Citations

Background: Many medications, electrolyte perturbations, and several diseases can prolong the QTc beyond its 99 th percentile value resulting in acquired QT prolongation (AQTP). In contrast, approximately 1 in 2,000 people have congenital long QT syndrome (LQTS) hallmarked by pathological QT prolongation. Recently, we developed an AI-ECG model to distinguish these two groups, however this model does not elucidate which ECG segments distinguish LQTS from AQTP. Methods: Using the cohort from our previous study, all patients with LQTS evaluated in the Mayo Clinic Genetic Heart Rhythm Clinic and controls were included. Next, every patient/control with ≥1 ECG above age- and sex-specific 99 th percentile for QTc was selected and matched at 1:100 ratio. Subsequently, 5 ML algorithms (logistic regression, Naïve Bayes, random forest, Gradient boosting and XGBoost) were trained using 52 features representing segments of the 12-lead ECG (e.g. wave peak times, amplitudes, areas under wave, duration; 52x12 features). Training and testing sets were spilt at 80:20 ratio and 5-fold cross validation was performed to prevent overfitting. Following analysis, the top 100 features were re-analyzed to refine results. Results: Among >1,600 patients with LQTS, 690 had ≥ 1 ECG with a QTc above the established threshold compared to 28,186 controls. Following age- and sex-matching and splitting, 22,410 (training), and 5,776 (testing) ECGs were used. Of the 5 ML algorithms, XGBoost demonstrated best performance (AUC 0.913, accuracy 0.836, sensitivity 0.857, specificity 0.835) to distinguish LQTS from AQTP. Following filtering for the top 100 features, performance of the algorithm remained high with AUC of 0.912 (accuracy 0.84, sensitivity 0.841, specificity 0.84). The features with the greatest impact on classification output included time from T wave onset to T wave peak (leads V1, V4, V4), QRS interval duration (leads V1, V3, V4, aVR), and amplitude at end of ST segment (aVF). Conclusions: Distinguishing monogenetically driven LQTS from multi-factorial AQTP is critical in clinical practice for proper management, mitigation of offending QT-prolonging factors, and treatment. Building on our previously developed AI-ECG-LQTS ‘mutation detector’, this model identifies some of the elements within the ‘black box’ that distinguish an ECG and QTc stemming from a patient with LQTS compared to a similar prolonged QTc value that is arising due to non-genetic, acquired QT-prolonging factors.

Background: Coronary in-stent restenosis (ISR) secondary to neointimal hyperplasia or neoatherosclerosis remains a significant challenge following percutaneous coronary interventions (PCI), with no consensus on the optimal revascularization strategy. We compared the outcome of PCI for ISR using drug-coated balloons (DCB) and drug-eluting stents (DES) and investigated the time trends in their clinical outcomes. Methods: PubMed, Embase, Scopus, and the Cochrane Library databases were searched through May 2024. We included randomized controlled trials (RCTs) comparing DCB versus DES among patients with coronary ISR. The primary outcome was target lesion revascularization (TLR). Secondary outcomes included all-cause mortality, myocardial infarction (MI), stent thrombosis, and late lumen loss (LLL). Random-effects models were employed to analyze outcomes within 1-year and beyond 1-year intervals. Meta-regression analysis was used to investigate the effect of age, sex, history of diabetes, hypertension, dyslipidemia, smoking, and ejection fraction on all outcomes by applying mixed-effect models. Results: We included 10 RCTs (1034 patients in the DCB group and 943 patients in the DES group). We found similar incidence of 1-year TLR (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.86, 2.14; P 0.194; I 2 43.3%) and >1-year TLR (OR 0.94; 95% CI 0.57, 1.56; P 0.817; I 2 0%) with the use of DCB versus DES. The risks of all-cause mortality, MI, and stent thrombosis were comparable between DCB and DES in 1-year and beyond 1-year follow-ups. At 6-9 months angiographic follow-up, DCB was associated with non-significantly lower LLL compared to DES (standardized mean difference [SMD] -0.12 millimeters; 95% CI -0.29, 0.05; P 0.170; I 2 71.7%). Meta-regression indicated that higher prevalence of diabetes was associated with an increased risk of 1-year revascularization after DCB compared to DES (Estimate 0.07; P 0.003; I 2 0%). Additionally, male sex was associated with an increased LLL in DCB versus DES (Estimate 0.034; P 0.001; I 2 41.8%). No association was found between other baseline characteristics and measured clinical outcomes. Conclusion: DCB demonstrated comparable PCI outcomes compared to DES in patients with coronary ISR.

