Citations

Background: Artificial intelligence (AI) can be used to predict a person’s age from the electrocardiogram (ECG) (AI-ECG age) and has been proposed as a measurement of biological age. The difference between AI-ECG age and chronological age (defined as delta-age) is an independent predictor of mortality in the general population. This study assessed the relationship between AI ECG estimated age and mortality among adults living with congenital heart disease (CHD). Methods: A previously validated neural network to estimate AI-ECG age was used to analyze standard digital 12-lead ECGs in a cohort of subjects aged >18 years seen in the adult CHD (ACHD) clinic between 1992 to 2023. A single ECG, collected during the year of the first visit to the ACHD clinic was analyzed to compute the delta-age.. A positive delta-age indicates an AI ECG estimated age higher than the subject’s chronological age. The relationship between the delta-age and mortality was evaluated using Cox proportional hazard models adjusting for influential clinical factors including chronologic age, sex, ACHD severity, NYHA class and history of arrhythmia. Results: Of 5,780 subjects tested (50% females), the mean chronological age was 39.1 ± 15.0 years. AI ECG estimated age was 52.3 ± 16.6 years. Complexity of CHD was classified as mild, moderate, and severe in 7.4%, 73.9% and 18.7% of patients respectively. Patients with severe CHD had the highest delta-age of 17.1 (±18.2) years followed by moderate 12.7 (±13.6) y and simple 7.7 (±11.5) y. Patients with single ventricle had the highest deviation in AI estimated age [median delta-age 21.0 (IQR 28.6) y] followed by those with a systemic right ventricle [median delta-age of 16.3 (IQR 29.3) y]. During a median follow-up of 6.4 y (25th – 75th centile 1.58 – 13.7 y), mortality occurred in 839 (14.5%) patients. After adjusting for chronological age, CHD severity, and other clinical variables, delta-age gap was associated with increased mortality risk (HR 1.06 (1.03 – 1.09) per 5-year increment in delta-age, p<0.005), Table 1. Conclusion: The difference between AI ECG and chronological age is an independent predictor of all-cause mortality in ACHD patients.

Background: Echocardiographic evaluation of Aortic valve stenosis (AS) severity relies on aortic valve area, peak jet velocity, and mean transaortic gradient. In pursuit of improving accuracy, the transaortic flow rate (FR), defined as the ratio of stroke volume to systolic ejection time, has been introduced. However, its prognostic value in AS patients remains controversial. Aim: This study aims to systematically review the predictive value of FR in AS patients and provide quantitative pooled analysis results where applicable. Methods: A systematic search of PubMed/Medline, Embase, Scopus, Web of Science, and Cochrane was conducted for observational studies on AS patients published up to March 15, 2024. Studies were included if they assessed the clinical prognostic utility of FR with at least three months of follow-up. Pooled estimates and 95% CI for FR's hazard ratio (HR) in each binary outcome were calculated using a random effects model. Results: Nineteen studies with 9456 patients (mean age 75) underwent descriptive analysis, and 17 eligible studies were included in the meta-analysis. For predicting all-cause mortality, the pooled HR for low FR measured at rest (cut-off value 200-210 mL/s) was 1.32 (95% CI: 1.01–1.63, I2: 69%, p<0.05) (Figure 1. A). For FR measured during stress echocardiography, the pooled HR was higher at 1.58 (95% CI: 1.20–1.96, I2: 0%, p<0.05). Additionally, every 100 mL/s increase in FR significantly reduced all-cause mortality; the HR was 0.61 (95% CI: 0.47–0.75, I2: 47%) for FR measured at rest (Figure 1. B), and 0.61 (95% CI: 0.31–0.91, I2: 65%) for FR measured during stress echo. For the combined endpoint of mortality and hospitalization, the HRs were as follows: 2.54 (95% CI: -0.99–6.08, I2: 48%) and 2.57 (95% CI: 0.69–4.44, I2: 0%) for the low FR group at rest and during stress echo, respectively. For every 100 mL/s increase in FR, the HRs were 0.19 (95% CI: -0.19–0.58, I2: 61%) at rest and 0.36 (95% CI: 0.18–0.54, I2: 0%) during stress echo. Conclusion: FR is a prognostic marker for all-cause mortality in AS patients, indicating its potential for risk stratification. Incorporating FR into clinical assessments could help personalize follow-up and monitoring strategies.

