Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

The incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation: comparison of warfarin and dabigatran.

BACKGROUND: Cerebral microthromboembolism after atrial fibrillation (AF) ablation has been reported in 4-20% with perioperative warfarin. Dabigatran is a new anticoagulant in patients with nonvalvular AF. We investigated the incidence of asymptomatic cerebral microthromboembolism after AF ablation with perioperative warfarin or dabigatran using diffusion-weighted and T2-weighted magnetic resonance imaging (MRI). METHODS AND RESULTS: Our study included 210 consecutive patients with AF (111 paroxysmal and 99 persistent) who underwent complex fractionated atrial electrogram-guided ablation (combined with pulmonary vein isolation, n = 110). Catheter irrigation was performed in all cases. Uninterrupted warfarin therapy was used in 180 patients (warfarin group) and interrupted only on the morning of the procedure with dabigatran in 30 (dabigatran group). All patients underwent cerebral MRI the day after ablation. New microthromboemboli were detected in 10.0% of the warfarin group and 26.7% of the dabigatran group (P < 0.05). The incidence of hemopericardium treated with pericardiocentesis was lower in the warfarin group than in the dabigatran group (2.5% vs 11.1%, P < 0.05). In multivariate analysis, the use of cardioversion was a predictor of new microthromboembolism development after AF ablation. CONCLUSIONS: The incidence of asymptomatic cerebral microthromboembolism and hemopericardium after AF ablation was significantly lower with perioperative warfarin therapy than with dabigatran therapy. Dabigatran may not be an effective alternative to warfarin for AF ablation, especially in patients who undergo cardioversion.

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram.

BACKGROUND: The incidence of cerebral thromboembolism after pulmonary vein isolation (PVI) ranges from 2% to 14%. This study investigated the incidence of cerebral thromboembolism after complex fractionated atrial electrogram (CFAE) ablation with or without PVI. METHODS: One hundred consecutive atrial fibrillation (AF) patients (50 paroxysmal and 50 persistent, including 10 longstanding) who underwent CFAE ablation combined with (n = 41, PVI+CFAE group) or without (n = 59, CFAE group) PVI were studied. Coronary angiography (CAG) was conducted with AF ablation in 5 cases in which coronary artery stenosis was suspected on 3D-computed tomography. PVI was performed before CFAE ablation without circular catheter during AF. After termination of AF, additional ablation was performed to complete PVI with a circular catheter. All patients underwent cerebral magnetic resonance imaging (MRI) including diffusion-weighted MRI and T2-weighted MRI the day after ablation. RESULTS: New thromboembolism was detected in 7.0%, and there was no significant difference between the 2 strategies (7.3% in PVI+CFAE group, 6.8% in CFAE group). CHADS2 score (1.6 ± 1.0 vs 0.8 ± 0.9, P < 0.05), left atrial volume (LAV; 83.8 ± 27.1 vs 67.8 ± 21.8, P < 0.05), and left ventricular ejection fraction (LVEF, 53.1 ± 9.2 vs 65.1 ± 9.7, P < 0.01) were significantly different when comparing patients with or without thromboembolism. In multivariate analysis, LVEF (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.84-0.99; P < 0.05) and concomitant CAG (OR 18.82; 95% CI, 1.77-200.00; P < 0.05) were important predictors of new cerebral thromboembolism. CONCLUSIONS: The incidence of cerebral microthromboembolism after CFAE ablation was not greater than previous reports in PVI. Cautious management is required during AF ablation, especially in the patients with low LVEF.

Left ventricular dysfunction assessed by cardiac time interval analysis among different geometric patterns in untreated hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy is a powerful independent predictor of morbidity and mortality in hypertensive patients. Abnormal LV geometric patterns are also associated with hypertensive complications, and concentric hypertrophy is associated with the highest mortality in hypertensive patients. However, the relationship between geometric patterns and cardiac dysfunction is not fully established. We hypothesized that the Tei index, which is a measure of global cardiac function, is a feasible parameter for estimating cardiac dysfunction among the different LV geometric patterns in hypertensive patients. METHODS AND RESULTS: We enrolled 60 consecutive patients with untreated essential hypertension. Subjects were divided into 4 groups: normal geometry, concentric remodeling, eccentric hypertrophy and concentric hypertrophy. We measured ejection fraction, mitral E/A ratio, Tei index, ejection time, and isovolumic contraction and relaxation times. There were significant correlations between LV mass index and systolic blood pressure (P<0.01), ejection fraction (P<0.05), mitral E/A ratio (P<0.05) and Tei index (P<0.0001). In multiple regression analysis, only the Tei index independently correlated with LV mass index (P<0.01). Concentric hypertrophy significantly increased the Tei index compared with the other 3 groups. CONCLUSIONS: The Tei index provides a better marker for LV dysfunction by hypertensive hypertrophy than conventional parameters. LV function in concentric hypertrophy was most impaired among all the geometric patterns in untreated hypertensive patients.

