The SLCO1B1 c.521T > C variant, which reduces hepatic statin uptake, has been linked to an increased risk of statin-associated muscle symptoms (SAMS), particularly with simvastatin. This study aimed to assess its association with SAMS and prescription of contemporary lipid-lowering therapy in patients with severe hypercholesterolemia. We included 219 patients with a mean age of 53.9 ± 12.7years who attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521T > C variant. Treating physicians and patients were unaware of genotyping results. Six patients (2.7%) were homozygous and 68 patients (31.1%) were heterozygous for the c.521T > C variant. After treatment optimization, the median LDL cholesterol levels were 63 (IQR 40-124) mg/dL and 74 (IQR 43-129) mg/dL in mutation carriers and non-carriers, respectively (p = 0.35). Self-reported SAMS did not differ between mutation carriers and non-carriers (25.7% vs. 27.6%; p = 0.76). In addition, statin usage (70.3% vs. 73.1%; p = 0.66) and prescription rates of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) (32.4% vs. 31.0%; p = 0.83) did not differ according to mutation status. In patients with severe hypercholesterolemia on contemporary statin therapy, the SLCO1B1 c.521T > C variant was not associated with SAMS, reduced statin use, or increased prescription of PCSK9 inhibitors. The SLCO1B1 c.521T > C variant appears to have no clear clinical relevance, but testing for it may potentially be harmful, as fear of side effects could result in statin undertreatment.

To investigate clinical outcomes and cardiac remodeling according to cardiac magnetic resonance (CMR) of the invasively measured different flow/gradient entities of severe aortic stenosis (AS) with preserved left ventricular ejection fraction (EF) after transcatheter aortic valve implantation (TAVI). All consecutive patients with preserved EF and severe AS undergoing right heart catheterization and treated with TAVI between 2007 and 2017 were split into four groups: normal-flow high-gradient (NF-HG n = 113, 25.9%); low-flow high-gradient (LF-HG n = 190, 43.6%); normal-flow low-gradient (NF-LG n = 50, 11.5%); and low-flow low-gradient (LF-LG n = 83, 19%). Patients with LF were older (81.9 ± 6 vs. 80.1 ± 6, p = 0.004); had a higher rate of atrial fibrillation (45.8% vs. 27.6%, p < 0.001); and had a higher EuroScore (p = 0.002). Significant improvement of functional status was noted in all four subgroups. However, the benefit at 30days was more pronounced in HG patients. In CMR, at 6months, we observed a significant regression of LV mass in NF-HG, LF-HG, and LF-LG but not in NF-LG patients. Patients with HG AS showed a lower rate of all-cause mortality at 5years follow-up compared to LG AS (42.3% vs. 58%; p = 0.024). No difference in long-term mortality was observed between LF and NF AS (43.6% vs. 50%, p = 0.87). In patients with severe AS and preserved EF, patients with all invasively measured flow-gradient entities improved functionally after TAVI. High-gradient AS-regardless of the flow status-showed the most pronounced LV mass regression at 6-month CMR follow-up, had the best clinical improvement, and the lowest 5-year all-cause mortality after TAVI.

Sparse data are available on the long-term course of acute pulmonary embolism (PE) after ultrasound-assisted catheter-directed thrombolysis (USAT). We included consecutive patients with intermediate-high or high-risk acute PE treated with USAT (alteplase 20mg over 15h) and therapeutic anticoagulation at a tertiary center, who underwent a structured post-interventional follow-up. The following outcomes were analyzed for patients with at least 3months of follow-up: all-cause death, persistent dyspnea, symptomatic post-PE cardiac impairment, chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic pulmonary disease (CTEPD). Symptomatic post-PE cardiac impairment was defined as residual respiratory symptoms with at least one echocardiographic parameter of right ventricular dysfunction. Among 300 patients (41% women, median age 65 [52-74] years), 254 (85%) had intermediate-high and 46 (15%) had high-risk PE. Follow-up data beyond the first 3months (median 6.1 [3.6-12] months) were available for 260 (88%) survivors. At follow-up, 45 (17%) patients reported persistent respiratory symptoms and 18 (6.9%) met the criteria for post-PE cardiac impairment. CTEPH was diagnosed in 7 (2.7%) patients, deemed pre-existing in all cases based on radiological reassessment of index imaging. CTEPD was confirmed in 2 (0.8%) patients. The 1-year death rate was 2.9% after intermediate-high risk and 21% after high-risk PE. After a median of 6months after acute PE, almost one in five patients treated with USAT had persistent respiratory symptoms, although post-PE cardiac impairment was rare. CTEPH was diagnosed in 2.7% of patients and deemed pre-existing in all cases.

