibility with existing electronic health records; and the lack of standardized, evidence-based workflows for clinicians to efficiently interpret and act upon wearable data. This review summarizes the current landscape of wearable technologies in cardiovascular medicine by highlighting key clinical applications, evidence gaps in the existing literature, the role of artificial intelligence, and barriers to implementation. We discuss strategies to enhance clinical integration and strengthen the current evidence base while also providing practical guidance to help clinicians navigate commonly encountered clinical scenarios.
16 May 2026
Read appraisal →JACC. Cardiovascular interventions
Durability of Mitral Valve Transcatheter Edge-to-Edge Repair: An Expert Overview
BACKGROUND: Mitral regurgitation (MR) is a globally endemic heart disease burden with significant morbidity and mortality. Mitral transcatheter edge-to-edge repair (M-TEER) has emerged as a minimally invasive treatment with established safety and intermediate-term efficacy. OBJECTIVES: The aim of this study was to determine M-TEER durability and the incidence, risk factors, and treatment strategies of M-TEER failure. METHODS: A comprehensive literature review was performed, identifying 457 records, from which 33 full-text papers were included. Definitions of MR recurrence, reintervention, and M-TEER durability and failure were provided. On the basis of these definitions, weighted means with 95% CIs were calculated for the rates of MR recurrence, reintervention, and their composite for both the overall population and the primary and secondary MR subgroups. RESULTS: The pooled weighted means of MR recurrence and reintervention ranged between 5% and 10% in the first months after the index procedure, remained relatively stable for the first 3 years, and increased at 5 years to 17% and 9%, respectively. MR recurrence and reintervention weighted means were numerically higher in primary than secondary MR, and 41% of primary MR patients experienced MR recurrence or reintervention at 5 years. Redo transcatheter edge-to-edge repair for M-TEER failure seemed safer than surgery but was associated with 1-year MR recurrence rates between 20% and 40%. Mitral valve replacement was the most common surgical technique for M-TEER failure. CONCLUSIONS: The incidence of M-TEER failure after a successful index procedure increases after 3 years and is more pronounced with primary than secondary MR. More systematic, longer term follow-up data after M-TEER are required to better define M-TEER durability.
14 May 2026
Read appraisal →European journal of clinical pharmacology
Comparison of loop diuretics for chronic heart failure: a systematic review and meta-analysis
BACKGROUND: Loop diuretics relieve congestion in chronic heart failure (CHF). We systematically reviewed randomised clinical trials (RCTs) evaluating their effects. METHODS: A systematic search was conducted across major databases. We included RCTs that compared a loop diuretic to another loop diuretic, placebo, or "no intervention". The primary outcome was all-cause mortality, and secondary outcomes were all-cause hospitalisation, serious adverse events (SAEs), and change in body weight (kg). RESULTS: This review included 23 RCTs that enrolled 4,902 patients. Treatment with alternative loop diuretics (torsemide, azosemide and piretanide) compared with furosemide did not reduce all-cause mortality (risk ratio 1.00, 95% CI 0.89, 1.12); I2 = 0%; p = 0.95), nor did it reduce all-cause hospitalisations (risk ratio 0.99, 95% CI 0.84, 1.17); I2 = 53,46%, p = 0.92). In a pooled analysis of alternative loop diuretics (including torsemide and piretanide) the risk of SAEs was higher compared to furosemide (risk ratio 1.32, 95% CI 1.03, 1.68); I2 = 0%), although this finding was based on a limited number of trials with inconsistent definitions and should therefore be interpreted cautiously. The pooled meta-analysis of change in body weight did not show a difference between loop diuretics (mean difference 0.00 kg, 95% CI -1.19, 1.20; I2 = 92.43), indicating substantial heterogeneity. Azosemide resulted in a significant weight loss reduction compared to furosemide (mean difference - 1.00 kg, 95% CI -1.42, -0.58) based on a single small study. CONCLUSIONS: The choice of loop diuretic did not seem to influence the risk of mortality. In a pooled analysis of torsemide and piretanide, the risk of SAEs was higher when compared to furosemide, but the certainty of this finding is limited. Azosemide was associated with weight loss compared to furosemide in one small trial.
14 May 2026
Read appraisal →European journal of heart failure
Surrogate markers of clinical endpoints in clinical trials of heart failure.
