Search Results (1,353)

Background/Objectives: Cardiovascular toxicity and pre-existing cardiovascular disease can affect cancer-treatment tolerance, functional recovery, and survivorship. This narrative review aimed to summarize current evidence and propose an author-derived risk-adaptive clinical framework for adult cardio-oncology rehabilitation (CORE), organized around exercise prescription, multimodal monitoring, and implementation. Methods: PubMed/MEDLINE and the Web of Science Core Collection were searched from database inception through 27 July 2026. Guidelines, systematic reviews, randomized and non-randomized clinical studies, feasibility studies, and selected mechanistic sources were prioritized according to their relevance to the three review domains. Evidence was classified as direct clinical, guidance/synthesis, feasibility/implementation, or mechanistic/conceptual; no PRISMA protocol, formal risk-of-bias assessment, or meta-analysis was undertaken. Results: Clinical trials support improvements in cardiorespiratory fitness, selected cardiovascular risk factors, and functional outcomes in some settings, but effects on cancer therapy-related cardiac dysfunction, cardiovascular events, and mortality remain uncertain. Direct evidence is dominated by breast-cancer cohorts and women, although mixed-cancer, lymphoma, and lung-cancer studies broaden the functional evidence base. An evidence-informed approach is to individualize aerobic and resistance exercise to treatment context, symptoms, functional capacity, and clinical stability, with reassessment linked to actionable findings; the proposed pathway remains conceptual and non-validated. Artificial intelligence, digital twins, omics, and monitoring-guided exercise-dose adjustment remain investigational. Conclusions: CORE is best regarded as exercise-centered care linked to guideline-based risk assessment and clinically indicated reassessment. Prospective studies should test therapy-specific timing, risk-stratified delivery, monitoring-guided dose adjustment, clinical endpoints, equity, and cost-effectiveness. Full article

Background: Cardiac arrhythmias in children and adolescents may present with nonspecific symptoms such as precordial pain, palpitations, and syncope. We evaluated the clinical characteristics and rhythm findings of symptomatic pediatric patients and examined cross-sectional associations between reported symptoms and selected rhythm diagnoses, with particular attention to the diagnostic and management yield of ambulatory Holter monitoring. Because symptom timing is not always captured during diagnostic monitoring, associations between reported symptoms and detected rhythm abnormalities must be distinguished from temporal symptom–rhythm correlation and causation. Methods: We conducted an observational study of 119 children and adolescents aged 1–18 years, who were evaluated at a tertiary pediatric hospital for symptoms potentially suggestive of cardiac rhythm abnormalities. Data included demographic characteristics, clinical symptoms, personal and family history, resting electrocardiography, ambulatory Holter monitoring, and exercise testing where clinically indicated. The primary analysis was cross-sectional. Because symptom timing during ambulatory monitoring was not recorded, the study was not designed to establish temporal symptom–rhythm correlation or causality. Descriptive analyses were performed for the final 119-participant cohort. Selected symptom–rhythm associations were evaluated using the contingency table methods with odds ratios (ORs), 95% confidence intervals (CIs), and Fisher’s exact tests where appropriate. Holm’s adjustment was applied to the prespecified family of reconstructed symptom–rhythm comparisons. Results were interpreted according to both statistical evidence and effect-size precision. Results: The cohort comprised 119 participants, including 75 females (63.0%) and 44 males (37.0%). The most frequently reported symptoms were precordial pain (105/119, 88.2%), palpitations (80/119, 67.2%), and syncope or lipothymia (39/119, 32.8%). A family history of sudden cardiac death was reported by 28 participants (23.5%). Forty-two participants (35.3%) had a normal resting ECG, while 77 (64.7%) underwent ambulatory Holter monitoring. Among those undergoing Holter monitoring, 65/77 (84.4%) had rhythm abnormalities detected exclusively by ambulatory monitoring and not identified on the resting ECG. Holter findings resulted in at least one documented management change in 38/77 participants (49.4%). Management categories were not mutually exclusive and included lifestyle or activity adjustment in 21 participants, initiation of antiarrhythmic therapy in 19, medication monitoring in 19, and targeted cardiac imaging, including cardiac magnetic resonance imaging, in 5. In this cross-sectional analysis, reported syncope/lipothymia was strongly associated with the presence of complete atrioventricular block (10/39 [25.6%] versus 1/80 [1.3%]; OR 27.24, 95% CI 3.34–222.29; Fisher’s exact p < 0.001; Holm’s adjusted p approximately 0.0004). The unadjusted association between syncope/lipothymia and the WPW-labelled diagnosis did not remain statistically significant after Holm’s adjustment. No statistically significant associations were identified between syncope/lipothymia and PSVT or VT. Conclusions: In this pediatric cohort, ambulatory Holter monitoring identified rhythm abnormalities not detected on resting ECG in a substantial proportion of monitored participants and resulted in documented changes in clinical management in approximately half of those monitored. Reported syncope/lipothymia was strongly associated with the presence of complete atrioventricular block in the reconstructed cross-sectional analysis. Because symptom timing during monitoring was not recorded, these findings do not establish that the detected rhythm abnormalities caused the reported symptoms or that symptoms predict future rhythm outcomes. Further studies using prospectively defined symptom–rhythm event recording and longitudinal follow-up are needed to evaluate temporal correlation and prognosis. Full article

