Molecular autopsy and family screening in a young case of sudden cardiac death reveals an unusually severe case of FHL1 related hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a prevalence of about 1:200. It is characterized by left ventricular hypertrophy, diastolic dysfunction and interstitial fibrosis; HCM might lead to sudden cardiac death (SCD) especially in the young. Due to low autopsy frequencies of sudden unexplained deaths (SUD) the true prevalence of SCD and especially of HCM among SUD remains unclear. Even in cases of proven SCD genetic testing is not a routine procedure precluding appropriate risk stratification and counseling of relatives. METHODS: Here we report a case of SCD in a 19-year-old investigated by combined forensic and molecular autopsy. RESULTS: During autopsy of the index-patient HCM was detected. As no other possible cause of death could be uncovered by forensic autopsy the event was classified as SCD. Molecular autopsy identified two (probably) pathogenic genetic variants in FHL1 and MYBPC3. The MYBPC3 variant had an incomplete penetrance. The FHL1 variant was a de novo mutation. We detected reduced FHL1 mRNA levels and no FHL1 protein in muscle samples suggesting nonsense-mediated mRNA decay and/or degradation of the truncated protein in the SCD victim revealing a plausible disease mechanism. CONCLUSION: The identification of the genetic cause of the SCD contributed to the rational counseling of the relatives and risk assessment within the family. Furthermore our study revealed evidences for the pathomechanism of FHL1 mutations.

Differentiation of Impaired From Preserved Hemodynamics in Patients With Fontan Circulation Using Real-time Phase-velocity Cardiovascular Magnetic Resonance.

PURPOSE: Progressive impairment of hemodynamics in patients with Fontan circulation is common, multifactorial, and associated with decreased quality of life and increased morbidity. We sought to assess hemodynamic differences between patients with preserved (preserved Fontans) and those with impaired circulation (impaired Fontans) after pulmonary vasodilation using oxygen and under forced breathing conditions. MATERIALS AND METHODS: Real-time phase-contrast cardiovascular magnetic resonance was performed using non-ECG triggered echo-planar imaging (temporal resolution=24 to 28 ms) in the ascending aorta (AAo) and superior vena cava (SVC)/inferior vena cava (IVC) on room air, after 100% oxygen inhalation (4 L/min; 10 min) and on forced breathing in 29 Fontan patients (17.2±7.3 y) and in 32 controls on room air (13.4±3.7 y). The simultaneously recorded patients' respiratory cycle was divided into 4 segments (expiration, end-expiration, inspiration, and end-inspiration) to generate respiratory-dependent stroke volumes (SVs). The imaging data were matched with physiological data and analyzed with home-made software. RESULTS: The mean SVi (AAo) was 46.1±11.1 mL/m in preserved Fontans versus 30.4±6.2 mL/m in impaired Fontans (P=0.002) and 51.1±6.9 mL/m in controls (P=0.107). The cutoff value for differentiation of Fontan groups was SVi (AAo, end-expiratory) of 32.1 mL/m. After hyperoxygenation, the mean SVi (AAo) increased to 48.7±12.7 mL/m in preserved Fontans (P=0.045) but remained unchanged in impaired Fontans (31.1±5.8 mL/m, P=0.665). Simultaneously, heart rates decreased from 75.2±15.9 to 70.8±16.4 bpm (preserved; P=0.000) but remained unchanged in impaired circulation (baseline: 84.1±9.8 bpm, P=0.612). Compared with physiological respiration, forced breathing increased the maximum respiratory-related cardiac index difference (ΔCImax) in preserved Fontans (SVC: 2.5-fold, P=0.000; and IVC: 1.8-fold, P=0.000) and to a lower extent in impaired Fontans (both veins, 1.5-fold; P(SVC)=0.011, P(IVC)=0.013). There was no impact on mean blood flow. CONCLUSIONS: Oxygen affected the pulmonary vascular system by vasodilation and increased SVi in preserved Fontans but had no effect on impaired Fontans. Forced breathing increased ΔCImax but did not change the mean blood flow by sole activation of the ventilatory pump. End-expiratory aortic SVi represents a valuable measure for classifying the severity of Fontan hemodynamics impairment.

Implantation of the new Nit-Occlud PDA-R device in children below 10 kilogram.

BACKGROUND: Interventional closure of patent ductus arteriosus (PDA) has become a common and safe procedure in most pediatric cath labs. Interventional treatment of PDAs still remains a challenge in those children with low body weight and a large PDA. The Nit-Occlud PDA-R® device was developed and especially designed for large PDAs. We report our most recent experience in children with a body weight lower than 10 kg. MATERIALS AND METHODS: The PDA-R® device was used in seven children (age 1-10, median 6 months) with a body weight from 4.1 to 9.7 kg (median 5.9 kg): ductal length was 12 mm (median), with a large ampulla (median 9 mm) which exceeded the diameter of the aorta (median 6 mm) and large diameter (median minimal diameter 4 mm). In six cases, the Nit-Occlud PDA-R was selected with an aortic disc of 12 mm and in one case an occluder with an aortic disc of 14 mm. RESULTS: Occlusion of the PDA was documented by angiography and/or echocardiography in all cases. At a mean follow-up of 21.4 months, no flow obstruction to the left or right pulmonary artery or new onset coarctation of the aorta was noted. CONCLUSIONS: The Nit-Occlud PDA-R® device is suitable in children with a body weight below 10 kg when a relative large PDA is present.

