Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

MSA-VT Score for Assessment of Long-Term Prognosis after Electrical Storm Ablation.

INTRODUCTION: Prognosis after electrical storm (ES) ablation remains severe, especially in patients with recurrent sustained monomorphic ventricular tachycardia (SMVT) or progressive heart failure (HF). However, single-factor-based prediction is suboptimal and may be refined by more complex algorithms. We sought to evaluate if a novel score MSA-VT (M = moderate/severe mitral regurgitation, S = severe HF at admission, A = atrial fibrillation at admission, VT = inducible SMVT after ablation) may improve prediction of death and recurrences compared to single factors and previous scores (PAINESD, RIVA and I-VT). METHODS: A total of 101 consecutive ES ablation patients were retrospectively analyzed over a 32.8-month (IQR 10-68) interval. The MSA-VT score was calculated as the sum of the previously mentioned factors' coefficients based on hazard ratio values in Cox regression analysis. The AUC for death prediction by MSA-VT was 0.84 (p < 0.001), superior to PAINESD (AUC 0.63, p = 0.03), RIVA (AUC 0.69, p = 0.02) and I-VT (0.56, p = 0.3). MSA-VT ≥ 3 was associated with significantly higher mortality during follow-up (52.7%, p < 0.001). CONCLUSIONS: Prediction by single factors and previously published scores after ES ablation may be improved by the novel MSA-VT score; however, this requires further external validation in larger samples.

Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.

Complex Substrate Leading to PVC-Mediated Systolic Dysfunction in addition to Sustained Monomorphic VT in Repaired Tetralogy of Fallot.

Frequent premature ventricular complexes (PVCs) are associated with deleterious effects on left ventricular (LV) function in various clinical scenarios. Repaired tetralogy of Fallot (rTOF) is frequently affected by sustained ventricular arrhythmias dependent on complex post-surgical substrates. However, there is limited data regarding the potential of arrhythmogenic isthmuses to generate frequent PVCs and PVC-mediated LV systolic dysfunction development in rTOF. We present a case of rTOF experiencing relatively infrequent episodes of internal shocks for episodes of sustained monomorphic ventricular tachycardia and a high burden of PVCs associated with left ventricular systolic function deterioration, in which the successful substrate ablation of the anatomical VT isthmuses also led to PVC abolition and consequently to LV systolic function normalization. In such cases, understanding the pathogenic mechanisms that lead to LV dysfunction is only possible by rigorous clinical reasoning, which leads to a tailored specific treatment.

Non-revascularized chronic total occlusions impact on substrate and post-ablation results in drug-refractory electrical storm.

Background and aims: There is limited data concerning the effect of non-revascularized chronic total occlusions (NR-CTOs) after VT ablation. This study sought to evaluate the impact of NR-CTOs after ablation for electrical storm (ES). Methods: Post-hoc retrospective analysis of data regarding 64 consecutive post-myocardial infarction patients (out of which 12 patients with NR-CTOs and 52 without NR-CTOs) undergoing substrate ablation for ES with an available median follow-up of 37.53 (7.25-64.65) months. Ablation result was assessed by inducibility of sustained monomorphic VT (SMVT) during final programmed ventricular stimulation (PVS). The primary endpoints were all-cause mortality and VT/VF recurrences after ablation, respectively, stratified by the presence of NR-CTOs. The secondary endpoint was to assess the predictive effect of NR-CTOs on all-cause mortality and VT/VF recurrences in relation to other relevant prognostic factors. Results: At baseline, the presence of NR-CTOs was associated with higher bipolar BZ-to-total scar ratio (72.4% ± 17.9% vs. 52% ± 37.7%, p = 0.022) and more failure to eliminate the clinical VT (25% (3) vs. 0% (0), p < 0.001). During follow-up, overall all-cause mortality and recurrences were more frequent in the NR-CTO subgroup (75% (9) vs. 19.2% (10), log rank p = 0.003 and 58.3% vs. 23.1% (12), log rank p = 0.042 respectively). After adjusting for end-procedural residual SMVT inducibility, NR-CTOs predicted death during follow-up (HR 3.380, p = 0.009) however not recurrence (HR 1.986, p = 0.154). Conclusions: NR-CTO patients treated by RFCA for drug-refractory ES demonstrated a higher ratio of BZ-to-total-scar area. In this analysis, NR-CTO was associated with worse acute procedural results and may as well impact long-term outcomes which should be further assessed in larger patient populations.

Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review.

Hypertrophic cardiomyopathy (HCM) is an inherited primary myocardial disease characterized by asymmetrical/symmetrical left ventricle (LV) hypertrophy, with or without LV outflow tract (LVOT) dynamic obstruction, and poor prognosis. Cardiac resynchronization therapy (CRT) has emerged as a minimally invasive tool for patients with heart failure (HF) with decreased LV ejection fraction (LVEF) and prolonged QRS duration of over 120 ms with or without left bundle branch block (LBBB). Several HCM patients are at risk of developing LBBB because of disease progression or secondary to septal myomectomy, while others might develop HF with decreased LVEF, alleged end-stage/dilated HCM, especially those with thin myofilament mutations. Several studies have shown that patients with myectomy-induced LBBB might benefit from left bundle branch pacing or CRT to relieve symptoms, improve exercise capacity, and increase LVEF. Otherwise, patients with end-stage/dilated HCM and prolonged QRS interval could gain from CRT in terms of NYHA class improvement, LV systolic performance increase and, to some degree, LV reverse remodeling. Moreover, several electrical and imaging parameters might aid proper selection and stratification of HCM patients to benefit from CRT. Nonetheless, current available data are scarce and further studies are still required to accurately clarify the view. This review reassesses the importance of CRT in patients with HCM based on current research by contrasting and contextualizing data from various published studies.

Cardiac Magnetic Resonance Imaging in Appraising Myocardial Strain and Biomechanics: A Current Overview.

Subclinical alterations in myocardial structure and function occur early during the natural disease course. In contrast, clinically overt signs and symptoms occur during late phases, being associated with worse outcomes. Identification of such subclinical changes is critical for timely diagnosis and accurate management. Hence, implementing cost-effective imaging techniques with accuracy and reproducibility may improve long-term prognosis. A growing body of evidence supports using cardiac magnetic resonance (CMR) to quantify deformation parameters. Tissue-tagging (TT-CMR) and feature-tracking CMR (FT-CMR) can measure longitudinal, circumferential, and radial strains and recent research emphasize their diagnostic and prognostic roles in ischemic heart disease and primary myocardial illnesses. Additionally, these methods can accurately determine LV wringing and functional dynamic geometry parameters, such as LV torsion, twist/untwist, LV sphericity index, and long-axis strain, and several studies have proved their utility in prognostic prediction in various cardiovascular patients. More recently, few yet important studies have suggested the superiority of fast strain-encoded imaging CMR-derived myocardial strain in terms of accuracy and significantly reduced acquisition time, however, more studies need to be carried out to establish its clinical impact. Herein, the current review aims to provide an overview of currently available data regarding the role of CMR in evaluating myocardial strain and biomechanics.

Sex- and age-specific normal values for automated quantitative pixel-wise myocardial perfusion cardiovascular magnetic resonance.

AIMS: Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers. METHODS AND RESULTS: A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = -0.43, P < 0.001 and r = -0.34, P < 0.001, respectively). CONCLUSION: Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use.

Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation-Family Case Report and Review of the Literature.

PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (PRKAG2) of 5' Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. PRKAG2 mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff−Parkinson−White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for PRKAG2 mutations should be considered.

Right atrial lipoma: A case report and literature review.

