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Biomedical subjects

Minoru Horie

Publications and source records attributed to Minoru Horie.

At least 19 recordsLinked to original sources
PubMed2026

Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification.

BACKGROUND AND AIMS: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with β-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on β-blocker monotherapy. METHODS: The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated. RESULTS: A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced ≥1 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at β-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before β-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE. CONCLUSIONS: These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on β-blocker monotherapy at low and high risk for future AEs while treated with β-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.

Humans↗
PubMed2007

Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by periodic paralysis, mild dysmorphic features, and QT or QU prolongation with ventricular arrhythmias in electrocardiograms (ECGs). Mutations of KCNJ2, encoding the human inward rectifying potassium channel Kir 2.1, have been identified in patients with ATS. We aimed to clarify the genotype-phenotype correlations in ATS patients. We screened 23 clinically diagnosed ATS patients from 13 unrelated Japanese families. Ten different forms of KCNJ2 mutations were identified in the 23 ATS patients included in this study. Their ECGs showed normal QTc intervals and abnormal U waves with QUc prolongation and a variety of ventricular arrhythmias. Especially, bidirectional ventricular tachycardia (VT) was observed in 13 of 23 patients (57%). Periodic paralysis was seen in 13 of 23 carriers (57%), dysmorphic features in 17 (74%), and seizures during infancy in 4 (17%). Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q) and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a heterologous expression system and showed strong dominant negative effects when co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV respectively compared to wild-type alone). Immunocytochemistry and confocal imaging revealed normal trafficking for mutant channels. In our study, all of the clinically diagnosed ATS patients had KCNJ2 mutations and showed a high penetrance with regard to the typical cardiac phenotypes: predominant U wave and ventricular arrhythmias, typically bidirectional VT.

Adolescent↗
PubMed2007

Multidetector-row computed tomography coronary angiography: optimization of image reconstruction phase according to the heart rate.

BACKGROUND: To optimize the image reconstruction phase of multidetector-row computed tomography (MDCT) coronary angiography according to the heart rate is crucial. METHODS AND RESULTS: Scan data were reconstructed for 10 different phases in 58 sequential patients who underwent 8-row cardiac MDCT. The obtained images were scored and compared in terms of motion artifacts and visibility of the vessels, and moreover, ECG record-based evaluations were added for clarification of the temporal relationships among these 10 phases. In the cases with lower heart rates (<65 beats/min), the best quality images were obtained when the end of the image reconstruction phase was positioned at the peak of the P wave. In some cases with higher heart rates (>65 beats/min), they were obtained in the late systolic period. CONCLUSION: As the heart rate increased, the optimal image reconstruction phase changed from mid diastole to late systole. However, it is recommended to try to decrease the heart rate of patients before data acquisition.

Aged↗
PubMed2006

Left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy demonstrated by multidetector-row computed tomography.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a condition in which the right ventricle is partially or totally replaced by the adipose tissue. Pathological abnormalities affect the left ventricle as well as the right ventricle, particularly the epimyocardium. Multidetector-row computed tomography, which allowed excellent visualization of not only the coronary arteries but also the myocardium with submillimeter spatial resolution and high signal-to-noise ratio, would be more suitable for the assessment of the extent of adipose tissue involvement in the right and left ventricular myocardium. We present a patient who was diagnosed as having ARVC with left ventricular involvement and underwent cardioverter defibrillator implantation.

Adult↗
PubMed2006

The association between high-density lipoprotein cholesterol level and cholesteryl ester transfer protein TaqIB gene polymorphism is influenced by alcohol drinking in a population-based sample.

Cholesteryl ester transfer protein (CETP) is a key enzyme in high-density lipoprotein (HDL) cholesterol metabolism. We studied the association between CETP TaqIB polymorphism and the HDL cholesterol levels considering environmental factors in a population-based sample consisting of 1729 participants who did not use lipid-lowering agents (659 men and 1070 women). The CETP TaqIB genotypes were determined by PCR-RFLP analysis. The serum HDL cholesterol levels of female participants with the B2B2 genotype were significantly higher than those with other genotypes (p<0.001). Multiple regression analysis with covariates such as age, waist to hip (W/H) ratio, alcohol drinking, current smoking, non-HDL cholesterol, and logarithm of triglyceride revealed that the CETP TaqIB genotype was an independent determinant of HDL cholesterol levels in men (p=0.049) and women (p<0.001). Subgroup analysis revealed that an interaction was observed between the CETP TaqIB polymorphism and alcohol consumption in the regulation of HDL cholesterol levels in men (p=0.049) and women (p=0.022). No interactions were observed between the CETP TaqIB polymorphism and current smoking status, body mass index, or W/H ratio in the regulation of HDL cholesterol levels. The association between the CETP TaqIB polymorphism and HDL cholesterol levels was more evident in alcohol consumers than in non-drinkers.

