Kholeif, Zeyad

Abstract Aims Nutritional counselling is a core component of cardiac rehabilitation (CR), yet the evidence base for specific dietary interventions within CR remains fragmented. This scoping review aimed to map the range of nutritional interventions evaluated in adult CR programmes, characterize their reported outcomes, and identify key gaps in current evidence and practice. Methods and results Following the Arksey and O’Malley framework and reporting according to PRISMA-ScR, a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception to June 2026. Eligible studies included randomized controlled trials, non-randomized trials, and observational studies evaluating an explicitly described nutritional intervention within a structured CR programme in adults with established cardiovascular disease. Of 2765 identified records, 35 studies met eligibility criteria. Interventions spanned Mediterranean and heart-healthy dietary patterns, calorie-restriction and weight-loss programmes, comprehensive lifestyle interventions, structured nutrition education and counselling, supplementation, functional foods, and individualized diet prescriptions. Across categories, improvements in body weight, central adiposity, and adherence to cardioprotective dietary recommendations were commonly reported, particularly when nutrition was delivered with repeated contact and individualized support. Effects on lipid profiles, inflammatory markers, blood pressure, functional capacity, and clinical outcomes were more variable. Conclusion Nutritional interventions within CR were most consistently associated with improvements in intermediate behavioural, anthropometric, and cardiometabolic outcomes, particularly when structured and reinforced over time. However, heterogeneity in study design, intervention delivery, comparator groups, outcome reporting, and follow-up duration precludes definitive conclusions about comparative efficacy, optimal intervention format, or the magnitude of benefit. Greater standardization, longer follow-up, and further evaluation of personalized nutritional strategies are needed to strengthen the nutritional component of CR.

ABSTRACT Background In patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), atrioventricular node ablation (AVNA) and permanent pacing are often pursued when rhythm control is not pursued. Biventricular pacing (BiVP) has demonstrated benefits over right ventricular pacing, while conduction system pacing (CSP) has emerged as an alternative. However, evidence directly comparing CSP with BiVP in this high‐risk population remains inconsistent. Objective To compare CSP versus BiVP in patients with AF and HFrEF undergoing AVNA, focusing on cardiac function, clinical outcomes, and procedural metrics. Methods Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through February 2026 for studies comparing CSP and BiVP in adults with AF and HFrEF undergoing AVNA. Outcomes included all‐cause mortality, heart failure hospitalization (HFH), changes in left ventricular ejection fraction (LVEF), QRS duration, New York Heart Association (NYHA) class, pacing threshold, procedure duration, and fluoroscopy duration. A random‐effects model was used to pool mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results Six studies (one randomized crossover trial and five observational studies; N = 766 patients: CSP = 356, BiVP = 410) were included. All‐cause mortality was significantly reduced in favor of CSP (RR 0.64 [CI: 0.44 to 0.94], p = 0.02, I 2 = 0%). There was also a trend towards lower HFH, but it marginally missed statistical significance (RR 0.77 [CI: 0.58 to 1.03], p = 0.08; I 2 = 0%). Additionally, CSP decreased NYHA class (MD ‐0.64 [CI: −1.18 to −0.10], p = 0.02; I 2 = 85%) and significantly reduced QRS duration (MD −33.56 ms [CI: −52.36 to −14.76], p = 0.0005; I 2 = 97%). LVEF improvement did not significantly differ between groups (MD 4.51% [95% CI: −1.50 to 10.52], p = 0.14; I 2 = 98%). Procedure duration and fluoroscopy times did not show statistically significant difference between the two groups (MD −11.54 min [CI: −50.05 to 26.97], p = 0.56, I 2 = 96%), and (MD −5.75 min [CI: −13.13 to 1.63], p = 0.13, I 2 = 88%), respectively. Overall pacing thresholds did not significantly differ between CSP and BiVP; however, modality‐specific subgroup analysis showed comparable thresholds between HBP and BiVP, whereas LBBP was associated with significantly lower pacing thresholds than BiVP. Conclusions Among patients with AF and HFrEF undergoing AVNA, CSP may offer symptomatic and electrocardiographic advantages over BiVP, with a possible signal toward improved major clinical outcomes that requires confirmation in larger randomized studies.

Background The purpose of this study was to assess the clinical benefits of guideline‐directed medical therapy (GDMT) for heart failure (HF) in adults with congenital heart disease and HF with reduced ejection fraction. Methods HF with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%. GDMT score was assessed at baseline encounter (baseline GDMT score) and 1‐year follow‐up. GDMT uptitration was calculated as defined as ∆GDMT score from baseline. Cox regression was used to assess the relationship between HF therapy (baseline and ∆GDMT score) and outcomes (HF hospitalization and mortality). Results Of 778 patients (age 44±16, 480 [62%] males), baseline GDMT score was 2 (1, 3) and ∆GDMT score was 0.62 (95% CI, 0.55–0.69). Of 778, only 258 (33%) had GDMT uptitration (∆GDMT score >0). Higher use of GDMT at baseline (adjusted HR per 1 point increase in GDMT score 0.81, 95% CI, 0.74–0.88, P <0.001), and increased use of GDMT over time (adjusted HR for 1 point increase in ∆GDMT score HR 0.70, 95% CI, 0.61–0.79, P <0.001) were associated with lower risk of HF hospitalization. Higher baseline GDMT score (adjusted HR 0.85, 95% CI, 0.76–0.94, P <0.001), and ∆ GDMT score (adjusted HR 0.82, 95% CI, 0.71–0.94, P <0.000) were also associated with lower mortality. Conclusions GDMT use at baseline and GDMT uptitration were associated with improved outcomes and suggest a dose‐dependent relationship between use of GDMT and risk of adverse outcomes. Furthermore, 67% of patients did not receive GDMT uptitration, suggesting suboptimal therapy, and opportunities for improvement.

