Effect of six month's treatment with omega-3 acid ethyl esters on long-term outcomes after acute myocardial infarction: The OMEGA-REMODEL randomized clinical trial.

BACKGROUND: Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain. AIMS: To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study. METHODS: Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG). RESULTS: A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HRadjusted = 0.460; 95%CI = 0.218-0.970; p = 0.041). CONCLUSION: In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes.

Prognostic value of visual and quantitative CMR regional myocardial function in patients with suspected myocarditis.

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HRadjusted = 1.132, 95% CI 1.020-1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification.

Impact of tafamidis on myocardial function and CMR tissue characteristics in transthyretin amyloid cardiomyopathy.

AIMS: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR-CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12-month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. METHODS AND RESULTS: ATTR-CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty-six tafamidis-treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV-GLS (-9.6 ± 3.2 to -9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV-function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (-10.9 ± 3.3 to -9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1-mapping did not change significantly from baseline to 12-month follow-up (P > 0.05). CONCLUSIONS: Compared with untreated ATTR-CM patients, initiation of tafamidis preserved CMR-measured biventricular function and reduced LV mass at 12 months. ECV and native T1-mapping did not change significantly comparable to baseline in both groups.

Current and Evolving Multimodality Cardiac Imaging in Managing Transthyretin Amyloid Cardiomyopathy.

Amyloid transthyretin (ATTR) amyloidosis is a protein-misfolding disease characterized by fibril accumulation in the extracellular space that can result in local tissue disruption and organ dysfunction. Cardiac involvement drives morbidity and mortality, and the heart is the major organ affected by ATTR amyloidosis. Multimodality cardiac imaging (ie, echocardiography, scintigraphy, and cardiac magnetic resonance) allows accurate diagnosis of ATTR cardiomyopathy (ATTR-CM), and this is of particular importance because ATTR-targeting therapies have become available and probably exert their greatest benefit at earlier disease stages. Apart from establishing the diagnosis, multimodality cardiac imaging may help to better understand pathogenesis, predict prognosis, and monitor treatment response. The aim of this review is to give an update on contemporary and evolving cardiac imaging methods and their role in diagnosing and managing ATTR-CM. Further, an outlook is presented on how artificial intelligence in cardiac imaging may improve future clinical decision making and patient management in the setting of ATTR-CM.

Myocardial analysis from routine 4D cardiac-CT to predict reverse remodeling and clinical outcomes after transcatheter aortic valve implantation.

PURPOSE: Our study aimed to determine whether 4D cardiac computed tomography (4DCCT) based quantitative myocardial analysis may improve risk stratification and can predict reverse remodeling (RRM) and mortality after transcatheter aortic valve implantation (TAVI). METHODS: Consecutive patients undergoing clinically indicated 4DCCT prior to TAVI were prospectively enrolled. 4DCCT-derived left- (LV) and right ventricular (RV), and left atrial (LA) dimensions, mass, ejection fraction (EF) and myocardial strain were evaluated to predict RRM and survival. RRM was defined by either relative increase in LVEF by 5% or relative decline in LV end diastolic diameter (LVEDD) by 5% assessed by transthoracic echocardiography prior TAVI, at discharge, and at 12-month follow-up compared to baseline prior to TAVI. RESULTS: Among 608 patients included in this study (55 % males, age 81 ± 6.6 years), RRM was observed in 279 (54 %) of 519 patients at discharge and in 218 (48 %) of 453 patients at 12-month echocardiography. While no CCT based measurements predicted RRM at discharge, CCT based LV mass index and LVEF independently predicted RRM at 12-month (ORadj = 1.012; 95 %CI:1.001-1.024; p = 0.046 and ORadj = 0.969; 95 %CI:0.943-0.996; p = 0.024, respectively). The most pronounced changes in LVEF and LVEDD were observed in patients with impaired LV function at baseline. In multivariable analysis age (HRadj = 1.037; 95 %CI:1.005-1.070; p = 0.022) and CCT-based LVEF (HRadj = 0.972; 95 %CI:0.945-0.999; p = 0.048) and LAEF (HRadj = 0.982; 95 %CI:0.968-0.996; p = 0.011) independently predicted survival. CONCLUSION: Comprehensive myocardial functional information derived from routine 4DCCT in patients with severe aortic stenosis undergoing TAVI could predict reverse remodeling and clinical outcomes at 12-month following TAVI.

Association of Adverse Clinical Outcomes With Peri-Infarct Ischemia Detected by Stress Cardiac Magnetic Imaging.

BACKGROUND: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction. OBJECTIVES: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers. METHODS: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery. RESULTS: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HRadjusted: 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%). CONCLUSIONS: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events.