"Take it or leave it": Analysis of pediatric heart offers for transplantation in Switzerland.

BACKGROUND: There is a shortage of donor hearts in Switzerland, especially for pediatric recipients. However, the rate and reason for refusals of pediatric donor hearts offered in Switzerland has not been systematically analyzed. METHODS: The national transplant database, Swiss Organ Allocation System, was searched for all hearts from Swiss and foreign donors younger than 16 years from 2015 to 2020. The numbers of accepted and refused hearts and early outcome were assessed, and the reasons for refusal were retrospectively analyzed. RESULTS: A total of 136 organs were offered to the three Swiss pediatric heart centers and foreign donor procurement organizations. Of these, 26/136 (19%) organs were accepted and transplanted: 18 hearts were transplanted in Switzerland, and 13 of these were foreign. Reasons for refusal were (1) no compatible recipient due to blood group or weight mismatch, 89.4%; (2) medical, meaning organ too marginal for transplantation, 7.4%; (3) logistic, 1.4%; and (4) other, 1.8%. Five organs were refused in Switzerland by one center but later accepted and successfully transplanted by another center. Hearts from outside Switzerland were transplanted significantly less than Swiss hearts (n = 16/120 vs. 10/16, p < .001). CONCLUSION: The most common reason for refusing a pediatric donor heart is lack of compatibility with the recipient. Few hearts are refused for medical reasons. A more generous acceptance seems to be justified in selected patients. Switzerland receives a high number of foreign offers, but their rate of acceptance is lower than that of Swiss donations.

Comparable bleeding and inflammation outcomes between heparin-coated and uncoated minimal invasive extracorporeal circuits in isolated coronary artery bypass surgery - A double-blinded randomized control trial.

OBJECTIVE: Minimally invasive extracorporeal circulation has been shown to be non-inferior or even superior to conventional cardiopulmonary bypass circuits in isolated coronary artery bypass grafting, but there is little evidence whether the addition of a heparin-coated circuit can further reduce the inflammatory response and amount of bleeding in these patients. METHODS: A single-center randomized control trial enrolled 49 adult patients scheduled to undergo isolated coronary artery bypass grafting with minimally invasive extracorporeal circulation (MiECC) between January 2015 and December 2018. Patients were randomized 1:1 to either the heparin-coated circuit group, or the uncoated (control) circuit group. The primary outcome was chest tube output 18 h after weaning from MiECC, and secondary outcomes included inflammatory (TNF-α, IL-6, IL-8, IL-10) and complement (C3a, C4d, C5a, sC5b-9) biomarkers, platelet count and function (D2D, TAT, SDC1, PF4), number of transfused blood products, and 30-day survival. RESULTS: Patients were randomized to undergo myocardial revascularization using heparin-coated circuits (n = 25), and to the uncoated MiECC circuit (n = 24), with comparable baseline demographics. No significant difference was observed in chest tube output and for all secondary outcomes. IL-6 and IL-8 were increased from baseline at 18 h after weaning (effect size 0.29 and 0.05, respectively) and sC5b-9 was lower (effect size 0.11) in the heparin-coated than in the uncoated MiECC, although not significantly different. CONCLUSIONS: Compared with an uncoated MiECC circuit, heparin-coated MiECC circuit was not associated with a reduction in postoperative bleeding, transfusion, inflammation, complement activation, and platelet biomarkers, following isolated coronary artery bypass grafting.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

The use of minimal invasive extracorporeal circulation for rewarming after accidental hypothermia and circulatory arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation has become a recommended treatment option for patients with severe hypothermia with cardiac arrest. Minimal invasive extracorporeal circulation (MiECC) may offer advantages over the current standard extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective cohort analysis of hospital database for patients with accidental hypothermia and extracorporeal rewarming with MiECC admitted between 2010 and 2019. RESULTS: Overall, six of 17 patients survived to hospital discharge. Eleven patients suffered accidental hypothermia in an alpine and six in an urban setting. Sixteen patients arrived at the hospital under ongoing cardiopulmonary resuscitation (CPR). CPR time was 90 minutes (0-150). Four patients survived from an alpine setting and two from an urban setting with CPR duration of 90 minutes (0-150) and 85 minutes (25-100), respectively. Asphyctic patients tended to have lower survival (one of seven patients). Two patients of six with major trauma survived. CONCLUSION: MiECC for extracorporeal rewarming from severe accidental hypothermia is a feasible alternative to ECMO, with comparable survival rates.

