Citations

Introduction/Background: Fibromuscular Dysplasia (FMD) is a non-atherosclerotic vascular disease that primarily affects medium-sized arteries and is characterized by abnormal cell development in the artery walls. Recent studies have suggested that various connective tissue features may be prevalent in patients with FMD, however the clinical significance of these findings on the disease course are uncertain. Research Questions/Hypothesis: We hypothesized that the presence of connective tissue features in patients with FMD might indicate a more severe disease course, potentially associated with increased severity of vascular complications. Goals/Aims: To evaluate the association between connective tissue features and the severity of vascular complications in FMD patients on outcomes including dissections and stroke. Methods/Approach: This cross-sectional study involved 2,454 patients diagnosed with FMD at a tertiary referral center. Patients were classified into two groups based on the presence (n=324) or absence (n=2130) of connective tissue features (pectus deformity of any kind, scoliosis, pneumothorax, inguinal hernia, uterine rupture, bowel perforation, Achilles tendon rupture). We evaluated the incidence of dissections and ischemic or hemorrhagic strokes using odds ratios and chi-squared tests. Results/Data: The cohort consisted of 2,454 participants with an average age of 64.8 years, of whom 89.1% were female and 92.4% identified as White. When comparing groups with and without connective tissue features, there were no significant differences in the prevalence of aneurysms at any site. Among the subgroup of FMD patients with connective tissue features (n=234), prevalent conditions included pectus (12.35%), scoliosis (47.22%), pneumothorax (16.67%), inguinal hernia (13.58%), uterine rupture (16.36%), bowel perforation (6.48%), and Achilles tendon rupture (1.85%). Vascular outcome analysis showed significant differences: the odds of experiencing a stroke were higher in patients with these features (odds ratio: 1.60; P-value: <0.01), whereas the odds of experiencing dissections were lower (odds ratio: 0.77; P-value: 0.03). Conclusion: The presence of connective tissue features in patients with FMD is associated with 60% higher odds of experiencing a stroke, equivalent to a 1.6-fold increase, compared to those without these features. This association may represent a novel finding in the literature, warranting further investigation.

Introduction/Background: Patients with heart failure and those waiting for a heart transplant often experience a significant decrease in their ability to perform daily activities and exercise, leading to a lower quality of life. Although exercise-based cardiac rehabilitation (EBCR) is a possible treatment option, its effectiveness has not been well measured, resulting in limited adoption. Research Questions/Hypothesis: Could physical rehabilitation before receiving a heart transplant improve functional status and better outcomes? Goals/Aims: Our objective is to evaluate the effect of pre-transplant physical therapy on the standardized improvement of AM-PAC scores, measured from the earliest pre-transplant assessment to the most recent pre-transplant evaluation. Our second objective is to assess the impact of the latest Pre-Transplant AM-PAC Score on the number of hospital-free days following transplantation. Methods: We conducted a retrospective study on 91 heart transplant patients who received Impella support from January 2019 to April 2023, approved by the Mayo Clinic Institutional Review Board. We collected data on demographics, AMPAC scores, and outcomes at three time points. Continuous variables were compared using the T-test or Mann-Whitney test, and categorical variables using the Chi-square or Fisher's exact test. We used a linear regression model to investigate the relationship between rehabilitation duration and AMPAC scores. Quantile regression was preferred due to the non-normal distribution of the outcome, hospital-free days. Results: We conducted a linear regression analysis and found a statistically significant association between increased hours spent in PT and greater improvement. After one hour of physical therapy, there was an average increase of 1.07 (95% CI 0.1, 2; p=0.03) in AMPAC scoore. We also compared the change in the AMPAC score with hospital-free days, and it was statistically significant in quantile regression analysis, indicating an increase of 0.28 (95% CI 0.2, 0.55; P=0.03) points in the AMPAC Score, corresponding to an additional hospital-free day. Conclusion: Increased hours spent in physical therapy show a significant positive association with greater improvement in standardized AM-PAC Mobility scores and hospital-free days. These findings encourage increasing uptake and support of cardiac rehabilitation programs.

