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.

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.

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.

Abstract Introduction Coronary artery calcification (CAC) is associated with and identifies patients at higher risk of major adverse cardiovascular events (MACE). However, the prevalence, characteristics, and outcomes of cancer patients with CAC on CT before or after chest radiation therapy (RT) are not well addressed. Methods Retrospective cohort study of all breast cancer patients who underwent chest RT at Mayo Clinic Rochester in 2010. All pre-RT CTs were reviewed and the extent of CAC was recorded in addition to history of pre-RT atherosclerotic risk factors (hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and smoking), history of pre-RT cardiovascular disease (CVD), and RT dosage. MACE (sudden cardiac death (SCD), acute coronary syndrome (ACS), and stroke), and CAC progression in follow-up were recorded. CAC extent was quantified before and on 5-year follow-up CT scan in all patients, and a positive change was considered progression. Patients were divided into 2 groups based on the presence of CAC before RT: present (group 1) or absent (group 2). Results Our cohort was comprised of 244 breast cancer patients who received chest RT. A total of 39 patients (16.9%) had evidence of CAC on CT prior to RT. Compared with patients without CAC before RT (n=205), those with CAC before RT were found to be older (71.8±7.7 vs 58.9±11.3, p&lt;0.01), had higher pre-RT history of HTN (84.6% vs 47.8%); p&lt;0.01), DM (20.5% vs 4.4%; p&lt;0.01), dyslipidemia (74.2% vs 40%; p&lt;0.01), CAD (23.1% vs 3.9%; p&lt;0.01), and stroke (7.69% vs 1.45%; p=0.04). Following RT, patients in group 1 were more likely to exhibit ACS (33.3% vs 2.9%; p&lt;0.01), and stroke (22.6% vs 5.2%; p&lt;0.01). Multinomial logistic regression identified pre-RT CAD pre-RT CAC (β=1.01 (0.33–1.69), OR=7.60 (1.93–29.93); p=0.02) pre-RT CAD (β=0.78 (0.06–1.49), OR=4.74 (1.14–19.74); p=0.03) as independent predictors for the development of MACE after RT. Progression in CAC after RT was found in 61.9% of all patients (13/21) who developed MACE. Conclusion MACE in breast cancer patients undergoing RT can be predicted before RT based on the CV risk factor and disease profile. The strongest predictor for MACE, however, is evidence of CAC before RT. These data provide a unique window for the identification and follow-up of breast cancer RT patients who have a risk of MACE. Funding Acknowledgement Type of funding source: None

AbstractQTc interval prolongation can lead to life‐threatening complications such as Torsade de Pointes (TdP), ventricular tachycardia (VT) and sudden cardiac death (SCD). It can occur with tyrosine kinase inhibitors (TKIs) but comparative real‐world analyses on the incidence and complication rates are scarce. We retrospectively reviewed all cancer patients treated with TKI therapy at Mayo Clinic between January 2005 and December 2018 and had at least two ECGs (before and after TKI). For each TKI type, we determined the administration rate and incidence of QTc prolongation. QTc prolongation was defined as a corrected QT interval (by Fridericia formula) ≥450 ms in men and ≥470 ms in women. A total of 618 cancer patients were included with 902 TKI administrations, of which 654 (72.5%) were accounted for by pazopanib, sunitinib, imatinib, nilotinib and dasatinib. QTc prolongation (any grade) was reported in 28.8%, most commonly with nilotinib (38.7%) and dasatinib (41.7%). A QTc interval ≥500 ms and a QTc increase ≥60 ms was documented in 46 and 63 administrations, respectively. Life‐threatening toxicity was seen in 14 cases (5.4% of QTc prolongation cases) including VT in 9, SCD in 3 and TdP in two administrations. The response to QTc prolongation was: discontinuation in 68%, dose reduction in 13.5%, temporary hold in 8.1% and no action in 10.4%. In conclusion, QTc prolongation with TKI therapy is very common (∼1/3 of cases) and in 5% (1.7% overall) associated with life‐threatening complications. These data support recommendations for careful ECG monitoring in cancer patients undergoing TKI therapy.

Abstract Objective QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥500 ms, the rate of increase of the QTc interval by ≥60 ms, and the development of complications (VT, TdP, and SCD). Results In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib, and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥500 ms was documented in 53 (18.3%) and QTc progression ≥60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Table 1 demonstrates the findings for each TKI. Findings for TKIs in all patients Total Prolonged QTc QTc ≥500 QTc progression ≥60 VT SCD TdP Imatinib 165 54 13 10 2 Nilotinib 75 33 8 19 Dasatinib 115 58 10 16 2 1 Sunitinib 134 31 1 2 1 1 Pazopanib 165 36 5 6 2 1 Others 248 77 16 18 2 1 1 Conclusion The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib, and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. Acknowledgement/Funding None