Long-Term Clinical and Imaging Follow-Up After Reinforced Pulmonary Autograft Ross Procedure.

The Ross operation remains a controversially discussed procedure when performed in the full root technique because concern exists regarding late dilatation of the pulmonary autograft and regurgitation of the neo-aortic valve. In 2008, we published our short-term experience when using external reinforcement of the autograft, which was inserted into a prosthetic Dacron graft. This detail was thought to prevent neoaortic root dilatation. Since 2006, 22 adult patients have undergone a Ross procedure using this technique. Indications were aortic regurgitation (n = 2), aortic stenosis (n = 15), and combined aortic stenosis and insufficiency (n = 5). A bicuspid aortic valve was present in 10 patients. Prior balloon valvuloplasty had been performed in seven patients. No early or late deaths occurred in this small series. One patient required aortic valve replacement early postoperatively, but freedom from late reoperation is 100% in the 21 remaining patients. Echocardiography confirmed the absence of more than trivial aortic insufficiency in 15 patients after a mean of 70 months (range, 14 to 108 months). No autograft dilatation was observed during follow-up and all patients are in New York Heart Association Class I. Autograft reinforcement is a simple and reproducible technical adjunct that may be especially useful in situations known for late autograft dilatation, namely, bicuspid aortic valve, predominant aortic insufficiency, and ascending aortic enlargement. The mid- to long-term results are encouraging because no late aortic root enlargement has been observed and the autograft valve is well functioning in all cases.

Minimally invasive extracorporeal circulation resuscitation in hypothermic cardiac arrest.

Current guidelines for the treatment of hypothermic cardiocirculatory arrest recommend extracorporeal life support and rewarming, using cardiopulmonary bypass or extracorporeal membrane oxygenation circuits. Both have design-related shortcomings which may result in prolonged reperfusion time or insufficient oxygen delivery to vital organs. This article describes clear advantages of minimally invasive extracorporeal circulation systems during emergency extracorporeal life support in hypothermic arrest. The technique of minimally invasive extracorporeal circulation for reperfusion and rewarming is represented by the case of a 59-year-old patient in hypothermic cardiocirculatory arrest at 25.3°C core temperature, with multiple trauma. With femoro-femoral cannulation performed under sonographic and echocardiographic guidance, extracorporeal life support was initiated using a minimally invasive extracorporeal circulation system. Perfusing rhythm was restored at 28°C. During rewarming on the mobile circuit, trauma surveys were completed and the treatment initiated. Normothermic weaning was successful on the first attempt, trauma surgery was completed and the patient survived neurologically intact. For extracorporeal resuscitation from hypothermic arrest, minimally invasive extracorporeal circulation offers all the advantages of conventional cardiopulmonary bypass and extracorporeal membrane oxygenation systems without their shortcomings.

Acute aortic dissection determines the fate of initially untreated aortic segments in Marfan syndrome.

BACKGROUND: The aim of the current study was to investigate incidence and causes of surgical interventions in primarily nontreated aortic segments after previous aortic repair in patients with Marfan syndrome. METHODS AND RESULTS: Retrospective analysis of 86 consecutive Marfan syndrome patients fulfilling Ghent criteria that underwent 136 aortic surgeries and were followed at this institution in the past 15 years. Mean follow-up was 8.8±6.8 y. Thirty-day, 6-month, 1-year, and overall mortality was 3.5%, 5.8%, 7.0%, and 12.8%, respectively. Ninety-two percent of patients initially presented with aortic root, ascending aortic or arch lesions, whereas 8% presented with descending aortic or thoraco-abdominal lesions. Primary presentation was acute aortic dissection (AAD) in 36% (77% type A, 23% type B) and aneurismal disease in 64%. Secondary complete arch replacement had to be performed in only 6% of patients without AAD, but in 36% with AAD (P=0.0005). In patients without AAD, 11% required surgery on primarily nontreated aortic segments (5 of 6 patients experienced type B dissection during follow-up), whereas in patients after AAD, 48% underwent surgery of initially nontreated aortic segments (42% of patients with type A and 86% of those with type B dissection; P=0.0002). CONCLUSIONS: The need for surgery in primarily nontreated aortic segments is precipitated by an initial presentation with AAD. Early elective surgery is associated with low mortality and reintervention rates. Type B dissection in patients with Marfan syndrome is associated with a high need for extensive aortic repair, even if the dissection is being considered uncomplicated by conventional criteria.

