Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the Pre- and Post-Diagnostic Phases in Children and Adolescents.

BACKGROUND: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.Methods and Results:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. CONCLUSIONS: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

Disrupted regulation of ghrelin production under antihypertensive treatment in spontaneously hypertensive rats.

BACKGROUND: Ghrelin is an acylated peptide hormone mainly secreted from the stomach. When administrated externally it modulates vascular tone mainly through the regulation of autonomic nerve activity. However, the effects of blood pressure (BP) on the production and secretion of ghrelin remain to be clarified. METHODS AND RESULTS: We examined the stomach and plasma levels of ghrelin in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats after a 4-week-intervention with antihypertensive agents (candesartan-cilexetil [ARB], doxazosin [DZN], metoprolol [MP], reserpine [RES]) to clarify the influence of BP on the secretion of ghrelin. The effect of these agents on ghrelin production and secretion were examined by comparing vehicle-treated controls (WKY-Intact, SHR-Intact). Treatment with the 4 antihypertensive drugs all yielded a significant decline in systolic BP in both SHR and WKY. Under these conditions, significantly lower levels of stomach and plasma ghrelin were detected in WKY treated with ARB (P<0.05), DZN (P<0.05), MP (P<0.05) and RES (P<0.05) compared with WKY-Intact, whereas no significant change in the ghrelin levels in the stomach and plasma were detected in SHR under the same treatments. CONCLUSIONS: The findings imply that the production and secretion of ghrelin are controlled by the ambient vascular tone and vice versa in normotensive WKY. This inter-relationship between ghrelin and BP seems to be disrupted in SHR.

Irrelevant B-type natriuretic peptide levels in patients with mechanical prostheses in the mitral position presenting with congestive heart failure.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) level is reported to be a strong marker of congestive heart failure (CHF). Heterogeneity of the BNP levels among individuals with CHF, however, can cause confusion in interpreting the results. The influence of mitral mechanical prostheses on BNP levels in patients presenting with CHF is not well known. METHODS AND RESULTS: In the present study 214 consecutive patients with CHF diagnosed using the Framingham criteria were enrolled and divided into 2 groups with and without mitral mechanical prostheses (prosthesis group, n=31; native group, n=183). The plasma BNP levels were measured, and clinical examinations including echocardiography were performed at the same time to assess cardiac performance. There was no difference in the left ventricular ejection fractions between the 2 groups. Despite having a lower body mass index, larger prevalence ratio of atrial fibrillation and larger size of the left atrium, the prosthesis group had a significantly lower logBNP level than the native group (prosthesis group vs native group: 5.12+/-1.01 vs 6.21+/-0.92, P<0.001; BNP level: 167+/-324 pg/ml vs 498+/-380 pg/ml). On multivariate analysis the presence of a mitral mechanical prosthesis was extracted as an independent predictor for decreased BNP level in patients with CHF. CONCLUSIONS: Plasma BNP level cannot correctly reflect the severity of CHF in patients with mechanical prostheses in the mitral position.

Safety and Efficacy of Minimally Interrupted Dabigatran vs Uninterrupted Warfarin Therapy in Adults Undergoing Atrial Fibrillation Catheter Ablation: A Randomized Clinical Trial.

Importance: Uninterrupted dabigatran therapy reduces stroke risk in patients with nonvalvular atrial fibrillation (NVAF) undergoing ablation and is associated with a lower bleeding risk than uninterrupted warfarin therapy. Minimally interrupted direct oral anticoagulant therapy is widely used, but data from controlled studies are insufficient. Objective: To compare the safety and efficacy of minimally interrupted dabigatran vs uninterrupted warfarin therapy in patients undergoing catheter ablation for NVAF. Design, Setting, and Participants: The ABRIDGE-J (ABlation peRIoperative DabiGatran in use Envisioning in Japan) trial is a open-label, randomized clinical trial performed in 28 Japanese treatment centers. A total of 504 patients scheduled for NVAF ablation were enrolled; 500 were randomized to the study treatments; 499 received at least 1 dose of dabigatran etexilate (n = 248) or warfarin potassium (n = 251); and 442 underwent ablation (220 in the dabigatran group and 222 in the warfarin group). Data were collected from May 1, 2014, through September 14, 2015, and analyzed from March 7, 2017, through January 28, 2019. Interventions: Appropriate dose anticoagulation was administered 4 weeks before and at least 3 months after ablation in all patients. Dabigatran therapy was interrupted before catheter ablation (holding of 1-2 doses) and resumed after ablation. Main Outcomes and Measures: Primary end points were the incidence of embolism during the perioperative period and atrial thrombus just before the ablation. The main secondary end point was the incidence of major bleeding events until 3 months after ablation. Results: Of the 442 patients who underwent ablation, 74.9% were men and the median age was 66 years (interquartile range, 59-71 years). Before ablation, 1 cerebral infarction and 1 thrombus in the left atrium occurred in the warfarin group, but no events occurred in the interrupted dabigatran group. After ablation, the mean (SD) incidence of major bleeding events was significantly lower with dabigatran (3 patients [1.4% {0.8%}; 95% CI, 0.4%-4.2%]) vs warfarin (11 patients [5.0% {1.5%}; 95% CI, 2.8%-8.8%]; P = .03). No thromboembolic events occurred after ablation in the dabigatran group; 1 (0.5%) occurred in the warfarin group. Conclusions and Relevance: In patients undergoing ablation for NVAF, anticoagulation with minimally interrupted dabigatran therapy did not increase thromboembolic events and was associated with fewer bleeding complications than uninterrupted warfarin therapy. Trial Registration: umin.ac.jp Identifier: UMIN000013129.

