A novel Desmoplakin mutation associated with left dominant arrhythmogenic cardiomyopathy and cutaneous phenotype

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Study of myocardial deformation parameters in patients with hypertrophic cardiomyopathy

Μyocardial deformation parameters of the left ventricle and the left atrium represent echocardiographic indices, measured by the two-dimensional speckle tracking method, from data of two-dimensional echocardiography. The first results for their prognostic value in hypertrophic cardiomyopathy appear promising but rely mainly on small retrospective studies. This study is the first prospective observational study to examine the prognostic significance of left ventricular and left atrial myocardial deformation parameters for sudden cardiac events, atrial fibrillation and heart failure events in a large cohort of patients with hypertrophic cardiomyopathy. The study included patients with diagnosed hypertrophic cardiomyopathy, without concomitant severe valvular disease, prior myocardial infarction and without history of atrial fibrillation. Finally, the study population consisted of 250 patients (mean age 50.8 ± 15.8 years, 67.2% males). The myocardial deformation parameters of the left ventricle that were examined were global longitudinal strain (GLS), strain rate during systole, early and late diastole (GLS-SRs, GLS-SRe and GLS-SRa, respectively), the circumferential and radial strain and the mechanical dispersion of the left ventricle (MD). With respect to the left atrium, the myocardial deformation parameters studied were the reservoir strain corresponding to ventricular systole (LAεres), the conduit strain corresponding to early ventricular diastole (LAεcon), the booster strain corresponding to late ventricular diastole (LAεboost) and the corresponding values of strain rate (LAε-SRs, LAε-SRe and LAε-SRa). During a mean follow-up of 2.4 ± 1.2 years, 19 patients suffered a sudden cardiac event. GLS, GLS-SRs, radial strain, MD, LAεres, LAεcon and LAεboost predicted sudden events. The optimal cut-off values were for LAεres -14%, GLS-SRs> -0.8s-1, radial strain 67ms. The optimal cut-off values of the three strain parameters of the left atrium, GLS> -14% and GLS-SRs> -0.8s-1, provided a significant increase in the prognostic value of the presence of ≥ 2 risk factors for sudden death. However, only LAεres -14% conferred a significant increase in the prognostic value of the European Cardiology Society's (HCMRisk-SCD) sudden death prediction algorithm (change in C-statistic from 0.77 to 0.83, p = 0.02 with the inclusion of LAεres -14% in the model). GLS and LAεres had the highest value for predicting atrial fibrillation and heart failure events. However, in multivariable analyses only LAεres remained an independent predictor of the secondary endpoints. Finally, LAεres was an independent predictor of exercise capacity and ventilatory efficiency, measured during the cardiopulmonary exercise testing. In conclusion, GLS and LAeres were the most important prognostic factors with respect to left ventricular and left atrial myocardial deformation parameters, respectively, in hypertrophic cardiomyopathy. However, only LAεres was an independent predictor for all the endpoints of the study.Οι παράμετροι μυοκαρδιακής παραμόρφωσης της αριστερής κοιλίας και του αριστερού κόλπου αποτελούν υπερηχοκαρδιογραφικούς δείκτες που μετρώνται με τη μέθοδο του δισδιάστατου speckle tracking από δεδομένα της απλής δισδιάστατης υπερηχοκαρδιογραφίας. Τα πρώτα αποτελέσματα για την αξία τους ως προγνωστικοί παράγοντες στην υπερτροφική μυοκαρδιοπάθεια φαίνεται να είναι ενθαρρυντικά ωστόσο βασίζονται κυρίως σε μικρές ανασκοπικές μελέτες. Η παρούσα μελέτη αποτελεί την πρώτη προοπτική μελέτη παρατήρησης που μελέτησε την προγνωστική σημασία των παραμέτρων μυοκαρδιακής παραμόρφωσης της αριστερής κοιλίας και του αριστερού κόλπου για τον αιφνίδιο θάνατο και τα ισοδύναμά του, για την εμφάνιση κολπικής μαρμαρυγής και για συμβάματα καρδιακής ανεπάρκειας σε ένα μεγάλο πληθυσμό ασθενών με υπερτροφική μυοκαρδιοπάθεια. Η παρούσα μελέτη συμπεριέλαβε ασθενείς με διεγνωσθείσα υπερτροφική μυοκαρδιοπάθεια, χωρίς σοβαρή βαλβιδική νόσο, χωρίς ιστορικό εμφράγματος του μυοκαρδίου και χωρίς ιστορικό κολπικής μαρμαρυγής. Τελικά, τον πληθυσμό της μελέτης αποτελούσαν 250 ασθενείς (μέση ηλικία 50.8±15.8 έτη, 67.2% άρρενες). Οι παράμετροι μυοκαρδιακής παραμόρφωσης της αριστερής κοιλίας που μελετήθηκαν ήταν το συνολικό επίμηκες strain (GLS), ο ρυθμός μεταβολής του κατά τη συστολή, την πρώιμη και όψιμη διαστολή (GLS-SRs, GLS-SRe και GLS-SRa, αντίστοιχα), το ακτινικό και το κυκλοτερές strain και η μηχανική διασπορά της αριστερής κοιλίας (MD). Αναφορικά με τον αριστερό κόλπο, οι παράμετροι μυοκαρδιακής παραμόρφωσης που μελετήθηκαν ήταν το strain δεξαμενής που αντιστοιχεί στη συστολή της κοιλιας (LAεres), το strain αγωγού που αντιστοιχεί στην πρώιμη διαστολή της κοιλίας (LAεcon), το strain εξώθησης που αντιστοιχεί στην όψιμη διαστολή της κοιλίας (LAεboost) και οι αντίστοιχες τιμές του ρυθμού μεταβολής του strain (LAε-SRs, LAε-SRe και LAε-SRa). Κατά τη διάρκεια μέσης παρακολούθησης 2.4 ± 1.2 ετών, 19 ασθενείς υπέστησαν αιφνίδιο καρδιακό σύμβαμα. To GLS, GLS-SRs, ακτινικό strain, MD, LAεres, LAεcon και LAεboost προέβλεπαν τα αιφνίδια συμβάματα. Οι βέλτιστες τιμές πρόβλεψης ήταν για το LAεres -14%, GLS-SRs> -0.8s-1, για το ακτινικό strain 67ms. Οι βέλτιστες τιμές των τριών strain του αριστερού κόλπου, το GLS >-14% και GLS-SRs >-0.8s-1 προσέφεραν σημαντική αύξηση στην προγνωστική αξία της παρουσίας ≥2 παραγόντων κινδύνου για αιφνίδιο θάνατο. Ωστόσο, μόνο το LAεres -14% προσέφεραν σημαντική αύξηση στην προγνωστική αξία του αλγορίθμου πρόβλεψης αιφνιδίου θανάτου της Ευρωπαϊκής Καρδιολογικής Εταιρίας (HCM Risk-SCD) ( αύξηση του C-statistic από 0.77 σε 0.83, p = 0.02 με την συμμετοχή του LAεres -14% στο μοντέλο). Το GLS και το LAεres είχαν την υψηλότερη αξία για την πρόβλεψη της κολπικής μαρμαρυγής και των συμβαμάτων καρδιακής ανεπάρκειας. Ωστόσο, στα πολυπαραγοντικά μοντέλα μόνο το LAεres ήταν ανεξάρτητος προγνωστικός παράγοντας των δευτερογενών καταληκτικών σημείων. Τέλος, το LAεres ήταν ανεξάρτητος προβλεπτικός παράγοντας της ικανότητας για άσκηση και των επιπέδων αερισμού όπως μετρώνται κατά την καρδιοαναπνευστική δοκιμασία κόπωσης. Συμπερασματικά, το GLS και το LAεres ήταν οι πιο σημαντικοί προγνωστικοί παράγοντες αναφορικά με τις παραμέτρους μυοκαρδιακής παραμόρφωσης της αριστερής κοιλίας και του αριστερού κόλπου, αντίστοιχα, στην υπερτροφική μυοκαρδιοπάθεια. Το LAεres ήταν ο μόνος ανεξάρτητος προγνωστικός παράγοντας για όλα τα καταληκτικά σημεία

Pregnancy outcome in women with congenital heart disease: A single-center experience

Objective: Pregnancies in patients with adult congenital heart disease (ACHD) are often complicated. We aimed to highlight the nature and the rate of these complications in a single-center patient population. Methods: We retrospectively studied all the pregnancies of women who presented on an outpatient basis, and all pregnancies were reviewed for maternal and fetal outcomes. Results: Of 117 pregnancies from 52 ACHD patients (age at pregnancy 28.3 ± 6.6 years), 10 were therapeutically aborted. A proportion of 41.1% of the remaining 107 pregnancies were complicated either with cardiac (3.7%), obstetric (15.0%), or fetal/neonatal (11.2%) adverse events or with spontaneous abortion (17.8%). Hospitalization during pregnancy was required in 10 patients. Elective cesarean sections were initially planned for 31% of the 87 pregnancies, which were finally completed, while 8% required an emergency cesarean section, mostly for obstetric reasons. NYHA class deterioration after pregnancy was detected in 9.3% of our cohort. Modified WHO class III/IV, prior medication use, and higher body mass index (BMI) were related to cardiac complications during pregnancy or NYHA deterioration. Conclusion: Pregnancies in ACHD patients are at high risk for complications. Advanced modified WHO class, prior medication use, and high BMI were related to adverse cardiac events. Keywords: Pregnancy, Adult congenital heart disease, Cardiac complications, Obstetric complications, Neonatal complication