Dimensions of the ascending aorta in conotruncal heart defects.

Dilatation of the ascending aorta is an important sequel in conotruncal anomalies, such as tetralogy of Fallot (TOF) or d-transposition of the great arteries (TGA). We measured dimensions and their progression at different levels of the ascending aorta in 80 patients. In TOF patients, mean z-score for aortic annulus was 1.65 (range -3.16-6.47), for sinus 1.93 (range -2.28-5.39), for st-junction 4.15 (range 0.0-8.18), and for ascending aorta 3.51 (range -1.23-6.36). Over time, annulus z-scores increased in the univariate analysis [0.07/year, 95 % confidence interval (CI) 0.01-0.14; p = 0.02], and this was unique to male patients (0.08/year, 95 % CI 0.00-0.15; p = 0.05). z-scores of the ascending aorta decreased (-0.1/year, 95 % CI -0.18 to -0.02; p = 0.02), and this was confined to patients without aortic regurgitation (AR; -0.09/year, 95 % CI -0.18 to -0.01; p = 0.04). In TGA, mean z-score for the aortic annulus was 2.13 (range -3.71-8.39), for sinus 1.77 (range -3.04-6.69), for st-junction 1.01 (range -5.44-6.71), and for ascending aorta 0.82 (range -4.91-6.46). In bivariate analysis, annulus z-scores decreased in females (-0.14/year, 95 % CI -0.25 to -0.03; p = 0.01) and in patients without AR (-0.07/year, 95 % CI -0.14-0.0; p = 0.03). z-scores of the ascending aorta increased significantly in males (0.08/year, 95 % CI 0.0 to 0.16; p = 0.05) and in patients with AR (0.12/year, 95 % CI 0.03-0.21; p = 0.01). In conclusion, TOF and TGA z-scores of the ascending aorta differ significantly from those of the normal population. Progression of z-scores over time is influenced by diagnosis, sex, and presence of AR.

Ultrasound-assisted catheter-directed thrombolysis versus surgical pulmonary embolectomy for intermediate-high or high-risk pulmonary embolism: a randomized phase II non-inferiority trial.

OBJECTIVES: We hypothesized that ultrasound-assisted thrombolysis (USAT) is non-inferior to surgical pulmonary embolectomy (SPE) to improve right ventricular (RV) function in patients with acute pulmonary embolism (PE). METHODS: In a single-centre, non-inferiority trial, we randomly assigned 27 patients with intermediate-high or high-risk acute PE to undergo either USAT or SPE stratified by PE risk. Primary and secondary outcomes were the baseline-to-72-h difference in right-to-left ventricular (RV/LV) ratio and the Qanadli pulmonary occlusion score, respectively, by contrast-enhanced chest-computed tomography assessed by a blinded CoreLab. RESULTS: The trial was prematurely terminated due to slow enrolment. Mean age was 62.6 (SD 12.4) years, 26% were women, and 15% had high-risk PE. Mean change in RV/LV ratio was -0.34 (95% CI -0.50 to -0.18) in the USAT and -0.53 (95% CI -0.68 to -0.38) in the SPE group (mean difference: 0.152; 95% CI 0.032-0.271; Pnon-inferiority = 0.80; Psuperiority = 0.013). Mean change in Qanadli pulmonary occlusion score was -7.23 (95% CI -9.58 to -4.88) in the USAT and -11.36 (95% CI -15.27 to -7.44) in the SPE group (mean difference: 5.00; 95% CI 0.44-9.56, P = 0.032). Clinical and functional outcomes were similar between the 2 groups up to 12 months. CONCLUSIONS: In patients with intermediate-high and high-risk acute PE, USAT was not non-inferior when compared with SPE in reducing RV/LV ratio within the first 72 h. In a post hoc superiority analysis, SPE resulted in greater improvement of RV overload and reduction of thrombus burden.