AIMS: We aimed to determine whether treatment related changes in surrogate markers predict longer-term therapeutic effects on all-cause mortality and heart failure (HF) hospitalization in randomized trials of HF. METHODS: Systematic literature search included randomized trials of interventions in patients with HF until October 2024. Random-effects meta-regression models with inverse variance weighting were calculated between fifteen surrogate markers and the clinical endpoints of (i) all-cause mortality and (ii) HF hospitalization. The degree of heterogeneity of each model explained by the surrogate marker was determined with R2. Surrogate threshold effects (STEs) were also calculated. RESULTS: Ninety-six randomized trials with median follow-up 12 months were included, enrolling a total of 120 304 patients with HF. Treatment related changes in natriuretic peptides (NPs) were weakly correlated with all-cause mortality (64 comparisons, P = .002, R2 = 12%, and STE = -34%) and HF hospitalization (41 comparisons, P < .001, R2 = 32%, and STE = -30%). Changes in LVEF were moderately correlated with mortality (69 comparisons, P < .001, R2 = 59%, and STE = +6%) and strongly correlated with HF hospitalization (45 comparisons, P < .001, R2 = 90%, and STE = +2%), although this finding was only observed in trials of HFrEF. LV end-diastolic diameter was correlated with HF hospitalization but not mortality. Other echocardiographic markers were not predictive of clinical endpoints. Treatment related changes in patient reported outcomes and exercise capacity were either weakly correlated with clinical outcomes or derived from small clinical trials. CONCLUSION: In HF trials, most surrogate markers, including NPs and echocardiographic measures were only weakly or moderately correlated with treatment effects on all-cause mortality. There is insufficient evidence to support the use of a single biomarker or echocardiographic measure in regulatory trials of HF.
14 May 2026
Read appraisal →The New England journal of medicine
Left Ventricular Unloading in High-Risk Percutaneous Coronary Intervention
BACKGROUND: Complex percutaneous coronary intervention (PCI) in patients with severely impaired left ventricular function carries a high risk of death and complications. Whether percutaneous left ventricular unloading improves outcomes remains unclear. METHODS: We randomly assigned 300 patients with severe left ventricular dysfunction and extensive coronary artery disease in a 1:1 ratio to a strategy of elective unloading with a microaxial flow pump or to standard care during planned complex PCI. The primary outcome was a hierarchical composite that included death from any cause, disabling stroke, spontaneous myocardial infarction, hospitalization for cardiovascular causes, or periprocedural myocardial injury at a minimum of 12 months, as analyzed according to a win ratio. RESULTS: A total of 148 patients were assigned to receive a microaxial flow pump and 152 to receive standard care. At a median of 22 months (interquartile range, 16 to 30), 36.6% of pairwise comparisons favored the microaxial flow pump, and 43.0% favored standard care (win ratio, 0.85; 95% confidence interval [CI], 0.63 to 1.15; difference, -6.4 percentage points; P = 0.30). Death from any cause occurred in 47 patients in the microaxial-flow-pump group and 33 in the standard-care group (hazard ratio, 1.54; 95% CI, 0.99 to 2.41). There was no material between-group difference in the risk of bleeding or vascular complications. CONCLUSIONS: Among patients with severely impaired left ventricular function undergoing complex PCI, elective left ventricular unloading with a microaxial flow pump did not reduce the risk of major adverse clinical outcomes at a minimum of 12 months. (Funded by the U.K. National Institute for Health and Care Research; CHIP-BCIS3 ClinicalTrials.gov number, NCT05003817.).
12 May 2026
Read appraisal →European heart journal
Tricuspid valve replacement outcomes by baseline tricuspid regurgitation severity: the TRISCEND II trial
BACKGROUND AND AIMS: The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS: The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS: One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (-11.6, 11.9), massive/torrential -5.8% (-17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (-3.0, 22.7), massive/torrential -15.2% (-28.9, -1.5)]. CONCLUSIONS: Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.
