Nobuyuki Tsujii

Optimal pacing sites for cardiac resynchronization therapy for patients with a systemic right ventricle with or without a rudimentary left ventricle.

AIMS This study aims to assess the impact of pacing sites on the effectiveness of cardiac resynchronization therapy (CRT) in systemic right ventricle (sRV) patients with/without a rudimentary left ventricle (rLV). METHODS AND RESULTS We evaluated 13 procedures in 11 sRV patients with a wide QRS (>150 ms). Based on the digitalization results of ventriculography, long-axis dyssynchrony (LD) was defined as extremely delayed right ventricular (RV) outflow tract movement: ≥100 ms delay from the RV apical contraction, and short-axis dyssynchrony (SD) was defined as a paradoxical contraction between the rLV and sRV caused by a conduction delay between the two ventricles. During the follow-up period (2.1 ± 1.9 years), the response rates were 71% (5/7) and 33% (2/6) in the sRV patients with and without an rLV, respectively (P = ns). Following the CRT, the QRS duration remained similar between the responders and nonresponders. Among five responders with an rLV, the leads were placed in the longitudinal RV direction in two with LD, longitudinal RV direction with fusion of the intrinsic QRS in two with LD + SD, and laterally on opposite sides of both ventricles in one with SD. Among two responders without an rLV, the leads were placed in the longitudinal RV direction in those two with LD. CONCLUSIONS In sRV patients with LD with/without an rLV, the leads should be placed at furthest sites in the longitudinal RV direction. In patients with an rLV and SD, the leads should be placed laterally on opposite sides of both ventricles.

The clinical characteristics of sudden cardiac arrest in asymptomatic patients with congenital heart disease

Sudden cardiac arrest (SCA) is a major cause of death in patients with congenital heart disease (CHD). Systemic ventricular dysfunction is a reported risk factor for SCA. We retrospectively analyzed the medical records of 46 patients (age >6 years) who experienced SCA. The following underlying cardiac defects were observed: biventricular repair with affected subpulmonary right ventricle (n = 18, 39 %), biventricular repair with systemic right ventricle and Eisenmenger syndrome (n = 6 each, 13 %), Fontan circulation and unrepaired CHD (n = 5 each, 11 %), and others (n = 6, 13 %). Twenty-one patients (46 %) had no history of arrhythmias, and 21 of 43 (49 %) showed systemic ventricular ejection fraction >55 %. According to the New York Heart Association classification, 18 patients (39 %) were class I and 28 (61 %) were class II/III. SCA occurred at a younger age in class I (16 ± 5 years) than in the other classes (23 ± 10 years; P = 0.004). QRS duration was similar between the groups (136 ± 38 vs. 141 ± 50 ms; P not significant). Seven patients in class I (15 % of all SCAs) had no history of arrhythmias or features of hemodynamic abnormalities. The proportion of patients with biventricular repair and affected subpulmonary right ventricle was higher than that of patients with other defects, and the majority of SCA patients had more complicated defects than a simple repaired ventricular septal defect or an atrial septal defect. No symptoms of heart failure, history of arrhythmias, or features of hemodynamic abnormalities were observed in 15 % of the patients who experienced SCA. Prolonged QRS duration might be a predictor of SCA even in asymptomatic CHD patients. Prevention of SCA in CHD patients may require more detailed evaluation than is typically considered necessary.

Influenza-associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S-deficient boy

Influenza infections often cause pneumonia, but there is limited information on thrombotic microangiopathy (TMA) in these circumstances. We report the case of an 11‐year‐old boy who developed TMA during the acute phase of H1N1 influenza. Plasma von Willebrand factor (VWF) was elevated, whereas a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was mildly reduced in the absence of ADAMTS13‐neutralizing autoantibody, resulting in low ratio of ADAMTS13 to VWF. The patient was treated intensively, including plasma exchange, and he recovered from the TMA. He developed pulmonary embolism (PE), however, after removal of the central venous catheter. The findings suggested that influenza‐associated cytokines enhanced the release of unusually large VWF multimers from vascular endothelial cells and promoted the formation of platelet thrombi and TMA. Subsequent analysis further indicated the presence of familial protein S deficiency, and it seemed likely that the PE was more related to this heterozygous protein S defect.