Effects of valsartan on fibrinolysis in hypertensive patients with metabolic syndrome.

BACKGROUND: The purpose of this study was to analyze the effect of valsartan on abnormal adipocyte metabolism and prothrombotic state in hypertensive patients with metabolic syndrome (MetS). METHODS AND RESULTS: We conducted a multicenter, prospective, randomized, parallel-group controlled trial in 150 hypertensive patients with MetS. They were randomly assigned to receive either 80-160 mg valsartan per day (valsartan group, n=79) or other conventional treatment without a renin-angiotensin system (RAS) inhibitor (non-RAS inhibitor group, n=71). After 1 year, there were no significant differences between the 2 groups in the changes in systolic and diastolic blood pressures (valsartan: 153±15/86±15 to 138±16/77±12 mmHg; non-RAS inhibitor: 150±14/82±15 to 137±15/76±10 mmHg). There was a significant difference in the change in the levels of plasminogen activator inhibitor-1 (PAI-1) between the 2 groups after 1 year (valsartan: 3.7±3.2 ng/ml; non-RAS inhibitor: 5.8±3.3 ng/ml, P=0.04). There was no significant difference between groups in the change in the concentration of adiponectin after 1 year (valsartan: 0.3±0.4 µg/ml; non-RAS inhibitor: 0.9±0.4 µg/ml, P=0.22). The animal study showed aortic PAI-1 protein expression was reduced in double knockout mice of angiotensin II type 1a receptor and apolipoprotein E (apoE) compared with the apoE knockout mice. CONCLUSIONS: Valsartan reduced plasma PAI-1 levels compared to non-RAS inhibitor in hypertensive patients with MetS, which suggests it may be useful for improving fibrinolytic function.

Association between serum urate level and carotid atherosclerosis: an insight from a post hoc analysis of the PRIZE randomised clinical trial.

OBJECTIVES: Elevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricaemia remains uncertain. The aim of this analysis was to assess an association between changes in SU level and carotid intima-media thickness (IMT) to examine whether an optimal SU concentration exists to delay atherosclerotic progression. METHODS: This was a post hoc analysis of the PRIZE (programme of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicentre, randomised controlled) study of Japanese adults with asymptomatic hyperuricaemia. The primary endpoint of this analysis was an association between changes in SU levels and mean common carotid artery IMT (CCA-IMT) after 24 months of febuxostat treatment. RESULTS: Among subjects treated with febuxostat (n=239), a total of 204 who had both data on SU and mean CCA-IMT at baseline and 24 months were included in this analysis. The mean baseline SU level was 7.7±1.0 mg/dL, and febuxostat treatment significantly reduced SU concentrations at 24 months (estimated mean change ‒3.051 mg/dL, 95% CI ‒3.221 to ‒2.882). A multivariable linear regression analysis revealed that a reduction in SU level was associated with changes in mean CCA-IMT values at 24 months (p=0.025). In contrast, the achieved SU concentrations were not associated with changes in mean CCA-IMT at 24 months. CONCLUSION: A greater reduction in SU, but not its achieved concentrations, may be associated with delayed progression of carotid IMT in patients with asymptomatic hyperuricaemia treated with febuxostat. TRIAL REGISTRATION NUMBER: UMIN000012911.

Reevaluation of quantitative flow cytometric analysis for TLR2 on monocytes using F(ab')2 fragments of monoclonal antibodies.

