The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Effects of pitavastatin in Japanese patients with chronic heart failure: the Pitavastatin Heart Failure Study (PEARL Study).

BACKGROUND: Recent clinical trials using rosuvastatin, a hydrophilic statin, did not show beneficial effects on cardiovascular events in patients with heart failure. We examined the cardioprotective effects of pitavastatin, a lipophilic statin, on Japanese patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 574 Japanese patients with CHF were randomly assigned to the pitavastatin group (n=288) or the control group (n=286). There was no significant difference between the 2 groups for the primary outcome, which was a composite of cardiac death and hospitalization for worsening HF (adjusted hazard ratio (aHR): 0.922, 95% confidence interval (CI): 0.632-1.345, P=0.672). A strongly significant statistical interaction between the effect of pitavastatin and left ventricular ejection fraction (LVEF) was found (P=0.004). In patients with LVEF ≥30%, a significant reduction in the primary outcome (aHR: 0.525, 95% CI: 0.308-0.896, P=0.018) was observed in the pitavastatin group. Pitavastatin did not show any effects on the primary outcome (aHR: 1.582, 95% CI: 0.890-2.813, P=0.118) in the subgroup of patients with LVEF <30%. CONCLUSIONS: Pitavastatin did not reduce cardiac death or hospitalization for worsening HF in Japanese patients with CHF. (UMIN-ID: UMINC000000428).

Rationale and design of a study to evaluate effects of pitavastatin on Japanese patients with chronic heart failure: the pitavastatin heart failure study (PEARL study).

BACKGROUND: HMG-CoA reductase inhibitors (statins) are known to have pleiotropic effects in addition to their lipid-lowering effect. Many studies have suggested cardioprotective effects of statins, however, recent large-scale clinical trials using rosuvastatin, a hydrophilic statin, have failed to show beneficial effects on cardiovascular events in patients with severe heart failure. We have designed the study to evaluate the effects of pitavastatin, a lipophilic statin, on Japanese patients with mild to moderate heart failure. METHODS AND RESULTS: Five hundred seventy-seven patients with chronic heart failure were enrolled. We used a prospective, randomized, open-label, and blinded-endpoint evaluation (PROBE) design. Patients aged 20-79 years old with symptomatic (NYHA functional class II or III) heart failure and a left ventricular ejection fraction of ≤ 45% were randomly allocated to either receive pitavastatin (2mg/day) or not in addition to conventional therapy for heart failure by using the minimization method. Follow-up will be continued until March 2011. The primary endpoint is a composite of cardiac death and hospitalization for worsening heart failure. CONCLUSIONS: The PEARL study will provide important data on the role of pitavastatin in the treatment of Japanese patients with mildly symptomatic heart failure (UMIN-ID: UMINC000000428).

Association between high molecular weight adiponectin levels and metabolic parameters.

AIM: Low plasma adiponectin levels have been demonstrated to be linked to obesity and insulin resistance. It has also been suggested that high molecular weight (HMW) adiponectin is more important for vascular protection than the total amount of adiponectin, although clinical data of HMW adiponectin are lacking. The purpose of this study was to investigate HMW adiponectin levels in Japanese rural residents and to elucidate their clinical significance. METHODS: We measured plasma HMW adiponectin levels in 1,183 subjects (643 men) who participated in our annual health check program in Kashima-city, Saga, Japan. RESULTS: The median plasma level of HMW adiponectin was significantly lower in men than women (2.6, 1.64.0 vs 6.5, 3.78.6 microg/mL, p<0.001), respectively. Multivariate linear regression analysis showed that body weight, B-type natriuretic peptide (BNP) and high density lipoprotein cholesterol were independently associated with HMW adiponectin in both genders. Triglyceride and serum creatinine levels were associated with HMW adiponectin in men only. CONCLUSIONS: HMW adiponectin levels were lower in men than in women and were associated with BNP independently. A prospective follow-up of the subjects in this study is required to determine the usefulness of HMW adiponectin as a biomarker for predicting the development of cardiovascular disease.

Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening.

Inflammation in the injured vessel wall plays an essential role in the mechanism of restenosis. Pentraxin3 (PTX3) is synthesized at the inflammatory site in response to primary inflammatory stimuli. To establish the clinical significance of plasma PTX3 levels in the pathophysiology of inflammation in the injured vessels, we serially measured the levels in 20 patients undergoing elective coronary stenting. Plasma PTX3 levels increased 15 min after coronary stenting, and reached a maximum at 24h in the coronary sinus (P<0.001 versus baseline) and peripheral blood (P<0.001 versus baseline). The transcardiac gradient of PTX3 at 15 min after PCI was higher in patients with than those without restenosis (0.40+/-0.64 versus -0.19+/-0.33 ng/ml, P=0.02). Furthermore, the increase in PTX3 at 24h was positively correlated with the increase in activated Mac-1 on the surface of neutrophils at 48 h (r=0.48, p<0.05) in the coronary sinus. Stepwise multiple regression analysis demonstrated that the relative increase in PTX3 at 24h was the most powerful predictor of late lumen loss (r=0.547, P=0.007). Coronary stenting enhanced circulating PTX3 levels in association with an inflammatory response. PTX3 may be a useful marker for evaluation of inflammatory reaction and neointimal thickening after vascular injury.