ABSTRACT Observational studies comparing Impella and venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in cardiogenic shock have reported inconsistent findings. We performed an updated systematic review and meta‐analysis, with exploratory matched‐cohort analyses where directly reportable propensity score–matched event‐level data were available. We searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception through March 2026 for observational studies comparing Impella versus VA‐ECMO in adult patients with cardiogenic shock. The primary outcome was in‐hospital mortality. Secondary outcomes included all‐cause mortality, ICU outcomes, access site bleeding requiring transfusion, peripheral vascular complications, renal outcomes, and stroke. Random‐effects models using restricted maximum likelihood were applied. Fifteen observational studies including 22,618 patients were analyzed. In the primary crude analysis, Impella was not associated with a statistically significant difference in in‐hospital mortality (RR 0.84, 95% CI 0.66−1.07; p = 0.15) with substantial heterogeneity ( I ² = 92.9%). However, leave‐one‐out analysis identified an influential registry study; its exclusion markedly reduced heterogeneity and favored Impella ( p < 0.01). In exploratory propensity score‐matched analysis, Impella was also associated with lower in‐hospital mortality (RR 0.69, 95% CI 0.56−0.85, p < 0.01). Thirty‐day and 6‐month all‐cause mortality were neutral, whereas 12‐month mortality modestly favored Impella ( p = 0.048). Sensitivity analyses similarly resolved heterogeneity and favored Impella for selected secondary outcomes, including 6‐month mortality, acute kidney injury, and ischemic stroke. ICU mortality was neutral, while ICU length of stay was shorter with Impella ( p = 0.01). Impella was also associated with lower access site bleeding requiring transfusion ( p < 0.01), peripheral vascular complications ( p < 0.01), and hemorrhagic stroke ( p < 0.01). In this updated meta‐analysis of observational studies, the primary crude analysis of in‐hospital mortality was neutral overall but highly heterogeneous, whereas sensitivity and exploratory matched‐cohort analyses showed a more consistent association favoring Impella. Impella was also associated with lower bleeding and vascular complications and shorter ICU length of stay, although several outcomes remained sensitive to study‐level influence. These findings should be interpreted cautiously given the observational design, predominance of serious risk of bias, and strong potential for confounding by indication.

ABSTRACT Background The optimal long‐term antithrombotic strategy after apparently successful catheter ablation of atrial fibrillation (AF) remains uncertain, particularly in patients who meet conventional guideline thresholds for oral anticoagulation (OAC). Objectives To compare continuation versus cessation strategies of long‐term OAC after successful AF ablation and to quantify net clinical benefit (NCB) integrating thromboembolic and bleeding outcomes. Methods We searched PubMed, Cochrane CENTRAL, and Embase from inception through February 2026 for randomized and comparative observational studies evaluating long‐term OAC continuation versus cessation (no OAC and/or switch to aspirin) after successful AF ablation. Risk of bias was assessed using RoB2 for randomized trials and a modified Newcastle–Ottawa Scale (NOS) for observational studies. Random‐effects meta‐analyses used a restricted maximum likelihood estimator with Hartung–Knapp adjustment. NCB was calculated as: thromboembolic event rate − (1.5 × major bleeding rate). Results Six studies met the inclusion criteria (four randomized trials and two observational cohorts). Stroke/transient ischemic attack (TIA) events were reported in six studies and were not significantly different between OAC continuation and cessation strategies (OR 0.69; 95% CI 0.24–1.99; p = 0.49). Systemic embolism (three studies) did not differ between groups ( p = 0.12). Major bleeding (five studies) was numerically higher with continued OAC but not statistically significant (OR 2.07; 95% CI 0.88–4.86; p = 0.09). In NCB analysis, continued OAC yielded more negative or near‐neutral NCB values, whereas, the cessation strategies were less negative or marginally positive; the fixed‐effect risk difference in NCB (continued OAC vs cessation) was +0.00067 (95% CI −0.00279 to +0.00413). Conclusion This meta‐analysis suggests that after successful AF ablation, continuing OAC does not significantly reduce stroke risk compared to cessation or switching to aspirin, but it may increase major bleeding. While NCB trends favor cessation, the low absolute event rates and the risk of silent AF recurrence necessitate caution.

