Alsidawi, Said

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) (<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 < 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.

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.

Introduction: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. In the quest for improved therapeutic strategies, the addition of Sodium Glucose Transporter Inhibitors (SGLTis) to the treatment regimen has garnered considerable attention. This meta-analysis endeavors to shed light on the efficacy of SGLTis in short-term cardio-renal protection post-AMI. By synthesizing evidence from diverse studies. Methods: Adhering to the PRISMA guidelines, a meticulous systematic review and meta-analysis were conducted. Comprehensive literature searches across PubMed, Web of Science, Scopes, and Google Scholar were performed. Inclusion criteria comprised four Randomized Controlled Trials (RCTs), one retrospective cohort, and one observational study, investigating the effects of SGLTis versus placebo on AMI patients, irrespective of diabetic status. Our analysis included the following outcomes: acute kidney injury, all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels. Results: Our analysis encompassed six scientific articles involving 7238 patients. SGLTIs exhibited a notable favorable effect solely on acute kidney injury (P value=0.001, 95% CI [0.46-0.82]). Conversely, no significant benefit was observed in other short-term outcomes, including all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels. These results align with previous studies suggesting the renal protective effects of SGLTIs but highlight the need for further research to clarify their overall cardiovascular benefits in AMI patients. Conclusion: Incorporating SGLTis into the therapeutic armamentarium of AMI patients, irrespective of diabetic status, demonstrated a discernible advantage solely concerning acute kidney injury. However, no appreciable benefit was discerned across other assessed metrics. These findings underscore the need for further exploration and tailored therapeutic strategies in the management of post-AMI patients.

Introduction: Pulmonary hypertension (PHTN) is common in patients with chronic kidney disease (CKD), however categorization as precapillary or postcapillary is challenging due to the need for invasive right heart catheterization (RHC). Studies have validated transthoracic echocardiography (TTE) to characterize PHTN and ECG-artificial intelligence (AI) to predict diastolic dysfunction risk. The utility of these noninvasive tools in patients with CKD is unknown. Methods: Retrospective analysis of patients with end stage CKD who underwent RHC between 2011 and 2021. Patients with PHTN (pulmonary artery pressure >20mmHg on RHC) were categorized as having precapillary (pulmonary capillary wedge pressure, PCWP, ≤15mmHg and pulmonary vascular resistance, PVR, >2WU) or postcapillary PHTN (PCWP >15mmHg and PVR ≤2WU for isolated postcapillary or PVR >2WU for combined). TTE and ECG within 3 months of RHC were obtained. TTE measurements were used to calculate ePLAR (echocardiographic pulmonary to left atrial ratio); tricuspid regurgitant peak velocity (TRV max ) divided by mitral E/e’. ECGs were analyzed with an AI risk tool for diastolic dysfunction (score 0-3, increasing with increasing risk). Receiver operating curves (ROC) evaluated the performance of these tests. Results: 60 patients were included; 16 (27%) with precapillary and 44 (73%) with postcapillary PHTN. ROC analysis found good accuracy for both ECG-AI diastolic dysfunction risk score to predict precapillary PHTN with AUC 0.724 (sensitivity=60% and specificity=88% for an ECG score value ≤1) and ePLAR with AUC 0.715 (sensitivity=75% and specificity=70% for ePLAR >0.17m/sec). Highest accuracy for detection of precapillary PHTN was reached by combination of ePLAR and ECG-AI tool, with AUC 0.756 (sensitivity=73%, accuracy of 86% for a value ≤1.17). Conclusions: ECG-AI generated diastolic risk score of 0-1 (low risk) and high ePLAR showed good accuracy in characterizing precapillary PHTN in patients with end stage CKD. The combination of these noninvasive tools further increased the diagnostic accuracy, reflecting its potential utility in classification of patients with CKD and PHTN, a crucial determinant of the ideal therapeutic plan in kidney transplant candidates.

Background: Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States. Research Questions: This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM. Methods: In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks. Results: Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of <40% and 2% experienced an LVEF of <50%. Conclusions: This is the largest observational study to date demonstrating the effectiveness and safety of mavacamten with substantial sustained reductions in resting and Valsalva LVOTg, and progressive improvements in NYHA class without considerable changes in mean LVEF up to 72 weeks.