Adult↗
PubMed2006

Scintigraphic evaluation of cardiac metabolism and sympathetic nerve function in alcoholic cardiomyopathy.

A 70-year-old man with alcoholic cardiomyopathy underwent 99mtechnetium-sestamibi (MIBI), iodine-123-labeled metaiodobenzylguanidine (MIBG) scintigraphy and Iodine-123-labeled beta-methyl-iodophenyl pentadecanoic acid (BMIPP) scintigraphy. 99mtechnetium-MIBI identified myocardial damage in the inferior wall of left ventricle. (123)I BMIPP showed low uptake in the inferior wall of the myocardium, concordant to perfusion. (123)I BMIPP and (123)I MIBG showed reduced uptake in the inferior segment of the myocardium, indicating impairment of fatty acid metabolism and sympathetic abnormalities. Damaged myocardium was demonstrated in alcoholic cardiomyopathy. Beta blocker (carvedilol) and angiotensin-receptor blocker (valsartan) were started at low doses, then increased gradually, leading to the improvement of cardiac performance. Cardiac sympathetic nerve function, impaired due to alcoholic cardiomyopathy, was improved with beta-blocker therapy. Cardiac scintigraphy may be useful to assess the extent of myocardial improvement and the response to therapy.

3-Iodobenzylguanidine↗
PubMed2006

Tumor necrosis factor-alpha inhibits the cardiac delayed rectifier K current via the asphingomyelin pathway.

Tumor necrosis factor-alpha (TNF-alpha) affects contractility and ionic currents in the heart. However, the electrophysiological effects, especially on delayed rectifier K currents (IK), have not yet been fully elucidated. We examined the effects of TNF-alpha on IK. Using a voltage-clamp method, IK was measured in guinea pig ventricular myocytes in the basal state and after pharmacological intervention. To specify the site of the action of TNF-alpha, the myocytes were incubated with pertussis toxin or N-oleoylethanolamine, a ceramidase inhibitor, and IK was measured. TNF-alpha suppressed IK when it was enhanced by isoproterenol, histamine or forskolin but not in the basal state or when IK was augmented by an internal application of cyclic AMP. Both pre-incubation with pertussis toxin and N-oleoylethanolamine abolished the inhibitory action of TNF-alpha on isoproterenol-augmented IK. TNF-alpha inhibits IK, mainly IKs, when it is augmented by PKA as a result of the generation of sphingosine.

Amidohydrolases↗
PubMed2006

The occurrence of systemic lupus erythematosus in an asymptomatic carrier of human T-cell lymphotropic virus type I.

A 63-year-old asymptomatic carrier of human T-cell lymphotropic virus type I (HTLV-1) infection was admitted because of chest oppression, a high-grade fever, polyarthralgia, and erythematous rashes. Laboratory examination revealed lymphocytopenia, proteinuria, and high titers of antinuclear antibodies and antidouble-stranded DNA antibody; thus, she was diagnosed as having systemic lupus erythematosus (SLE). This case indicates that HTLV-1 infection might be related with the pathogenesis of SLE.

Carrier State↗
PubMed2006

Angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes.

BACKGROUND: Angiotensin II (Ang II) has diverse actions on cardiac electrical activity. Little information is available, however, regarding immediate electrophysiological effects of Ang II on cardiac repolarization. METHODS AND RESULTS: The present study investigated the immediate effects of Ang II on the slow component of delayed rectifier K+ current (IKs) and action potentials in guinea pig atrial myocytes using the whole-cell patch-clamp technique. Bath application of Ang II increased the amplitude of IKs (EC50, 6.16 nmol/L) concentration dependently. The stable analogue Sar1-Ang II was also effective at increasing IKs. The voltage dependence of IKs activation and the kinetics of deactivation were not significantly affected by these agonists. The enhancement of IKs was blocked by the Ang II type 1 (AT1) receptor antagonist valsartan (1 micromol/L) and was markedly attenuated by inclusion of GDPbetaS (2 mmol/L) in the pipette, indicating an involvement of G protein-coupled AT(1) receptor. The stimulatory effect was also significantly reduced by the phospholipase C inhibitor compound 48/80 (100 micromol/L) and the protein kinase C inhibitors bisindolylmaleimide I (200 nmol/L) and H-7 (10 micromol/L), suggesting that AT1 receptor acts through phospholipase C-protein kinase C signaling cascade to potentiate I(Ks). As expected from its stimulatory action on IKs, Sar1-Ang II markedly shortened the action potential duration, which could be reversed by valsartan. CONCLUSIONS: The potentiation of IKs via AT1 stimulation in atrial myocytes, accompanied by a shortening of the action potential duration, suggests a potential mechanism by which elevated levels of Ang II may promote atrial fibrillation in heart failure and warrants further investigation.

