Citations

Background: Cardiac amyloidosis (CA) in conjunction with atrial fibrillation (AF) presents unique management challenges. CHA2DS2VASc score in these patients is believed to underestimate the risk of ischemic stroke, necessitating a better predictive model in these patients. Methods: Data was obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aOR). AutoScore; an interpretable machine learning framework, was used to develop a stroke risk prediction model, the predictive accuracy of which was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis. Results: A total of 11,860,804 (CA-AF 22,687 [0.19%] and no-CA-AF 11,838,117) patients were identified from 2015-2019. The adjusted odds of mortality (aOR 1.41 and 1.29), stroke (aOR 1.78 and 1.74), non-intracranial hemorrhage (aOR 2.10 and aOR 1.85), and intracranial hemorrhage (aOR 14.4 and aOR 4.26) were significantly higher in CA-AF compared with non-CA-AF at both index admission and 30-days, respectively. The CHA 2 DS 2 VASc score had a poor discriminative accuracy for stroke at 30-days in CA-AF (AUC 49%, 95%CI 47%-51%, p=0.54). The machine learning autoscore integrative model revealed that the predictive ability of our newly proposed E-CHADS score (end-stage renal disease (ESRD), congestive heart failure, hypertension, active cancer, dementia, and diabetes mellitus) for 30-day risk of ischemic stroke in CA-AF was excellent (for a cutoff of 52 points random forest score) with an AUC of 80% (95%CI 74%-86%) Conclusion: Cardiac amyloidosis carries a high risk of ischemic stroke that is not accurately predicted by the CHA 2 DS 2 VASc score. Our proposed model (E-CHADS) identifies 3 new variables (ESRD, dementia, and cancer) that have higher discriminative accuracy for ischemic stroke in these patients.

Introduction: Congenital heart disease (CHD) is the 1st leading cause of deaths among all deaths associated with congenital birth defects in (Organization for Economic Cooperation and Development) OECD countries, constituting a significant health concern that imposes a substantial burden on healthcare systems and society. Methods: Using the Global Burden of Disease methodology, this study assesses the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with CHD in 38 OECD countries by sex, year, and location, covering the period from 1990 to 2019. The results are presented in both all age counts and age standardized rates (ASR) per 100,000 person-years. Results: From 1990 to 2019, the total number of prevalent cases of CHD increased from 1,469,128 (95%UI: 1,292,909-1,671,743) to 1,590,654 (1,387,114-1,815,338). In contrast, CHD-related deaths decreased from 37,291 (31,629-47,869) in 1990 to 13,886 (10,668-16,919) in 2019. The annual percentage of change (APC) in age-standardized mortality (ASMR) decreased by 60%, while the ASIR showed almost no change but decreased by 3%. Notably, the highest APC in ASIR was observed in Czechia (27%), Sweden (21%), Hungary (18%), and the United States (11%), while Turkey (28%) and Canada (21%) had the lowest APC increases. The highest APC increase in ASIR among females was observed in France (29%) Conclusions: Despite a decrease in the burden of CHD over the last three decades, it remains a significant concern in OECD countries. The impact of CHD is felt by individuals, families, healthcare systems, and the economy, emphasizing the ongoing need for comprehensive strategies to address this burden.

