Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation.

OBJECTIVES: Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited. METHODS: All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models. RESULTS: The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%). CONCLUSIONS: Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.

Myocardial recovery in children supported with a durable ventricular assist device-a systematic review.

OBJECTIVES: A small percentage of paediatric patients supported with a ventricular assist device (VAD) can have their device explanted following myocardial recovery. The goal of this systematic review is to summarize the current literature on the clinical course in these children after weaning. METHODS: A systematic literature search was performed on 27 May 2022 using Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar to include all literature on paediatric patients supported by a durable VAD during the last decade. Overlapping study cohorts and registry-based studies were filtered out. RESULTS: Thirty-seven articles were included. Eighteen of them reported on the incidence of recovery in cohort studies, with an overall incidence rate of 8.7% (81/928). Twenty-two of the included articles reported on clinical outcomes after VAD explantation (83 patients). The aetiologies varied widely and were not limited to diseases with a natural transient course like myocarditis. Most of the patients in the included studies (70; 84.3%) were supported by a Berlin Heart EXCOR, and in 66.3% (55/83), only the left ventricle had to be supported. The longest follow-up period was 19.1 years, and multiple studies reported on long-term myocardial recovery. Fewer than half of the reported deaths had a cardiac cause. CONCLUSIONS: Myocardial recovery during VAD support is dependent on various contributing components. The interactions among patient-, device-, time- and hospital-related factors are complex and not yet fully understood. Long-term recovery after VAD support is achievable, even after a long duration of VAD support, and even in patients with aetiologies different from myocarditis or post-cardiotomy heart failure. More research is needed on this favourable outcome after VAD support.

Outcomes in small children on Berlin Heart EXCOR support: age and body surface area as clinical predictive factors.

OBJECTIVES: The Berlin Heart EXCOR (BHE) offers circulatory support across all paediatric ages. Clinically, the necessary care and the outcomes differ in various age groups. The EUROMACS database was used to study age- and size-related outcomes for this specific device. METHODS: All patients <19 years of age from the EUROMACS database supported with a BHE between 2000 and November 2021 were included. Maximally selected rank statistics were used to determine body surface area (BSA) cut-off values. Multivariable Cox proportional hazard regression using ridge penalization was performed to identify factors associated with outcomes. RESULTS: In total, 303 patients were included [mean age: 2.0 years (interquartile range: 0.6-8.0, males: 48.5%)]. Age and BSA were not significantly associated with mortality (n = 74, P = 0.684, P = 0.679). Factors associated with a transplant (n = 175) were age (hazard ratio 1.07, P = 0.006) and aetiology other than congenital heart disease (hazard ratio 1.46, P = 0.020). Recovery rates (n = 42) were highest in patients with a BSA of <0.53 m2 (21.8% vs 4.3-7.6% at 1 year, P = 0.00534). Patients with a BSA of ≥0.73 m2 had a lower risk of early pump thrombosis but a higher risk of early bleeding compared to children with a BSA of <0.73 m2. CONCLUSIONS: Mortality rates in Berlin Heart-supported patients cannot be predicted by age or BSA. Recovery rates are remarkably high in the smallest patient category (BSA <0.53 m2). This underscores that the BHE is a viable therapeutic option, even for the smallest and youngest patients.

Cerebrovascular accidents in paediatric patients supported by the Berlin Heart EXCOR.

OBJECTIVES: Ventricular assist device support as a bridge to transplant or recovery is a well-established therapy in children on the cardiac transplant waiting list. The goal of this study was to investigate the incidence of and the associated factors for cerebrovascular accidents in paediatric patients supported by a Berlin Heart EXCOR. METHODS: All patients <19 years of age supported by a Berlin Heart EXCOR between January 2011 and January 2021 from the European Registry for Patients with Mechanical Circulatory Support were included. RESULTS: In total, 230 patients were included. A total of 140 (60.9%) patients had a diagnosis of dilated cardiomyopathy. 46 patients (20.0%) sustained 55 cerebrovascular accidents, with 70.9% of the episodes within 90 days after the ventricular assist device was implanted. The event rate of cerebrovascular accidents was highest in the first era (0.75). Pump thrombosis and secondary need for a right ventricular assist device were found to be associated with a cerebrovascular accident (hazard ratio 1.998, P = 0.040; hazard ratio 11.300, P = 0.037). At the 1-year follow-up, 44.4% of the patients had received a transplant, 13.1% were weaned after recovery and 24.5% had died. Event rates for mortality showed a significantly decreasing trend. CONCLUSIONS: Paediatric ventricular assist device support is associated with important adverse events, especially in the early phase after the device is implanted. Pump thrombosis and the need for a secondary right ventricular assist device are associated with cerebrovascular accidents. Furthermore, an encouragingly high rate of recovery in this patient population was shown, and death rates declined. More complete input of data into the registry, especially concerning anticoagulation protocols, would improve the data.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

State-of-the art review: Noncompaction cardiomyopathy in pediatric patients.

