Rmilah, Anan Abu

ABSTRACT Left bundle branch block (LBBB) is the most common conduction abnormality following transcatheter aortic valve replacement (TAVR) and has been associated with adverse clinical outcomes. While multiple predictors of post‐TAVR LBBB have been proposed, data remain limited. This systematic review and meta‐analysis aims to identify and summarize predictors of new‐onset LBBB post‐TAVR. A systematic literature search was performed to identify studies that reported predictors of new‐onset post‐TAVR LBBB. Extracted data included patient factors, electrocardiographic (ECG) and anatomic parameters, and device‐related factors. A random‐effects model was used to calculate crude risk ratios (RRs), mean differences, and 95% confidence intervals (CI) of the predictors. Of 450 articles screened, 17 studies comprising a total of 6357 patients were included. Among these, 26.4% developed post‐TAVR LBBB. Increased risk was associated with diabetes mellitus (RR: 1.22, p < 0.001), use of 29‐mm valve (RR: 1.59, p < 0.001), and use of Medtronic CoreValve (MCV) (RR: 2.25, p = 0.008). Significant differences were found between patients with and without LBBB in interventricular septal thickness (IVS; by −0.66 mm), membranous septal length (MSL; by −0.9 mm), left ventricular outflow tract (LVOT) diameter (by −0.48 mm), PR interval (by +13.95 ms), and prosthesis implantation depth (by +2.6 mm). Diabetes Mellitus, use of 29‐mm valve or MCV, decreased IVS thickness, shorter MSL, smaller LVOT diameter, increased prosthesis implantation depth, and prolonged PR duration were all associated with an elevated risk of post‐TAVR LBBB. Early identification of these predictors may help reduce the risk of conduction abnormalities after TAVR.

ABSTRACT Background Mitral transcatheter edge‐to‐edge repair (TEER) is approved for patients with severe functional mitral regurgitation (FMR) beyond optimal medical therapy (OMT). Aims We aimed to assess TEER's efficacy beyond OMT in patients with severe FMR. Methods A systematic review and meta‐analysis were conducted, including randomized controlled trials from PubMed, Cochrane, Scopus, and EMBASE up to September 2024. Primary outcome: heart failure hospitalization (HFH); secondary outcomes: cardiovascular (CV) mortality, all‐cause mortality, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Time‐to‐event data from Kaplan−Meier curves were reconstructed for individual patient data. Results Three studies (1423 patients) were included. TEER significantly reduced HFH (RR 0.73, 95% CI 0.58−0.92, p < 0.01) and CV mortality (RR 0.79, 95% CI 0.66−0.95, p = 0.01), and improved KCCQ scores (mean difference 14.32, 95% CI 10.85−17.80, p < 0.01) compared to OMT. No significant difference was found for all‐cause mortality (RR 0.80, 95% CI 0.63−1.02, p = 0.07). Prognostic meta‐analysis showed a 34% reduced risk of HFH (HR 0.66, 95% CI 0.45−0.96, p = 0.03), but no effect on all‐cause or CV mortality. Reconstructed Kaplan−Meier analysis confirmed a 34% reduced risk of HFH (HR 0.65, p < 0.001), with effect attenuation after 15 months in landmark analysis (HR 0.64, p = 0.07). RMST analysis showed a 2.9‐month longer HFH‐free survival with TEER ( p < 0.01). Conclusion In patients with FMR, TEER significantly reduces HFH, improves functional status, and lowers CV mortality at 24 months but does not significantly affect all‐cause mortality. The device group experienced a modest, but significant, 2.9‐month longer HFH‐free survival compared to the control group. However, the reduction in HFH showed attenuation beyond 15 months.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is increasingly recognized as a multisystem disorder with significant cardiovascular implications, particularly in its association with atrial fibrillation (AF). As the most common sustained cardiac arrhythmia, AF contributes to substantial morbidity and mortality, making it essential to explore its links with MASLD. The relationship between these conditions is underpinned by shared pathophysiological mechanisms, including systemic inflammation, insulin resistance, oxidative stress, and activation of the renin-angiotensin-aldosterone system. These processes drive atrial remodeling and electrical instability, predisposing individuals with MASLD to AF. Epidemiological studies further support this connection, showing an independent association between MASLD and an increased risk of AF, particularly in those with metabolic comorbidities such as obesity and type 2 diabetes. Beyond increasing AF susceptibility, MASLD may also influence disease progression and response to treatment, affecting anticoagulation safety, rhythm-control strategies, and the success of catheter ablation. Given these clinical implications, therapies targeting metabolic dysfunction—such as statins, renin-angiotensin-aldosterone system inhibitors, and structured lifestyle modifications—may offer dual benefits in mitigating both MASLD and AF risk. However, significant knowledge gaps remain regarding the causal direction of this association, the impact of MASLD severity on AF burden, and the most effective management strategies for patients with both conditions. Future research should prioritize longitudinal studies, mechanistic investigations, and randomized controlled trials to deepen our understanding of this relationship, ultimately guiding more personalized and integrated treatment approaches. Incorporating MASLD screening into cardiovascular risk assessment may enhance early detection and improve outcomes for at-risk populations.

