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.

Atrial Pacing Negatively Affects Left Atrial Morphological and Functional Parameters Similarly to Atrioventricular Dyssynchrony.

Background and Objectives: Atrioventricular (AV) dyssynchrony as well as atrial and ventricular pacing affect left atrial (LA) function. We conducted a study evaluating the effect of atrial and ventricular pacing on LA morphological and functional changes after dual-chamber pacemaker implantation. Materials and Methods: The study prospectively enrolled 121 subjects who had a dual-chamber pacemaker implanted due to sinus node disease (SND) or atrioventricular block (AVB). Subjects were divided into three groups based on indication and pacemaker programming: (1) SND DDDR 60; (2) AVB DDD 60 and (3) AVB DDD 40. Subjects were invited to one- and three-month follow-up visits. Three subsets based on pacing burden were analyzed: (1) high atrial (A) low ventricular (V); (2) high A, high V and (3) low A, high V. LA function was assessed from volumetric parameters and measured strains from echocardiography. Results: The high A, low V group consisted of 38 subjects; while high A, high V had 26 and low A, high V had 23. A significant decrease in reservoir and contractile LA strain parameters were only observed in the high A, low V pacing group after three months (reservoir 25.9 ± 10.3% vs. 21.1 ± 9.9%, p = 0.003, contractile -14.0 ± 9.0% vs. -11.1 ± 7.8, p = 0.018). While the re-established atrioventricular synchrony in the low A, high V group maintained reservoir LA strain at the baseline level after three months (21.4 ± 10.4% vs. 22.5 ± 10.4%, p = 0.975); in the high A, high V group, a further trend to decrease was noted (20.3 ± 8.9% vs. 18.7 ± 8.3%, p = 0.231). Conclusions: High atrial pacing burden independently of atrioventricular dyssynchrony and ventricular pacing impairs LA functional and morphological parameters. Changes appear soon after pacemaker implantation and are maintained.

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.

The Impact of Polymorphisms in ATP-Binding Cassette Transporter Genes on Anthracycline-Induced Early Cardiotoxicity in Patients with Breast Cancer.

BACKGROUND: Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. METHODS: The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. RESULTS: After a cumulative dose of 236.70 mg/m2 of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, p = 0.019). CONCLUSIONS: The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results. We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p < 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p < 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p < 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p < 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p < 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p < 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p < 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

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.

The incremental value of myocardial viability, evaluated by 18F-fluorodeoxyglucose positron emission tomography, and cardiovascular magnetic resonance for mortality prediction in patients with previous myocardial infarction and symptomatic heart failure.

OBJECTIVES: To find the imaging mortality predictors in patients with previous myocardial infarction (MI), symptomatic heart failure (HF), and reduced left ventricle (LV) ejection fraction (EF). METHODS: for the study 39 patients were selected prospectively with prior MI, symptomatic HF, and LVEF ≤40%. All patients underwent transthoracic echocardiography (TTE), single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), 18F-FDG positron emission tomography (FDG PET). 31 patients underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Patients were divided into two groups: 1 group - cardiac death; 2 group - no cardiac death. Myocardial scars were assessed on a 5-point-scale. Follow-up data was obtained. RESULTS: Imaging features disclosed significant difference (p < 0.05) of defect score (CMR and SPECT-PET), LV end-diastolic diameter (EDD) (TTE), LVEDD index (CMR), LV global longitudinal strain (CMR) and LV global circumferential strain (CMR) between the groups. Predictors of cardiac death were: LVEDD index (TTE) and LV global longitudinal strain. The cut-off values to predict cardiac death were: defect score (CMR) 25 (AUC, 79.5%; OR 1.8, 95% CI 1.2-2.7), SPECT-PET defect score 22 (AUC, 73.9%; OR 0.5, 95% CI 0.3-0.7), LVEDD (TTE) 58 mm (AUC, 88.4%; OR 23.6, 95% CI 2.6-217.7), LVEDDi 30 mm/m2 (TTE) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LVEDDi 33.6 mm/m2 (CMR) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LV global longitudinal strain -13.4 (AUC, 87.8%; OR 2.1, 95% CI 1.2-3.7) and LV global circumferential strain -16.3 (AUC, 76.1%; OR 1.9, 95% CI 1.2-3.0). CONCLUSIONS: Imaging features, such as defect score (CMR) >25, SPECT-PET defect score >22, LVEDD (TTE) >58 mm, LVEDDi (TTE) >30 mm/m2, LVEDDi (CMR) >33.6 mm/m2, LV global longitudinal strain -13.4 and LV global circumferential strain -16.3, may increase sensitivity and specificity of FDG PET and LGE CMR predicting of late mortality.

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.

