Hafez, Abdelrahman

ABSTRACT Background Left atrial appendage occlusion (LAAO) has emerged as a non‐pharmacological alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). Following the publication of recent CHAMPION‐AF and CLOSURE‐AF trials, an updated synthesis of evidence is warranted to clarify the long‐term comparative efficacy and safety of LAAO versus OAC in patients with AF. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing LAAO with OAC in adults with AF. A comprehensive search of major databases was performed from inception to April 2026. The primary efficacy outcomes were major adverse cardiovascular events (MACE) and stroke. The primary safety outcome was non–procedure‐related bleeding. Random‐effects models were used to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results Six RCTs including 7,004 patients (3,681 LAAO; 3,323 OAC) were analyzed. No statistically significant difference was observed for MACE (7.5% vs 6.9%; RR 1.03, 95% CI 0.79‐1.34) or stroke (3.7% vs 3.2%; RR 1.07, 95% CI 0.80‐1.43). LAAO was associated with a significantly lower risk of non‐procedure‐related bleeding (9.8% vs 16.7%; RR 0.63, 95% CI 0.52‐0.77), corresponding to an absolute risk reduction of 6.9% and an approximate number needed to treat of 15 based on crude pooled event rates over the observed trial follow‐up. Trial sequential analysis indicated that the accumulated evidence for MACE and stroke remained inconclusive. Comparator‐type subgroup analyses showed no significant interaction for MACE ( p = 0.67) or stroke ( p = 0.81) between contemporary predominantly‐DOAC and VKA comparator trials. Conclusions LAAO was associated with lower non‐procedure‐related bleeding, while no statistically significant differences were observed for MACE or stroke. The available efficacy evidence remains inconclusive regarding equivalence or non‐inferiority, and larger trials are needed. These findings support individualized consideration of LAAO when the long‐term bleeding burden of anticoagulation is clinically important.

Background:The development of symptoms or left ventricular dysfunction in severe aortic stenosis (AS) is associated with high morbidity and mortality. While elective transcatheter aortic valve replacement (TAVR) is supported by robust randomized evidence, data on TAVR performed in non-elective settings (urgent, emergent, or salvage) remain limited and heterogeneous. In these settings, outcomes may be influenced more by baseline clinical severity than by procedural factors. This study aimed to systematically evaluate the safety and effectiveness of non-elective TAVR and to compare the associated outcomes with those of elective TAVR.Methods:This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered with PROSPERO. The PubMed, Embase, and Scopus databases were searched for studies published after 2002 evaluating urgent, emergent, or salvage TAVR in adult patients with severe AS. Eligible studies were required to include elective TAVR as a comparator. Outcomes included mortality and major procedural complications. Prespecified era-based analyses and sensitivity analyses excluding studies at critical risk of bias were performed. Risk of bias was assessed using the ROBINS-I tool.Results:A total of 17 observational studies published between 2015 and 2025 were included, comprising 215,141 patients. Compared with elective patients, those undergoing non-elective TAVR had more advanced heart failure, higher NYHA class, greater comorbidity burden, and higher surgical risk scores, whereas baseline echocardiographic severity of AS was similar. Pooled outcomes for non-elective TAVR showed in-hospital, 30-day, and 1-year mortality rates of 5.1%, 12.4%, and 26.7%, respectively. Non-elective TAVR was associated with higher mortality at all time points compared with elective procedures; meanwhile, rates of stroke, vascular complications, and permanent pacemaker implantation were similar, while major bleeding and acute kidney injury were more frequent. Era-based analyses showed a stable relative mortality risk over time.Conclusions:Although non-elective TAVR is associated with worse outcomes than elective procedures, these differences appear to be largely driven by baseline clinical severity rather than by the transcatheter intervention. In unstable patients with severe AS, non-elective TAVR remains the most effective definitive treatment option compared with balloon aortic valvuloplasty or conservative management.The PROSPERO Registration:CRD420251239620, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251239620.

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality. Accurate diagnosis of ischemia-causing coronary stenoses is essential for guiding revascularization and improving outcomes. Although invasive fractional flow reserve (FFR) remains the gold standard for functional lesion assessment, its use is limited by procedural invasiveness, cost, and complexity. CT-derived FFR (FFRct), based on computational fluid dynamics (CFD), was the first major advance in noninvasive physiological assessment, but its adoption has been hindered by intensive off-site computation and dependence on high-quality imaging. This review summarizes the evolution from invasive FFR to AI-driven functional assessment of coronary lesions. We examine the principles and validation of CFD-based FFRct and then focus on the shift toward artificial intelligence, including both machine learning (ML) and deep learning (DL) approaches. These methods range from models using engineered geometric and plaque features trained on large synthetic datasets to end-to-end systems that learn directly from imaging data. We discuss key validation studies evaluating diagnostic accuracy, prognostic value, and clinical utility, with attention to performance in challenging settings such as intermediate stenoses, heavy calcification, and patients with comorbidities. We also highlight major barriers to widespread adoption, including dependence on input data quality, limited explainability, regulatory hurdles, and integration into clinical workflows. Finally, we outline future directions, including AI-enabled virtual PCI planning, multimodal risk stratification, and broader access to functional cardiac assessment. AI has the potential to transform noninvasive coronary imaging by enabling a single CCTA scan to provide rapid, integrated evaluation of anatomy, plaque characteristics, and physiological significance, supporting more personalized care and better clinical outcomes.