In patients with refractory infections, reliable markers that monitor the severity and healing process are needed. The expression level of toll-like receptor 2 (TLR2) on monocytes is such candidate. In the conventional assay system, the whole IgG (wIgG) form of anti-TLR2 mAb has been used with control IgG, which blocks nonantigen-specific bindings. However, the competitive reactions against Fcγ receptors (FcγRs) between labeled anti-TLR2 mAbs and control IgG should be considered. Our goal was to precisely quantify TLR2 expression level on monocytes by flow cytometry (FCM). In this study, we prepared anti-TLR2 mAbs, D45 (IgG2a), and D29 (IgG1), as well as their fragment antigen-binding [F(ab')(2) ] fragments to avoid nonantigen-specific binding to FcγRs. And then, we determined TLR2 expression levels on monocytes by using these mAbs/fragments and our calibration system using recombinant TLR2 beads. The binding of PE-labeled D45 wIgG to monocytes was completely blocked with unlabeled D45 wIgG, but not with unlabeled D45 F(ab')(2) fragment. Although the nonantigen-specific binding of D29 wIgG to nonstimulated monocytes was negligible, it was enhanced in interleukin-10-stimulated monocytes. It proved difficult to completely block nonantigen-specific binding of D45 and D29 wIgGs by treatment with control IgG. It was demonstrated that the use of fluorescent-labeled antigen-binding region lacking the fragment crystallizable portion of anti-TLR2 mAb [such as the PE-labeled F(ab')(2) fragment] is indispensible for quantification of TLR2 levels on monocytes in flow cytometry. .

Acute and chronic effects of smoking on arterial stiffness.

BACKGROUND: The brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are used to evaluate arterial distensibility. The purpose of this study was to elucidate the acute and chronic effects of smoking on arterial stiffness as measured by baPWV and CAVI. METHODS AND RESULTS: Ten male smokers were studied to evaluate the acute effect of smoking on arterial stiffness. To elucidate the chronic effect of smoking on arterial stiffness, 160 male active smokers were analyzed. CAVI and baPWV were calculated by measuring the pulse volume record, blood pressure (BP), and vascular length from heart to ankle. CAVI and baPWV were measured using a VaSera VS-1000. In the acute study, baPWV and CAVI increased immediately after smoking 1 cigarette. In the chronic study, baPWV and CAVI significantly correlated with mean BP (MBP) and the Brinkman index. In multiple regression analysis, baPWV independently correlated with MBP, and CAVI independently correlated with the Brinkman index, but not with MBP. Receiver-operating characteristics (ROC) curves of baPWV and CAVI to predict Brinkman index ≥500 demonstrated that the area under the ROC curve of CAVI was higher than that of baPWV. CONCLUSIONS: Smoking causes a significant increase in arterial stiffness as measured by baPWV and CAVI. CAVI correlated with the Brinkman index, which suggests that CAVI is a useful index of the degree of arterial stiffness caused by smoking.

Effect of Waon therapy on oxidative stress in chronic heart failure.

BACKGROUND: A previous report by our team showed that Waon therapy, using a far infrared-ray dry sauna at 60°C, improves cardiac and vascular function in patients with chronic heart failure (CHF). The purpose of the present study was to clarify the effect of Waon therapy on oxidative stress in CHF patients and investigate its mechanism by animal experiments. METHODS AND RESULTS: Forty patients with CHF were divided into control (n=20) and Waon therapy (n=20) groups. All patients received standard optimal medications for CHF. Waon therapy group was treated with Waon therapy daily for 4 weeks. After 4 weeks of Waon therapy, concentrations of hydroperoxide and brain natriuretic peptide (BNP) decreased significantly (hydroperoxide, 422±116 to 327±88U.CARR, P<0.001; BNP, 402±221 to 225±137pg/ml, P<0.001), and the nitric oxide metabolites increased (71.2±35.4 to 92.0±40.5mmol/L, P<0.05). In contrast, none of these variables changed over the 4-week interval in the control group. Furthermore, animal experiments were performed using TO-2 cardiomyopathic hamsters. On immunohistochemistry, cardiac expression of 4-hydroxy-2-nonenal, a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. On Western blotting, cardiac expressions of heat shock protein (HSP) 27, manganese superoxide dismutase and HSP32, which reduce oxidative stress, were significantly upregulated in the 4-week Waon therapy compared to untreated hamsters. CONCLUSIONS: Waon therapy decreases oxidative stress in patients and hamsters with heart failure.

Percutaneous Extraction for Misplacement of Pacemaker Leads Within the Coronary Artery and Left Ventricle.

A 75-year-old man, who underwent inadvertent misplacement of pacemaker leads into the left coronary artery and left ventricle through the subclavian artery, was referred to our hospital. We safely performed percutaneous lead extraction in collaboration with surgeons and with the patient under general anesthesia. (Level of Difficulty: Advanced.).