Persistent atrial fibrillation (AF) is associated with complex structural, electrical, and functional myocardial remodeling that contributes to impaired cardiac performance, symptom burden, and adverse cardiovascular outcomes. Although restoration of sinus rhythm through electrical cardioversion remains a cornerstone of rhythm-control therapy, treatment success is traditionally defined by rhythm maintenance and recurrence rates, while myocardial functional recovery receives substantially less attention. This review aims to summarize current evidence regarding myocardial dysfunction in persistent AF, evaluate available approaches for assessing myocardial recovery after cardioversion, and explore future directions for function-guided rhythm-control strategies. A narrative review of contemporary literature was performed, focusing on studies published in major cardiovascular journals and current international guidelines. Evidence regarding myocardial remodeling, reverse remodeling after restoration of sinus rhythm, echocardiographic assessment, myocardial strain imaging, biomarker dynamics, and post-cardioversion management strategies was synthesized and critically evaluated. Persistent AF induces multidimensional myocardial dysfunction through tachycardia-mediated injury, structural remodeling, neurohormonal activation, inflammation, and fibrosis. Emerging evidence suggests that restoration of sinus rhythm may initiate a process of reverse remodeling characterized by improvements in left ventricular systolic function, global longitudinal strain, atrial mechanical performance, and biomarker profiles. Advanced echocardiographic techniques and serial biomarker assessment provide valuable opportunities to quantify myocardial recovery beyond conventional rhythm-based endpoints. However, current clinical practice and guideline-directed management remain predominantly focused on rhythm outcomes, while functional recovery is not routinely incorporated into therapeutic decision-making. Based on available evidence, a conceptual framework termed the “Post-Cardioversion Functional Window” is proposed to describe a period of potentially enhanced myocardial recovery during which systematic functional assessment may facilitate individualized management and future risk stratification. Myocardial recovery after restoration of sinus rhythm represents an underrecognized component of contemporary AF management. Integration of echocardiographic, biomarker-based, and clinical functional assessment may improve understanding of post-cardioversion remodeling and support the development of personalized rhythm-control strategies. Future prospective studies are needed to validate myocardial recovery endpoints and determine their role in guiding therapeutic decisions after cardioversion. Full article

