Effects of cardiac rehabilitation on in vivo nailfold microcirculation in patients with cardiovascular disease.

This study aimed to explore the impact of cardiac rehabilitation (CR) on in vivo and ex vivo microcirculation, exercise capacity, and oxidative stress in patients with cardiovascular disease (CVD). The study included patients with acute coronary syndrome (ACS; n = 45; age, 69.0 ± 14.1 years) and heart failure (HF; n = 66; age, 77.3 ± 10.7 years) who underwent supervised CR during hospitalization. The control group comprised patients without CVD (NCVD; n = 20; age, 75.9 ± 11.2 years). In vivo microcirculatory observations using nailfold video capillary endoscopy at rest and during hyperemia, exercise capacity, and oxidative stress were assessed at baseline and 12 weeks after discharge. Baseline capillary densities were significantly lower in the ACS (5.0 ± 1.7 capillaries/mm2) and HF (4.9 ± 1.7 capillaries/mm2) groups than in the NCVD group (6.5 ± 1.1 capillaries/mm2, p < 0.01). Similarly, capillary density during reactive hyperemia was significantly lower in the ACS (5.8 ± 1.7 capillaries/mm2) and HF (5.4 ± 1.8 capillaries/mm2) groups than in the NCVD group (7.3 ± 1.4 capillaries/mm2, p < 0.01). Patients with ACS and HF had increased capillary densities at 12 weeks compared with at baseline (p < 0.05). This improvement was particularly pronounced among post-discharge outpatient CR participants (n = 20). Grip strength, exercise capacity, and oxidative stress improved at 12 weeks. Baseline capillary density changes were positively correlated with grip strength changes (r = 0.45, p < 0.001). CR significantly improved nailfold capillary density in patients with ACS and HF 12 weeks after discharge.

Pathophysiology and Treatment of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition in which an organic thrombus remains in the pulmonary artery (PA) even after receiving anticoagulation therapy for more than 3 months and is complicated by pulmonary hypertension (PH), leading to right-sided heart failure and death. CTEPH is a progressive pulmonary vascular disease with a poor prognosis if left untreated. The standard treatment for CTEPH is pulmonary endarterectomy (PEA), which is usually performed only in specialized centers. In recent years, balloon pulmonary angioplasty (BPA) and drug therapy for CTEPH have also shown good results. This review discusses the complex pathogenesis of CTEPH and presents the standard of care, PEA, as well as a new device called BPA, which is showing remarkable progress in efficacy and safety. Additionally, several drugs are now demonstrating established evidence of efficacy in treating CTEPH.

Early diastolic mitral regurgitation in left ventricular aneurysm.

Diastolic mitral regurgitation is a type of functional mitral regurgitation that develops via a reversal of the left atrioventricular pressure gradient during diastole. This study aimed to explore the mechanism underlying early diastolic mitral regurgitation (EDMR) in patients with left ventricular (LV) aneurysms after anterior myocardial infarction (AMI) by assessing the intraventricular pressure difference using vector flow mapping. We enrolled 23 consecutive patients with LV aneurysms (with and without EDMR) and 15 healthy men as controls. In the control group, LV suction began from the apex during early diastole. In contrast, the blood that pooled in the apical aneurysm during systole generated a relatively higher pressure at the apex than at the basal LV during early diastole; consequently, the pressure reversal phenomenon occurred in the LV. Compared to the EDMR- group, the EDMR + group (n = 7) exhibited a significantly higher diastolic time ratio ([time from the second heart sound to the pressure inversion point]/[total diastolic time]) (P < 0.001). The diastolic time ratio was significantly correlated with log BNP, but not with E/A, E/E', or the left atrial expansion index. In conclusion, EDMR in LV aneurysm may be due to a prolonged diastolic time ratio leading to prolonged pressure inversion in the LV during early diastole.

Effects of whole-body neuromuscular electrical stimulation device on hemodynamics, arrhythmia, and sublingual microcirculation.