Background: The Fontan procedure has transformed the management of congenital heart defects (CHD) characterized by single ventricle physiology, yet it predisposes individuals to Fontan-associated liver disease (FALD), potentially leading to end-stage liver disease (ESLD). Combined heart and liver transplantation (CHLT) emerges as a therapeutic option, but evidence on its efficacy, safety, and outcomes remains limited. Objectives: This systematic review and single-arm meta-analysis aims to comprehensively evaluate the literature on CHLT in Fontan patients, focusing on patient characteristics, perioperative outcomes, and post-transplant morbidity and mortality. Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted following PRISMA guidelines. Studies meeting the intervention of CHLT in Fontan patients were included and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software. Results: Four studies met inclusion criteria, comprising 67 Fontan patients undergoing CHLT. All included studies were observational retrospective cohorts performed in the United States. One-year survival rate post-CHLT was 84% (95% CI 66%-94%), Figure 1A. Rates of liver and heart graft rejection were low 10% (95% CI 3%-33%) and 8% (95% CI 2%-31%), respectively, Figure 1B. Postoperative complications included acute kidney injury 72% (95% CI 46%-88%), temporary dialysis 31% (95% CI 14%-55%), neurologic events 14% (95% CI 5%-34%), infection 24% (95% CI 6%-63%), and unplanned medical procedures 41% (95% CI 24%-60%), Figure 1C. Conclusion: CHLT in Fontan patients demonstrates promising survival rates, but graft rejection and postoperative complications pose challenges. The rate of renal complications is particularly notable and requires further evaluation. Future research should prioritize comparative different management strategies and long-term follow-up to refine protocols and optimize outcomes.

Introduction/Background: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant aortic aneurysm syndrome characterized by arterial tortuosity resulting in arterial aneurysms and dissections, with unique craniofacial and skeletal features including bifid uvula, cleft palate and hypertelorism. While the presence of atrial fibrillation (Afib) and arrhythmias have been reported in LDS patients, limited investigation has been completed regarding the associated risk and severity of vascular complications in relationship to these arrhythmias1,2. Research Questions/Hypothesis: Are there any differences in vascular outcomes in patients with LDS when experiencing various forms of tachyarrhythmia? Goals/Aims: To evaluate the relationship between various types of arrhythmias and vascular outcomes in patients with LDS, including arterial dissection, stroke, revascularization, and death. Methods/Approach: A large sample of LDS patients (n=436) from a single tertiary referral center was assessed for ICD-10 diagnoses of arrhythmia and outcomes of interest. Arrhythmias assessed included Afib, atrial flutter (AFL), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT). Outcomes were arterial dissection, hemorrhagic and ischemic stroke, revascularization, and all-cause mortality. Results/Data: Our cohort (n=436) had an average age of 47 and was 57.8% female. A total of 26 patients had a documented history of tachyarrhythmia: 16 (3.4%) Afib, 2 (0.5%) AFL, 6 (1.4%) SVT, and 2 (0.5%) PVC. LDS patients with Afib were at significantly higher risk of arterial dissection (25% vs 6.0%, OR: 5.3, p<0.01), revascularization (18.8% vs 3.3%, OR: 8.1, p<0.01), stroke (25% vs 3.6%, OR: 9.0, p<0.001), and death (25% vs 4.3%, OR: 7.4, p<0.01) compared to those without a documented history of arrhythmia. Other arrhythmia types evaluated were not significant. Predictors of any arrhythmia type included hypertension (78% vs 31%, OR: 1.5, p<0.001) and heart failure (39% vs 5.0%, OR: 2.3, p<0.001). Conclusion: Although rare, Afib in LDS patients is associated with adverse vascular outcomes and mortality compared to those without a history of arrhythmia. Furthermore, the magnitude of increased risk is striking. Early identification and management of Afib in LDS patients may be critical in mitigating the risk of potential vascular complications.