Noncompaction cardiomyopathy (NCCM) is a disease characterized by hypertrabeculation, commonly hypothesized due to an arrest in compaction during fetal development. In 2006, NCCM was classified as a distinct form of cardiomyopathy (CMP) by the American Heart Association. NCCM in childhood is more frequently familial than when diagnosed in adulthood and is associated with other congenital heart diseases (CHDs), other genetic CMPs, and neuromuscular diseases (NMDs). It is yet a rare cardiac diseased with an estimated incidence of 0.12 per 100.000 in children up to 10 years of age. Diagnosing NCCM can be challenging due to non-uniform diagnostic criteria, unawareness, presumed other CMPs, and presence of CHD. Therefore, the incidence of NCCM in children might be an underestimation. Nonetheless, NCCM is the third most common cardiomyopathy in childhood and is associated with heart failure, arrhythmias, and/or thromboembolic events. This state-of-the-art review provides an overview on pediatric NCCM. In addition, we discuss the natural history, epidemiology, genetics, clinical presentation, outcome, and therapeutic options of NCCM in pediatric patients, including fetuses, neonates, infants, and children. Furthermore, we provide a simple classification of different forms of the disease. Finally, the differences between the pediatric population and the adult population are described.

Pediatric Ventricular Assist Device Support in the Netherlands.

BACKGROUND: This study aimed to evaluate the changes in heart transplantation (HTx) waiting list mortality following the introduction of the Berlin Heart EXCOR (BH EXCOR) in the Netherlands, as well as the occurrence of adverse events in these children. METHODS: A retrospective, single-center study was conducted including all pediatric patients (≤18 years) awaiting HTx. Patients were grouped in two eras based on availability of the BH EXCOR in our center, era I (1998-2006; not available) and era II (2007 to July 31, 2018; available). RESULTS: In total, 87 patients were included, 15 in era I and 72 in era II. Extracorporeal membrane oxygenator support was required in 1 (7%) patient in era I and in 13 (18%) patients in era II. Overall mortality (7/15 in era I vs 16/72 in era II; 47% vs 22%, P = .06) and transplantation rates (8/15 in era I vs 47/72 in era II; 53% vs 65%, P = .39) did not differ significantly. Eleven (39%) patients of the pediatric ventricular assist device (VAD) population died, with the predominant cause being cerebrovascular accidents (CVAs) in eight (29%) patients. Furthermore, 14 (50%) of the pediatric VAD patients survived to transplantation. Adverse events most frequently occurring in VAD patients included CVA in 14 (50%), mostly (68%) within 30 days after VAD implantation, and bleeding requiring rethoracotomy in 14 (50%), all within 30 days after VAD implantation. CONCLUSIONS: The introduction of the BH EXCOR has positively impacted the survival of pediatric patients with end-stage heart failure in our center. The predominant cause of death changed from end-stage heart failure in era I to CVA in era II. We emphasize the need for large prospective registry-based studies.

Early markers of atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Postprocedural atrial extrasystole (AES) frequency predicts atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) in patients with paroxysmal AF. However, the predictive value of preprocedural AES frequency is unknown. We investigate whether preprocedural AES frequency is a feasible marker to predict (timing of) AF recurrence after PVI. METHODS: Patients (N = 684) with paroxysmal or persistent AF undergoing first-time PVI were evaluated for (a) the frequency of AES/day on Holter recordings without AF prior to PVI, (b) AF episodes during the 90 days blanking period, and (c) AF recurrences afterward. The correlation between AES/day and both development and timing of AF recurrences was tested. RESULTS: Preprocedural AES/day was similar in patients with paroxysmal (66 [20-295] AES/day) and persistent AF (115 [12-248] AES/day, P = .915). During the blanking period, 302 (44.2%) patients showed AF episodes. AF recurred in 379 (55.4%) patients at 203 (105-400) days after PVI. AF recurred more frequently in patients with persistent (N = 104 [69.3%]) than in patients with paroxysmal AF (N = 275 [51.5%], P < .001). Frequency of AES prior to PVI was not correlated with development (P = .203) or timing (P = .478) of AF recurrences. AF recurrences occurred both more frequently (P < .001) and earlier (P < .000) in patients with AF during the blanking period. CONCLUSION: AES/day prior to PVI is not correlated with (timing of) AF during the blanking period or AF recurrences, and is therefore not a feasible marker for AF recurrences in patients with PAF. AF during the blanking period is correlated with AF recurrence.

