AIM:The American College of Cardiology/American Heart Association Scientific Statement, "Clinical Considerations for the Care of the Tactical Athlete With Cardiovascular Abnormalities," was written to provide guidance and education for clinicians caring for the tactical athlete (ie, firefighters, law enforcement officers, military) with cardiovascular disease or risk for cardiovascular disease, and for the organizations overseeing the care and wellness of these athletes. The considerations are shaped by the interaction between occupational demands and fit for full duty assessments, including risk discussions about how a cardiovascular event in a tactical athlete could impact teammates' well-being, community safety, and overall mission success. METHODS:This scientific statement is organized into 11 sections focused on cardiovascular disease processes and other topics that are relevant when considering the potential risks and benefits of performing tasks specific to the tactical athlete. Task forces, comprised of experts in tactical athlete domains, sports cardiology, and the respective topics covered, were assigned to each section, and specific "Clinical Considerations Tables" for clinicians to reference were prepared. Comprehensive literature reviews and an emphasis on tactical athlete-focused data, as available, were integral in the writing of all clinical considerations presented. The framework mirrors that of the recently published, "Clinical Considerations for Competitive Sports Participation for Athletes With Cardiovascular Abnormalities: A Scientific Statement From the American Heart Association and American College of Cardiology." STRUCTURE:The specific sections in this document include: Section 1: Tactical Tasks Classification; Section 2: The Tactical Athlete Preparticipation Cardiac Evaluation; Section 3: Ethical and Legal Aspects of Tactical Clinical Management; Section 4: Genetic Cardiomyopathies; Section 5: Myocarditis and Other Acquired Cardiac Conditions; Section 6: Congenital Heart Disease; Section 7: Aortopathy, Bicuspid Aortic Valve, and Spontaneous Coronary Artery Dissection; Section 8: Syncope, SCA, Arrhythmias, and Devices; Section 9: Cardiac Channelopathies; Section 10: Older Tactical Athlete; Section 11: Environmental Exposures, PED/S, and Additional Cardiac Conditions and Considerations. Each section provides a summary detailing the rationale for key clinical considerations and the respective Clinical Considerations Table(s).
BACKGROUND:The impact of recent trends in the burden of myocarditis has not been reported in detail. OBJECTIVES:This study aims to estimate the global, regional, and national burden of myocarditis from 1990 to 2023, using data from the GBD (Global Burden of Disease, Injuries, and Risk Factors Study) 2023. METHODS:As part of the GBD 2023, the authors used all available administrative health facility and vital registration data to estimate myocarditis prevalence, incidence, disability-adjusted life years (DALYs), mortality, and mortality-to-incidence ratio (MIR) for every country, stratified by age, sex, and quintiles of a Socio-demographic Index (SDI). The MIR represents the relative mortality burden compared with disease incidence at the population level. The prevalence of heart failure attributable to myocarditis was estimated using a model-based attribution approach. RESULTS:In 2023, the global age-standardized rates of prevalence, incidence, DALY, and mortality of myocarditis were 4.84 (95% uncertainty interval [UI]: 3.98-5.80), 12.46 (95% UI: 9.86-15.70), 8.41 (95% UI: 5.63-12.59) and 0.21 (95% UI: 0.14-0.29) per 100,000 population, respectively. Although global age-standardized prevalence and incidence rates remained stable from 1990 to 2023, the absolute number of incident cases increased by 54.28% from 0.67 million (95% UI: 0.52-0.85 million) to 1.04 million (95% UI: 0.83-1.32 million). Age-standardized DALYs and mortality rates decreased by 62.48% and 60.00%, respectively, over the same period. The MIR decreased across all age groups from 1990 to 2023 and remained highest among the youngest and oldest populations, with the ratio in those <5 years of age declining from 17.82% in 1990 to 6.32% in 2023. Across SDI strata, incidence rates remained stable from 1990 to 2023, while mortality rates declined in all quintiles and remained lowest in high SDI regions, whereas the MIR decreased from 2.33 in 1990 to 1.30 in 2023. In 2023, prevalence was highest in the high SDI quintile (6.30 [95% UI: 5.15-7.48] per 100,000 population) and lowest in the low-middle SDI quintile (4.10 [95% UI: 3.38-5.02]), reflecting disparities aligned with health resource availability. Age-standardized prevalence rates of heart failure attributable to myocarditis declined from 2.33 (95% UI: 1.90-2.90) per 100,000 population in 1990 to 1.76 (95% UI: 1.41-2.29) in 2023, with a U-shaped distribution across age groups showing the highest burden in those <5 years of age and >75 years of age in 2023. CONCLUSIONS:Although age-adjusted DALYs and mortality rates of myocarditis decreased globally from 1990 to 2023, incidence and prevalence remained stable, suggesting potential improvements in outcomes over time. However, absolute burden has grown due to population growth and aging, and important disparities persist across age groups and SDI strata. These findings highlight the need for targeted strategies to improve early diagnosis and reduce the burden of myocarditis, particularly in vulnerable populations and lower-resource settings, while being interpreted in the context of evolving diagnostic and coding practices.
