Distribution and Characteristics of Hypouricemia within the Japanese General Population: A Cross-Sectional Study.

Background and objectives: There is insufficient epidemiological knowledge of hypouricemia. In this study, we aimed to describe the distribution and characteristics of Japanese subjects with hypouricemia. Materials and Methods: Data from subjects who underwent routine health checkups from January 2001 to December 2015 were analyzed in this cross-sectional study. A total of 246,923 individuals, which included 111,117 men and 135,806 women, met the study criteria. The participants were divided into quartiles according to their serum uric acid (SUA) levels. We subdivided the subjects with hypouricemia, which was defined as SUA level ≤ 2.0 mg/dL, into two groups and compared their characteristics, including their cardiovascular risks. Results: The hypouricemia rates were 0.46% overall, 0.21% for the men and 0.66% for the women (P < 0.001). The number of the subjects with hypouricemia showed two distributions at SUA levels of 0.4⁻1.1 mg/dL (lower hypouricemia group), which included a peak at 0.7⁻0.8 mg/dL, and at SUA levels of 1.4⁻2.0 mg/dL (higher hypouricemia group). The men in the higher hypouricemia group had lower body mass indexes (BMI) and triglyceride (TG) levels and had higher fasting blood glucose levels than those in the lower hypouricemia group. The women in the higher hypouricemia group were younger; had lower BMI, total protein, TG, total cholesterol and low-density lipoprotein cholesterol levels; and had higher estimated glomerular filtration rates levels compared to those in the lower hypouricemia group. Conclusions: The characteristics of the individuals in the lower and higher hypouricemia groups differed significantly, indicating different pathophysiologies within each group.

Uric Acid Level and New-Onset Atrial Fibrillation in the Japanese General Population　- Longitudinal Study.

BACKGROUND: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated. Methods and Results: We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0-4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5-6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15-2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, -0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes. CONCLUSIONS: Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.

Association of Serum Triglycerides With Arterial Stiffness in Subjects With Low Levels of Low-Density Lipoprotein Cholesterol.

BACKGROUND: The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C). Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80-119, 120-159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C <79 mg/dL (OR, 3.611, 95% CI, 2.475-5.337; P<0.0001) and 80-119 mg/dL (OR, 1.881; 95% CI, 1.602-2.210; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL. In the multivariate analysis, high TG was significantly associated with high baPWV in LDL-C ≤79 mg/dL (OR, 2.558; 95% CI, 1.348-4.914; P=0.0040) and LDL-C 80-119 mg/dL (OR, 1.677; 95% CI, 1.315-2.140; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL. CONCLUSIONS: High TG and increased arterial stiffness showed an independent relationship in a Japanese general population with LDL-C ≤119 mg/dL. TG-lowering therapy might be an additional therapeutic consideration in these subjects.

High Pulse Wave Velocity Has a Strong Impact on Early Carotid Atherosclerosis in a Japanese General Male Population.

BACKGROUND: Although there have been several reports on the risk factors associated with intima-media thickness (IMT), many questions remain. The purpose of this study was to investigate the association between IMT and cardiovascular risk factors in a Japanese general population.Methods and Results:The study group consisted of 1,583 male subjects undergoing routine health checkups. IMT of the common carotid artery was measured by high-resolution ultrasonography. Brachial-ankle pulse wave velocity (baPWV) was measured using an automated device. Univariate analysis demonstrated that carotid IMT significantly associated with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), baPWV, fasting glucose, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Multiple logistic regression analysis for carotid atherosclerosis (carotid IMT ≥1.0 mm) was performed using obesity (BMI ≥25.0 kg/m2), high BP (SBP ≥130 mmHg or DBP ≥85 mmHg), dyslipidemia (LDL-C ≥140 mg/dL, TG ≥150 mg/dL, or HDL-C <40 mg/dL), impaired fasting glucose (IFG) (fasting glucose ≥110 g/dL), and high baPWV (≥1,400 cm/s). Carotid atherosclerosis was significantly associated with only high baPWV (OR: 2.22, 95% CI: 1.24-4.17, P<0.01). CONCLUSIONS: High baPWV was a stronger predictor of early carotid atherosclerosis than high BP, dyslipidemia, or IFG in a Japanese general male population.

Uric Acid Level and Prevalence of Atrial Fibrillation in a Japanese General Population of 285,882.