Sex-specific distributions and determinants of thoracic aortic diameters in the elderly.

OBJECTIVE: To provide population-based distributions of thoracic aortic diameters in men and women aged 55 years or older and to identify determinants of thoracic aortic diameters. METHODS: From 2003 to 2006, 2505 participants (1208 men, mean age 69.1±6.8 years) from the prospective population-based Rotterdam Study underwent non-enhanced cardiac CT. The diameter of the ascending (AA) and descending aorta (DA) was measured at the level of the pulmonary bifurcation. RESULTS: The mean diameter of the ascending and descending aorta was substantially larger in men (38±4 mm and 30±2 mm) than in women (35±3 mm and 27±2 mm). An ascending aortic diameter of larger than 40 mm was found in 228 (18.9%) men and 76 (5.9%) women and a descending aortic diameter larger than 40 mm was found in two men and no women. Male sex was found to be independently associated with larger DA diameter (standardised ß 0.24, 95% CI 0.19 to 0.30), while a statistically non-significant trend was found for the AA diameter (standardised ß 0.06, 95% CI 0.00 to 0.12). Age, height, weight and traditional cardiovascular risk factors were also associated with larger AA and/or DA diameters. Diabetes was associated with smaller AA and DA diameters. We found no evidence for effect modification by sex. CONCLUSIONS: In persons aged 55 years or older, an ascending aortic diameter of 40 mm or larger was found in 18.9% of men and 5.9% of women. Given the importance of sex, sex-specific distribution values may prove useful in clinical practice, even when correcting for body surface area or height.

Clinical outcomes of paediatric patients supported by the Berlin Heart EXCOR: a systematic review.

Ventricular assist devices (VADs) are widely accepted as therapy to bridge children to heart transplantation. We provide a systematic review of the current state of clinical outcomes in children after paediatric VAD support by the Berlin Heart EXCOR (BH EXCOR) device. A systematic literature search was performed in April 2018. Studies reporting clinical outcomes in at least 15 children supported by a BH EXCOR VAD were included. Additionally, we focused on outcomes in small children and compared outcomes of children supported by a left ventricular assist device (LVAD) versus children supported by a biventricular assist device (BiVAD). Eighteen publications fulfilled the inclusion criteria and were included in this systematic review. Mortality rates ranged from 6.3% [confidence interval (CI) 0.0-18.1%] to 38.9% (2.8-75.0%) while transplantation rates ranged from 37.0% (CI 18.8-55.2%) to 72.5% (CI 63.9-81.2%) and successful weaning rates from 0.0% to 20.7% (CI 6.0-35.5%). In children under 1 year of age, mortality rates ranged from 20.0% to 55.5% and transplantation rates ranged from 0.0% to 62.5%. BiVAD support seemed to result in worse clinical outcomes than LVAD support. Incidence of stroke ranged from 5.0% to 47.0% in all children supported with the BH EXCOR. Although a high incidence of adverse events such as stroke and pump thrombosis is reported, VAD support should be considered in children with end-stage heart failure awaiting heart transplantation. Further research is warranted, especially on optimal timing of device implantation and anticoagulation regimens.

Endemic and emerging acute virus infections in Indonesia: an overview of the past decade and implications for the future.

Being the largest archipelago country in the world, with a tropical climate and a unique flora and fauna, Indonesia habitats one of the most diverse biome in the world. These characteristics make Indonesia a popular travel destination, with tourism numbers increasing yearly. These characteristics also facilitate the transmission of zoonosis and provide ideal living and breading circumstances for arthropods, known vectors for viral diseases. A review of the past 10 years of literature, reports of the Ministry of Health, Republic of Indonesia and ProMED-mail shows a significant increase in dengue infection incidence. Furthermore, chikungunya, Japanese encephalitis and rabies are proven to be endemic in Indonesia. The combination of cohort studies, governmental data and ProMED-mail reveals an integrated overview for those working in travel medicine and public health, focusing on both endemic and emerging acute virus infections. This review summarizes the epidemiology of acute virus infections in Indonesia, including outbreak reports, as well as public health response measurements and their potential or efficacy. Knowledge about human behaviour, animal reservoirs, climate factors, environment and their role in emerging virus infection are discussed. We aim to support public health authorities and health care policy makers in a One Health approach.