Cardiac lipomas are generally asymptomatic even in large dimensions. Echocardiograms can identify tumors, but cardiac magnetic resonance imaging or cardiac computerized tomography can differentiate cardiac lipomas from other cardiac tumors. The present study is a case report of an asymptomatic 30-year-old man diagnosed with atrial lipoma. The patient received cardiac surgery and the intervention consisted of exclusion of the right atrial (RA) tumor and reconstruction of the right atrium with 'XenoSure' patch in extracorporeal circulation through a minimally invasive approach. A short PubMed literature review was performed and 26 cases of RA lipomas with available details were found. Cardiac tumors may cause clinical presentation through different pathways. Symptoms related to an RA lipoma were present in 21 out of 26 patients (80%). The symptoms varied greatly, dyspnea being the most common of them. In one case, the lipoma was found during the autopsy of a patient after sudden death. Large cardiac lipomas can lead to complications such as obstruction of ventricular outflow tract, electric disorders, embolism or pericardial effusion. Obstruction of the right ventricular outflow tract was reported in 11 out of 26 patients (42%) diagnosed with RA lipoma. Generally, atrial lipoma can have various sizes. The most useful imaging technique was transthoracic echocardiography. Accurate diagnosis and evaluation of cardiac lipoma is dependent on multimodality imaging methods, including cardiac magnetic resonance. Surgery is the treatment of choice, but the risk-benefit ratio must be considered, and shared decision making must be taken into account. The present review data showed that 23 out of 25 patients (92%) underwent surgery. Among these patients, only 1 out of 23 received a minimally invasive approach in 2021. Cardiac lipomas are rare entities, usually asymptomatic, that can occur at any age. The most useful diagnostic method of cardiac tumors is echocardiography, but nuclear magnetic resonance can also specify the type and characteristics of tumors.

Case Report: Pulmonary Vein Isolation as a Tailored Treatment for Recurrent Ventricular Tachycardia During Hemodialysis in a Patient With Right Coronary Artery Chronic Total Occlusion.

Background: Catheter ablation of the ventricular substrate can reduce ventricular tachycardia (VT) recurrence and mortality in an electrical storm (ES). However, identification and specific treatment of plausible triggers is mandatory and may lead to the resolution of ES. Objective: This case presentation seeks to exemplify how pulmonary vein isolation (PVI) may represent a tailored treatment of ES in cases of ventricular substrate, which only becomes arrhythmogenic during high-rate episodes of paroxysmal atrial fibrillation (PAF). Results: A 54-year-old male with a history of inferior myocardial infarction (MI) and long-term hemodialysis was referred for repetitive implantable cardioverter-defibrillator (ICD) shocks for apparently scar-related monomorphic VT episodes preceded by PAF initiation strictly during hemodialysis. He had recently undergone ICD implantation for similar episodes of ES preceded by the rapid-ventricular response (RVR) PAF during hemodialysis. The patient had no other history of VTs. Electrocardiogram (EKG) changes occurred exclusively during PAF and suggested functional myocardial ischemia. Coronary angiography demonstrated isolated right coronary artery (RCA) chronic total occlusion (CTO). Cardiac magnetic resonance demonstrated RCA-territory residual myocardial viability and mild LV systolic dysfunction. Surgical revascularization was not feasible due to a history of bilateral above-the-knee post-traumatic amputation and severe calcification of internal mammary (IMA) and radial arteries. Subsequent CTO-percutaneous coronary intervention attempt was unsuccessful. The difficulty of assessing LV-substrate ablation end-points due to the "functional" character of the substrate, which only became arrhythmogenic during hemodialysis-related PAF, was considered. Consequently, PVI was performed rather than VT/VF substrate ablation. Twelve months after PVI, the patient remains free of PAF and VT/VF despite chronic hemodialysis sessions. Conclusion: The ES episodes can be triggered by situational factors, such as RVR-PAF and functional ischemia, during hemodialysis in patients with CTO with otherwise no episodes of VT. Tailored treatment of such factors may lead to long-term VT freedom.

Right atrial phasic function and outcome in patients with heart failure and reduced ejection fraction: Insights from speckle-tracking and three-dimensional echocardiography.