Hyperuricemia, characterized by elevated serum uric acid levels, has been linked to cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, metabolic syndrome, and coronary artery disease. This relationship, however, is complex; while some studies indicate a strong association, others suggest that it may be influenced by confounding factors. The rising global prevalence of hyperuricemia underscores the necessity for a deeper understanding of its cardiovascular implications. Hyperuricemia results from an imbalance in uric acid production and excretion, driven by dietary factors, obesity, insulin resistance, and other conditions. Elevated uric acid levels contribute to cardiovascular risk through mechanisms such as inflammation, oxidative stress, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system. This review highlights the importance of ongoing research to clarify hyperuricemia’s role in cardiovascular disease and suggests that urate-lowering therapies, such as xanthine oxidase inhibitors, may confer cardiovascular benefits; however, evidence remains conflicting. The Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial indicated an increased risk of cardiovascular and all-cause mortality with febuxostat compared with allopurinol, raising safety concerns. In contrast, the Febuxostat versus Allopurinol Streamlined Trial (FAST) demonstrated that febuxostat was noninferior to allopurinol, with even lower all-cause mortality. These opposing findings emphasize the complexity of treatment decisions and the need for individualized management strategies for hyperuricemia. Clinical decisions should consider individual patient risks and characteristics. Ultimately, this comprehensive analysis aims to enhance prevention and management strategies for cardiovascular diseases related to hyperuricemia. The overview includes discussions on major studies such as the Framingham Heart Study, CARES, FAST, PRIZE, and FREED trials, examining their results. It explores whether hyperuricemia is a causal factor versus an associated risk factor and whether it serves as a marker or mediator of disease. Additionally, the review addresses novel biomarkers and predictive models, the management of hyperuricemia in the context of cardiovascular risk, the role of urate-lowering therapies in cardiovascular disease, variability in guidelines and recommendations, and the impact of hyperuricemia in special populations such as those with diabetes and chronic kidney disease. The cardiovascular risk associated with hyperuricemia across various demographics is also discussed. Furthermore, the review suggests that existing risk scores might be modified to include uric acid levels in patients with hyperuricemia.

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although lipoprotein(a) [Lp(a)] is known to be a well-established risk factor for atherosclerotic cardiovascular disease, its role in the development of AF, independent of this association, remains unclear. Methods and results Adult patients from the three Mayo Clinic sites with a baseline Lp(a) and without AF history were included. Patients were categorized into two groups based on their Lp(a) levels: high Lp(a) (≥50 mg/dL) and low Lp(a) (&lt;50 mg/dL). Survival probabilities free from incident AF were compared between Lp(a) groups, during a follow-up period up to 15 years, using the Kaplan–Meier curve and the log-rank test. Multivariable Cox regression analysis was also conducted. A total of 75 376 patients were included (median age: 55 years, 59% males), with a median follow-up duration of 8.8 (inter-quartile range: 3.4, 14.8) years. Incident AF was detected in 5738 (7.6%) patients. Survival probability free from incident AF was significantly lower in patients with elevated Lp(a) (86%) compared with those with low Lp(a) (88%, log-rank P &lt; 0.001). Multivariable analysis adjusted for potential risk factors of AF showed a statistically significant association of elevated Lp(a) with an 11% increase in AF risk (adjusted hazard ratio: 1.11, 95% confidence interval: 1.05–1.18). Conclusion Our study suggests that elevated Lp(a) (≥50 mg/dL) is an independent risk factor for incident AF. Future prospective studies are warranted to validate our results and to test if reducing Lp(a) could mitigate the burden of AF.

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

Abstract Aims Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. Methods and results A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration [high Lp(a) ≥ 50 mg/dL and low Lp(a) &lt; 50 mg/dL]. Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) vs. those with low Lp(a). A total of 1209 patients were included, with mean age 65.9 ± 11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 [interquartile range (IQR) 7.4] years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR vs. non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, P = 0.008. The rate of ISR was significantly higher among patients with high Lp(a) vs. patients with low Lp(a) values (17.0% vs. 11.6%, P = 0.010). High Lp(a) values were independently associated with ISR events (hazard ratio 1.67, 95% confidence interval 1.18–2.37, P = 0.004), and this association was more prominent after the first year following the PCI. Conclusion Lipoprotein(a) is an independent predictor for long-term ISR and should be considered in the evaluation of patients undergoing PCI.