BACKGROUND: The association between serum uric acid (UA) levels and atrial fibrillation (AF) in the general population in Japan is not well known.Methods and Results:In total, 285,882 consecutive subjects (men, 130,897; women, 154,985; age, 58±15 years) not receiving treatment for hyperuricemia who underwent health checkups were enrolled. Subjects were stratified into deciles according to age, body mass index, estimated glomerular filtration rate, systolic blood pressure, and UA level. AF prevalence was calculated for each decile. The odds ratio that defined the decile with the lowest AF prevalence as reference was calculated in each sex. In men, the mean UA was 6.0±1.4 mg/dl; AF prevalence was 1.8% and was lowest in the decile with UA 4.4-4.9 mg/dl. Deciles with both high and low UA (5.4-5.6 mg/dl to >7.8 mg/dl and <4.3 mg/dl) were associated with significantly higher AF prevalence. In women, the mean UA was 4.5±1.1 mg/dl; AF prevalence was 0.7% and was lowest in the decile with UA 3.6-3.8 mg/dl. Deciles with highest UA (5.0-5.2 mg/dl to >5.9 mg/dl) were associated with significantly higher AF prevalence. The analysis adjusted for other clinical covariates demonstrated an independent association between UA and AF in both sexes. CONCLUSIONS: In a representative Japanese general population, UA level was significantly associated with AF, independently of other cardiovascular risk factors. (Circ J 2016; 80: 2453-2459).

Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population.

BACKGROUND: The prevalence of diabetes mellitus (DM) has been increasing. The present study was carried out to examine the relationship between this increase and fatty liver. METHODS: Japanese participants who underwent regular health examinations in 1991, 1996, 2001, 2006, and 2011 were enrolled. Fatty liver was diagnosed using ultrasonography. DM was defined as requiring the use of medication for DM, having a fasting blood glucose level ≥ 126 mg/dl, or hemoglobin A1c level ≥ 6.5 %. RESULTS: Logistic regression analysis on data from 11,235 participants (6,882 men and 4,271 women) in 2011 revealed that the association between fatty liver and DM was independent of age, body composition, and other confounders [odds ratio (OR) 1.97, 95 % confidence interval (95 % CI) 1.66-2.32 in men, and OR, 3.12; 95 % CI, 2.29-4.26 in women]. In 2006, 5,318 participants did not have DM and were able to be followed up in 2011. Fatty liver in 2006 was an independent predictor of DM in 2011 [OR 1.73 (95 % CI 1.20-2.50) in men, 4.13 (2.16-8.10) in women]. The prevalence of DM increased significantly during the 20-year period examined among both men (6.0, 8.9, 10.0, 10.8, 12.0 %, P < 0.001) and women (3.3, 4.5, 4.2, 4.1, 5.1 %, P = 0.004), accompanied with an increased prevalence of fatty liver among both men (10.8, 26.3, 33.8, 36.7, and 38.0 %, P < 0.001) and women (6.5, 16.7, 22.2, 21.3, and 20.8 %, P < 0.001). CONCLUSION: Fatty liver independently predicts both present and future DM. Fatty liver may play an important role in the recent increases in the prevalence of DM.

The role of infection in the development of non-valvular atrial fibrillation: up-regulation of Toll-like receptor 2 expression levels on monocytes.

Many studies have suggested that inflammation may participate in the pathogenesis of non-valvular atrial fibrillation (AF). However, it has been unknown by exposure to what the inflammation is caused. Recently, we reported that Toll-like receptor 2 (TLR2) level on monocytes was significantly up-regulated in viral and bacterial infections, but not in non-infectious inflammatory states. Our purpose was to test the hypothesis that expression of TLR2 levels may be up-regulated in patients with non-valvular AF. A total of 48 consecutive patients with non-valvular AF who were hospitalized for catheter ablation were enrolled in this study. TLR2 levels were assayed by using flow-cytometric analysis and compared with volunteers in sinus rhythm (control group, n = 24). Additionally, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assayed, and the left atrial volume indexes (LAVI) in the non-valvular AF group were measured. The results demonstrated that TLR2 levels in the non-valvular AF group were significantly higher than in the control group (median, 4682 vs. 3866 sites/cell; P < 0.01). Moreover, non-valvular AF patients had significantly higher IL-6 levels than controls. However, there was no significant difference in CRP levels between the two groups. It was observed in 44 AF patients, in whom pulmonary vein isolation was confirmed to be successful, that the LAVI significantly diminished 1 month after ablation (median, 33.6 vs. 29.5 ml/m²; P < 0.001), but not the TLR2 and IL-6 levels. Our results implied that an infectious inflammation may participate in the pathogenesis of non-valvular AF.

Classification of acute myocardial ischemia by artificial neural network using echocardiographic strain waveforms.

