The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceri...The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceride-rich lipoproteins, lipoprotein(a), and vascular inflammation. The emergence of PCSK9-targeted small interfering RNA therapies, CETP inhibitors, and Lp(a)-directed antisense and RNA based agents has enabled complementary modulation of diverse lipid pathways through distinct molecular targets. However, this increasingly multidrug approach may also increase treatment complexity, healthcare burden, and adherence challenges, particularly among high-risk patients already receiving multidrug cardiometabolic therapy. Although intensive and sustained LDL-C lowering remains foundational to preventive cardiology, the real-world effectiveness of increasingly complex treatment strategies may ultimately depend on long-term adherence, affordability, patient capacity, and implementation feasibility. We propose a Clinical Prioritization and Personalization Framework centered on individualized risk-based intensification, comprehensive residual risk management, and optimization of treatment delivery to achieve sustainable, patient-centered cardiovascular protection.
BACKGROUND: Mavacamten is a cardiac myosin inhibitor used for patients with obstructive hypertrophic cardiomyopathy (oHCM). The efficacy and safety of this negative inotropic agent in oHCM and concomitant left bundle bra...BACKGROUND: Mavacamten is a cardiac myosin inhibitor used for patients with obstructive hypertrophic cardiomyopathy (oHCM). The efficacy and safety of this negative inotropic agent in oHCM and concomitant left bundle branch block (LBBB) remains largely unknown. This study aimed to explore the interaction between mavacamten treatment and LBBB on longitudinal changes in left ventricular (LV) systolic function and mechanical dyssynchrony. METHODS: This multicenter observational study included 127 patients with oHCM treated with mavacamten. Echocardiographic assessment was performed at 4, 8, 12 and 24 weeks after treatment initiation. LV dyssynchrony was visually assessed by the presence of septal flash (SF) and graded using speckle tracking strain imaging of the mid-septal wall. RESULTS: Baseline LVEF was not significantly different between the LBBB (60% [58; 65]) and non-LBBB cohort (60% [57; 67]) (P = 0.58). For the LBBB cohort, limited mechanical dyssynchrony was observed at baseline, with no patients expressing a LBBB strain stage ≥3 before mavacamten initiation. After 6 months of treatment, there was a significant decrease in LVEF in the LBBB-HCM patients, with a median ∆LVEF of -11% [-28; -5] and LVEF of 46% [35; 58] (P < 0.001). In addition, there was a significant increase in mechanical dyssynchrony, as reflected by higher LBBB-stages (P = 0.007). In multivariable analysis, atrial fibrillation (AF) (P = 0.005), baseline LVEF (P < 0.001) and LBBB status (P < 0.001) were associated with incident LV systolic dysfunction. CONCLUSIONS: In patients with oHCM receiving mavacamten, the presence of LBBB is associated with an increased risk of developing LV systolic dysfunction. These findings underscore the importance of careful patient selection, monitoring and individualized patient management in this population.
Garatachea N, Echevarría-Polo M, Hernández-Vicente A
… +7 more, García-Giménez JL, Casabó-Vallés G, Mena-Mollá S, Fabregat-Andrés Ó, Grazioli G, de la Guía-Galipienso F, Sanchis-Gomar F
Coronary artery ectatic/aneurysmatic disease (CAE/CAA) is a rare but clinically significant condition characterized by abnormal dilatation of the coronary arteries, either diffusely (CAE) or focally (CAA). Its pathophysi...Coronary artery ectatic/aneurysmatic disease (CAE/CAA) is a rare but clinically significant condition characterized by abnormal dilatation of the coronary arteries, either diffusely (CAE) or focally (CAA). Its pathophysiology is multifactorial, involving atherosclerosis, genetic predisposition, systemic autoimmunity, and infectious triggers, with distinct etiologies in adults (e.g., atherosclerosis, connective tissue disorders) and children (e.g., Kawasaki disease, multisystem inflammatory syndrome in children). CAE/CAA is associated with increased risks of thrombosis, embolization, and acute coronary syndromes, even in the absence of obstructive coronary artery disease. Diagnostic evaluation relies on multimodality imaging, including transthoracic echocardiography (especially in children), computed tomography coronary angiography, cardiovascular magnetic resonance angiography, and invasive coronary angiography with intravascular ultrasound. Each modality offers unique advantages, but challenges such as radiation exposure, contrast use, expertise and availability persist. Therapeutic management remains empirical due to a lack of randomized trials. In adults, risk factor modification, statins, angiotensin converting enzyme inhibitors / angiotensin receptor blockers, calcium channel blockers are commonly used. Optimal strategies for antiplatelet/anticoagulant treatment are currently under debate. In children, anticoagulation and antiplatelet therapy are recommended for large aneurysms, particularly in Kawasaki disease. Future research should focus on elucidating pathophysiology, comparing imaging modalities, and establishing evidence-based treatment strategies to improve outcomes in this complex patient population.