Increased circulating platelet-derived microparticles are associated with stent-induced vascular inflammation.

Inflammation as well as platelet activation at the site of local vessel-wall injury plays an essential role in the mechanism of restenosis after Percutaneous coronary intervention (PCI). Platelet-derived microparticles (PDMPs) released from activated platelets are thought to play a role in the inflammatory process, possibly interacting with leukocyte integrin Mac-1. We serially measured circulating PDMPs, high-sensitive C-reactive protein (hs-CRP) and activated Mac-1 on the surface of neutrophils in 61 patients undergoing coronary stenting. PDMPs, hs-CRP and Mac-1 increased after coronary stenting in a time-dependent manner with the maximum response at 48 h in coronary sinus blood (PDMPs: 10.3+/-8.9-32.8+/-13.8 U/ml; P<0.001, hs-CRP: 0.27+/-0.23-1.46+/-0.99 mg/dl; P<0.001, activated Mac-1, 134+/-19% relative increase, P<0.001). PDMPs were correlated with hs-CRP (R=0.58, P<0.001) and the relative increase in Mac-1 (R=0.69, P<0.001) 48 h after coronary stenting. Multiple regression analysis showed that each of PDMPs (R=0.40, P<0.05), hs-CRP (R=0.33, P<0.05) and Mac-1 (R=0.48, P<0.01) was an independent predictor of the late lumen loss. Coronary stenting enhanced circulating PDMPs in association with an inflammatory response in the injured vessel wall. PDMPs may be a useful marker for evaluation of stent-induced inflammatory status and a powerful predictor of restenosis equivalent to activated Mac-1.

Comparison of changes in circulating platelet-derived microparticles and platelet surface P-selectin expression after coronary stent implantation.

Platelet-derived microparticles (PDMPs) are released from activated platelets and may participate in the inflammatory process in response to vessel wall injury. This study was designed to compare the clinical significance of circulating PDMPs with that of P-selectin on the platelet membrane surface. In 20 patients with stable angina undergoing coronary stent implantation, circulating PDMPs were serially measured by enzyme-linked immunosorbent assay, and P-selectin expression on the surface of platelets was simultaneously analyzed by flow cytometry. PDMPs increased 24-48 h after coronary stenting in the coronary sinus (8.7 +/- 8.9 to 31.8 +/- 19.8 U/ml, P < 0.001) with a maximum at 48 h. In contrast, the mean channel fluorescence intensity for P-selectin increased 15 min after coronary stenting in the coronary sinus (19.5 +/- 5.6 to 25.2 +/- 7.5, P < 0.01) and remained elevated for 48 h; the changes were less striking in peripheral blood. The relative increase in PDMPs was not correlated with the increase in P-selectin expression at 15 min or 24 h after coronary stenting, but was correlated at 48 h (R = 0.48, P < 0.05). Both circulating PDMPs and P-selectin expression were enhanced in association with stent-induced platelet activation; however, the time course of changes in these two platelet activation markers was different. Therefore, the clinical relevance of circulating PDMPs may differ from that of P-selectin expression on the platelet membrane surface.

An appropriate indication for the initiation of beta-blocker therapy in dilated cardiomyopathy.

BACKGROUND: Although long-term treatment with beta-blockers has been shown to improve morbidity and mortality in dilated cardiomyopathy (DCM), patient responses are heterogeneous. METHODS: To establish the appropriate indication for the initiation of beta-blocker therapy, we retrospectively analyzed 38 DCM patients treated with beta-blockers (metoprolol or carvedilol) and examined differences in baseline profiles between patients who could continue the therapy (responders) and those who could not (non-responders). RESULTS: In 13 non-responders, the duration from onset of symptoms to beta-blocker initiation was longer (p < 0.05), systolic blood pressure was lower (p < 0.001), serum sodium concentration was lower (p < 0.05), left ventricular posterior wall thickness was thinner (p < 0.05), left ventricular end-diastolic pressure was higher (p < 0.05) and left ventricular wall stress was lower (p < 0.05) than in 25 responders. In 19 patients receiving carvedilol, 5 non-responders showed higher levels of human atrial natriuretic peptide (p < 0.05) and brain natriuretic peptide (p < 0.01) than 13 responders. Discriminant analysis with a linear discriminant function showed the following equation predicted response to beta-blocker therapy: h = 0.004 x systolic blood pressure - 0.002 x brain natriuretic peptide + 0.667 (R2 = 0.67, p < 0.001). The probability of predicting the response was 94.1% with h > or = 0.5. CONCLUSION: We conclude that h > or = 0.5 is the appropriate indication for the initiation of beta-blocker therapy in DCM.