11 May 2026
Read appraisal →European journal of heart failure
Efficacy of finerenone in patients with heart failure and mildly reduced or preserved ejection fraction: a prespecified analysis of heart rate and heart rhythm in the FINEARTS-HF trial
AIMS: The association between heart rate (HR) and clinical outcomes is well understood in patients with heart failure with reduced ejection fraction (HFrEF) but less clear in those with HFmrEF/HFpEF, especially among individuals with atrial fibrillation (AF). In a prespecified analysis of the FINEARTS-HF trial, we examined the association between baseline HR and clinical outcomes by heart rhythm and evaluated finerenone's effect across the spectrum of HR. METHODS: The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events. Heart rhythm (sinus rhythm or AF) was determined from the baseline ECG. Patients with pacemaker rhythm or missing HR/rhythm data were excluded. RESULTS: Among patients with sinus rhythm (SR n = 3497; 62%), higher baseline HR was associated with a higher incidence rate for the primary outcome. In patients with AF (n = 2190; 38%), no association between HR and outcomes was observed. The effect of finerenone on the primary outcome was consistent across the HR spectrum, regardless of rhythm (P for interaction = 0.96 in SR; 0.49 in AF). In patients with SR, there was no significant HR change with finerenone versus placebo. In AF patients, finerenone led to a small but statistically significant HR reduction: a placebo-corrected decrease of 1.35 bpm (95% CI: 0.41-2.29) from baseline to 12 months. CONCLUSIONS: Among patients with HFpEF/HFmrEF in FINEARTS-HF, higher baseline HR was associated with a higher risk of the primary outcome in patients with SR but not in those with AF. Finerenone's effect on the primary outcome was consistent across the HR spectrum, irrespective of rhythm. TRIAL REGISTRATION: ClinicalTrials.gov NCT04435626.
10 May 2026
Read appraisal →European journal of heart failure
Erythropoiesis-stimulating agents to reduce heart failure hospitalization: a systematic review and meta-analysis
AIMS: Anaemia is common in patients with chronic heart failure (CHF), worsening functional status and prognosis. The role of erythropoiesis-stimulating agents (ESAs) to reduce hospitalization remains unclear. METHODS AND RESULTS: A pre-registered systematic search was performed of randomized controlled trials in adults with CHF and anaemia, comparing any ESA at any dose versus placebo or no treatment.Fourteen trials were included with 3128 participants, with moderate quality of evidence for most outcomes and variable risk of bias. Meta-analysis during 5604 person-years of follow-up demonstrated no significant difference in first CHF hospitalization comparing ESAs with control: Peto odds ratio (OR) 0.93, 95% CI 0.78-1.10, P = .37; trial heterogeneity I2 = 36%. ESAs significantly reduced total CHF hospitalization with 622 events/2698 person-years, compared with 761/2914 person-years for control: incidence rate ratio 0.81, 95% CI 0.73 to 0.90, P < .001; no heterogeneity between trials, I2 = 0%. There were no significant differences between treatment groups for all-cause mortality (OR 1.01, 95% CI 0.86-1.18, P = .88; I2 = 35%) or incident adverse events. Patients randomized to ESAs increased their haemoglobin level [mean difference (MD) 1.6 g/dL compared with control, 95% CI 1.6-1.7, P < .001] and exercise tolerance (MD 69 metres, 95% CI 17-122, P = .009), with lower NYHA class on follow-up (MD -0.73 class, 95% CI -1.11 to -0.36, P < .001). CONCLUSION: ESA treatment in patients with CHF and mild anaemia can reduce recurrent CHF hospitalization and improve functional capacity, without any impact on adverse events. Including ESAs in CHF management could be considered in patients with anaemia at high risk of recurrent hospital admissions.
10 May 2026
Read appraisal →European journal of heart failure
The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST.