Atrial cardiomyopathy (AtCM) represents an important substrate underlying atrial fibrillation (AF), increased arrhythmia recurrence after catheter ablation, and other adverse outcomes. Several non-invasive markers have been proposed as surrogates of AtCM, but their comparative performance and clinical relevance remain insufficiently validated. In this retrospective study, 200 patients undergoing first-time catheter ablation for symptomatic AF were included. All patients underwent high-density left atrial electroanatomical mapping, which served as reference standard for AtCM assessment based on the extent of left atrial low-voltage substrate (LA-LVS). Non-invasive AtCM markers derived from 12-lead electrocardiography (ECG), transthoracic echocardiography, and blood-based biomarkers were systematically compared with LA-LVS extent and their predictive value for arrhythmia recurrence during follow-up was assessed. Among non-invasive AtCM markers, amplified P-wave duration (PWD) and P-wave amplitude in lead I showed the strongest association with LA-LVS extent. In multivariable logistic regression analysis, prolonged amplified PWD (≥ 150ms) was independently associated with relevant AtCM (odds ratio 11.46, 95% confidence interval 2.27-57.90, p = 0.003). During a median follow-up of 277days, arrhythmia recurrence occurred in 21.9% of patients. In Cox regression analysis, amplified PWD ≥ 150ms was the only non-invasive AtCM marker independently associated with arrhythmia recurrence (hazard ratio 2.01, 95% confidence interval 1.07-3.78, p = 0.031). In patients undergoing first-time AF ablation, amplified PWD emerged as the most robust non-invasive marker of AtCM, independently associated with invasively assessed LA-LVS and arrhythmia recurrence. Advanced surface ECG analysis may represent a practical and widely applicable tool for AtCM-associated risk stratification in routine clinical practice.

Previous studies have suggested that patients admitted on the weekend may experience worse outcomes compared to weekday admissions, a phenomenon known as the "weekend effect." Atrial fibrillation (AF) management has evolved substantially in recent years, prompting a re-evaluation of whether the weekend effect persists in this population using more recently updated national data. We conducted a retrospective review using the 2022 National Inpatient Sample (NIS), analyzing adult hospitalizations with a primary diagnosis of atrial fibrillation. Weekday admissions were compared to weekend admissions. The primary outcome was receipt of cardioversion. Secondary outcomes included mortality, length of stay (LOS), and total hospital charges. Multivariate linear and logistic regression models were used to adjust for demographic, clinical, and hospital-level confounders. Among 277,440 hospitalizations for atrial fibrillation, 61,305 (22.1%) occurred on weekends. Weekend admissions were less likely to undergo cardioversion (19.0% vs 22.0%; aOR 0.83, 95% CI 0.79-0.88; p < 0.001). In-hospital mortality was similar in weekend admissions (1.0%) compared to weekdays (0.8%) with an adjusted odds ratio (aOR) of 1.21 (95% CI 0.97-1.52; p = 0.090). Hospital charges were lower among weekend admissions ($48,478 vs $50,588; p = 0.022). There were no significant differences in length of stay (3.59 vs 3.58days; p = 0.545) between groups. Weekend admissions for atrial fibrillation are less likely to undergo cardioversion. There was no significant difference in in-hospital mortality or length of stay. This pattern may reflect differences in care delivery or patient selection by day of admission, although the underlying mechanism cannot be determined using administrative data.