Background: Patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) often require vasoactive medications to maintain organ perfusion. However, there are limited data on the real-world use of vasoactive medications in this population. Methods: We used the Vizient® Clinical Data Base to identify patients aged ≥18 years who were admitted between 2015-2019 with AMI-CS and required mechanical ventilation. We report the proportion of patients receiving vasoactive medications by day as well as site-level variability for vasoactive medication strategies using the median odds ratio (MOR), which quantifies the odds that a patient receives a strategy at two randomly selected sites after adjusting for covariates. Results: We identified 10,758 patients from 160 centers admitted with AMI-CS. The median age was 65.8 years, 29.8% were female, 83.6% received vasoactive medications in the first 5 days, and 56.9% received temporary mechanical support. The most used vasoactive medication on day 1 was norepinephrine (48.2%), followed by epinephrine (31.5%), and dopamine (16.9%) ( Figure ). On day 1, 65.9% and 36.2% of patients receiving vasoactive medications were prescribed ≥2 or ≥3 different medications, respectively, including 111 different combinations. Among patients receiving inotropes (N=4,485), there was a nearly 3-fold difference in milrinone use across sites after accounting for differences in patient characteristics (MOR 2.89; 95% confidence interval [CI]: 2.39-3.38). For patients receiving either norepinephrine, dopamine, or epinephrine on day 1 (N=3,224), there was a nearly 2-fold difference in the use of norepinephrine as a first-line vasopressor across sites (MOR 1.84; 95% CI: 1.59-2.06). Conclusion: Norepinephrine is the most commonly used vasoactive medication in patients with AMI-CS. However, there is substantial site-level variability in vasoactive medication strategies, which require further study.

Introduction: The safety and efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) remain unknown in patients with BMI ≥ 40 kg/m 2 . We aim to evaluate the risk of recurrent VTE and major bleeding in patients with a BMI ≥ 40 when started on DOACs versus VKAs. Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism”, “Vitamin K antagonists” and “direct oral anticoagulants”. After the screening, We extracted the data till May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, morbidly obese (BMI ≥ 40 kg/m 2 ), who were on DOACs or VKAs for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. VKAs, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R. Results: Our analysis included a total of 16 studies (n= 62704 patients). Obese patients on DOACs had a significant reduction in the risk of recurrent VTEs compared to VKAs OR 0.72 (95% CI: 0.59 - 0.88, I2 :19%). Also, DOACs were associated with a lower risk of major bleeding compared to VKAs in morbidly obese patients (OR = 0.65, 95% CI: 0.58 - 0.74, I2 :0%). For non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.76, 95% CI: 0.47-1.21). (Figure1) Conclusions: Among morbidly obese patients (BMI ≥ 40), DOACs are associated with a significantly lower risk of recurrent VTEs, and major bleeding compared to VKA. For non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of obese patients in clinical trials is needed to provide us with robust data for informed clinical decision-making.

Introduction: Cardiac rehabilitation (CR) is known to improve peak oxygen uptake (VO 2 peak) and body composition (BC). However, not all CR patients improve VO 2 peak and it remains unclear if non-responders also exhibit limited improvement in BC. This study aimed to examine if non-responders to VO 2 peak also demonstrate limited improvement in BC and whether BC is related to VO 2 peak changes in CR patients. Methods: Retrospective analysis of patients who completed CR between 2015 and 2022 at Mayo Clinic. The study included 143 patients who completed both dual-energy X-ray absorptiometry and cardiopulmonary exercise testing before and after CR. Patients were grouped by VO 2 peak response to CR (36 non-responders=Δ≤0 vs 107 responders=Δ>0 mL/kg/min). Within and between-group differences were assessed by paired and independent t-tests respectively. Regression models were used to evaluate whether baseline BC or ΔBC predict VO 2 peak changes. Results: As an entire cohort there were significant mean improvements in VO 2 peak and BC (Table 1, p<0.05). VO 2 peak increased in 75% of patients (responders: Δ 2.9±2 vs non-responders: Δ -2.1 ±2, mL/kg/min, p<0.05). There were no significant differences in baseline characteristics between groups including BC (Table 2, p>0.05); however, non-responders had significantly shorter duration and exercise sessions compared to responders (Table 2, p<0.001). Non-responders for VO 2 peak exhibited a significant improvement in body fat mass, body lean percentage, body fat percentage, and fat mass index (all p<0.001), with no differences in ΔBC between groups (Table 3). Regression models revealed no significant BC predictors for VO 2 peak. Conclusion: Despite significant improvements in BC, 25% of patients did not improve VO 2 peak with CR. These data suggest VO 2 peak improvement is not related to baseline BC or change in BC. These findings suggest the need for additional strategies to maximize improvements in VO 2 peak for patients undergoing CR.