Background: Heart transplantation (HTx) is a life-saving procedure for patients with end-stage heart disease. Sarcoid myocarditis (SM) is a rare condition characterized by granulomatous inflammation of the myocardium. The mainstay of therapy is immunosuppression but the incidence of cardiac sarcoidosis leading to advanced heart failure is increasing. HTx is a valid option in such cases however post-HTx outcomes in sarcoid population have been poorly investigated. Methods: A retrospective analysis of the National Inpatient Sample (NIS) from 2016 to 2021 was conducted. Outcomes compared between sarcoid and non-sarcoid HTx groups were mortality, length of stay (LOS), hospital charges, transplant rejection and graft failure. Mann-Whitney U test was utilized to compare differences between non-parametric variables, while multivariable logistic regression was applied to adjust for confounders. Results: During our study period a total of 17,635 patients underwent HTx out of which 235 (0.013%) had HTx due to sarcoid myocarditis. Multivariable analysis revealed a comparable mortality between sarcoid and non-sarcoid HTx (Adjusted Mortality: aOR 1.35; CI 0.40-4.56; p=0.61). Median length of stay in sarcoid myocarditis group was 29[IQR19-55] vs 28[IQR16-50] p=0.57. Total hospitalization charges were also comparable 956,893[IQR 649,498-1,451,199] vs 800,898[IQR 533,047-1,349,074], p=0.18. There was no significant increase in transplant rejection (aOR 1.43; CI 0.64-3.20; p=0.37) or graft failure (aOR 1.92; CI 0.55- 6.70; p=0.30) in the sarcoid myocarditis group (Table 1, Table 2). Conclusion: Sarcoid myocarditis patients undergoing HTx showed comparable mortality, LOS, total hospital charges, transplant rejection, or graft failure rates to patients undergoing HTx for other causes.While these findings suggest that SM, while rare, does not adversely affect transplant outcomes, we strongly advocate for more studies to adjust for limitations.

Introduction: Calcium scoring computed tomography (CAC) is a widely available and inexpensive modality of screening for atherosclerosis. This study aims to improve the predictive value of CAC by incorporating pericardial fat characteristics in a CatBoost model. Methods: A sample of 7,000 non-contrast clinically indicated CAC scans were randomly selected from a cohort of consecutive Olmsted County MN residents. Known history of atherosclerotic cardiovascular disease or impaired images were excluded. A pericardial fat segmentation model, trained on 191 images of the same dataset with a dice similarity score of 94%, was applied to 6,194 CT scans; Volume and mean Hounsfield unit (mHU) of the output masks were added to age at imaging, radiologist-measured calcium score, male gender, diabetes, and smoking (Figure 1). A 70,20 and 10% split was used to produce the training, validation and test set, respectively. Features were inputted to CatBoost classifier, as the best model tested, to predict four outcomes: acute coronary syndrome (ACS), heart failure (HF), ischemic stroke, and all-cause mortality. Model was evaluated by area under the ROC curve (AUC) on the unseen test set. Results: Mean age was 55.2 (8.8), 55.2 (8.8) and 54.8 (8.5) years in the training, validation and test sets, respectively, and 65%, 67% and 66% of the populations were male. The mean AUC, obtained through bootstrapping with 100 iterations, was 0.81 [0.77-0.85], 0.86 [0.60-0.92], 0.80 [0.73-0.87] and 0.87 [0.81-0.91] for HF, ACS, stroke and death, respectively; The same analysis excluding pericardial fat measurements showed a 3% reduction in the AUC for all of the investigated outcomes (Figure 2). Conclusion: Our study presents a robust risk prediction model for ACS, HF, stroke, and mortality based on CAC scans. The improved performance of the model by incorporating pericardial fat characteristics, highlights the potentials of deep learning in timely inexpensive risk prediction in large populations.