Echocardiographic strain waveforms are highly variable, so their interpretation is experience-dependent and subjective. We tested whether an artificial neural network (ANN) can distinguish between strain waveforms obtained at baseline and during experimentally induced acute ischemia. An open-chest model of coronary occlusion and acute ischemia was used in 14 adult pigs. Strain waveforms were obtained using a GE Vivid 7 ultrasound system. An ANN design was implemented in MATLAB, and backpropagation and "leave-one-out" processes were used to train and test it. Specificity of 86% and sensitivity of 87% suggest that ANNs could aid in diagnostic prescreening of echocardiographic strain waveforms.

Parametric detection and measurement of perfusion defects in attenuated contrast echocardiographic images.

OBJECTIVE: Attenuation of radio frequency (RF) signals limits the use of contrast echocardiography. The harmonic-to-fundamental ratio (HFR) of the RF signals compensates for attenuation. We tested whether HFR analysis measures the left ventricular nonperfused area under simulated experimental attenuation. METHODS: Radio frequency image data from short axis systolic projections were obtained from 11 open-chest dogs with left anterior descending or left circumflex coronary artery occlusion followed by left atrial bolus injection of a perflutren microbubble contrast agent. Clinical attenuation was simulated by calibrated silicone pads interposed between the epicardial surface and the transducer to induce mild (7-dB) and severe (14-dB) reduction of the backscattered RF signals. Harmonic-to-fundamental ratio values were calculated for each image pixel for 0-, 7-, and 14-dB attenuation conditions and reproducibly showed a "perfused area" and a "nonperfused area." A reference nonperfused area was obtained by manual delineation in high-quality contrast scans. RESULTS: Correlations of the HFR-detected and manually outlined perfusion defect areas were R = 0.92 for 0 dB, R = 0.94 for 7 dB, and R = 0.90 for 14 dB; the mean difference was less than 0.36 cm(2) (negligible) in all 3 attenuation settings. Conclusions. Attenuation compensation by our HFR method allows precise measurement of myocardial perfusion defect areas in contrast scans with simulated high level of attenuation.

A pilot study to assess the use of protein a immunoadsorption for chronic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a leading cause of end-stage heart failure and cardiac transplantation. Anticardiac antibodies are common and removal of these through immunoadsorption (IA) is associated with improvement in global cardiac function. The effect of IA on regional function and quality of life (QOL) without intravenous immunoglobulin (IVIG) substitution has not been described. We performed a pilot trial using Immunosorba columns in four patients with chronic DCM and NYHA Class II-III congestive heart failure. Subjects were followed for 6 months with serial echocardiograms and validated QOL assessments. Regional and global left ventricular (LV) end-systolic deformations were assessed by two-dimensional strain echocardiography. Total IgG decreased 95% (from 1,210 +/- 274 mg/dl to 57 +/- 16 mg/dl, P = 0.003) and IgG3 decreased 61% (from 33 +/- 16 mg/dl to 13 +/- 7 mg/dl, P = 0.024). QOL improved from baseline to 6 months as assessed by the Living with Heart Failure questionnaire (from 54 +/- 18 to 19 +/- 7, P = 0.029). Mean LV ejection fraction improved from 35 to 40% at Day 5 and to 44% at 6 months (P = NS). The LV end diastolic and end systolic volumes decreased (220-202 ml, 159-130 ml, P = NS) at 6 months. Global end-systolic strain improved from -7.3% at baseline to -8.5% at Day 5 and -8.8% at 6 months (P = NS). Regional LV function and response to IA was not uniform. Even without IVIG substitution, IA for the treatment of chronic DCM is associated with improved QOL up to 6 months after treatment. A randomized, sham-controlled trial is required to confirm the benefits of IA for DCM.

Left ventricular isovolumic flow sequence during sinus and paced rhythms: new insights from use of high-resolution Doppler and ultrasonic digital particle imaging velocimetry.

OBJECTIVES: We sought to clarify the role of isovolumic intervals during a cardiac cycle by in vivo visualization of left ventricular (LV) intracavitary flow dynamics. BACKGROUND: Asynchronous LV deformation during isovolumic contraction (IVC) and isovolumic relaxation (IVR) might represent a transient feature of myocardial wall mechanics that reverses the direction of blood flow. METHODS: In 10 beating porcine hearts, the changes in LV intracavitary flow were recorded at baseline and after LV epicardial and right atrial pacing with high-resolution Doppler and contrast echocardiography. Two-dimensional vector flow fields were generated offline from B-mode contrast images with particle imaging velocimetry. RESULTS: During IVC, flow from the LV apex accelerated toward the base, whereas blood from the base was redirected toward the outflow through formation of an anterior vortex. Conversely, during IVR, flow was initially directed toward the apex and then briefly reversed toward the base. Epicardial pacing from the LV base altered the stages of flow redirection during the pre-ejection period and delayed mitral valve closure (28 +/- 14 ms vs. 61 +/- 13 ms, p < 0.001) and aortic valve opening (77 +/- 18 ms vs. 111 +/- 18 ms, p = 0.004). CONCLUSIONS: Isovolumic intervals are not periods of hemodynamic stasis but, rather, phases with dynamic changes in intracavitary flow. Experimentally induced aberrant epicardial electrical activation alters stages of flow redirection and prolongs the pre-ejection period. Normal electromechanical activation through the His-Purkinje system in mammalian hearts maintains an inherent synchrony with the sequence of intracavitary flow redirection.