Introduction: Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (LVEF) on cardiac imaging. Cost-effective alternatives to cardiac imaging are currently not available. Artificial intelligence (AI) models have been developed to detect a reduced LVEF from 12-lead electrocardiograms (ECGs) in the general population. Hypothesis: AI-ECG model can detect a reduced LVEF after anthracycline therapy (i.e. cardiotoxicity). Methods: We included an unbiased oncological population of 989 female breast cancer patients receiving (neo)adjuvant anthracycline chemotherapy. Average follow-up time was 9.83±4.2 years. Patients with incomplete transthoracic echocardiography (TTE) data, HER-2-directed therapy, significant comorbidities, upfront metastatic disease, second primary malignancy or pre-existing cardiovascular disease were excluded from the analyses. Patients with LVEF decline for reasons other than anthracycline-induced cardiotoxicity were also excluded. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for various levels of LVEF <50%. Results: Using 1,877 ECGs from 703 unique patients, the AI-ECG model detected an LVEF <50% and ≤35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively. Conclusions: These data support the use of AI-ECG for cardiomyopathy (cardiotoxicity) screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly testing and could enable patients to monitor themselves over long periods of time.

Introduction: Multiple Valvular Heart Disease (VHD), defined as at least moderate stenotic or regurgitant lesions in ≥2 valves, mixed VHD as combination of lesions in the same valve and mitral annular calcification (MAC) are common conditions. Association between multiple-mixed VHD (MMVHD), MAC and MACE in patients exposed to Radiation Therapy (RT) and/or chemotherapy (CT) who underwent Transcatheter Aortic Valve Replacement (TAVR) has not been studied. Aim: Assess the presence of MMVHD and MAC in cancer patients with prior RT and/or CT and their correlation with MACE (cardiovascular death, myocardial infarction, revascularization, stroke and hospitalization for heart failure) after TAVR. Methods: 544 patients were included and divided into 3 groups: 187 with prior chest RT and CT (RT/CT), 155 CT only, and 202 without CT/RT as controls (Table 1). Data was obtained from the pre-procedure echocardiogram and quantified in a 1-6 scale (none, mild, mild/moderate, moderate, moderate/severe and severe). Fisher’s exact test or chi-square were used to compare categorical. Multiple VHD-MACE correlation was evaluated through multivariable Cox analysis using a proportional hazards model. Results: The prevalence of Multiple VHD was 37.4% in RT/CT, 23.2% in CT, and 13.9% in controls p<0.001(Figure 1). The RT/CT group had a significantly higher prevalence of severe MAC. Multiple VHD predicted MACE at 18 months after TAVR in RT/CT (HR 3.42, CI 1.93-6.08, p<0.001) and in CT (HR 2.55, CI 1.39-4.66, p=0.002) (Table 2). In RT/CT, severe MAC also predicted MACE (HR 3.68, CI 2.13-6.37, p<0.001), while it was not a predictor in the other groups. Stenotic or regurgitant VHD was more prevalent in the RT/CT group (Figure 2). Conclusions: Multiple VHD was found higher in RT/CT and predicted MACE at 18 months post-TAVR, including CT only patients. Severe MAC was also a strong predictor of the outcome in RT/CT patients. Pre-TAVR evaluation of MMVHD lesions is crucial for optimal patient management.

