Systemic Manifestations of COPD and the Impact of Dual Bronchodilation with Tiotropium/Olodaterol on Cardiac Function and Autonomic Integrity.

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 µg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests' results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests' results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m2 (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study.

Left atrium volume and function changes during stress in patients with primary mitral regurgitation and preserved left ventricular ejection fraction.

INTRODUCTION: Patients with primary mitral regurgitation (MR) usually remain asymptomatic for a long time due to compensatory mechanisms and an adequate treatment could be delayed. Stress echocardiography and speckle-tracking analysis could help to evaluate impaired left atrium (LA) function before the manifestation of clinically significant myocardial changes in asymptomatic patients with primary MR and preserved left ventricular (LV) ejection fraction (EF). METHODS: This study prospectively enrolled 91 patients with preserved LV EF (≥60%) at rest, of which 60 patients had moderate-to-severe MR and 31 were healthy controls. Rest and stress (bicycle ergometry) echocardiography and speckle-tracking offline analysis were performed. RESULTS: In MR group LA volume indices were higher at rest and during stress, while LA reservoir, conduit, and contractile fractions were decreased (p < .005). LA deformation parameters at rest were similar in both groups. During maximum stress LA conduit, contractile fractions and reservoir strain were lower (p < .05) in patients with MR. Indices of LA volume were related to SPAP at rest and during stress. Higher NT-proBNP concentrations was associated with higher LA volume indices, decreased contractile and reservoir functions during peak stress (p < .05). LA volume indices, LA EF, and filling index at rest could predict exercise-induced pulmonary hypertension (EIPH) (p < .05). CONCLUSIONS: In patients with primary MR and preserved LV EF, LA parameters are related to SPAP and NT-pro-BNP concentration. LA volume indices, LA EF and LA filling index are predictors of EIPH.

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.

Acquired Cardiovascular Diseases in Patients with Pulmonary Hypertension Due to Congenital Heart Disease: A Case Report.

Background: Advances in the diagnosis and treatment of congenital heart diseases (CHDs) have resulted in improved survival rates for CHD patients. Up to 90% of individuals with mild CHD and 40% with complex CHD now reach the age of 60. Previous studies have indicated an elevated risk of atherosclerotic cardiovascular disease (ASCVD) and associated risk factors, morbidity, and mortality in adults with congenital heart disease (ACHD). However, there were no comprehensive guidelines for the prevention and management of acquired cardiovascular diseases (CVDs) in ACHD populations until recently. Case presentation: A 55-year-old man with Eisenmenger syndrome and comorbidities (arterial hypertension, heart failure, dyslipidemia, hyperuricemia, and a history of pulmonary embolism (PE)) presented with progressive breathlessness. The electrocardiogram (ECG) revealed signs of right ventricle (RV) hypertrophy and overload, while echocardiography showed reduced RV function, RV overload, and severe pulmonary hypertension (PH) signs, and preserved left ventricle (LV) function. After ruling out a new PE episode, acute coronary syndrome (ACS) was diagnosed, and percutaneous intervention was performed within 24-48 h of admission. Conclusions: This case highlights the importance of increased awareness of acquired heart diseases in patients with pulmonary hypertension due to CHD.