Routine histopathology of septal myectomy for hypertrophic obstructive cardiomyopathy in a greek cohort

Hypertrophic cardiomyopathy (HCM) is a diverse inherited disease affecting 1 in 500 individuals irrespective of gender and ethnicity. A fraction of HCM patients will eventually develop drug refractory dynamic obstruction of the left ventricular outflow tract. For such patients, septal myectomy is the procedure of choice to alleviate their symptoms and improve their quality of life. The current histopathological study, the first from the Greek region, aims to examine the hallmark histopathological characteristics of Hypertrophic Obstructive Cardiomyopathy in a population of patients undergoing septal myectomy at a single center over a ten year period. Medical records and histopathology specimens of thirty nine (n=39) patients were evaluated. The sample comprised 22 males (56.4%) and 17 females (43.6%). Mean patient age at myectomy was 53.9±16.7 years, ranging from 12 to 79 years. Maximal IVS thickness on echocardiography was available for 35 patients with a median value of 2.08cm. Peak resting LVOT Pressure Gradient was available for 33 patients with a mean value of 104.88±44.20 mmHg. Central tendency of each histopathological attribute expressed as the median value was: moderate for myocyte hypertrophy, mild for cytoplasmic vacuolization, moderate for subendocardial fibrosis, moderate for interstitial fibrosis, mild for replacement fibrosis, moderate for myofibrillar disarray and mild for capillary stenosis. Myocyte hypertrophy, present in all specimens, was positively correlated with maximal IVS thickness (tau-b=0.43, p=0.002). Replacement fibrosis was positively correlated with the grade of microvascular stenosis (tau-b=0.45, p=0.004). LVEF was negatively correlated with the grade of interstitial fibrosis (taub=−0.43, p=0.035) and with the extent of myocardial fiber disarray (tau-b=−0.42, p=0.034). Histopathological attributes were not correlated with patient gender or age thus proving that HCM has a histological phenotype unique to each patient, mainly depending on each specific sarcomeric mutatio

Unmet Needs in the Assessment of Right Ventricular Function for Severe Tricuspid Regurgitation

Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease that has been long overlooked, but lately its independent association with adverse cardiovascular outcomes was recognized. The time point to intervene and repair the tricuspid valve is defined by the right ventricular (RV) dilation and dysfunction that comes up at a later stage. While guidelines favor tricuspid valve repair before severe RV dysfunction ensues, the definition of RV dysfunction in a universal manner remains vague. As a result, the candidates for transcatheter or surgical TR procedures are often referred late, when advanced RV dysfunction is established, and any derived procedural survival benefit is attenuated. Thus, it is of paramount importance to establish a universal means of RV function assessment in patients with TR. Conventional echocardiographic indices of RV function routinely applied have fundamental flaws that limit the precise characterization of RV performance. More recently, novel echocardiographic indices such as strain via speckle-tracking have emerged, demonstrating promising results in the identification of early RV damage. Additionally, evidence of the role of alternative imaging modalities such as cardiac computed tomography and cardiac magnetic resonance, for RV functional assessment in TR, has recently arisen. This review provides a systematic appraisal of traditional and novel multimodality indices of RV function in severe TR and aims to refine RV function assessment, designate future directions, and ultimately, to improve the outcome of patients suffering from severe TR

Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality

Background: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to identify the clinical impact and prognostic significance of AF on a large cohort of patients with HCM. Methods: Echocardiographic and clinical correlates, risk factors for AF and thromboembolic stroke and the prognostic significance of AF were evaluated in 509 patients with an established diagnosis of HCM. Results: A total of 119 patients (23.4%) were diagnosed with AF during the index evaluation visit. AF patients had a higher prevalence of stroke and presented with worse functional impairment. Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40). AF was an important risk factor for overall mortality (HR=3.4, 95% CI: 1.7-6.5), HCM-related mortality (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even after adjusting for statistically significant clinical and demographic risk factors. However, AF did not affect the risk for sudden death. Conclusions: LA size is an independent predictor of both AF and thromboembolic stroke. Moreover, patients with AF, regardless of type, have significantly higher mortality rates than patients without AF