Disease severity, arrhythmogenesis, and fibrosis are related to longer action potentials in tetralogy of Fallot.

BACKGROUND: Arrhythmias may originate from surgically unaffected right ventricular (RV) regions in patients with tetralogy of Fallot (TOF). We aimed to investigate action potential (AP) remodelling and arrhythmia susceptibility in RV myocardium of patients with repaired and with unrepaired TOF, identify possible correlations with clinical phenotype and myocardial fibrosis, and compare findings with data from patients with atrial septal defect (ASD), a less severe congenital heart disease. METHODS: Intracellular AP were recorded ex vivo in RV outflow tract samples from 22 TOF and three ASD patients. Arrhythmias were provoked by superfusion with solutions containing reduced potassium and barium chloride, or isoprenaline. Myocardial fibrosis was quantified histologically and associations between clinical phenotype, AP shape, tissue arrhythmia propensity, and fibrosis were examined. RESULTS: Electrophysiological abnormalities (arrhythmias, AP duration [APD] alternans, impaired APD shortening at increased stimulation frequencies) were generally present in TOF tissue, even from infants, but rare or absent in ASD samples. More severely diseased and acyanotic patients, pronounced tissue susceptibility to arrhythmogenesis, and greater fibrosis extent were associated with longer APD. In contrast, APD was shorter in tissue from patients with pre-operative cyanosis. Increased fibrosis and repaired-TOF status were linked to tissue arrhythmia inducibility. CONCLUSIONS: Functional and structural tissue remodelling may explain arrhythmic activity in TOF patients, even at a very young age. Surprisingly, clinical acyanosis appears to be associated with more severe arrhythmogenic remodelling. Further research into the clinical drivers of structural and electrical myocardial alterations, and the relation between them, is needed to identify predictive factors for patients at risk.

Benefit From a Humanitarian Pediatric Congenital Heart Surgery Program Over a 10-Year Period.

Background: The charity organization Kinderherzen retten e.V. (KHR) enables humanitarian congenital heart surgery for pediatric patients from low- and middle-income countries at the University Heart Center Freiburg, Germany. The aim of this study was to assess periprocedural and mid-term outcomes of these patients for evaluation of KHR sustainability. Methods: Part one of the study comprised retrospective medical chart analyses of the periprocedural course of all KHR-treated children from 2008 to 2017, and part two a prospective evaluation of their mid-term outcome, assessed by questionnaires concerning survival, medical history, mental and physical development, and socioeconomic situation. Results: Of the 100 consecutively presented children from 20 countries (median age 3.25 years), 3 patients were not invasively treatable, 89 underwent cardiovascular surgery, and 8 received a catheter intervention only. There were no periprocedural deaths. Median postoperative duration of mechanical ventilation, intensive care stay, and total hospital stay was 7 (interquartile range [IQR] 4-21) hours, 2 (IQR 1-3) days, and 12 (IQR 10-16) days, respectively. Mid-term postoperative follow-up demonstrated a 5-year survival probability of 94.4%. The majority of patients received continued medical care in their home country (86.2% of patients), were in good mental and physical condition (96.5% and 94.7% of patients, respectively), and able to engage in age-appropriate education/employment (98.3% of patients). Conclusions: Cardiac, neurodevelopmental, and socioeconomic outcomes of patients treated via KHR was satisfactory. Thorough pre-visit evaluation and close contact with local physicians are crucial when providing this high-quality, sustainable, and viable therapeutic option for these patients.

Arrhythmic risk during pregnancy in patients with congenital heart disease.

Arrhythmias play a significant role in the morbidity and mortality of patients with adult congenital heart disease (CHD). Pregnancy-associated physiological changes in hormonal status, hemodynamics, and myocardial structure further enhance arrhythmic risk in CHD patients, leading to increased adverse maternal and foetal events and making arrhythmias one of the most common complications during pregnancy. Nearly all CHD patients are affected by asymptomatic rhythm disturbances during the ante-, peri-, or post-partum periods, and almost one tenth of patients develop sustained, symptomatic arrhythmias requiring treatment. The majority of arrhythmias originate from the atrium, mostly in the form of supraventricular tachycardia or atrial fibrillation. Patients with CHD often tolerate these even more poorly during pregnancy than before pregnancy. Sustained ventricular tachycardia or ventricular fibrillation are rare, but potentially life-threatening for mother and foetus. Risk stratification models developed specifically for arrhythmias during pregnancy in CHD patients are lacking, but direct or indirect signs of heart failure, previous history of arrhythmia, and complex CHD may be associated with higher arrhythmic risk in these patients. Rigorous individual assessment before, and careful monitoring during pregnancy in a multidisciplinary team is crucial to ensure the best possible pregnancy outcome for patients with CHD.

Quantitative collagen assessment in right ventricular myectomies from patients with tetralogy of Fallot.