Background: Surgical correction of severe degenerative Mitral Regurgitation (DMR) is indicated in the presence of symptoms and signs of left ventricular (LV) dysfunction. However, conventional clinical and resting echocardiographic parameters may underestimate myocardial impairment. Cardiopulmonary exercise testing (CPET) and exercise stress echocardiography (ESE) may provide a more complete functional and haemodynamic assessment. Objectives: To characterize preoperative CPET and ESE findings in patients with severe DMR and to explore, in a hypothesis-generating analysis, their association with early functional and left ventricular outcomes after surgery. Methods: We included patients with severe DMR who underwent CPET and ESE before surgery. Functional improvement was defined as an improvement of at least one NYHA class from the preoperative baseline to early follow-up. LV function was evaluated as the continuous change in LVEF from discharge to early follow-up (Delta LVEF = follow-up LVEF − discharge LVEF). Baseline parameters were compared between patients who did and did not improve functionally. Random forest analyses were used only as an exploratory secondary analysis to assess whether baseline variables showed any non-linear signal of association with the outcomes and to document the instability of variable-importance rankings. Results and Conclusions: We included 60 patients, of whom 72% were in NYHA class II and all had preserved LV function. At CPET, rest and peak oxygen uptake were 6 +/− 1.5 and 17.2 +/− 5 mL/kg/min, respectively; the VE/VCO₂ slope was 33 +/− 8.9 and the Oxygen Uptake Efficiency Slope was 1.6 (1.3–1.9). At ESE, LVOT-VTI increased from 18.3 +/− 3.9 cm at rest to 24.5 +/− 4.9 cm at peak; stroke volume from 51.0 (43.0–60.0) mL to 72.5 +/− 21.6 mL; and cardiac output from 3.8 (3.2–5.1) L/min to 9.0 +/− 3.2 L/min. No baseline clinical, CPET or ESE parameter significantly distinguished patients who improved functionally from those who did not, and early Delta LVEF was negligible. Random forest analyses did not discriminate above chance and variable-importance rankings were unstable. Patients with severe DMR and preserved LVEF showed objectively abnormal exercise responses despite mild symptoms, supporting the use of CPET and ESE for preoperative functional and haemodynamic characterization; larger prospective studies are required before any predictive or decision-support use can be proposed. Full article

Background: Device-independent, lifestyle-integrated active pursed-lip diaphragmatic breathing (PLDB) may overcome respiratory rehabilitation barriers in chronic heart failure (CHF). This retrospective real-world study evaluated its prognostic association with functional capacity, quality of life (QoL), and major adverse cardiovascular events (MACE). Methods: A total of 58 CHF patients (NYHA II–IV) were categorized by 6-month post-discharge PLDB adherence into a Respiratory Training Group (RTG; n = 20) and Control Group (n = 38). Functional, structural, QoL metrics, and MACE outcomes were analyzed. Results: After 6 months, the RTG demonstrated significant intra-group improvements in 6 min walk test (6MWT) distance (302.00 [243.60, 408.15] m to 386.00 [339.50, 439.00] m, p = 0.006; baseline-adjusted between-group gain: +76.16 m), handgrip strength (p = 0.046), LVEF (p = 0.003), and scores on the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (p < 0.001), Generalized Anxiety Disorder-7 (GAD-7) (p = 0.010), and Self-rating Somatic Symptom Scale-China (SSS-CN) (p = 0.004). Post-intervention, the RTG outperformed controls in handgrip strength (p = 0.012), MLHFQ (p = 0.001) and SSS-CN (p = 0.020). The RTG exhibited a significantly lower MACE incidence (5.0% vs. 42.1%, p = 0.003) and superior MACE-free survival (log-rank p = 0.005). Multivariable Cox regression confirmed high PLDB adherence was independently associated with a lower MACE risk (adjusted HR = 0.103, 95% CI: 0.014–0.779, p = 0.028). Conclusions: High adherence to a 6-month lifestyle-integrated PLDB program correlates with clinically meaningful improvements in exercise capacity, cardiac function, and QoL, and is independently associated with a lower risk of short-term MACE in CHF patients. Full article

Background: Heart failure is a chronic and progressive condition that substantially affects patients’ physical, emotional, social, and spiritual well-being. Although the clinical burden of heart failure is well documented, limited qualitative evidence exists regarding how Saudi adults experience and interpret the condition within their cultural, familial, and religious contexts. This study explored the experiences of Saudi adults living with heart failure and their perceptions of its impact on health-related quality of life. Methods: A qualitative descriptive study informed by an interpretivist perspective was conducted using semi-structured interviews with 25 Saudi adults diagnosed with heart failure. Participants were recruited from specialized heart failure and cardiac outpatient clinics within a tertiary medical city in Riyadh, Saudi Arabia. Interviews were audio-recorded, transcribed verbatim, and analyzed using Braun and Clarke’s reflexive thematic analysis. Results: Four themes were identified: (1) emotional distress and fear, (2) loss of independence and increased dependency, (3) social role disruption, and (4) coping and adaptation strategies. Participants described significant psychological burden, reduced autonomy, and changes in family and social roles following their diagnosis. Conclusions: Heart failure was experienced as more than a physical illness, affecting participants’ emotional well-being, social identity, family relationships, and spiritual life. The findings underscore the importance of holistic and culturally responsive care that addresses psychological, social, spiritual, and family-related needs alongside symptom management. Full article