BACKGROUND: Atrial phasic function can be assessed using speckle-tracking and three-dimensional (3D) echocardiography. The extent and role of right atrial (RA) dysfunction in left-sided heart failure (HF) is incompletely understood. We aimed to characterize RA phasic function in HF with reduced ejection fraction (HFrEF) and to assess its prognostic significance. METHODS: We prospectively enrolled 60 patients with HFrEF and 29 normal controls. RA phasic function was assessed using strain curves derived from speckle-tracking echocardiography and 3D volumetric analysis. Patients were followed for a composite endpoint of cardiac death or rehospitalization for HF. RESULTS: After a mean follow-up of 19 (9) months, 33 patients reached the primary endpoint. Patients with HFrEF and adverse outcomes showed an impairment of both reservoir, conduit, and booster pump RA function when compared to controls. After adjustment for age, left ventricular systolic and diastolic function, right ventricular systolic function and pulmonary artery pressure, RA maximal and minimal volumes, as well as passive emptying fraction, remained independent predictors of death or rehospitalization (hazard ratio [HR], 3.207; 95% confidence interval [CI], 1.288-7.984; P = 0.012; HR, 2.362, 95% CI, 1.004-5.552; P = 0.049; and HR, 2.367; 95% CI, 1.066-5.259; P = 0.034, respectively). CONCLUSION: All three components of RA phasic function are impaired in left-sided HF. 3D RA maximal and minimal volumes, as well as 3D RA passive emptying fraction, are independent predictors of adverse outcomes in HFrEF.

Three-dimensional right ventriculo-arterial coupling as an independent determinant of severe heart failure symptoms in patients with dilated cardiomyopathy.

BACKGROUND: Right ventricular-pulmonary artery coupling (RVPAC) is a predictor of outcome in pulmonary hypertension. However, the role of this parameter in dilated cardiomyopathy (DCM) remains to be established. The aim of this study was to assess the contribution of RVPAC to the occurrence of severe heart failure (HF) symptoms in patients with DCM using three-dimensional (3D) echocardiography. METHODS: We prospectively screened 139 outpatients with DCM, 105 of whom were enrolled and underwent 3D echocardiographic assessment. RVPAC was estimated non-invasively as the 3D right ventricular stroke volume (SV) to end-systolic volume (ESV) ratio. Severe HF symptoms were defined by New York Heart Association (NYHA) class III or IV. We evaluated differences in RVPAC across NYHA classes and the ability of RVPAC to predict severe symptoms. RESULTS: Mean left ventricular (LV) ejection fraction was 28±7%. Mean RVPAC was 0.77±0.30 and it was significantly more impaired with increasing symptom severity (p = 0.001). RVPAC was the only independent determinant of severe HF symptoms, after adjusting for age, diuretic use, LV systolic function, LV diastolic function, and pulmonary artery systolic pressure (OR 0.035 [95% CI, 0.004-0.312], p = 0.003). By receiver-operating characteristic analysis, the RVPAC cut-off value for predicting severely symptomatic status was 0.54 (area under the curve = 0.712, p < 0.001). CONCLUSION: 3D echocardiographic SV/ESV ratio is an independent correlate of severe HF symptoms in patients with DCM. 3D RVPAC might prove to be a useful risk stratification tool for these patients, should it be further validated in larger studies.

Non-invasive right ventriculo-arterial coupling as a rehospitalization predictor in dilated cardiomyopathy: A comparison of five different methods.

BACKGROUND: Right ventricular (RV) pulmonary artery coupling (RVPAC) is a predictor of outcome in left-sided heart failure (HF). Several echocardiographic estimates for RVPAC have been proposed. AIMS: This study aimed to compare multiple non-invasive methods to calculate RVPAC and to assess its prognostic role in patients with dilated cardiomyopathy (DCM). METHODS: We prospectively enrolled 60 stable patients with DCM. RVPAC was estimated using five methods: as the tricuspid annular plane excursion/pulmonary artery systolic pressure (PASP) ratio; as the RV global longitudinal strain/PASP ratio; as the RV free wall strain (RVFW-LS)/PASP ratio; as the three-dimensional (3D) RV ejection fraction (RVEF)/PASP ratio; and as the 3D RV stroke volume (SV)/end-systolic volume (ESV) ratio. Patients were followed for a mean period of 18 (9) months for the endpoint of HF rehospitalizations. RESULTS: Twenty-nine patients (48%) reached the endpoint. All RVPAC estimates were more impaired in those patients reaching the endpoint (P <0.001 for all) and all predicted rehospitalizations in un-adjusted analysis. RVFW-LS/PASP and RVEF/PASP remained independent predictors of events, after adjustment for clinical and echocardiographic confounders. Using cut-offs obtained from receiver operating characteristic (ROC) analysis, we found that patients with RVFW-LS/PASP >-0.40 and patients with RVEF/PASP <1.30 had a higher risk of HF rehospitalization (log-rank P = 0.001 and P = 0.002, respectively). CONCLUSION: RVFW-LS/PASP and RVEF/PASP as non-invasive estimates of RVPAC are independent predictors of HF rehospitalization in patients with DCM.