Atrial Pacing Affects Left Atrial Morphological and Functional Parameters Early after Pacemaker Implantation.

Background and Objectives: Chronic atrial stimulation might impair left atrial (LA) function. We aimed to assess the impact of atrial pacing burden on LA volumetric and functional parameters after implantation of a dual-chamber pacemaker. Materials and Methods: The prospective study included 121 subjects with sinus node disease (SND) or atrioventricular block (AVB) that received a dual-chamber pacemaker. After device implantation, the subjects were divided into three groups: (1) SND with a lower rate (LR) set to 60 bpm and rate response enabled; (2) AVB with an LR set to 60 bpm and no rate response; and (3) AVB with an LR set to 40 bpm and no rate response. Subjects were followed at one and three months. Two subsets of patients with high and low atrial pacing burdens accompanied by low ventricular pacing percentage were analyzed. LA function was evaluated with volumetric and strain parameters from transthoracic echocardiography. Results: The high atrial low ventricular pacing group consisted of 38 subjects, and the low atrial low ventricular group consisted of 22 subjects. When looking at the change in volumetric parameters, we observed a tendency for volumes to increase in both groups; however, only minimal LA volume reached statistical significance at three months in the high atrial pacing group. A trend towards the lowering of an active emptying fraction at one month (p = 0.076) became significant at three months (p = 0.043), and was also only observed in the same group. Moreover, a decrease in the tendency to reach statistical significance at three months for reservoir and contractile strain parameters and stiffness index was only observed in the high atrial pacing group. Meanwhile, in the low atrial pacing burden group, all parameters remained significantly unchanged. Conclusions: The burden of right atrial pacing in patients with preserved left ventricular function negatively influences functional and morphologic LA parameters. Moreover, negative effects take place soon after pacemaker implantation and appear to be sustained.

Comparative Analysis of Myocardial Viability Multimodality Imaging in Patients with Previous Myocardial Infarction and Symptomatic Heart Failure.

Background and Objectives: To compare the accuracy of multimodality imaging (myocardial perfusion imaging with single-photon emission computed tomography (SPECT MPI), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), and cardiovascular magnetic resonance (CMR) in the evaluation of left ventricle (LV) myocardial viability for the patients with the myocardial infarction (MI) and symptomatic heart failure (HF). Materials and Methods: 31 consecutive patients were included in the study prospectively, with a history of previous myocardial infarction, symptomatic HF (NYHA) functional class II or above, reduced ejection fraction (EF) ≤ 40%. All patients had confirmed atherosclerotic coronary artery disease (CAD), but conflicting opinions regarding the need for percutaneous intervention due to the suspected myocardial scar tissue. All patients underwent transthoracic echocardiography (TTE), SPECT MPI, 18F-FDG PET, and CMR with late gadolinium enhancement (LGE) examinations. Quantification of myocardial viability was assessed in a 17-segment model. All segments that were described as non-viable (score 4) by CMR LGE and PET were compared. The difference of score between CMR and PET we named reversibility score. According to this reversibility score, patients were divided into two groups: Group 1, reversibility score > 10 (viable myocardium with a chance of functional recovery after revascularization); Group 2, reversibility score ≤ 10 (less viable myocardium when revascularisation remains questionable). Results: 527 segments were compared in total. A significant difference in scores 1, 2, 3 group, and score 4 group was revealed between different modalities. CMR identified "non-viable" myocardium in 28.1% of segments across all groups, significantly different than SPECT in 11.8% PET in 6.5% Group 1 (viable myocardium group) patients had significantly higher physical tolerance (6 MWT (m) 3892 ± 94.5 vs. 301.4 ± 48.2), less dilated LV (LVEDD (mm) (TTE) 53.2 ± 7.9 vs. 63.4 ± 8.9; MM (g) (TTE) 239.5 ± 85.9 vs. 276.3 ± 62.7; LVEDD (mm) (CMR) 61.7 ± 8.1 vs. 69.0 ± 6.1; LVEDDi (mm/m2) (CMR) 29.8 ± 3.7 vs. 35.2 ± 3.1), significantly better parameters of the right heart (RV diameter (mm) (TTE) 33.4 ± 6.9 vs. 38.5 ± 5.0; TAPSE (mm) (TTE) 18.7 ± 2.0 vs. 15.2 ± 2.0), better LV SENC function (LV GLS (CMR) −14.3 ± 2.1 vs. 11.4 ± 2.9; LV GCS (CMR) −17.2 ± 4.6 vs. 12.7 ± 2.6), smaller size of involved myocardium (infarct size (%) (CMR) 24.5 ± 9.6 vs. 34.8 ± 11.1). Good correlations were found with several variables (LVEDD (CMR), LV EF (CMR), LV GCS (CMR)) with a coefficient of determination (R2) of 0.72. According to the cut-off values (LVEDV (CMR) > 330 mL, infarct size (CMR) > 26%, and LV GCS (CMR) < −15.8), we performed prediction of non-viable myocardium (reversibility score < 10) with the overall percentage of 80.6 (Nagelkerke R2 0.57). Conclusions: LGE CMR reveals a significantly higher number of scars, and the FDG PET appears to be more optimistic in the functional recovery prediction. Moreover, using exact imaging parameters (LVEDV (CMR) > 330 mL, infarct size (CMR) > 26% and LV GCS (CMR) < −15.8) may increase sensitivity and specificity of LGE CMR for evaluation of non-viable myocardium and lead to a better clinical solution (revascularization vs. medical treatment) even when viability is low in LGE CMR, and FDG PET is not performed.