Fibrinogen is an essential component of hemostasis and clot formation that stabilizes the platelet-dependent primary hemostatic process. Low fibrinogen levels can be primary (congenital) or secondary (acquired). Acquired hypofibrinogenemia may result from chronic diseases (e.g., liver, autoimmune diseases, and malignancies) or major hemorrhage (e.g., trauma, surgery). Low fibrinogen levels are both a symptom and a precipitating factor for coagulopathy and ongoing bleeding. Fibrinogen repletion with fibrinogen-containing products is important for managing coagulopathic bleeding with suspected or documented hypofibrinogenemia. Different available fibrinogen sources include fibrinogen concentrate, cryoprecipitate, and frozen plasma and vary based on multiple factors including fibrinogen content, purity, other clotting or non-clotting proteins (e.g., immunomodulating proteins or proteins of unknown function), preparation time, safety, volumes, and availability. Fibrinogen replacement strategies have been studied in trauma but also in patients undergoing spine, cytoreductive, and cardiac surgery. In this review, we discuss the physiological actions of fibrinogen, strategies for control of coagulopathic bleeding related to hypofibrinogenemia, and the therapeutic, logistical, and economic factors that influence treatment decisions. In addition, current guidelines and clinical studies were considered regarding the formation of evidence-based treatment strategies that can be individualized at the patient’s bedside. Full article

Background: Heart failure (HF) substantially affects health-related quality of life (HRQoL), but evidence across left ventricular ejection fraction (LVEF) categories in Jordan remains limited. Methods: This multicenter cross-sectional study included 516 adults with HF attending outpatient cardiac clinics in northern Jordan between May and November 2025. SF-36 Version 1.0 items were recoded to eight 0–100 domains, and unweighted SF-36 physical and mental four-domain composite scores were analyzed using expanded multivariable ordinary least-squares models with HC3 robust standard errors. A total of 476 participants had complete data for all model variables. Results: The mean SF-36 physical and mental four-domain composite scores were 48.80 (SD 21.14) and 51.88 (SD 20.57), respectively. Both scores differed across EF categories before adjustment (physical p < 0.001; mental p < 0.001), but the adjusted EF omnibus tests were not significant (physical p = 0.111; mental p = 0.613). Lower physical scores were associated with NYHA class II and III, physical inactivity, sleeping difficulty, retirement, and higher anxiety and depression scores, whereas self-care efficacy was positively associated with physical HRQoL. Lower mental scores were associated with NYHA class II and III, physical inactivity, and higher anxiety and depression scores, while self-care efficacy was positively associated with mental HRQoL. Conclusions: In this cross-sectional sample, functional limitation, anxiety and depressive symptoms, physical inactivity, and self-care efficacy were more consistently associated with HRQoL than EF category after adjustment. These findings support multidimensional assessment alongside cardiac measures. Full article

Cardiovascular disease is a leading cause of morbidity and premature mortality in many inherited syndromic and metabolic disorders. However, its cardiac manifestations are often recognized late and are rarely described collectively within a single cohort. We reviewed eight years of outsourced next-generation sequencing (NGS) requested through the pediatric genetics service of a single tertiary center in Taiwan and identified 22 patients with molecularly confirmed genetic disorders and documented cardiovascular involvement. For each patient, the causative genotype—including lysosomal storage diseases, RASopathies, CHARGE syndrome, connective-tissue disorders, primary cardiomyopathies and channelopathies, neuromuscular disorders, contiguous-gene syndromes, and other metabolic and syndromic conditions—was mapped to a structured echocardiographic phenotype. Septal defects or shunts and valvular regurgitation were the most common findings (10/22 and 9/22, respectively), followed by septal hypertrophy, valvular stenosis, and great-vessel or aortic abnormalities. Two children had left ventricular systolic dysfunction, and one died following an out-of-hospital cardiac arrest. Several cardiac lesions clustered by disease category, most notably valvular thickening in mucopolysaccharidoses and elastin arteriopathy in Williams–Beuren syndrome. These genotype-to-cardiac phenotype patterns support the need for gene-informed, systematic cardiac surveillance rather than symptom-driven referral in children with these disorders. Full article

