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.

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 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 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 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.

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.

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.

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.

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.

Fever pattern and C-reactive protein predict response to rescue therapy in Kawasaki disease.

BACKGROUND: Evidence to guide rescue therapy in refractory Kawasaki disease (KD) is lacking. The aim of this study was to determine the most important variables in predicting non-response to rescue therapy in refractory KD. METHODS: We retrospectively analyzed 171 patients diagnosed with refractory KD resistant to initial i.v. immunoglobulin (IVIG). Participants received rescue therapy consisting of IVIG monotherapy or IVIG plus prednisolone. Characteristics and laboratory variables were compared between rescue therapy non-responders and responders. Multivariate logistic regression analysis was performed to determine the independent predictors of non-response to rescue therapy. RESULTS: Among the 171 participants, 54 (31.6%) were non-responders to rescue therapy. On univariate analysis, fever pattern after initial IVIG, day of illness at rescue therapy, rescue therapy regimen and six laboratory variables (pre-IVIG sodium, C-reactive protein [CRP]; post-IVIG white blood cell count, platelet count, sodium, CRP) were useful in discriminating between non-responders and responders. These nine variables were included in multivariate logistic regression analysis. Persistent fever after initial IVIG (aOR, 2.39; 95%CI: 1.07-5.37) and post-IVIG CRP (aOR, 1.09; 95%CI: 1.02-1.17, per 1 mg/dL increase) were identified as independent predictors of non-response to rescue therapy. IVIG rescue monotherapy (aOR, 3.05; 95%CI: 1.05-8.84) also predicted non-response after adjusting for fever pattern and post-IVIG CRP. CONCLUSIONS: Persistent fever and elevated CRP after initial IVIG are predictive of non-response to rescue therapy for refractory KD. For patients at high risk of non-response, IVIG plus prednisolone, or even further intensified rescue therapy regimens may be preferable.

Clinical implications of mitral valve geometric alterations in children with dilated cardiomyopathy.

We aimed to elucidate the relationship between severity of secondary mitral regurgitation and mitral valve geometry in children with dilated cardiomyopathy. The medical records of 16 children with dilated cardiomyopathy (median age, 1.2 years; range, 0.4-12.3 years) were reviewed. Mitral valve geometry was evaluated by measuring coaptation depth using echocardiographic apical four-chamber views at the initial presentation. Patients were dichotomised according to the mitral regurgitation severity: patients with moderate or severe secondary mitral regurgitation (n=6) and those with mild secondary mitral regurgitation (n=10). A total of 58 healthy children were considered as normal controls, and a regression equation to predict coaptation depth by body surface area was derived: coaptation depth [mm]=4.37+1.34×ln (body surface area [m2]) (residual standard error, 0.49; adjusted R2, 0.68; p<0.0001). Compared with patients with mild secondary mitral regurgitation, those with moderate or severe secondary mitral regurgitation had significantly larger coaptation depth z-scores (6.4±2.3 versus 1.9±1.4, p<0.005), larger mitral annulus diameter z-scores (3.6±2.6 versus 0.9±1.8, p<0.05), higher left ventricular sphericity index (0.89±0.07 versus 0.79±0.06, p<0.005), and greater left ventricular fraction shortening (0.15±0.05 versus 0.09±0.05, p<0.05). In conclusion, geometric alteration in the mitral valve and the left ventricle is associated with the severity of secondary mitral regurgitation in paediatric dilated cardiomyopathy, which would provide a theoretical background to surgical intervention for secondary mitral regurgitation in paediatric populations.

Experiences With Aggressive Cardiac Rehabilitation in Pediatric Patients Receiving Mechanical Circulatory Supports.

Although some patients with fulminant myocarditis can be rescued owing to the improvements in mechanical circulatory support therapy, there are few reports providing evidence of cardiac rehabilitation during mechanical circulatory supports, particularly among pediatric patients. We treated two pediatric patients who underwent aggressive cardiac rehabilitation during mechanical support. Five days after the initiation of extracorporeal membrane oxygenation therapy aggressive cardiac rehabilitation was started in a 10-year-old girl with fulminant myocarditis. After explantation of the device, she was discharged on postoperative day 23. A 6-year-old girl with fulminant myocarditis started receiving cardiac rehabilitation two days after the initiation of an extracorporeal left ventricular assist device, despite having hemiplegia due to a recent broad stroke. She achieved an exercise capacity of supported walking for 280 meters after 127 days of cardiac rehabilitation and then went abroad to undergo heart transplantation when she was in the best physical condition possible. Early initiation of cardiac rehabilitation may be safe and effective for successful pediatric mechanical circulatory support therapy; this acts as a bridge to explantation or heart transplantation.

Central extracorporeal membrane oxygenation requiring pulmonary arterial venting after near-drowning.

Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning.

Serum hyaluronic acid concentration in Fontan circulation: correlation with hepatic function and portal vein hemodynamics.

Although liver fibrosis causes significant morbidity in the late postoperative period of the Fontan procedure, the diagnostic value of hyaluronic acid (HA), a serum marker of liver fibrosis, has not been established in Fontan patients. The purpose of this study was to determine whether increased serum HA concentration in Fontan patients is associated with an increase in inspiratory-to-expiratory flow rate ratio (Qin/Qex) of the portal vein (PV), which is indicative of liver fibrosis. We retrospectively studied 28 consecutive patients with Fontan circulation who underwent cardiac catheterisation for various indications. The median age at examination was 5.5 years (range 2.2-5.6). The median HA concentration was 17.7 ng mL(-1) (range 10.0-82.1), which was used to divide our 28 patients into two groups. Patients in the high-HA group had significantly greater Qin/Qex of the PV than those in the low-HA group (1.25 ± 0.12 vs. 1.12 ± 0.11, p < 0.05). Platelet counts were significantly lower in the high-HA group (216 ± 74 vs. 294 ± 104 × 10(9) L(-1), p < 0.05). No significant difference was found in inferior vena caval pressure. In conclusion, increase of HA concentration in Fontan patients accompanies the change in PV hemodynamics peculiar to liver cirrhosis and might be an early indicator of liver fibrosis.