BACKGROUND:Extreme temperature events are projected to increase with climate change; yet, associations of short-term heat and cold exposure with heart failure (HF) exacerbations remain incompletely characterized, especially in high-latitude settings. OBJECTIVES:The purpose of this study was to investigate the associations of short-term exposure to cold spells, heat waves, and nonoptimal ambient temperature with HF hospitalization in Sweden. METHODS:We conducted a nationwide time-stratified case-crossover study including 482,000 HF hospitalizations recorded in the Swedish National Patient Register (2006-2021). Cold spells and heat waves were defined as ≥2 consecutive days with daily mean temperature ≤5th percentile (October to March) or ≥95th percentile (April to September), respectively, using municipality-specific temperature distributions. We applied conditional logistic regression combined with distributed lag nonlinear models to estimate lag-specific (lag 0-6 days) and cumulative associations with the odds of HF hospitalization. RESULTS:During the cold season, cold spells and lower ambient temperature exposures were associated with a higher risk of HF hospitalization at lag 2 to 6 days (significant at lag 3-5 days). Cumulative associations over lag 2 to 6 days showed ORs of 1.085 (95% CI: 1.042-1.129) for cold spells and 1.008 (95% CI: 1.005-1.011) per 10-percentile-point decrease in temperature. During the warm season, higher temperature exposure was associated with higher odds at lag 1 to 3 days with attenuation at longer lags, with a cumulative association over lag 0 to 3 days (OR: 1.009; 95% CI: 1.006-1.013, per 10-percentile-point increase in temperature). Heat waves showed nonsignificant positive associations with HF hospitalizations that were more likely to capture acute exacerbations, whereas no associations were observed using the broader HF definition that included chronic conditions. CONCLUSIONS:In this Swedish nationwide study, short-term exposure to cold spells, lower temperatures, and higher temperatures was associated with a higher risk of HF hospitalization, with delayed cold effects and more immediate heat effects.
