Hearts, Volume 7, Issue 2 (June 2026) – 10 articles

Background: Unhealthy alcohol use may lead to arrhythmia and cardiomyopathy, but its impact on sudden death is not well understood. Objective: To investigate the association of unhealthy alcohol use with sudden death. Methods: We conducted a case-control study in Wake County, a large (~1 million inhabitants), diverse county in North Carolina. We screened and adjudicated victims of sudden, unexpected, out-of-hospital deaths in adults aged 18–64 years reported by emergency medical services between 2013 and 2015. We randomly selected sex- and age-matched control patients from a university health system from the same county and time period. Characteristics of sudden death victims and controls were ascertained via standardized chart reviews. Unhealthy alcohol use was identified via chart review and was defined as any evidence of excessive alcohol use, such as it being stated in the social history or medical history, alcohol abuse being listed as a possible contributor to death, or alcohol-related diagnoses. We used logistic regression to estimate odds ratios (ORs) for the association of unhealthy alcohol use and sudden death, adjusting for age, sex, race, and other psychiatric diagnoses, including depression, anxiety, schizophrenia, bipolar disorder, and substance use disorders other than tobacco and alcohol. We also calculated the E-value to estimate the impact of any unmeasured confounders. Results: We identified 399 sudden death victims, of whom 374 (94%) had alcohol use data available. Among these 374 included victims, 256 (68%) were male, and 239 (62%) were White, with a median age at death of 55 years (IQR 48, 60). The demographic characteristics of the 1114 matched controls were similar to those of sudden death victims. Unhealthy alcohol use was present in 115 (31%) sudden death victims and 27 (2%) controls. In analyses adjusted for demographics only, unhealthy alcohol use was associated with a higher incidence of sudden death, with an OR of 17.5 (95% CI 11.4, 27.8). When further adjusted for other psychiatric diagnoses, the OR was 11.2 (95% CI 7.1, 18.0). The calculated E-value was 21.8, meaning an unmeasured confounder would need to be associated with both unhealthy alcohol use and sudden death by 21.8-fold to explain away the observed OR. Conclusions: Unhealthy alcohol use was strongly associated with higher sudden death risk in working-age adults. Our calculated E-value indicates it is unlikely that any unmeasured confounders alone would account for the observed association. Our findings suggest that interventions to reduce unhealthy alcohol use may be an effective strategy to prevent sudden death in working-age adults. Full article

Background: Regular physical activity induces physiological cardiac remodeling (“athlete’s heart”), which may overlap with pathological hypertrophy. Regional echocardiographic and electrocardiographic data among young African adults are limited. This study evaluated how graded physical activity relates to cardiac structure and function among university students in Ghana. Methods: In this comparative cross-sectional study, 174 apparently healthy students aged 18–30 years were categorized into four physical activity groups in the preceding six months: level 1, no regular exercise (n = 29, 16.7%); level 2, <30 min/day of exercise (n = 41, 23.6%); level 3, 30 to 60 min/day of moderate exercise (n = 29, 16.7%); and level 4, >1 h/day of vigorous exercise (n = 75, 43.1%). Anthropometry, blood pressure, 12-lead electrocardiography, and comprehensive transthoracic echocardiography were obtained. Cardiac indices were compared across activity levels using the Kruskal–Wallis or Welch’s ANOVA test, with post hoc comparisons and regression analyses performed where appropriate. Results: Participants were predominantly male (56.3%), with a mean age of 22.3 ± 3.50 years, BMI of 23.0 ± 4.39 kg/m², systolic blood pressure of 118 ± 13.0 mmHg, diastolic blood pressure of 71.3 ± 9.11 mmHg, and heart rate of 66.9 ± 10.9 bpm. Compared with sedentary participants, those in level 4 had a higher IVSd (9.87 ± 1.61 vs. 8.17 ± 1.47 mm, p < 0.001), LVIDd (43.6 ± 6.96 vs. 40.2 ± 3.58 mm, p = 0.002), LVPWd (10.1 ± 1.95 vs. 8.91 ± 1.60 mm, p = 0.003), and LVM (54.6 ± 7.45 vs. 47.1 ± 6.57 g, p < 0.001). EDV and ESV also increased with activity (90.1 ± 24.8 vs. 69.7 ± 17.8 mL, p < 0.001; 32.4 ± 12.8 vs. 25.6 ± 6.52 mL, p = 0.023). Systolic function was preserved across groups, with an EF of 59.3 ± 4.86% in level 4 vs. 58.3 ± 5.34% in level 1 (p = 0.707). Level 4 participants had a higher SV (57.6 ± 16.7 vs. 46.3 ± 10.4 mL, p = 0.003), CO (3.83 ± 1.17 vs. 3.05 ± 0.70 L/min, p = 0.022), and CI (2.19 ± 0.66 vs. 1.77 ± 0.37 L/min/m², p = 0.015). Bradycardia was most frequent in level 4 (35.8% vs. 18.2% in level 1, p = 0.041), and PR interval was longer in participants exercising ≥30 min/day than in those exercising <30 min/day (166 ± 23.2 vs. 162 ± 21.8 ms, p = 0.031). Conclusions: In young African university students, greater physical activity was associated with mild physiological remodeling, including a higher left ventricular wall thickness, cavity size, and mass, while systolic and diastolic indices remained preserved. The mean values in the most active group were 9.87 mm IVSd and 10.1 mm LVPWd with preserved EF, supporting activity-related adaptation rather than overt pathological hypertrophy and highlighting the need for population-specific cardiovascular interpretation. Full article

