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.

Tricuspid regurgitation: Frequency, clinical presentation, management and outcome among patients with severe left-sided valvular heart disease in Europe. Insights from the ESC-EORP Valvular Heart Disease II survey.

AIMS: Tricuspid regurgitation (TR) is commonly observed in patients with severe left-sided valvular heart disease (VHD). This study sought to assess TR frequency, management and outcome in this population. METHODS AND RESULTS: Among 6883 patients with severe native left-sided VHD or previous left-sided valvular intervention enrolled in the EURObservational Research Programme prospective VHD II survey, moderate or severe TR was very frequent in patients with severe mitral VHD (30% when mitral stenosis, 36% when mitral regurgitation [MR]), especially in patients with secondary MR (46%), and rare in patients with severe aortic VHD (4% when aortic stenosis, 3% when aortic regurgitation). An increase in TR grade was associated with a more severe clinical presentation and a poorer 6-month survival (p < 0.0001). Rates of concomitant tricuspid valve (TV) intervention at the time of left-sided heart valve surgery were high at the time of mitral valve surgery (50% when mitral stenosis, 41% when MR). Concordance between class I indications (patients with severe TR) for concomitant TV surgery at the time of left-sided valvular heart surgery according to guidelines and real-practice decision-making was very good (88% overall, 95% in patients operated on for MR). CONCLUSION: In this large international prospective survey among patients with severe left-sided VHD, moderate/severe TR was frequent in patients with mitral valve disease and was associated with a poorer outcome as TR grade increased. In patients with severe TR, compliance to guidelines for class I indications for concomitant TV surgery at the time of left-sided heart valve surgery was very good.

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.

Safety and performance of the Vienna self-expandable transcatheter aortic valve system: 6-month results of the VIVA first-in-human feasibility study.

Background: The novel Vienna TAVI system is repositionable and retrievable, already pre-mounted on the delivery system, eliminating the need for assembly and crimping of the device prior to valve implantation. Aims: The purpose of this first-in-human feasibility study was to determine the safety, feasibility, clinical and hemodynamic performance of the Vienna TAVI system at 6-month follow-up. (ClinicalTrials.gov identifier NCT04861805). Methods: This is a prospective, non-randomized, single-arm, single-center, first-stage FIH feasibility study, which is followed by a second-stage pivotal, multicenter, multinational study in symptomatic patients with severe aortic stenosis (SAS). The first-stage FIH study evaluated the safety and feasibility, clinical and hemodynamic performance of the device in 10 patients with SAS based on recommendations by the VARC-2. Results: All patients were alive at 3-month follow-up. 1 non-cardiovascular mortality was reported 5 months after implantation. There were no new cerebrovascular events, life-threatening bleeding or conduction disturbances observed at 6-month follow-up. The mean AV gradient significantly decreased from 48.7 ± 10.8 to 7.32 ± 2.0 mmHg and mean AVA increased from 0.75 ± 0.18 to 2.16 ± 0.42 cm2 (p < 0.00001). There was no incidence of moderate or severe total AR observed. In the QoL questionnaires, the patients reported a significant improvement from the baseline 12-KCCQ mean score 58 ± 15 to 76 ± 20. NYHA functional class improved in two patients, remained unchanged in one patient. There was an increase in mean 6-min-walk distance from baseline 285 ± 97 to 347 ± 57 m. Conclusions: This study demonstrates that using Vienna TAVI system has favourable and sustained 6-month safety and performance outcomes in patients with symptomatic severe aortic stenosis.

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.

Risk Factors of Early Atrial Fibrillation Recurrence Following Electrical Cardioversion When Left Ventricular Ejection Fraction Is Preserved.

