Prevalence of bleeding events in real-world Japanese registry for Percutaneous Ventricular Assist Device.

PURPOSE: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella. METHODS: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed. RESULTS: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events. CONCLUSION: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events.

Outcomes of Veno-Arterial Extracorporeal Membrane Oxygenation With Percutaneous Left Ventricular Unloading in Fulminant Myocarditis.

Fulminant myocarditis requiring peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has a high mortality rate. We investigated clinical outcomes of combined use of VA-ECMO and percutaneous left ventricular assist device (VAD) (Impella) for fulminant myocarditis in 104 consecutive patients enrolled in the Japan Registry for Percutaneous VAD (J-pVAD) between October 2017 and January 2020. Patients were followed until hospital discharge and predictors of survival were analyzed with a Cox proportional hazards model. The median support duration of combined use of VA-ECMO and Impella (ECMO/Impella) was 6 days, and the median left ventricular ejection fraction improved from 15% to 52% during support ( p < 0.0001). Overall, 66 patients (63%) survived to discharge. Multivariate analysis revealed ECMO/Impella support at a transplant center as an independent predictor of survival ( p = 0.0231). Patients treated at transplant centers had better 60 days survival rates when compared to nontransplant centers (83% vs. 55%, p = 0.005). However, baseline characteristics and treatment strategies differed between the two groups. This real-world national registry database suggested the difference in survival after ECMO/Impella support for fulminant myocarditis between transplant and nontransplant centers, which may indicate hospital variations regarding patient management, although further controlled studies are needed.

Short-Term Outcomes of Impella Support in Japanese Patients With Cardiogenic Shock Due to Acute Myocardial Infarction　- Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD).

BACKGROUND: The Impella®percutaneous left ventricular assist device has been available in Japan since 2017. This is the first large-scale registry study to analyze the efficacy and safety of Impella in Japanese patients with acute myocardial infarction with cardiogenic shock (AMICS).Methods and Results: The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) has registered all consecutive Japanese patients treated with Impella. We extracted data for 593 AMICS patients from J-PVAD and analyzed 30-day survival and safety profiles. Overall 30-day survival was 63.1%. The 30-day survival of the Impella alone and Impella plus venoarterial extracorporeal membrane oxygenation (ECPELLA) groups was 80.9% and 45.7%, respectively. The Impella alone group was older and had a lower rate of cardiac arrest, milder consciousness disturbance, less inotrope use, lower serum lactate concentrations, higher B-type natriuretic peptide concentrations, and higher left ventricular ejection fraction (LVEF) than the ECPELLA group. Cox regression analysis revealed that older age and comorbid renal disturbance were common risk factors affecting 30-day mortality in both groups. Major adverse events were hemolysis (10.8%), hemorrhage/hematoma (7.6%), peripheral ischemia (4.4%), stroke (1.3%), and thrombosis (0.7%). LVEF improved in both groups during support. CONCLUSIONS: AMICS treatment with Impella showed favorable 30-day survival and safety profiles. The survival rate of patients treated with Impella alone was particularly high. Further studies are needed to improve outcomes of patients with ECPELLA support.

Three-year experience of catheter-based micro-axial left ventricular assist device, Impella, in Japanese patients: the first interim analysis of Japan registry for percutaneous ventricular assist device (J-PVAD).

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p < 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles.

Outcomes of hypertrophic cardiomyopathy in Japanese children: a retrospective cohort study.

There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan.

Outcomes of Restrictive Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric restrictive cardiomyopathy (RCM) in Japan; therefore, this retrospective multicentered study was designed to investigate the long-term survival rate of pediatric patients with RCM in Japan.Methods and Results: A multicentered, retrospective observational study was performed between 1990 and 2014 and included patients diagnosed with RCM who were aged <18 years from 18 Japanese institutions. A total of 54 patients were diagnosed with RCM. The median age at diagnosis was 4.4 years, and the median duration of observation was 2.2 years at the time of this study. Of these patients, 54% had symptoms, including heart failure. Twelve patients died without heart transplantation, mostly due to heart failure. The median time to death from diagnosis was 2.5 years. Freedom from death at 1, 5, and 10 years was 91%, 68%, and 62%, respectively. Death occurred within 5 years of diagnosis in most patients. Twenty-two patients underwent heart transplantation. Freedom from heart transplantation at 1, 5, and 10 years was 77%, 58%, and 53%, respectively. Freedom from death or heart transplantation at 1, 5, and 10 years was 72%, 40%, and 34%, respectively. The presence of symptoms was a risk factor for death or transplantation. CONCLUSIONS: The prognosis of pediatric RCM is poor, and the heart transplantation rate is low in Japan.

