Citations

Background: Pulmonary hypertension (PH) is a life-threatening disease affecting up to 1% of the global population. Diagnosis can be challenging and is often delayed due to the need for advanced imaging and invasive procedures. The use of artificial intelligence applied to ECGs (ECG-AI) has been shown to detect subtle patterns in voltage-time data and may be a valuable tool for the early detection of PH. Hypothesis and Purpose: To evaluate the performance of a previously trained, ECG-AI algorithm to detect PH (ECG-AI PH) using real-world data (RWD) collected in a multicenter, validation study. A joint primary hypothesis required sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) to exceed the null values of 76%, 70%, 10% and 90%. Study Design and Methods: This retrospective validation study was conducted at 5 geographically diverse U.S. health systems. Adult subjects were eligible for inclusion if they had a 12-lead ECG paired with an echocardiogram (Echo) in which tricuspid regurgitation velocity (TRV) was recorded, following presentation with dyspnea. Patients were classified according to echocardiographic criteria as either PH (PH+, TRV >3.4 m/s) or controls (PH-, TRV ≤2.8 m/s) to simulate the real-world use of ECG-AI, where a positive result could lead to a follow-up Echo. The study database was locked before processing the digital ECGs with ECG-AI PH. Performance was also estimated in a subset of subjects that later had a right heart catheterization using mPAP ≥ 20mmHg as the definition of PH. Results: A total of 14281 subjects (53% female, 63% aged 50+ years) met the inclusion criteria, including 3019 PH+ cases and 11262 PH- controls (Figure). Sn and Sp were 84.0% (95% CI: 82.6%, 85.3%) and 71.7% (95% CI: 70.9%, 72.6%), respectively. The positive and negative predictive values were 18.9% (95% CI: 18.4%, 19.4%) and 98.3% (95% CI: 98.1%, 98.4%), respectively, at 7.3% prevalence. Each endpoint met pre-defined performance criteria. In the subset of 1683 subjects with a follow up RHC, performance remained robust (Sn 85% (1155/1358); Sp 46% (151/325)). Conclusion: While ECG-AI PH was first developed as an investigational tool to detect PH, continued development as software as a medical device for clinical use demonstrated that the algorithm retained strong performance to detect PH in diverse, non-overlapping clinical settings and patient populations.

Background: Transvenous lead extraction (TLE) is the standard of care for cardiac implantable electronic device (CIED) infections. Data regarding the optimal timing of CIED reimplantation after TLE are not well established. Objective: This study aims to assess the 5-year outcomes of early (≤7 days) versus non-early (>7 days) CIED reimplantation following TLE for CIED infection using a multi-national database. Methods: Using the TriNetX Analytics Research Network, we included patients aged ≥18 years who underwent TLE for CIED infection between 1/1/2014 and 1/1/2020. Patients were further categorized into two groups: early CIED reimplantation (≤7 days from TLE) and non-early CIED reimplantation. Propensity score matching (PSM) was performed by including patient demographics, LVEF, cardiac comorbidities and medications. The study outcomes included all-cause mortality and cardiac adverse events during a 5-year study period. Results: A total of 1668 patients in the early CIED reimplantation group and 1550 in the non-early group were identified. After PSM, 1327 patients in each group were analyzed. Compared to non-early group, early CIED reimplantation group was associated with significantly higher odds of all-cause hospitalization (odds ratio [OR]: 1.837, 95% confidence interval [CI]: 1.532-2.203) and repeated device infection (OR: 1.569, 95% CI: 1.314-1.873) at 5-year follow-up. However, no significant differences were observed in all-cause mortality (OR: 0.927, 95% CI: 0.778-1.104), HF exacerbation (OR: 1.021, 95% CI: 0.855-1.218), cardiac arrest (OR:0.924, 95% CI: 0.739-1.157), stroke (OR: 1.169, 95% CI: 0.915-1.494), cardiac thrombus (OR: 1.163, 95% CI: 0.749-1.808), major bleeding (OR: 1.079, 95% CI: 0.857-1.358) and venous thromboembolism (OR: 0.923, 95% CI: 0.759-1.123) between the two groups. Conclusion: Early reimplantation of CIED following TLE of infected devices was associated with worse outcomes in all-cause hospitalization and repeated device infection. Further large prospective studies are needed to define the optimal timing of device reimplantation.