Background: Invasive management strategies for myocardial infarction (MI) and multivessel coronary artery disease (MV-CAD) include complete revascularization (successful revascularization of all coronary artery lesions or segments ≥1.5 mm in diameter with ≥50% diameter stenosis) and incomplete revascularization (including culprit-only revascularization). However, non-culprit lesion management strategy in elderly patients remains ambiguous due to a lack of representation of this cohort in randomized trials (RCTs) and higher cardiovascular complication risks. Methods: We performed a meta-analysis comparing clinical outcomes of elderly individuals (age ≥65 years) with MI and MV-CAD submitted to complete vs. incomplete (including culprit-only) percutaneous coronary intervention (PCI). The outcomes of interest were all-cause death, cardiovascular mortality, recurrent MI, and any revascularization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: Thirteen studies (3 RCTs, 1 post hoc analysis of previous RCT, and 9 observational studies) with a total of 12,289 patients were included. Complete revascularization (CR) was performed in 5,232 patients, while 7,057 patients underwent incomplete revascularization (IR). The mean age was 80.46 years for CR and 80.73 years for IR and the mean durations of follow-ups ranged from 12-78 months. As compared to IR, the CR group was associated with significantly lower risk of all-cause mortality (OR 0.59, 95% CI 0.49 to 0.71, p<0.0001) (Figure 1), cardiovascular mortality (OR 0.56, 95% CI 0.40 to 0.77, p=0.0005), recurrent MI (OR 0.62, 95% CI .47 to 0.81, p=0.0005) (Figure 2), and any revascularization (OR 0.47, 95% CI 0.26 to 0.86, p=0.01). Conclusion: Among elderly patients with MI and MV-CAD, CR is associated with a lower risk of all-cause mortality, cardiovascular mortality, recurrent MI, and any revascularization.

Background: Ambiguity surrounds invasive management of non-ST-segment elevation myocardial infarction (NSTE-MI) in older adults (≥70 years), and the number of elderly patients undergoing invasive treatment in clinical practice remains relatively low. Data comparing the efficacy of invasive versus conservative medical management for NSTEMI in this population is conflicting due to the under-representation or exclusion of the older population from randomized controlled trials (RCTs). Methods: We performed a meta-analysis of RCTs to evaluate the long-term outcomes of invasive versus conservative medical strategies in older patients with NSTEMI. Random effects meta-analysis was conducted to estimate the odds ratio (OR) with 95% CI for the individual endpoints of all-cause mortality, cardiovascular (CV) mortality, recurrent myocardial infarction (MI), unplanned revascularization, and readmission for cardiovascular causes. Results: A total of nine RCTs with 4,336 patients (Invasive: 2,368; Control: 1,968) with median follow-ups ranging from 6-63.6 months were included. Compared with a conservative strategy, an invasive strategy was associated with a significantly decreased risk of recurrent MI (OR 0.62, 95% CI 0.47-0.81; p<0.001) (Figure 1) and unplanned revascularization (OR 0.38, 95% CI 0.25-0.56; p<0.001). There was no difference in all-cause mortality (OR 0.81, 95% CI 0.39-1.35; p=0.42) (Figure 2), CV mortality (OR 0.72, 95% CI 0.43-1.23; p=0.23), or readmission for cardiovascular causes (OR 1.21, 95% CI 0.63-2.33; p=0.57) between invasive and conservative management strategies. Conclusion: In older patients ≥70 years old with NSTE-MI, an invasive strategy reduced the risk of recurrent MI and revascularization when compared with conservative management. However invasive strategy did not offer any benefit in mortality or cardiac-cause related readmission over conservative management.

