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Biomedical subjects

Hiroshi Mabuchi

Publications and source records attributed to Hiroshi Mabuchi.

At least 73 records · Page 4Linked to original sources
PubMed2004

Diagnostic value of abnormal Q waves for identification of preclinical carriers of hypertrophic cardiomyopathy based on a molecular genetic diagnosis.

AIMS: There are currently no established diagnostic criteria for the identification of abnormal Q waves in patients with hypertrophic cardiomyopathy (HCM), resulting in various definitions being applied in each previous study. The aim of this study was to determine the most accurate diagnostic definition of abnormal Q waves for HCM based on a molecular genetic diagnosis, and also to apply abnormal Q waves to the identification of preclinical carriers. METHODS AND RESULTS: We applied three different criteria used in previous reports for abnormal Q waves in 148 genotyped subjects. Of the three criteria, Criterion 3 (Q wave >3mm in depth and/or >0.04s in duration in at least two leads except aVR) showed the highest sensitivity (50% in the young, 29% in adults) while retaining a high specificity (90% in the young, 97% in adults), resulting in the highest accuracy (69% in the young, 52% in adults). Using Criterion 3, abnormal Q waves were present 27.6% of preclinical carriers, and in 5.4% of non-carriers (P<0.01). CONCLUSIONS: These findings suggest that Criterion 3 may be the most accurate diagnostic definition for HCM. Understanding the diagnostic value of abnormal Q waves may be useful in screening preclinical carriers of HCM.

Adolescent↗
PubMed2004

Clinical applications of long-term LDL-apheresis on and beyond refractory hypercholesterolemia.

Premature coronary heart disease (CHD) can result from high LDL cholesterol levels even in the absence of any other risk factors. A striking example is found in children who have the homozygous form of familial hypercholesterolemia (FH) with extremely high levels of LDL-cholesterol, and severe atherosclerosis and CHD often develop during the first decades of life. LDL-apheresis was developed for the treatment of severe type of FH patients who are resistant to lipid-lowering drug therapy. Clinical efficacy and safety of the therapeutic tool which directly removes LDL from circulation have already been established in the treatment for refractory hypercholesterolemia in FH patients. The most recently developed method enables lipoproteins to be adsorbed directly from whole blood, using polyacrylate column. In addition to benefits derived from the stabilization or regression of arterial lesions, we highlight other possible clinical applications of LDL-apheresis. However, most of these clinical benefits came from case reports or retrospective studies. Mechanisms related these clinical improvement remain unclear, and prospective randomized controlled trials should be performed for the new clinical indications of LDL-apheresis.

Anticholesteremic Agents↗
PubMed2004

Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG.

Patients with LQTS (long QT syndrome) with a mutation in a cardiac ion channel gene, leading to mild-to-moderate channel dysfunction, may manifest marked QT prolongation or torsade de pointes only upon an additional stressor. A 59-year-old woman had marked QT prolongation and repeated torsade de pointes 3 months after initiation of probucol, a cholesterol-lowering drug. We identified a single base substitution in the HERG gene by genetic analysis. This novel missense mutation is predicted to cause an amino acid substitution of Met(124)-->Thr (M124T) in the N-terminus. Three other relatives with this mutation also had QT prolongation and one of them had a prolonged QT interval and torsade de pointes accompanied by syncope after taking probucol. We expressed wild-type HERG and HERG with M124T in Xenopus oocytes and characterized the electrophysiological properties of these HERG channels and the action of probucol on the channels. Injection of the M124T mutant cRNA into Xenopus oocytes resulted in expression of functional channels with markedly smaller amplitude. In both HERG channels, probucol decreased the amplitude of the HERG tail current, decelerated the rate of channel activation, accelerated the rate of channel deactivation and shifted the reversal potential to a more positive value. The electrophysiological study indicated that QT lengthening and cardiac arrhythmia in the two present patients were due to inhibition of I(Kr) (rapidly activating delayed rectifier K(+) current) by probucol, in addition to the significant suppression of HERG current in HERG channels with the M124T mutation.

Animals↗
PubMed2004

Primary cardiovascular events and serum lipid levels in elderly Japanese with hypercholesterolemia undergoing 6-year simvastatin treatment: a subanalysis of the Japan lipid intervention trial.