Background and objectives: To identify clinical, echocardiographic, and laboratory parameters that affect the early recurrence of atrial fibrillation (AF) after restoring sinus rhythm (SR) by electrical cardioversion (ECV), and to determine whether left atrial (LA) strain, as a noninvasive indicator reflecting fibrosis, is associated with laboratory indicators affecting the development of fibrosis, interleukin 6 (IL-6) or tumor necrosis factor α (TNF-α). Materials and Methods: The study included 92 persistent AF patients who underwent elective ECV. The effective maintenance of SR was evaluated after 40 ± 10 days of ECV. Echocardiography, inflammatory markers (high-sensitivity c-reactive protein (hs-CRP), IL-6, and TNF-α), and natriuretic peptides (N-terminal pro b-type natriuretic peptide (NT-proBNP) and N-terminal pro a-type natriuretic peptide (NT-proANP)) were assessed. Results: After a 40 ± 10 days observation period, 51 patients (55.4%) were in SR. Patients with AF recurrence had a significantly longer duration of AF (p = 0.008) and of arterial hypertension (p = 0.035), lower LA ejection fraction (p = 0.009), lower LA strain (p < 0.0001), higher left ventricular global longitudinal strain (p = 0.001), and a higher E/e' ratio (p < 0.0001). LA strain was an independent predictor of early AF recurrence (OR: 0.65; 95% Cl 0.5−0.9, p = 0.004). LA strain < 11.85% predicted AF recurrence with 70% sensitivity and 88% specificity (AUC 0.855, 95% CI 0.77−0.94, p < 0.0001). LA strain demonstrated the association with NT-proBNP (r = −0.489, p < 0.0001) and NT-proANP (r = −0.378, p = 0.002), as well as with hs-CRP (r = −0.243, p = 0.04). Conclusions: LA strain appeared to be the most accurate predictor of early AF recurrence after ECV in patients with persistent AF. LA strain inversely correlated with NT-proBNP and NT-proANP, but no significant association with any of the inflammatory markers was identified.

The Predictive Value of Tissue Doppler Indices for Early Recurrence of Atrial Fibrillation After Electrical Cardioversion.

PURPOSE: Spectral tissue Doppler-derived E/e' ratio has been proposed as the best parameter for prediction of atrial fibrillation (AF). Relaxation and contraction are equivalent parts of a continuous cardiac cycle, where systolic and diastolic abnormalities have a variable contribution to the left ventricle (LV) failure. The aim of this study was to investigate whether the E/(e'xs') ratio is a better index than E/e' to predict AF recurrence and to determine the changes of spectral tissue Doppler indices 1 month after the electrical cardioversion (ECV). PATIENTS AND METHODS: The study included 77 persistent AF patients with restored sinus rhythm (SR) after ECV. Only patients with normal LV ejection fraction (EF) were included. Echocardiography and NT-proBNP laboratory findings were performed. A primary outcome was the early (within 1 month) recurrence of AF. RESULTS: After a 1 month follow-up period, 39 patients (50.6%) were in SR. E/e' (HR=1.74, P=0.001) and E/(e'×s') ratios (HR=8.17, P=0.01) were significant predictors of AF recurrence. E/(e'×s') in combination with LV end-diastolic diameter >49.3 mm and NT-proBNP >2000 ng/L demonstrated a higher contribution in the model to predict AF recurrence compared to the E/e' ratio (18.94, P=0.005 vs 1.95, P=0.001). On ROC analysis, E/(e'×s') and E/e' showed similar diagnostic accuracy (E/(e'×s'), AUC=0.71, P=0.002 and E/e', AUC=0.75, P<0.0001). Average e' value significantly decreased after 1 month in SR (from 10.76±1.24 to 8.96±1.47 cm/s, P=0.01), E wave did not change significantly and E/e' ratio tended to improve. A decrease of average e' and an increase of average s' values led to significant improvement of E/(e'xs') ratio. CONCLUSION: E/(e'xs') and E/e' ratios are comparable to predict early AF recurrence after ECV in patients with persistent AF. The e' value decreased significantly after 1 month follow-up period after ECV for persistent AF patients.

Right Ventricle Mechanics and Function during Stress in Patients with Asymptomatic Primary Moderate to Severe Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction.