Background: The progression of CHF after MI has been traditionally evaluated by serial changes in EF. However, mechanical parameters can provide a greater insight into cardiac function. Wall strain measures myocardial deformation, and reflects contractile function as a percentage change in length. Wall stress represents the force per unit area on the myocardium, as an evaluation of LV afterload. The relationship between wall stress and wall strain is termed Young’s modulus, and it represents cardiac elasticity. This study leverages in-vivo Young’s modulus analysis derived from cardiac MRI, which has the potential to quantify the extent of myocardial remodeling, and aid in early detection of heart failure progression. Hypothesis: We hypothesize that Young’s modulus offers a more detailed assessment of regional wall motion abnormality than conventional imaging measures alone. Methods: Male Yucatan mini-swine underwent 90-minute balloon occlusion-reperfusion of the left anterior descending coronary artery to induce MI (N=13). Cardiac MRIs were obtained at baseline and 1-month post-MI. Cardiac wall stress and wall strain were calculated separately in the anteroseptal (infarcted) and inferolateral (non-infarcted) regions, and in the longitudinal and circumferential fiber orientations. These measurements were correlated to determine the Young’s modulus of the LV. Results: Anteroseptal and inferolateral longitudinal Young’s modulus increased from 28.01±8.14 to 67.14±15.08 kPa (p < 0.05) from 13.88±1.92 to 38.80±7.29 kPa (p < 0.001), respectively. Anteroseptal and inferolateral circumferential Young’s modulus increased from 34.61±10.33 to 119.17±30.94 kPa (p < 0.05) and from 16.77±1.32 to 58.76±18.98 kPa (p < 0.001), respectively. The regional changes were accompanied by a decrease in EF from 60.6±1.5 to 50.9±3.3% (p < 0.01). Discussion: Our findings show that Young’s modulus is a valuable parameter in quantifying regional changes that occur with LV systolic dysfunction after ischemic insult; specifically that regional abnormalities occur in the non-infarcted area as well as the infarcted area––a change that would not be picked up by global LV EF. Thus, quantifying regional and directional cardiac elasticity non-invasively is a novel parameter that warrants further study. Prior research has explored the in-vitro characteristics of cardiac elasticity, but there is limited research that details the in-vivo changes within any disease affecting myocardial fiber contractility.

Kounis syndrome (KS) is a dangerous and rare acute coronary syndrome elicited in the setting of an allergic, hypersensitivity, or anaphylactic reaction. The syndrome is caused by mast cell activation leading to a release of proinflammatory mediators that can promote coronary vasospasm, atheromatous plaque erosion with rupture, or both. We present the case of a 48-year-old female with a past medical history of type 2 diabetes, hypertension, and chronic kidney disease stage 3 who presented via ambulance with anaphylaxis following an unknown allergen exposure. She was immediately given intramuscular epinephrine with resolution of symptoms, but she continued to have chest discomfort with radiation to her back. Initial EKG showed deep ST depressions in numerous leads (mainly the inferior and anterolateral leads) with ST elevations in leads V1 and aVR, consistent with diffuse subendocardial ischemia (Figure 1). Initial troponin was 2,122 which peaked at 5,328. Coronary angiogram was immediately obtained which showed patent coronary arteries with minimal narrowing of the distal left anterior descending artery. Because of this, cardiac MRI was obtained which showed subendocardial delayed enhancement at the basal and mid left ventricle with associated subendocardial perfusion defects and myocardial edema. These were felt to be in the distributions of the left circumflex and left anterior descending arteries and likely due to vasospasm, so the patient was initiated on diltiazem. Allergy evaluated the patient and felt her symptoms represented KS. They recommended outpatient workup to identify an allergy trigger and discharge with an epinephrine pen. KS is a rare presentation of acute coronary syndrome in the setting of an allergic, hypersensitivity, or anaphylactic reaction. Clinicians must be aware of this phenomenon to be able to promptly diagnose and evaluate these patients as late diagnosis can lead to significant morbidity and mortality.