Background: Obesity and metabolic syndrome (MS) often co-exist; however, these conditions can exist independently as metabolically healthy obesity (MHO) and as metabolic obesity (MO). Methods: We investigated the association between metabolic status and body weight and risk of obstructive angiographic coronary artery disease (CAD), long-term major adverse cardiovascular events (MACEs), and all-cause mortality in women with signs/symptoms of ischemic heart disease (IHD) enrolled in the original cohort of the Women’s Ischemia Syndrome Evaluation (WISE) study (1997–2001) followed for mortality for a median of 8.6 years (range: 0–11.3 years). Normal weight (NW) was defined as a body mass index (BMI) < 25 kg/m², overweight (OW) was defined as a BMI of 25–29 kg/m², obesity (O) was defined as ≥30 kg/m². MS was defined according to the NCEP ATP III Harmonized definition, metabolically healthy (MHO) was defined as obesity in the absence of MS, and MO was defined as MS in NW individuals. Results: 503 women were evaluated including 20.7% MH-NW, 14.7% MH-OW, 8.5% MHO, 6.2% MO, 21.9% MS-OW, 28.0% MS-O. Compared to MH-NW (reference), MHO was associated with a lower risk of MACEs (aHR 0.50; 95% CI 0.29, 0.85, p = 0.011) and mortality (aHR 0.50; 95% CI 0.27, 0.95, p = 0.035). MO was associated with higher odds of obstructive CAD (aOR 2.10; 95% CI 1.33, 3.33, p = 0.002) and a higher risk of MACEs (aHR 1.67, 95% CI 1.07, 2.59, p = 0.023). Conclusions: In women with suspected IHD, compared with MH-NW, MHO was associated with a lower risk of MACEs and mortality, whereas MO had higher odds of obstructive CAD and a greater MACE risk. These findings challenge simplistic BMI-based risk paradigms and emphasize the benefits of using metabolic status assessment over weight alone. Full article