OBJECTIVES: To determine the relationship between serum lipid levels and the incidence of coronary events in older Japanese hypercholesterolemic patients without prior coronary heart disease (CHD). DESIGN: Post hoc subanalysis of the results in the Japan Lipid Intervention Trial. SETTING: A large-scale cohort observational study conducted throughout Japan. PARTICIPANTS: Men aged 35 to 70 and postmenopausal women younger than 70 with serum total cholesterol (TC) level of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421 total patients). After exclusion of 5,127 patients because of prior CHD and 4,934 patients because of incomplete data, 42,360 patients were divided into an older (9,860 patients, aged 65-70, mean age 67.1) and younger (32,500 patients, younger than 65, mean age 54.9) group and analyzed. MEASUREMENTS: Fasting serum lipid levels were measured every 6 months. Major coronary events, including fatal or nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint and other cardiovascular diseases, including onset of angina pectoris, cerebrovascular events, and any causes of death, as the secondary endpoints were monitored. RESULTS: Simvastatin treatment in older patients was as safe and effective as in younger patients. Incident rates of major coronary events were 1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years in the younger group. The incidence of a major coronary event was correlated to serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups. The absolute risk of major coronary events in the older group was higher than in the younger group at any level of LDL-C, whereas the relative risk increased by 1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older group, the risk of major coronary events also increased as triglyceride level increased, whereas the risk decreased as high-density lipoprotein cholesterol level increased above 60 md/dL. CONCLUSION: The LDL-C level-dependent increase of relative risk of CHD was similar in elderly and younger patients, whereas the absolute risk at any LDL-C level in elderly patients was higher than in younger patients.

Adult↗
PubMed2004

Increased circulating matrix metalloproteinase-2 in patients with hypertrophic cardiomyopathy with systolic dysfunction.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular (LV) wall thinning associated with LV dilatation and systolic dysfunction. Recently, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were reported to be involved in ventricular remodeling, however, little is known about MMPs and TIMPs in patients with HCM. METHODS AND RESULTS: Enzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS> or =25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124 +/- 84, 792 +/- 49, 809 +/- 26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3 +/- 4.7, 34.6 +/- 2.2, 33.7 +/- 1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlated significantly with FS and LV dimension, negatively and positively, respectively. CONCLUSIONS: These results suggest that changes in the release and activity of MMP-2 and TIMP-2 may be associated with the mechanisms responsible for cardiac remodeling in patients with HCM.

Cardiomyopathy, Hypertrophic↗
PubMed2004

Difference in the risk factors for coronary, renal and other peripheral arteriosclerosis in heterozygous familial hypercholesterolemia.

BACKGROUND: The aim of the present study was to clarify the risk factors of several types of arteriosclerosis lesions in Japanese individuals with heterozygous familial hypercholesterolemia (FH): renal arteriosclerosis (RAS), abdominal aortic sclerosis (AOS), iliac arteriosclerosis (IAS) and coronary artery disease (CAD). METHODS AND RESULTS: Coronary angiography (CAG) and abdominal aortic angiography (AAA) were performed in 117 consecutive heterozygous FH subjects (79 men, 38 women; age 22-76). RAS (stenotic lesion or aneurysm) was observed in 39 cases (33%), predominantly in the proximal portion (74%) and both sides equally (right/left = 27/23). Most cases of RAS (64%) presented with <25% stenosis. The differences in the contributing risk factors for the progression and development of RAS, AOS, IAS and CAD in FH were then analyzed. Multiple logistic regression analyses showed independent risk factors for formation of atherosclerosis in each artery were: age alone for RAS; age and plasma low-density lipoprotein cholesterol (LDL-C) for AOS; age, LDL-C and high-density lipoprotein cholesterol (HDL-C) for IAS; and HDL-C and diabetes mellitus for CAD. CONCLUSION: In Japanese subjects with heterozygous FH, there are distinct risk factors for the development and progression of atherosclerosis in the renal, iliac, abdominal aorta, and coronary arteries.

Arteriosclerosis↗
PubMed2004

Association between CTLA-4 +49 A/G polymorphism and type 1B diabetes in Japanese population.

+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However, a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with more severe cell dysfunction than their type 1A counterparts.

Adult↗
PubMed2004

Identification of two novel missense mutations (p.R1221C and p.R1357W) in the ABCC6 (MRP6) gene in a Japanese patient with pseudoxanthoma elasticum (PXE).