Circulating factors, in both donor and ex-situ heart perfusion, correlate with heart recovery in a pig model of DCD.

BACKGROUND: Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. METHODS: Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 minutes. Hearts were explanted and underwent ex-situ perfusion for 3 hours in an unloaded mode, followed by left ventricular loading for 1 hour, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. RESULTS: Circulating adrenaline, both in the donor and at 10 minutes ex-situ heart perfusion, negatively correlated with cardiac recovery (p < 0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p < 0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 minutes. CONCLUSIONS: In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

Open- vs. closed-chest pig models of donation after circulatory death.

Background: During donation after circulatory death (DCD), cardiac grafts are exposed to potentially damaging conditions that can impact their quality and post-transplantation outcomes. In a clinical DCD setting, patients have closed chests in most cases, while many experimental models have used open-chest conditions. We therefore aimed to investigate and characterize differences in open- vs. closed-chest porcine models. Methods: Withdrawal of life-sustaining therapy (WLST) was simulated in anesthetized juvenile male pigs by stopping mechanical ventilation following the administration of a neuromuscular block. Functional warm ischemic time (fWIT) was defined to start when systolic arterial pressure was <50 mmHg. Hemodynamic changes and blood chemistry were analyzed. Two experimental groups were compared: (i) an open-chest group with sternotomy prior to WLST and (ii) a closed-chest group with sternotomy after fWIT. Results: Hemodynamic changes during the progression from WLST to fWIT were initiated by a rapid decline in blood oxygen saturation and a subsequent cardiovascular hyperdynamic (HD) period characterized by temporary elevations in heart rates and arterial pressures in both groups. Subsequently, heart rate and systolic arterial pressure decreased until fWIT was reached. Pigs in the open-chest group displayed a more rapid transition to the HD phase after WLST, with peak heart rate and peak rate-pressure product occurring significantly earlier. Furthermore, the HD phase duration tended to be shorter and less intense (lower peak rate-pressure product) in the open-chest group than in the closed-chest group. Discussion: Progression from WLST to fWIT was more rapid, and the hemodynamic changes tended to be less pronounced in the open-chest group than in the closed-chest group. Our findings support clear differences between open- and closed-chest models of DCD. Therefore, recommendations for clinical DCD protocols based on findings in open-chest models must be interpreted with care.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): fourth Paediatric EUROMACS (Paedi-EUROMACS) report.

OBJECTIVES: The use of ventricular assist devices (VADs) in children is increasing. However, absolute numbers in individual centres and countries remain small. Collaborative efforts such as the Paedi-European Registry for Patients with Mechanical Circulatory Support (EUROMACS) are therefore essential for combining international experience with paediatric VADs. Our goal was to present the results from the fourth Paedi-EUROMACS report. METHODS: All paediatric (<19 years) patients from the EUROMACS database supported by a VAD were included. Patients were stratified into a congenital heart disease (CHD) group and a group with a non-congenital aetiology. End points included mortality, a transplant and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident and pump thrombosis. RESULTS: A total of 590 primary implants were included. The congenital group was significantly younger (2.5 vs 8.0 years, respectively, P < 0.001) and was more commonly supported by a pulsatile flow device (73.5% vs 59.9%, P < 0.001). Mortality was significantly higher in the congenital group (30.8% vs 20.4%, P = 0.009) than in the non-congenital group. However, in multivariable analyses, CHD was not significantly associated with mortality [hazard ratio (HR) 1.285; confidence interval (CI) 0.8111-2.036, P = 0.740]. Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with body surface area (HR 0.524, CI 0.333-0.823, P = 0.005), CHD (HR 1.641, CI 1.054-2.555, P = 0.028) and pulsatile flow support (HR 2.345, CI 1.406-3.910, P = 0.001) in multivariable analyses. CONCLUSIONS: This fourth Paedi-EUROMACS report highlights the increasing use of paediatric VADs. The patient populations with congenital and non-congenital aetiologies exhibit distinct characteristics and clinical outcomes.

Giant cardiac fibroma: an unusual cause of failure to thrive.

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

Safety and efficacy of surgical correction of anomalous aortic origin of coronary arteries: experiences from 2 tertiary cardiac centres.