Background: LQTS is a genetic heart disease associated with an increased risk of sudden death. Despite advances in genetic testing, a small subset of patients still lacks identifiable genetic markers. Consequently, the true prevalence and clinical phenotype of genotype negative remains to be determined. Objective: To determine the prevalence and clinical characteristics of patients with a clinical diagnosis of LQTS but a negative genetic test. Methods: A retrospective review was conducted on patients evaluated and treated at a tertiary hospital between 2000 and 2024, focusing on those with a clinical diagnosis of LQTS, but a negative genetic test for all LQTS-associated genes, with available follow-up of at least 1 year. Results: After exclusion for follow-up and lack of genetic testing, the study cohort consisted of 1834 patients with LQTS including 1708 (93%) with a (likely) pathogenic (LP/P), LQTS-causative variant. Also, in 95 patients (5%), their variant of uncertain significance was clinically upgraded to a LP/P-variant, leaving only 31 patients classified as phenotype positive but genotype negative (1.6%). Of these, 16/31 underwent next-generation genetic sequencing, revealing the genetic cause in 6/16 cases (37%; 0.3% of all patients). For the remaining 25 genotype negative LQTS patients (1.3%), the mean age at diagnosis was 26 ± 15 years, with 19 (76%) being female, and an average initial QTc of 497 ± 41 ms. In total, 11 patients (44%) experienced a cardiac event before diagnosis [1 sudden cardiac arrest (SCA), 1 Torsades, 1 VT, 8 syncopes] and 1 patient had his first cardiac event during follow-up; 7/12 patients had more than one subsequent event. Twenty patients were proband (80%) and 6 had a family history of SCA. Eleven patients received an ICD (44%), left cardiac sympathetic denervation was performed in 4 (16%), and 2 patients experienced arrhythmia-related deaths (8%). The mean follow-up since diagnosis was 7 ± 5 years. Conclusion: With a prevalence of genotype-negative LQTS of 2%, the number of these patients is much lower than previously suggested, underscoring the advancements in identifying new genetic markers and the role of phenotype-enhanced variant adjudication and next-generation sequencing. Additionally, significant disease severity was observed in the remaining patients, emphasizing the pivotal role of genotype-phenotype correlations and risk stratification in managing and counseling patients lacking identified LQTS-causing mutations.

Background: Bilateral cardiac sympathetic denervation (BCSD) has shown promise in treating patients with nonischemic cardiomyopathy (NICM) suffering from refractory multifocal premature ventricular contractions (PVCs) and ventricular tachycardia (VT). Despite its growing use, the effectiveness of BCSD across different NICM etiologies has not been extensively studied. Research Question: How effective is BCSD across a variety of NICM etiologies? Goals: To evaluate the effectiveness of BCSD on left ventricular ejection fraction (LVEF) and PVC burden in patients with NICM. Methods: We conducted a subset analysis on a previous retrospective, observational study of NICM patients who underwent BCSD. Eight NICM etiologies were assessed. Results: 43 NICM patients underwent BCSD (mean age 52.3±14.7 years; 30% females). Overall, LVEF significantly improved (38.7±7.9% to 46.2±9.6%, p <0.001), and PVC burden (PVCb) significantly decreased (23.7±9.9% to 1.3±1%, p <0.001). A similar phenomenon was seen in idiopathic/dilated cardiomyopathy (CM) (LVEF: +8.7%, p <0.001; PVCb: -20.6%, p <0.001), post-viral CM (LVEF: +4.8%, p =0.2; PVCb: -24.2%, p <0.001), familial CM (LVEF: +10%; PVCb: +23.3%), giant cell CM (LVEF: +10%; PVCb: + 30.5%), and arrhythmogenic right ventricular CM (LVEF: +12.5%, p=0.09; PVCb -30.6%, p =0.001). Catecholaminergic polymorphic VT had a non-significant increase in LVEF (+5%, p=0.5) but a significant decrease in PVCb (-21.8%, p=0.02), whereas sarcoidosis had the opposite effect with significant increase in LVEF (LVEF: +13.4%, p=0.3) but non-significant decrease in PVCb (-16.1%, p=0.02). Lastly, hypertrophic CM remained unchanged in LVEF (30%) but PVCb decreased (-8%). Conclusion: BCSD demonstrates efficacy in improving LVEF and reducing PVCb across almost all NICM with refractory VT. However, a case-by-case evaluation is still needed for its use.