BACKGROUND:Lipoprotein(a) [Lp(a)] is a largely genetically determined causal risk factor for atherosclerotic cardiovascular disease and aortic stenosis, likely mediated in part by oxidized phospholipids (OxPL) bound to apolipoprotein(a) [apo(a)] and apolipoprotein B (apoB). Lepodisiran, an extended-duration small interfering RNA demonstrated large and durable reductions in Lp(a) in a phase 2 trial. OBJECTIVES:The purpose of this study was to assess effects of lepodisiran on OxPL-apo(a) and -apoB levels, their relationship to Lp(a) and apoB lowering, whether reductions are proportional to particle reduction, and whether changes correlate with biomarkers of systemic inflammation. METHODS:The randomized, placebo-controlled phase 2 trial enrolled 320 participants at 66 global centers. The current post hoc analysis included 213 of 320 participants who received placebo or lepodisiran 16, 96, or 400 mg at baseline and day 180 and had OxPL levels measured at baseline, day 240, and day 360. Placebo-adjusted percent change from baseline in OxPL-apo(a) and -apoB were assessed. Correlations between percent change in Lp(a), OxPL-apo(a), and -apoB were also determined. RESULTS:Median baseline OxPL-apo(a) and -apoB levels were 122.0 nmol/L (Q1, Q3: 105.1, 137.7 nmol/L) and 27.7 nmol/L (Q1, Q3: 22.5, 36.2 nmol/L) for all participants. Placebo-adjusted geometric mean percent changes in OxPL-apo(a) at day 240 were -21.9% (95% CI: -45.0% to 11.0%), -65.1% (95% CI: -73.8% to -53.6%), and -94.2% (95% CI: -95.7% to -92.2%) in the 16-, 96-, and 400-mg dose groups, respectively. Percent changes in OxPL-apoB at day 240 in these dose groups were -39.5% (95% CI: -51.2% to -25.0%), -76.9% (95% CI: -80.6% to -72.5%), and -88.5% (95% CI: -90.4% to -86.3%), respectively. The percent change in OxPL-apo(a) at day 360 were -23.7% (95% CI: -47.0% to 9.8%), -41.6% (95% CI: -56.4% to -21.6%), and -80.7% (95% CI: -85.7% to -73.9%) in the 16-, 96-, and 400-mg dose groups, respectively. The percent changes in OxPL-apoB at day 360 in these dose groups were -30.6% (95% CI: -46.4% to -10.2%), -57.1% (95% CI: -65.2% to -47.2%), and -79.9% (95% CI: -83.8% to -75.2%), respectively. Percent change in OxPL-apo(a) correlated more closely than OxPL-apoB with percent change in Lp(a) than did OxPL-apoB. There was no significant correlation between changes in high-sensitivity C-reactive protein and OxPL. CONCLUSIONS:Lepodisiran produced sustained reductions in OxPL-apoB and OxPL-apo(a) levels that correlated with Lp(a) lowering. These findings provide additional biological rationale for the ongoing lepodisiran phase 3 cardiovascular outcomes trial, but do not establish clinical benefit. (A Study of LY3819469 in Participants With Elevated Lipoprotein(a) [Lp(a)]; NCT05565742).
BACKGROUND:Although guideline-recommended intensive lipid-lowering therapy (LLT) reduces recurrent cardiovascular events after acute coronary syndrome (ACS), timely implementation of intensive LLT and achievement of low-density lipoprotein cholesterol (LDL-C) target remain suboptimal in routine clinical practice. OBJECTIVES:The purpose of this study was to determine whether a protocol-based implementation strategy improves timely achievement of guideline-recommended LDL-C target after ACS. METHODS:We conducted a cluster-randomized trial involving patients with ACS. Ten centers were randomly assigned 1:1 to protocol-based or standard lipid management. In the protocol-based group, LLT was initiated or intensified during the index hospitalization according to a prespecified algorithm based on baseline LLT status and LDL-C levels using high-intensity statins, ezetimibe, and PCSK9 inhibitors. LDL-C was reassessed at 4 weeks, with treatment escalation when indicated. In the protocol-based group, an LDL-C level of approximately 55 mg/dL was used as the protocol-specified operational threshold for intensification, whereas LDL-C <70 mg/dL was the treatment goal in both groups. The primary and key secondary endpoints were achievement of LDL-C <70 mg/dL and <55 mg/dL at 6 months, respectively. RESULTS:Between November 2024 and July 2025, 330 patients were enrolled, and 329 patients comprised the study population after 1 patient withdrew consent. The primary efficacy analysis included 315 patients with complete 6-month LDL-C data. Baseline characteristics were balanced between groups. The mean age was 69 years, 18% were women, and the median LDL-C level was 110 mg/dL. At 6 months, LDL-C <70 mg/dL was achieved in 86.4% vs 73.7% (between-group difference, 12.6 percentage points [95% CI: 3.8-21.5 percentage points]; P = 0.005); the corresponding difference was 12.8 percentage points (95% CI: -2.0 to 27.6 percentage points; P = 0.08) in a hospital-level sensitivity analysis. Similar findings were observed for LDL-C <55 mg/dL (60.8% vs 34.5%; between-group difference, 26.3 percentage points [95% CI: 18.5-34.0 percentage points]; P < 0.001). At 6 months, use of high-intensity statins, ezetimibe, and PCSK9 inhibitors was higher in the protocol-based group. CONCLUSIONS:A protocol-based implementation strategy for early intensive LLT significantly improved achievement of the guideline-recommended LDL-C target after ACS. These findings support a structured, algorithm-based care pathway to facilitate timely initiation and intensification of LLT and improve implementation of guideline-recommended lipid management in routine clinical practice. (Brief and Protocol-Based Intensive Lipid Management in Patients with Acute Coronary Syndrome; jRCT1020240029).
BACKGROUND:Following transcatheter aortic valve replacement (TAVR), subclinical leaflet thrombosis-visualized on cardiac computed tomography (CT) as hypoattenuated leaflet thickening (HALT)-is common and might be associated with thromboembolic events. OBJECTIVES:The NOTION-4 trial investigates different antithrombotic treatment strategies for the prevention of HALT. METHODS:NOTION-4 was a randomized controlled trial enrolling patients without an indication for oral anticoagulation shortly after successful TAVR. Patients were randomized to lifelong single antiplatelet therapy (SAPT) or 3 months of direct oral anticoagulant (DOAC) therapy followed by lifelong SAPT (DOAC-3m). The primary endpoint was HALT prevalence at 12 months. The trial was powered for superiority of the experimental strategy. RESULTS:Of 352 patients randomized 1:1, 5 were screen failures or withdrew consent, leaving 176 in the SAPT group and 171 in the DOAC-3m group. At 3 months, HALT was observed in 31.8% of patients receiving SAPT compared with 12.1% of those receiving DOAC-3m. At 1 year, HALT occurred in 32.2% of SAPT patients and 28.3% of DOAC-3m patients with available CT scans (risk difference: -3.9%; 95% CI: -14.4% to 6.6%; P = 0.54). The combined risk of all-cause mortality, stroke, or major/life-threatening bleeding at 12 months was 2.3% in the SAPT group vs 8.2% in the DOAC-3m group (risk difference: 5.9%; 95% CI: 1.2% to 10.6%). CONCLUSIONS:Among TAVR patients without an indication for oral anticoagulation, 3 months of DOAC therapy significantly reduced the prevalence of HALT at 3 months compared with SAPT; however, this effect was attenuated by 9 months after discontinuation of DOAC therapy. (The Nordic Aortic Valve Intervention Trial 4 [NOTION-4]; NCT06449469).
Background Vutrisiran, an RNA interference therapeutic, reduced all-cause mortality and recurrent cardiovascular events in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the HELIOS-B trial. Whether concomitant disease-modifying or heart failure therapy modifies the efficacy of vutrisiran has not been described. Objectives We aimed to characterize patterns of concomitant therapy use in HELIOS-B, describe medication initiation rates by treatment arm, and evaluate whether concomitant therapy modified vutrisiran’s treatment effect. Methods In HELIOS-B, 654 randomized patients with ATTR-CM received vutrisiran or placebo. We assessed baseline use and postrandomization initiation of tafamidis, sodium-glucose cotransporter-2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRA), beta-blockers, and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors), and used time-updated Lin-Wei-Yang-Ying models to evaluate treatment effect modification on the primary composite endpoint of all-cause mortality and recurrent cardiovascular events. Results At baseline, 40% of participants were receiving tafamidis and 77% at least 1 heart failure medication. MRAs and SGLT2 inhibitors were the most frequently initiated therapies during follow-up, with initiation rates numerically higher across all heart failure medication classes in the placebo group. There was no statistically significant evidence that the treatment effect of vutrisiran was modified by baseline or time-updated use of any medication class (P-interaction: tafamidis 0.95, SGLT2 inhibitors 0.59, MRA 0.92, beta-blockers 0.75, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors 0.82). Conclusions In HELIOS-B, there was no statistically significant evidence that the treatment benefit of vutrisiran on all-cause mortality and recurrent cardiovascular events was modified by concomitant use of tafamidis or heart failure therapies. These findings support the consistency of vutrisiran’s efficacy across the spectrum of contemporary ATTR-CM pharmacotherapy. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149)
BACKGROUND:Vutrisiran, an RNA interference therapeutic that suppresses hepatic transthyretin production, improved survival and cardiovascular outcomes in transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy). Tafamidis, a transthyretin stabilizer, also improves clinical outcomes. Although combining these therapies is mechanistically appealing, clinical evidence supporting this approach is limited. OBJECTIVES:We sought to evaluate whether the treatment effects of vutrisiran differed according to baseline tafamidis use in HELIOS-B. METHODS:In HELIOS-B, patients with ATTR-CM were randomized to vutrisiran 25 mg or placebo every 3 months for up to 36 months, with tafamidis use permitted and stratified. We assessed treatment effects according to baseline tafamidis use for the primary outcome of all-cause mortality and recurrent cardiovascular events and secondary endpoints, including individual components of the primary outcome, composite of all-cause mortality, cardiovascular events and outpatient worsening heart failure events, functional capacity (6-minute walk distance), and health status (Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OSS]). RESULTS:Among 654 participants, 259 (40%) were receiving tafamidis at baseline. Patients on tafamidis were slightly younger and had higher baseline 6-minute walk distance and higher KCCQ-OSS, while baseline characteristics were generally balanced between randomized groups. The treatment effect estimates of vutrisiran compared with placebo for the primary outcome were directionally consistent across baseline tafamidis strata (rate ratio: 0.79 [95% CI: 0.51-1.21] with tafamidis vs 0.67 [95% CI: 0.49-0.93] without), with no statistically significant interaction (Pinteraction = 0.55). Similar patterns were observed for all-cause mortality, cardiovascular events, and outpatient worsening heart failure (all Pinteraction > 0.20), although the magnitudes of the estimated effects were numerically smaller among patients receiving tafamidis at baseline. Vutrisiran preserved 6-minute walk distance in both baseline tafamidis strata (Pinteraction = 0.24), whereas improvement in KCCQ-OSS appeared attenuated among patients receiving tafamidis at baseline. CONCLUSIONS:Treatment effect estimates for vutrisiran on clinical outcomes were consistent across baseline tafamidis strata, with no statistically significant interaction according to baseline tafamidis use, with reduced effect size noted in those receiving baseline stabilizers in comparison to monotherapy. These data underscore the need for future prospective studies examining combination therapy in this population. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).
BACKGROUND:Patients with myocardial infarction and large thrombus burden face greater infarct size and higher mortality, yet no effective therapy exists for this high-risk subgroup. OBJECTIVES:To investigate the effects of stent-retriever thrombectomy in addition to conventional percutaneous coronary intervention (PCI) versus conventional PCI alone on infarct size. METHODS:In this open-label, multicenter, superiority trial, 160 patients with ST-segment elevation myocardial infarction and large thrombus burden at angiography (TIMI thrombus grade ≥3 in infarct-related artery) were consented and 156 randomly assigned to undergo stent-retriever thrombectomy followed by conventional PCI or conventional PCI alone. Primary outcome was infarct size extension assessed by area under the curve (AUC) for creatine kinase (CK)-MB. Safety outcome was major adverse cardiovascular events (MACE; comprising cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), at 3 and 30 days. RESULTS:Infarct size (CK-MB AUC) was lower in the stent-retriever group (n=78) versus the conventional group (n=76) (3965 IU/L·h; interquartile range [IQR] 2480-5092 versus 5250; IQR 3506-7449; difference -1359, 95% CI -2231 to -522; p=0.001). At exploratory cardiac magnetic resonance findings, infarct size was lower in the stent-retriever group (n=64; left ventricle, 17%; IQR 11-28) versus the conventional PCI group (n=59; 28.0%; IQR 18-33; difference -7.0, 95% CI -12 to -2.0), whereas left ventricular volumes and ejection fraction did not differ. There was no MACE at 3 days and 1 at 30 days in the stent-retriever group versus 2 and 3, respectively, in the conventional PCI group. CONCLUSIONS:Stent-retriever thrombectomy followed by conventional PCI in patients with large thrombus burden undergoing primary PCI ≤8 hours of symptom onset was associated with reduced infarct size versus conventional PCI alone.
