Femoral arterial thrombosis after cardiac catheterization in infancy: impact of Doppler ultrasound for diagnosis.

Femoral arterial thrombosis (FAT) is a nonnegligible complication after cardiac catheterization (CC) in infancy. The aim of this study was to evaluate the impact of Doppler ultrasound (US) for diagnostic work-up after catheterization. We compared standard follow-up (FU) without Doppler US by relying on clinical signs of FAT with advanced FU using Doppler US of the femoral vessels. Between January and December 2009, we evaluated the rate of FAT in infants <12 months of age using a multicenter, prospective observational survey. We analysed 171 patients [mean age 4.1 ± 3.3 (SD) months; mean body weight 5.3 ± 1.8 kg] from 6 participating centres. The mean duration of catheter studies was 57.7 ± 38.0 min. The overall rate of FAT based on clinical diagnosis was 4.7% and was comparable in both groups [3.4% undergoing standard FU vs. 7.4% undergoing advanced FU (p = 0.15)]. However, the overall rate of thrombosis as screened by Doppler US was greater at 7.1 %, especially in patients after advanced FU [18.5% advanced vs. standard FU 1.7% (p < 0.01)]. In conclusion, FAT remains a relevant and underestimated complication after catheterization in young infants when relying only on clinical signs of FAT. Therefore, to start effective treatment as soon as possible, we recommend Doppler US to be performed the day after CC.

Device closure of ventricular septal defects by hybrid procedures: a multicenter retrospective study.

OBJECTIVE: This study reports on the feasibility, efficacy, and outcome of hybrid procedures to close ventricular septal defects (VSD), reflecting the experience of 11 centers in Germany, Austria, and Switzerland. BACKGROUND: Beating heart closure of VSD has attracted interest in small infants, complex anomalies and postinfarction scenarios where patients are at high risk during surgery. Perventricular or intraoperative device placement allows access to the lesions where percutaneous delivery is limited. METHODS: Between December 2001 and April 2009, placement of Amplatzer septal occluders was attempted in 26 patients. The defects were located in the perimembranous (n = 5) and muscular septum (n = 21). In 20 patients, a perventricular approach was used, and, in six, the occluders were placed under direct visualization being part of a complex heart surgery. RESULTS: In 23 of 26 procedures, device placement was successful (88.5%). The mean defect size was 7.8 mm (range, 3.5-20). The occluder types were perimembranous VSD occluder (n = 4), muscular VSD occluder (n = 20), postinfarct VSD occluder (n = 1), and ASD occluder (n = 1) with a ratio device/defect of 0.9-2.4 (median 1.15). Device removal was necessary in three due to arrhythmia, malpositioning, and additional defects. Pericardial effusion occurred once. In the remaining 22 patients, there were no procedure or device-related complications. During mean follow up of 1.4 years (range, 1 day-3.9 years), a residual shunt that was more than trivial was observed in one patient out of 21 successful procedures. CONCLUSIONS: Perventricular and intraoperative device closure of VSD is as effective as a surgical patch and averts the increased morbidity of conventional surgical repair in a subgroup of high-risk patients.

Effect and safety of treatment with ACE-inhibitor Enalapril and ß-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial.

BACKGROUND: X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the ß-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. METHODS TRIAL DESIGN: Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. INCLUSION CRITERIA: DMD boys aged 10-14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS < 28%. Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events. RESULTS: From 3/2010 to 12/2013, 38 patients from 10 sites were centrally randomized after run-in, with 21 patients continuing enalapril and metoprolol medication and 17 patients receiving placebo. Until end of study 12/2015, LV-FS < 28% was reached in 6/21 versus 7/17 patients. Cox regression adjusted for LV-FS after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio: 0.38; 95% confidence interval: 0.12 to 1.22; p = 0.10). Analysis of secondary outcome measures revealed a time-dependent deterioration of LV-FS with no statistically significant differences between the two study arms. Blood pressure, maximal heart rate and mean-NN values were significantly lower at the end of open run-in treatment compared to baseline. Outcome analysis 19 months after randomization displayed significantly lower maximum heart rate and higher noradrenalin and renin values in the intervention group. No difference between treatments was seen for quality of life. As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed. CONCLUSIONS: Our analysis of enalapril and metoprolol treatment in DMD patients with preserved left ventricular function is suggestive to delay the progression of the intrinsic cardiomyopathy to left ventricular failure, but did not reach statistical significance, probably due to insufficient sample size. CLINICAL TRIAL REGISTRATION: DRKS-number 00000115, EudraCT-number 2009-009871-36.

