Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial.

Importance: Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach). Objective: To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events. Design, Setting, and Participants: The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023. Interventions: Alirocumab or placebo in addition to high-intensity statin therapy. Main Outcomes and Measures: Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes. Results: Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02). Conclusions and Relevance: At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Long-Term Risk of Hospitalization and Death in Patients With Mechanical Prosthetic Heart Valves.

Mechanical prosthetic heart valves (MPHVs) are commonly used for valvular heart disease in patients with a long life expectancy. Few longitudinal data on the specific causes of hospitalization in patients with MPHV are available. We investigated the risk of all-cause hospitalization and mortality in patients with MPHV. We performed a prospective, observational, ongoing study including consecutive patients with MPHVs who were referred to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist management. Study end points were all-cause, cardiovascular hospitalization, and overall mortality. We included 305 patients with MPHV (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5%, and mitroaortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery, and bleeding. The predictors of cardiovascular hospitalization were atrial fibrillation (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.04 to 2.95, p = 0.035), previous stroke/transient ischemic attack (HR 2.96, 95% CI 1.59 to 5.48, p = 0.001), and peripheral artery disease (HR 2.42, 95% CI 1.09 to 5.36, p = 0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95% CI 1.054 to 1.122, p <0.001), whereas the time in therapeutic range higher than the median was inversely associated (HR 0.436, 95% CI 0.242 to 0.786, p = 0.006). In conclusion, patients with MPHV had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high; however, it may be decreased by maintaining a good quality of anticoagulation.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).

Clinical frailty and triggers in Takotsubo syndrome: the notable role of a new classification.

AIMS: Takotsubo syndrome (TTS) is a mainly transient and acute heart failure mimicking an acute coronary syndrome. Originally described in postmenopausal women, over time TTS has been associated with an increasingly advanced age. Emotional and physical triggers precipitating TTS have been correlated in most cases. The aim of our work was to detect differences between patients with or without recognizable triggers preceding the onset of symptoms. METHODS: We enrolled 22 consecutive patients. They were all women with an average age of 71 ±â€Š12 (range 40-90) years. Twelve patients correlated the onset of TTS symptoms with a trigger (group 1) and 10 patients (group 2) denied any correlation with stressful events. RESULTS: Patients in group 1 showed a higher average age than group 2 (76 ±â€Š10 vs. 64 ±â€Š12 years; P = 0.023), a longer hospitalization period (22 ±â€Š12 vs. 11 ±â€Š10 days; P = 0.01) and greater value of frailty score (P = 0.004). Despite a decrease and subsequent recovery of systolic function, there was no significant difference between groups. Group 1 showed a longer corrected QT (QTc) (505 ±â€Š53 vs. 453 ±â€Š42 ms, P = 0.03), a greater decrease in QTc at discharge (-57 ±â€Š44 vs. 0.3 ±â€Š39 ms; P = 0.004), with the result that at discharge both groups showed a comparable QTc. CONCLUSION: Our results emphasized that typical TTS female patients with precipitating triggers have advanced age, clinical frailty and QTc abnormalities.