Description of Case: A 40-year-old woman presented with a 3-month history of dyspnea. A murmur was found on examination. Echocardiography reported moderate mitral stenosis and regurgitation with diffuse thickening and calcification of the anterior mitral leaflet (Fig1.A), thought to be due to rheumatic disease. She had runs of supraventricular tachycardias not controlled with diltiazem. Her dyspnea progressively worsened; transesophageal echocardiography(TEE) showed severe mitral stenosis and mitral regurgitation (mean gradient 18 mmHg; Fig1.B) with a dense CW Doppler (Fig 1.C) and a mass on left atrial free wall. Cardiac MRI revealed diffuse left atrial thickening with delayed enhancement of the left atrium, left atrial appendage, and extending into the right upper and left inferior pulmonary veins. The mass was initially suspected to be a thrombus. She was placed on rivaroxaban and scheduled to undergo mitral valve replacement. When she presented to our emergency department with dizziness she was found to have paroxysmal atrial fibrillation and pulmonary embolism. On admission she had an intermittent opening snap and a 1/6 mid-diastolic rumble with a 2/6 holosystolic murmur at the apex. Work-up for infectious disease and antiphospholipid syndrome was negative. NT-proBNP was mildly elevated. At surgery the mass invaded the mitral valve and the anterior, septal, and superior part of the left atrial lateral wall and could only be partially excised (Fig1.D). Pathology showed high-grade undifferentiated pleomorphic cardiac sarcoma. Discussion: This case highlights the diagnostic challenges associated with primary cardiac tumors masquerading as valvular pathology. The presentation included dyspnea, typical auscultation of mitral stenosis and features of stenosis on echocardiography. Presumptive diagnoses included rheumatic heart disease, calcific degeneration, infective endocarditis, and autoimmune processes; the atrial mass was initially thought to be a thrombus. A thorough, multidisciplinary approach to diagnosis, utilizing multimodality imaging techniques and ultimately tissue biopsy were required to make the correct diagnosis. Maintaining a broad differential when dealing with valvular masses is key, since relying solely on imaging findings may not suffice for definitive tissue diagnosis.

Background: Current guidelines discourage athletes with a positive genetic test for arrhythmogenic cardiomyopathy (ACM) from participating in sports. The evidence that exercise may act as a disease-accelerator is most compelling for PKP2-mediated ACM. As such, shared decision making (SDM) and return-to-play (RTP) for athletes with ACM may be possible for some genotypes. Objective: To examine the management, RTP, outcomes, and evolution of phenotype among athletes with genotype positive ACM. Methods: A retrospective review of the electronic medical records was performed on all self-identified athletes with genotype positive ACM. They were evaluated, risk stratified, and treated in Mayo Clinic’s (MC) Windland Smith Rice Genetic Heart Rhythm Clinic. Results: Among the 621 patients with genotype-positive ACM, there were 38 athletes [16 females (42%); mean age at either clinical diagnosis or positive genetic test 28 ± 19 years; mean follow-up 4 ± 4 years] participating in sports at all levels. The majority, 21 (55%), had PKP2-ACM and 7 (18%) had DSP-ACM. Prior to their first MC evaluation, 15 athletes (39%) were engaged in long distance running, swimming, cycling, or triathlons. Seven athletes (18%) had a non-lethal breakthrough cardiac event (BCE) after diagnosis, but prior to MC evaluation. During 150+ athlete-years of follow-up, there have been no ACM-associated deaths, but 5 athletes (13%) experienced a non-lethal BCE. Twenty-two athletes (58%) were phenotype negative at time of first MC evaluation including 10 endurance athletes (45%). Of these, 3 (14%) converted to phenotype positive (average age at conversion 25 ± 15 years), while 7/16 (44%) phenotype positive athletes exhibited further disease progression (average age at progression 32 ± 18 years). For these 10 athletes who either converted or progressed, treatment intensification included an ablation in 4, ICD in 2, and a heart transplant in 2. Seven resumed athletic activity in some capacity after conversion/progression and a non-lethal BCE occurred in 3. Conclusions: This is the first single center cohort of patients with ACM being empowered to remain an athlete. In contrast to athletes with other genetic heart diseases (GHDs), these athletes have exhibited more cardiac events, although nonfatal, and higher rates of disease conversion/progression than our other GHDs. Further studies are needed to determine how to effectively and safely enable appropriate sports participation in genetically-mediated ACM