High spatial resolution speckle tracking improves accuracy of 2-dimensional strain measurements: an update on a new method in functional echocardiography.

BACKGROUND: We previously found that a 2-dimensional (2D) strain echocardiography method had some limitations in the assessment of low magnitudes and rates of deformation. Here, we study whether a recently introduced high spatial resolution speckle tracking (HRT) method improves accuracy of 2D strain measurements. METHODS: A gelatin block was cyclically compressed by a hydraulic piston. Regional deformations measured by 2D-HRT were compared with reference strains obtained from an embedded pair of sonomicrometry crystals. Global deformations (along the gelatin block) were compared to strains calculated from tracings of piston motion. We tested a wide range of strains (5.4%-21.5%) and combined each measurement with simulated heart rates (24-196/min). RESULTS: Regional deformations measured by 2D-HRT demonstrated excellent correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = -0.3 +/- 1.3%) with sonomicrometry. Close correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = 0.5 +/- 1.2%) was observed also for global strains measured by 2D-HRT and compared with tracings of piston motion. There was good reproducibility of all tests: interobserver and intraobserver variabilities were 3.2% and 3.4% for regional strains and 3.1% and 3.5% for global strains, respectively. CONCLUSION: In our in vitro setting, the 2D-HRT method produced precise and accurate measurements of strains for clinically relevant ranges of deformation magnitudes and ranges.

Parametric harmonic-to-fundamental ratio contrast echocardiography: a novel approach to identification and accurate measurement of left ventricular area under variable levels of ultrasound signal attenuation.

OBJECTIVES: We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation. BACKGROUND: Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography. METHODS: RF data from short axis systolic and diastolic scans were obtained from 14 open-chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7dB or 14dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0dB, 7dB and 14dB attenuation conditions, and LV area obtained by summation of "LV cavity pixels". A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts. RESULTS: Correlation of the HFR-defined and reference areas at systole was R=0.95, R=0.94, and R=0.91 for 0dB, 7dB and 14dB levels of attenuation, respectively, and at diastole was R=0.95 for 0dB, 7dB and 14dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm(2) (i.e. negligible) in all attenuation settings. CONCLUSION: Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals.

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.

Usefulness of a novel ultrasound transducer for continuous monitoring treadmill exercise echocardiography to assess coronary artery disease.

BACKGROUND: The feasibility of a novel ultrasound probe, which can be attached to the left ventricular (LV) apex chest wall and allows free rotation around its long axis direction for the continuous monitoring of LV wall motion, was tested. METHODS AND RESULTS: There were 36 subjects who had coronary artery disease (CAD). By attaching a novel ultrasound probe to the chest wall, the LV apical views were recorded during treadmill exercise stress echocardiography (Echo). The continuous monitoring of LV wall motion was satisfactorily feasible in 30 of 36 patients. The visualization rate of the overall LV segments was higher at rest (90%) compared to that during peak exercise (77%). The segments were better visualized in apical portions (90-100%) than in mid (77-96%) or basal portions (68-87%). The sensitivity, specificity, and accuracy for detecting CAD were 61, 100 and 77%, respectively. The wall motion score index 3 and 6 min after exercise decreased significantly compared to those at peak exercise. The number of segments with dyssynergy was highest at the peak exercise. Ischemic ST-T depression on electrocardiography was observed only at peak stress periods. CONCLUSIONS: Continuous monitoring treadmill exercise Echo using a novel ultrasound probe seems feasible for the non-invasive and physiological assessment of CAD.

Increased Tei index suggests absence of adequate coronary reperfusion in patients with first anteroseptal acute myocardial infarction.