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.

HFE Gene Variants' Impact on Anthracycline-Based Chemotherapy-Induced Subclinical Cardiotoxicity.

Progress in oncology has allowed to improve outcomes in many breast cancer patients. The core stone of breast cancer chemotherapy is anthracycline-based chemotherapy. Unfortunately, anthracyclines cause cardiotoxicity which is a limiting factor of its use and lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. With evolution of echocardiography subclinical damage is identified, and more sensitive evaluation can be performed. This leads to understanding the heart damage beyond cumulative dose in early phase and importance of other risk factors. There are many risk factors for anthracycline-based chemotherapy cardiotoxicity (ABCC) like arterial hypertension, obesity, diabetes, genetic predisposition, etc. One of possible pathophysiological pathways is iron metabolism, especially HFE gene-regulated iron metabolism pathway. Pre-existing genetic iron metabolism dysregulation increases risk for ABCC. Clinical studies and experimental models in mice have shown potential impact of HFE gene SNP on ABCC. The main objective of our study was to identify the impact of HFE C282Y and H63D SNP on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. Data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in the outpatient clinic were analyzed and SNP RT-PCR tests were performed. Statistically significant association between H63D and ABCC after completion of chemotherapy was observed (p < 0.005). Consequently, our study demonstrated that H63D SNP has an important role in the development of ABCC. HFE SNP mutation status could be used as one of important tools to identify high-risk patients for ABCC.

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.

Impact of Arterial Hypertension on Doxorubicin-Based Chemotherapy-Induced Subclinical Cardiac Damage in Breast Cancer Patients.

Advances in oncologic therapies have allowed to achieve better outcomes and longer survival in many patients with breast cancer. Anthracyclines are cytotoxic antibiotics widely used in daily oncology practice. However, anthracyclines cause cardiotoxicity which is a limiting factor of its use. Cumulative dose of anthracyclines is the major cause of induced cardiotoxicity. According to previous clinical trials, the major predisposing high-risk factors for anthracycline-based chemotherapy-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as diabetes and hypertension. Experimental studies in animals confirm that hypertension may be a significant factor predisposing anthracycline-based chemotherapy cardiotoxicity. The main objective of our study was to identify the effect of pre-existing arterial hypertension on the development of subclinical cardiac damage during or after doxorubicin-based chemotherapy in breast cancer patients. The study was performed prospectively between March 2016 and January 2017 in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics Department of Oncology and Department of Cardiology. Data of 73 women with breast cancer treated with doxorubicin-based chemotherapy in outpatient clinic were analyzed. Statistically significant association between pre-existing arterial hypertension and left ventricular systolic dysfunction after completion of chemotherapy was observed (P < 0.004). Our study demonstrated that pre-existing arterial hypertension has a very important role in the development of anthracycline-based chemotherapy-induced cardiotoxicity, despite arterial hypertension control quality. Consequently, further studies evaluating impact of other risk factors and how early and sufficient management of arterial hypertension could influence the development of cardiotoxicity are needed to avoid permanent cardiac damage.

Accuracy of three-dimensional systolic dyssynchrony and sphericity indexes for identifying early left ventricular remodeling after acute myocardial infarction.