Neuromuscular electrical stimulation has been used to treat cardiovascular diseases and other types of muscular dysfunction. A novel whole-body neuromuscular electrical stimulation (WB-NMES) wearable device may be beneficial when combined with voluntary exercises. This study aimed to investigate the safety and effects of the WB-NMES on hemodynamics, arrhythmia, and sublingual microcirculation. The study included 19 healthy Japanese volunteers, aged 22-33 years, who were not using any medication. Electrocardiogram (ECG), echocardiography, and blood sampling were conducted before a 20-min WB-NMES session and at 0 and 10 min after termination of WB-NMES. Their tolerable maximum intensity was recorded using numeric rating scale. Arrhythmia was not detected during neuromuscular electrical stimulation or during 10 min of recovery. Blood pressure, heart rate, left ventricular ejection fraction, and diastolic function remained unchanged; however, mild mitral regurgitation was transiently observed during WB-NMES in a single male participant. A decrease in blood glucose and an increase in blood lactate levels were observed, but no changes in blood fluidity, sublingual microcirculation, blood levels of noradrenaline, or oxidative stress were shown. WB-NMES is safe and effective for decreasing blood glucose and increasing blood lactate levels without changing the blood fluidity or microcirculation in healthy people.

Extended Sedentary Time Increases the Risk of All-Cause Death and New Cardiovascular Events in Patients With Diabetic Kidney Disease.

BACKGROUND: Sedentary behavior may be an independent risk factor for cardiovascular events. This study aimed to clarify the effects of extended sedentary time in patients with diabetic kidney disease (DKD) on the risk of all-cause death and new events.Methods and Results:A prospective cohort study was performed over 39 months. The study included 173 patients with DKD who completed the International Physical Activity Questionnaire (IPAQ) (101 men; mean age, 71±11 years); 37 patients (21.4%) were diagnosed with cardiovascular disease (CVD). New events were defined as all-cause death, cerebral stroke, or CVD requiring hospitalization or commencing hemodialysis (HD). Data were analyzed using a multivariate Cox proportional hazard regression model with variables, including sedentary time. There were 34 cases of new events during the observation period, including 4 cases of stroke, 20 cases of CVD, 4 cases of HD implementation, and 6 cases of death. Hazard ratio (HR) calculations for the new event onset group identified sedentary time as a significant independent variable. The independent variable that was identified as a significant predictor of new events was the sedentary time (60 min/day; HR: 1.23, 95% CI: 1.05-1.45, P=0.012). CONCLUSIONS: Extended sedentary time increased the risk of new cardiovascular or renal events and/or all-cause death in patients with DKD.

Clinically feasible method for assessing leukocyte rheology in whole blood.

This study reports a novel method for assessment of leukocyte rheological activation with a new designed microchannel array chip to mimic the human microvascular network for microchannel array flow analysis (MCFAN). Study subjects were 79 healthy volunteers and 42 patients with type 2 diabetes mellitus (DM) and 36 patients with acute coronary syndrome (ACS). Using the anticoagulants heparin and ethylene-diamine-tetraacetic acid (EDTA)-2Na which inhibits platelets and leukocytes by chelating Ca2+, we were able to quantify leukocyte rheological activation by the subtraction of passage time of blood treated with both heparin and EDTA-2Na from that of blood treated with heparin only. We confirmed that passage times of whole blood with heparin + EDTA-2Na were always shorter than those of whole blood with only heparin in healthy subjects and patients with DM or ACS under suction pressures of - 30 cmH2O. There was a significant correlation between delta whole blood passage time {(heparin tube) - (EDTA-2Na + heparin)} and serum levels of myeloperoxidase and adhesive leukocyte number, respectively, even in blood from patients with DM or ACS, who suffered from inflammation. In conclusion we have developed a clinically feasible method for assessing leukocyte rheological activation in whole blood in ex vivo.

Renin-Angiotensin System Inhibitors Can Prevent Intravenous Lipid Infusion-Induced Myocardial Microvascular Dysfunction and Leukocyte Activation.

BACKGROUND: Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells. CONCLUSIONS: Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.

Pravastatin improves postprandial endothelial dysfunction and hemorheological deterioration in patients with effort angina pectoris.

Postprandial hypertriglyceridemia and hyperglycemia may promote endothelial and hemorheological dysfunction. The present study investigated the effects of pravastatin on endothelial function and hemorheology in patients with stable angina pectoris (AP) before and after eating a test meal. We recruited 26 patients with stable AP who had impaired glucose tolerance and mild dyslipidemia and six healthy men as controls to assess endothelial function and hemorheological behavior. In each group, we measured forearm blood flow (FBF) during post-ischemic reactive hyperemia and obtained blood samples before and 2 h after the test meal. Pravastatin 20 mg/day was then commenced in the 26 AP patients. The above tests were repeated after 2 days and 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in the AP patients than in the controls (p < 0.05). Fasting and postprandial FBF during reactive hyperemia time-dependently improved after pravastatin treatment (p < 0.05 vs. baseline data for each phase). Pravastatin treatment for 6 months, but not for 2 days, inhibited leukocyte activation and improved hemorheological parameters. In conclusion, pravastatin treatment for 6 months improved fasting and postprandial endothelial and hemorheological dysfunction in AP patients.