BACKGROUND: The estimation of coronary reperfusion in acute myocardial infarction (AMI) is important. The left ventricular (LV) Tei index is a noninvasive and sensitive parameter expressing overall LV function. We hypothesized that patients without good coronary reperfusion have worse LV function with a higher or worse Tei index compared to those with good reperfusion. METHODS AND RESULTS: In 85 patients with first anteroseptal AMI, without other cardiac lesions such as prior myocardial infarction, LV hypertrophy or valvular disease, the Tei index was measured using Doppler echocardiography immediately after patients' arrival to the hospital, and the Thrombolysis in Myocardial Infarction (TIMI) grade was evaluated through subsequent coronary angiography. The Tei index was significantly greater in patients who did not have TIMI score of 3 compared to those with a TIMI of 3 (0.60+/-0.13 vs 0.46+/-0.06, p<0.0001). A Tei index >0.50 as the criteria for the absence of TIMI 3 had the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 75, 86, 94, 54 and 78%, respectively. CONCLUSION: An increased Tei index suggests the absence of adequate coronary reperfusion in patients with first anterior AMI without other lesion.

Prediction of prognosis in the UM-X7.1 hamster model of congestive heart failure using the Tei index.

BACKGROUND: Cardiac function is difficult to evaluate in small animal models of heart disease. The Doppler Tei index is a simple and non-invasive measure that can express global cardiac function even in small animal models of congestive heart failure. However, its ability to predict prognosis has not been evaluated. METHODS AND RESULTS: We tested the hypothesis that cardiac functional indices, such as the Tei index, can predict the prognosis of hamsters with cardiac dysfunction. The Tei index, defined as the sum of the isovolume contraction and relaxation time divided by ejection time, and the percent fractional shortening of the left ventricle was measured in 48 anesthetized male hamsters (19.7+/-0.4 weeks old) with cardiac dysfunction (UM-X7.1), using Doppler and 2-dimensional echocardiography. The hamsters were separated into 2 groups based on the median Tei index (0.50) and % fractional shortening (FS) (21%). Kaplan-Meier analysis determined the survival rates of the groups. Both the Tei index and %FS enabled significant distinction of better and poorer survival (p < 0.01), and the survival curves were less overlapped when the animals were separated according to the Tei index. CONCLUSION: The Tei index can predict prognosis in a small animal model of heart failure.

Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients with localized basal inferior left ventricular remodeling: insights from tissue Doppler strain imaging.

OBJECTIVES: The purpose of this research was to test whether papillary muscle (PM) dysfunction attenuates ischemic mitral regurgitation (MR) in patients with left ventricular (LV) remodeling of a similar location and extent. BACKGROUND: Papillary muscle dysfunction could attenuate tethering and MR because of PM elongation. However, variability in the associated LV remodeling, which exaggerates tethering, can influence the relationship between PM dysfunction and MR. METHODS: In 40 patients with a previous inferior myocardial infarction but without other lesions, the LV volume, sphericity, PM tethering distance, PM longitudinal systolic strain, and MR fraction were quantified by echocardiography. The patients were divided into two groups: group 1 with significant basal inferoposterior LV bulging but without advanced LV bulging involving other territories, therefore with a similar location and extent of LV remodeling, and group 2 without significant LV bulging. RESULTS: The medial PM tethering distance was significantly correlated with the %MR fraction (r2 = 0.64, p < 0.01), and multiple regression analysis identified an increase in the tethering distance as the only independent determinant of the MR fraction in all subjects and also in group 1. The PM longitudinal systolic strain had no significant relationships with MR fraction in all subjects with variable degrees of LV remodeling, but it had a significant inverse correlation with the MR fraction (r2 = 0.33, p < 0.01) in group 1 with LV remodeling of a similar location and extent, indicating that PM dysfunction is associated with less MR. CONCLUSIONS: Papillary muscle dysfunction, reducing its longitudinal contraction to induce leaflet tethering, attenuates ischemic MR in patients with basal inferior LV remodeling.

Repeated sauna therapy increases arterial endothelial nitric oxide synthase expression and nitric oxide production in cardiomyopathic hamsters.

BACKGROUND: Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. METHODS AND RESULTS: Normal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39 degrees C followed by 20 min at 30 degrees C. This procedure raised the rectal temperatures by about 1 degrees C. Arterial endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein expressions were examined, and serum concentrations of nitrate were measured. The expression of eNOS mRNA in the aortas of normal controls did not change, whereas those of the TO-2 hamsters decreased with age. Four weeks of sauna therapy significantly increased eNOS mRNA expression in the aortas of TO-2 hamsters compared with those that did not undergo sauna therapy. Sauna therapy also upregulated aortic eNOS protein expression. Serum nitrate concentrations of the TO-2 hamsters were increased by 4 weeks of sauna therapy compared with those that did not undergo sauna. CONCLUSION: Repeated sauna therapy increases eNOS expression and NO production in cardiomyopathic hamsters with heart failure.