Determining Optimal Intervals for In-Person Visits During Video-Based Telemedicine Among Patients With Hypertension: Cluster Randomized Controlled Trial.

BACKGROUND: Introducing telemedicine in outpatient treatment may improve patient satisfaction and convenience. However, the optimal in-person visit interval for video-based telemedicine among patients with hypertension remains unreported in Japan. OBJECTIVE: We determined the optimal in-person visit interval for video-based telemedicine among patients with hypertension. METHODS: This was a cluster randomized controlled noninferiority trial. The target sites were 8 clinics in Japan that had a telemedicine system, and the target patients were individuals with essential hypertension. Among patients receiving video-based telemedicine, those who underwent in-person visits at 6-month intervals were included in the intervention group, and those who underwent in-person visits at 3-month intervals were included in the control group. The follow-up period of the participants was 6 months. The primary end point of the study was the change in systolic blood pressure, and the secondary end points were the rate of treatment continuation after 6 months, patient satisfaction, health economic evaluation, and safety evaluation. RESULTS: Overall, 64 patients were enrolled. Their mean age was 54.5 (SD 10.3) years, and 60.9% (39/64) of patients were male. For the primary end point, the odds ratio for the estimated difference in the change in systolic blood pressure between the 2 groups was 1.18 (90% CI -3.68 to 6.04). Notably, the criteria for noninferiority were met. Patient satisfaction was higher in the intervention group than in the control group. Furthermore, the indirect costs indicated that lost productivity was significantly lesser in the intervention group than in the control group. Moreover, the treatment continuation rate did not differ between the intervention and control groups, and there were no adverse events in either group. CONCLUSIONS: Blood pressure control status and safety did not differ between the intervention and control groups. In-person visits at 6-month intervals may cause a societal cost reduction and improve patient satisfaction during video-based telemedicine. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000040953; https://tinyurl.com/2p8devm9.

The relationship between tissue RBC n-3 fatty acids and pulse wave velocity.

Consumption of n-3 fatty acids is well-known to prevent deaths from coronary heart disease. However, not many studies have investigated the effects of n-3 fatty acids on arteriosclerosis in free living subjects. The pulse wave velocity between the brachia and ankles (baPWV) of 161 healthy male subjects was measured and the fatty acid composition of the total phospholipid fraction of their red blood cells (RBC) analyzed. There was a significant inverse correlation between the eicosapentaenoic acid concentrations in the RBC phospholipid fraction and baPWV of the subjects after adjustment for age, pulse rate and diastolic pressure, or further for body mass index, smoking status, diabetes and the ratio of low-density cholesterol to high-density cholesterol. Although baPWV values may not directly indicate arteriosclerosis, the present study suggests that long-term n-3 fatty acid intake is beneficial for the vascular system.

The effects of eicosapentaenoic acid-fortified food on inflammatory markers in healthy subjects--A randomized, placebo-controlled, double-blind study.

Epidemiological studies showed that habitual fish intakes were associated with lower blood inflammatory markers. In the present study the effects of a fish oil-containing food on inflammatory markers were investigated in healthy, mostly middle-aged subjects (59 men and 82 women) with normal to mildly elevated triglyceride levels. Study subjects were randomly allocated to two groups in a double-blind manner; one group ingested an eicosapentaenoic acid (EPA)-rich fish oil-fortified drink (0.60 g EPA+0.26 g docosahexaenoic acid/d. EPA group, n=68) for 12 wk. The rest of the subjects took a placebo (control group, n=73). Plasma levels of high sensitivity C-reactive protein (hs-CRP) and soluble tumor necrosis factor-receptors 1 and 2 (sTNF-Rs 1 and 2) were measured at the start and end of intervention. EPA concentrations in the total RBC phospholipid fraction significantly increased by 79% in the EPA group at the end of the study, and they changed very little in the control group (+0.68%). The inflammatory markers did not change in either group. It is likely that fish oil does not change hs-CRP or sTNF-Rs 1 or 2 in subjects without active inflammation.

Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: We previously reported that administration of fish oil rich in docosahexaenoic acid (DHA) increased the plasma ratio of epinephrine to norepinephrine (NE) at rest in young adults who were under chronic stress and that this effect was achieved mainly through depression of NE. However, not many reports have documented the effects of eicosapentaenoic acid (EPA) and DHA on blood catecholamine levels in healthy humans. Therefore, we performed another intervention study to test their effect on catecholamines with healthy subjects under no chronic stress. METHODS: Twenty-one healthy young adults (15 men and 6 women) were randomly assigned to an omega-3 group (n = 9) or a control group (n = 12) in a double-blind manner. Twenty capsules of shellfish-derived lipids containing 762 mg of EPA plus DHA per day were administered to the omega-3 group for 2 mo. The controls took the same amount of placebo capsules. Fasting blood samples after a 30-min rest with a catheter in a forearm vein were obtained at the start and the end of the study for catecholamine measurements. RESULTS: EPA but not DHA concentrations in red blood cells significantly increased in the omega-3 group compared with the control group (P < 0.001). Plasma NE concentrations were significantly decreased in the omega-3 group (from 1.49 +/- 0.39 nmol/L to 1.05 +/- 0.14 nmol/L) compared with the control group (from 1.12 +/- 0.24 nmol/L to 1.39 +/- 0.32 nmol/L) with analysis of covariance (P < 0.001). The differences remained significant (P = 0.01) even after deletion of three subjects in the omega-3 group who had the highest baseline NE values and one in the control group who had the lowest baseline NE value to nullify a significant baseline differences in NE between groups. CONCLUSION: This study demonstrated that EPA plus DHA supplementation lowered plasma NE concentrations in normal volunteers even at the small dose of 762 mg of EPA plus DHA per day. This effect of EPA plus DHA to lower plasma NE concentrations may be important to understand some of the effects of fish oils on diseases.

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans.

A large number of papers have reported that administration of n-3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n-3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n = 41) whose serum TG concentrations were 100-300 mg/dL were recruited and randomly assigned to either an n-3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n-3 FA group were administered 125 mL of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8, and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n-3 FA group, with no significant changes in the control group. TG levels decreased more in the n-3 FA group than in the control group at weeks 4 (P < 0.05), 8 (P < 0.01), and 12 (P < 0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n-3 FA group than in the control at weeks 8 (P < 0.01) and 12 (P < 0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n-3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.

Multistep ion channel remodeling and lethal arrhythmia precede heart failure in a mouse model of inherited dilated cardiomyopathy.

BACKGROUND: Patients with inherited dilated cardiomyopathy (DCM) frequently die with severe heart failure (HF) or die suddenly with arrhythmias, although these symptoms are not always observed at birth. It remains unclear how and when HF and arrhythmogenic changes develop in these DCM mutation carriers. In order to address this issue, properties of the myocardium and underlying gene expressions were studied using a knock-in mouse model of human inherited DCM caused by a deletion mutation ΔK210 in cardiac troponinT. METHODOLOGY/PRINCIPAL FINDINGS: By 1 month, DCM mice had already enlarged hearts, but showed no symptoms of HF and a much lower mortality than at 2 months or later. At around 2 months, some would die suddenly with no clear symptoms of HF, whereas at 3 months, many of the survivors showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration (APD) was prolonged. Transient outward (I(to)) and ultrarapid delayed rectifier K(+) (I(Kur)) currents were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In LVs at 3-months, more frequent spontaneous activity, greater prolongation of APD and further down-regulation in above K(+) channels were observed. At 1 month, in contrast, infrequent spontaneous activity and down-regulation of Kv4.2, but not Kv1.5 or KChIP2, were observed. CONCLUSIONS/SIGNIFICANCE: Our results suggest that at least three steps of electrical remodeling occur in the hearts of DCM model mice, and that the combined down-regulation of Kv4.2, Kv1.5 and KChIP2 prior to the onset of HF may play an important role in the premature sudden death in this DCM model. DCM mice at 1 month or before, on the contrary, are associated with low risk of death in spite of inborn disorder and enlarged heart.

Causes of abnormal Ca2+ transients in Guinea pig pathophysiological ventricular muscle revealed by Ca2+ and action potential imaging at cellular level.

BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under a variety of pathophysiological conditions including ventricular tachycardia. To clarify whether these abnormal Ca(2+) transients can be attributed to abnormal action potential generation or abnormal Ca(2+) handling/excitation-contraction (EC) coupling, we developed a procedure to determine Ca(2+) and action potential signals at the cellular level in isolated heart tissues. METHODOLOGY/PRINCIPAL FINDINGS: After loading ventricular papillary muscle with rhod-2 and di-4-ANEPPS, mono-wavelength fluorescence images from rhod-2 and ratiometric images of two wavelengths of emission from di-4-ANEPPS were sequentially obtained. To mimic the ventricular tachycardia, the ventricular muscles were field-stimulated in non-flowing Krebs solution which elicited abnormal Ca(2+) transients. For the failed and alternating Ca(2+) transient generation, there were two types of causes, i.e., failed or abnormal action potential generation and abnormal EC coupling. In cells showing delayed initiation of Ca(2+) transients with field stimulation, action potential onset was delayed and the rate of rise was slower than in healthy cells. Similar delayed onset was also observed in the presence of heptanol, an inhibitor of gap junction channels but having a non-specific channel blocking effect. A Na(+) channel blocker, on the other hand, reduced the rate of rise of the action potentials but did not result in desynchronization of the action potentials. The delayed onset of action potentials can be explained primarily by impaired gap junctions and partly by Na(+) channel inactivation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that there are multiple patterns for the causes of abnormal Ca(2+) signals and that our methods are useful for investigating the physiology and pathophysiology of heart muscle.

Aberrant cell-to-cell coupling in Ca2+-overloaded guinea pig ventricular muscles.

To investigate how intercellular coupling can be changed during Ca2+ overloading of ventricular muscle, we studied Ca2+ signals in individual cells and the histochemistry of the major gap junction channel, connexin43 (Cx43), using multicellular preparations. Papillary muscles were obtained from guinea pig ventricles and loaded with rhod-2. Sequential Ca2+ images of surface cells were obtained with a confocal microscope. In intact muscles, all cells showed simultaneous Ca2+ transients in response to field stimulation over a field of view of 0.3 x 0.3 mm2. In severely Ca2+-overloaded muscles, obtained by high-frequency stimulation in nonflowing Krebs solution, cells became less responsive to stimulation. Furthermore, nonsimultaneous but serial onsets of Ca2+ transients were often detected, suggesting a propagation delay of action potentials. The time lag of the onset between two aligned cells was sometimes as long as 100 ms. Similar lags were also observed in muscles with gap junction channels inhibited by heptanol. To investigate whether the phosphorylation state of Cx43 is affected in Ca2+-overloaded muscles, the distributions of phosphorylated and nonphosphorylated Cx43 were determined using specific antibodies. Most of the Cx43 was phosphorylated in the nonoverloaded muscles, whereas nonphosphorylated Cx43 was significantly elevated in severely Ca2+-overloaded muscles. Our results suggest that the propagation delay of action potential within a small area, a few square millimeters, can be a cause of abnormal conduction and a microreentry in Ca2+-overloaded heart. Inactivation of Na+ channels and inhibition of gap junctional communication may underlie the cell-to-cell propagation delay.

Intravascular ultrasound assessment of atherosclerotic plaque in the aorta.

BACKGROUND: Intravascular ultrasound (IVUS) has been used for assessment of the coronary arteries. However, few IVUS studies have been reported on the aorta. MATERIALS AND METHODS: To assess the presence of atherosclerotic disease in the aorta by the use of IVUS, 29 patients with heart disease (24 men and 5 women; mean age, 61+/-11 years) including ischemic heart disease (n=21) and valvular disease or dilated cardiomyopathy (n=8) were enrolled in the study. An IVUS catheter was inserted through the femoral artery, and IVUS images were obtained in the descending aorta (DA) at the level of the pulmonary artery bifurcation, and in the proximal and distal regions of the abdominal aorta (AA) at the level of the renal artery bifurcation. Percent plaque area (%PA) was calculated as vessel cross-sectional area surrounded by media minus lumen cross-sectional area divided by vessel cross-sectional area. RESULTS: %PAs differed significantly between the three aortic levels: DA, 14.9+/-5.5%; proximal AA, 19.0+/-6.9%; and distal AA, 28.3+/-9.7% (p<0.05). However, PA did not differ significantly between the three levels (DA, 94.7+/-38.0 mm2; proximal AA, 90.9+/-35.0 mm2; distal AA, 79.7+/-32.3 mm2). %PA and PA in the DA and proximal AA correlated with age (r=0.39-0.46, p<0.05), but not with coronary angiography findings or multiple risk factors. CONCLUSIONS: The aortic plaque is clearly observed by IVUS. The plaque is diffuse at the 3 levels, had little relationship with risk factor of arteriosclerosis or coronary artery disease, and aging affected the increase of plaque.