Background and objectives. Mitral regurgitation (MR) is usually dynamic and increasing with exertion. Stress may provoke symptoms, cause the progression of pulmonary hypertension (PH) and unmask subclinical changes of the left and right ventricle function. The aim of this study was to evaluate changes of right ventricle (RV) functional parameters during stress and to find out determinants of RV function in patients with MR. Materials and methods. We performed a prospective study that included patients with asymptomatic primary moderate to severe MR and preserved left ventricular (LV) ejection fraction (EF) at rest (≥60%). Conventional 2D echocardiography at rest and during stress (bicycle ergometry) and offline speckle tracking analysis were performed. Results. 80 patients were included as MR (50) and control (30) groups. Conventional functional and myocardial deformation parameters of RV were similar in both groups at all stages of exercise (p > 0.05). The grade of MR (p = 0.004) and higher LV global longitudinal strain (p = 0.037) contributed significantly to the changes of tricuspid annular plane systolic excursion (TAPSE) from rest to peak stress. Changes of MR ERA from the rest to peak stress were related to RV free wall longitudinal strain (FWLS) and four chambers longitudinal stain (4CLS) at rest (p = 0.011; r = -0.459 and p = 0.001; r = -0.572, respectively). Significant correlations between LV EF, stroke volume, cardiac output and RV fractional area change, S', TAPSE, FWLS, 4CLS were obtained. However, systolic pulmonary artery pressure and RV functional, deformation parameters were not related (p > 0.05). Conclusions. Functional parameters of LV during exercise and severity of MR were significant determinants of RV function while PH has no correlation with it in patients with primary asymptomatic moderate to severe MR.

Long-term ischemic mitral regurgitation: which parameters predict decrease or increase in the degree after five years?

BACKGROUND: Ischemic mitral regurgitation (IMR) is a frequent valvular heart disease and is related to worse prognosis. The aim of this study was to investigate the dynamics in the degree of IMR from the acute phase of inferoposterior myocardial infarction (MI) to 5-years follow-up and to identify the predictors of change in the degree of mitral regurgitation (MR). METHODS: We included patients with first ever acute inferoposterior MI and examined them in two phases: at the time of acute MI then 5 years later. Based on two-dimensional transthoracic echocardiography, the patients were divided into the non-significant MR (NMR) group and IMR group. The parameters of left ventricle (LV), mitral apparatus and clinical data were assessed in both phases. The predictors of a decrease or an increase in the degree of mitral regurgitation after 5 years were identified. RESULTS: The values of the parameters of mitral apparatus and LV chambers increased with higher degrees of IMR. The tenting height, systolic blood pressure and posteromedial papillary muscle (PMPM) displacement during the acute phase were the most important in predicting the change in the degree of MR after 5 years. CONCLUSIONS: The assessment of mitral apparatus in acute phase of MI can be most useful to determine the change of the degree of MR long-term post MI. Although LV remodelling itself contributes to IMR, this influence is directly dependent on alterations in mitral geometry.

Long-term outcomes and predictors of recurrent aortic regurgitation after aortic valve-sparing and reconstructive cusp surgery: a single centre experience.

BACKGROUND: Aortic valve sparing surgery (AVS), in combination with aortic cusp repair (ACR), still raises many questions about the increased surgical complexity and applicability for patients with pure aortic valve regurgitation (AR). The aim of this study was to investigate our long-term outcomes and predictors of recurrent AR (> 2+) after AVS and reconstructive cusp surgery. METHODS: We reviewed data of 81 patients who underwent AVS (a reimplantation technique) with concomitant ACR for AR and or dilatation of the aortic root at our institution during the period from April 2004 to October 2016. On preoperative echocardiography, the majority of the patients, 70 (86.4%) presented with severe AR grade (> 3+) and 28 (34.5%) of the patients had the bicuspid phenotype. Time to event analysis (long-term survival, freedom from reoperation, and recurrence of AR > 2+) was performed with the Kaplan-Meier method. Multivariate Cox regression risk analysis was performed to identify independent predictors of recurrent AR (> 2+). The mean follow-up was 5.3 ± 3.3 years and 100% complete. RESULTS: The in-hospital (30-day) mortality rate after elective surgery was 1.2%. The overall actuarial survival rates were 92.9 ± 3.1% and 90.4 ± 3.9% at five and 10 years, respectively. Actuarial freedom from recurrent AR (> 2+) was 83.7 ± 4.5% within the cohort at five and 10 years. The cumulative freedom from all causes of cardiac reoperation was 94.2 ± 2.8% within the cohort at 10 years. Neither bleeding nor thromboembolic or permanent neurologic events were reported during follow-up. By multivariate analysis, independent predictors of reccurent AR (> 2+) were an effective height lower than 9 mm (p= 0.02) and intraoperative residual mild AR (p= 0.0001). CONCLUSIONS: AVS with ACR, combined in a systematic fashion, is a safe and reproducible option with low risk of long-term valve related events and normal life expectancy for patients with pure aortic regurgitation. The competent aortic valve and effective height, not lower than 9 mm intraoperatively, are mandatory to achieve long-lasting AV competency.