OBJECTIVES: This study aims to describe the outcomes of surgical correction for anomalous aortic origin of coronary artery (AAOCA) with regard to symptom relief. METHODS: We performed a retrospective multicentre study including surgical patients who underwent correction for AAOCA between 2009 and 2022. Patients who underwent concomitant cardiac procedures were also included. However, to analyse symptom relief, we only assessed the subgroup of symptomatic patients who underwent isolated correction for AAOCA. RESULTS: A total of 71 consecutive patients (median age 55, range 12-83) who underwent surgical correction for AAOCA were included in the study. Right-AAOCA was present in 56 patients (79%), left-AAOCA in 11 patients (15%) and single coronary ostium AAOCA in 4 patients (6%). Coronary unroofing was performed in 72% of the patients, coronary reimplantation in 28% and an additional neo-ostium patchplasty in 13% of the patients. In 39% of the patients, a concomitant cardiac procedure was performed. During follow-up, no cardiovascular-related death was observed. Three patients (4.2%) had a myocardial infarction and underwent postoperative coronary artery bypass grafting. Six patients (8.5%) needed postoperative temporary mechanical circulatory support. Among the 34 symptomatic patients who underwent isolated AAOCA correction, 70% were completely asymptomatic after surgery, 12% showed symptom improvement and no symptom improvement was observed in 18% of the patients (median follow-up 3.5 years, range 0.3-11.1). CONCLUSIONS: Correction for AAOCA can be safely performed with or without concomitant cardiac procedures. Performing AAOCA correction leads to a significant improvement in symptoms for most patients.

Surgical versus transcatheter repair for secondary mitral regurgitation: A propensity score-matched cohorts comparison.

OBJECTIVES: To compare the efficacy and clinical outcomes of transcatheter edge-to-edge mitral valve repair (TMVr) and surgical mitral valve repair (SMVr) among patients with secondary mitral regurgitation (SMR). METHODS: Consecutive patients with SMR treated using either TMVr (n = 199) or SMVr (n = 222) at 2 centers were included and retrospectively analyzed. To account for differences in patient demographic characteristics, 1:1 propensity score matching was performed. The primary endpoint was all-cause death within 2 years after the procedure. RESULTS: The study population consisted of 202 matched patients. At 2 years, all-cause mortality was 24.3% for TMVr and 23.0% for SMVr (hazard ratio, 0.97; 95% confidence interval, 0.55-1.71; P = .909). Severe heart failure symptoms at 2 years were less prevalent after SMVr (New York Heart Association functional class III or IV: 13.5% vs 29.5%; P = .032) than after TMVr. A higher proportion of the SMVr patients had SMR reduction to none or mild at discharge (90.8% vs 72.0%; P < .001) and 2 years (86.5% vs 59.6%; P < .001). Among patients who achieved none or mild MR at discharge, 7 patients (10.1%) in the SMVr group and 15 (34.9%) in the TMVr group had progression to moderate or greater MR at 2 years (P = .003). Left ventricular ejection fraction (LVEF) significantly improved (+10.1% ± 11.1%; P < .001) after SMVr (LVEF at 2 years: 45.7% ± 12.8%), whereas it remained unchanged (-1.3% ± 8.9%; P = .260) after TMVr (LVEF at 2 years: 34.0% ± 13.2%). CONCLUSIONS: In this propensity score-matched analysis, there was no significant difference in 2-year survival between TMVr and SMVr, despite greater and more durable SMR reduction, as well as LVEF improvement in the surgical group.

Mortality and neurologic injury after surgical repair with hypothermic circulatory arrest in acute and chronic proximal thoracic aortic pathology: effect of age on outcome.

BACKGROUND: The goal of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology. METHODS AND RESULTS: A university center audit was done of 523 consecutive patients (median age, 64 years; interquartile range, 56-71 years) between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients) was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2% (P<0.001). Neurological injury was observed in 16.9% of patients with acute type A aortic dissection (chronic ascending aortic aneurysms, 7.9%; P=0.002). Multivariable regression analysis revealed hypothermic circulatory arrest >40 minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60-11.06; P=0.004) and redo surgery (OR, 3.44; 95% CI, 1.11-10.64; P=0.03) but not age (OR, 1.98; 95% CI, 0.73-5.38; P=0.18) as independent predictor of mortality. Emergency surgery (OR, 3.27; 95% CI, 1.31-8.15; P=0.01) and extracardiac arteriopathy (OR, 2.38; 95% CI, 1.26-4.50; P=0.008) but not age (OR, 1.80; 95% CI, 0.93-3.48; P=0.08) were independent predictors of neurological injury. CONCLUSIONS: Age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality, whereas emergency surgery and extracardiac arteriopathy predict neurological injury.

