Left atrial geometric and functional remodeling parameters measured by cardiac magnetic resonance imaging and outcome prediction in patients with severe aortic stenosis.

BACKGROUND: Emerging studies are beginning to describe the role of afflicted left atrium (LA) function and strain in cardiovascular diseases including aortic stenosis (AS), especially for risk stratification and outcome prediction. Cardiac magnetic resonance imaging (CMR) is becoming increasingly useful in determining LA parameters; however, in patients with AS, this approach has not been applied yet. AIMS: This study sought to evaluate the role of CMR in characterizing LA geometry and function in patients with severe AS. METHODS: We prospectively evaluated 70 patients with symptomatic severe AS and 70 controls. LA volumes, function, and strain were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, and heart failure hospitalization) was evaluated over a median of 13 months. Time-to-event outcomes were analyzed accordingly. RESULTS: Besides increased LA volumes (LAVs) and LA sphericity index (LASI) (P <0.001), LA phasic functions and strain were considerably defective in patients with AS (all P <0.001). LV mass (LVM), end-diastolic and end-systolic volumes were also significantly associated withal LA strain parameters (P <0.001). Regarding outcome prediction, decreased total (LA-εt), active (LA-εa), and passive strain (LA-εp), along with enhanced LASI were independently associated with outcome (P <0.001). Time-to-event analysis showed a significantly higher risk to reach the composite outcome for LA-εt <31.1% (hazard ratio [HR], 6.981; 95% confidence interval [CI], 2.74-17.77; P <0.001), LA-εp <14.5% (HR, 2.68; 95% CI, 1.00-7.18; P <0.01), and LA-εa <21.2% (HR, 2.02; 95% CI, 1.07-3.83, P <0.03). CONCLUSION: Patients with severe AS have a significantly remodeled LA, with impaired phasic function and strain. Amongst all CMR parameters, LAVmin, LASI, LAPF, and LA-εp appear to be independent predictors for outcomes.

The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy.

Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 ± 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p < 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p < 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p < 0.0001). Kaplan−Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p < 0.001; HR = 1.93, p < 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Left Atrial Geometry and Phasic Function Determined by Cardiac Magnetic Resonance Are Independent Predictors for Outcome in Non-Ischaemic Dilated Cardiomyopathy.

Left atrial (LA) geometry and phasic functions are frequently impaired in non-ischaemic dilated cardiomyopathy (NIDCM). Cardiac magnetic resonance (CMR) can accurately measure LA function and geometry parameters. We sought to investigate their prognostic role in patients with NIDCM. We prospectively examined 212 patients with NIDCM (49 ± 14.2-year-old; 73.5% males) and 106 healthy controls. LA volumes, phasic functions, geometry, and fibrosis were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. LA phasic functions, sphericity index (LASI) and late gadolinium enhancement (LA-LGE) were considerably impaired in the diseased group (p < 0.001) and significantly correlated with impaired LV function parameters (p < 0.0001). After multivariate analysis, LA volumes, LASI, LA total strain (LA-εt) and LA-LGE were associated with increased risk of composite outcome (p < 0.001). Kaplan-Meier analysis showed significantly higher risk of composite endpoint for LA volumes (all p < 0.01), LASI > 0.725 (p < 0.003), and LA-εt < 30% (p < 0.0001). Stepwise Cox proportional-hazards models demonstrated a considerable incremental predictive value which resulted by adding LASI to LA-εt (Chi-square = 10.2, p < 0.001), and afterwards LA-LGE (Chi-Square = 15.8; p < 0.0001). NIDCM patients with defective LA volumes, LASI, LA-LGE and LA-εt had a higher risk for an outcome. LA-εt, LASI and LA-LGE provided independent incremental predictive value for outcome.

Left Ventricular Geometry and Replacement Fibrosis Detected by cMRI Are Associated with Major Adverse Cardiovascular Events in Nonischemic Dilated Cardiomyopathy.

To investigate the relationship between left ventricular (LV) long-axis strain (LAS) and LV sphericity index (LVSI) and outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) and myocardial replacement fibrosis confirmed by late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging (cMRI), we conducted a prospective study on 178 patients (48 ± 14.4 years; 25.2% women) with first NIDCM diagnosis. The evaluation protocol included ECG monitoring, echocardiography and cMRI. LAS and LVSI were cMRI-determined. Major adverse cardiovascular events (MACEs) were defined as a composite outcome including heart failure (HF), ventricular arrhythmias (VAs) and sudden cardiac death (SCD). After a median follow-up of 17 months, patients with LGE+ had increased risk of MACEs. Kaplan-Meier curves showed significantly higher rate of MACEs in patients with LGE+ (p < 0.001), increased LVSI (p < 0.01) and decreased LAS (p < 0.001). In Cox analysis, LAS (HR = 1.32, 95%CI (1.54-9.14), p = 0.001), LVSI [HR = 1.17, 95%CI (1.45-7.19), p < 0.01] and LGE+ (HR = 1.77, 95%CI (2.79-12.51), p < 0.0001) were independent predictors for MACEs. In a 4-point risk scoring system based on LV ejection fraction (LVEF) < 30%, LGE+, LAS > -7.8% and LVSI > 0.48%, patients with 3 and 4 points had a significantly higher risk for MACEs. LAS and LVSI are independent predictors of MACEs and provide incremental value beyond LVEF and LGE+ in patients with NIDCM and myocardial fibrosis.