AIMS: Qiliqiangxin (QLQX), a Chinese traditional medicine, improved outcomes in patients with heart failure and reduced ejection fraction (HFrEF) when added to guideline-directed therapy. As treatment effects in heart failure (HF) may vary with left ventricular ejection fraction (LVEF), this post hoc analysis of the QUEST (Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality) trial examined whether baseline LVEF modified the efficacy and safety of QLQX. METHODS: QUEST randomized 3110 patients with symptomatic HF and LVEF ≤40%. The primary outcome was cardiovascular death or first HF hospitalization. Baseline LVEF was categorized as ≤25% (n = 482), >25-30% (n = 692), >30-35% (n = 829), and >35% (n = 1107). RESULTS: Mean LVEF was 32% (median 33%, interquartile range 28%-37%). Patients with LVEF ≤25% had the highest rate of the primary outcome (25.4 per 100 patient-years), while rates were similar across higher LVEF groups (18.7-19.8). After multivariable adjustment, lower LVEF was independently associated with higher risks of the primary outcome and mortality. The effect of QLQX on the primary outcome was consistent across LVEF categories (hazard ratio [95% CI] from the lowest to highest: 0.91 [0.64-1.30], 0.65 [0.47-0.89], 0.94 [0.71-1.26], and 0.71 [0.55-0.91], respectively; Pinteraction = .28), and as a continuous variable (Pinteraction = .45). Similar results were observed for individual components and total HF hospitalizations (all Pinteraction > .10). The safety of QLQX was also consistent across LVEF categories. CONCLUSION: In patients with HFrEF, lower LVEF was associated with worse cardiovascular outcomes. QLQX reduced cardiovascular events consistently across the range of LVEF examined in QUEST, despite the limited use of sodium-glucose co-transporter 2 inhibitors. CHICTR REGISTRATION: ChiCTR1900021929.
10 May 2026
Read appraisal →Open heart
Relative apical sparing of left ventricular longitudinal strain for the diagnosis of cardiac amyloidosis: a systematic review and meta-analysis
BACKGROUND: Cardiac amyloidosis (CA) is underdiagnosed due to non-specific clinical and echocardiographic features. This systematic review and meta-analysis evaluated the diagnostic accuracy of the left ventricular relative apical sparing (RELAPS) pattern on speckle-tracking echocardiography. METHODS: A literature search of PubMed, Scopus and Cochrane was conducted through August 2025. RELAPS was defined as the average apical longitudinal strain divided by the sum of average basal and average middle left ventricular longitudinal strains. Diagnostic accuracy was assessed using a bivariate random-effects model. Subgroup analyses by CA subtype and echocardiogram software, and meta-regression for clinical variables, were performed. Optimal cut-offs were determined by maximising the Youden index. Analyses were conducted in R V.4.4.1. RESULTS: Forty-one studies (3473 CA; 4525 comparators) were included. Pooled analysis yielded an area under the receiver operating characteristic curve (AUC-ROC) of 0.818, with sensitivity 65.9% (95% CIs 59.2% to 72.0%) and specificity 83.1% (CI 78.5% to 86.8%). The diagnostic oods ratio (DOR) was 9.54 (CI 7.41 to 12.10). In subtype analyses, immunoglobulin light chains (AL-CA) showed AUC-ROC 0.876, sensitivity 59.8% (CI 41.1% to 76.0%) and specificity 92.7% (CI 83.6% to 96.9%); transthyretin (ATTR-CA) showed AUC-ROC 0.822, sensitivity 63.8% (CI 51.2% to 74.8%) and specificity 84.4% (CI 76.7% to 89.9%), with no significant differences between subtypes (sensitivity p=0.760; specificity p=0.172). Three echocardiography software systems were evaluated. GE EchoPAC (26 studies) achieved an AUC-ROC of 0.822 (sensitivity 70.4% (CI 64.1% to 76.0%), specificity 81.2% (CI 75.7% to 85.7%)). Philips QLAB (four studies) performed comparably (AUC-ROC 0.904; sensitivity 67.6% (CI 31.2% to 90.6%), specificity 92.7% (CI 73.6% to 98.3%)). In contrast, TomTec (four studies) had an AUC-ROC of 0.806, but its sensitivity (31.1% (CI 9.4% to 66.3%)) was significantly lower than GE EchoPAC's (p<0.001), despite a similar specificity (93.6% (CI 78.8% to 98.3%)). CONCLUSION: RELAPS provides moderate diagnostic accuracy for identifying CA, with good specificity and modest sensitivity. Performance varies by analysis software and threshold, underscoring the need for standardised measurement and prespecified cut-offs.