The Prognostic Value of One-Year Changes in Biventricular Mechanics for Three-Year Survival in Patients with Precapillary Pulmonary Hypertension: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Background and Objectives: The management of patients with pulmonary hypertension (PH) poses a considerable challenge. While baseline cardiac magnetic resonance imaging (cMRI) indices are recognized for survival prognosis in PH, the prognostic value of one-year changes in biventricular mechanics, especially as assessed using feature tracking (FT) technology, remains underexplored. This study aims to assess the predictive value of one-year change in cMRI-derived biventricular function and mechanics parameters, along with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and six-minute walking test (6MWT) results for three-year mortality in precapillary PH patients. Materials and Methods: In this retrospective study, 36 patients diagnosed with precapillary pulmonary hypertension (mPAP 55.0 [46.3-70.5] mmHg, pulmonary capillary wedge pressure 10.0 [6.0-11.0] mmHg) were included. Baseline and one-year follow-up cMRI assessments, clinical data, and NT-proBNP levels were analyzed. FT technology was utilized to assess biventricular strain parameters. Patients were categorized into survival and non-survival groups based on three-year outcomes. Statistical analyses, including univariate logistic regression and Cox regression, were performed to identify predictive parameters. Results: The observed three-year survival rate was 83.3%. Baseline right ventricle (RV) ejection fraction (EF) was significantly higher in the survival group compared to non-survivors (41.0 [33.75-47.25]% vs. 28.0 [23.5-36.3]%, p = 0.044), and values of ≤32.5% were linked to a 20-fold increase in mortality risk. RV septum longitudinal strain (LS) and RV global LS exhibited significant improvement over a one-year period in the survival group compared to the non-survival group (-1.2 [-6.4-1.6]% vs. 4.9 [1.5-6.7]%, p = 0.038 and -3.1 [-9.1-2.6]% vs. 4.5 [-2.1-8.5]%, p = 0.048, respectively). Declines in RV septum LS by ≥2.95% and in RV GLS by ≥3.60% were associated with a 25-fold and 8-fold increase in mortality risk, respectively. Conclusions: The decrease in right ventricular septal and global longitudinal strain over a one-year period demonstrates a significant predictive value and an association with an increased three-year mortality risk in patients with precapillary PH.

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

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

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

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

Effect of Short-Term Treatment with Continuous Positive Airway Pressure on Cardiopulmonary Exercise Tolerance, Pulmonary and Cardiac Function in Patients with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a condition with a high prevalence, linked to an increased risk of cardiovascular disease as well as increased morbidity and death. CPAP is currently considered the "gold standard" treatment for OSA, but more thorough research and testing are required to assess its efficacy on cardiopulmonary function. Objectives: To evaluate pulmonary function of OSA patients, cardiopulmonary exercise tolerance test (CPET) performance, cardiac magnetic resonance imaging (MRI) parameters, and polysomnographic changes before and after 3 months of CPAP therapy. Materials and methods: A total of 34 patients diagnosed with moderate or severe OSA, as well as 17 patients as a control group for the evaluation of the cardiac MRI, were included in this study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Lung function tests, CPETs, cardiac MRIs, and polysomnography were performed at the time of the study's enrolment before the initiation of the CPAP therapy and after 3 months of the CPAP treatment. Results: The patients' VO2max during the CPAP treatment tended to increase, but no statistical significance was found (before treatment it was 17.52 ± 3.79 mL/kg/min and after 3 months of treatment, it was 18.6 ± 3,4 mL/kg/min; p = 0.255). The CPAP treatment had positive effects on pulmonary ventilation at the anaerobic threshold (VEAT): 44.51 L/min (43.21%) during the baseline visit and 38.60 L/min (37.86%) after the 3-month treatment period (p = 0.028). The ventilator equivalent for the carbon dioxide slope (VE/VCO2) at peak exercise decreased from 23.47 to 20.63 (p = 0.042). The patients' pulmonary function tests were without abnormalities and did not change after treatment. When assessing cardiac the MRIs, the RV ejection fraction was lower in the OSA group compared to that of the control subjects (53.69 ± 8.91 and 61.35 ± 9.08, p = 0.016). Both LA and RA global longitudinal strains (GLS) improved after 3 months of treatment with CPAP (20.45 ± 7.25 and 26.05 ± 14.00, p = 0.043; 21.04 ± 7.14 and 26.18 ± 7.17, p = 0.049, respectively). Additionally, it was found that CPAP therapy led to statistical improvements in RV end-diastolic volume (164.82 ± 32.57 and 180.16 ± 39.09, p = 0.042). The AHI and oxygen desaturation index (ODI) significantly changed after 3 months of the initiation of the CPAP treatment (p = 0.049 and p = 0.001, respectively). The REM sleep duration decreased, while the duration of non-REM sleep increased after treatment initiation with CPAP (p = 0.016 and p = 0.017, respectively). Conclusions: Short-term CPAP treatment improves pulmonary ventilation, sleep efficiency, and sleep architecture. Significant alterations in both atrias' GLS and RV end-diastolic volume were observed after 3 months of treatment. Longer-term follow-up and a larger patient sample are needed to confirm the reproducibility of our results.

Impact of Carpal Tunnel Syndrome Surgery on Early Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis.

