Daisuke Fujimatsu

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 24–48u2009h after coronary stenting in the coronary sinus (8.7u2009±u20098.9 to 31.8u2009±u200919.8u2009U/ml, Pu2009<u20090.001) with a maximum at 48u2009h. In contrast, the mean channel fluorescence intensity for P-selectin increased 15u2009min after coronary stenting in the coronary sinus (19.5u2009±u20095.6 to 25.2u2009±u20097.5, Pu2009<u20090.01) and remained elevated for 48u2009h; the changes were less striking in peripheral blood. The relative increase in PDMPs was not correlated with the increase in P-selectin expression at 15u2009min or 24u2009h after coronary stenting, but was correlated at 48u2009h (Ru2009=u20090.48, Pu2009<u20090.05). 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.

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)

BACKGROUNDnHMG-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.nnnMETHODS AND RESULTSnFive 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.nnnCONCLUSIONSnThe 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).

An Appropriate Indication for the Initiation of Beta-Blocker Therapy in Dilated Cardiomyopathy

Backgrounds: Although long-term treatment with beta-blockers has been shown to improve morbidity and mortality in dilated cardiomyopathy (DCM), patient re- sponses 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 × systolic blood pressure – 0.002 × brain natriuretic peptide + 0.667 (R2 = 0.67, p < 0.001). The probability of predicting the response was 94.1% with h ≧0.5. Conclusion: We conclude that h≧0.5 is the appropriate indication for the initiation of beta-blocker therapy in DCM.

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 (nxa0=xa090) or a usual care group (nxa0=xa091). 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; pxa0=xa00.572]. 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.