27 Apr 2026
Read appraisal →Journal of the American College of Cardiology
Cardiovascular Science, Medicine, and Society: The Brave New World: The ACC Braunwald Lecture 2025
Recent scientific and technological advances have dramatically expanded the possibilities in cardiovascular medicine. Landmark clinical trials have introduced transformative therapies for lipid disorders, heart failure, and obesity, offering clinicians powerful new tools to manage increasingly complex patient populations. Discoveries in molecular medicine, including gene therapies and RNA therapeutics, have ushered in new biopharmaceutical platforms and promise the potential for curative or infrequent dosing regimens. Minimally invasive, percutaneous, and robotic surgical techniques, along with next-generation devices and interventional procedures, are enhancing patient outcomes and broadening access to advanced care. The rapid rise of artificial intelligence and digital health technologies is reshaping how we gather, interpret, and act on data across the care continuum. Together, these developments mark the arrival of a brave new world in cardiovascular medicine. Yet the promise of this new era is tempered by unequal access, ethical dilemmas, and potential unintended consequences at both the patient and societal levels. This review is written in honor of Dr Eugene Braunwald, who has been a pioneer in cardiovascular science and technological innovation. The paper summarizes recent milestones in cardiovascular medicine and offers a forward-looking perspective on how to realize the full potential of innovation by translating scientific progress into equitable, responsible care and improved health outcomes.
25 Apr 2026
Read appraisal →The American journal of cardiology
Mavacamten and Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Trials
Myosin inhibitors represent a novel therapeutic class for hypertrophic cardiomyopathy (HCM). While both mavacamten and aficamten have been evaluated in randomized trials, comparative evidence across the 2 agents remains limited. We performed a systematic review and meta-analysis of 8 randomized controlled trials of myosin inhibitors in HCM. Outcomes included improvement in the New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), postexercise and resting left ventricular outflow tract (LVOT) gradients, mean rest LVOT peak gradient, mean Valsalva LVOT peak gradient, change in left ventricular ejection fraction (LVEF), peak oxygen uptake, N-terminal pro-B-type natriuretic peptide (NT-proBNP), treatment-emergent adverse events, and serious adverse events. Pooled effects were estimated twice using random-effects models, once stratified by drug and once pooled altogether. Results showed that myosin inhibitors improved clinical and hemodynamic outcomes versus placebo. Both mavacamten and aficamten yielded improvements in New York Heart Association functional class and KCCQ-CSS, while reducing LVOT gradients and proBNP levels. Effect magnitudes were generally larger with mavacamten; aficamten demonstrated concordant but smaller effects and was the only agent to increase peak oxygen uptake. Safety was favorable for both agents, with pooled estimates indicating a marginally more favorable safety profile for aficamten. In conclusion, myosin inhibitors improve functional status, quality of life, and hemodynamics in HCM with an acceptable safety profile. Mavacamten generally demonstrates more robust benefits, while aficamten appears to have a more favorable safety profile. Additional trials directly comparing these agents are warranted to better clarify relative efficacy and safety.
17 Apr 2026
Read appraisal →Heart (British Cardiac Society)
Subphenogroups of acute heart failure with preserved ejection fraction: comprehensive proteomics and pathway analysis
BACKGROUND: Heterogeneity of heart failure with preserved ejection fraction (HFpEF) results in significant challenges for treatment development. Identifying and characterising distinct HFpEF phenogroups may aid in tailoring therapeutic strategies for these patients. The objective of this study was to assess proteomic patterns of HFpEF phenogroups identified through a machine-learning-based clustering model, with the aim of uncovering specific biological pathways associated with each phenogroup. METHODS: This study represents a post-hoc analysis of the ongoing Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a multicentre prospective observational study of hospitalised patients with acute decompensated HFpEF. Of the overall cohort (N=1238), this study analysed 198 patients with HFpEF with available proteomics data. These patients were classified into four phenogroups using the machine-learning-based clustering model. The SomaScan assay V.4.1 was used to measure levels of >7000 plasma proteins, and subsequent pathway analysis was conducted to determine the biological differences among the phenogroups. RESULTS: We identified four distinct phenogroups: Phenogroup 1 ('rhythm trouble'), Phenogroup 2 ('ventricular-arterial uncoupling'), Phenogroup 3 ('low output and systemic congestion') and Phenogroup 4 ('systemic failure'). The proteomics revealed distinct protein expression profiles among the phenogroups, with ribonuclease 4, tax1-binding protein 1, regenerating islet-derived protein 3-gamma and alpha-1-antichymotrypsin being the most significant markers to specific identified phenogroups. Pathway analysis suggested differences in immune response, autonomic activation, cellular homeostasis and tissue repair mechanisms across the phenogroups. CONCLUSIONS: Using a comprehensive plasma proteomics approach, our study identified distinct proteomic profiles of HFpEF phenogroups, which in turn suggest specific underlying biological processes. These profiles suggest the involvement of inflammatory activation, tissue injury and regenerative responses, immune modulation and systemic stress signalling as key components of HFpEF pathophysiology. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.