Outcomes of Dilated Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis. CONCLUSIONS: In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

Poor Myocardial Compaction in a Patient with Recessive MYL2 Myopathy.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.

Relationship between post-IVIG IgG levels and clinical outcomes in Kawasaki disease patients: new insight into the mechanism of action of IVIG.

INTRODUCTION/OBJECTIVES: The dosing of intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD) has been a matter of debate for decades, with recent studies implicating that larger doses lead to better outcomes. Despite this, few have investigated post-IVIG infusion immunoglobulin G (IgG) levels in relation to outcomes of KD such as response to IVIG and development of coronary artery abnormalities (CAAs). The present study investigated how varying levels of post-infusion IgG affected these outcomes. METHOD: We collected demographic and laboratory data, including post-infusion IgG, from children with KD who were admitted to six hospitals in Japan between 2006 and 2012. We conducted multivariate analyses to examine the relationship between independent variables and non-response to IVIG and development of CAAs. We used random forest, a decision tree-based machine learning tool, to investigate the marginal effect of varying post-infusion IgG levels on non-response to IVIG and development of CAAs. RESULTS: Of 456 patients included in the study, 130 (28.5%) were non-responders and 38 (8.3%) developed CAAs. Sodium, post-infusion IgG, and AST were significantly associated with non-response. Post-infusion IgG and sodium were significantly associated with CAA development. The random forest plots revealed a decrease in non-response and CAA rates with increasing post-infusion IgG until post-infusion IgG was near the median (2821 mg/dL), after which the non-response and CAA rates leveled off. CONCLUSIONS: Greater post-infusion IgG is associated with better response to IVIG and decreased CAA development in KD patients, but this effect levels off at post-infusion IgG levels greater than the median. Key points • Though previous studies have shown that post-intravenous immunoglobulin (IVIG) infusion immunoglobulin G (IgG) is associated with non-response to IVIG therapy and coronary artery abnormality (CAA) development in Kawasaki disease (KD) patients, no study has investigated the relationship between varying levels of post-infusion IgG and these clinical outcomes. • Our study showed that non-response to IVIG therapy and CAA development in Kawasaki disease patients follow a decreasing trend with increasing post-infusion IgG at post-infusion IgG levels below the median. • At values of post-infusion IgG greater than the median, non-response and CAA development rates remain relatively constant with increasing post-infusion IgG. • Our study suggests that when post-infusion IgG is greater than the median, IgG may have fully bound to the therapeutic targets of KD, and in these patients, there may be limited benefit in administering additional IVIG.

Ecthyma gangrenosum in a 3-year-old boy post-heart transplantation.

Ecthyma gangrenosum (EG) is a serious bacterial infection in immunocompromised patients. EG in transplant recipients is rarely reported and may go unrecognized, which may delay initiation of appropriate treatment. We report a case of EG in a pediatric heart transplant recipient who was treated successfully with antibiotics and surgical debridement.

Cardiac Rhythm Disturbances in Heterotaxy Syndrome.

OBJECTIVE: Heterotaxy syndrome is associated with complex cardiac malformations and cardiac conduction system abnormalities. Those with right atrial isomerism (RAI) have dual sinus nodes and dual atrioventricular nodes predisposing them to supraventricular tachycardia (SVT). Those with left atrial isomerism (LAI) lack a normal sinus node and are at risk of sinus node dysfunction (SND) and atrioventricular block (AV block). We report the occurrence and risk factors associated with arrhythmias in heterotaxy syndrome. METHODS: A retrospective review of all heterotaxy syndrome patients born and treated at our institution between 2000 and 2014 was performed. RESULTS: A total of 40 patients were identified; 16/40 (40%) with LAI and 24/40 (60%) with RAI. There were 12 deaths during follow-up [LAI 3/16 (19%), RAI 9/24 (38%); p = 0.30]. Twenty-one patients had arrhythmias during a mean follow-up period of 5.4 years; 14/16 (87%) in LAI and 7/24 (29%) in RAI (p < 0.001). Freedom from arrhythmia at 1,3,5 years of age was 75.0%, 37.9%, 22.7% in LAI, and 83.3%, 77.5%, 69.6% in RAI, respectively(p = 0.00261). LAI had a three-fold increase in developing arrhythmias. Left atrial isomerism was the only factor identified to be associated with arrhythmia occurrence. CONCLUSIONS: Arrhythmias were commonly seen in heterotaxy syndrome particularly in left isomerism with more than half of the patients having arrhythmias by 3 years of age. Atrial situs was the only risk factor identified to be associated with arrhythmias, and close follow-up is warranted in these patients.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation.