Background: New-onset atrial fibrillation (AF) is common among kidney transplant (KTx) recipients and is associated with reduced patient survival. Predictors of AF after KTx are not well understood, although AF can be associated with traditional and non-traditional risk factors. While artificial intelligence-enabled electrocardiography (AI-ECG) has shown promise in predicting incident AF, its predictive and prognostic implications in the KTx population have not yet been evaluated. Hypothesis: AI-ECG can predict new-onset AF and carries prognostic implications in patients undergoing KTx. Aims: To evaluate the clinical implications of applying AI-ECG to the preoperative ECGs of recipients of a KTx. Methods: Patients without a history of AF who underwent KTx at three referral centers between 2011 and 2021, with at least one preoperative ECG, were included in this retrospective study. Preoperative ECGs were analyzed using a previously developed AI-ECG algorithm to estimate the probabilities of new-onset AF. Based on these probabilities, patients were categorized into two groups: high and low probability of incident AF. The optimal cut-off value for the AI-ECG tool was determined using ROC analysis. The incidence of new-onset AF and mortality at 5 years post KTx were compared between these two groups using univariate and multivariate Cox regression analyses. Results: In total, 6246 patients were included (mean age 52.9 ±14.3 years, 58.7% males). A pre-transplant AI-ECG probability of AF >10% was identified as the most accurate cutoff point to distinguish between patients at low risk and high risk of incident AF (ROC = 0.72). The study found that a preoperative AI-ECG high risk of AF demonstrated not only a strong association with new-onset AF (HR 2.54, 95%CI 2.02-3.19, p<0.001 on multivariable analysis, Figure 1A ) but was also associated with an increased risk of mortality both on univariate (HR 2.73, 95%CI 2.34-3.18, p<0.001) and multivariate (HR 1.57, 95%CI 1.29-1.91, p<0.001 ) analysis at 5-year follow-up ( Figure 1B ). Conclusion: The application of AI-ECG to a single widely available test may help assess the risk of new-onset AF and mortality in patients undergoing KTx. Accurate risk stratification may identify a high-risk subgroup of transplant recipients who can benefit from closer AF monitoring, risk factor modification, and early management.

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy. People with HCM are at risk of cardiac arrest. ACC/AHA guideline-supported indications for ICD placement include cardiac arrest or VT, family history of sudden cardiac death in a close relative ≤50, massive septal hypertrophy (MSH - septal thickness ≥30mm), apical pouch, and non-sustained ventricular tachycardia (NSVT). Methods: People attending any Mayo Clinic site on > 1 occasion who underwent ICD placement for HCM who had documented cardiac magnetic resonance (CMR) results were included in the study from time of ICD placement to last device interrogation. Outcome was incidence rate of first appropriate shock. Multivariable cox regression was used to examine the association between septal thickness and shock rate, controlling for current age, sex and secondary vs primary prevention device. An interaction term for association between septal thickness and each ICD indication in turn was incorporated into regression, and stratum specific estimates produced using linear computation. Results: 326 people were included in the study, of whom 50 experienced at least one appropriate ICD shock over 1,487.95 person years (incidence rate 3.36 per 100 person years, NNT 29.76 per year). MSH was strongly associated with shock rate (HR 2.29 [1.19 to 4.40], p=0.013). In people without MSH, there was a 50% reduction in shocks where a subjective measure (syncope or family history of sudden cardiac death) was present (table 1). In this cohort, NSVT resulted in a threefold increase in incidence of shock (HR 3.15 [1.446 to 6.47], p=0.003). In the presence of MSH, there was a four-fold increase in shock rate in people who underwent ICD insertion for family history of sudden cardiac death or for syncope (table 2). There was no difference in shock rates in people with NSVT prior to ICD placement based on septal thickness (HR 0.76 [0.21 to 2.74], p=0.679). There was strong evidence of interaction between NSVT and MSH on shock rates (LR χ2 =6.94, p=0.008), such that presence of both risk factors did not increase shock rate. Concurrent presence of late gadolinium enhancement (LGE) >15% on CMR and MSH was associated with a significant increase in shock rate (3.58 [1.43 to 8.98], p=0.006). Conclusion: MSH is a helpful indicator of who will benefit from ICD placement among people with a pre-existing indication for a device, particularly among those with a more subjective indication for a device.