INTRODUCTION: Low-density lipoprotein-cholesterol (LDL-C) is a well-established causal risk factor for atherosclerosis and remains the cornerstone of primary prevention. Lipoprotein(a) [Lp(a)] and high-sensitivity C-reac...INTRODUCTION: Low-density lipoprotein-cholesterol (LDL-C) is a well-established causal risk factor for atherosclerosis and remains the cornerstone of primary prevention. Lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) are considered risk-enhancing factors in current guidelines. Interleukin-6 (IL-6), a pro-inflammatory cytokine upstream of CRP, has recently emerged as a potential therapeutic target. We sought to compare the longitudinal associations of LDL-C, Lp(a), hsCRP, and IL-6, both individually and in relation to one another, with atherosclerotic cardiovascular disease (ASCVD) events in two large, contemporary primary prevention cohorts. METHODS: Participants with baseline measurements of LDL-C, Lp(a), hsCRP, and IL-6 from the United Kingdom (UK) Biobank and the Multi-Ethnic Study of Atherosclerosis (MESA) were included in this study. The primary endpoint was incident ASCVD (defined as composite of myocardial infarction, stroke, or cardiovascular death). Cox proportional hazards models were used to calculate hazard ratios across biomarker quartiles, adjusting for traditional risk factors and other biomarkers. RESULTS: The mean age (SD) was 56.8 (8.1) years in UK Biobank and 62.2 (10.2) years in MESA. In fully adjusted models including all covariates, the HRs for ASCVD comparing top vs bottom quartiles in UK Biobank were: LDL-C 1.10 (95% CI: 0.97-1.25), Lp(a) 1.15 (1.03-1.29), hsCRP 1.19 (1.04-1.37), and IL-6 1.67 (1.44-1.93). In MESA, corresponding HRs were: LDL-C 1.26 (1.02-1.56), Lp(a) 1.23 (0.99-1.53), hsCRP 1.13 (0.88-1.44), and IL-6 1.60 (1.24-2.07). CONCLUSION: In two large primary prevention cohorts, IL-6 demonstrated the strongest association with ASCVD, independent of LDL-C, Lp(a), and hsCRP when mutually adjusted. These data suggest that IL-6 may be a key driver of ASCVD, with potential implications for risk prediction and therapeutic targeting for prevention of ASCVD.
This narrative review examines the interplay between frailty, heart failure (HF), and endothelial dysfunction, with a specific focus on the role of exercise-based cardiac rehabilitation (CR) in older and frail adults. Fr...This narrative review examines the interplay between frailty, heart failure (HF), and endothelial dysfunction, with a specific focus on the role of exercise-based cardiac rehabilitation (CR) in older and frail adults. Frailty and HF frequently coexist and share pathophysiological mechanisms - including chronic inflammation, oxidative stress, and impaired nitric oxide (NO) signaling - that exacerbate endothelial dysfunction and contribute to reduced functional capacity and poor prognosis. We synthesize current evidence linking endothelial impairment to both frailty and HF progression, and we evaluate findings from clinical trials investigating exercise-centered CR, hybrid CR, and cardiac telerehabilitation in this population. Across studies, CR consistently improves physical performance, exercise tolerance, and quality of life, with several trials reporting measurable enhancements in endothelial function, such as improved flow-mediated dilation or increased mobilization of endothelial progenitor cells. Benefits appear strongest when programs are multidomain and individualized to the frailty phenotype, integrating aerobic, resistance, balance, and mobility training. However, heterogeneity in study designs, limited enrollment of frail older adults, and the frequent designation of endothelial outcomes as secondary endpoints constrain the ability to draw firm mechanistic conclusions. Overall, available evidence indicates that CR is a feasible and effective therapeutic strategy to counteract vascular dysfunction, reduce frailty severity, and potentially disrupt the negative cycle that accelerates HF progression in older patients. Future studies should prioritize frail populations, adopt standardized endothelial assessments as primary outcomes, and evaluate long-term clinical impact. Tailored CR models, including hybrid and telerehabilitation programs, are likely essential to improve access, adherence, and vascular outcomes in this vulnerable group.