AIM: Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients. METHODS: We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data. RESULTS: Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers. CONCLUSIONS: Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure.

Identification of a Novel Titin Variant Underlying Myocardial Involvement in Neurofibromatosis Type 1.

Because of the rare co-occurrence, it remains a question whether cardiomyopathy is a true association of neurofibromatosis type 1. A boy with café-au-lait spots manifested restrictive cardiomyopathy. Whole exome sequencing confirmed the genetic diagnosis of neurofibromatosis and further identified a novel titin (TTN) missense variant. The significance of the variant is supported by its de novo origin, in silico predictions, and evolutionary conservation. Modern genetics raises an intriguing explanation for the unexpected phenotype and adds to the evolving role of TTN variants in cardiomyopathy.

Effect of i.v. immunoglobulin in the first 4 days of illness in Kawasaki disease.

BACKGROUND: Although early treatment of Kawasaki disease (KD) with i.v. immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities, the effectiveness of IVIG by day 4 of illness remains to be determined. METHODS: This was a multi-institutional, retrospective cohort study. Patients diagnosed with KD at ≤4 days of illness were divided into two groups: those who received initial IVIG before and on day 5 of illness. Baseline characteristics were adjusted using propensity scores. The primary endpoint was the need for additional treatment. RESULTS: Of 339 patients diagnosed with KD by day 4, 181 and 158 received IVIG before and on day 5 of illness, respectively. Patients in the early treatment group had more adverse prognostic factors: infancy, early onset of the principal symptoms, and abnormal laboratory data. We thus adjusted baseline characteristics before treatment decisions using propensity scores. Propensity score matching of the two groups yielded 100 observations. More patients required additional treatment in the matched early treatment group: 37% vs 24% (adjusted OR, 1.7; 95%CI: 1.06-2.8; P = 0.047). The difference was more pronounced for risk of relapse after initial resolution of fever: 14% vs 5.0% (adjusted OR, 3.2; 95%CI: 1.3-7.7; P = 0.02). The risk of coronary artery lesion did not differ significantly. CONCLUSIONS: IVIG treatment by day 4 of illness is associated with the requirement for additional treatment even after adjustment of baseline characteristics. Increased resistance to IVIG when given by day 4 should be considered in order to improve the treatment regimen for early-diagnosed KD.

A Qualitative Assessment of Adolescent Girls' Perception of Living with Congenital Heart Disease: Focusing on Future Pregnancies and Childbirth.

PURPOSE: Congenital heart disease (CHD) is the most common birth anomaly in Japan, occurring in approximately 10.6 of every 1,000 live births. Advancements in medical and surgical care have increased births by women diagnosed with CHD. The study's purpose was to examine the perceptions of pregnancy and childbirth among adolescent girls with CHD. DESIGN AND METHODS: Twelve semi-structured interviews were conducted, and the data were analyzed using a modified grounded-theory approach. RESULTS: Three categories and 16 subcategories were extracted. Adolescent girls with CHD reported feelings of distress and anxiety while struggling with their disease, and feared how their disease might negatively influence their future pregnancy. These concerns were related to a desire to become familiar with CHD. The girls also explored how their disease would be managed during pregnancy and childbirth. Overall, these perceptions were influenced by the girls' acceptance of their disease, and support from family, friends, and healthcare professionals. CONCLUSIONS: Healthcare professionals might assess adolescent girls' awareness of their disease before discussing pregnancy and childbirth risks. To encourage them to understand and cope with their disease, healthcare professionals might provide interventions tailored to the timing, stage, and degree of pregnancy and childbirth awareness. This could allow safer life planning, especially concerning pregnancy and childbirth decisions. PRACTICE IMPLICATIONS: To address adolescent girls' needs, healthcare professionals should continuously assess their awareness of pregnancy and childbirth as well as their psychological status, alongside CHD issues.

Minimally invasive, pericardial implantable cardioverter-defibrillator placement in a young child.

We report the successful minimally invasive placement of a pericardial implantable cardioverter-defibrillator (ICD) in a 16-kg child. A transvenous ICD dual coil was advanced through a small subxiphoid incision and screwed into the oblique sinus pericardium under fluoroscopic guidance. An additional sense-pace lead was sutured onto the right ventricular apex, and the generator was placed in the upper abdominal wall through the same incision. Threshold testing demonstrated successful defibrillation at 15 J. After implantation, the patient had two episodes of appropriate shock for ventricular fibrillation. The ICD system continues to show stable impedance at 6 months of follow-up.