12 Apr 2026
Read appraisal →Journal of the American Heart Association
Left Atrial Volume Index and Left Ventricular Mass Index Determine the Benefits of Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction
BACKGROUND: It is unclear whether patients with heart failure with preserved ejection fraction respond to spironolactone based on cardiac structure or function. METHODS: A post hoc analysis was performed among participants with left ventricular (LV) ejection fraction ≥50% and evidence of abnormal LV diastolic function or filling pressures in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial). Log-rank tests and Cox regression models were used for comparison between groups. RESULTS: Totally, 757 subjects were qualified and stratified by parameters on cardiac structure or function. In patients with increased left atrial volume index, spironolactone reduced cardiovascular mortality (adjusted hazard ratio [HR], 0.48 [95% CI, 0.24-0.98]; P=0.042, log-rank; interaction P=0.045). Meanwhile, in patients with increased LV mass index, spironolactone decreased heart failure hospitalization (adjusted HR, 0.51 [95% CI, 0.32-0.80]; P=0.009, log-rank; interaction P=0.041) and the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death (adjusted HR, 0.63 [95% CI, 0.43-0.93]; P=0.045, log-rank; interaction P=0.029). Then, in participants with increased left atrial volume index and LV mass index, who matched at 1:1 ration by propensity score matching, spironolactone reduced cardiovascular mortality (adjusted HR, 0.31 [95% CI, 0.11-0.92]; P=0.039, log-rank), heart failure hospitalization (adjusted HR, 0.26 [95% CI, 0.10-0.68]; P=0.005, log-rank), and the composite outcome (adjusted HR, 0.33 [95% CI, 0.15-0.72]; P=0.006, log-rank). CONCLUSIONS: Spironolactone reduced cardiovascular mortality, heart failure hospitalization, or the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death in patients with heart failure with preserved ejection fraction with increased left atrial volume index or LV mass index.
8 Apr 2026
Read appraisal →Journal of ethnopharmacology
Efficacy and safety of Qiliqiangxin capsule as adjunctive therapy in heart failure with reduced ejection fraction: A systematic review and meta-analysis of randomized controlled trials
ETHNOPHARMACOLOGICAL RELEVANCE: The Qiliqiangxin (QLQX) capsule is a prominent traditional Chinese medicine formulation developed based on the collateral disease theory, specifically for the treatment of heart failure (HF). Its composition includes 11 medicinal botanicals, such as Huang Qi, Ren Shen, and Dan Shen, and is designed to tonify qi, activate blood circulation, and promote diuresis. Supported by over 20 years of extensive clinical application, modern pharmacological research, and stringent quality control, QLQX has been incorporated into the national heart failure guidelines in China. AIM OF THE STUDY: This study evaluates the efficacy and safety of QLQX as adjunctive therapy for heart failure with reduced ejection fraction (HFrEF). METHODS: We systematically searched seven databases until February 24, 2025, for randomized controlled trials (RCTs) evaluating QLQX in patients with HFrEF. Two independent researchers screened trials, extracted data, and assessed the risk of bias using the Cochrane RoB 2.0 tool. Meta-analyses were conducted for efficacy and safety outcomes, with evidence quality evaluated through the GRADE framework. RESULTS: Twenty-four RCTs (n = 5580) were included. Compared with conventional treatments (CTs) alone, QLQX adjunctive therapy significantly reduced the risk of cardiovascular death (RR = 0.82, 95 %CI [0.69, 0.96], P = 0.02), hospitalization for HF (RR = 0.78, 95 %CI [0.67, 0.91], P = 0.001), and composite cardiovascular events by 18 % (RR = 0.82, 95 %CI [0.73, 0.92], P = 0.0005), with evidence quality rated as moderate. QLQX significantly improved cardiac function parameters compared to controls: increased left ventricular ejection fraction (MD = 7.14, 95 % CI [6.75, 7.54], P < 0.05), reduced left ventricular end-diastolic diameter (MD = -5.25, 95 % CI [-5.75, -4.75], P < 0.05), improved NYHA class (RR = 1.19, 95 %CI [1.14, 1.25]), decreased NT-proBNP (SMD = -2.01, 95 %CI [-2.26, -1.95], P < 0.05), and increased 6-min walking distance (MD = 44.80, 95 %CI [42.37, 47.22], P < 0.05). CONCLUSION: QLQX adjunct therapy effectively reduces cardiovascular death and HF hospitalization while improving cardiac function in HFrEF, with favorable safety. Large-scale multicenter RCTs with extended follow-up are required to confirm long-term benefits and address existing study limitations.