Background: Catheter ablation of frequent premature ventricular complexes (PVCs) has been demonstrated to improve left ventricular ejection fraction (LVEF) in patients with PVC-induced cardiomyopathy. However, this improvement is not uniformly observed across all patients. Objective: To identify predictors of LVEF improvement following catheter ablation. Methods: This retrospective analysis included adult patients (≥18 years) who underwent PVC catheter ablation at Mayo Clinic, Rochester, between 2021 and 2024. Patients were grouped based on whether they experienced an LVEF improvement of ≥5%. Data on baseline comorbidities,, ECG characteristics, baseline transthoracic echocardiography (TTE), procedural details, and follow-up outcomes at 3-6 months (via Holter monitoring and TTE) were collected. Propensity matching (1:1) was performed using age(caliper=5), sex, and baseline LVEF(caliper=5). Comparative analyses used chi-square and t-tests. Variables with a p-value <0.1 were included in multivariate regression analysis. Results: After propensity matching, 98 patients with LVEF improvement and 98 controls were included. Table 1 summarizes baseline and procedural characteristics, and outcomes. Immediate PVC suppression was more common in the EF improvement group (74.2% vs. 60.4%, p=0.04), and fewer patients in this group were placed on long-term anti-arrhythmic medications (11.2% vs. 27.8%, p<0.01). Multivariate analysis showed that patients without PVC-related symptoms (OR=3.16, p=0.038) had higher odds of LVEF improvement, while those with CKD (OR=0.36, p=0.007) or a coupling interval ≥500 ms (OR=0.38, p=0.002) had lower odds of improvement.

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in women. Although the role of sex-hormones in the pathogenesis of SCAD is unclear, menopausal hormone therapy (HT) after SCAD is generally dissuaded. This limits management options for women with menopausal symptoms, the burden of which among SCAD patients is unknown. Aims: To quantify the burden of menopausal symptoms among women with a history of SCAD. Methods: We surveyed 1617 participants in the Mayo Clinic SCAD "Virtual" Multi-Center Registry on the topic of menopausal symptoms. Among women who had completed key portions of the survey (N = 846), 666 were identified as being either peri or post-menopausal based on patient report. Results: Menopausal symptom prevalence was high in women with SCAD (Figure). Many women (45%) experienced weight changes in the prior 6 months, and most (75%) never used HT for their menopausal symptoms. Forty-five (6%) women experienced menopause at age 45 or younger, and five (1%) experienced menopause at 40 or younger. At the time of the survey, intravaginal estrogen (11.4%) was the most common HT used, while all other individual HT therapies were used by fewer than 5%. Conclusions: Peri- and postmenopausal women with SCAD experience a high burden of menopausal symptoms, and very few use HT outside of intravaginal estrogen. These findings highlight the need for further exploration of treatment strategies for women with menopausal symptoms following SCAD including assessment of benefits versus harms in the subset of women with premature menopause.