Introduction: Acute Coronary Syndrome (ACS) is a major global health issue, with smoking as a significant modifiable risk factor. Smoking cessation reduces recurrent coronary events, making it crucial in ACS management. Current protocols recommend smoking cessation education during hospitalization and referral to smoking cessation or outpatient cardiac rehabilitation programs, where nicotine replacement therapy (NRT) and bupropion are available. NRT, including patches, gum, and lozenges, helps alleviate withdrawal symptoms by providing a controlled nicotine dose. Hypothesis: We hypothesize that cautious initiation of NRT during hospitalization benefits ACS patients, with the benefits outweighing the risks. This study seeks to provide clarity and contribute to evidence-based guidelines for ACS management. Methods: In this retrospective cohort study, data were gathered from the TriNetX database. The study compared two cohorts: 122,198 patients who received NRT and were hospitalized for acute myocardial infarction (AMI) or unstable angina (UA), and 160,387 patients who did not receive NRT but were admitted for the same conditions. The follow-up period began on the day of the index event and continued for 30 days. Cardiovascular outcomes were compared between propensity score-matched patients with and without NRT. Results: Patients receiving NRT had a reduced risk of several cardiovascular outcomes compared to those who did not receive NRT, including atrial fibrillation and flutter (RR [95% CI]=0.822[0.792-0.854, p<0.01]) and ventricular fibrillation and flutter (RR [95% CI]=0.715[0.654-0.781, p<0.01]). The risk of death was also reduced (RR [95% CI]=0.701[0.678-0.726, p<0.01]). Hospital readmissions were less frequent in the NRT group (RR [95% CI]= 0.960[0.955-0.965, p<0.01]). Additionally, the risk of cardiac arrest was lower (RR [95% CI]= 0.698[0.660-0.738, p<0.01]), and supraventricular tachycardia (SVT) was less common (RR [95% CI]= 0.883[0.827-0.942, p<0.01]). These results highlight the potential benefits of NRT in reducing the risk of various cardiac events following AMI or UA. Conclusions: The cautious initiation of NRT during hospitalization can benefit ACS patients where the benefits outweigh the risks. This study aims to provide clarity and contribute to evidence-based guidelines for ACS management.

The growing adoption of advanced imaging modalities, such as transesophageal echocardiography (TEE), has led to more frequent detection of cardiac structural abnormalities. While intracardiac cardiac tumors and shunts are infrequent and typically asymptomatic, their existence can precipitate severe outcomes, including stroke, myocardial infarction and sudden death. Case Description: A 69-year-old female presented with left sided facial droop, slurred speech and left arm weakness. A computed tomography angiography revealed focal occlusion of the distal right middle cerebral artery. She was initiated on thrombolytic therapy and experienced resolution of symptoms. Transthoracic echocardiogram revealed right to left shunting consistent with a patent foramen ovale (PFO). Further workup with TEE confirmed the presence of a PFO but also detected a mobile echogenic mass on the aortic valve leaflet, indicative of papillary fibroelastoma (PFE). Cerebral infarction was attributed to an embolic event, with the PFO and PFE being likely culprits. Discussion: Current guidelines give a conditional recommendation, low certainty of evidence, for PFO closure in adults older than 60 years, although some observational studies have shown some risk reduction in older patients. The key trials showing clinical benefit of PFO closure were in adults younger than the age of 60. For left sided cardiac tumors, such as PFE, guidelines give a 2A recommendation for resection. Addressing the risk for recurrent stroke in this 69-year-old patient was an essential part of stroke care, as such, a multi-disciplinary team of experts including cardiology, neurology, and cardiothoracic surgery was conveyed. The decision was to proceed with surgical intervention in addition to antiplatelet therapy to achieve optimal risk reduction. The patient subsequently underwent successful surgical removal of the PFE with native valve preservation and PFO closure. Conclusion: Cardiac PFEs and PFOs can be associated with increased stroke risk. Employing appropriate imaging techniques and timely interventions are of utmost importance in stroke management.