Intrauterine cardiomyopathy and cardiac mitochondrial proliferation in mitochondrial trifunctional protein (TFP) deficiency.

Because of a switch in energy-producing substrate utilization from glucose in the fetal period to fatty acids postnatally, intrauterine morbidity of fatty acid oxidation defects has widely been denied. We report the intrauterine development of severe cardiomyopathy in a child with mitochondrial trifunctional protein deficiency after 27 weeks of gestation. The child was born at 31 weeks of gestation and died on day 3 of life. Severe cardiac mitochondrial proliferation was observed. Molecular analysis of both TFP genes was performed and confirmed a homozygous mutation in the TFP alpha-subunit introducing a stop codon at amino acid position 256 (g.871C>T, p.R256X). Despite severe intrauterine decompensation in our patient, no HELLP-syndrome or acute fatty liver of pregnancy was observed in the mother. In the pathogenesis of maternal HELLP-syndrome, toxic effects of accumulating long-chain hydroxy-acyl-CoAs or long-chain hydroxy-acylcarnitines are suspected. In our patient, acylcarnitine analysis on day 2 of life during severest metabolic decompensation did not reveal massive accumulation of long-chain hydroxy-acylcarnitines in blood, suggesting other pathogenic factors than toxic effects. The most important pathogenic mechanism for the development of intrauterine cardiomyopathy appears to be significant cardiac energy deficiency. In conclusion, our report implicates that fatty acid oxidation does play a significant role during intrauterine development with special regard to the heart. Severe cardiac mitochondrial proliferation in TFP deficiency suggests pathophysiologically relevant energy deficiency in this condition.

Outcome of patients with classical infantile pompe disease receiving enzyme replacement therapy in Germany.

PURPOSE: Enzyme replacement therapy (ERT) has been shown to improve outcome in classical infantile Pompe disease. The purpose of this study was to assess mortality, morbidity, and shortcomings of ERT in a larger cohort of patients treated outside clinical trials. To accomplish this, we retrospectively analyzed the data of all 23 subjects with classical infantile Pompe disease having started ERT in Germany between January 2003 and December 2010. RESULTS: Ten patients (43%) deceased and four others (17%) became ventilator dependent. Seven infants (30.5%) made no motor progress at all, while seven (30.5%) achieved free sitting, and nine (39%) gained free walking. Besides all the seven patients (100%) attaining no improvement of motor functions, four out of the seven (57%) achieving to sit without support, and three out of the nine (33%) being able to walk independently, secondarily deteriorated, and died or became ventilator dependent. Sustained reduction of systolic function despite reversal of cardiac hypertrophy (n = 3), gastroesophageal reflux (n = 5), swallowing difficulties or failure to thrive (n = 11), recurrent pneumonias (n = 14), port system complications (n = 4), anesthesia-related incidents (n = 2), severe allergic reactions (n = 6), hearing loss (n = 3), and orthopedic deformities (n = 4) were problems frequently encountered. CONCLUSION: Although this study has important shortcomings due to its retrospective nature and because important variables potentially influencing outcome were not available for a substantial amount of patients, these data suggest that classical infantile Pompe disease still remains a life-threatening condition associated with high morbidity and often dismal prognosis. Currently, a relevant number of patients do not benefit definitely from ERT.

Is heart rate variability an objective parameter with which to manage treatment of infants with heart failure due to left-to-right shunting?

Treatment in heart failure could be guided by additional non-clinical measures, such as neurohumoral levels. Variability in heart rate is known to reflect neurohumoral stimulation. With this in mind, we sought to assess retrospectively the variability in heart rate to guide the treatment of infants in heart failure. We analysed retrospectively the data from 20 infants with a significant left-to-right shunt. All were unsuitable for cardiac surgery or interventional therapy at the time the treatment had commenced. None of the infants improved while receiving diuretics, spironolactone, and digoxin alone, but improved after the addition of propanolol or metoprolol. None of the infants had problems during or after the subsequent operation. Parasympathetic activity reflected by parameters of variability in heart rate, such as the square root of adjacent RR-intervals, and the amount of adjacent RR-intervals greater than 50 milliseconds, improved in nearly all infants during beta blockade. On the other hand, parameters of variability in heart rate reflecting sympathetic activity did not change. Parasympathetic activity reflected the clinical state of nearly all the infants. These parameters, therefore, seem to be a good non-clinical parameter, showing the optimal treatment for heart failure in an ambulatory setting.