Percentiles for left ventricular rotation: comparison of reference values to paediatric patients with pacemaker-induced dyssynchrony.

AIM: Left ventricular rotation is an interesting mechanism to investigate patients with heart disease. In children, reference values have to be defined prior to assess pathology. METHODS AND RESULTS: One hundred and seventy-four healthy individuals (0-20 years) were investigated by two-dimensional speckle tracking echocardiography, percentiles were created addressing the amount and time-to-peak values (TTP) of rotational parameters normalized to percentage of cardiac cycle (cc). Patients with right ventricular (RV) pacemaker stimulation were integrated into percentiles describing their rotational delay. Feasibility was 87.4% in healthy individuals (8.5 ± 6.2 years), 42 patients (13.0 ± 6.6 years, mean RV-stimulation time: 6.1 ± 4.3 years) were enrolled. Apical rotation (Rot(ap)) varied and was higher than basal rotation (Rot(bas)) throughout all ages. Peak torsion (Tor(max)) normalized to left ventricle (LV) length (Tor(maxi)) was elevated in early childhood and decreased until adulthood. TTP values revealed greater dispersion between apical and basal rotation at younger age and a decrease during maturation. Patients with RV pacing had decreased Tor(max) (10.0 ± 6.0 vs. 13.7 ± 6.6°, P < 0.05), Rot(ap) (6.7 ± 4.8 vs. 9.3 ± 5.7°, P < 0.05) and Rot(bas) (-3.3 ± 2.6 vs. -4.5 ± 2.7°, P < 0.05). Patients with impaired ejection fraction (EF) had abnormal delays between Rot(ap) and Rot(bas). CONCLUSIONS: Percentile illustrations of LV rotation reveal a high amount and dispersion of Rot(ap) and Tor(maxi) in young children as well as a higher rotational delay compared with older ages. Abnormal delays in RV pacing are associated with reduced EF.

Left ventricular rotation and right-left ventricular interaction in congenital heart disease: the acute effects of interventional closure of patent arterial ducts and atrial septal defects.

BACKGROUND: Left ventricular rotation is physiologically affected by acute changes in preload. We investigated the acute effect of preload changes in chronically underloaded and overloaded left ventricles in children with shunt lesions. METHODS: A total of 15 patients with atrial septal defects (Group A: 7.4 ± 4.7 years, 11 females) and 14 patients with patent arterial ducts (Group B: 2.7 ± 3.1 years, 10 females) were investigated using 2D speckle-tracking echocardiography before and after interventional catheterisation. The rotational parameters of the patient group were compared with those of 29 matched healthy children (Group C). RESULTS: Maximal torsion (A: 2.45 ± 0.9°/cm versus C: 1.8 ± 0.8°/cm, p < 0.05), apical peak systolic rotation (A: 12.6 ± 5.7° versus C: 8.7 ± 3.5°, p < 0.05), and the peak diastolic torsion rate (A: -147 ± 48°/second versus C: -110 ± 31°/second, p < 0.05) were elevated in Group A and dropped immediately to normal values after intervention (maximal torsion 1.5 ± 1.1°/cm, p < 0.05, apical peak systolic rotation 7.2 ± 4.1°, p < 0.05, and peak diastolic torsion rate -106 ± 35°/second, p < 0.05). Patients in Group B had decreased maximal torsion (B: 1.8 ± 1.1°/cm versus C: 3.8 ± 1.4°/cm, p < 0.05) and apical peak systolic rotation (B: 8.3 ± 6.1° versus C: 13.9 ± 4.3°, p < 0.05). Defect closure was followed by an increase in maximal torsion (B: 2.7 ± 1.4°/cm, p < 0.05) and the peak diastolic torsion rate (B: -133 ± 66°/second versus -176 ± 84°/second, p < 0.05). CONCLUSIONS: Patients with chronically underloaded left ventricles compensate with an enhanced apical peak systolic rotation, maximal torsion, and quicker diastolic untwisting to facilitate diastolic filling. In patients with left ventricular dilatation by volume overload, the peak systolic apical rotation and the maximal torsion are decreased. After normalisation of the preload, they immediately return to normal and diastolic untwisting rebounds. These mechanisms are important for understanding the remodelling processes.

Eosinophilic myocarditis in an adolescent: a case report and review of the literature.

Eosinophilic myocarditis is a rare disease occurring mainly in adulthood. It is generally known to be caused by autoimmune diseases, parasitic infections, hypersensitivity to drugs or substances, and after vaccinations. We describe the case of a 15-year-old adolescent, who presented initially with flu-like symptoms, as well as syncope. Subsequently, catecholaminergic treatment had to be initialised because of cardiac failure. Peripheral eosinophil count was normal at admission and at the time of endomyocardial biopsy. The biopsy, however, proved the diagnosis of eosinophilic myocarditis, but the causative agent remained unclear despite intensive diagnostic work-up. Cardiac magnetic resonance imaging showed signs of acute myocardial oedema and a delayed enhancement in the basal inferolateral segments consistent with acute myocarditis. Under treatment with corticosteroids, angiotensin-converting enzyme inhibitor, and warfarin, we accomplished a rapid and complete recovery of cardiac function and histology. This unique case of eosinophilic myocarditis is rare in childhood. The differential diagnosis and diagnostic pathway is discussed, and a review of the literature and therapeutic options based on the literature is performed.