Kemal Nisli

Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome

Background: Desmosomes are cellular junctions important for intercellular adhesion and anchoring the intermediate filament (IF) cytoskeleton to the cell membrane. Desmoplakin (DSP) is the most abundant desmosomal protein with 2 isoforms produced by alternative splicing. Methods: We describe a patient with a recessively inherited arrhythmogenic dilated cardiomyopathy with left and right ventricular involvement, epidermolytic palmoplantar keratoderma, and woolly hair. The patient showed a severe heart phenotype with an early onset and rapid progression to heart failure at 4 years of age. Results: A homozygous nonsense mutation, R1267X, was found in exon 23 of the desmoplakin gene, which results in an isoform specific truncation of the larger DSPI isoform. The loss of most of the DSPI specific rod domain and C-terminal area was confirmed by Western blotting and immunofluorescence. We further showed that the truncated DSPI transcript is unstable, leading to a loss of DSPI. DSPI is reported to be an obligate constituent of desmosomes and the only isoform present in cardiac tissue. To address this, we reviewed the expression of DSP isoforms in the heart. Our data suggest that DSPI is the major cardiac isoform but we also show that specific compartments of the heart have detectable DSPII expression. Conclusions: This is the first description of a phenotype caused by a mutation affecting only one DSP isoform. Our findings emphasise the importance of desmoplakin and desmosomes in epidermal and cardiac function and additionally highlight the possibility that the different isoforms of desmoplakin may have distinct functional properties within the desmosome.

Cardiac Hydatid Disease: CT and MRI Findings

OBJECTIVE The purpose of this article is to review the CT and MRI findings of cardiac hydatid disease. CONCLUSIONS CT and MRI are helpful for localizing and defining the morphologic features of hydatid cysts. Specific signs include calcification of the cyst wall, presence of daughter cysts, and membrane detachment. CT best shows wall calcification, whereas MRI depicts the exact anatomic location and nature of the internal and external structures.

MR imaging features of ventricular noncompaction: Emphasis on distribution and pattern of fibrosis

OBJECTIVE The purpose of this study is to describe morphologic features and delayed contrast-enhancement pattern of the noncompaction of the left ventricle in cardiac magnetic resonance (MR) imaging. METHODS We retrospectively reviewed morphological cardiac MR imaging findings of ventricular noncompaction in 15 patients (eight men, seven women, and ages 6 months to 73 years old, mean 22 year). In 10 patients delayed contrast enhanced images were obtained after the morphological examination. RESULTS In all patients, noncompaction was seen in the apical and midventricular-lateral segment. Basal-septal segment involvement was not determined in any patients. Noncompacted/compacted ratio was 2-4.5 (mean 3). In nine patients, right ventricular involvement was observed in addition to left ventricular noncompaction. Delayed contrast-enhancement was seen in eight out of 10 patients not only involved segments but also normal segments of the heart. CONCLUSION Cardiac MR imaging is a valuable imaging method in patients with suspected ventricular noncompaction by showing increased trabeculations, deep intertrabecular recesses and fibrosis. Fibrosis is a common finding in ventricular noncompaction.

Congenital heart disease in children with Down's syndrome: Turkish experience of 13 years.

Background — Down’s syndrome (DS) is the most common chromosomal abnormality due to a trisomy of chromosome 21 commonly associated with congenital heart defects (CHDs). This study aimed to evaluate the frequency and types of CHD patterns in Turkish children with DS. Method — The data relate to paediatric patients with DS who underwent cardiologic screening between 1994 and 2007 and were reviewed in our Paediatric Cardiology unit. Results — Four hundred and twenty-one out of the 1042 paediatric patients with DS studied over a 13-year period had associated CHD. Of these, 320 (77.6%) had a single cardiac lesion, while the remaining 92 patients (22.4%) had multiple defects. The most common single defect was an atrioventricular septal defect (AVSD) found in 141 patients (34.2%), followed by 69 patients (16.7%) showing secundum type atrial septal defect, and ventricular septal defect in 68 patients (16.5%). AVSDs were the leading type, isolated or combined with other cardiac anomalies with an overall occurrence of 19.8% of paediatric patients with DS, and 49.2% of paediatric patients with both DS and CHD. Conclusion — This is the first study concerning the frequency and type of CHD observed in Turkish children with DS.The high frequency of AVSD in Turkish children with DS implied that early screening for CHDs by echocardiography is crucial. The correction of AVSDs in paediatric patients with DS should be performed in the first 6 months of life to avoid irreversible haemodynamic consequences of the defect.