Ratio between Right Ventricular Longitudinal Strain and Pulmonary Arterial Systolic Pressure: Novel Prognostic Parameter in Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: We aimed to evaluate whether right ventricle (RV) longitudinal strain indexed to pulmonary arterial systolic pressure (PASP) has prognostic significance in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Patients undergoing CRT were prospectively included. The primary endpoint was adverse cardiovascular events (death and HF-related hospitalizations). RV global longitudinal strain (RVGLS) and RV free wall strain (RVfwS) were measured by speckle tracking and indexed to echocardiographic estimated PASP. RESULTS: A total of 54 patients (64.0 ± 13.8 years; 58% male) were included. After 33 ± 12.9 months, the primary endpoint occurred in 18 patients. Baseline RVGLS/PASP and RVfwS/PASP showed good discriminative ability for response to CRT (AUC = 0.88, 95% CI (0.74-1) and AUC = 0.87, 95% CI (0.77-1)). RVGLS/PASP and RVfwS/PASP were significantly associated with high risk of events at univariate analysis (HR 0.039, 95% CI (0.001-0.8) p < 0.05, respectively HR = 0.049, 95% CI (0.0033-0.72), p < 0.05). Upon multivariate Cox regression analysis, RVGLS/PASP and RVfwS/PASP remained associated with high risk of events (HR 0.018, 95% CI (0.0005-0.64), p = 0.02 and HR 0.015, 95% CI (0.0004-0.524), p = 0.01) after correction for gender, etiology, QRS duration and morphology. Conclusions: Indexing RV longitudinal strain (global and free wall) by PASP provides a parameter, which independently identifies patients with high risk of cardiovascular events and predicts non-response to CRT.

The prognostic value of right ventricular longitudinal strain and 3D ejection fraction in patients with dilated cardiomyopathy.

Several studies showed that right ventricular (RV) dysfunction is a powerful predictor in heart failure (HF). Advanced echocardiographic techniques such as speckle-tracking imaging and three-dimensional (3D) echocardiography proved to be accurate tools for RV assessment, but their clinical significance remains to be clarified. The aim of this study was to evaluate the role of two-dimensional (2D) RV strain and 3D ejection fraction (RVEF) in predicting adverse outcome in patients with non-ischemic dilated cardiomyopathy (DCM). We prospectively screened 81 patients with DCM and sinus rhythm, 50 of whom were enrolled and underwent comprehensive echocardiography, including RV strain and 3D RV volumetric assessment. Patients were followed for a composite endpoint of cardiac death, nonfatal cardiac arrest and acute worsening of HF requiring hospitalization. After a median follow-up of 16 months, 29 patients reached the primary endpoint. Patients with events had more impaired RV global longitudinal strain (- 10.5 ± 4.5% vs. - 14.3 ± 5.2%, p = 0.009), RV free wall longitudinal strain (- 12.9 ± 8.7% vs. - 17.5 ± 7.1%, p = 0.046) and 3D RVEF (38 ± 8% vs. 47 ± 9%, p = 0.001). By Cox proportional hazards multivariable analysis, RV global longitudinal strain and RVEF were independent predictors of outcome after adjustment for age and NYHA class. RVEF remained the only independent predictor of events after further correction for echocardiographic risk factors. By receiver-operating characteristic analysis, the optimal RVEF cut-off value for event prediction was 43.4% (area under the curve = 0.768, p = 0.001). Subjects with RVEF > 43.4% showed more favourable outcome compared to those with RVEF < 43.4% (log-rank test, p < 0.001). In conclusion, 3D RVEF is an independent predictor of major adverse cardiovascular events in patients with DCM.

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy.

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown. METHODS: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. LA 2D volumetric and STE parameters were analyzed in 86 LVH patients (43 HCM and 43 isolated HTN subjects) and 33 age- and sex-matched controls. RESULTS: The volumetric study showed that LA reservoir and conduit function were impaired in the HCM group compared to controls, while, in the HTN group, only LA conduit function was deteriorated. The HCM group had all three STE-derived LA functions impaired compared to controls. The HTN group, consistently with volumetric analysis, had solely LA conduit function reduced compared to controls. Ratios of LA booster-pump strain (S) and strain rate (SR) to interventricular septum (IVS) thickness were the most accurate parameters to discriminate between HCM and HTN. The subgroup harboring sarcomeric pathogenic (P)/likely pathogenic (LP) variants had reduced LA booster-pump S and SR compared with the genotype-negative subgroup. CONCLUSIONS: LA reservoir, conduit, and pump functions are decreased in HCM compared to HTN patients with similar LVH. We report the ratios between LA contraction S/SR and IVS thickness as novel parameters with high accuracy in discriminating LVH due to HCM. The presence of P/LP variants in sarcomeric or sarcomeric-associated genes could be associated with more severe LA dysfunction.

Right ventricular-arterial coupling - A new perspective for right ventricle evaluation in heart failure patients undergoing cardiac resynchronization therapy.

BACKGROUND: Right ventricular - arterial (RV-PA) coupling can be estimated by echocardiography using the ratio between (TAPSE) and pulmonary arterial systolic pressure (PASP). TAPSE/PASP ratio proved to be a prognostic parameter in patients with heart failure and reduced ejection fraction (HFrEF). OBJECTIVE: To evaluate the significance of RV-PA coupling in patients with HFrEF undergoing cardiac resynchronization therapy (CRT). METHODS: Patients undergoing CRT in our center between January 2017 and November 2019 were eligible. Response to CRT was defined by a reduction of more than 15% of left ventricle systolic volume (LVESV) one year after CRT. Primary endpoint was a composite of HF hospitalizations and death during follow-up. RESULTS: 54 patients (Age 64.0 ± 13.8 years; 58% male; left ventricular ejection fraction (LVEF) 28.4 ± 1.3%) were prospectively included. After a mean follow-up of 31 ± 12.9months, the primary endpoint had occurred in 18 (33.3%) patients. A lower TAPSE/PASP ratio was associated with baseline worse HF symptoms, lower LVEF and long-term less LV reverse remodeling (P < .05). After one year CRT improved RV systolic function (TAPSE, RV global longitudinal strain, P < .05), but not TAPSE/PASP ratio (P = .4). The ratio TAPSE/PASP (AUC=0.834) ≥ 0.58 mm/mm Hg showed good sensitivity (90%) and specificity (81.8%) for predicting response to CRT while a ratio <0.58 mm/mm Hg was associated with a higher risk of death and HF hospitalizations during the follow-up (HR 5.37 95%CI [1.6-18], P < .001). CONCLUSION: RV-PA coupling evaluation using TAPSE/PASP ratio predicts CRT response. A lower TAPSE/PASP ratio is associated with a higher risk of adverse cardiovascular events.

Forgotten No More-The Role of Right Ventricular Dysfunction in Heart Failure with Reduced Ejection Fraction: An Echocardiographic Perspective.

During the last decade, studies have raised awareness of the crucial role that the right ventricle plays in various clinical settings, including diseases primarily linked to the left ventricle. The assessment of right ventricular performance with conventional echocardiography is challenging. Novel echocardiographic techniques improve the functional assessment of the right ventricle and they show good correlation with the gold standard represented by cardiac magnetic resonance. This review summarizes the traditional and innovative echocardiographic techniques used in the functional assessment of the right ventricle, focusing on the role of right ventricular dysfunction in heart failure with reduced ejection fraction and providing a perspective on recent evidence from literature.