Abdalla, Hesham

Multimodality imaging plays a pivotal role in ventricular tachycardia (VT) ablation by providing critical insights into arrhythmogenic substrates and guiding procedural strategies. This updated review explores the integration of various imaging techniques, including echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), electroanatomical mapping (EAM), and nuclear imaging, to optimize VT ablation outcomes. Echocardiography, particularly transthoracic echocardiography (TTE), is an essential first-line tool for evaluating structural heart disease and left ventricular function. Moreover, echocardiography aids in risk stratification and procedural planning by detecting regional wall motion abnormalities and thrombus formation. Meanwhile, intracardiac echocardiography (ICE) enhances ablation precision by providing real-time catheter visualization, improving procedural success, and reducing complications such as cardiac tamponade. Nonetheless, CMR is the gold standard for myocardial tissue characterization, enabling the identification of scar burden and conduction channels critical for VT pathogenesis. Late gadolinium enhancement (LGE) facilitates preprocedural planning by localizing arrhythmogenic substrates, predicting VT recurrence risk, and informing ablation strategies. Additionally, T1- and T2-mapping techniques refine the assessment of myocardial fibrosis and inflammation, further improving patient selection and outcomes. MDCT complements CMR by offering high-resolution anatomical visualization and aids in delineating scar distribution, epicardial fat, and vascular structures, informing safe and effective ablation approaches. The integration of these imaging modalities significantly enhances VT ablation precision, reduces recurrence rates, and improves patient outcomes.

Abstract: Cardiovascular disease (CVD) remains the leading cause of death worldwide. While advances in treatment have improved outcomes, the greatest gains in public health will come from primary prevention. Risk stratification is the foundation of CVD prevention. Traditional tools, such as pooled cohort equations (PCEs) and SCORE2, do not capture non-traditional risk factors and individual variability, driving efforts to refine existing approaches. We critically discuss emerging risk determinants for primary CVD prevention. Coronary artery calcium scoring can reclassify CVD risk but has limitations related to cost, access, and unvalidated improvements in clinical endpoints. Biomarkers such as apolipoprotein B and lipoprotein(a) may identify residual risk beyond LDL-C, particularly in patients with lipid discordance, but remain underused due to uncertain thresholds and the lack of prospective triallevel outcome data. Trials of colchicine in primary prevention have yielded mixed results, making the role of targeting inflammation unclear in CVD prevention. Polygenic risk scores can stratify genetic risk but face challenges in sensitivity, specificity, and generalizability. Multiomics approaches, while offering the promise of deeper phenotyping, lack established clinical applications and consensus on when their use is appropriate. Artificial intelligence may allow better prediction across cohorts but requires broader validation. Clonal hematopoiesis of indeterminate potential, a marker of inflammation and age-related CVD risk, lacks evidence supporting routine screening or intervention in younger, asymptomatic individuals. The proliferation of new risk stratification tools poses a key challenge: determining when additional data meaningfully alter clinical decisions. Until robust outcome-based evidence emerges, risk enhancers should guide, but not dictate, therapy in selected patients.

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is a genetic heart disease inherited in an autosomal dominant pattern. Studies have shown that novel first-in-class targeted myosin inhibitor-Mavacamten significantly improves LV diastolic function, systolic anterior motion measures, exercise capacity and left ventricular outflow (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). HCM primarily affects the left side of the heart, making pulmonary hypertension (PH) a common complication. However, the clinical significance and prognostic impact of PH in HCM are not yet fully understood. Purpose This study evaluated the effects of Mavacamten on echo-Doppler-derived pulmonary artery systolic pressure (PASP) in oHCM patients. Methods 70 Adult patients (53% male, mean age 60±12 years) meeting the imaging criteria for oHCM and receiving Mavacamten treatment were identified. Baseline clinical and imaging characteristics were analyzed. The impact of Mavacamten on echo-Doppler-derived PASP was assessed. Clinical and echocardiographic follow-ups were conducted at a median of 12 weeks (IQR: 7–24 weeks) and 74 weeks (IQR: 38–97 weeks) after the baseline echocardiographic assessment. Results The mean PASP of the cohort was 32 ± 10 mmHg, with 39% of patients having PASP >30 mmHg. When stratified by baseline PASP (using a 30-mmHg cut-off ), patients with elevated PASP were older and had more pronounced diastolic dysfunction. At the first follow-up, PASP decreased from 33 ± 10 mmHg to 29 ± 6 mmHg, and at the second follow-up, it further decreased to 27 ± 9 mmHg (p < 0.001). PASP decrease was more pronounced in patients with elevated PASP at baseline (Figures 1, 2). When analyzing changes in echocardiographic parameters over time according to baseline PASP levels, the group with elevated PASP at baseline demonstrated more pronounced changes. While LVOT gradient changed significantly from baseline to both follow-ups in both the elevated and normal PASP groups, certain parameters of diastolic dysfunctions including the E/e' ratio, showed significant changes only in the elevated PASP group (Figure 1). We observed that in univariate regression analysis, age was significantly associated with elevated baseline PASP along with MR and echocardiographic parameters indicative of diastolic dysfunction such as left atrial volume index (LAVI), TR velocity, and E/e. In multivariate analysis TR velocity remained significantly associated with PASP (β=23.05, 95% CI 3.17 to 167.8; p=0.002), highlighting a significant relationship between diastolic dysfunction parameters and PASP. Conclusion This study demonstrates that Mavacamten therapy significantly improves echocardiographic parameters and reduces PASP in patients with oHCM, with particularly pronounced benefits in those with elevated baseline PASP. These findings highlight the potential of Mavacamten as a targeted therapy for addressing both LVOT obstruction and associated PH in oHCM.Changes of echocardiographic parameters PASP over time in oHCM

Background: Cardiac amyloidosis (CA) patients with reduced left ventricular ejection fraction (EF) are at increased risk for mortality. The benefit of cardiac resynchronization therapy (CRT) in terms of mortality reduction has not been established in this population. Aim: To evaluate the survival benefit of CRT, either CRT-D or CRT-P, in a large cohort of patients with cardiac amyloidosis and reduced EF. Methods: We retrospectively analyzed patients with confirmed CA and reduced EF (<40%) between 2009 and 2023 across Mayo Clinic sites. Patients were stratified into three groups: no device, CRT with pacemaker function (CRT-P), and CRT with defibrillator function (CRT-D). CRT devices were indicated for low ejection fraction less than 40% and patients who had chronic heart failure with a wide QRS. Kaplan-Meier survival estimates were generated, and log-rank tests were used for comparison. A secondary analysis was conducted combining CRT-P and CRT-D versus no device (EF <40%), and a tertiary analysis compared CRT-P versus CRT-D. Results: Among 184 patients [36 AL (20%), 148 ATTR (80%)], 38 (19%) had no cardiac device and EF <40%, 20 (11%) received CRT-P, and 116 (63%) received CRT-D. The median follow-up was 3.4 years (1.7, 5.0). The probability of survival was significantly higher in the CRT group compared to the no device-EF<40 group (Log Rank p=0.013; figure B). Among patients receiving CRT, there was no significant difference in all-cause mortality between those receiving CRT-P and those receiving CRT-D (Log Rank p=0.5; figure C). Conclusion: In patients with cardiac amyloidosis and reduced EF, CRT is associated with significantly improved survival compared to no device. No mortality difference was observed between CRT-P and CRT-D. Prospective studies are warranted.

Background: Noncompaction cardiomyopathy (NCCM) is a distinct myocardial disorder associated with a high risk of ventricular arrhythmias and sudden cardiac death. Although implantable cardioverter-defibrillators (ICDs) are frequently used in this population, data on predictors of shock therapy remain limited. Aim: Evaluation of a large cohort of patients with NCCM and ICDs to identify incidence and clinical factors associated with ICD shock Methods: This retrospective cohort study included patients with confirmed NCCM between 2002 and 2023 at all Mayo Clinic sites. Baseline clinical data, genetic findings, cardiac imaging parameters, and device-related outcomes were collected through detailed chart review. Multivariable Logistic regression was used to identify independent predictors. Results: Among 145 patients with NCCM who received ICDs, the median age was 45 years (IQR: 34–56), with 75 (52%) female and 120 (83%) White. The median left ventricular ejection fraction (LVEF) was 35% (IQR: 22.5–47.5%), and the median follow-up from ICD implantation was 6.4 years (IQR: 2.9–11.0). Most ICDs (124, 85.5%) were implanted for primary prevention. Appropriate shocks were observed in 37 patients (25.5%), with 14 (9.8%) experiencing three or more appropriate shocks. Inappropriate shocks occurred in 15 patients (10.3%). Device-related complications were reported in 22 patients (15.2%), including infections in 4 (2.8%), lead fractures or dislodgement in 17 (11.9%), and pneumothorax in 1 (0.7%). Clinical predictors of shocks are illustrated in the figure. Conclusion: ICD therapy for NCCM patients prevented SCD in 25.5% of patients. Syncope, RBBB, troponin T >30 ng/L, and imaging-based apical trabeculations were independently associated with ICD shocks in patients with NCCM. These factors may aid in risk stratification and clinical decision-making.

Aortic stenosis is a progressive condition with substantial implications for morbidity and mortality. In recent years, attention has shifted toward risk stratification and the development of individualized management plans to optimize treatment outcomes. The management of asymptomatic patients has become a topic of significant controversy, as emerging studies challenge traditional watchful waiting guidelines and propose the potential benefits of early intervention. While early intervention may reduce overall morbidity and mortality in this patient population, the associated procedural risks remain a critical consideration. This review seeks to analyze the existing literature, offering an updated perspective on patient risk stratification and evidence evaluating both management approaches.

Background Lipoprotein(a) [Lp(a)] is an independent, causal risk factor for cardiovascular disease. However, it is still unclear whether controlling low-density lipoprotein cholesterol (LDL-C) to optimal levels can attenuate cardiovascular risk mediated by elevated Lp(a), especially in the setting of secondary prevention. Methods Adult patients with a baseline Lp(a) measurement who underwent percutaneous coronary intervention (PCI) and reached their LDL-C target levels (<70 mg/dl) at Mayo Clinic sites between 2006 and 2017 were included. Primary outcomes included major adverse cardiovascular events (MACE) and all-cause mortality. Kaplan–Meier curves were created to compare the survival probabilities among patients with Lp(a) ≥ 50 mg/dl compared with Lp(a) < 50 mg/dl. Multivariable Cox regression analyses were performed to quantify the association of elevated Lp(a) with our relevant outcomes and to control for possible confounders. Results In total, 878 patients (median age: 68 years, and 74% males) who underwent PCI were included for analysis. Of them, 29.7% had elevated Lp(a) ≥ 50 mg/dl. Kaplan–Meier curves did not reveal any significant difference in survival probabilities for elevated Lp(a) for any outcome including MACE (P = 0.91), all-cause mortality (P = 0.26), or the separate MACE components. Similarly, the multivariable analysis showed no significant association for MACE (hazard ratio: 1.07, 95% confidence interval: 0.84–1.37) or all-cause mortality (hazard ratio: 0.98, 95% confidence interval: 0.74–1.30). Conclusion In patients who underwent PCI and have their LDL-C controlled below 70 mg/dl, no significant association was found between elevated Lp(a) ≥ 50 mg/dl and risk for MACE or all-cause mortality.

Background: Secondary prevention after percutaneous coronary interventions (PCIs) is still challenging and lipoprotein(a) [Lp(a)] is believed to be a residual risk factor in this setting. However, the effect of Lp(a) in case of well-controlled low-density lipoprotein cholesterol (LDL-C) is still unclear. The interaction between Lp(a) and LDL-C has been studied in primary prevention but still needs to be investigated in secondary prevention. Hypothesis: Achieving adequate LDL-C control after PCI may reduce the cardiovascular (CV) risk associated with Lp(a). Methods: A retrospective study of consecutive patients who underwent PCI and reached their LDL-C target levels (<70mg/dL) at three academic centers sites between 2006 and 2017. All included patients must have an Lp(a) measurement before the PCI intervention. Clinical outcomes on 10-year follow-up were collected by reviewing the electronic patients' records. The primary outcomes included all-cause mortality (ACM) and major adverse CV events (MACE) including non-fatal MI, ischemic stroke, coronary revascularization, and CV death. Kaplan-Meier curves were created to compare the survival probabilities among patients with high Lp(a) (≥50mg/dL) versus those with low Lp(a) (<50mg/dL). Univariate and multivariate Cox regression analyses were performed to quantify the association of elevated Lp(a) with outcomes and control for potential confounders. Results: In total, 878 patients (median age = 68 years, 74% males) were included in the analysis. Of them, 242 (27.6%) had high Lp(a) ≥50mg/dL. Kaplan Meier analyses did not reveal any significant difference in survival probabilities across the Lp(a) groups for any of the outcomes (Figure 1). The results were consistent in univariate (MACE, HR: 1.08 [95%CIs 0.85-1.35]; ACM, HR: 0.97 [95% CI 0.76-1.23]) and multivariate analyses (MACE, HR: 1.14, [95% CIs 0.90-1.45]; ACM, HR: 1.08 [95% CI 0.84-1.39]). Conclusion: These findings suggest that, in patients who underwent PCI and achieved an LDL-C target of <70 mg/dL, elevated Lp(a) levels were not associated with and increased risk of MACE or mortality. Controlling the LDL-C should still be the cornerstone in secondary prevention after PCI, however, larger prospective studies are still warranted to validate our results.

Lipoprotein (a) is a complex lipid molecule that has sparked immense interest in recent years, after studies demonstrated its significant association with several cardiovascular conditions. Lp(a) promotes cardiovascular disease through its combined proatherogenic, pro-inflammatory, and prothrombotic effects. While the measurement of Lp(a) has become widely available, effective methods to reduce its concentration are currently limited. However, emerging data from ongoing clinical trials involving antisense oligonucleotides have indicated promising outcomes in effectively reducing Lp(a) concentrations. This may serve as a potential therapeutic target in the management and prevention of myocardial infarction, calcific aortic stenosis, and cerebrovascular accidents. In contrast, the role of Lp(a) in atrial fibrillation, in-stent restenosis, cardiac allograft vasculopathy, and bioprosthetic aortic valve degeneration remains unclear. This review article aims to thoroughly review the existing literature and provide an updated overview of the evidence surrounding the association of Lp(a) and these cardiovascular diseases. We seek to highlight controversies in the existing literature and offer directions for future investigations to better understand Lp(a)’s precise role in these conditions, while providing a summary of its unique molecular characteristics.