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

Background: We conducted an updated meta-analysis of the routine use of cerebral embolic protection (CEP) devices in Transcathter Aortic Valve Replacement (TAVR). This analysis follows the recent BHF PROTECTED TAVI trial which is the largest randomized controlled trial to date. Methods: Electronic databases were searched through April 2025 for eligible randomized controlled trials (RCTs). The primary outcome was overall incidence of stroke, disabling stroke and non-disabling stroke all reported at 2-5 days and 30 days were primary outcomes for our analyses. Results: 8 RCTs with a total of 11,692 patients were included. No statistically significant difference was found between CEP group and the control group in overall stroke incidence at 2-5 days and 30 days as the following (RR=0.95, 95%CI: [0.75,1.19], p=0.64) and (RR=0.93, 95%CI: [0.57,1.53], p=0.79). Similarly, the pooled analysis revealed no statistically significant difference between the two groups in terms of disabling stroke at 2-5 days (RR=0.70, 95%CI: [0.41,1.18], p=0.18), and at 30 days (RR=1.18, 95%CI: [0.36,3.87], p=0.78). CEP group and control group didn’t show statistically significant difference in non- disabling stroke at 2-5 days and 30 days as the results showed: (RR=1.17, 95%CI: [0.84,1.63], p=0.36) and (RR=0.86, 95%CI: [0.49,1.51], P=0.61) respectively. Conclusion: Our meta-analysis found no statistically significant evidence that cerebral embolic protection (CEP) devices reduce the incidence of stroke—disabling or non-disabling in the 2-5 days following TAVR or after 30 days. Major bleeding, major vascular complication and AKI showed no statistically significant results indicating a neutral safety profile.

Background: Resistant hypertension (RH), defined as uncontrolled blood pressure (BP) despite ≥3 antihypertensive agents at maximally tolerated doses, remains a significant therapeutic challenge. Device-based renal denervation (RDN), using either radiofrequency (RF) or ultrasound (US) ablation, has shown promise in reducing BP. While both methods have demonstrated efficacy versus sham controls in randomized controlled trials (RCTs), direct comparisons remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of RF- and US-based RDN in patients with resistant hypertension. Methods: Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through April 2025 for RCTs comparing RDN versus sham in RH. Eligible trials reported systolic or diastolic BP outcomes via ambulatory, office, or home measurements. Pooled mean differences (MD) and risk ratios (RR) were calculated using a random-effects model. Subgroup analyses were conducted by RDN modality and follow-up duration. Results: Seventeen RCTs met inclusion criteria. RDN significantly reduced ambulatory systolic BP (MD: −3.14 mmHg; 95% CI: −5.30 to −0.98; p=0.004) and diastolic BP (MD: −1.40 mmHg; 95% CI: −2.45 to −0.35; p=0.009) compared to sham. RF-based RDN showed consistent statistically significant reductions in both SBP and DBP across ambulatory and in-office measurements. In contrast, US-based RDN demonstrated variable efficacy, with only daytime DBP showing a marginal benefit (MD: −1.32 mmHg; p=0.04). Safety outcomes, including mortality, acute kidney injury, hypertensive crisis, and hypotension, were similar between groups. Conclusion: RDN offers a significant BP-lowering effect in resistant hypertension, with RF-based RDN yielding more consistent benefits across diverse measurement settings. US-based RDN showed limited but promising effects. Both techniques demonstrated acceptable safety profiles. Further head-to-head trials are needed to confirm long-term comparative effectiveness.

Introduction: Chronic total occlusion (CTO) is commonly encountered in patients with coronary artery disease and is associated with adverse outcomes, including increased short- and long-term mortality. While percutaneous coronary intervention (PCI) has shown potential clinical benefits in CTO patients, its comparative effectiveness against optimal medical therapy (OMT) remains debated. This meta-analysis aims to evaluate the impact of CTO-PCI versus OMT on key cardiovascular outcomes. Methods: We conducted a comprehensive search of Pubmed, Scopus, Web of science and Cochrane. We assessed outcomes including all-cause mortality, cardiac death, myocardial reinfarction, major adverse cardiac events (MACE), stroke, and repeat revascularization. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical significance was defined as p<0.05. Results: 25 studies with a total of 22102 patients were included. Compared to OMT alone, CTO-PCI was associated with a significant reduction in the overall all-cause mortality (RR: 0.66; 95% CI: 0.53–0.82; p=0.0002), cardiovascular mortality (RR: 0.65; 95% CI: 0.52–0.82; p=0.0003) and MACE (RR: 0.84; 95% CI: 0.71–0.98; p=0.03). No statistically significant differences were observed between CTO-PCI and OMT in rates of Stroke (RR: 1.01; 95% CI: 0.68–1.50; p=0.96), Subsequent PCI/CABG (revascularization) (RR: 1.01; 95% CI: 0.78–1.29; p=0.97) or Heart Failure Hospitalization (RR: 0.77; 95% CI: 0.37–1.59; p=0.48) Conclusion: This is the largest and most updated systematic review meta analysis for CTO-PCI vs OMT. Our findings show that CTO-PCI is associated with significantly lower all-cause and cardiovascular mortality compared to OMT. However, no significant differences were observed between the two strategies in the incidence of stroke, need for subsequent revascularization (PCI/CABG), or heart failure hospitalization.