Action Potentials↗
PubMed2006

The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome.

BACKGROUND: Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the I(Ks) current, are still based largely on case reports. METHODS AND RESULTS: We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (557+/-65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. beta-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD. CONCLUSIONS: J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which beta-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc < or =550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered.

Adolescent↗
PubMed2006

Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure.

OBJECTIVES: This study sought to evaluate the relationship between brain natriuretic peptide (BNP), renal function, and the severity of congestive heart failure (CHF). BACKGROUND: Both BNP and renal function are prognostic predictors in CHF patients. METHODS: We measured the plasma BNP level in the aortic root and coronary sinus in 366 consecutive patients with CHF. Estimated glomerular filtration rate (eGFR) by the Cockcroft-Gault equation was used as an indicator of renal function. RESULTS: By stepwise multivariate analyses, hemodynamic parameters such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP) but not eGFR were independent predictors of a transcardiac increase (coronary sinus-aortic root) in BNP. Regarding the plasma level of BNP in the aortic root, not only LVEF (p < 0.0001) and LVEDP (p < 0.0001) but also eGFR (p < 0.0001) were independent predictors. Patients were divided into two groups, patients with an eGFR > or =60 ml/min (group 1, n = 229) and patients with an eGFR <60 ml/min (group 2, n = 137). There was no difference in LVEF, LVEDP, or the transcardiac gradient of BNP between the two groups, but the plasma level of BNP in the aortic root was approximately two-fold greater in group 2 than in the group 1. CONCLUSIONS: These findings suggest that decreased clearance from the kidney contributes to the elevated BNP in CHF patients with renal dysfunction, especially in patients with an eGFR <60 ml/min.

Aged↗
PubMed2006

Impact of endothelial dysfunction on left ventricular remodeling after successful primary coronary angioplasty for acute myocardial infarction--analysis by quantitative ECG-gated SPECT--.

BACKGROUND: We hypothesized that endothelial cell integrity in the risk area would influence left ventricular remodeling after acute myocardial infarction. PATIENTS AND METHODS: Twenty patients (61 +/- 8 y.o.) with acute myocardial infarction underwent 99mTc-tetrofosmin imaging in the subacute phase and three months after successful primary angioplasty due to myocardial infarction. All patients were administered angiotensin-converting enzyme inhibitor after revascularization. Cardiac scintigraphies with quantitative gated SPECT were performed at the sub-acute stage and again 3 months after revascularization to evaluate left ventricular (LV) remodeling. The left ventricular ejection fraction (EF) and end-systolic and end-diastolic volume (ESV, EDV) were determined using a quantitative gated SPECT (QGS) program. Three months after myocardial infarction, all patients underwent cardiac catheterization examination with coronary endothelial function testing. Bradykinin (BK) (0.2, 0.6, 2.0 microg/min) was administered via the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by Doppler flow velocity measurement. Patients were divided into two groups by BK-response: a preserved endothelial function group (n = 10) and endothelial dysfunction group (n = 10). RESULTS: At baseline, both global function and LV systolic and diastolic volumes were similar in both groups. However, LV ejection fraction was significantly improved in the preserved-endothelial function group, compared with that in the endothelial dysfunction group (42 +/- 10% to 48 +/- 9%, versus 41 +/- 4% to 42 +/- 13%, p < 0.05). LV volumes progressively increased in the endothelial dysfunction group compared to the preserved-endothelial, function group (123 +/- 45 ml to 128 +/- 43 ml, versus 111 +/- 47 ml to 109 +/- 49 ml, p < 0.05). CONCLUSION: In re-perfused acute myocardial infarction, endothelial function within the risk area plays an important role with left ventricular remodeling after myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed2006

Proteomic analysis reveals significant alternations of cardiac small heat shock protein expression in congestive heart failure.