Effects of pitavastatin on walking capacity and CD34+/133+ cell number in patients with peripheral artery disease.

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34+/133+ cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner-Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient's preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34+/133+ cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

Contrast echocardiography for the diagnosis of left ventricular thrombus in anterior myocardial infarction.

Although detecting left ventricular thrombus in anterior myocardial infarction is important for the prevention of embolic events, imaging of apical thrombus is often difficult using conventional echocardiography. We examined whether contrast echocardiography improves sensitivity and specificity in detecting thrombus in the left ventricle in comparison with conventional echocardiography alone in patients with anterior myocardial infarction. Participants in this single-center prospective study comprised 392 patients with anterior myocardial infarction admitted between 2000 and 2006. After conventional echocardiography, all patients underwent contrast echocardiography (left ventricular opacification and myocardial contrast echocardiography) during intravenous drip infusion of contrast media at rest. Left ventricular thrombus was diagnosed based on left ventriculography or multidetector-row computed tomography (MDCT). Mural left ventricular thrombus was confirmed by left ventriculography and/or MDCT in 32 of 393 patients (8 %). Sensitivity and specificity of conventional echocardiography alone were 88 % and 96 %, respectively, compared with 100 % each with contrast echocardiography. Among the 32 patients with left ventricular thrombus, 25 patients (78 %) showed no perfusion in the anterior wall on myocardial contrast echocardiography, even with a four-beat interval. In conclusion, contrast echocardiography offers a clinically feasible and useful method for noninvasively evaluating left ventricular thrombus in anterior myocardial infarction.

Flecainide Toxicity From Clinical Pharmacology Perspectives.

We report a case comparing the measured half-life of flecainide with the half-life stated on the label. An 84-year-old woman presented with symptoms of anorexia and exertional dyspnea. She had undergone mitral and aortic valve replacements and excision of the membranous septum in the atrium for mitral and aortic stenosis and cor triatriatum. She was regularly administered 100 mg/day flecainide for paroxysmal atrial fibrillation. A previous electrocardiogram (ECG) showed a regular sinus rhythm. However, upon admission, the ECG revealed a heart rate of 94 bpm and an accelerated idioventricular rhythm originating from the left ventricle. Flecainide toxicity was suspected, leading to the discontinuation of flecainide treatment. The following day, the serum flecainide concentration was 1,348 ng/mL, exceeding the therapeutic window of 200-1,000 ng/mL. After discontinuing flecainide, the accelerated idioventricular rhythm ceased, and a regular sinus rhythm temporarily returned. We measured blood drug concentrations several times; our calculated half-life was 56.8 h, approximately five times longer than the half-life of 11.0 h stated on the package insert. To ensure safe and effective therapy with antiarrhythmic drugs, prioritizing therapeutic drug monitoring and carefully monitoring pharmacokinetics is important, particularly during the elimination phase.

Giant Left Ventricular Thrombus Rapidly Developing in an Extremely Short Period of Time in a Patient With Severe Systolic Dysfunction.

Although left ventricular thrombi (LVTs) are closely related to the prognosis of patients with systolic dysfunction, anticoagulation therapy is not recommended for the primary prevention of LVTs in patients with sinus rhythm heart failure. We report a case of a patient with systolic dysfunction who developed a giant LVT in an extremely short period of time (one month) after an infection. The LVT led to acute limb ischemia, gangrene, and death. Additionally, we incidentally detected pulmonary thrombosis in this patient.

Skeletal Muscle Quality Assessment in Patients With Cardiac Disease Associated With Type 2 Diabetes Mellitus: A Pilot Study.