BACKGROUND: Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronar...BACKGROUND: Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronary artery disease (CAD) have an increased risk of serious illness, adverse coronary events, and mortality following infection. The COVID-CT registry will assess whether COVID-19 alters progression of coronary atherosclerotic plaque in patients with previously defined anatomic CAD on coronary computed tomographic angiography (CCTA). Mediators and covariates such as disease severity, inflammation, and neighborhood deprivation will also be assessed. DESIGN: The COVID-CT registry is a multicenter, longitudinal observational registry enrolling patients including patients with pre-pandemic atherosclerosis observed by CCTA from New York City and Long Island to determine the impact of COVID-19 infection. The primary aim is to test the hypothesis that patients with previously defined anatomic CAD by CCTA who are subsequently infected with SARS-CoV-2 have accelerated progression of total and noncalcified atherosclerotic plaque volumes when compared to uninfected patients. We hypothesize that systemic inflammation is a key promoter in the formation and progression of atherosclerotic plaque. Additionally, we will test whether measurement of the perivascular fat attenuation index detects high risk, coronary artery inflammation following COVID infection. SUMMARY: The impact of this first in-kind registry will be foundational for revising standard diagnostic pathways and risk assessment used to guide preventive care for millions of patients with CAD at increased risk from viral infection.
BACKGROUND: The predictive value of lipoprotein(a) (Lp[a]), high-sensitivity C-reactive protein (hsCRP), and remnant cholesterol (RC) beyond low-density lipoprotein cholesterol (LDL-C) varies across cardiovascular diseas...BACKGROUND: The predictive value of lipoprotein(a) (Lp[a]), high-sensitivity C-reactive protein (hsCRP), and remnant cholesterol (RC) beyond low-density lipoprotein cholesterol (LDL-C) varies across cardiovascular disease (CVD) outcomes. This analysis evaluates the extent to which concentrations of these non-LDL-C biomarkers improve MI-specific risk prediction in a primary prevention population. METHODS: We analyzed 306,183 UK Biobank participants free of cardiovascular disease at baseline with available Lp(a), RC, and hsCRP measurements. RC was calculated as total cholesterol minus LDL-C minus high-density lipoprotein cholesterol (HDL-C). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression across biomarker quintiles and cumulative biomarker burden. The primary endpoint was the first MI event. RESULTS: Over 15 years of follow-up, 10,824 MI events occurred. In fully adjusted models comparing quintile 5 with quintile 1, HRs (95% CI) were 1.09 (1.08-1.11) for Lp(a), 1.14 (1.13-1.16) for RC, and 1.08 (1.06-1.10) for hsCRP. Per-SD increases were associated with higher MI risk for RC 1.22 (1.20-1.25), Lp(a) 1.16 (1.13-1.18), and hsCRP 1.13 (1.10-1.15). The risk of MI increased stepwise with cumulative biomarker burden; compared with individuals with no biomarker in the top quintile, HRs (95% CI) were 1.45 (1.39-1.51), 2.14 (2.02-2.26), and 2.83 (2.48-3.24) for those with one, two, or all three elevated biomarkers, respectively. CONCLUSIONS: Lp(a), RC, and hsCRP each provide independent and complementary information for MI risk. Their combined elevation identifies individuals at higher MI risk, suggesting selective testing of all three biomarkers in primary prevention.