Enjoying hobbies is related to desirable cardiovascular effects.

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Usefulness of the adenosine triphosphate with a sufficient observation period for detecting reconduction after pulmonary vein isolation.

BACKGROUND: Although reconduction after pulmonary vein (PV) isolation is considered to play a key role in the recurrence of paroxysmal atrial fibrillation (AF), there have been few reports regarding the precise time course of early reconduction. Several studies have suggested that transient PV reconduction facilitated by adenosine may predict long-term AF recurrence. This study was designed to clarify the incidence and time course of early reconduction after PVI during the procedure and to confirm whether the use of ATP after a certain observation period was useful to detect early reconduction after PVI. METHODS: In 21 patients (18 males, 56 +/- 11 years) with drug refractory AF, radiofrequency circumferential PV antrum ablation was performed in all 4 PVs. After the completion of isolation, electrograms in each PV were repeatedly recorded (1.98 +/- 0.57 times per PV) using a circular mapping catheter for an observation period of 87 +/- 29 minutes. After isolation of all 4 PVs, 30 mg of adenosine triphosphate (ATP) was administered during isoproterenol infusion. RESULTS: PV electrical isolation was initially achieved in all 81 PVs. During the observation period, 12 (15%) PVs in 10 (48%) of 21 patients exhibited spontaneous reconduction. Among the remaining 69 PVs, 8 (12%) additional PVs had reconduction with the use of ATP. All PV reconduction was successfully eliminated by 4.5 +/- 2.2 additional radiofrequency applications. CONCLUSION: A sufficient observation period and the use of ATP are useful to detect early reconduction after PV isolation.

A technique for diagnosis of accessory pathway using the H-H and A-A intervals of the first entrained cycle during ventricular overdrive pacing.

Although advancement of succeeding atrial activation by a ventricular extrastimulus (VES) on His refractoriness during supraventricular tachycardia (SVT) has been used as evidence of an accessory pathway (AP), the sensitivity of this method is suboptimal. This study was designed to compare the His-His (H-H) and atrial-atrial (A-A) intervals of the first entrained cycle during ventricular overdrive pacing (VOD) for the diagnosis of AP, in comparison to the conventional VES method. In 55 patients with SVT, a VES was elicited on His refractoriness during SVT. VOD was subsequently performed at cycle lengths 30 to 40 ms shorter than SVT cycle lengths. When the A-A interval became equal to the pacing cycle length after some beats of VOD, the cycle was considered the first entrained cycle and the H-H interval preceding the A-A interval was measured. VES advanced the next atrial activation in 16 patients (52%) with an AP, but in no patient without an AP. The H-H interval of the first entrained cycle was longer than the pacing cycle length by > or =15 ms in all patients with an AP, but was equal to the pacing cycle length in all patients without an AP. The criterion of H-H greater than A-A by > or =15 ms for the first entrained cycle provided higher diagnostic yield for AP compared with the VES method(100% vs 52%, p <0.001). In conclusion, this new criterion reliably diagnoses the presence of an AP in patients with SVT, with higher sensitivity compared with the VES method.

A case of acute coronary syndrome caused by delayed coronary ischemia after transcatheter aortic valve implantation.

An 84-year-old female patient suffered from dyspnea due to severe aortic stenosis. Several comorbidities and her advanced age made her acceptable for transcatheter aortic valve implantation (TAVI). The TAVI procedure was performed via a femoral access and a 26-mm CoreValve prosthesis (Medtronic, Minneapolis, MN, USA) was implanted. The prosthesis was deployed at a high position because of short distance between the annulus base and coronary arteries. Aortic angiography indicated normal contrast flow into both coronary arteries. Six months later she was readmitted to our hospital because of acute coronary syndrome. Although selective intubation of coronary arteries could not be achieved because of high valve position, both coronary arteries seemed to be well contrasted. As a consequence, the second coronary angiography was undertaken because of recurring chest pains. The aortic root angiogram showed a decreased contrast flow into both coronary arteries. During the examination she deteriorated rapidly, developed cardiopulmonary arrest, and a percutaneous cardiopulmonary support and an intra-aortic balloon pump needed to be inserted. She was then transferred to the operating room for aortic valve replacement. This is the first case of delayed coronary ischemia after TAVI, necessitating the removal of an implanted CoreValve and its replacement with a new prosthetic valve. .