Background and Objectives: Cardiac amyloidosis is an infiltrative, progressive, and restrictive cardiomyopathy that leads to heart failure, reduces life quality, and causes death. This is a multisystem disorder caused by mutations of the transthyretin protein and is associated not only with cardiac diseases or carpal tunnel syndrome but also with nerve, liver, lung, gastrointestinal tract, kidney, or eye pathologies. Carpal tunnel syndrome is an early red-flag symptom of transthyretin (TTR) cardiac amyloidosis; therefore, screening for unsuspected cardiac amyloidosis can be performed through histological testing of flexor retinaculum specimens gathered during carpal tunnel release surgery. Our case highlights that early detection and accurate diagnosis of a disease are important factors for improving clinical outcomes in patients with TTR amyloidosis. Case Summary: We report the case of a 71-year-old man who presented with bilateral carpal tunnel syndrome. Amyloid deposits were detected after carpal tunnel release surgery through histological testing of the synovial tissue. The patient was sent for a cardiological evaluation. Physical examination, laboratory tests, and the ECG revealed no significant changes. The diagnosis of amyloidosis was confirmed with multimodality imaging in the early stage, which helped to start specific medicamental treatment with the transthyretin stabilizer tafamidis. Conclusions: Our objective is to highlight the early recognition and specific medicamental treatment of cardiac amyloidosis for better patient prognosis and outcomes.

Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model.

The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling.

The association of left ventricular histologically verified myocardial fibrosis with pulmonary hypertension in severe aortic stenosis.

OBJECTIVES: To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS). METHODS: About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg. RESULTS: Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (r = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (r = -0.6, p < 0.001), global longitudinal (r = -0.5, p = 0.02) and circumferential strain (r = -0.5, p = 0.05), elevated NT-proBNP (r = 0.5, p = 0.005) and elevated PASP (r = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS. CONCLUSIONS: The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.

Surgical dilemma - spare or replace regurgitant aortic valve: Late comparative outcomes of two strategies.

BACKGROUND: To evaluate different aortic root surgery techniques and their contemporary clinical outcomes in patients with regurgitant aortic valve and aortic root aneurysm. METHODS: The study consisted of 141 adult patients who underwent aortic valve reimplantation (David group = 73) or aortic valve replacement surgery (Bentall group = 68) for aortic valve regurgitation (AR) and dilatation of the aortic root at our institution within the same period (April 2004-October 2016). Kaplan-Meier method was used to estimate survival and other clinically relevant outcomes between the groups. RESULTS: The completeness of clinical follow-up was 100%, with a mean time of 8.0 ± 3.8 years. Thirty-day (in-hospital) mortality rates were equivalent between groups (1.3 and 1.5%, p = 1.0). The overall survival rates at 10 years were significantly better for the David group patients comparing to Bentall group patients (95.3 ± 2.6% vs 79.7 ± 6.8%; p = 0.04) with similar freedom from AV related reoperation (94.4 ± 2.7% vs 98.5 ± 1.5%; p = 0.2). Freedom from bleeding events at 10 years was 90.7 ± 3.6% for Bentall group patients and none were observed among David group patients (p = 0.01). CONCLUSIONS: Aortic valve and root surgery can be performed with equivalent safety and efficacy using either valve-sparing (David procedure) or valve-replacing (Bentall procedure) techniques in selected patients. Furthermore, patients after the David procedure demonstrated significantly improved survival and low risk of bleeding in comparison to the Bentall procedure with an acceptable risk of reoperation at 10 years follow-up.

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p < 0.001). Conventional RV longitudinal and global function parameters (S', fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p < 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process­increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.

The Treatment Strategy for the Atrial Septal Defect in the Presence of Severe Pulmonary Hypertension.

Atrial septal defect is one of the most common congenital heart diseases in adults. The defect often leads to volume overload in the right heart coupled with the potential risk of right heart failure and pulmonary arterial hypertension. These conditions lead to worsening in quality of life, decrease in physical capacity, and even to fatal outcomes. The main strategy for treatment of atrial septal defect is a transcatheter or surgical closure of the defect, but in patients with severe pulmonary arterial hypertension, it is recommended to manage pulmonary arterial hypertension and after that treat the defect invasively. This strategy is called "treat and repair" strategy. We present an illustrative case report of management and treatment of atrial septal defect, complicated with severe pulmonary arterial hypertension. In this case, surgical closure of the defect was contraindicated because of the high pulmonary vascular resistance. Therefore, the "treat and repair" strategy was approached. After specific medical treatment of pulmonary arterial hypertension, surgical closure of the defect was chosen and proven successful.