AIMS: Patients with tetralogy of Fallot (TOF) are often affected by right ventricular fibrosis, which has been associated with arrhythmias. This study aimed to assess fibrosis distribution in right ventricular outflow tract (RVOT) myocardium of TOF patients to evaluate the utility of single histology-section analyses, and to explore the possibility of fibrosis quantification in unlabelled tissue by second harmonic generation imaging (SHGI) as an alternative to conventional histology-based assays. METHODS AND RESULTS: We quantified fibrosis in 11 TOF RVOT samples, using a tailor-made automated image analysis method on Picrosirius red-stained sections. In a subset of samples, histology- and SHGI-based fibrosis quantification approaches were compared. Fibrosis distribution was highly heterogeneous, with significant and comparable variability between and within samples. We found that, on average, 67.8 mm2 of 10 µm thick, histologically processed tissue per patient had to be analysed for accurate fibrosis quantification. SHGI provided data faster and on live tissue, additionally enabling quantification of collagen anisotropy. CONCLUSION: Given the high intra-individual heterogeneity, fibrosis quantification should not be conducted on single sections of TOF RVOT myectomies. We provide an analysis algorithm for fibrosis quantification in histological images, which enables the required extended volume analyses in these patients.

Musicians use speech-specific areas when processing tones: The key to their superior linguistic competence?

It is known that musicians compared to non-musicians have some superior speech and language competence, yet the mechanisms how musical training leads to this advantage are not well specified. This event-related fMRI study confirmed that musicians outperformed non-musicians in processing not only of musical tones but also syllables and identified a network differentiating musicians from non-musicians during processing of linguistic sounds. Within this network, the activation of bilateral superior temporal gyrus was shared with all subjects during processing of the acoustically well-matched musical and linguistic sounds, and with the activation distinguishing tones with a complex harmonic spectrum (bowed tone) from a simpler one (plucked tone). These results confirm that better speech processing in musicians relies on improved cross-domain spectral analysis. Activation of left posterior superior temporal sulcus (pSTS), premotor cortex, inferior frontal and fusiform gyrus (FG) also distinguishing musicians from non-musicians during syllable processing overlapped with the activation segregating linguistic from musical sounds in all subjects. Since these brain-regions were not involved during tone processing in non-musicians, they could code for functions which are specialized for speech. Musicians recruited pSTS and FG during tone processing, thus these speech-specialized brain-areas processed musical sounds in the presence of musical training. This study shows that the linguistic advantage of musicians is linked not only to improved cross-domain spectral analysis, but also to the functional adaptation of brain resources that are specialized for speech, but accessible to the domain of music in the presence of musical training.

Retrograde transcatheter aortic valve closure in an infant with failing Norwood stage I palliation: a case report.

BACKGROUND: Aortic valve regurgitation leading to coronary steal phenomenon can severely impair cardiac function in hypoplastic left heart syndrome, thus worsening long-term outcome. CASE PRESENTATION: A German infant with borderline aortic and mitral valve, hypoplastic left ventricle, ventricular septal defect, and hypoplastic aortic arch with critical coarctation initially underwent aortic arch reconstruction and aortic valve dilation with the aim of biventricular correction later on. Unfortunately, severe cardiac dysfunction necessitated a change in strategy entailing modified stage I Norwood palliation. Increasing aortic regurgitation with coronary steal was revealed postoperatively, which required redo surgery to oversew the valve. However, pronounced aortic regurgitation recurred, causing severe cardiac decompensation with repeated resuscitation. As a bailout strategy, we performed aortic valve closure via transfemoral retrograde implantation of an Amplatzer Duct Occluder II device. This led to the patient's rapid stabilization while circumventing highly risky renewed surgery in such a critically ill infant. CONCLUSIONS: Retrograde transcatheter aortic valve closure may be considered a feasible alternative in infants with a failing single ventricle due to aortic regurgitation, with critical device evaluation being crucial for successful device implantation in this young age group.

Left recurrent laryngeal nerve palsy following aortic arch stenting: A case report.

BACKGROUND: Aortic arch stenting is continuously emerging as a safe and effective option to alleviate aortic arch stenosis and arterial hypertension. CASE SUMMARY: We present a 15-year-old girl with aortic arch hypoplasia who had undergone implantation of an uncovered 22 mm Cheatham-Platinum stent due to severe (native) aortic arch stenosis. On follow-up seven months later, she presented a significant re-stenosis of the aortic arch. A second stent (LD Max 26 mm) was implanted and both stents were dilated up to 16 mm. After an initially unremarkable post-interventional course, the patient presented with hoarseness five days after the intervention. MRI and CT scans ruled out an intracranial pathology, as well as thoracic hematoma, arterial dissection, and aneurysm around the intervention site. Laryngoscopy confirmed left vocal fold paresis attributable to an injury to the left recurrent laryngeal nerve (LRLN) during aortic arch stenting, as the nerve loops around the aortic arch in close proximity to the area of the implanted stents. Following a non-invasive therapeutic approach entailing regular speech therapy, the patient recovered and demonstrated no residual clinical symptoms of LRLN palsy after six months. CONCLUSION: Left recurrent laryngeal nerve palsy is a rare complication of aortic arch stenting not previously reported.

Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility.

AIMS: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling. METHODS AND RESULTS: Transgenic rabbits were generated by oocyte-microinjection of ß-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.8 ± 2 ms vs. 166.4 ± 3, P < 0.0001). Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Ventricular tachycardia/fibrillation (VT/VF) inducibility was increased in SQT1. Systolic function was unaltered but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged/normalized QT and action potential duration (APD) in SQT1 rabbits by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype. CONCLUSION: Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies.