Association of uncertain significance genetic variants with myocardial mechanics and morphometrics in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Careful interpretation of the relation between phenotype changes of the heart and gene variants detected in dilated cardiomyopathy (DCM) is important for patient care and monitoring. OBJECTIVE: We sought to assess the association between cardiac-related genes and whole-heart myocardial mechanics or morphometrics in nonischemic dilated cardiomyopathy (NIDCM). METHODS: It was a prospective study consisting of patients with NIDCM. All patients were referred for genetic testing and a genetic analysis was performed using Illumina NextSeq 550 and a commercial gene capture panel of 233 genes (Systems Genomics, Cardiac-GeneSGKit®). It was analyzed whether there are significant differences in clinical, two-dimensional (2D) echocardiographic, and magnetic resonance imaging (MRI) parameters between patients with the genes variants and those without. 2D echocardiography and MRI were used to analyze myocardial mechanics and morphometrics. RESULTS: The study group consisted of 95 patients with NIDCM and the average age was 49.7 ± 10.5. All echocardiographic and MRI parameters of myocardial mechanics (left ventricular ejection fraction 28.4 ± 8.7 and 30.7 ± 11.2, respectively) were reduced and all values of cardiac chambers were increased (left ventricular end-diastolic diameter 64.5 ± 5.9 mm and 69.5 ± 10.7 mm, respectively) in this group. It was noticed that most cases of whole-heart myocardial mechanics and morphometrics differences between patients with and without gene variants were in the genes GATAD1, LOX, RASA1, KRAS, and KRIT1. These genes have not been previously linked to DCM. It has emerged that KRAS and KRIT1 genes were associated with worse whole-heart mechanics and enlargement of all heart chambers. GATAD1, LOX, and RASA1 genes variants showed an association with better cardiac function and morphometrics parameters. It might be that these variants alone do not influence disease development enough to be selective in human evolution. CONCLUSIONS: Combined variants in previously unreported genes related to DCM might play a significant role in affecting clinical, morphometrics, or myocardial mechanics parameters.

Potential Prognostic Relevance of Left-Ventricular Global Longitudinal Strain and of the Summation of the Mitral and Tricuspid Regurgitation Volume in Patients with Non-Ischemic Dilated Cardiomyopathy.

BACKGROUND: The aim of this pilot study was to determine the potential prognostic relevance of novel multidirectional myocardial and volumetric echocardiographic parameters in patients with non-ischemic dilated cardiomyopathy (NIDCM). METHODS: Multidirectional myocardial parameters (longitudinal, radial, and circumferential left-ventricular (LV) strain using speckle tracking echocardiography) and a new volumetric parameter (the sum of the mitral and tricuspid regurgitation volume (mitral-tricuspid regurgitation volume) were assessed. The cardiovascular (CV) outcome was a composite of cardiac death and hospitalization for heart failure (HF) at 1 year. RESULTS: Approximately 102 patients were included in this pilot study. The mean LV ejection fraction (LVEF) was 28.4 ± 8.9%. During a follow-up of 1 year, the CV outcome occurred in 39 patients (10 HF deaths, and 36 hospitalizations for HF). The LV global longitudinal systolic strain (GLS) and mitral-tricuspid regurgitation volume were the main parameters that were seen to be significantly altered in the comparison of patients with events vs. those without events (GLS (absolute values) 7.4 ± 2.7% vs. 10.3 ± 2.6%; mitral-tricuspid regurgitation volume 61.1 ± 20.4 mL vs. 40.9 ± 22.9 mL, respectively; p-value < 0.01). In line with these findings, in a multivariate continuous logistic regression analysis, the GLS and mitral-tricuspid regurgitation volume were the main parameters associated with worse CV outcomes (GLS: OR 0.77 (95%CI 0.65-0.92); mitral-tricuspid regurgitation volume OR 1.09 (95%CI 1.01-1.25)), whereas the radial and circumferential LV global strain and mitral regurgitation volume and tricuspid regurgitation volume were not linked to the CV outcome. Furthermore, in a receiver operating characteristic curve analysis, a GLS cutoff of <7.5% and mitral-tricuspid regurgitation volume > 60 mL were the identified values for the parameters associated with worse CV outcomes. CONCLUSIONS: The findings of this pilot study suggest that the GLS and a novel volumetric parameter (the sum of the mitral and tricuspid regurgitation volume) are linked to worse CV outcomes in patients with non-ischemic dilated cardiomyopathy. Hence, these promising results warrant further validation in larger studies.