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.

Fatal pulmonary tumour thrombotic microangiopathy in patient with ovarian adenocarcinoma: review and a case report.

BACKGROUND: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female. CASE PRESENTATION: 51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma. CONCLUSIONS: An early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms.

Echocardiographic predictors of exercise induced pulmonary hypertension in patients with asymptomatic moderate to severe mitral regurgitation and preserved left ventricular ejection fraction.

BACKGROUND: The significant role of mitral regurgitation (MR) in development of pulmonary hypertension (PH) has been proved in previous studies. Experts suggest systolic pulmonary arterial pressure (SPAP) ⩾60 mmHg during exercise as a significant threshold of negative prognostic value in patients with MR. PURPOSE: The aim of this study was to evaluate the changes of SPAP and to ascertain the determinants of exercise induced pulmonary hypertension (EIPH) in patients with asymptomatic primary MR. METHODS: We performed a prospective study that included 50 patients with asymptomatic primary moderate to severe MR with preserved left ventricular ejection fraction (LV EF ⩾60%) at rest. They were divided into two groups according to the presence (PH group; n = 13) or absence (non-PH group; n = 37) of EIPH. Rest and stress (bicycle ergometry) echocardiography and speckle-tracking offline analysis were performed. RESULTS: An increment of SPAP from rest to peak stress was higher in PH group (p < 0.001). Multivariate regression analysis showed that MR effective regurgitation orifice area (EROA; p = 0.008) and regurgitant volume (RVol; p = 0.006) contributed significantly to SPAP at rest. Higher increment of MR EROA during stress and worse parameters of LV diastolic function at rest (E, A, E/e') correlated significantly with higher SPAP during peak stress and they had a major role in predicting EIPH according to univariate logistic regression analysis. In ROC analysis SPAP >33.1 mmHg at rest could predict EIPH with 84.6% sensitivity and 87.1% specificity (95%CI 0.849-1.000; p < 0.001). CONCLUSIONS: Parameters of MR severity (EROA and RVol) were significant determinants of SPAP at rest, while the increment of MR EROA during stress and parameters of resting LV diastolic function were the best predictors of significant EIPH.

Different Causes of Functional Tricuspid Valve Regurgitation Are Linked to Differences in Tricuspid Valve and Right-Sided Heart Geometry and Function: 3D Echocardiography Study.

Background and Objectives: The aim of this study was to clarify the tricuspid valve (TV) and right ventricular (RV) geometry and function characteristics using 3D echocardiography-based analysis and to identify echocardiographic predictors for severe tricuspid regurgitation (TR) in different etiologies of functional TR (fTR). Methods and Results: The prospective study included 128 patients (median age 64 years, 57% females): 109 patients with moderate or severe fTR (69-caused by dominant left-sided valvular pathology (LSVP), 40 due to precapillary pulmonary hypertension (PH)), and 19 healthy controls. The 2D and 3D-transthoracic echocardiography analysis included TV, right atrium, RV geometry, and functional parameters. All the RV geometry parameters as well as 3D TV parameters were increased in both fTR groups when compared to controls. Higher RV diameters, length, areas, volumes, and more impaired RV function were in PH group compared to LSVP group. PH was associated with larger leaflet tenting height, volume, and more increased indices of septal-lateral and major axis tricuspid annulus (TA) diameters. LVSP etiology was associated with higher anterior-posterior TA diameter and sphericity index. Univariate and multivariate logistic regression and ROC analyses revealed that different fTR etiologies were associated with various 2D and 3D echocardiographic parameters to predict severe TR: major axis TA diameter and TA perimeter, the leaflet tenting volume had the highest predictive value in PH group, septal-lateral systolic TA diameter-in LSVP group. The 3D TA analysis provided more reliable prediction for severe fTR. Conclusions: TV and RV geometry vary in different etiologies of functional TR. Precapillary PH is related to more severe RV remodeling and dysfunction and changes of TV geometry, when compared to LSVP group. The 3D echocardiography helps to determine echocardiographic predictors of severe TR in different fTR etiologies.

Global and regional right ventricular mechanics in repaired tetralogy of Fallot with chronic severe pulmonary regurgitation: a three-dimensional echocardiography study.

BACKGROUND: Data about the right ventricular (RV) mechanics adaptation to volume overload in patients with repaired tetralogy of Fallot (rToF) are limited. Accordingly, we sought to assess the mechanics of the functional remodeling occurring in the RV of rToF with severe pulmonary regurgitation. METHODS: We used three-dimensional transthoracic echocardiography (3DTE) to obtain RV data sets from 33 rToF patients and 30 age- and sex- matched controls. A 3D mesh model of the RV was generated, and RV global and regional longitudinal (LS) and circumferential (CS) strain components, and the relative contribution of longitudinal (LEF), radial (REF) and anteroposterior (AEF) wall motion to global RV ejection fraction (RVEF) were computed using the ReVISION method. RESULTS: Corresponding to decreased global RVEF (45 ± 6% vs 55 ± 5%, p < 0.0001), rToF patients demonstrated lower absolute values of LEF (17 ± 4 vs 28 ± 4), REF (20 ± 5 vs 25 ± 4) and AEF (17 ± 5 vs 21 ± 4) than controls (p < 0.01). However, only the relative contribution of LEF to global RVEF (0.39 ± 0.09 vs 0.52 ± 0.05, p < 0.0001) was significantly decreased in rToF, whereas the contribution of REF (0.45 ± 0.08 vs 0.46 ± 0.04, p > 0.05) and AEF (0.38 ± 0.09 vs 0.39 ± 0.04, p > 0.05) to global RVEF was similar to controls. Accordingly, rToF patients showed lower 3D RV global LS (-16.94 ± 2.9 vs -23.22 ± 2.9, p < 0.0001) and CS (-19.79 ± 3.3 vs -22.81 ± 3.5, p < 0.01) than controls. However, looking at the regional RV deformation, the 3D CS was lower in rToF than in controls only in the basal RV free-wall segment (p < 0.01). 3D RV LS was reduced in all RV free-wall segments in rToF (p < 0.0001), but similar to controls in the septum (p > 0.05). CONCLUSIONS: 3DTE allows a quantitative evaluation of the mechanics of global RVEF. In rToF with chronic volume overload, the relative contribution of the longitudinal shortening to global RVEF is affected more than either the radial or the anteroposterior components.

Regional shape, global function and mechanics in right ventricular volume and pressure overload conditions: a three-dimensional echocardiography study.

Our aim was to assess the regional right ventricular (RV) shape changes in pressure and volume overload conditions and their relations with RV function and mechanics. The end-diastolic and end-systolic RV endocardial surfaces were analyzed with three-dimensional echocardiography (3DE) in 33 patients with RV volume overload (rToF), 31 patients with RV pressure overload (PH), and 60 controls. The mean curvature of the RV inflow (RVIT) and outflow (RVOT) tracts, RV apex and body (both divided into free wall (FW) and septum) were measured. Zero curvature defined a flat surface, whereas positive or negative curvature indicated convexity or concavity, respectively. The longitudinal and radial RV wall motions were also obtained. rToF and PH patients had flatter FW (body and apex) and RVIT, more convex interventricular septum (body and apex) and RVOT than controls. rToF demonstrated a less bulging interventricular septum at end-systole than PH patients, resulting in a more convex shape of the RVFW (r = - 0.701, p < 0.0001), and worse RV longitudinal contraction (r = - 0.397, p = 0.02). PH patients showed flatter RVFW apex at end-systole compared to rToF (p < 0.01). In both groups, a flatter RVFW apex was associated with worse radial RV contraction (r = 0.362 in rToF, r = 0.482 in PH at end-diastole, and r = 0.555 in rToF, r = 0.379 in PH at end-systole, respectively). In PH group, the impairment of radial contraction was also related to flatter RVIT (r = 0.407) and more convex RVOT (r = - 0.525) at end-systole (p < 0.05). In conclusion, different loading conditions are associated to specific RV curvature changes, that are related to longitudinal and radial RV dysfunction.