Spontaneous coronary artery dissection (SCAD) is a rare, but increasingly recognised cause of myocardial infarction. Our aim was to provide comprehensive real-world data on the prevalence of SCAD among patients who present with ST-segment elevation myocardial infarction (STEMI). Retrospective analysis of medical records and review of coronary angiograms allowed identification of all SCAD cases in a cohort of consecutive patients with STEMI, and review of clinical data provided further characterisation. Among 2707 consecutive STEMI patients, the prevalence of SCAD was 0.9% (n = 24). In 9 cases, the diagnosis of SCAD diagnosis had been missed during clinical routine (37.5%). Compared to non-SCAD-STEMI, SCAD patients were younger (median age 53.5 vs. 66.0years, p = 0.001) and more likely to be female (75.0% vs. 29.7%, p < 0.001). The most common symptom was typical angina (chest pain limited to the thorax, 75%). Importantly, six patients (25%) experienced cardiac arrest, either as the presenting symptom before (n = 2) or after first medical contact (n = 3), or during hospitalisation (n = 1). The most common angiographic pattern was SCAD type 4 (complete vessel occlusion, 37.5%), followed by type 2a (29.2%) and 2b (25%). Intravascular imaging was used in 25% (n = 6). 58.3% of patients with SCAD-STEMI underwent percutaneous coronary intervention (PCI). Complications occurred in 50% of PCI, mostly due to propagation of intramural hematoma. All patients survived to hospital discharge. Long-term follow-up was available in 50% of patients. While event rate was low, recurrence of SCAD did occur, in some cases after several years. In a Western European cohort of STEMI patients, SCAD was the underlying cause in approximately 1% of all cases. The true incidence may be higher since cardiac arrest occurred in one quarter of all patients within the cohort. Interventional treatment, while often required in SCAD-STEMI, is fraught by a high complication rate.

The presence of higher body mass index (BMI) accompanied by better outcomes in patients with heart failure with reduced ejection fraction (HFrEF) is described as the obesity paradox. However, recent evidence has questioned the existence of this phenomenon by adjusting for better prognostic factors and using superior anthropometric measures of obesity. Nevertheless, data regarding the association between BMI and mortality in HFrEF patients with the use of contemporary guideline-directed medical therapy (GDMT), including SGLT2is, is scarce. To assess the association between BMI and mortality in patients with HFrEF treated with modern GDMT across a wide BMI spectrum. The data of 420 consecutive patients (male sex: 75%, age: 62 [51-71] years, NT-proBNP at admission: 5678 [2647-10501] pg/mL, LVEF: 24 [20-30] %, coronary artery disease: 44%, atrial fibrillation: 45%, normal weight: 33% [group 1: BMI < 25kg/m2], overweight: 31% [group 2: BMI: 25-29.9kg/m2], obese: 36% [group 3: BMI ≥ 30kg/m2], type 2 diabetes [T2D]: 35%, eGFR < 60mL/min/1.73m2: 55%) hospitalised for HFrEF in 2021-2024 with available BMI were analysed retrospectively. The application of GDMT at hospital discharge was compared between three groups of patients (group 1, 2, and 3). All-cause mortality (ACM) was assessed using Kaplan-Meier curves and the log-rank test. Predictors of ACM were estimated with uni- and multivariate Cox proportional hazards regression. In a sensitivity analysis, BMI groups were propensity score-matched (PSM) at a 1:1:1 ratio, adjusting for possible confounders. At hospital discharge, triple therapy (TT: RASi + βB + MRA) was applied in 82% (RASi: 92%, βB: 85%, MRA: 95%), while quadruple therapy (QT: TT + SGLT2i) was implemented in 58% of the total cohort (SGLT2i use: 64%). At discharge, higher BMI category was significantly (p < 0.05) associated with increased use of MRA (group 1, 2, 3: 93%, 92%, and 100%), SGLT2i medications (group 1, 2, 3: 58%, 61%, and 71%), and QT (group 1, 2, 3: 51%, 56%, and 65%). During a median follow-up of 534days, ACM was lower with increasing BMI subgroup category (p = 0.021). In the multivariate analysis, BMI subgroup category was not associated with ACM, whereas age, T2D, peripheral artery disease, NT-proBNP at discharge, and use of QT at discharge were independent predictors of ACM. In the sensitivity analysis, no significant differences were seen in the ACM of each BMI category after PSM. In a consecutive cohort of patients hospitalised due to HFrEF with high rates of modern GDMT use across a wide BMI spectrum, higher BMI subgroup category was not associated with better survival after adjustment for comorbidities and prognostic factors.