Mechanism of recurrent/persistent ischemic/functional mitral regurgitation in the chronic phase after surgical annuloplasty: importance of augmented posterior leaflet tethering.

BACKGROUND: Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. METHODS AND RESULTS: In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (P<0.01), whereas PML tethering significantly worsened (P<0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (P<0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (r2=0.60, P<0.0001), increased PML tethering was the primary determinant of late MR (r2=0.75, P<0.0001). CONCLUSIONS: Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.

Mutations in the genes for sarcomeric proteins in Japanese patients with onset sporadic hypertrophic cardiomyopathy after age 40 years.

This study was conducted to assess the hypothesis that mutations in the genes for sarcomeric proteins are the molecular cause for older-onset sporadic hypertrophic cardiomyopathy (HC) in Japanese patients. Molecular genetic approaches have demonstrated that familial HC is caused by mutations in genes encoding sarcomeric proteins. Recent studies have shown that sarcomeric gene mutations can also be a molecular cause of older-onset and/or sporadic HC. However, genetic studies to date have examined only a limited number of older Caucasian patients with HC. Clinical evaluations were performed in patients with HC onset after 40 years of age, and the sequence encoding the beta-cardiac myosin heavy chain, cardiac troponin T, cardiac troponin I, cardiac myosin binding protein-C, myosin ventricular regulatory light chain, and myosin ventricular essential light chain genes was analyzed. When a putative mutation was identified, clinical evaluations and genetic studies were subsequently performed on all first-degree relatives. Forty-one patients with sporadic HC onset after 40 years of age (31 men, 10 women; mean age 63+/-10 years at the time of study) were studied. Four novel missense mutations in the cardiac myosin binding protein-C gene (arginine to tryptophan at codon 160, glutamic acid to lysine at codon 334, glycine to arginine at codon 507, and threonine to methionine at codon 1,046) and a previously reported missense mutation in the beta-cardiac myosin heavy chain gene (arginine to histidine at codon 663) were identified in 5 of the 41 patients. No family members carried these mutations or had clinical evidence of HC. In conclusion, mutations in the cardiac myosin binding protein-C are the most common cause of older-onset sporadic HC in Japan.

Significance of asymmetric basal posterior wall thinning in patients with cardiac Fabry's disease.

Although classic Fabry's disease results in multiple causes of death, the cardiac variant of Fabry's disease affects only the cardiac system and results in initial symmetric left ventricular (LV) hypertrophy and later LV dysfunction, asymmetric basal posterior LV wall thinning, restrictive mitral flow, and functional mitral regurgitation with end-stage chronic heart failure (CHF), leading to death. The purpose of this study was to investigate whether these findings predict prognoses in patients with cardiac Fabry's disease. In 13 consecutive men with cardiac Fabry's disease, LV wall thickness, the ejection fraction, mitral E-wave deceleration time, the LV Tei index, and functional mitral regurgitation were measured by echocardiography. Patients were followed for 5 to 96 months (mean 41 +/- 9). Eight patients developed New York Heart Association class III CHF, and 6 experienced cardiac death. A LV Tei index >0.60 and basal posterior LV wall thinning with a ratio of ventricular septal to posterior wall thickness >1.3 significantly preceded CHF and death (Tei index: 4.4 and 5.1 years; posterior wall thinning: 4.0 and 4.7 years), respectively (p <0.05). In conclusion, an increased LV Tei index and asymmetric basal posterior LV wall thinning are important echocardiographic findings that precede CHF and cardiac death in patients with cardiac Fabry's disease.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina.

OBJECTIVES: Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease. METHODS: Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis. Sixty-two consecutive patients with stable angina were grouped as follows: those with insignificant (<50%) coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on circulating CD14+ monocytes was analyzed by flow-cytometry in all patients. RESULTS: Toll-like receptor 2 had a positive correlation with the vessel score and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like receptor 4 also positively correlated with the vessel score and Gensini score (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation existed between the expression of Toll-like receptor 1 and the vessel score or Gensini score. Further, there was no significant correlation between high-sensitivity C-reactive protein and the vessel score or Gensini score. CONCLUSION: These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.

Mechanism of persistent ischemic mitral regurgitation after annuloplasty: importance of augmented posterior mitral leaflet tethering.

BACKGROUND: We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated. METHODS AND RESULTS: In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001). CONCLUSIONS: Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.