Background Type 2 diabetes mellitus (T2DM) is associated with changes in skeletal muscle quantity and quality, such as increased ectopic fat. Cardiac rehabilitation (CR) aims to improve the exercise capacity and muscle strength. This study aimed to determine the relationship between qualitative changes in the skeletal muscles and exercise function in patients with and without diabetes mellitus. Methods The study included patients with cardiovascular diseases who entered CR. Of 72 CR patients (68.1±9.0 years) who underwent a cardiopulmonary exercise test and skeletal muscle assessment at discharge, 15 patients with T2DM and 15 without DM were selected using propensity score matching by age and gender. Results No significant differences in the skeletal muscle echo intensity (EI) (T2DM: 58.4, Non-DM: 53.4, p=0.32), skeletal muscle index (T2DM: 7.5 kg/m2, Non-DM: 7.2 kg/m2, p=0.36), or the weight-bearing index (WBI)(T2DM: 0.44, Non-DM: 0.50, p=0.35) existed between the two groups. The phase angle (PhA) (T2DM: 3.67°, Non-DM: 4.49°, p<0.05) and peak oxygen uptake (T2DM: 12.3 mL/kg/min, Non-DM: 14.8 mL/kg/min, p<0.05) were significantly lower in the T2DM group. PhA values showed a significant correlation with the WBI, a parameter of lower limb muscle strength (r=0.50, p<0.05). Conclusion The coexistence of cardiovascular disease and T2DM resulted in a decrease in the PhA, indicating a qualitative decrease in skeletal muscle mass. The PhA is also associated with lower limb muscle strength.

Relationship Between Increased Oxygen Uptake and Lactate Production With Progressive Incremental Electrode Skeletal Muscle Stimulation: A Pilot Study.

Background Belt electrode skeletal muscle stimulation (B-SES) is an alternative exercise therapy for those with difficulty performing voluntary exercise. However, it is unknown whether oxygen uptake (VO2) in B-SES is comparable to cardiopulmonary exercise test (CPX) as assessed by voluntary exercise. This study aimed to evaluate oxygen uptake (VO2) and lactate (LA) production in incremental B-SES compared to ergometer CPX and to determine the relationship with ergometer CPX. Methods This study included 10 healthy young Japanese participants. Using a crossover design, all participants underwent incremental B-SES CPX and ergometer CPX using a 20 W ramp. Serum lactic acid concentration (LA) was measured serially before, during, and after B-SES. The tolerability of B-SES was adjusted with the change in LA level (⊿LA). Results Peak VO2 during B-SES (14.1±3.3 mL/kg/min) was significantly lower than ergometer peak VO2 (30.2±6.2 mL/kg/min, P<0.001). B-SES peak VO2 was similar to the anaerobic threshold (AT) VO2 on ergometer CPX (15.1±2.6 mL/kg/min). LA (Rest: 1.4±0.3, Peak: 2.8±0.8 mmol) and plasma noradrenalin (Rest: 0.2±0.1, Peak: 0.4±0.1 ng/mL) levels increased after B-SES. No significant correlation was observed between B-SES peak VO2 and ergometer CPX. However, after adjusting for B-SES, tolerability, it (peak VO2 of B-SES /⊿LA) correlated with peak VO2 (r=0.688, p=0.028) on the ergometer. Conclusion Peak VO2 of the passively progressive B-SES almost reached the AT value of the ergometer CPX without adverse events. Peak VO2 of B-SES adjusted with ⊿LA may be used to predict peak VO2 in ergometer CPX.

Effects of salt intake reduction by urinary sodium to potassium ratio self-monitoring method.

Effective and feasible educational methods are needed to control salt intake. We performed a single-center, non-randomized controlled study to investigate the effectiveness and feasibility of self-monitoring using a urinary sodium/potassium (Na/K) ratio-measuring device in patients with difficulty in reducing salt intake. This study included 160 patients with hypertension, chronic kidney disease, or heart disease who were followed up in the outpatient clinic of the Dokkyo Medical University Nikko Medical Center. Urinary Na/K ratio measuring Na/K ratio meter were loaned for 2-6 weeks to the treatment (T) group (n = 80) and not to the patients in the control (C) group (n = 80). In the T group, patients were instructed to measure the urinary Na/K ratio at least three times a day and maintain a Na/K ratio below 2.0. Salt reduction education and home blood pressure measurement guidance continued in both groups. The mean device loan period in the T group was 25.1 days, the mean number of measurements was 3.0 times/day, and the proportion of patients achieving three measurements per day was 48.8% (39/80). Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake by -1.9 g/day at the second visit (p < 0.001) in the T group. In contrast, no change was observed over time in the C group. Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake in patients with difficulty reducing salt intake.