Introduction: Metabolic pharmacotherapies [Glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i)] have shown benefit in patients with heart failure and preserved ejection fraction (HFpEF). It remains unclear whether the two classes would have additive effects. Methods: We performed a retrospective study using a de-identified federated database with 89 contributing health care organizations (HCO), including over 126 million patients (TriNetX Research Network, Cambridge, MA; date of data access: May 23, 2024). TriNetX regularly aggregates clinical data directly from participating HCOs, and performs extensive data quality and accuracy assessment. While TriNetX obfuscates institutional information relating to participating HCOs, a typical HCO includes a large academic health center with inpatient, outpatient, and specialty care services. We identified all patients with a diagnosis of Heart failure with preserved ejection fraction (HFpEF, ICD-10: I50.3), and SGLT2i usage. We then categorized this patient population into two cohorts, including patients with concomitant GLP1RA use, and patients without GLP1RA use. For both cohorts, we collected data on patient demographics, and the outcomes of all-cause mortality, and all-cause hospitalization, occurring up to 10-years after the index diagnosis. We evaluated differences in outcome risk using hazards ratios and 95% confidence intervals. Results: Prior to propensity score matching, we identified 114,329 patients, with 7931 patients receiving SGLT2i +GLP1RA vs 106398 receiving SGLT2i-alone. Majority (55.7%) identified as white and 24.4% as African Americans and >90% of the patients had a diagnosis of type 2 diabetes mellitus. After propensity matching, the rate of all-cause hospitalization within the combination group was lower than SGLT2i group (29.6% vs 32.4%, HR 0.76 [0.73- 0.79], P<0.001). All-cause mortality for the combination group was 6.8% versus 10.6% within the SGLT2i-alone group (HR 0.52 [0.47-0.56], P<0.001)). Conclusion: In this propensity-matched cohort, patients with HFpEF receiving GLP1RA and SGLT2i had lower rates of hospitalizations and all-cause mortality compared with those receiving SGLT2i alone. Large randomized controlled trials are warranted to corroborate these findings.

Background: The Society for Cardiovascular Angiography and Interventions (SCAI) staging system is a crucial tool for categorizing cardiogenic shock (CS) and guiding interventions. SCAI staging is traditionally static and may not capture dynamic changes. We evaluated the impact of axillary mechanical circulatory support and SCAI stage transition in patients with CS supported until heart transplantation. Methods: A retrospective study was conducted on patients with Impella support as bridge to transplant. Hemodynamic and vasoactive support parameters were collected and SCAI stage recorded at baseline and after 72 hours. Results: 36 patients were included in the analysis. The median age was 61 (52 – 68) with an EF of 19% (15-26%) (Figure 1). Before Impella placement, the distribution of patients across SCAI stages was as follows: 19 patients in SCAI B, 8 patients in SCAI C, and 9 patients in SCAI D. After 72 hours of Impella support, 7 patients initially classified as SCAI C transitioned to SCAI B with one deteriorating to SCAI D (Figure 2). Patients in SCAI D showed notable improvement, with 8 out of 9 patients transitioning to SCAI B. For patients initially SCAI B, RA changed from 10 to 11 mmHg, and PCWP decreased from 23 to 17 mmHg. The Fick CI increased from 2.53 to 3.02 L/min/m 2 (p=0.04), and the vasoactive inotropic score (VIS) decreased from 7.5-5.0 (p=0.05). In patients initially classified as SCAI C, RA pressure decreased from 13 to 8 mmHg, and PCWP reduced from 32 to 30 mmHg. The Fick CI improved from 1.79 to 2.61 L/min/m 2 (p<0.001), while the VIS decreased from 9.2 to 6.3 (p=0.004). For those initially in SCAI D, RA pressure reduced from 8 to 5 mmHg, and PCWP decreased from 27 to 18 mmHg. The Fick CI increased from 1.55 to 2.67 L/min/m 2 (p=0.002), and the VIS was notably reduced from 4.75 to 3.8 (p=0.36). All 36 patients survived to heart transplantation without major pre-transplant complications. Conclusion: SCAI stage C-E mortality ranges from 25 – 50% or worse. Implementing Impella 5.5 support reduced SCAI severity and may be associated with improved survival in HFCS. We demonstrated lower VIS after Impella 5.5 and a 100% event free survival to heart transplantation despite a 25% baseline SCAI D cohort. Larger data should be evaluated to assess this trend.