Cardiac myosin-binding protein C (cMyBP-C) is a cardiac-restricted sarcomeric protein; after cardiomyocyte injury, circulating intact cMyBP-C and/or cMyBP-C fragments, collectively referred to here as the cMyC biomarker signal, appear rapidly in blood. In suspected acute coronary syndrome (ACS), its most important potential role is not as another marker of injury but as a decision-enhancing biomarker beyond symptoms, electrocardiography, cardiac troponin T and I concentrations measured with high-sensitivity assays (hs-cTnT and hs-cTnI), time from pain onset, and pre-test probability. This narrative review separates three clinical tasks frequently conflated in the biomarker literature: diagnosis of acute myocardial infarction, emergency-department triage, and prediction of short-term or post-infarction risk. We integrate cMyBP-C sarcomeric architecture, N-terminal regulatory biology, phosphorylation, proteolysis, circulating fragments, assay epitopes, analytical stability, diagnostic algorithms, point-of-care testing, ST-segment elevation myocardial infarction reperfusion biology, and major confounders including renal dysfunction, heart failure, age, sex, and chronic ventricular remodeling. Current evidence supports further evaluation of cMyC as an adjunct in early presenters and accelerated diagnostic pathways. However, diagnostic safety and efficacy have not been consistently reproduced across platforms and populations, and external validation—particularly of rule-out performance—remains insufficient for routine clinical use. Recurrent injury assessment and post-infarction risk phenotyping remain promising but incompletely validated applications. Before guideline adoption, cMyC needs phenotype-specific, multicenter implementation trials demonstrating incremental net benefit, cost-effectiveness, and patient-level safety compared with contemporary hs-cTnT- and hs-cTnI-based clinical decision algorithms. Full article

Cardiac contractility modulation (CCM) is an implantable device-based therapy that delivers biphasic, non-excitatory electrical signals to the ventricular myocardium during the absolute refractory period. By enhancing contractile performance without inducing depolarization or altering ventricular activation, CCM acts as bioelectronic myocardial conditioning. Current evidence supports its use in selected patients with symptomatic heart failure, reduced or mildly reduced left ventricular ejection fraction, narrow QRS duration, persistent symptoms despite guideline-directed medical therapy, and no indication for cardiac resynchronization therapy. In this population, CCM improves functional status and quality of life, whereas evidence for reductions in mortality or recurrent heart failure hospitalization remains less definitive. Whether CCM also reduces arrhythmic burden remains uncertain. Candidates for CCM frequently exhibit atrial and ventricular remodeling, neurohormonal activation, implantable cardioverter-defibrillators, and vulnerability to atrial fibrillation, ventricular arrhythmias, and device therapies. Mechanistically, CCM may render the failing myocardium less arrhythmogenic through coordinated effects on calcium handling, electromechanical remodeling, fibrosis-related substrate, contractile efficiency, and heart-failure stability. However, pivotal trials were not designed to assess arrhythmic endpoints, leaving the relationship between CCM and arrhythmic burden insufficiently characterized. This review summarizes CCM evidence, mechanistic rationale, available arrhythmic signals, device-related considerations, and future research priorities for prospective studies in this evolving field. Full article