Introduction: Identifying patients at risk for ischemic events after percutaneous coronary intervention (PCI) relies on traditional analysis of limited clinical and imaging variables. Machine learning (ML) has shown promise in effectively predicting cardiovascular risk in population studies. While existing ML models mainly predict mortality and incorporate clinical variables, there is a lack of tools that have utilized genetic data and that predict ischemic events. Aims: This study aims to develop and validate a ML model incorporating genotyping and clinical data to enhance prediction of ischemic outcomes for PCI patients utilizing large prospectively derived diverse datasets. Methods: Patients from the TAILOR-PCI trial (n=5302) were utilized for model development. 50% of the sample was utilized for Boruta feature selection and 50% for training and testing using cross validation. Features included demographics, medical history, medications, PCI characteristics, and genetic data (specifically, CYP2C19 *2, *3, *17 alleles). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. Multiple ML classification algorithms, including Support Vector Machine (SVM) polynomial, Random Forest, Light gradient boost, XG Boost, among others, were benchmarked for their prediction performance on rare events. The top performing classifiers were externally validated on an independent dataset from the PRECISION PCI study (n=3,745). Results: Mean participant age of the training set was 64.2 ± 11.0 years, with 75.4% being male. During follow-up of 12 months, among 4,572 patients in the entire cohort 343 (7.5%) met the primary outcome. The SVM polynomial model demonstrated the highest area under the curve (AUC) of 0.67 for predicting the primary outcome with test dataset. The sensitivity, specificity, precision, and recall were 0.87, 0.28, 0.07, and 0.87 respectively (Figure). Peripheral arterial disease, body mass index, and age were among the top variables by feature importance. Conclusion: ML models incorporating both clinical and genetic data are feasible and highly promising in predicting major adverse cardiac events that may help guide use of anti-platelet drug therapy. The AUC values are reasonable given imbalances and misclassifications in datasets, and further model optimization with prospective utilization of the model will be paramount.

Background: Our team recently developed an Artificial Intelligence model that enables the identification of increased left ventricular filling pressures using a single-lead electrocardiogram (AI-ECG) with excellent performance (AUC 0.91). However, its ability to predict incident heart failure (HF) in the community is yet to be evaluated. Hypothesis: We tested the hypothesis that the output from the AI-ECG will predict the long-term incidence of heart failure (HF) and HF with preserved ejection fraction (HFpEF), and would refine the HF predictive capabilities of the AHA Predicting Risk of Cardiovascular Disease EVENTs (PREVENT TM ) Equations. Methods: Leveraging the resources of the Rochester Epidemiology Project (REP) we analyzed data from patients who sought primary care in Olmsted County, MN, between 1997-2003 with passive follow-up until April 2024. We included those with a digital ECG at baseline and excluded those who were part of the original algorithm development or history of heart failure. The diagnosis of heart failure was ascertained by using ICD codes (ICD9-428,ICD10-I.50) and a word search for the terms related to heart failure. HFpEF was ascertained using the Ejection Fraction (EF) data closest to the heart failure diagnosis date, using EF more than 40% as the criterion. We tested the association between AI-ECG predicted probabilities and new-onset HF and HFpEF using Cox proportional hazard models. These models were also adjusted for cardiovascular risk factors and were stratified to evaluate the effect of the AI-ECG output on PREVENT TM -predicted HF at 10 years. Results: We included 20,276 subjects, mean age 55±14.03, 52% women, 92% non-Hispanic white. After 18.2±8.5 years of follow-up, 4,008 (19.76%) were diagnosed with HF and 3,812 (18.8%) HFpEF. Risks of HF and HFpEF significantly increased in patients with increased left ventricular filling pressures by AI-ECG, independent of risk factors, all p for trend <0.001, see Fig A-B , respectively. AI-ECG enhanced the prediction capabilities of the PREVENT TM score across all risk groups, see Fig-C. Conclusions: AI-ECG-Derived increased left ventricular filling pressure is associated with new-onset HF and HFpEF in the community and was associated with incidental heart failure at any PREVENT TM risk category. Those results suggest a potential role of AI ECG in predicting heart failure.