Three cases of catecholaminergic polymorphic ventricular tachycardia with prolonged QT intervals including two cases of compound mutations.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the leading causes of sudden arrhythmic death in the young. The QT interval in CPVT patients is typically within the normal range. However, those with prolonged QT interval have often been diagnosed with mutation-negative long QT syndrome (LQTS). We report three CPVT patients with prolonged QT interval. Case 1 and 2 were diagnosed as LQTS at first. Genetic test using next-generation sequencing (NGS) revealed RyR2 mutations. We should consider genetic test using NGS to identify the genes responsible for CPVT in mutation-negative LQTS.

Prediagnostic electrocardiographic and echocardiographic findings of biopsy-proven hypertrophic cardiomyopathy.

We present two cases of biopsy-proven hypertrophic cardiomyopathy (HCM). Both cases showed abnormal electrocardiographic (ECG) findings more than 8 years before diagnosis. A 16-year-old healthy male experienced a rescued cardiac arrest. Another male adolescent showed abnormal Q wave and thickened ventricular wall at 15 years old. Retrospective analyses of ECGs performed at 6 years old indicated abnormal ECG findings. However, the diagnosis was normal because no ventricular wall thickening was present in echocardiography. For early diagnosis of HCM to prevent sudden cardiac arrest or death, it is essential to establish ECG and echocardiographic criteria to screen HCM in the young.

Effects of a fish-based diet and administration of pure eicosapentaenoic acid on brachial-ankle pulse wave velocity in patients with cardiovascular risk factors.

BACKGROUND AND PURPOSE: Brachial-ankle pulse wave velocity (baPWV) and ratio of plasma eicosapentaenoic acid to arachidonic acid (EPA/AA ratio) are surrogate markers for coronary artery disease (CAD). We aimed to evaluate the effects of a fish-based diet and administration of EPA on baPWV and plasma EPA/AA ratio. METHODS AND RESULTS: The changes in baPWV and plasma EPA/AA ratio were compared before and after a 6-month fish-based diet in 191 patients with cardiovascular risk factors. A fish-based diet resulted in significant increment of plasma EPA/AA ratio (0.40±0.18 vs. 0.49±0.27, p<0.001), with baPWV remaining unchanged. Multivariate analysis revealed that systolic blood pressure (SBP) (6-month SBP-baseline SBP) and CAD were positively associated with increased baPWV (CAD: odds ratio=2.040, p=0.0436, SPB: odds ratio=1.056, p=0.0003). When the patients were divided into three groups: CAD, low-risk, and high-risk with no prior history of CAD according to the number of risk factors at baseline, comparison among the three groups disclosed an inter-group difference in the magnitude of change in baPWV (low-risk: -35±164cm/s, high-risk: -14±190cm/s, CAD: 39±164cm/s, p=0.0071 for trend). In 191 patients who had received a 6-month fish-based diet, 21 patients (primarily CAD patients) sequentially received high purity EPA (1800mg/day) for 6 months. It resulted in marked increment of plasma EPA/AA ratio (0.65±0.57 vs. 1.19±0.46, p<0.001), accompanied by significant reduction in baPWV (1968±344cm/s vs. 1829±344cm/s, p=0.0061). There was a significant negative correlation between changes in baPWV and changes in plasma EPA/AA ratio in patients with a fish-based diet and sequential administration of EPA (r=-0.446, p=0.017). CONCLUSION: A fish-based diet was effective against increased baPWV only in low-risk patients, with slight increment of plasma EPA/AA. In high-risk patients and CAD patients, administration of EPA for preventing progression of baPWV endorsed the validity of high purity EPA administration recommended in the current guidelines.

Relationship between vascular endothelial growth factor and left ventricular dimension in patients with acute myocardial infarction.