Introduction: Remote monitoring using implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillator (CRT-D) can be used as an adjunctive diagnostic tool to traditional hospital and clinic visits to monitor the volume status of patients with heart failure (HF). Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through February 4th, 2021) for randomized controlled trials (RCTs) evaluating ICDs/CRT-D remote monitoring versus standard of care in patients with HF. Of 642 articles retrieved after removing duplicate items, we included 11 RCTs encompassing 5,965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods, random effects model and weakly informative prior. Results: The ARD for mortality was centered at -0.01 (95%CrI: -0.03; 0.01, Tau: 0.02), with 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at -0.03 (95%CrI: -0.11; 0.05, Tau: 0.10), with 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for HF admissions was centered at -0.00 (95%CrI: -0.07; 0.06, Tau: 0.08), with 57% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0 [Figure]. Conclusions: This meta-analysis suggests that ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause mortality, and cardiovascular mortality compared with standard care. However, ICD-CRT/D remote monitoring was associated with minimal probability of difference in HF hospitalizations.

Introduction: Patients with a history of inflammatory bowel disease (IBD) are at a higher risk of atrial fibrillation (AF). There is a lack of evidence supporting catheter ablation in this group and predictors of procedural outcomes are unknown. Hypothesis: We assessed the hypothesis that patients with a history of IBD have worse procedural outcomes with more peri-procedural complications, especially in those whose disease is less well controlled. Methods: A single-center 1:1 propensity matched study of patients with no history of IBD and patients with IBD who underwent primary AF catheter ablation from January 2010 to December 2021 was conducted. The primary outcome was procedural efficacy defined by clinical AF recurrence and repeat catheter ablation. The secondary outcome was an assessment of safety looking at eight peri-procedural events. Univariate and multivariate binary logistic regression analysis was conducted to determine predictors of AF recurrence. Results: Our cohort was comprised of 94 patients, 47 patients with a history of IBD (mean age 64.7 ± 6.4 years) and 47 patients with no history of IBD (66.7 ± 7.1 years). Both groups had similar echocardiographic, baseline, and arrhythmia characteristics. All patients underwent pulmonary vein isolation and procedural endpoints were ascertained in all patients. At one-year post-ablation, the study group was statistically more likely to develop AF recurrence (OR 2.38, 95% CI 1.09 - 4.86, p=0.03) but were equally likely to undergo repeat catheter ablation (OR 2.56, 95% CI 0.62 - 10.6, p=0.19). Procedural safety was statistically similar in both groups. Four patients in the study group and three patients in the control group developed subcutaneous hematomas at the site of instrumentation (p=0.70). Multivariate analysis found pre-procedural c-reactive protein (CRP) (OR 1.04, 95% CI 1.00 - 1.12) and AF diagnosis to ablation time (OR 1.15, 95% CI 1.03 - 1.24) were independent predictors of post-procedure AF recurrence. Conclusions: Our study suggests patients with IBD are at a higher risk of developing AF recurrence after catheter ablation. Multivariate analysis showed CRP and AF diagnosis to time to ablation were both independent risk factors.

Introduction: Influenza infection is associated with increased cardiovascular morbidity and mortality. Many observational and clinical trials suggested that influenza vaccine can reduce cardiovascular outcomes. Methods: We searched EMBASE, PubMed, and Cochrane Library (inception through May 24th, 2022) for randomized controlled trials (RCTs) evaluating influenza vaccine and its association with cardiovascular outcomes. We used Mantel-Haenszel method with Paule-Mandel estimator of tau2 and Hartung-Knapp-Sidik-Jonkman adjustment (due to the small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI). Results: Eight RCTs with a total of 14,420 patients were included in our analysis. Influenza vaccine as compared with control/placebo was associated with significantly lower risk of major adverse cardiovascular events (MACE) at follow-up [RR: 0.75; 95%CI: 0.57; 0.97; I2:56%] [Figure]. There was no significant difference between influenza vaccine and placebo/control in terms of all-cause mortality [RR: 0.84; 95%CI: 0.54; 1.33; I2:50%], cardiovascular mortality [RR: 0.77; 95%CI: 0.39; 1.50; I2:57%], or myocardial infarction [RR: 0.75; 95%CI: 0.52; 1.10; I2:0%]. Conclusion: Our meta-analysis suggests that influenza vaccine compared with control/placebo was associated with lower rates of MACE without a significant difference in the mortality or myocardial infarction rates.