Background: Cardiac allograft vasculopathy (CAV) is one of the leading causes of graft failure and death after heart transplantation (HTx). Conventionally, CAV is characterized by concentric intimal thickening, however the long-term progression patterns of plaque morphology are not yet well understood. Research Question: This study aimed to assess the plaque morphology, including histology and eccentricity, in a temporal manner post-HTx using virtual histology intravascular ultrasonography (VH-IVUS). Methods: We included 50 patients who underwent serial VH-IVUS assessment at three assessment points (A1:0-1 year, A2:3-5 years, A3:7-10 years) after HTx. Differences in VH-IVUS findings between timepoints A1 to A2 (early period) and A2 to A3 (late period) were investigated. Plaque volume index was defined as (plaque volume/vessel volume) × 100%. Eccentricity index (EI) was defined as (maximum intimal thickness – minimum intimal thickness)/maximum intimal thickness and was evaluated in 39 patients with significant plaque (maximal intimal thickness >0.50 mm at the A3) at each timepoint. The serial changes of EI and relationship between EI and other VH-IVUS findings were investigated. Results: Of 50 patients, mean age was 51±13 years, 36 (72%) were males. In both early and late periods, the plaque volume (PV) index showed a significant increase, however, the rate of progression was significantly slower in late period. (5.8% [0.9, 13.2] vs 2.4% [-0.2, 7.4], p=0.015). The EI showed a trend of decrease in the early period, compared to increases in the late period (-0.040 [-0.103, 0.004] vs 0.003 [-0.030, 0.052], p=0.036). Patients with EI change in late period higher than median value had significantly lower proportion of fibrous plaque (70.8% [67.2, 75.1] vs 62.7 [55.5, 66.9], p=0.002) and higher dense calcium (1.1% [0.9, 1.9], 4.5% [1.8, 6.9], p=0.022) at A3. Conclusion: In heart transplant patients, coronary artery plaque progression in the late period showed more eccentric progression with lower fibrous plaque composition, a pattern commonly observed in typical and conventional coronary atherosclerosis. These findings may provide a novel mechanism and therapeutic insight into the temporal patterns in CAV progression during long term follow up.

Introduction: Cancer therapy-induced cardiotoxicity (CTRCD) is one of the most significant adverse effects of oncologic treatment, responsible for considerable morbidity and mortality. Heart failure stands out due to its higher frequency and severity with the focus of most studies being left ventricular dysfunction and remodeling. The right ventricle (RV) may also be damaged by CTRCD, however the effects on RV function have not been elucidated. Research Question: What are the echocardiographic changes in RV due chemotherapy treatment? Objective: To conduct a systematic review and meta-analysis evaluating the RV echocardiographic parameters in patients undergoing chemotherapy treatment. Methods: Pubmed, Embase and Cochrane were systematically searched for studies that assessed RV echocardiographic changes in patients due to chemotherapy treatment. Statistical analysis was performed using the R statistical environment, with a summary estimate using Mean Differences (MD), adopting a random-effects model to account for variability among studies and a two-tailed significance level of 5%. A correlation coefficient of 0.5 was assumed for the paired measurements. Heterogeneity was assessed using the I2 statistic. Results: We included 641 patients from 11 studies, 75.5% of whom were women and with a mean age of 50.2±6.1 years. RV function was significantly lower after cancer treatment, with reduction in the fractional area change (MD -3.53%; CI -5.25, -1.41; p<0.0011 - Figure 1A), RV global longitudinal strain (MD 2.27%; CI 1.24, 3.29; p<0.0011 - Figure 1B) and in RV free wall strain (MD 3.22%; CI 1.76, 4.67; p<0.0001 - figure 1C). Additionally, the pulmonary artery systolic pressure was significantly higher (MD 1.36mmHg; CI 0.32, 2.4; p=0.01 - Figure 1D) and the tricuspid annular plane systolic excursion was significantly reduced (MD -1.98mm; CI -3.27, -0.68; p=0.0027 - Figure 1E) after chemotherapy. Conclusion: RV dysfunction is common in CTRCD and its echocardiographic quantification should be included in clinical practice follow-up during cancer treatment. Further research is needed to elucidate the underlying factors contributing to RV dysfunction in CTRCD and to develop methods for its early detection.