Relationship of Natriuretic Peptides with Left Atrial Structure and Function within 1 Month after Electrical Cardioversion in Patients with Persistent Atrial Fibrillation.

Atrial fibrillation (AF) despite the absence of heart failure is related to increased levels of natriuretic peptides (NPs). NPs have not been widely investigated in relation to left atrium (LA) function after sinus rhythm (SR) restoration and duration of AF. The aim of the study was to determine the changes of NPs levels and to define their relation with LA phasic function after electrical cardioversion (ECV). Methods. The study included 48 persistent AF patients with restored SR after ECV. NT-proANP and NT-proBNP were measured for all patients before the ECV. LA phasic function (reservoir, conduit, and pump phases) was assessed using echocardiographic volumetric analysis within the first 24 hours after ECV. Patients were repeatedly tested after 1 month in case of SR maintenance. Results. After 1 month, SR was maintained in 26 (54%) patients. For those patients, NT-proBNP decreased significantly (p=0.0001), whereas NT-proANP tended to decrease (p=0.13). Following 1 month after SR restoration, LA indexed volume decreased (p=0.0001) and all phases of LA function improved (p=<0.01). Patients with AF duration < 3 months had lower NT-proANP compared to patients with AF duration from 6 to 12 months (p = 0.005). Higher NT-proANP concentration before ECV was associated with lower LA reservoir function during the first day after SR restoration (R=-0.456, p=0.005), whereas higher NT-proBNP concentration after 1 month in SR was significantly related to lower LA reservoir function (R=-0.429, p=0.047). Conclusions. LA indexed volume, all phases of LA function, and NT-proBNP levels improved significantly following 1 month of SR restoration. Preliminary results suggest that higher baseline NT-proANP levels and higher NT-proBNP for patients with maintained SR for 1 month are related to lower LA reservoir function. The longer duration of persistent AF is associated with higher NT-proANP concentration.

Early and long-term results of aortic valve sparing aortic root reimplantation surgery for bicuspid and tricuspid aortic valves.

INTRODUCTION: To evaluate early and long-term clinical outcomes following aortic valve sparing aortic root reimplantation surgery in patients with leaking bicuspid and tricuspid aortic valves. METHODS: The study consisted of 92 consecutive adult patients (tricuspid aortic valve group = 63 and bicuspid aortic valve group = 29) who underwent aortic valve sparing aortic root reimplantation surgery with or without aortic cusp repair for dilatation of the aortic root and/or aortic valve regurgitation at our institution from April 2004 to October 2016. Clinical outcomes were investigated using Kaplan-Meier and log-rank tests between groups. RESULTS: The follow-up was 100% complete with a mean time of 5.3 ± 3.3 years. The 30-day in-hospital mortality was 3.1% in tricuspid aortic valve group and 3.4% in bicuspid aortic valve group patients. The overall survival rates at 10 years did not differ between bicuspid aortic valve and tricuspid aortic valve patient groups (96.6 ± 3.3% vs. 90.3 ± 4.2%, p = 0.3). Freedom from recurrent aortic valve regurgitation (>2+) at 10 years was 90.5 ± 4.1% in tricuspid aortic valve group and 75.7 ± 8.7% in bicuspid aortic valve group (p = 0.06). Freedom from aortic valve reoperation at 10 years was 100% in tricuspid aortic valve group and 83.9 ± 7.4% in bicuspid aortic valve group (p = 0.002). CONCLUSION: Aortic valve sparing aortic root reimplantation surgery is a safe and efficient technique, providing acceptable long-term survival with low rates of valve-related complications in both tricuspid aortic valve and bicuspid aortic valve patient groups. However, aortic valve reoperation rates at 10 years follow-up were higher in bicuspid aortic valve group patients compared to tricuspid aortic valve group patients.

The predictive value of left ventricular myocardium mechanics evaluation in asymptomatic patients with aortic regurgitation and preserved left ventricular ejection fraction. A long-term speckle-tracking echocardiographic study.