BACKGROUND: Although vascular endothelial growth factor (VEGF) is elevated in patients with acute myocardial infarction (AMI), the clinical significance of its elevation remains unclear. The present study was designed to determine the relationship between VEGF and left ventricular dimension in patients with AMI. METHODS AND RESULTS: Plasma VEGF levels were examined by enzyme-linked immunosorbent assay daily for one week and then weekly for four weeks in 38 patients with AMI (65.4 ± 1.7 years). Left ventriculography was performed at 14 days, 6 months, and 2 years after the onset of AMI. Plasma VEGF levels were significantly elevated and reached a peak on day 6. Peak plasma VEGF levels positively correlated with both end-diastolic and end-systolic volume indices at 14 days after the onset of AMI. When patients with AMI were divided into two groups according to plasma VEGF levels on admission, left ventricular volume indices were higher in the high VEGF group than in the low VEGF group at the subacute phase of AMI (14 days). These differences were no longer present in the chronic phase of AMI. CONCLUSION: Plasma VEGF levels were increased in patients with AMI, and peak levels were associated with left ventricular volume indices in the subacute phase, suggesting an important role of endogenous VEGF in the left ventricular dimension in patients with AMI.

Hepatocyte growth factor improves the survival of rats with pulmonary arterial hypertension via the amelioration of pulmonary hemodynamics.

Hepatocyte growth factor (HGF) is a multifunctional growth factor with mitogenic, anti-apoptotic and anti-fibrotic activities. In this study, we investigated the effect of administration of recombinant human HGF on pulmonary arterial hypertension. Pulmonary arterial hypertension was induced in rats by a single injection of monocrotaline (MCT) and recombinant human HGF (0.12 mg/day) was administered into the right ventricle cavity using osmotic pumps, which were implanted subcutaneously 21 days after MCT injection. Continuous intravenous delivery of recombinant human HGF for 14 days led to prolonged survival of animals suffering from severe MCT-induced pulmonary arterial hypertension. Although a bolus injection of recombinant human HGF did not affect pulmonary arterial pressure, a 14-day administration of recombinant human HGF attenuated the inflammatory cell infiltrate, matrix accumulation and vascular medial thickening. As a consequence, the pulmonary lumen was enlarged and the pulmonary arterial pressure was significantly reduced. Additionally, continuous administration of recombinant human HGF suppressed lung tissue expression of platelet-derived growth factor, which plays an important role in the development of pulmonary arterial hypertension. These results indicate that recombinant human HGF possibly has a great potential for improving symptoms and altering the clinical course of pulmonary arterial hypertension.

Successful treatment of spontaneous coronary bypass rupture using a polytetrafluoroethylene-covered stent.

A 57-year-old man with coronary bypass surgery experienced spontaneous rupture of a vein graft 16 months following his operation. Multislice computed tomography revealed a perforation of the saphenous vein graft to the obtuse marginal branch. 3D imaging was useful for diagnosis and in planning treatment. Hesitation to perform surgical treatment occurred due to inflammation in the patient, therefore we successfully implanted a polytetrafluoroethylene-covered stent to occlude the site of perforation. The use of a covered stent for a patient showing clear leakage of dye during angiography should be considered as an alternative to surgical intervention for a ruptured vein.

Rapid progression of aortic regurgitation with thoracic aortic aneurysm due to Takayasu arteritis associated with ulcerative colitis.

A 25-year-old woman with ulcerative colitis developed heart failure due to severe aortic regurgitation. Although chest X-ray 18 months previously showed a normal cardiac shadow, thoracic aortic aneurysm progressed due to Takayasu arteritis. Aortic valve and ascending aorta replacement were performed successfully, but re-valve replacement for severe aortic regurgitation due to prosthetic valve detachment and aortic root replacement for valsalva sinus rupture were required. Human leukocyte antigen analysis showed B35 and B52, the typical haplotype in cases with coexistence of both diseases and associated sustained inflammation. Close observation and early aortic root replacement were needed in this case.

Mid-term mortality of very elderly patients with acute myocardial infarction with or without coronary intervention.

BACKGROUND: The risk benefit of percutaneous coronary intervention (PCI) in very elderly patients with acute myocardial infarction (AMI) is currently unclear. Here, we aim to identify the characteristics of these patients and clarify their mid-term mortality rate with or without PCI. METHODS AND RESULTS: 77 patients (> or =80 years) were chosen from 506 patients with AMI, and treated with (n=32) or without (n=45) PCI. The mean age and time from onset to admission increased in patients having undergone no PCI. The reasons for PCI refusal were patient/family preference (40%), renal dysfunction (17.8%), or cognitive impairment (13.3%). Patients treated with PCI had lower mid-term mortality than those without PCI (34.4% vs 62.2%; p=0.02), while patients taking beta-blockers displayed a significantly lower mortality rate than those without (18.2% vs 63.6%; p=0.0003). Cognitively impaired patients had a higher mortality rate compared with cognitively normal patients (80.0% vs 46.3%; p=0.005). Multivariate analysis indicated that systolic blood pressure on admission, PCI, and beta-blocker therapy independently decreased mid-term mortality in these patients. CONCLUSIONS: PCI and beta-blocker therapy displayed significantly beneficial effects on mid-term mortality in very elderly AMI patients. Elderly-specific trials concerning coexisting disorders are needed to further examine the treatment-related benefits.