Left ventricular dysfunction occurs early in the ischemic cascade. Strain parameters such as global longitudinal strain (GLS) and global circumferential strain (GCS) detect subtle contractile changes, but strain reduction may be observed in situations not related to ischemia. This study assessed whether GLS and GCS may support the identification of a low likelihood of myocardial ischemia in the absence of scarring. Patients were selected from an all-comers registry who underwent vasodilator-perfusion cardiac magnetic resonance imaging (CMR) and showed no evidence of ischemic late gadolinium enhancement. Patients with perfusion deficits were compared with a control group without ischemia and with normal morphological and functional volumetric parameters. GLS and GCS were quantified, and their ability to differentiate ischemic from non-ischemic patients was evaluated using receiver operating characteristic analysis. Among 1434 patients with perfusion analysis, 451 had normal findings and 112 demonstrated a perfusion defect without LGE. GLS and GCS were significantly reduced in ischemic patients (- 16.66 ± 4.6% vs. - 18.5 ± 3.7%, p < 0.001). GLS and GCS showed only modest discriminatory ability in identifying myocardial ischemia, with AUCs of 0.627 and 0.674, respectively. Optimal cut-off values identified using the Youden index were -18.25% for GLS and -18.85% for GCS. At these thresholds, GLS yielded a sensitivity of71%and specificity of52%, and GCS a sensitivity of65%and specificity of63%, resulting in high negative predictive values (GLS, 88%; GCS, 88%) but limited overall accuracy. Strain analysis may provide supportive information indicating a low likelihood of ischemia in patients without LGE. Although sensitivity and specificity were only moderate, the consistently high NPV suggests a potential complementary role for strain as part of a multimodal diagnostic work-up, while limited sensitivity precludes its use as a standalone diagnostic marker.

The aim of this study was to evaluate the short-term potential of very-high-intensity lipid-lowering therapy on lesion-level atheroma burden. The investigator-initiated, double-blind, placebo-controlled FITTER trial (enrollment November 2020 to August 2023) randomized patients presenting with acute coronary syndrome (ACS) and relevant non-culprit coronary artery disease (fractional flow reserve: 0.67-0.85) to receive either evolocumab or placebo for 12weeks in addition to high-intensity statin therapy to evaluate the short-term potential of lipid-lowering therapy on non-culprit plaque features. Present lesion-level analysis assessed the effects on coronary segments with advanced atherosclerotic plaque characteristics with increased cardiovascular risk and includes all patients who underwent successful serial intravascular ultrasound-near-infrared spectroscopy (IVUS-NIRS) imaging and with presence of IVUS-derived atherosclerotic lesions. A total of 126 lesions were identified in 85 patients (mean age 65.1 ± 8.3, 18.8% female), of which 65 lesions were found in the evolocumab group (44 patients) and 61 in the placebo group (41 patients). Compared to placebo, patients treated with evolocumab did not demonstrate significant reductions in maximum lipid core index within any 4mmsegment (maxLCBI4mm, between-group difference, -9.6 [95% CI, -52.8 to 33.6]; p = 0.7) or percent atheroma volume (PAV, between-group difference, 1.0% [95% CI, -1.3 to 3.2]; p = 0.4). However, an overall reduction in maxLCBI4mm (overall change, -54.2 [95% CI, -89.6 to -18.7]; p = 0.003) and PAV (overall change, -2.0% [95% CI, -3.9 to -0.1]; p = 0.04) was observed. Compared with placebo, the addition of evolocumab did not yield incremental improvements in lesion-level atheroma burden in the first 12weeks after ACS. However, in the pooled analysis, significant short-term reductions in atheroma volume and plaque lipid content were observed. clinicaltrials.gov NCT04141579.