Background/Objectives: Ischemic heart disease (IHD) is a major cause of cardiovascular mortality, and emergency medical service (EMS) crews often make the first decision on whether an IHD-coded patient should be transported to hospital or managed at the scene. Evidence from Central Asian EMS systems is sparse, and it remains unclear whether routinely coded comorbidity information adds decision-relevant information beyond acute presentation. We aimed to identify predictors of the EMS hospitalization/transport decision among IHD calls in Astana, Kazakhstan. Materials and Methods: We conducted a retrospective call-level cohort study of 9985 consecutive EMS calls coded as IHD (ICD-10 I20-I25) over a five-year period. The endpoint was field disposition—hospitalization/transport versus being left at the scene—and should not be interpreted as confirmed ACS, mortality, clinical appropriateness or any other patient outcome. Group comparisons used the Mann–Whitney U and Pearson chi-square tests, and independent associations were estimated using explanatory multivariable logistic regression. Results: Overall, 2676 calls (26.8%) resulted in hospitalization/transport. The strongest independent predictors were cardiogenic shock (aOR 15.06), acute/unstable IHD versus chronic I25 (aOR 8.52) and heart failure (aOR 2.46). Other arrhythmias (aOR 1.84), atrial fibrillation (aOR 1.60), male sex (aOR 1.65) and age <45 years (aOR 1.88) were also associated with higher transport odds, whereas age ≥75 years (aOR 0.61), specialized crews (aOR 0.84) and high dispatch urgency (categories 1–2; aOR 0.84) were associated with lower odds. Model discrimination was moderate (AUC 0.69; optimism-corrected AUC 0.69), plausibly reflecting the absence of ECG findings, vital signs, symptom severity and hospital outcome data. Conclusions: The expected acuity markers dominated EMS transport decisions, but routinely coded cardiac comorbidities were independently associated with disposition in this understudied setting. The model is not deployable for individual triage; these variables should be considered candidate inputs for future models that incorporate richer clinical data, outcome linkage and prospective validation. Full article

Background/Objectives: Amb a 1 is the major allergenic component of Ambrosia artemisiifolia pollen and a clinically relevant marker of genuine ragweed sensitization. Heart failure is increasingly recognized as a systemic syndrome shaped by immune activation, endothelial dysfunction, fibrosis, neurohormonal imbalance, pulmonary comorbidity, and environmental exposures. This narrative review aims to synthesize the translational evidence linking Amb a 1-specific IgE, IgE-mediated inflammation, allergic airway disease, and cardiovascular remodeling in heart failure. Methods: A targeted narrative review was performed, integrating evidence on component-resolved ragweed diagnosis, IgE-FcεRI signaling, mast cell and eosinophil biology, pollen exposure, cardiovascular inflammation, and heart failure pathophysiology. Results: No dedicated clinical studies have validated Amb a 1-specific IgE as a diagnostic, prognostic, or therapeutic biomarker in heart failure. However, adjacent evidence supports biologically plausible links between allergen-specific IgE responses and cardiovascular dysfunction, including mast cell activation, cytokine release, endothelial perturbation, oxidative stress, microvascular dysfunction, pulmonary-cardiac interaction, and myocardial fibrosis. Amb a 1-specific IgE may therefore identify a seasonally vulnerable heart failure phenotype, particularly in patients with allergic rhinitis, asthma, eosinophilic inflammation, or recurrent symptom worsening during ragweed season. A systemic/indirect pathway operating through allergic airway disease is distinguished from a postulated direct cardiac pathway; the latter remains strictly speculative, as no direct evidence demonstrates that inhaled Amb a 1 reaches or activates cardiac mast cells in vivo. Conclusions: Amb a 1-specific IgE should not currently be used to infer cardiac causality or modify heart failure therapy. Prospective, phenotype-rich, exposure-informed studies are needed to determine whether ragweed sensitization has clinically meaningful implications for heart failure endotyping, seasonal risk assessment, and cardio-allergology care. These findings may inform patient-centered heart failure management by improving the interpretation of seasonal dyspnea, allergic comorbidity, and symptom fluctuations in ragweed-endemic regions. Full article

Acute coronary syndrome (ACS) remains a leading cause of cardiovascular morbidity and mortality worldwide. Although traditional cardiovascular risk factors remain central to ACS development, recreational drug use is increasingly recognized as a clinically relevant trigger, particularly in younger patients with fewer conventional risk factors. This narrative review synthesized evidence identified through searches of PubMed/MEDLINE and Scopus up to June 2026, including clinical guidelines, systematic reviews, observational studies, mechanistic investigations, and clinically informative case-based evidence. Cannabis, cocaine, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), opioids, lysergic acid diethylamide (LSD), synthetic cannabinoids, and polysubstance use may promote myocardial ischemia and infarction through overlapping mechanisms, including sympathetic activation, coronary vasospasm, endothelial dysfunction, oxidative stress, inflammation, platelet activation, thrombosis, arrhythmogenesis, and myocardial oxygen supply–demand mismatch. Clinical presentation may be typical or atypical and may overlap with intoxication, withdrawal, anxiety, neurological symptoms, or non-cardiac chest pain, making diagnosis challenging. Underreporting of recreational drug use is common, and targeted toxicology screening may improve diagnostic accuracy and risk stratification, particularly in patients younger than 50 years, those with few traditional cardiovascular risk factors, or those presenting with otherwise unexplained ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), coronary vasospasm, arrhythmias, or cardiac arrest. Acute management should generally follow standard ACS guidelines, while considering drug-specific issues such as stimulant-induced vasospasm, sympathetic excess, cautious use of beta-blockers during acute intoxication, and preference for primary percutaneous coronary intervention when fibrinolysis carries increased risk. Long-term care should combine evidence-based secondary prevention with substance-use counseling, addiction medicine referral, cardiac rehabilitation, and behavioural interventions. This review summarizes the pathophysiology, clinical manifestations, epidemiology, treatment considerations, preventive strategies, and knowledge gaps related to recreational drug-associated ACS. Full article

Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose of HXP-GPOVac administered to adults previously primed with two doses of either HXP-GPOVac or BNT162b2. Methods: Study GPO NDV-HXP-S 203 was an open-label phase II extension enrolling adults (18–75 years) who previously completed a two-dose primary series in Study 202 with either HXP-GPOVac or BNT162b2 (Pfizer–BioNTech; Comirnaty). All participants received a single additional 10 µg intramuscular dose of HXP-GPOVac ≥ 6 months after their second primary dose. Solicited local/systemic adverse events (AEs) were recorded for 7 days, unsolicited AEs through Day 28, and serious AEs (SAEs) and adverse events of special interest (AESIs) throughout follow-up. Neutralizing antibody titers (pseudovirus 50% neutralization titer, NT₅₀) and anti-spike IgG (BAU/mL) were assessed pre-dose (Day 1) and post-vaccination through 12 months; a predefined subset underwent IFN-γ and IL-5 ELISpot. SARS-CoV-2 infection during follow-up was assessed using anti-nucleocapsid (anti-N) IgG. Symptomatic COVID-19 was identified through symptom-reported, symptom-triggered RT-PCR testing; sequencing was performed when feasible. Results: All 219 participants received HXP-GPOVac (167 primed with HXP-GPOVac and 52 with BNT162b2). Any solicited local reaction occurred in 22.2% (37/167) of HXP-GPOVac-primed and 26.9% (14/52) of BNT162b2-primed participants; any solicited systemic reaction occurred in 10.8% (18/167) and 13.5% (7/52), respectively. No vaccine-related unsolicited AEs or AESIs were reported. Three deaths occurred during the 12-month follow-up; one (a sudden cardiac death in an HXP-GPOVac-primed participant) was assessed by the safety medical team as possibly related to vaccination, and two were assessed as not related. Neutralizing antibody GMTs increased from 46.33 at baseline to 1569.04 at Day 15 in HXP-GPOVac-primed participants and from 77.25 to 841.34 in BNT162b2-primed participants; corresponding SCRs were 78.8% and 76.9%. Anti-spike IgG GMCs increased from 48.79 to 1480.14 BAU/mL and from 194.48 to 1547.88 BAU/mL, respectively. Responses declined over time but remained above baseline through 12 months. In the cellular immunity subset, post-vaccination IFN-γ responses increased, with comparatively modest IL-5 responses and no pattern suggestive of Th2 predominance. Conclusions: A single additional dose of HXP-GPOVac administered ≥6 months after primary vaccination with HXP-GPOVac or BNT162b2 was generally well tolerated and elicited robust recall humoral responses, with supportive findings of cellular immunity. Trial registration: Thai Clinical Trials Registry, TCTR20230213001. Full article