Background: Autologous arteriovenous fistulas (AVF) are the preferred choice for hemodialysis access due to their longevity, lower complication rates, and mortality benefit. Their use is limited by vein size and necessary maturation period, excluding up to a third of patients. A novel solution to this problem is pump-assisted vein dilation (PAVD), where the vein is “pre-matured” using a miniatured centrifugal pump that draws blood from a central vein, delivering it into the recipient vein (e.g., cephalic) under pressure. The aim of this study is to report the initial safety studies in sheep and a first-in-human (FIH) pilot study as a prelude to a phase 2 clinical study. Methods: Preclinical Study: Three anesthetized male sheep (50-70 kg) underwent cephalic PAVD using the Amplifi Vein Dilation System for 7 days (mean). These subjects and two control animals (no-PAVD) underwent brachiocephalic AVF creation and observation for 6 weeks, with weekly surveillance fistulagrams and duplex ultrasound (U/S). AVFs were then explanted for histological analysis. Clinical Study: Ten patients were recruited for a phase 1 study. They underwent cephalic PAVD for 7 days (mean), followed by brachiocephalic AVF creation and surveillance at 2 and 6 wks. Data on vein diameter and flow rates of the AVF were collected, as well as safety data on complications such as bleeding, infection, and embolism. Results: Preclinical Study: PAVD increased mean±SD vein diameter (mm) from 4.5±1.0 to 8.4±1.0 (p=0.005); leading to greater cephalic vein diameter at the time of AVF creation in the PAVD group vs no-PAVD (8.2±1.3 vs. 3.3±0.7; p<0.05). After 6 wks of maturation, mean vein diameter was still greater in the PAVD group compared to no-PAVD (12.8±2.8 vs. 8.4±0.7; p<0.05). Mean flow increased at 41 mL/min/day versus control animals at 5.2 mL/min/day. Clinical Study: All subjects saw an increase in vein diameter with PAVD at baseline vs. at 6 wks (2.3±0.5 vs. 5.2±0.7; p<0.05), as well as mean flows (mL/min) (285±30 vs. 724±149). There were no Amplifi-related or procedure-related serious adverse events. Conclusion: The translation of PAVD for AVF creation from bench-to-bedside provides safety and efficacy data on a novel solution that can increase the availability of autologous AVFs in patients excluded due to size criteria. The Amplifi vein dilation system can effectively and rapidly dilate peripheral veins without stimulating neointimal hyperplasia. PAVD should be explored in a phase 2 clinical study.

Background: Acute limb ischemia (ALI) requires prompt revascularization to preserve the extremity and minimize the effects of systemic reperfusion. Once ALI is recognized, delays in revascularization are generally due to system issues (e.g., transfer) and there is a need for a method of temporary extremity perfusion to reduce warm ischemic time. Lower Extremity Extracorporeal Distal Revascularization (LEEDR) is a percutaneous technique that uses a pump and circuit to deliver oxygenated blood into a pedal artery. Hypothesis: Extracorporeal perfusion can improve survival from ALI. Aims: The aim of this study is to use a swine model of prolonged hindlimb ischemia to compare survival and functional outcomes of LEEDR versus control (warm ischemia). Methods: Anesthetized female Yorkshire swine (40-60kg) underwent hindlimb ischemia using endovascular balloon occlusion and were randomized to control (n=6) or LEEDR (n=6). Controls underwent 9 hours of ischemia. LEEDR animals underwent contralateral femoral and ipsilateral posterior tibial artery cannulation followed by 8 hours of extracorporeal perfusion into the ischemic limb. Subjects were revascularized by removing the endovascular balloons, restoring extremity blood flow, and undergoing a 4-hour critical care period before extubation and observation for 48 hours. Primary outcome was survival and secondary outcomes included functional extremity scores (Tarlov Gait Score), compartment pressures (mmHg) and biochemical markers of reperfusion. Results: Survival was higher in animals undergoing LEEDR (83% vs. 0%; p=0.001), with most control animals succumbing to acute lung injury. LEEDR animals had a higher functional gait score (5.9±0.3 vs. 2.5±0.7; p<0.001) and lower compartment pressure (8±2 vs. 28±4; p=0.002) compared to controls. Biochemically, the LEEDR group had lower potassium (4.5±0.3 vs. 5.3±0.4; p=0.001) and lactate (1.2±0.5 vs. 2.0±0.7; p<0.001) measurements compared to controls during reperfusion and recovery. Conclusion: LEEDR can effectively mitigate 8 hours of extremity ischemia in a swine model, reducing mortality from reperfusion, while improving functional gait score and eliminating compartment syndrome. This percutaneous approach to ALI opens a new field of extracorporeal limb salvage, which can temporize extremity perfusion improving outcomes in patients who have traditionally had limited options due to prolonged warm ischemia.