BACKGROUND: The management of asymptomatic patients with aortic regurgitation (AR) and preserved left ventricular (LV) ejection fraction (LVEF) remains challenging. The purpose of the study was to assess the early changes of LV mechanics by 2D speckle-tracking echocardiography (2D-STE) in order to predict a decrease in LVEF. METHODS: Sixty-seven patients (age, 47 ± 15 years) with asymptomatic moderate (n = 27) and severe AR (n = 40) with preserved LVEF were prospectively followed for about 5 years. Sixty healthy age-matched controls were included in the study. Standard echocardiography and 2D-STE were performed at the baseline and follow-up. The primary endpoint was a deterioration of the LVEF (≤50%). RESULTS: At baseline, global LV longitudinal peak systolic strain (GLS) and strain rate (GLSRs) were decreased in patients with severe AR compared to controls (-18.9 ± 2.4 vs 20.0 ± 2.1%; -1.05 ± 0.19 vs -1.18 ± 0.15 1/s, P < .05, respectively). In the moderate AR group, GLS was not different from that of the control group, but GLSRs was significantly lower than in controls. The primary endpoint was reached in 12 patients with severe AR, while this was not observed in patients with moderate AR. In multivariate analysis, GLS was an independent predictor of LVEF. According to ROC curve analysis, probability of primary endpoint occurrence was significantly greater in patients with GLS values ≥-18.5% (AUC: 0.89, P < .01). CONCLUSIONS: The reduction of LV longitudinal deformation is a sign of early subclinical LV dysfunction. GLS is a prognostic predictor of LV dysfunction and may be potentially useful for optimal timing of surgery for patients with significant AR.

Two-dimensional speckle-tracking echocardiography for evaluation of dilative ascending aorta biomechanics.

BACKGROUND: Two-dimensional (2D) echocardiography is one of the most feasible, noninvasive methods for assessing the aortic diameter and biomechanical changes. We studied possible interfaces between noninvasive biomechanical and speckle-tracking (ST) echocardiographic data from dilated aortas. METHODS: Altogether, 44 patients with dilative pathology of ascending aorta (DPAA) were compared with subjects without ascending aortic dilation (diameter <40 mm). DPAA patients formed two groups based on diameter size: group 1, ≤45 mm diameter; group 2, >45 mm. Conventional and 2D-ST echocardiography were performed to evaluate peak longitudinal strain (LS), longitudinal (LD) and transverse (TD) displacement, and longitudinal velocity (VL). Aortic strain, distensibility, elastic modulus, stiffness index ß of Valsalva sinuses and ascending aorta were also evaluated. SPSS version 20 was used for all analyses. RESULTS: All linear diameters of the ascending aorta were increased in group 2 (>45 mm diameter) (p < 0.05). LD of the anterior aortic wall (p < 0.05) and TD of both aortic walls (p < 0.001) were least in group 2. VL of the posterior and anterior walls diminished in group 2 (p = 0.01). Aortic strain and distensibility were least (p = 0.028 and p = 0.001, respectively) and elastic modulus and stiffness index ß values were greatest in group 2, although without statistical significance. CONCLUSIONS: Ascending aortas of both DPAA groups had reduced elasticity and increased stiffness. The greatest changes in biomechanical parameters occurred in ascending aortas >45 mm. Longitudinal ascending aortic wall motion was mostly impaired in patients with aortas >45 mm (i.e., anterior aortic wall LD, VL of the posterior and anterior walls. TD of the posterior and anterior aortic walls was significantly lower in >45 mm aortic diameter patients. TD of 5.2 mm could predict aortic dilation >45 mm (area under the curve 0.76, p < 0.001, confidence interval 0.65-0.87; sensitivity 87%; specificity 63%). Greater aortic dilation is associated with reduced aortic stiffness parameters and increased elastic modulus and stiffness index ß. Lower LD and LS were associated with less aortic strain and distensibility. There were no significant differences in 2D-ST echocardiographic or stiffness parameters between patients with tricuspid or bicuspid aortic valves.

Left Ventricular Mechanics in Functional Ischemic Mitral Regurgitation in Acute Inferoposterior Myocardial Infarction.