BACKGROUND AND AIMS: Identifying vulnerable coronary plaques (VP) is essential for stratifying cardiovascular risk in stable coronary artery disease (CAD). This is the first study to assess diagnostic performance in dete...BACKGROUND AND AIMS: Identifying vulnerable coronary plaques (VP) is essential for stratifying cardiovascular risk in stable coronary artery disease (CAD). This is the first study to assess diagnostic performance in detecting VP of CCTA advanced plaque analysis, including maximal plaque burden (PB) and necrotic core area, angiography-derived radial wall strain (RWS) and Murray's quantitative flow ratio (μFR) by using Intravascular Ultrasound with Near-Infrared Spectroscopy (IVUS-NIRS) as gold standard. METHODS: We analyzed fifty lesions from forty-three patients who underwent coronary angiography with IVUS-NIRS following CCTA. VP were defined using IVUS-NIRS criteria as maximal Lipid Core Burden Index ≥325. Regression analyses evaluated associations between the imaging parameters and VP. Receiver-operating-characteristic (ROC) curves and the corresponding areas under the curve (AUCs) were calculated to quantify the diagnostic performance of each model. RESULTS: VP was found in 19 out 50 lesions (38%) and in 16 out of 43 patients (37%). About CCTA, PB and necrotic core area showed the highest accuracy in identification of VP (AUC = 0.839 and AUC = 0.876, respectively). Regarding invasive evaluation, angiography-derived RWS demonstrated significant discriminative ability for detecting VP, whereas μFR did not (AUC = 0.921 and AUC = 0.637, respectively). Two multivariate models were tested: the first, combining PB and RWS, achieved an AUC of 0.959; the second model, based only on CCTA-derived parameters (PB and necrotic core area), yielded an AUC of 0.939. Although the difference between the two AUCs was not statistically significant, the combined model substantially improved the positive predictive value compared to the CCTA-only model (93.8% vs. 76.2%). CONCLUSIONS: Integrating CCTA-derived PB with angiography-derived RWS provides high discrimination of VP and may guide selective referral to IVUS-NIRS for definitive characterization.
Muscogiuri G, Guaricci AI, Fusini L
… +58 more, Senatieri A, Abete R, Aquaro GD, Baggiano A, Barison A, Bogaert J, Calo' L, Camastra G, Carella MC, Carigi S, Carrabba N, Casavecchia G, Censi S, Cicala G, De Cecco CN, Ciccone MM, De Lazzari M, Di Giovine G, Dobrovie M, Focardi M, Gaibazzi N, Gismondi A, Gravina M, Guglielmo M, Lanzillo C, Lombardi M, Lorenzoni V, Lozano-Torres J, Margonato D, Martini C, Marzo F, Masci PG, Masi A, Moro C, Mushtaq S, Nese A, Palumbo A, Pavon AG, Pedrotti P, Marra MP, Pradella S, Presicci C, Rabbat MG, Raineri C, Rodriguez-Palomares JF, Sbarbati S, Varga-Szemes A, Squeri A, Sverzellati N, Symons R, Tat E, Timpani M, Todiere G, Valentini A, Volpe A, Sironi S, Schwitter J, Pontone G
AIMS: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy of sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). The aim of current analysis is to evalu...AIMS: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy of sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). The aim of current analysis is to evaluate the prognostic impact of late gadolinium enhancement-papillary muscles (LGE-PMs) at cardiovascular magnetic resonance (CMR) and specifically its capability to re-stratify the arrhythmic risk on top to the DERIVATE-ICM Risk Score previously published. METHODS: Eighty-hundred-thirty-nine patients (mean age 65 ± 11 years; males:721[86%]) with ICM and TTE-LVEF <50% were enrolled from the DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy- Ischemic Cardiomyopathy). Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1054 days, MAACE occurred in 86 (9.7%). DERIVATE-ICM Risk Score quartiles Q2-Q3 (HR:2.124 [95% CI:1.084-4.162]; p = 0.028), Q4 (HR: 3.865 [95% CI: 1.875-7.970]; p < 0.001) and the involvement of isolated posteromedial (P)PM (HR:1.985 [95% CI:1.073-3.673]; p = 0.029) were independent predictors of MAACE. The Kaplan-Meier survival curves showed a higher event-free rate in absence of LGE-PPM in patients categorized in the DERIVATE-ICM Risk Score quartiles Q2-Q3 (p = 0.018). Finally, adding LGE-PPM involvement on top of the model included TTE LVEF<35% plus DERIVATE-ICM Risk Score quartiles Q2-Q3 provided a significant improvement of prognostic stratification (p = 0.044). CONCLUSION: This study suggests that, in a wide population of ICM patients, LGE-PPM is independently associated with the occurrence of MAACE. In the intermediate quartiles of the DERIVATE-ICM Risk Score, the absence of LGE-PPM, when added to the Score, may contribute to downward re-stratification of arrhythmic risk. CLINICAL TRIAL REGISTRATION: RCT#NCT03352648.