OBJECTIVE: Left ventricle (LV) geometry and dyssynchrony are associated with LV remodeling after acute myocardial infarction (AMI). The aim of this prospective study was to assess the diagnostic value of new three-dimensional echocardiography (3DE) parameters [sphericity (SI) and systolic dyssynchrony indexes (SDI)] for the prediction of LV remodeling after AMI and to compare them with two-dimensional echocardiography (2DE) parameters. METHODS: 2DE and 3DE were performed in 75 patients with AMI within 3 days from the onset of MI and 6 months later. LV remodeling was defined as a ≥15% increase in the LV end-diastolic volume (EDV) at follow-up. 3D SI was calculated by dividing EDV by the volume of a sphere whose diameter was derived from the major end-diastolic LV long axis. SDI was considered as a standard deviation of the time from cardiac cycle onset to minimum systolic volume in 16 LV segments. RESULTS: LV remodeling was identified in 34 (45%) patients using the 2DE method and in 22 (29%) patients using the 3DE method. Evaluated 3DE parameters, such as EDV [area under the receiver operating characteristic (ROC) curve (AUC) 0.742, sensitivity 71%, specificity 79%], end-systolic volume (AUC 0.729, sensitivity 69%, specificity 78%), SDI (AUC 0.777, sensitivity 73%, specificity 77%), and SI, had significant prognostic value for LV remodeling. According to the AUC, the highest predictive value had 3D SI (AUC 0.957, sensitivity 90%, specificity 91%). CONCLUSION: 3DE parameters, especially 3D SI and SDI, play important roles in the prediction of LV remodeling after AMI and can be used in clinical practice.

Positron Emission Tomography in the Diagnosis and Management of Coronary Artery Disease.

Cardiac positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are encouraging precise non-invasive imaging modalities that allow imaging of the cellular function of the heart, while other non-invasive cardiovascular imaging modalities are considered to be techniques for imaging the anatomy, morphology, structure, function and tissue characteristics. The role of cardiac PET has been growing rapidly and providing high diagnostic accuracy of coronary artery disease (CAD). Clinical cardiology has established PET as a criterion for the assessment of myocardial viability and is recommended for the proper management of reduced left ventricle (LV) function and ischemic cardiomyopathy. Hybrid PET/CT imaging has enabled simultaneous integration of the coronary anatomy with myocardial perfusion and metabolism and has improved characterization of dysfunctional areas in chronic CAD. Also, the availability of quantitative myocardial blood flow (MBF) evaluation with various PET perfusion tracers provides additional prognostic information and enhances the diagnostic performance of nuclear imaging.

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.

Assessment of mitral apparatus in patients with acute inferoposterior myocardial infarction and ischaemic mitral regurgitation with two-dimensional echocardiography from anatomically correct imaging planes.

BACKGROUND: Ischaemic mitral regurgitation (IMR) is associated with adverse prognosis after myocardial infarction (MI) as a result of left ventricular remodelling and geometric deformation of the mitral apparatus (MA). AIM: The aim of this study was to assess MA from anatomically correct imaging planes in acute inferoposterior MI and IMR. METHODS: Ninety-three patients with no structural cardiac valve abnormalities and the first acute inferoposterior MI were prospectively enrolled into the study. Two-dimensional transthoracic echocardiography for MA assessment was performed within 48 h of presentation after reperfusion therapy. Based on the degree of mitral regurgitation (MR), patients were divided into either a no significant MR (NMR) group (n = 52 with no or mild, grade 0-I MR) or an IMR group (n = 41 with grade ≥ 2 MR). The control group consisted of 45 healthy individuals. RESULTS: Ischaemic MR was related with dilatation of the left ventricle chambers, decrease in ejection fraction, increase in mitral annulus diameter and area, and changes in subvalvular apparatus when compared with the NMR group or healthy individuals. CONCLUSIONS: Ischaemic MR in acute inferoposterior MI is related with worse lesions in MA geometry that cause insufficiency of mitral valve function.

Pharmacological treatment changes of chronic heart failure during cardiac resynchronization therapy: A 1-year follow-up study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is associated with improved morbidity and mortality in patients with chronic heart failure (HF) on optimal medical therapy. We aimed to evaluate changes of medical therapy during CRT and its influence on the CRT response. METHODS: We evaluated 85 HF patients' pharmacological treatment changes during 1-year follow-up of CRT. Statistical analysis was performed using IBM SPSS statistical software (SPSS v.21.0 for Mac OS X). RESULTS: Beta-blockers (BAB) were used in 81.2% of patients before CRT, and consumption increased after CRT implantation (96.5% at 1-year follow-up visit) (p<0.002). Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) consumption and dose didn't significantly change statistically during the study. 55.3% of patients were taking spironolactone before CRT, and this number increased at discharge till 76.5% (p<0.001) and till 70.6% (p=0.01) at 1-year follow-up visit. The average dose of spironolactone during the study significantly decreased statistically. The use of diuretics was higher after CRT device implantation, compared with the period before CRT 80% to 84.7% (p<0.001), but torasemide dose hadn't significantly changed statistically and remained almost the same. Cardiovascular medication consumption was significantly lower before CRT, compared with discharge (p<0.001) and follow-up (p<0.001) periods. However, no statistically significant relation between pharmacological treatment and echocardiographic response was found. CONCLUSIONS: The present study confirmed that pharmacological treatment has changed during the period before and after CRT. But no statistically significant relation between pharmacological treatment and echocardiographic response was found.

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.