UNLABELLED: Ischemic mitral regurgitation (MR) is an established adverse prognostic factor after myocardial infarction (MI). Functional ischemic mitral regurgitation in acute phase of MI remains under-investigated due to its often transient and dynamic nature. We aimed to assess left ventricular (LV) mechanics by speckle-tracking echocardiography in acute inferoposterior MI and ischemic mitral regurgitation (MR). METHODS: Sixty-nine patients with no structural cardiac valve abnormalities and first acute inferoposterior MI were prospectively enrolled into the study. Two-dimensional transthoracic echocardiography for regional myocardial function and valve assessment was performed within 48 hours of presentation after reperfusion therapy (percutaneous coronary intervention). Based on degree of MR, patients were divided into no significant MR (NMR) group (N = 34, with no or mild (grade 0-I) MR) and ischemic MR (IMR) group (N = 35, with grade ≥2 MR). Thirty-five age- and gender-matched healthy individuals served as a normal reference group. Offline 2D speckle tracking analysis was performed with GE EchoPAC software. RESULTS: LV ejection fraction and longitudinal myocardial deformation parameters were significantly better in healthy subjects, but did not differ between both study groups. All circumferential myocardial deformation parameters were significantly worse in IMR group compared to healthy subjects and NMR group. Global, basal, and mid-ventricular radial strain was significantly lower in IMR group compared to both-healthy subjects and NMR group. CONCLUSION: Ischemic mitral regurgitation in acute inferoposterior MI is associated with worse radial and circumferential LV deformation parameters assessed by 2D speckle tracking echocardiography.

Role of MMP-2 (-1306 C/T) Polymorphism in Age-Related Macular Degeneration.

PURPOSE: To determine if the frequency of the MMP-2 (-1306 C/T) genotype has an influence on the development of early age-related macular degeneration (AMD). METHODOLOGY: The study enrolled 387 patients with early AMD and a random sample of 682 healthy persons (control group). The genotyping of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. RESULTS: The analysis of the MMP-2 (-1306 C/T) gene polymorphism did not reveal any differences in the genotype distribution between the patients with AMD and the control subjects. When the study population was divided into age groups, the C/C genotype was more prevalent in the AMD patients aged <65 years than those aged ≥65 years (65.19% versus 53.88%, p = 0.0294), and the C/T genotype was more frequent in the AMD patients aged ≥65 years when compared with the AMD patients aged <65 years (40.78% versus 26.52%, p = 0.0037). Moreover, in the female group younger than 65 years, the frequency of the C/C genotype was greater in the AMD group than the control group (75% versus 58.91%, p = 0.0232). CONCLUSIONS: This study showed a significantly greater prevalence of the C/C and C/T genotypes in the patients with AMD younger than 65 years and those aged ≥65 years, respectively. Moreover, the AMD women aged <65 years were the carriers of the C/C genotype significantly more frequently than their control counterparts.

The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration.

BACKGROUND: Matrix metalloproteinases (MMP) are responsible for the degradation of extracellular matrix components and play an important role in the physiological and pathological remodeling of tissues. PURPOSE: To assess the impact of MMP-2 Rs2285053 (C->T), MMP-3 Rs3025039 (5A->6A), and MMP-9 Rs3918242 (C->T) single nucleotide polymorphism on the development of early age-related macular degeneration (AMD). METHODS: The study group comprised 148 patients with AMD, and the control group enrolled 526 randomly selected persons. The genotyping of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using the real-time PCR method. RESULTS: The frequency of the MMP-2 (-735) C/T and MMP-3 (-1171) 5A/6A genotypes did not differ significantly between the patients with AMD and the control group, while the MMP-9 (-1562) C/C genotype was more frequently detected in patients with AMD than the control group (73.7% vs. 64.6%, p=0.048). Logistic regression analysis showed that the MMP-9 (-1562) C/C genotype increased the likelihood of developing early AMD (OR=1.51, 95% CI: 1.01-2.21; p=0.046). After the subdivision into the groups by age, a significant difference only in the frequency of the MMP-9 (-1562) C/C genotype was found comparing the AMD patients and the control group younger than 65 years (79.7% vs. 66.4%, p=0.039). CONCLUSIONS: Only MMP-9 Rs3918242 (C->T) single nucleotide polymorphism was found to play a significant role in the development of AMD, and the effect was more pronounced at the age of less than 65 years.

Left ventricular remodelling after acute myocardial infarction: impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene.

INTRODUCTION: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) had effects on cardiac remodelling after acute myocardial infarction. METHODS: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24-72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group (n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification. RESULTS: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct (p=0.008), leucocyte count at admission (p=0.040), global left ventricular longitudinal strain (p=0.021) and MM genotype of AGT (p=0.024) were independent predictors of ventricular remodelling after myocardial infarction. CONCLUSIONS: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction.