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Prognosis of early pre-discharge and late left ventricular dilatation by cardiac magnetic resonance imaging after acute myocardial infarction.

ABSTRACT: To study the long-term prognosis of early pre-discharge and late left ventricular (LV) dilatation in patients with first ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) and contemporary medical therapy. Long-term follow-up > 15 years was available in 53 consecutive patients (55 ± 13 years) with first STEMI. Late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (CMR) was obtained at baseline 5 ± 3 days and follow-up 8 ± 3 months after STEMI to measure LV function, volumes and infarct size. Early pre-discharge dilatation was defined as increased left ventricular end-diastolic volume index (LVEDVi) at baseline CMR with > 97 ml/m² for males and > 90 ml/m² for females. Late dilatation was defined as initially normal LVEDVi, which increased ≥ 20% at follow-up. Early dilatation was present in 7 patients (13%), whereas late dilatation occurred in 11 patients (21%). Patients with early LV dilatation had highest mortality (57%), whereas patients with late dilatation had similar mortality (27%) compared to patients without dilatation (26%). Multivariate Cox analysis showed that age (P < 0.001), ejection fraction at baseline (P < 0.01) and early dilatation (P < 0.01) were independent predictors of death. Early dilatation qualified as an exclusive independent predictor of long-term mortality after adjustment for age and ejection fraction (P < 0.05, hazard ratio: 2.2, 95% confidence interval: 1.2 to 7.9). Early pre-discharge LV dilatation by CMR enabled strong long-term risk stratification after STEMI. The high mortality of early LV dilatation underscores the clinical importance of this post-infarction complication, which occurred despite PCI and contemporary medical therapy.

SUBMITTER: Sinn MR

PROVIDER: S-EPMC8105219 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPatients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.MethodsWe performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.ResultsFrom July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m2 (95% CI, -4.9 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.ConclusionsIn patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.

Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses We report temporal and regional changes in steady state mRNA levels in the mouse LV following a surgically-induced AMI. Three regions of the infarcted LV were surveyed: IF, FW and IVS. For each region, mRNA levels were assayed at t=0 and six time points after occlusion of the left anterior descending coronary artery (t = 15 min, 1 h, 4 h, 12 h, 24 h, 48 h). As control, an identical time course was carried out in the mouse LV after sham surgery in which the suture was passed under the artery, but not ligated. For sham surgical mice and naïve mice (t=0), the IVS and the LV free wall were harvested and assayed. The AMI and sham time courses were repeated for a total of two independent repetitions of the experiment. For each repetition, 96 GeneChips were hybridized. Thus, for two repetitions, 192 GeneChips (2 x 96) were hybridized. In addition, the naïve time point was assayed a second time during Repetition 1 for six additional GeneChips (two tissues x three chips). The overall total number of samples is 198 GeneChips (192 + 6). Total RNA was isolated from each individual tissue sample. Equal weights of total RNA from 4-10 mice were combined for each LV region, time point and treatment. Copy RNA mixtures were synthesized from each total RNA pool and hybridized to the Affymetrix GeneChip set MG U74 v2 (A, B, and C) that carries 36,899 probe sets. The global normalization of fluorescence emissions for the 198 GeneChips used in this study and their conversion to relative transcript concentrations measured in relative fluorescence units (RFU) was conducted using Robust Multi-array Averaging (RMA; www.bioconductor.org). Each of the 198 Accessions is titled as follows: time point / treatment / tissue, repetition, GeneChip. The additional assays of naïve mice in Repetition 1 are labeled “Naive2”.

Project description:Background Despite limitations as a stand-alone parameter, left ventricular (LV) ejection fraction is the preferred measure of myocardial function and marker for postinfarction risk stratification. LV myocardial uniformity alterations may provide superior prognostic information after acute myocardial infarction, which was the subject of this study. Methods and Results Consecutive patients with acute myocardial infarction (n=1082; median age: 63 years; 75% male) undergoing cardiac magnetic resonance at a median of 3 days after infarction were included in this multicenter observational study. Circumferential and radial uniformity ratio estimates were derived from cardiac magnetic resonance feature tracking as markers of mechanical uniformity alterations (values between 0 and 1 with 1 reflecting perfect uniformity). The clinical end point was the 12-month rate of major adverse cardiac events, consisting of all-cause death, reinfarction, and new congestive heart failure. Patients with major adverse cardiac events (n=73) had significantly impaired circumferential uniformity ratio estimates (0.76 [interquartile range: 0.67-0.86] versus 0.84 [interquartile range: 0.76-0.89]; P<0.001) and radial uniformity ratio estimates (0.69 [interquartile range: 0.60-0.79] versus 0.76 [interquartile range: 0.67-0.83]; P<0.001) compared with patients without events. Although uniformity estimates did not provide independent prognostic information in the overall cohort, a circumferential uniformity ratio estimate below the median of 0.84 emerged as an independent predictor of outcome in postinfarction patients with LV ejection fraction >35% (n=959), even after adjustment for established risk factors (hazard ratio: 1.99; 95% CI, 1.06-3.74; P=0.033 in multivariable Cox regression analysis). In contrast, LV ejection fraction was not associated with adverse events in this subgroup of patients with acute myocardial infarction. Conclusions Cardiac magnetic resonance-derived estimates of mechanical uniformity alterations are novel markers for risk assessment after acute myocardial infarction, and the circumferential uniformity ratio estimate provides independent prognostic information for patients with preserved or only moderately reduced LV ejection fraction.

Project description:BackgroundMyocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment.MethodsForty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups.ResultsLV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = - 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF.ConclusionsReduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.

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Prognosis of early pre-discharge and late left ventricular dilatation by cardiac magnetic resonance imaging after acute myocardial infarction.

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