Introduction: Assessing baseline cardiovascular (CV) risk factors is crucial for identifying cancer patients at higher risk of cardiotoxicity (CT). While both CT specific scores, including Heart Failure Association-International Cardio Oncology Society (HFA-ICOS) and our institutional score, as well as general CV scores like Atherosclerotic cardiovascular disease (ASCVD), have been used to assess CT risk; in lymphoma patients undergoing anthracycline therapy, their utility remains unknown. Aim: Evaluate the performance of each risk score to predict CT in a cohort of newly diagnosed lymphoma patients undergoing anthracycline treatment, followed for a median of 5.4 years. Methods: 326 Hodgkin and non-Hodgkin lymphoma patients treated and followed from 2013 to 2021 were prospectively assessed. Baseline measurements of the three risk scores were obtained. ASCVD score was not assessed in patients >80 or <40 years old or without baseline cholesterol. CT was defined during or after one year of chemotherapy as severe, moderate, or mild according to 2022 ESC guidelines. Logistic regression and AUC were used to assess the association of each score and compare the models. Results: Among 326 patients, 78 developed CT (8 severe, 21 moderate, 49 mild). A high-risk score from HFA-ICOS was significantly associated with severe and moderate CT(OR: 6.1, p=0.001), sensitivity 37%, and specificity 88%. A very high-risk classification of the institutional score was associated with severe and moderate CT (OR: 8.4, p=0.006), sensitivity 44%, and specificity 81%. No association was found between the ASCVD score stratification and CT. When mild CT was included in the analysis, the AUC values were lower (see Table 1). Conclusions: Cardio-oncology risk scores were associated with severe and moderate CT, outperforming ASCVD, but their predictive capacity was weak. Incorporating other serum or imaging biomarkers into the models may improve the predictive accuracy of CT risk assessment.

Background: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to prevent atrial fibrillation (AF). However, inconsistent results of MRAs effect on perioperative AF have been reported in the literature in patients undergoing cardiac surgery. To our knowledge, this is the first metanalysis to assess the effect of MRAs on occurrence of perioperative AF in patients undergoing cardiac surgery. Method: We searched different electronic databases from inception to April 30th, 2023, for randomized controlled trials (RCTs) and observational studies that evaluated the use of MRAs in patients with heart failure and left ventricular ejection fraction (LVEF) 30-50% who were referred for Coronary Artery Bypass Grafting (CABG) and/or valve surgery without any AF history. Primary outcome was occurrence of perioperative AF. Three independent reviewers selected and appraised the data. A random-effects meta-analysis was performed to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Result: We included 4 studies, 1 RCT and 3 observational cohorts, with a cumulative number of 1,128 patients with mean age 65.15 years. 412(36.5%) received an MRA (spironolactone or eplerenone). The follow up duration was 5 days to 1 month. During follow-up, 118 (28.64%) patients treated with MRAs, developed AF, compared to 224 (31.28%) patients, without MRA treatment. However, metanalysis showed that there is no significant reduction in occurrence of perioperative AF in MRA treated patients (OR: 0.88 CI: 0.58-1.33 p=0.55), I2 53%; Figure] Conclusion: Experimental data have shown that MRA blockade prevents perioperative AF in animal models but our metanalysis demonstrated that MRAs were not protective for perioperative AF in patients undergoing cardiac surgery. Larger trials in humans are warranted to evaluate its efficacy, particularly in patients undergoing cardiac surgery.

Background: Impaired left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe aortic stenosis (AS). However, its prognostic value in patients with moderate AS is still unknown. The aim of this study is to investigate the impact of LV GLS on outcomes of patients with moderate AS. Methods: PubMed/Medline, Scopus, and Google Scholar databases were systematically reviewed to find relevant studies through June 2023 reporting data on the relationship between the LV GLS and long-term mortality in patients with moderate AS. Binary random effects models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). I2 statistics were used to interpret heterogeneity, with I2>75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p<0.05 was considered statistically significant. Results: A total of 172 studies were reviewed, and 4 studies between 2000-2023 were included in our meta-analysis with a median follow-up of 48.5 months and GLS cut-off varying from 11% to 16%. The pooled univariate analysis revealed a significant association between LV GLS and long-term mortality in patients with moderate AS with a pooled OR of 2.02 (95CI 1.04-3.93) p=0.04, I2=94.25%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.56 (95CI 1.21-2.01) p<0.01, I2=89.48%. Sensitivity analysis, using leave-one-out method, demonstrated robustness and stability of the results with aOR 1.56 (95CI 1.21-2.01) p<0.01. Conclusions: In patients with moderate AS, impaired LV GLS is associated with an increased risk for all-cause mortality. If further randomized studies confirm the prognostic ability of impaired GLS, moderate AS can be redefined, and GLS can be considered in determining the optimal timing for aortic valve intervention.