Pseudoxanthoma elasticum (PXE) is a rare, inherited, systemic disease of elastic tissue that in particular affects the skin, eyes, and cardiovascular system. Recently, the ABCC6 (MRP6) gene was found to cause PXE. A defective type of ABCC6 gene (16pl3.1) was determined in two Japanese patients with PXE. In order to determine whether these patients have a defect in ABCC6 gene, we examined each of 31 exons and flanking intron sequences by PCR methods (SSCP screening and direct sequencing). We found two novel missense variants in exon 26 and 29 in a compound heterozygous state in the first patient. One is a missense mutation (c.3661C>T; p.R1221C) in exon 26 and the other is a missense mutation (c.4069C>T; p.R1357W) in exon 29. These mutations have not been detected in our control panel of 200 alleles. To our knowledge, this is the first report of mutation identification in the ABCC6 gene in Japanese PXE patients. The second patient was homozygous for 2542_2543delG in ABCC6 gene and heterozygous for 6 kb deletion of LDL-R gene. This case is the first report of a genetically confirmed case of double mutations both in PXE and FH loci.

Adult↗
PubMed2004

Lispro is superior to regular insulin in transient intensive insulin therapy in type 2 diabetes.

OBJECTIVE: The optimal approach to relatively recent onset type 2 diabetes patients is still unknown. We speculated that the use of short-acting insulin analogs might be of particular benefit in this context. PATIENTS AND METHODS: To explore this possibility, we compared the effect on beta- and alpha-cell function of transient intensive insulin therapy using lispro versus human regular insulin in a total of 21 type 2 diabetic patients who were randomly assigned to 14-days intensive insulin therapy consisting of bedtime NPH insulin plus three injections of mealtime lispro (n=11) or regular insulin (n=10). The dosages of both types of insulin were adjusted to attain preprandial glucose levels of <6.1 mmol/l within 1 week with similar rates of glucose decline. An oral glucose tolerance test (OGTT) was performed at day 0 (baseline), 7, and 14; plasma glucose, serum insulin, and plasma glucagon responses over 0-120 minutes were measured, and calculated as the area under the curve (AUC). RESULTS: Lispro led to a significant reduction in glucose-AUC and also an increase in insulin-AUC versus regular insulin on day 7. Glucagon secretion following OGTT was well suppressed with lispro on day 14 compared to regular insulin. CONCLUSION: Two-week intensive insulin therapy with lispro appeared to be more effective than that with regular insulin in type 2 diabetes in attaining both more rapid beta-cell rest and greater suppression of glucagon. These changes may provide significant long-term benefits.

Adult↗
PubMed2004

Clinical efficacy and safety of rosuvastatin in Japanese patients with heterozygous familial hypercholesterolemia.

Rosuvastatin is a new statin that has been shown to produce substantial dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western and Japanese hypercholesterolemic patients. Rosuvastatin efficacy and safety were assessed in an open-label, dose-titration trial of 37 Japanese patients with heterozygous familial hypercholesterolemia. After an 8-week dietary lead-in period, patients received rosuvastatin on the following schedule: 10 mg/day during weeks 0-6; 20 mg/day during weeks 6-12, and 40 mg/day for weeks 12-18. Mean percentage reductions from baseline in LDL-C (49.2-56.7%), total cholesterol (39.4-45.4%), and non-high-density lipoprotein cholesterol (non-HDL-C) (46.7-54.3%) were highly significant at each dose (p < 0.0001). Similar significant reductions in triglycerides (18.2-25.0%; p < 0.006) and increases in HDL-C (9.6-13.6%; p < 0.005) were observed. Rosuvastatin was well tolerated. Two patients withdrew from the study because of adverse events unrelated to the study treatment. No patients had clinically significant elevations in liver transaminases. Two patients exhibited a single increase in creatine kinase (one unrelated to study treatment, the other possibly related) with no muscle symptoms. Rosuvastatin produced significant beneficial changes in all lipid parameters in Japanese patients with heterozygous familial hypercholesterolemia and was well tolerated.

Asian People↗
PubMed2003

Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient.

AIM: The effects of treatment with hydrochlorothiazide (HCTZ) combined with amiloride were elucidated and compared to HCTZ treatment alone and combined with acemetacin or triamterene in a Japanese adult patient with congenital nephrogenic diabetes insipidus. METHODS: The study was divided into seven periods: (1) HCTZ and acemetacin; (2) control period; (3) HCTZ; (4) a second control period; (5) HCTZ and amiloride; (6) a third control period, and (7) HCTZ and triamterene. Fluid intake, urine volume, urinary Na, K, creatinine, and osmolality and serum Na, K, Cl, CO2, and osmolality were measured, and free water clearance and proximal and distal tubular Na reabsorption rates were calculated. RESULTS: Without drug administration, the urine volume was about 8,000 ml/day. The urine volume was reduced to about 6,000 ml/day with HCTZ. A further urine volume reduction to about 5,000 ml/day was obtained with the second drug administration, and the effects were similar among the three regimens. Serum and urinary osmolality and free water clearance were also similar among the three combinations, whereas the urinary potassium excretion was the least, and the serum potassium concentration was the highest with HCTZ plus amiloride. Besides, no alkalosis was observed only with this combination. CONCLUSION: HCTZ plus amiloride may be superior to HCTZ plus acemetacin and HCTZ plus triamterene in preventing hyperkaliuria, hypokalemia, and metabolic alkalosis.

Adult↗
PubMed2003

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency.

Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than 2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Three of the five heterozygotes' alpha-1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre-beta-1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of alpha-1 containing apoA-I but no apoA-II, represent an improved anti-atherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles.

Adult↗
PubMed2003

Haplotype analyses of cholesteryl ester transfer protein gene promoter: a clue to an unsolved mystery of TaqIB polymorphism.

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins. TaqIB polymorphism (B2 allele) identified in intron 1 is associated with lower plasma CETP concentrations and higher HDL cholesterol levels and may play an antiatherogenic role in humans. However, its molecular mechanism remains unclear. To evaluate the association between the promoter polymorphisms and CETP/HDL cholesterol levels, ten novel and three previously reported polymorphisms located within 3.3 kb of the CETP gene promoter were investigated in a sample of 357 elderly Japanese men. All the promoter polymorphisms were in linkage disequilibrium with each other and with TaqIB. The -2505A allele, the "S" allele of the [gaaa](n) repeat ("S" denotes [gaaa](n)=329 bp and longer, "L" denotes >329 bp) and TaqIB2 allele were significantly associated with both lower plasma CETP concentrations and higher HDL cholesterol levels whereas -971G/A and -629A/C were significantly associated with CETP concentrations but not with HDL-C levels. The 12-polymorphism haplotypes consisting of -2804, -2505, [gaaa](n), -1930, -1674, -1129, -1046, -971, -875, -827, -629, and TaqIB were analyzed. These 12 polymorphisms generated eight main haplotypes, accounting for 86% of the observed haplotypes. The G/A/S/T/T/C/T/A/C/C/A/B2 haplotype was significantly associated with lower CETP concentrations (2.0+/-0.6 micro g/ml) and higher HDL cholesterol levels (55.1+/-12.7 mg/dl) than the other seven main haplotypes. The 5- and 3-polymorphism haplotype analyses consisting of -2505 and the [gaaa](n) repeat indicated the -2505C/A polymorphism might explain the variation in the CETP concentrations best, and the [gaaa](n) repeat and/or the -2505C/A polymorphism may independently determine the variation in HDL cholesterol levels, whereas the -629A/C and TaqIB polymorphisms were not instrumental in determining CETP concentrations as well as HDL cholesterol levels, although the latter has been frequently examined in many association studies.

Aged↗
PubMed2003

A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients.

OBJECTIVES: We studied the clinical features of hypertrophic cardiomyopathy (HCM) caused by a novel mutation in the myosin binding protein-C (MyBP-C) gene in patients and family members of Japanese descent. BACKGROUND: Previous reports have demonstrated that the clinical features of HCM associated with mutations in the MyBP-C gene include late onset and a favorable clinical course. Recently, some mutations in genes encoding sarcomeric proteins have been reported to be a cause of dilated cardiomyopathy (DCM), as well as HCM. However, mutations of the MyBP-C gene have not been reported as a cause of DCM up to now. METHODS: We analyzed MyBP-C gene mutations in 250 unrelated probands with HCM and in 90 with DCM. We used electrocardiography (ECG) and echocardiography to determine clinical phenotypes. RESULTS: We identified 17 individuals in 8 families (7 HCM, 1 DCM) with an Arg820Gln mutation in the MyBP-C gene. Overall, 2 (40%) of 5 carriers age >70 years displayed "burnt-out" phase HCM, and one of them had been diagnosed as having DCM before genetic identification. The disease penetrance in subjects age >50 years was 70% by echocardiography and 100% by ECG, and that in those age <50 years was 40% and 50%, respectively. CONCLUSIONS: Elderly patients with Arg820Gln mutation may show "burnt-out" phase HCM, and patients with this mutation may be included among those diagnosed as having DCM. Screening of patients with DCM, as well as HCM, for this mutation is of significant importance because patients with this mutation may be diagnosed clinically as having DCM.

