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Biomedical subjects

Naohito Yamasaki

Publications and source records attributed to Naohito Yamasaki.

12 recordsLinked to original sources

Long-term prognosis of dilated cardiomyopathy revisited: an improvement in survival over the past 20 years.

BACKGROUND: Because of their favorable prognostic effects, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and beta blockers have become background therapy in dilated cardiomyopathy (DCM). However, there are few reports concerning the long-term prognosis of Japanese patients with DCM in relation to these treatments. METHODS AND RESULTS: One hundred and fifty patients with DCM were divided into 2 groups: group A (n=46) (diagnosis: 1982-1989) and group B (n=104) (diagnosis: 1990-2002). During follow-up period of 6.9+/-4.8 years, 62 patients died and 1 patient had a heart transplant. The survival rate at 5 and 10 years was 60.9% and 34.8%, respectively, in group A patients, and 80.9% and 65.3%, respectively, in group B patients (p=0.0079). In group A patients, ACEI/ARB or beta blockers were less frequently used (p<0.0001), whereas antiarrhythmics (class Ia or Ib) were more often used (p<0.0001). The patients treated with ACEI/ARB and beta blockers showed a better survival rate than those without (p<0.0001). The patients with antiarrhythmics showed a worse survival rate than those without (p<0.0001). CONCLUSION: The prognosis of Japanese patients with DCM has significantly improved over the past 20 years. This improvement may be explained partly through the increased use of ACEI/ARB and beta blockers and a declining use of antiarrhythmics.

Adrenergic beta-Antagonists↗

Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac Myosin-binding protein C gene among Japanese.

OBJECTIVES: We studied the longitudinal evolution of hypertrophic cardiomyopathy (HCM) caused by a founder frameshift mutation in the cardiac myosin-binding protein C (MyBPC) gene. BACKGROUND: Mutations in the MyBPC gene have been associated with delayed expression of HCM and a good prognosis. Few studies, however, demonstrated the phenotype-genotype correlations in the longitudinal study. METHODS: We studied long-term evolution of clinical features of 15 unrelated families who were found to have an identical frameshift mutation in the MyBPC gene: a one-base deletion of a thymidine at nucleotide 11645 (V592fs/8). RESULTS: Thirty-nine individuals in 15 families were genotype-positive. Thirty of the 39 individuals with the mutation were phenotype-positive. The disease penetrance was 100% in subjects > or =50 years and 65% in those <50 years. "End-stage" HCM (ejection fraction <50%) was observed in 7 (18%) of the 39 genotype-positive individuals (7 [23%] of the 30 phenotype-positive patients); 6 of them were 60 years or older. Seven patients were hospitalized for treatment of repeated congestive heart failure, and four patients died or had implantable cardioverter-defibrillator discharge (13%; incidence, 1.4%/year) during a mean follow-up period of 9.2 +/- 5.5 years. CONCLUSIONS: Elderly patients with a V592fs/8 mutation in the MyBPC gene may evolve into the "end-stage" HCM, characterized by left ventricular systolic dysfunction, cavity dilation, and irreversible heart failure. The clinical course in patients with this mutation is not benign in the long run, with progressive left ventricular remodeling with advancing age.

Adolescent↗

Functional assessment by myocardial performance index (Tei index) correlates with plasma brain natriuretic peptide concentration in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) might exhibit not only diastolic, but also latent systolic dysfunction. Therefore combined assessment of both systolic and diastolic function using myocardial performance index (Tei index) can be useful in HCM. Plasma brain natriuretic peptide (BNP) level is reported to be elevated in HCM, but the mechanism of BNP elevation in HCM remains to be established. METHODS AND RESULTS: The value of Tei index in 45 HCM patients was compared with that of 20 normal control subjects. The HCM patients showed a higher value of Tei index (0.55+/-0.12 vs 0.36+/-0.08, p < 0.0001) and longer isovolumic relaxation and contraction times than control subjects. The plasma BNP level correlated with Tei index in non-obstructive HCM (n = 35, r = 0.61, p < 0.0001), although the correlation was mild when overall HCM patients were included (r = 0.34, p = 0.02). The correlation was still significant after adjusting for age, or the extent and severity of left ventricular hypertrophy. Multiple stepwise regression analysis identified mitral E/A ratio (r = 0.49, F = 13.1) and Tei index (r = 0.37, F = 7.6) as independent predictors of higher plasma BNP level in non-obstructive HCM. CONCLUSIONS: Myocardial performance index was abnormal in HCM, reflecting both systolic and diastolic dysfunction in this disorder. Plasma BNP level correlated with functional assessment by Tei index in non-obstructive HCM.

Adult↗

[Aortic stenosis and mitral regurgitation complicated by hemolytic anemia and positive Direct Coombs test: a case report].

A 83-year-old man was admitted because of heart failure due to severe aortic stenosis and mitral regurgitation secondary to chordal rupture of the anterior leaflet. Mild anemia and elevated serum lactate dehydrogenase were present with reticulocytosis and haptoglobinemia. Direct Coombs test was positive. Coexistence of autoimmune hemolytic anemia was identified, but the main cause of his hemolysis was thought to be mechanical hemolysis due to stenotic valve and/or ruptured chordae because of the presence of red cell fragmentation. The patient successfully underwent double valve replacement. Improvement of anemia was coupled with reduction of the serum lactate dehydrogenase level. Valvular shear stress on the red cells and reduction of red cell deformability secondary to autoimmune hemolytic anemia were thought to be responsible for his hemolysis.

Aged↗

[Discrete subaortic stenosis with pressure recovery: a case report].

A 54-year-old woman with subvalvular aortic stenosis was admitted to our hospital. The pressure gradient across the left ventricular outflow tract was estimated as 88 mmHg (peak) and 45 mmHg (mean) by Doppler echocardiography, but only 14 mmHg (peak to peak) and 31 mmHg (mean) by cardiac catheterization. We considered this discrepancy attributable to the presence of moderate aortic regurgitation and the pressure recovery phenomenon. Pressure recovery has clinical relevance particularly in a patient with tunnel-like stenosis, with gradual lumen re-expansion beyond the limiting orifice. Therefore, if Doppler echocardiography shows significant left ventricular outflow tract gradient, precise evaluation of the stenosis geometry is required to investigate the effect of pressure recovery.

Blood Pressure↗

Csm, a cardiac-specific isoform of the RNA helicase Mov10l1, is regulated by Nkx2.5 in embryonic heart.

Nkx2.5 (also called Csx) is an evolutionarily conserved cardiac transcription factor of the homeobox gene family. Nkx2.5 is required for early heart development, because Nkx2.5 null mice die before completion of cardiac looping. To identify genes regulated by Nkx2.5 in the developing heart, we performed differential screening in combination with suppression subtractive hybridization using RNA isolated from wild-type and Nkx2.5 null hearts at embryonic day 8.5. One gene that we found to be markedly down-regulated in the hearts from Nkx2.5 null embryos is an isoform of Mov10 like-1 (Mov10l1), a putative RNA helicase expressed in testis. We named this novel isoform as Csm (cardiac-specific isoform of Mov10l1). Csm is identical with the 3' region of the Mov10l1 gene, but its transcript starts from the exon 16 of Mov10l1. The conceptual protein encoded by Csm cDNA contains a helicase motif as well as ATPase and RNA interaction motifs. Csm is expressed specifically in the heart, and its expression in the heart is restricted to cardiac myocytes. Csm potentiated phenylephrine-induced hypertrophic response in cardiac myocytes. Furthermore, transient cotransfection analysis showed that Nkx2.5 transactivates the Csm promoter, suggesting that Nkx2.5 is essential for embryonic Csm expression.

Amino Acid Sequence↗

A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.

OBJECTIVES: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. METHODS: We analyzed the patients' genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. RESULTS: The analysis showed that the patients homozygously retained a missense mutation, Gumacr;GC[435Gly]-->Aumacr;GC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. CONCLUSION: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450(C18) activities causes CMO II deficiency.

Amino Acid Substitution↗

Heart failure in the elderly.

Heart failure is common in the elderly population. Approximately 6 to 10 percent of the population 65 years or older have heart failure. Heart failure is the most common reason for hospitalization in elderly patients. Etiology of heart failure is often multifactorial in the elderly. The common causes of heart failure include ischemic heart disease, valvular heart disease, hypertensive heart disease, and cardiomyopathy. Exacerbation of heart failure in the elderly is often accompanied by precipitating factors which include arrhythmia, renal failure, anemia, infection, adverse effect of drugs and non-compliance with medication and/or diet. Diagnosis of heart failure may be difficult in the elderly because symptoms of heart failure are often atypical or even absent. Heart failure with preserved systolic function is common in the elderly because aging has a greater impact on diastolic function. It is important to recognize that very old patients with heart failure are underrepresented in clinical trials.