Abstract Introduction Aortic stenosis (AS) presents diagnostic challenges, especially in patients with discordant low gradient AS (LGAS), i.e., small aortic valve area (AVA) and low Doppler mean gradient (MG). LGAS is associated with worse outcomes compared to concordant AS. Aortic valve calcium score (AVCS) is a measure of AS severity independent of flow and helps diagnose severe AS. It is unknown if the degree of discordance in AVCS and MG is of any clinical significance. A high AVCS/MG ratio may indicate impaired ventricular function and response to pressure overload despite preserved LVEF, potentially contributing to worse outcomes. Purpose This study aims to elucidate the prognostic significance of the AVCS/MG ratio in patients with severe AS and preserved left ventricular ejection fraction (LVEF) undergoing TAVR. We hypothesized a higher AVCS/MG ratio correlates with increased mortality. Methods Patients who underwent transcatheter aortic valve replacement (TAVR) from 2010 to 2020 for native valve severe AS with LVEF≥50% were identified from an institutional database. AVCS were obtained within 90 days of pre-TAVR echocardiography. Patients were divided into tertiles based on their AVCS/MG ratio. Primary outcome was overall mortality. Results The analysis included 1067 patients (mean age 79±9 years, 43% female); overall AVA was 0.80±0.14 cm², LVEF 63±6%, MG 46±12 mmHg, AVCS 2630±1528 AU, and AVCS/MG ratio 58±31. Patients stratified by AVCS/MG tertiles showed no difference in overall comorbidity index across tertiles (Figure 1). However, the group in the highest tertile was the oldest (80±8 vs 79±8 vs 77±9 years), predominantly male (87% vs 61% vs 24%), with the highest prevalent atrial fibrillation (44% vs 28% vs 25%) and stroke volume index &lt;35 mL/m² (16% vs 11% vs 5%). 9-year survival was 15% vs 25% vs 36% (p&lt;0.001, Figure 2). In multivariate analysis adjusted for age, sex, comorbidities, LVEF and AVA, AVCS/MG ratio was independently associated with increased risk of mortality (HR 1.005; 95% CI [1.001-1.008], p=0.005). Conclusion Higher AVCS/MG discordance is associated with increased risk of mortality following TAVR. Serial AVCS measurements during progressive AS may help identify patients at higher risk who may potentially benefit from earlier aortic valve intervention.

Abstract Aims Lipoprotein(a) (Lp(a)) levels are known to be mainly genetically determined. However, only scarce data are available on the intra-individual variability of Lp(a) levels across time. Methods and results We included adult patients (≥18 years old) who had baseline and follow-up Lp(a) measurements (between 1997 and 2024) with a minimum of 1 year apart. Patients were categorized into three groups as follows: normal (&lt;30 mg/dL), borderline (30 to 50 mg/dL), and high Lp(a) (≥50 mg/dL). Multivariable logistic regression was conducted to assess the predictors of the intra-individual changes in Lp(a) ≥ 10 mg/dL. A total of 11 669 individuals (median age: 54 years, 60% males) were included in our analysis, with median time between measurements of 4.5 years [interquartile range (IQR): 2.2, 10.6]. The median Lp(a) was 16 mg/dL (IQR: 7, 52) at baseline, compared with 15 mg/dL (IQR: 7, 52) at follow-up. At follow-up, 96.4% of individuals with normal Lp(a) and 89.9% with high Lp(a) remained in their categories, while 51.2% with borderline Lp(a) changed their category. Of the included population, 24.9% had an intra-individual Lp(a) change ≥ 10 mg/dL. Female sex (P &lt; 0.001), history of ASCVD (P = 0.003), statin therapy (P = 0.003), and elevated LDL cholesterol (LDL-C) levels ≥ 100 mg/dL (P &lt; 0.001) were significantly associated with higher odds of intra-individual Lp(a) changes ≥ 10 mg/dL. Conclusion Lipoprotein(a) levels were generally stable over time; however, patients with borderline levels may require more than one Lp(a) measurement, especially if they are females, have a history of ASCVD, have elevated LDL-C levels, or are on statin therapy.