Functional Left Ventricular Remodeling Research Articles

Trimethylamine N-oxide as a Novel Biomarker for Left Ventricular Diastolic Dysfunction and Functional Remodeling in ST-Elevation Myocardial Infarction Patients

Abstract Background Over the last three decades, the mortality from ST-elevation myocardial infarction (STEMI) has halved. However, the incidence of heart failure or persistent angina remains high after STEMI, and the post-STEMI left ventricular (LV) systolic and diastolic function remains unpredictable. Thus, there is an unmet need to identify patients at risk of LV diastolic dysfunction or adverse remodeling. Purpose This study aims to investigate the potential of Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite associated with heart failure, and atherosclerosis, as a biomarker for adverse LV remodeling and diastolic dysfunction following STEMI. Methods In this prospective, observational cohort study, 210 STEMI patients with multivessel coronary artery disease (CAD) were enrolled after primary PCI. At 3 months follow-up, all patients underwent complete revascularization with FFR-guided PCI. Plasma TMAO, C-reactive protein (CRP), and brain natriuretic peptide (BNP) levels at 3 months follow-up and peak troponin level at primary PCI were collected. Echocardiographies were performed within 24 hours of STEMI and at 12-month follow-ups. Diastolic dysfunction was defined according to the ASE 2016 guidelines.(1) Functional LV remodeling (FLVR) was categorized into 4 categories according to Chimed et al.(2) Receiver operating characteristic (ROC) curve analysis, including the Delong test and Youden index, was performed to compare the biomarkers' diagnostic value and determine the optimal cutoffs for predicting diastolic dysfunction and FLVR, respectively. Results Of the 210 patients enrolled, 85 (40.48%) were female, with a median age of 65 years [interquartile range (IQR): 58.00, 76.00] and a median body mass index (BMI) of 27.39 kg/m² (IQR: [24.56, 30.69]). The area under the ROC curve for predicting post-PCI LV diastolic dysfunction ≥ grade II was 0.72 (95% CI 0.63–0.81; p<0.001) for TMAO (Figure 1). The optimal TMAO cutoff value of 3.80 yielded a sensitivity of 0.75 (95% CI 0.63–0.86) and a specificity of 0.82 (95% CI 0.76–0.88). For FLVR grade 3 or 4, the area under the ROC curve was 0.62 (95% CI 0.50–0.74) and 0.72 (95% CI 0.62 -0.83) for TMAO and BNP, respectively (Figure 2), but the AUC was not significantly different (p= 0.191). In multivariable logistic regression analysis, TMAO was independently associated with FLVR grade 3 or 4 (OR 1.18, 95% CI 1.00-1.38, p = 0.046) and diastolic dysfunction ≥grade 2 (OR 1.30, 95% CI 1.12-1.50, p < 0.001). Conclusion The novel parameter of TMAO is a useful predictor for LV diastolic dysfunction after STEMI. TMAO is independently associated with an increased risk of LV diastolic dysfunction and worse FLVR. These results suggest that monitoring plasma TMAO levels could be an effective and cost-efficient strategy for monitoring patients with an elevated risk of LV diastolic dysfunction or adverse LV remodeling.Figure 1Figure 2

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy: A Prognosis Study

ObjectivesThe aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM). BackgroundPatients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated. MethodsA total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test. ResultsDuring a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001). ConclusionsT1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.

Aortic stiffness and interstitial myocardial fibrosis by native T1 are independently associated with left ventricular remodeling in patients with dilated cardiomyopathy.

Increased aortic stiffness is related to increased ventricular stiffness and remodeling. Myocardial fibrosis is the pathophysiological hallmark of failing heart. We investigated the relationship between noninvasive imaging markers of myocardial fibrosis, native T1, and late gadolinium enhancement, respectively, and aortic stiffness in ventricular remodeling. Consecutive patients with known dilated cardiomyopathy (n=173) underwent assessment of cardiac volumes and function, T1 mapping, scar imaging, and pulse wave velocity, a measure of aortic stiffness. Asymptomatic healthy volunteers served as controls (n=47). Controls and patients showed an increase in pulse wave velocity with age, which was accelerated in the presence of cardiovascular disease. On the contrary, native T1 increased with age in patients, but not in controls. Pulse wave velocity was associated with native T1 in the presence of disease, but not in health. Native T1 showed a strong relationship with markers of structural and functional left ventricular remodeling and diastolic impairment. Ischemic and nonischemic pathophysiology of ventricular remodeling showed a similar slope of relationship between pulse wave velocity and native T1. However, in nonischemic patients, increase in pulse wave velocity was associated with greater increase in native T1. Aortic stiffness is related to age, and this process is accelerated in the presence of disease. On the contrary, increase in interstitial myocardial fibrosis is associated with age in the presence of disease. Patients with ischemic and nonischemic dilated cardiomyopathy have a similar relationship between native T1 and pulse wave velocity, which is stronger in the latter group.