BACKGROUND: Because congestive heart failure (CHF) is a complex syndrome with many different underlying mechanisms of worsening of heart function, it is important to recognize the global alternations in protein expression associated with the processes of CHF. METHODS AND RESULTS: The purpose of our study was to use a proteomic approach to investigate global alternations in protein expression in tachycardia induced CHF dogs. We compared the 2-dimensional electrophoresis protein patterns of left ventricular samples from the normal with those from failing myocardium. Differentially expressed cardiac proteins showed approximately 500 cardiac protein spots. A total of 20 spots (14 increased, 6 decreased) was altered in CHF, whereas the more distinguishably increased spots in CHF were identified by using mass spectrometry as alpha B crystallin, heat shock protein (HSP) 27, and HSP20, which maintain both the morphologic and functional integrity of the cardiomyocytes and increase tolerance against various types of stress. Because phosphorylation is one of the most important posttranslational modifications, we evaluated whether or not the overexpressed small HSPs were phosphorylated in CHF. Phosphoprotein staining and Western blotting demonstrated that the phosphorylation of alpha B crystallin at serine (Ser)-59 site and of HSP27 at both Ser-78 and Ser-82 sites increased in CHF. CONCLUSION: Proteomics studies can provide new insights into molecular mechanisms in CHF and phosphorylated small HSPs may be involved in preventing cardiac dysfunction.

Animals↗
PubMed2006

Serum level of uric acid, partly secreted from the failing heart, is a prognostic marker in patients with congestive heart failure.

BACKGROUND: A recent study suggested that xanthine oxidase is activated in congestive heart failure (CHF). However, whether uric acid (UA) is secreted from the failing heart remains unknown, so it is currently unclear whether serum UA can provide prognostic information independent of brain natriuretic peptide (BNP). METHODS AND RESULTS: Serum UA was measured in the aortic root (AO) and the coronary sinus (CS) of 74 patients with CHF. The serum UA level was significantly higher in the CS than in the AO. The transcardiac gradient of UA (CS-AO) increased with the severity of CHF, inversely correlated with left ventricular ejection fraction (LVEF) and positively correlated with left ventricular end-diastolic volume index. The plasma levels of norepinephrine, BNP, UA, and LVEF were monitored prospectively in 150 CHF patients for a mean follow-up of 3 years. High plasma levels of UA (p<0.001) and BNP (p<0.001) were shown by multivariate stepwise analysis to be independent predictors of mortality. CONCLUSIONS: High plasma UA level, partly secreted from the failing heart, is a prognostic predictor independent of BNP in patients with CHF. Monitoring a combination of BNP and UA may be useful for the management of patients with CHF.

Aged↗
PubMed2006

Blockade of angiotensin II type 1 receptor improves the arrhythmia morbidity in mice with left ventricular hypertrophy.

BACKGROUND: Stimulation of angiotensin II type 1 (AT(1)) receptors has been shown to generate the arrhythmogenic substrate in ventricular hypertrophy. We examined whether candesartan, an AT1 receptor blocker, has antiarrhythmic effects on mouse model of left ventricular hypertrophy created by transverse aorta constriction (TAC). METHODS AND RESULTS: Forty-eight male mice were divided into 3 groups: TAC, candesartan (TAC plus candesartan) and control groups. Echocardiographic examination was performed before the operation and 2 and 4 weeks after the operation. Four weeks after the operation, electrophysiological studies were conducted by inserting a 1.7 F octapolar electrode catheter through the right external jugular vein into the right ventricle. The effective refractory period of the atrioventricular node (AVNERP) in TAC group was significantly prolonged, and short episodes of ventricular tachycardia (VT) and atrial fibrillation (AF) could be induced in 12 of 16 mice (75%) and 8 of 16 (50%), respectively. In contrast, in candesartan group, the incidence of VT was significantly reduced (12.5%) and no AF was induced. Moreover, the drug produced a significant left ventricular hypertrophy regression and restored the AVNERP to normal. CONCLUSIONS: Candesartan reduced both ventricular and atrial arrhythmias in the TAC mice, presumably by preventing the electrical remodeling by inhibiting the AT(1) receptor.

Angiotensin II Type 1 Receptor Blockers↗