Adolescent↗
PubMed2003

Dual effects on HDL metabolism by cholesteryl ester transfer protein inhibition in HepG2 cells.

Cholesteryl ester transfer protein (CETP) promotes reverse cholesterol transport via exchange of cholesteryl ester and triglyceride among lipoproteins. Here, we focused on HDL metabolism during inhibition of CETP expression by using CETP antisense oligodeoxynucleotides (ODNs) in HepG2 cells. CETP secretion was decreased by 70% in mRNA levels and by 52% in mass 20 h after ODNs against CETP were delivered to HepG2 cells. Furthermore, as a consequence of the downregulation of CETP, the expression of scavenger receptor class B type I (SR-BI), an HDL receptor, was also reduced by approximately 50% in mRNA and protein levels, whereas the apolipoprotein A-I (apoA-I) expression and secretion were increased by 30 and 92%, respectively. In a functional study, the selective uptake of (125)I-[(14)C]cholesteryl oleate-labeled HDL(3) was decreased. Cholesterol efflux to apoA-I and HDL(3) was significantly increased by 88 and 37%, respectively. Moreover, the CE levels in cells after antisense treatment were elevated by 20%, which was related to the about twofold increase of cholesterol esterification and increased acyl-CoA:cholesterol acyltransferase 1 mRNA levels. Taken together, these findings suggest that although acute suppression of CETP expression leads to an elevation in cellular cholesterol stores, apoA-I secretion, and cellular cholesterol efflux to apoA-I, the return of HDL-CE to hepatocytes via an SR-BI pathway was inhibited in vitro. Thus antisense inhibition of hepatic CETP expression manifests dual effects: namely, increased formation of HDL and suppression of catabolism of HDL-CE, probably via the SR-BI pathway.

Amides↗
PubMed2003

Simultaneous, clonally identical T cell expansion in tonsil and synovium in a patient with rheumatoid arthritis and chronic tonsillitis.

In some patients with rheumatoid arthritis (RA), the disease improves following tonsillectomy. We describe a 28-year-old woman with treatment-resistant RA and chronic tonsillitis. Initially, her arthritis had been well controlled with methotrexate and corticosteroids, but the RA activity became difficult to control in spite of addition of bucillamine to the treatment regimen and repeated arthrocentesis with infusion of corticosteroid into her swollen joints. Closer examination revealed that the period of exacerbation of her chronic tonsillitis paralleled that of the systemic arthritis, and administration of antibiotics brought transient relief of the systemic symptoms. Her arthritis was ameliorated after successful tonsillectomy and synovectomy, with marked reduction of the serum rheumatoid factor concentration. Analysis of infiltrating T cell clones in tonsil and synovium using T cell receptor V(beta) repertoire and third complementarity-determining region size distribution analysis followed by nucleotide sequencing revealed common clonal T cell expansion in both tissues. This finding suggests the possible involvement of chronic focal infection in refractory RA.

Adult↗
PubMed2003

Hemodynamic changes and prognosis in patients with hypertrophic cardiomyopathy and abnormal blood pressure responses during exercise.

BACKGROUND: An abnormal blood pressure response (BPR) during exercise has been proposed as a risk factor for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). Some patients with HCM show systolic dysfunction during exercise. HYPOTHESIS: The aim of this study was to clarify the hemodynamic response during exercise and prognosis in patients with HCM and abnormal BPR. METHODS: Sixty-five patients with HCM underwent radionuclide monitoring of left ventricular function and measurement of blood pressure during supine ergometer exercise. Thereafter, cardiac events were recorded for an average period of 76 months. RESULTS: Seven of 65 patients had abnormal BPR, while the others had normal BPR. Changes of heart rate and systemic vascular resistance during exercise did not differ between the two groups. Stroke volume did not increase in the abnormal BPR group but did in the normal BPR group. During a mean follow-up period of 76 months, three of the seven patients (43%) with abnormal but only one patient (2%) with normal BPR suffered a malignant arrhythmia. CONCLUSIONS: Abnormal BPR occurred in about 11% of patients with nonobstructive HCM and was associated with a high prevalence of cardiac events. The predictor of abnormal BPR during exercise may not be an abnormal response of systemic vascular resistance and heart rate, but the lack of an appropriate increase in stroke volume.

Blood Pressure↗