Coronary microvascular dysfunction (CMD) has emerged as a crucial contributor to cardiovascular morbidity and mortality, particularly in patients with ischemia and non-obstructive coronary arteries (INOCA). The condition arises from a complex interplay of structural and functional abnormalities within the small coronary vessels, driven by underlying molecular mechanisms including endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and chronic inflammation. Lipid metabolism plays a central role in this pathology, especially in the setting of elevated low-density lipoprotein cholesterol (LDL-C). Furthermore, the protective capacity of high-density lipoprotein (HDL) is increasingly understood to depend on its functionality rather than absolute levels, as it can become dysfunctional and pro-inflammatory in pathological states. Emerging evidence has identified lipoprotein(a) [Lp(a)] and triglyceride-rich lipoproteins as significant, independent contributors to microvascular injury. Comprehensive clinical assessment of microvascular dysfunction therefore requires integration of advanced lipid profiling, including apolipoprotein B (ApoB), [Lp(a)], and the triglyceride-glucose (TyG) index with invasive and non-invasive measures of coronary flow reserve to more precisely stratify risk. In this narrative review, we synthesize current observational, mechanistic, and early interventional data linking diverse lipid phenotypes to coronary microvascular dysfunction. We propose a concept of lipid-driven CMD endotypes, such as ApoB-/particle overload, dysfunctional HDL, Lp(a)-mediated risk, and metabolic/TyG-high states, and map these to a practical, mechanism-informed management framework. While intensive LDL-C lowering with high-intensity statins and combination therapy remains guideline-directed care for high-risk patients, evidence for dedicated microvascular benefit from newer lipid and cardiometabolic agents is still largely hypothesis-generating. A personalized approach that aligns lipid phenotyping, CMD endotyping, and existing guideline-based therapies may help refine risk assessment and inform future trials.

Introduction: Preeclampsia is a multisystem progressive disease of pregnancy, characterized by a new onset of hypertension (≥ 140/90 mm Hg) with proteinuria after the 20th week of gestation. There is a conflict between United States guidelines that recommend Low-dose aspirin (LDA) and United Kingdom guidelines that recommend High-dose aspirin (HDA) for the prevention of preeclampsia in high-risk pregnant women. After the latest study that recommends HDA and the absence of pairwise meta-analyses comparing two doses, we aimed to conduct a comprehensive pairwise meta-analysis to assess whether HDA is better than LDA in the prevention of preeclampsia. Methods: We conducted a systematic search on PubMed, Scopus, Cochrane Central, and Web of Science (WOS) from inception until June 2025. All randomized controlled trials (RCTs) comparing LDA and HDA in high-risk pregnant women were included. Our primary outcome was the incidence of preeclampsia (PE), while secondary outcomes were Placental abruption, Pre-term delivery, and Intrauterine Growth Restriction (IUGR). Using random-effects models, we calculated risk ratios (RR) with 95% confidence intervals (CIs). Results: A total of 8 RCTs with 1,290 patients from the United States, Canada, England, and different Asian countries were included, among whom 642 (49.8%) patients were randomized to HDA. All studies compared HDA (≥ 150 mg) and LDA (75 mg to 81 mg). Patients with LDA had a higher risk of Preeclampsia (RR: 1.71, 95% CI: 1.19 to 2.44, p<0.001) compared to HDA. There was no significant difference between the LDA and HDA regarding Placental abruption, Pre-term delivery, and IUGR. With a pooled RR with a 95% CI (1.8, [0.91 to 3.54], P = 0.09), (1.25, [0.79 to 1.97], P = 0.34), (1.5, [0.93 to 2.42], P = 0.1), respectively. Conclusion: Among high-risk pregnant women, LDA was associated with a 71% higher incidence of preeclampsia than HDA. These results support the use of HDA as a preventive medication for preeclampsia in high-risk pregnant women.