Introduction: Older age and multimorbidity observed in individuals with dementia may impact both the care they receive and their outcomes in the setting of acute coronary syndrome (ACS). We conducted an analysis of ACS hospitalizations in the US to examine whether disparities exist between patients with and without dementia in percutaneous coronary intervention (PCI) use and ACS-related outcomes after accounting for age and comorbidities. Methods: We used the Nationwide Readmissions Database 2021 to identify adults hospitalized with a primary diagnosis of ACS, including STEMI and NSTEMI. Propensity scores for dementia were calculated using 33 baseline characteristics, including age, sex, insurance, income, hospital characteristics, Charlson comorbidity index, and other relevant comorbidities. We performed 1:1 nearest-neighbor matching with a caliper of 0.2 standard deviations. After matching, we compare the following outcomes of people with and without dementia: receipt of PCI, mechanical complications of ACS, cardiogenic shock, mechanical circulatory support, inpatient mortality, length of stay, and hospitalization cost, and reported odds ratios or mean difference, 95% confidence interval, p-value. Survey weights were applied to ensure national representativeness. Results: Among 295,396 patients hospitalized with ACS, 7,143 had dementia. After matching, 7,142 patients with and without dementia were identified for analysis ( Figure 1 ). Covariate balance was achieved (all standardized mean differences <.1). Patients with dementia were 28% less likely to undergo PCI (0.72 [0.67–0.77], p<.001) and 78% more likely to develop cardiogenic shock (1.76 [1.58–1.95], p<.001), 82% more likely to require mechanical circulatory support (1.82 [1.61–2.05], p<.001), and 16% more likely to die during hospitalization (1.16 [1.04–1.30], p<.01) ( Figure 2 ). No significant difference was observed in mechanical complications of ACS (0.89 [0.33–2.33], p=.81). Patients with dementia had longer hospital stays (9.27 vs. 5.89 days; mean difference 3.38 [3.06-3.7] days, p<.001) and higher hospitalization costs ($182,649 vs. $130,233; mean difference $52,416 [$44,618- $60,215], p<.001). Conclusion: In this analysis of US hospitalizations for ACS, dementia was independently associated with lower PCI rates and worse ACS-related outcomes despite accounting for age and comorbidities. Further research is needed to understand and address these inequities in ACS management in patients with dementia.

Background: Calcific aortic valve stenosis (CAVS) is characterized by the progressive accrual of aortic valvular calcium (AVC), resulting in impaired valvular compliance and mechanics and impaired cardiac function leading to heart failure (HF). In a phase 2 trial of 23 patients with moderate CAVS, ataciguat (ATA), a soluble guanylate cyclase activator, relative to placebo slowed the deposition of AVC, decreases in aortic valve area (AVA; by continuity equation), and increases in diastolic dysfunction and left ventricular (LV) mass. ATA may have other favorable effects on ventricular, valvular, and/or vascular pathophysiology relevant to patients with CAVS. Hypothesis: We hypothesized that slowing the rate of AVC deposition is associated with improvements in valvular compliance and in measures of cardiac structure and function. Methods: A phase 2 study randomized patients with moderate CAVS 1:1 to receive ATA 200 mg/day or placebo for up to 12 months (NCT02481258). The primary endpoint was change in AVC assessed by cardiac CT, and measures of aortic valve function and cardiac structure and function were also assessed. AVA was calculated by the Modified Gorlin (Hakki) equation to additionally assess valvular compliance. Correlations between AVC, AVA, and other measures of cardiac structure and function were assessed by exploratory linear mixed models. Results: Changes in AVC from baseline were negatively correlated with changes in AVA (slope = −0.0002 [95% CI −0.0004, 0.0001]; Figure 1), such that patients with the least AVC deposition had minimal changes in AVA. Reciprocally, changes from baseline in AVA were positively correlated with changes in cardiac output (CO; slope = 0.16 [95% CI 0.13, 0.18]; Figure 2). Treatment with ATA, compared with placebo, was associated with improvements in systolic function. Changes in AVC deposition correlated with changes in CO (slope = −0.0007 [95% CI −0.0021, 0.0008]; Figure 3), and measured improvements in CO were generally more observed in patients with less of an increase in AVC, which were more frequently observed in those treated with ATA compared with placebo. Conclusions: These data suggest that slowing the rate of AVC deposition with ATA may result in improvements in CO through improved myocardial function and valvular compliance. Larger controlled trials are needed to assess such favorable myocardial/valvular effects that may help to preserve functional capacity and slow progression to HF.