Electric pulses augment reporter gene expression in the beating heart.

BACKGROUND: Gene therapy of the heart has been attempted in a number of clinical trials with the injection of naked DNA, although quantitative information on myocellular transfection rates is not available. The present study aimed to quantify the efficacy of electropulsing protocols that differ in pulse duration and number to stimulate transfection of cardiomyocytes and to determine the impact on myocardial integrity. METHODS: Reporter plasmid for constitutive expression of green fluorescent protein (GFP) was injected into the left ventricle of beating hearts of adult, male Lewis rats. Four electrotransfer protocols consisting of repeated long pulses (8 × 20 ms), trains of short pulses (eight trains of either 60 or 80 × 100 µs) or their combination were compared with control procedures concerning the degree of GFP expression and the effect on infiltration, fibrosis and apoptosis. RESULTS: All tested protocols produced GFP expression at the site of plasmid injection. Continuous pulses were most effective and increased the number of GFP-positive cardiomyocytes by more than 300-fold compared to plasmid injection alone (p < 0.05). Concomitantly, the incidence of macrophage infiltration, fibrosis and cell death was increased. Trains of short pulses reduced macrophage infiltration and fibrosis by four- and two-fold, respectively, although they were 20-fold less efficient in stimulating cardiomyocyte transfection. GFP expression co-related to delivered electric energy, infiltration and fibrosis, although not apoptosis. CONCLUSIONS: The data imply that electropulsing of the myocardium promotes the overexpression of exogenous protein in mature cardiomyocytes in relation to an injury component. Fractionation of pulses is indicated as a option for sophisticated gene therapeutic approaches to the heart.

Atrioventricular conduction after transcatheter aortic valve implantation and surgical aortic valve replacement.

INTRODUCTION: Atrioventricular conduction abnormalities (AVCA) may complicate transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). The aim of this study was to prospectively evaluate AVCA after TAVI and SAVR. METHODS AND RESULTS: Among 50 patients undergoing TAVI and 25 patients undergoing SAVR a continuous 7-day Holter electrocardiogram (ECG) was recorded after the procedure. ECGs during TAVI and 12-lead ECGs before and 1 and 7 days after TAVI and SAVR were analyzed. At baseline, TAVI patients were older (mean 82.1 vs 75.4, P < 0.001), had a longer PR interval (median 200 milliseconds vs 175 milliseconds, P = 0.004) and broader QRS width (median 100 milliseconds vs 80 milliseconds, P = 0.007) than SAVR patients. New AVCA were observed among 29 TAVI patients (58%), mostly new left bundle branch block (76%). Predilatation induced new AVCA in 14 TAVI patients (28%). New AVCA resolved within 24 hours in 15 TAVI patients (30%), and persisted in 14 TAVI (28%) and 3 SAVR patients (12%, P = 0.12). Among patients with persistent QRS width <120 milliseconds during the first 24 hours after TAVI, QRS width remained stable during the remainder of the observation period. During Holter monitoring complete AV block was observed in 4 TAVI patients (8%) and 3 SAVR patients (12%; P = 0.68). CONCLUSIONS: Almost half of AVCA during TAVI are induced by predilatation, but half of them resolve within 24 hours. Persistent AVCA are more frequently observed after TAVI than SAVR. If QRS width is below 120 milliseconds the first day after TAVI, the risk of late AVCA seems low.

Transapical valve-in-valve implantation for regurgitant stented aortic bioprostheses.

Transcatheter aortic valve implantation (TAVI) is rapidly evolving as an alternative treatment option for elderly patients with severe symptomatic aortic stenosis and excessive risk for surgical intervention. Transcatheter valve-in-valve implantation is an alternative approach to redo-surgery for patients with degeneration of a bioprosthetic valve. Herein are reported three cases of successful transcatheter aortic valve-in-valve implantation for severely regurgitant bioprosthetic valves with a clinical follow up of more than 12 months.