Cardiovascular disease is traditionally interpreted through macrocirculatory parameters such as cardiac output, vascular resistance, and epicardial coronary anatomy. However, clinical outcomes frequently diverge from predictions based solely on these indices, particularly in syndromes such as heart failure with preserved ejection fraction (HFpEF), cardiogenic shock, and sepsis-associated myocardial dysfunction. Increasing evidence suggests that the integrity of the microvascular–immune interface plays a central role in determining tissue perfusion and cardiovascular resilience. This review proposes a staged framework of cardiovascular decompensation centered on progressive failure of this interface. In Stage 1, chronic cardiometabolic and inflammatory stress produces a primed but compensated microvascular state characterized by endothelial activation, glycocalyx vulnerability, pericyte remodeling, platelet sensitization, and reduced lymphatic reserve. Perfusion is preserved at rest, but vasodilatory reserve and microvascular stability are reduced, narrowing the effective perfusion window under physiologic stress. In Stage 2, acute insults such as infection, ischemia, or neurohumoral activation precipitate threshold instability within the microcirculation. Perfusion becomes governed by the arterial pressure–critical closing pressure (Pa − Pcrit) relationship rather than traditional arterial–venous gradients. As this window narrows, segmental capillary derecruitment and heterogeneous flow emerge, producing loss of hemodynamic coherence in which systemic blood pressure and cardiac output may appear preserved despite impaired tissue perfusion. In Stage 3, inflammatory amplification and immunothrombotic processes consolidate microvascular dysfunction. Pericyte contraction, endothelial injury, cytokine escalation, and neutrophil extracellular trap formation promote platelet–fibrin deposition and capillary obstruction, transforming reversible conductance failure into structural microvascular impairment. This framework provides a unifying physiologic lens for diverse cardiovascular syndromes, including Type 2 myocardial infarction, HFpEF decompensation, and cardiogenic shock. It also suggests that therapeutic efficacy may depend less on macrocirculatory normalization alone and more on preserving microvascular integrity before immunothrombotic consolidation occurs. Although this model remains hypothesis-generating, it highlights the microvascular–immune interface as a central determinant of cardiovascular stability and a potential target for future precision hemodynamic and immunomodulatory strategies. Full article

Background: Traditional intraoperative sizing for sutureless aortic valves, such as the Corcym Perceval Plus (CPP), often relies on subjective tactile feedback, which can lead to excessive over-sizing. Significant over-sizing is associated with complications like increased trans-prosthetic gradients, valve thrombosis, and conduction disturbances requiring permanent pacemakers. This study aims to develop an AI-driven predictive recommendation system using Multidetector Computed Tomography (MDCT) data to optimize valve sizing and improve patient outcomes. Methods: Data were collected from 380 consecutive patients who underwent aortic valve replacement with a CPP prosthesis between 2011 and 2026. Two machine learning models were trained using preoperative MDCT features, including annular area, perimeter, and diameters. The first model predicted “normal” clinical labels, while the second used “penalized” labels adjusted for postoperative hemodynamic performance to discourage over-sizing. The dataset was split into training (80%) and testing (20%) subsets. Results: The mean patient age was 77.6 years. The model using normal labels achieved an overall accuracy of 91.84% (68.75% on the test set). The penalized label model showed improved performance with an overall accuracy of 92.89% (72.16% on the test set). MDCT provided highly reproducible objective metrics superior to echocardiography for calculating optimal sizing. Conclusions: The AI-driven recommendation system proves to be a reliable and reproducible tool for preoperative planning. By transitioning from subjective tactile assessment to predictive modeling, surgeons can better select valve sizes that minimize complications, particularly in minimally invasive approaches. Full article

Background/Objectives: Intraoperative methadone has emerged as a significant pharmacological strategy in cardiac surgery to improve postoperative analgesic outcomes and reduce the reliance on rescue short-action opioids. This review aims to synthesize evidence regarding the safety and efficacy of intravenous methadone compared to other strategies for postoperative pain control in adult and pediatric cardiac surgeries. Methods: This narrative review relied on electronic searches in PubMed, Web of Science, Cochrane Library, and EMBASE up to January 2026. From 199 articles retrieved, 41 were included, focusing on analgesic efficacy, safety, pharmacokinetic variations during cardiopulmonary bypass (CPB), and cost-effectiveness. Results: The implementation of methadone results in up to 70% reduction in postoperative opioid requirements. Patients experience significantly lower pain scores from 24 to 72 h and improvement in satisfaction regarding pain management. In pediatric populations (neonates and children), the use of methadone leads to a significant reduction in opioid needs and a high rate of extubation in the operating room. Pharmacokinetically, a 48% drop in methadone concentration occurs during CPB due to hemodilution and sequestration. Safety data confirms that intraoperative use does not prolong mechanical ventilation; however, doses exceeding 0.25 mg/kg are linked to an increased incidence of delirium. Economically, methadone can be cost-effective, resulting in savings of up to $6355 per patient. Conclusions: Intraoperative methadone improves postoperative analgesia, opioid consumption, patient satisfaction, and costs after cardiac surgery. Its opioid-sparing effects make it particularly attractive for ERAS protocols, although vigilance against dose-related delirium and QT prolongation remains essential. Further research, especially in pediatrics, is needed to refine dosages and safety protocols. Full article

Background: Cardiomyopathy is a major cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). We evaluated whether N-terminal pro–brain natriuretic peptide (NT-proBNP) identifies severe systolic dysfunction and assessed its diagnostic performance. Methods: Male patients with genetically confirmed DMD and established cardiomyopathy were included if NT-proBNP measurement and echocardiographic ejection fraction (EF) were available within one month. Severe systolic dysfunction was defined as EF < 40%. Clinical, cardiac, and respiratory variables were analysed. ROC analysis with bootstrap validation and exploratory logistic regressions was performed. Results: NT-proBNP levels were significantly higher in patients with EF < 40% (median 843 vs. 81 pg/mL). A cut-off >200 pg/mL identified severe systolic dysfunction with 90.5% sensitivity and 90.9% specificity (AUC 0.96, 95% CI 0.88–1.00). During 24 months of follow-up, five deaths occurred. NT-proBNP showed moderate discrimination for mortality (AUC 0.79) and was associated with mortality in exploratory analysis. Conclusions: NT-proBNP was associated with severe systolic dysfunction in Duchenne cardiomyopathy and may complement imaging. Prospective validation is warranted. Full article

We describe the case of a 26-year-old man who presented with acute chest pain and was found to have single-vessel coronary occlusion most consistent with probable paradoxical embolism. Coronary angiography demonstrated complete occlusion of the ramus intermedius artery. Aspiration thrombectomy restored flow without stent implantation. Intravascular ultrasound showed no plaque rupture, atherosclerosis, or coronary dissection, supporting but not definitively confirming an embolic etiology. Transthoracic and transesophageal echocardiography subsequently identified a large patent foramen ovale with bidirectional shunting. Lower-extremity Doppler studies and an extensive hypercoagulable evaluation were negative. The patient later underwent successful percutaneous closure of the patent foramen ovale. This case highlights probable paradoxical coronary embolism as a rare cause of acute myocardial infarction in a young patient without significant atherosclerotic disease and underscores the value of multimodality imaging in supporting the diagnosis and guiding management. Full article

Background/Objectives: Twiddler’s syndrome is an uncommon but clinically important complication of implantable cardiac devices, in which generator rotation within the pocket results in lead torsion, lead retraction, and device malfunction. Recurrence can necessitate repeated surgical intervention and may be preventable through early risk identification and procedural strategies. Methods: We describe a single-centre case series of three female patients with pacemaker-associated Twiddler’s syndrome. Clinical presentation, timing of lead retraction, management strategies (including pocket location and fixation approach), recurrence, and follow-up outcomes were reviewed. Results: All patients were older women and developed symptomatic device failure early after implantation, with radiographic confirmation of lead retraction and coiling occurring within three weeks in all cases. Recurrence was observed when enhanced preventive measures were not employed. Notably, in one patient, recurrence occurred after an initial revision in a second prepectoral pocket, prompting subsequent reimplantation in a subpectoral location with reinforced fixation and structured patient and family counselling, after which no further recurrence occurred at one year. In the remaining cases, revision with reinforced generator fixation and counselling was associated with stable lead position and satisfactory device function during follow-up. Conclusions: Twiddler’s syndrome most commonly presents in the first weeks following implantation. Proactive identification of at-risk patients and consideration of reinforced fixation and pocket strategies at the index procedure may reduce recurrence and avoid repeat interventions. Full article