Background: Although no tests are currently available to predict post-stroke depression (PSD), a risk factor for diminished quality of life and stroke-related death, emerging evidence suggests that ischemic stroke (IS) may induce behavioral changes by damaging connections throughout the brain rather than via localized injury. Hypothesis: We sought to determine if active (surveys) and passive (accelerometer, GPS, and other sensors) smartphone data could quantify exploratory behavioral proxies of PSD. Methods: Thirty-four adults with a recent IS (n = 12) or transient ischemic attack (TIA) (n = 22) diagnosis were followed for 3 months. Participants used the Beiwe app to complete a weekly Patient Health Questionnaire-8 (PHQ-8) survey and were evaluated every 30 days with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Preliminary analysis of app survey compliance was adequate (86%), and the quantity of data collected was greater for Android than iOS phones. PHQ-8 indicated depression (moderate or severe) in 20% of participants. MADRS highly correlated with the most recent PHQ-8 ( r = 0.92, 95% CI (0.19, 0.99), P = 0.028). Several exploratory passive physical activity and social measures showed statistically significant change over time and/or associations with PHQ-8 and MADRS. Conclusion: Low-burden smartphone data holds promise for developing novel IS and TIA outcome measures as well as identifying patients most at risk of PSD.

Background: Naples prognostic score (NPS) is a recently developed tool for assessing inflammatory and nutritional status. It is commonly used to evaluate cancer patients. Purpose: We aimed to investigate the impact of NPS on clinical outcomes in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Methods: We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through June 2024. We conducted a systematic review and meta-analysis pooling dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). All analyses were performed using R V. 4.3.1. Results: We included five studies with a total of 12,785 patients. Comparing high NPS (3-4) to low NPS (0-2), high NPS (3-4) was significantly associated with an increased incidence of overall mortality (RR: 2.21, 95% CI [1.85, 2.65], P < 0.01), shock (RR: 1.85, 95% CI [1.33, 2.57], P < 0.01), acute kidney injury (RR: 1.54, 95% CI [1.15, 2.08], P < 0.01), left ventricular thrombus (RR: 2.93, 95% CI [1.44, 5.94], P < 0.01), and no-reflow (RR: 1.35, 95% CI [1.17, 1.57], P < 0.01). However, there was no significant difference between high NPS (3-4) and low NPS (0-2) regarding in-hospital mortality (RR: 1.82, 95% CI [0.99, 3.37], P = 0.06). Conclusion: Our meta-analysis highlights the importance of evaluating inflammation and malnutrition status in STEMI and shows that routine blood tests can provide prognostic insights. NPS can help predict different clinical outcomes in STEMI patients undergoing PPCI. While it does not affect in-hospital mortality, its simplicity and accessibility make it useful for clinical risk assessment and long-term prognosis. Further studies are needed to investigate its predictive value further.