High Incidence of Dilated Cardiomyopathy After Right Ventricular Inlet Pacing in Patients With Congenital Complete Atrioventricular Block

BACKGROUND Some patients with congenital complete atrioventricular block (CCAVB) develop dilated cardiomyopathy (DCM) after pacemaker implantation (PMI). We evaluated the relationship between pacing site and DCM incidence. METHODSANDRESULTS We retrospectively evaluated 38 patients with CCAVB; 8 (25%) of 32 patients who had PMI developed DCM/heart failure death (HFD) after PMI, although none of the 6 patients without PMI showed DCM/HFD. All DCM/HFD occurred within 50 months of PMI. Among the 32 patients with PMI, the DCM/HFD incidence was 55% (6/11) for right ventricular inlet (RVI), 18% (2/11) for RV apex (RVA), and 0% for left ventricle (LV) (P=0.013). At the endpoint, the LV ejection fraction and septal-to-posterior wall motion delay of patients with LV pacing were better than those for patients with other pacing sites. Among the 8 DCM/HFD patients, 2 in whom the pacing site was changed from RVI to LV apex or in whom therapy was upgraded to cardiac resynchronization remained alive with no heart failure symptoms, whereas the other 6 died of heart failure. CONCLUSIONS A total of 25% of the patients who underwent PMI because of CCAVB, but none in the non-PMI group, developed DCM/HFD. DCM/HFD incidence was higher in patients with RVI pacing. Ventricular dyssynchrony related to pacing site may be one cause of DCM in patients with CCAVB. (Circ J 2016; 80: 1251-1258).

Late Wall Thickening and Calcification in Patients After Kawasaki Disease

Objectives To evaluate the relationship between the initial diameters of the coronary arteries immediately after the onset of Kawasaki disease (KD) and late increased coronary wall thickening/coronary artery calcification (CAC). Study Design Sixty‐five patients (50 males and 15 females) who had undergone selective coronary angiography (CAG) <100 days after the onset of KD were studied late in disease by dual‐source computed tomography (DSCT). The maximum diameters of each segment were measured in the initial CAGs, and the relationship between the maximum diameters and the appearance of increased wall thickening/CAC was analyzed. The study cohort was divided into 2 groups: the branches group (BG) and bifurcation at the left coronary artery (LCA) group. The cutoff point of acute coronary artery dilatation for increased wall thickening/CAC was calculated for each group. Risk factors for the appearance of CAC in each group were investigated, as was the sex difference related to the prevalence of CAC in coronary artery lesions (CALs) of the initial CAGs. Results The cutoff points of acute coronary dilatation for increased wall thickening were 4.8 mm in the BG (n = 344; area under the curve [AUC], 0.89; P < .001) and 5.3 mm in the LCA group (n = 65; AUC, 0.87; P < .001). The interval from the onset of KD (P < .0001) and sex (P = .0084) were also related to the appearance of CAC in the BG. Conclusion Acute coronary dilatation of exceeding ˜5.0 mm can lead to late abnormalities of the coronary artery wall. The prevalence of CAC increases with age. There was a sex‐based difference in the late incidence of CAC in the CALs.

Cardiac Events and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease

Objectives To clarify the occurrence of cardiac events based on the maximal diameter of the maximal coronary artery aneurysm (CAA) in Kawasaki disease (KD). Study design Two hundred fourteen patients (160 male and 54 female) who had had at least 1 CAA in the selective coronary angiogram less than 100 days after the onset of KD were studied. We measured the maximal CAA diameters in the major branches of the initial coronary angiograms. Death, myocardial infarction and coronary artery revascularization were included as cardiac events in this study. We divided the patients into three groups based on the maximal CAA diameter (large ≥8.0 mm; medium ≥6.0 mm and <8.0 mm; small <6.0 mm). Further, we also analyzed the cardiac events based on laterality of maximal CAA (bilateral, unilateral) and body surface area (BSA). Results Cardiac events occurred in 44 patients (21%). For BSA < 0.50 m2, the 30‐year cardiac event‐free survival in the large and medium groups was 66% (n = 38, 95% CI, 49–80) and 62% (n = 27, 95% CI, 38–81), respectively. For BSA ≥ 0.50 m2, that in large group was 54% (n = 58, 95% CI, 40–67). There were no cardiac events in the medium group for BSA ≥0.50 m2 (n = 36) and the small group (n = 56). In the large analyzed group, the 30‐year cardiac event‐free survival in the bilateral and unilateral groups was 40% (n = 48, 95% CI, 27–55) and 78% (n = 48, 95% CI, 63–89), respectively (P < .0001). Conclusions The group with the highest risk of cardiac events was the patient group with the maximal CAA diameter ≥6.0 mm with BSA < 0.50 m2 and the maximal CAA diameter ≥8.0 mm with BSA ≥ 0.50 m2. At 30 years after the onset of KD, cardiac event‐free survival was about 60%. Given the high rate of cardiac events in this patient population, life‐long cardiovascular surveillance is advised.

Displacement of the anterior leaflet of the tricuspid valve: Rare variant of Ebstein's anomaly

In Ebsteins anomaly, the points of attachment, or hinges, of the septal and mural leaflets in the right ventricle are displaced away from the atrioventricular junction. In contrast, the junctional hinge of the anterior leaflet usually retains a normal position. Here, we report a case of giant right atrial aneurysm due to isolated displacement of the anterior leaflet of the tricuspid valve in an infant, a rare variant of Ebsteins anomaly. Enlargement of the right atrium, which was initially diagnosed during the fetal period, progressively and markedly dilated after birth and was successfully treated with surgical resection. Isolated displacement of the anterior leaflet should be recognized as a variant of Ebsteins anomaly.

Severe Hemolysis and Pulmonary Hypertension in a Neonate With Upshaw–Schulman Syndrome

Pulmonary involvement is extremely rare in thrombotic thrombocytopenic purpura. In this report, we present a girl patient with congenital thrombotic thrombocytopenic purpura, known as Upshaw–Schulman syndrome (USS), complicated with severe hemolysis and pulmonary hypertension (PH). The assay results of a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13) activity measured by FRETS-VWF73 and ADAMTS13-act-ELISA were different. Hyperbilirubinemia (total bilirubin, 25.3 mg/dL) interfered strongly with the FRETS-VWF73 assay. Plasma levels of ADAMTS13 activity by act-ELISA were <0.5% of normal. The diagnosis of USS was confirmed by ADAMTS13 gene analysis, which showed compound heterozygous mutations of p.G139Vfs*17 and p.I673F. The p.G139Vfs*17 mutation was previously unreported, and its effect in splicing was confirmed by reverse transcription polymerase chain reaction. The patient received oxygen therapy for PH and exchange blood transfusion for severe hemolysis. The PH resolved without specific treatment. Based on these findings, the PH may have been caused by free hemoglobin that scavenged nitrogen oxide or platelet thrombi in the lungs caused by ADAMTS13 deficiency. Thus, severe PH can occur in neonatal patients with USS, and severe hemolysis might result in overestimation of ADAMTS 13 activity. Both possibilities are important for the diagnosis and management of USS.

Barth syndrome associated with triple mutation

A full-term male infant weighing 2,582 g was born to a 33-year-old healthy mother. Both pregnancy and delivery were uneventful. Three hours after birth, he was transferred to the present hospital because of dyspnea, mixed respiratory-metabolic acidosis, and decreased left ventricle (LV) function on transthoracic echocardiography. Gallop rhythm, low oxygen saturation (86%), and auxocardia with cardiothoracic ratio 66% on chest X-ray were noted. Echocardiography showed globally decreased LV function with an ejection fraction of 25%, and enlarged LV dimension in diastole (158% of normal). The LV was highly and globally trabeculated (Fig. 1b). The ratio of non-compacted to compacted myocardium was >2.0 in all the segments. Electrocardiography showed LV hypertrophy and depressed ST segment in leads II, III, aVF, and V4–6. He was diagnosed with acute heart failure from LV non-compaction (LVNC) and dilated cardiomyopathy (DCM). He was intubated, and carvedilol was also later given along with the inotropic drugs. Although he was discharged at the age of 5 months, he had repeated acute aggravation of chronic heart failure, ventricular tachyarrhythmia, and reduced muscle mass. At 28 months of age, he had already lost weight and weighed 3.3 kg ( 7.8 SD). He did not have neutropenia nor monocytosis but developed 3-methylglutaconic aciduria at 6 months of age (3-methylglutaconic acid level, +4.1 SD). With regard to family history, his elder brother had died suddenly 17 h after birth, and his maternal grandmother had experienced two spontaneous abortions (Fig. 1a). The genetic analysis was approved by the Medical Research Ethics Committees in the institutions that participated, and written informed consent was obtained from infant’s parents. Targeted sequencing of the cardiomyopathy-associated genes confirmed that the patient had novel rare variants in tafazzin (TAZ), succinate dehydrogenase complex flavoprotein subunit A (SDHA), and a-dystrobrevin (DTNA). These variants were identified in exon 6 of TAZ, c.469C>T (p.Leu157Phe); exon 10 of SDHA, c.1351_1355delCGCCT (p. Arg451 fs); and exon 19 of DTNA, c.1763G>A (p.Ser588Asn; Fig. 1d–f). On in silico analysis these rare variants may be disease causing. In addition to the frameshift mutation in SDHA, the TAZ mutation was categorized as possibly damaging by Polyphen-2 (score 0.995), damaging by SIFT (score 0), and disease causing by Mutation Taster. On genetic analysis of TAZ, the patient was diagnosed with Barth syndrome. The DTNA mutation was categorized as possibly damaging by Polyphen-2 (score 0.486), tolerable by SIFT (score 0.007), and disease causing by Mutation Taster. On further sequencing analyses of genes from the patient’s parents, his mother was found to have the same TAZ mutation, while his father had the SDHA and DTNA mutations, all of which were hemior heterozygous in nature. The proband was confirmed to have both maternal and paternal mutations and was therefore considered as triple hemior heterozygote. His parents and living siblings had no clinical evidence of cardiomyopathy, but his father was suspected to have LVNC with normal cardiac function (Fig. 1c).

Rare Anomaly of Great Arteries

A full-term male infant was transferred to our neonatal intensive care unit because of tachypnea and mild hypoxia. Right atrium and right ventricle enlargement were suspected in the prenatal examination. Echocardiography was performed, and a rare combination of anomalies was observed. The ascending aorta and the main pulmonary artery joined together at the level of the innominate artery over the bridging vessel. The branching patterns of the pulmonary artery and the aorta were normal. There was a very small perimembranous ventricular septal defect. Computed tomography was performed to confirm the diagnosis (Figs. 1, 2). The observed combination had not been reported previously. It was not truncus arteriosus because the orifices of the pulmonary artery and the aorta were separated (Fig. 3). Two diagnoses for this rare combination were considered. The first diagnosis defines it as a variant of the aortopulmonary window. This diagnosis is not correct because the bridging part is not a window but rather a large tube. The second diagnosis defines it as a variant of the right aortic arch and the left-side patent ductus arteriosus. This diagnosis is not appropriate because the innominate artery arises from the bridging vessel. If this vessel is patent ductus arteriosus, there should not be branching. Although the diagnosis was not clear, we thought the spontaneous improvement of pulmonary hypertension could lead to systemic collapse. Ligation of the bridging vessel was performed to avoid such a situation. However, the pulmonary hypertension did not improve after surgery. The ventricular septal defect was so small that the reason for pulmonary hypertension was not clear. Catheter examination showed that although the resistance of the pulmonary artery was high, it responded to oxygen inhalation. The patient was discharged with pulmonary hypertension therapy.