Background: Nationally, many ASCVD patients fail to achieve an LDL-C <70 mg/dL, and uptake of both statin and non-statin therapies is low. The degree to which this varies across health systems is less clear. Methods: A cross sectional analysis was performed where lipid levels and lipid lowering therapies (LLT) were assessed using electronic health record data in patients with a previous diagnosis of ASCVD. The data was obtained across 14 US healthcare systems between 1/1/2021-12/31/2022. Proportions of patients with an active prescription of any statin, high intensity statin, ezetimibe, PCSK9i, and combination therapy (two or more agents) within 395 days of the most recent LDL-C value (index date) was evaluated overall and by participating site. Additionally, the proportion of patients with an LDL-C <70 mg/dL at the index date was also assessed. Results: Across 14 health systems, 1,118,623 patients with ASCVD were identified (median 61,840 per health system, range 8,161-182,315). Overall, 675,776 (60.4%) had an LDL-C level in the past year (range 39.1% - 70.8%). Of those with a lipid level, achievement of LDL-C <70 mg/dL ranged from 34.6-47.2%. In total, 42.6% were on any statin, 20.1% were on a high intensity statin, 4.3% on ezetimibe, and 1.2% on a PCSK9i. Only 2.9% were on combination therapy of a statin with ezetimibe or a PCSK9i. Variability was seen across health systems in utilization of each of these therapies, however even in the highest performing health systems, LLT uptake and achievement of LDL-C < 70mg/dL remained low ( Figure). Conclusion: Variability in utilization of LLT in ASCVD patients between health systems suggests that system-level factors may impact achieving guideline-based LDL-C goals. Despite the variability, the highest proportion of patients achieving an LDL-C <70mg/dL remained under 50% indicating the need for aggressive implementation efforts.

Acute atrial ischemia is a well-known cause of postoperative atrial fibrillation (POAF). However, mechanisms through which ischemia contributes to the development of POAF are not well understood. In this study, ex vivo Langendorff perfusion was used to induce acute ischemia/reperfusion in the heart to mimic POAF. Inducibility of atrial fibrillation (AF) was evaluated using programmed electrical stimulation and verified with open-atrium optical mapping. Compared with the control group without ischemia, 25 minutes of ischemia substantially increased the incidence of AF. The right atrium was more susceptible to AF than the left atrium. Administering insulin for 30 minutes before ischemia and during reperfusion with 25 minutes of ischemia greatly reduced the vulnerability to AF. However, insulin treatment during reperfusion only did not show substantial benefits against AF. Optical mapping studies showed that insulin mitigated ischemia-induced abnormal electrophysiology, including shortened action potential duration and effective refractory period, slowed conduction velocity, increased conduction heterogeneity, and altered calcium transients. In conclusion, insulin reduced the risk of acute ischemia/reperfusion–induced AF via improving the electrophysiology and calcium handling of atrial cardiomyocytes, which provides a potential therapy for POAF.