Aged↗

Long-term prognosis of patients with mildly dilated cardiomyopathy.

The long-term prognosis of patients with mildly dilated cardiomyopathy (MDCM) was investigated in 21 patients. MDCM was defined as left ventricular ejection fraction < or = 40% and left ventricular end-diastolic volume < or = 120 ml/m2 by left ventriculography. During a follow-up period of 6.8+/-3.7 years, there were 9 cardiac events (5 heart failure deaths, 2 sudden deaths, and 2 re-hospitalizations for heart failure). Only in the patients without cardiac events was there a significant decrease in left ventricular size (end-diastolic dimension decreased from 58+/-6 mm to 50+/-8 mm, p<0.001) and an improvement in systolic function (fractional shortening increased from 17+/-5% to 26+/-11%, p=0.007). However, left atrial dilation was observed in the patients with an event (from 39+/-5 mm to 43+/-5 mm, p=0.02). Based on proportional hazard analysis, left ventricular end-diastolic pressure and mean pulmonary artery pressure at diagnosis and left atrial dimension at the time of follow-up were significant predictors of poor outcome. A subset of patients with MDCM has impaired hemodynamics at diagnosis, left atrial dilation at follow-up and a poor prognosis, and must be followed carefully even if the left ventricular dilatation is mild.

Age of Onset↗

Myocardial enhancement on magnetic resonance imaging with gadolinium-diethylenetriamine pentaacetic acid and improvement of left ventricular function in patients with dilated cardiomyopathy.

OBJECTIVES: This study evaluated the significance of myocardial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement on magnetic resonance imaging for the improvement of left ventricular function in patients with dilated cardiomyopathy. METHODS: Twenty-seven patients with dilated cardiomyopathy (mean age 59 +/- 11 years) were studied. The magnitude of myocardial Gd-DTPA enhancement was quantitatively assessed using signal intensity ratio and compared to changes in left ventricular function and adverse cardiac events during a relatively long follow-up period. RESULTS: Regional high signal intensity ratio, defined as > or = mean + 2SD in seven normal subjects, was found in 14 patients: in three or more regions out of five myocardial regions analyzed in six patients (extensive enhancement) and in only one or two regions in eight patients (limited enhancement). The remaining 13 patients had no high signal ratio in any of the five regions analyzed (no enhancement). During the follow-up period of 3.9 +/- 1.9 years, four patients died of cardiac causes. The incidence of cardiac death was 33.3% in patients with extensive enhancement, 12.5% in those with limited enhancement and 7.7% in those without enhancement, but there was no statistical difference. Mild improvement in fractional shortening was observed in patients without enhancement during the follow-up (19 +/- 4%-->27 +/- 10%, p = 0.03). CONCLUSIONS: Evaluation of myocardial Gd-DTPA enhancement on magnetic resonance imaging may provide useful prognostic information for patients with dilated cardiomyopathy.

Adult↗

Thallium scintigraphy for the prognosis of idiopathic dilated cardiomyopathy.

OBJECTIVES: This study evaluated the significance of perfusion defects demonstrated by thallium-201 and age in the prognosis of patients with idiopathic dilated cardiomyopathy. METHODS: Seventy-four dilated cardiomyopathy patients underwent thallium scintigraphy as well as clinical and hemodynamic examination. RESULTS: Abnormal perfusion defects were present in 23 of 38 patients aged < 60 years (61%) and in 26 of 36 elderly patients aged > or = 60 years (72%; NS). Univariate analysis showed that such perfusion defects were a significant predictor of cardiac death only in patients aged < 60 years (p = 0.015). Stepwise discriminant analysis also revealed that perfusion defects were a significant predictor in patients aged < 60 years (Wilks' lambda 0.499, chi-square test 20.2, p = 0.003). Perfusion defects were not more important than the history of syncope or stroke in elderly dilated cardiomyopathy patients. Twenty-one patients died of disease-related causes during 58 +/- 43 months. The five-year survival rate was better in patients aged < 60 years without than in those with perfusion defects (100% vs 58.4%, respectively), but not affected in patients aged > or = 60 years (66.7% vs 62.2%). CONCLUSIONS: Thallium scintigraphy is valuable for the prognosis of patients with dilated cardiomyopathy aged < 60 years who are usually candidates for heart transplantation. Absence of thallium perfusion defects may indicate good long-term prognosis.

Cardiomyopathy, Dilated↗