Relationships of Whole-Heart Myocardial Mechanics and Cardiac Morphometrics by Transthoracic Echocardiography with Main Prognostic Factors of Heart Failure in Non-Ischemic Dilated Cardiomyopathy.

BACKGROUND: there are many prognostic factors of heart failure (HF) based on their evaluation from imaging, to laboratory tests. In clinical practice, it is crucial to use widely available, cheap, and easy-to-use prognostic factors, such as left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, 6 min walk test (6MWT), B-type natriuretic peptide (BNP), etc. We sought to evaluate the relationships between whole-heart myocardial mechanics and cardiac morphometrics with the main commonly used prognostic factors of HF in patients with non-ischemic dilated cardiomyopathy (NIDCM). METHODS AND RESULTS: two-dimensional (2D) echocardiography for myocardial mechanics (global longitudinal, radial, and circumferential strains of the left ventricle; right ventricular longitudinal strain; strain values of reservoir, conduit, and contraction function of both atria) and cardiac morphometric (diameters and volumes of both atria and ventricles) parameters were performed, and the HF main traditional prognostic factors were identified. We assessed 109 patients (68.8% male; 49.7 ± 10.5 years) with newly diagnosed NIDCM. Myocardial mechanics and morphometrics were weakly correlated with the patient's age, gender, and smoking (R = 0.2, p < 0.05). Stronger relationships were observed with NYHA class, 6MWT, and BNP (the strongest correlations were with LVEF: R = -0.499, R 0.462, R = -0.461, p < 0.001, respectively). There were moderately strong correlations with LVEF and other whole-heart myocardial mechanics or morphometrics. Moreover, LVEF with global regurgitation volume (GRV) and right ventricle free wall longitudinal strain (RVFWLS) were the most usually detected parameters in multivariate analysis to be associated with changes in HF prognostic factors. CONCLUSIONS: in NIDCM patients, the main prognostic factors of HF are correlated with whole-heart myocardial mechanics and morphometrics. However, LVEF, GRV, and RVFWLS are the most usually found 2D echocardiographic factors associated with changes in HF prognostic factors.

Association of Whole-Heart Myocardial Mechanics by Transthoracic Echocardiography with Presence of Late Gadolinium Enhancement by CMR in Non-Ischemic Dilated Cardiomyopathy.

Background: In patients with non-ischemic dilated cardiomyopathy (NIDCM), myocardial fibrosis (MF) is related to adverse cardiovascular outcomes. The purpose of this study was to evaluate the potential relationship between the myocardial mechanics of different chambers of the heart and the presence of MF and to determine the accuracy of the whole-heart myocardial strain parameters to predict MF in patients with NIDCM. Methods: We studied 101 patients (64% male; 50 ± 11 years) with a first-time diagnosis of NIDCM who were referred for a clinical cardiovascular magnetic resonance (CMR) and speckle tracking 2D echocardiography examination. We analyzed MF by late gadolinium enhancement (LGE), and the whole-heart myocardial mechanics were assessed by speckle tracking. The presence of MF was related to worse strain parameters in both ventricles and atria. The strongest correlations were found between MF and left ventricle (LV) global longitudinal strain (GLS) (r = −0.586, p < 0.001), global circumferential strain (GCS) (r = −0.609, p < 0.001), LV ejection fraction (LVEF) (r = 0.662, p < 0.001), and left atrial strain during the reservoir phase (LASr) (r = 0.588, p < 0.001). However, the binary logistic regression analysis revealed that only LV GLS, GCS, and LASr were independently associated with the presence of MF (area under the curves of 0.84, 0.85, and 0.64, respectively). None of the echocardiographic parameters correlated with fibrosis localization. Conclusions: In NIDCM patients, MF is correlated with reduced mechanical parameters in both ventricles and atria. LV GLS, LASr, and LV GCS are the most accurate 2D echocardiography predictive factors for the presence of MF.