Impact of decreased renal function on coagulation and fibrinolysis in patients with non-valvular atrial fibrillation.

BACKGROUND: The prothrombotic state in non-valvular atrial fibrillation (NVAF) increases the risk of thromboembolic events. It is also well known that a prothrombotic state exists in renal failure. Hemostatic disorders play a role in thromboembolic mortality in both NVAF and renal failure. However, little is known about the influence of renal function on hemostasis in patients with NVAF. METHODS AND RESULTS: A total of 190 consecutive outpatients with NVAF who were not receiving anticoagulant therapy were enrolled in the present study. Patients were stratified in groups based on estimated glomerular filtration rate (eGFR). Plasma concentrations of thrombin-antithrombin complex (TAT) and D-dimer were measured and the influence of renal function on coagulation and fibrinolysis was assessed. A relatively weak and inverse relationship of eGFR to TAT and D-dimer was observed (r=0.28, P=0.0001; r=0.30, P<0.0001). Both mean TAT and D-dimer concentrations in groups gradually and significantly increased as eGFR decreased (P<0.0001). On multivariate regression analysis, decreased eGFR concentration was a significant predictor for elevation of TAT (P<0.05) and D-dimer (P<0.01) in patients with NVAF. CONCLUSIONS: The enhanced coagulation activation appeared to be related to a reduction in residual renal function in patients with NVAF. This suggests that decreased renal function might be a candidate predictor of thromboembolic events in patients with NVAF.

Relationship between weather and onset of acute myocardial infarction: can days of frequent onset be predicted?

BACKGROUND: The aim of this study was to clarify the relationship between onset of acute myocardial infarction (AMI) and weather conditions, to determine whether days in which AMI onset is likely can be predicted. METHODS AND RESULTS: Of the 929 patients admitted to our hospitals in Kagoshima prefecture with AMI, subjects comprised 611 patients. Days of frequent onset (F-days) were defined as days with > or = 3 patients/day admitted for AMI, with days of non-frequent onset (N-days) defined as days with < 3 patients/day. Meteorological factors were measured, and daily differences in all parameters and intraday temperature differences on the onset day, and 1 and 2 days before onset were calculated. F-days were significantly associated with intraday temperature differences on the onset day (10.3 degrees C vs. 7.9 degrees C, p=0.005), 1 day before onset (10.7 degrees C vs. 7.9 degrees C, p=0.002), and 2 days before onset (11.3 degrees C vs. 7.9 degrees C, p=0.0001). A cutoff intraday temperature difference of > or = 9.4 degrees C on 1 and 2 days before onset was predictive of F-days with 89% sensitivity and 87% specificity. CONCLUSIONS: Intraday temperature differences offer a powerful predictor of F-days. Onset of AMI can be predicted based on weather conditions over the preceding 1-2 days.

AV nodal ablation and pacemaker implantation improves hemodynamic function in atrial fibrillation.

In drug refractory and highly symptomatic atrial fibrillation (AF) patients, hemodynamic effects of AV node ablation and pacing therapy (APT) were evaluated. Thirty-eight patients with drug refractory and symptomatic AF, underwent APT in eight centers in Japan. The outcome of this therapy was assessed in terms of quality-of-life, cardiac performance measured by echocardiogram, and plasma ANP and BNP levels before and after APT. Quality-of-life assessed by self-administered semi-quantitative questionnaires: WHO QOL 26 (3.0 +/- 0.5 vs 3.4 +/- 0.6, P < 0.01) and the Symptom Checklist: Frequency Scale (1.6 +/- 0.6 vs 0.7 +/- 0.7, P < 0.01) and Severity Scale (1.3 +/- 0.4 vs 0.6 +/- 0.6, P < 0.01), improved significantly 6 months after APT. Ejection fraction (EF) by echocardiogram improved 1 week after APT (59.0% +/- 13.3% vs 63.3% +/- 11.6%, P = 0.02). Plasma ANP levels in the group of ANP > 40 pg/mL at enrollment significantly decreased 1 month later (P = 0.03), and plasma BNP levels in the group of BNP > 20 pg/mL at enrollment significantly decreased 1 month later (P < 0.01). In conclusion, APT has beneficial hemodynamic effects, and plasma BNP levels can predict the most optimal candidates for ablation and pacing therapy.