Permanent cardiac pacing in a 2.5 month-old infant with severe cyanotic breath-holding spells and prolonged asystole.

We report the case of a 2.5 month-old infant with cyanotic breath-holding spells, loss of consciousness and seizures. Prolonged asystole up to 70 s despite cardiopulmonary resuscitation was documented by 24 hour Holter monitoring. An epicardial pacemaker was implanted followed by no further loss of consciousness and seizures during spells in a six month follow-up period.

Transcatheter closure of a fistula between the right pulmonary artery and left atrium using the Amplatzer septal occluder

A congenital fistula between the right pulmonary artery (RPA) and left atrium (LA) is a rare condition that results in central cyanosis. An 11-year-old boy was admitted with exertional dyspnea and easy fatigability. He had severe cyanosis of the lips and limbs with clubbing of the fingers. Systemic oxygen saturation was 70%. There was no abnormal finding on electrocardiography, chest radiography, and echocardiography. Agitated saline injection showed early appearance of contrast bubbles in the LA. A pulmonary arteriovenous fistula was suspected and diagnostic cardiac catheterization was performed. Angiography demonstrated a large fistula between the proximal RPA and LA. The narrowest part of the fistula was 13.8 mm in balloon sizing. A 14-mm Amplatzer septal occluder was deployed at the narrowest site; however, the device migrated to the LA and then to the aortic arch. The device was removed and was successfully reimplanted to the fistula. After the procedure, arterial oxygen saturation increased from 70% to 96% and control angiography demonstrated complete occlusion of the fistula. The patient was symptom-free on follow-up evaluations at 6, 12, and 18 months, with a mean oxygen saturation of 96%. This case represents the first pediatric patient in whom a septal occluder was used.

Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major

OBJECTIVE To comparatively evaluate P-wave dispersion (PWD) in patients with beta-thalassemia major (TM) and healthy control subjects for the early prediction of arrhythmia risk. METHODS Eighty-one children with beta-TM, aged 4-19 years, and 74 healthy children (control group) underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS There was a statistically significant difference between study and control groups in peak early (E) mitral inflow velocity and E/late (A) velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in beta-TM patients than in control subjects. CONCLUSIONS Increased PWD in our beta-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias.

Over 14 years of experience with cardiac myxomas

Atrial myxomas are the most commonly encountered tumours of the heart and can present at different ages with different clinical symptoms. They are one of the curable tumours of the heart. Appropriate surgical treatment and surgery must be performed with great precautions in order to prevent fatal systemic embolizations. In this retrospective study we will present our experience of 14∞∞years, between 1990 and 2004, in 27∞∞patients who had been operated for cardiac myxomas. Diagnosis of the myxomas were made by echocardiography in all cases. Surgical approach to the tumour was biatrial in nine, left atrial in 11, and transseptal in seven patients.Associated procedures included coronary artery bypass grafting in one, mitral valve repair with tricuspid annuloplasty in two patients, mitral valve replacement in one and bilateral femoral embolectomy in one patient. One hospital mortality occurred as a result of multiorgan failure in a patient with peripheral embolization. None of the patients required recurrent operation, however, mitral valve insufficiency was surgically corrected in one patient.

Investigation of cardiomyopathy in children with cirrhotic and noncirrhotic portal hypertension.

Background: Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well-defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT). Methods: This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged-QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged-QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated. Results: The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end-stage liver disease scores, Child-Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4). Conclusions: Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child-Pugh score.

Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers

Factors contributing to arteriopathy in patients with Turner syndrome (TS) remain unclear. We assessed arterial stiffness in young, normotensive patients with TS and correlated arterial stiffness with vascular biomarkers, GH treatment and oestrogen exposure. Sixty‐one patients with TS (mean age, 12·6 years; range 6·6–21·3 years) were matched for age and sex with 61 healthy peers. Associations between arterial stiffness and high‐sensitivity C‐reactive protein (hsCRP), B‐type natriuretic peptide (BNP), atrial NP (ANP), plasma aldosterone/plasma renin activity (PRA), IGF1 and IGFBP3 were examined after adjusting for well‐established confounders of vascular disease.