Background: Coronary computed tomography angiography (CCTA) is vital for diagnosing ischemic heart disease, yet its accuracy is affected by varying reader expertise. Artificial Intelligence (AI)-driven automated stenosis assessment offers promise for enhancing diagnostic consistency. Aim: We aim to evaluate an AI-CCTA assessment against invasive coronary angiography, invasive FFR, and expert readings. Methods: We performed a comprehensive search in Web of Science, Scopus, PubMed, Cochrane Library, and EMBASE from inception until March 2025. Two independent reviewers screened articles and extracted data on study design, patient demographics, AI methodology, stenosis thresholds, and outcomes. For statistical analysis, we constructed summary receiver operating characteristic (SROC) curves and used a bivariate random-effects model to derive pooled sensitivity, specificity, diagnostic odds ratios (DOR), and area under the curve (AUC). Forest plots were generated to visualize these metrics. Results: Our meta-analysis included 34 studies with 10,067 patients. AI-based CCTA demonstrated excellent diagnostic performance with an AUC of 0.932 for per-patient analysis. The pooled per-patient sensitivity was 0.89 (95% CI: 0.87–0.91) and specificity was 0.80 (95% CI: 0.74–0.86), with a DOR of 37.07 (95% CI: 24.57–55.92). AI validated against expert readers achieved the highest accuracy (0.94, 95% CI: 0.87-0.98). The >70% stenosis threshold demonstrated superior performance (accuracy: 0.89, specificity: 0.96) compared to the >50% threshold (accuracy: 0.86, specificity: 0.87). Per-vessel analysis showed comparable results with an AUC of 0.905. Conclusion: Our meta-analysis confirms that AI-assisted coronary CT angiography delivers high diagnostic performance for coronary stenosis detection, with strong AUC values, high sensitivity and specificity, and robust diagnostic odds ratios across both per-patient and per-vessel assessments.

Background: Hypertension is a major risk factor for cardiovascular disease, yet nearly 46% of adults with hypertension remain undiagnosed. Without timely intervention, it can lead to severe complications, including stroke, heart failure, and kidney disease. In sub-Saharan Africa (SSA), hypertension prevalence varies widely from 19.3% in Eritrea to 39.6% in Seychelles. Urbanization has played a key role in increasing hypertension rates through its impact on diet, physical activity, and obesity. Still, urban-rural differences remain modest. Understanding demographic and lifestyle predictors is crucial for SSA's targeted prevention and control efforts. Methods: We conducted a cross-sectional analysis using nationally representative, de-identified data from the Demographic and Health Surveys (2016–2024) in five SSA countries: Lesotho, Tanzania, Gabon, Benin, and South Africa. Adults aged ≥18 years with valid blood pressure and covariate data were included (N=38,085). Blood pressure was measured three times, and the average of the second and third readings was used when available. Hypertension was defined per the 2017 ACC/AHA guidelines (SBP ≥130 mmHg or DBP ≥80 mmHg). Independent variables included age, sex, BMI, education, wealth index, smoking status, and recent caffeine intake. Results: Urban residents (n=20,773) had a higher hypertension prevalence than rural residents (n=17,312) (44.8% vs. 36.7%, p<0.001), along with higher median BMI (24.9 vs. 22.3 kg/m 2 ) and obesity rates (23.5% vs. 11.3%). South Africa exhibited the highest rates (urban 68%, rural 61%), while Tanzania and Lesotho had the lowest (~39–40%). In pooled multivariable analysis, hypertension odds increased steadily with age (OR 4.57 for ≥60 vs 18–24, p<0.001). Obesity demonstrated a dose–response relationship: Class III obesity was associated with a fivefold increase in risk (OR 5.38, p<0.001). Men had higher odds than women (OR 1.65, p<0.001). Secondary education and middle wealth status conferred modest increases in risk. Caffeine use was marginally significant; smoking was not. Predictor importance ranked: age > BMI > sex > wealth > education > smoking > caffeine. Conclusion: Hypertension is highly prevalent in both urban and rural SSA, with age and obesity emerging as the most powerful predictors. South Africa stands out with younger adults most affected. Early detection, awareness campaigns, and obesity-focused interventions are needed to mitigate the growing burden of hypertension in SSA.

Background/Objectives: Esaxerenone, a novel non-steroidal mineralocorticoid receptor antagonist, has shown promising results in the treatment of essential hypertension (HTN). This study aims to comprehensively analyze the effectiveness of esaxerenone to control BP in patients with essential HTN. Methods: A systematic search was performed on PubMed, Scopus, Web of Science (WOS), and Cochrane Library from inception until January 2025 for randomized controlled trials (RCTs) comparing esaxerenone with standard HTN usual care. The primary outcome of interest was mean changes in sitting systolic (SBP) and diastolic blood pressure (DBP). Other secondary outcomes were mean changes in 24 h-SBP and 24 h-DBP, and target BP achievement. Safety outcomes, such as adverse events and increased levels of potassium/uric acid, were also assessed. Results: Our meta-analysis included four studies with a total of 1981 patients, all conducted in Japan. Esaxerenone demonstrated dose-dependent blood pressure reductions. At 5 mg, sitting DBP decreased by 4.22 mmHg (95% CI −8.72 to 0.29; p = 0.07) and SBP by 9.07 mmHg (95% CI −17.69 to −0.45; p = 0.04), while the 1.25 mg dose showed smaller, non-significant reductions. For 24 h measurements, only the 5 mg dose achieved significant reductions. Target BP achievement increased by 48% overall (RR 1.48, 95% CI 1.11 to 1.96; p = 0.007), with stronger effects at 5 mg (RR 2.05, 95% CI 1.03 to 4.08; p = 0.04). Esaxerenone significantly reduced nocturnal SBP by 10.62 mmHg (95% CI −14.01 to −7.23; p < 0.001). Conclusions: In patients with essential HTN, esaxerenone was shown to be safe and well-tolerated compared with usual care. Long-term data on safety is warranted.