Genotype-Phenotype Correlation in Familial BAG3 Mutation Dilated Cardiomyopathy.

We report the case of a 22-year-old male who visited a cardiologist after the first episode of atrial fibrillation (AF). Echocardiography and magnetic resonance imaging revealed decreased left ventricular (LV) systolic function with dilated LV. An intermittent second-degree AV (atrioventricular) block was detected during 24 h Holter monitoring. Genetic test revealed the pathogenic variant of the BAG3 (BLC2-associated athanogene 3) gene. Due to the high risk of heart failure (HF) progression and ventricular arrhythmias, an event recorder was implanted and a pathogenetic HF treatment was prescribed. The analysis of genealogy revealed that the patient's father, at the age of 32, was diagnosed with dilated cardiomyopathy (DCM) and recurrent AF episodes. Genetic testing also confirmed a pathogenic variant of the BAG3 gene. Currently, with the optimal treatment of HF, the patient's disease has been stable for three years and the condition is closely monitored on an outpatient basis. So, we demonstrate the importance of early detection for genetic testing and the unusual stability exhibited by the patient's optimal medical therapy for 3 years.

Early outcomes of patient-prosthesis mismatch following aortic valve replacement.

INTRODUCTION: Patient-prosthesis mismatch (PPM) has been associated with numerous short- and long-term adverse events. This study aimed to evaluate the effect of PPM on early postoperative results after aortic valve replacement (AVR) in daily practice. METHODS: In this single-centre retrospective study, 150 non-consecutive patients from March 2019 to January 2020 with clinically indicated AVR with/without concomitant surgery were analysed. The study protocol included operative mortality, complication rate, and pre- and postoperative echocardiographic data. PPM was considered severe with indexed effective orifice area at <0.65 cm2/m2, moderate at 0.65-0.85 cm2/m2 and none at >0.85 cm2/m2. RESULTS: Moderate PPM was observed in 16 patients (10.6%). No patient had severe PPM. PPM was not related to early mortality (r = 0.40, p = 0.630), intra- (r = -0.076, p = 0.352) and postoperative (r = -0.0134, p = 0.102) events. CONCLUSION: In this study, moderate PPM was a frequent finding after AVR, whereas severe PPM was not observed. PPM did not affect the early results after AVR. A long-term follow-up study in a large patient population is required to assess the actual influence of residual PPM.

Early Hemodynamics after Aortic Valve Replacement.

Background and objectives: The aims of this study were to investigate changes in the hemodynamics associated with different types of aortic prostheses and to evaluate patient-prosthesis mismatch (PPM) at rest and after exercise. Materials and Methods: We retrospectively analyzed 150 patients who presented with indications for aortic valve replacement (AVR) with/without concomitant surgery from March 2019 to January 2020. The study population included 90 (60%) men and 60 (40%) women (mean age, 67.33 ± 10.22 years; range, 37-88 years). Echocardiography data such as peak and mean transprosthetic pressure gradients (Gmax, Gmean), velocity (V), effective orifice area (EOA), and indexed EOA (iEOA) were derived at rest and after exercise at baseline and before discharge. The study patients performed the six-minute walk test (6MWT) on the 5th-7th postoperative day. Results: Stented tissue valves showed excellent performance at rest and after exercise in comparison with mechanical valves, which showed favorable hemodynamics at rest only. At the time of discharge, moderate PPM was observed in 7/74 patients (9.5%) at rest and 5/98 (3.3%) patients after exercise. None of the patients showed severe PPM. EOA and iEOA were not significantly different between the groups. However, the stented group showed more pronounced changes in EOA and iEOA after exercise, whereas the changes in the mechanical valve group did not reach significance. Conclusions: In the early postoperative period, mechanical valves and stented valves showed favorable resting hemodynamics. The PPM rate measured after exercise was lower than that at rest.