6 Apr 2026
Read appraisal →Heart rhythm
External validation of an explainable electrocardiogram-only deep learning algorithm for the prediction of response after cardiac resynchronization therapy
BACKGROUND: Cardiac resynchronization therapy (CRT) can improve clinical outcomes in patients with dyssynchronous heart failure, but many patients selected according to the current guidelines do not respond. OBJECTIVE: This study aimed to externally validate an explainable deep learning algorithm (the FactorECG algorithm) for predicting response after biventricular pacing. METHODS: We previously trained a deep learning algorithm on >1 million electrocardiogram (ECG) median beats to learn the underlying generative factors of the ECG and applied it to 1306 patients with CRT from the Netherlands. Using the extracted 21 explainable factors, a model predicting the risk of volumetric nonresponse and poor clinical outcomes was developed. In the present analysis, this model was externally validated in a cohort of 161 patients with CRT from the University of Virginia for volumetric nonresponse only. Subsequently, the added value of clinical and cardiac magnetic resonance imaging-derived predictors was investigated. RESULTS: The original model significantly outperformed American Heart Association criteria for left bundle branch block for the prediction of nonresponse {C-statistic 0.67 (95% confidence interval [CI] 0.59-0.76) vs 0.51 (95% CI 0.41-0.60), respectively}. A refitted FactorECG-based model performed similarly to a model also integrating indices of mechanical dyssynchrony (C-statistic 0.74 [95% CI 0.66-0.82] vs 0.70 [95% CI 0.62-0.77], respectively). A combination of both models improved response prediction (C-statistic 0.79 [95% CI 0.71-0.85]). CONCLUSION: In this external validation study, an explainable ECG-only algorithm for the prediction of nonresponse after CRT device implantation generalized well to a lower-risk population from a different hospital. Adding indices of mechanical dyssynchrony and right ventricular function might be of additional value when evaluating volumetric response.
4 Apr 2026
Read appraisal →Ann Thorac Surg
The Society of Thoracic Surgeons Intermacs 2025 Annual Report: Focus on Outcomes in Older Adults
The 16th Annual Report from the Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) includes 28,029 continuous-flow left ventricular assist devices (CF LVADs) implanted from 2015 to 2024. Survival remains excellent with the fully magnetically levitated CF LVAD (1-year survival: 85.9%, 5-year survival: 60.2%, 7-year survival: 51.8%). Patients also experience a low incidence of adverse events, including freedom from gastrointestinal bleeding (73.5%), device malfunction (81.8%), and stroke (87.1%) at 5 years, reinforcing the effectiveness of contemporary device platforms. However, despite these advancements, national durable LVAD implant volumes have remained stagnant. A focus on the subgroup of patients aged ≥65 years demonstrates excellent outcomes with respect to survival (1-year survival: 80.6%, 5-year survival: 51.1%), quality of life measures, and adverse events. Survival outcomes in this cohort are robust across a wide spectrum of clinical scenarios, including variation in acuity of illness, temporary mechanical circulatory support use, and psychosocial risk factors, historically associated with worse outcomes. Several clinical inferences may be drawn from these data. First, the increasingly elusive clinical equipoise between heart transplant listing vs a strategy of durable LVAD support merits an individualized and value-based approach to therapy in transplant-eligible older adults. Second, the prospect of 5-year survival exceeding 50%-even in septuagenarians-is a call to action to revise patient eligibility criteria, close the implementation gap, and realize the full potential of this life-saving therapy.
1 Jan 2026
Read appraisal →