Background: Resistant hypertension (RH), defined as uncontrolled blood pressure (BP) despite ≥3 antihypertensive agents at maximally tolerated doses, remains a significant therapeutic challenge. Device-based renal denervation (RDN), using either radiofrequency (RF) or ultrasound (US) ablation, has shown promise in reducing BP. While both methods have demonstrated efficacy versus sham controls in randomized controlled trials (RCTs), direct comparisons remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of RF- and US-based RDN in patients with resistant hypertension. Methods: Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through April 2025 for RCTs comparing RDN versus sham in RH. Eligible trials reported systolic or diastolic BP outcomes via ambulatory, office, or home measurements. Pooled mean differences (MD) and risk ratios (RR) were calculated using a random-effects model. Subgroup analyses were conducted by RDN modality and follow-up duration. Results: Seventeen RCTs met inclusion criteria. RDN significantly reduced ambulatory systolic BP (MD: −3.14 mmHg; 95% CI: −5.30 to −0.98; p=0.004) and diastolic BP (MD: −1.40 mmHg; 95% CI: −2.45 to −0.35; p=0.009) compared to sham. RF-based RDN showed consistent statistically significant reductions in both SBP and DBP across ambulatory and in-office measurements. In contrast, US-based RDN demonstrated variable efficacy, with only daytime DBP showing a marginal benefit (MD: −1.32 mmHg; p=0.04). Safety outcomes, including mortality, acute kidney injury, hypertensive crisis, and hypotension, were similar between groups. Conclusion: RDN offers a significant BP-lowering effect in resistant hypertension, with RF-based RDN yielding more consistent benefits across diverse measurement settings. US-based RDN showed limited but promising effects. Both techniques demonstrated acceptable safety profiles. Further head-to-head trials are needed to confirm long-term comparative effectiveness.

Background: Subaortic membrane (SAM) is a fibromuscular ridge beneath the aortic valve that causes fixed left ventricular outflow tract (LVOT) obstruction. Surgical resection is the standard treatment for symptomatic patients or those with high gradients; however, recurrence occurs in up to 14% of adults within 5 years. While radiofrequency ablation (RFA) is well-established in arrhythmia management, its role in treating SAM has not been previously described. Case Information: 53-year-old man with HTN, BMI 51.7, and well-controlled OSA presented with worsening exertional dyspnea and fatigue in April 2024. He had prior surgical SAM resection in 2018, complicated by third-degree AV block requiring pacemaker implantation. Follow-up echocardiography revealed SAM recurrence with peak LVOT gradient of 52 mmHg. Given elevated surgical risk, a novel catheter-based RFA approach was pursued. In July 2024, the patient underwent catheter-based RFA under general anesthesia. A ThermoCool SmartTouch SF catheter was advanced retroaortically across the aortic valve toward the subaortic ridge, guided by CARTO 3 with CartoSound. A semi-circular lesion set was delivered to the septum inferior to the membrane. Two steam pops occurred during ablation in this area. Serial transthoracic echocardiograms at 3 and 8 months demonstrated sustained LVOT gradient reduction, from 52 mmHg pre-ablation to 49 mmHg and 38 mmHg, respectively. Left ventricular ejection fraction (EF) remained stable at 61%, with no new wall motion abnormalities or pericardial effusion. The patient reported marked improvement in symptoms and normalization of daily activity tolerance. No procedural complications or hospital readmissions occurred. Decision-Making: Given the patient’s high surgical risk and recurrent symptoms, the multidisciplinary team determined that repeat sternotomy carried elevated morbidity. RFA offered a targeted, minimally invasive solution that leveraged electrophysiology tools and preserved structural integrity while maximizing safety. Conclusions: This first-in-human case illustrates the feasibility of intracardiac RFA for recurrent SAM. The patient experienced sustained LVOT gradient reduction, preserved EF, and marked symptomatic improvement. This novel approach may offer a viable option for select patients with recurrent subaortic obstruction and prior sternotomy, warranting further investigation to define lesion durability, depth of tissue effect, and conduction system safety.