Akihiro Masumoto

Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm.

OBJECTIVES We sought to determine whether a potent Rho-kinase inhibitor fasudil prevents the occurrence of myocardial ischemia in patients with microvascular angina attributable to coronary microvascular spasm. BACKGROUND Effective treatment of patients with angina who have normal coronary arteriograms (microvascular angina) has not yet been established. Rho-kinase-mediated calcium sensitization of the myosin light chain in smooth muscle cells has been implicated as substantially contributing to vascular hyperconstriction. METHODS We studied consecutive 18 patients with angina and normal epicardial coronaries in whom intracoronary acetylcholine (ACh) induced myocardial ischemia (ischemic electrocardiographic changes, myocardial lactate production, or both) without angiographically demonstrable epicardial coronary vasospasm. All patients underwent a second ACh challenge test after pretreatment with either saline (n = 5) or fasudil (4.5 mg intracoronarily, n = 13). RESULTS Myocardial ischemia was reproducibly induced by ACh in the saline group. In contrast, 11 of the 13 patients pretreated with fasudil had no evidence of myocardial ischemia during the second infusion of ACh (p < 0.01). The lactate extraction ratio (median value [interquartile range]) during ACh infusion was improved by fasudil pretreatment, from -0.16 (-0.25 to 0.04) to 0.09 (0.05 to 0.18) (p = 0.0125). CONCLUSIONS Fasudil ameliorated myocardial ischemia in patients who were most likely having coronary microvascular spasm. The inhibition of Rho-kinase may be a novel therapeutic strategy for this group of patients with microvascular angina.

The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study

Abstract Objectives We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease. Background Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis. Methods We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction. Results Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p Conclusions Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.

Rho-Kinase Inhibitor Improves Increased Vascular Resistance and Impaired Vasodilation of the Forearm in Patients With Heart Failure

Background—Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil. Methods and Results—Studies were performed in patients with HF (HF group, n=26) and an age-matched control group (n=26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemic vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly. Conclusions—These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.

Three-year follow-up of the Japanese patients with microvascular angina attributable to coronary microvascular spasm

BACKGROUND We recently reported that coronary microvascular spasm could cause angina in patients with chest pain and normal coronary arteriograms. However, the long-term prognosis of these patients or the effect of calcium channel blockers is not known. METHODS Of consecutive 283 patients who underwent acetylcholine testing for the evaluation of chest pain, we identified 68 patients with microvascular angina attributable to coronary microvascular spasm. All patients were discharged on calcium channel blockers and followed up for an average period of 3.3 years. RESULTS As compared with those having epicardial spasm (n=169), there was a female predominance in the microvascular spasm group (P<0.01), and 81% of the female patients were postmenopausal. During the follow-up, no patient died and one patient (1%) developed non-Q wave myocardial infarction. The frequency of chest pain was unchanged or increased in 24 patients (36%) and decreased or disappeared in 42 patients (64%). The angina status was improved only in 16 of 33 patients treated with calcium channel blockers alone. By contrast, it was improved in 18 of 21 patients on the combination of calcium channel blockers and angiotensin converting enzyme inhibitors (P<0.05). CONCLUSIONS Patients with microvascular angina in the present study were more women and had a different risk factor profile as compared with those having epicardial spasm. Long-term prognosis was excellent with regard to mortality, but angina persisted in many patients even on calcium channel blockers. The result warrants prospective studies to evaluate the efficacy of angiotensin converting enzyme inhibitors as adjunct to calcium channel blockers in this population.

Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina.

Epicardial coronary stenosis causes myocardial ischemia; however, the role of coronary microvessels is poorly understood in the pathogenesis of effort angina. We have previously demonstrated that Rho-kinase pathway is substantially involved in coronary arterial hyperconstriction in patients with vasospastic angina and those with microvascular angina. In the present study, we tested our hypothesis that Rho-kinase is involved in coronary microvascular constriction in patients with effort angina. Intracoronary administration of fasudil (300 μg/min for 15 min), a specific Rho-kinase inhibitor, significantly increased oxygen saturation in coronary sinus vein from 37 ± 3% to 41 ± 3% (P < 0.05) but not in six age-matched controls (from 42 ± 3% to 43 ± 3%, P = NS). Furthermore, the fasudil treatment significantly ameliorated pacing-induced myocardial ischemia in patients with effort angina (magnitudes of symptom: 1.5 ± 0.6 to 0.6 ± 0.4, P < 0.01; ischemic ST-segment depression, 1.8 ± 0.3 to 1.0 ± 0.2 mm, P < 0.01; percent lactate production, 50 ± 17% to 0.4 ± 7%, P < 0.01) without significant hemodynamic changes. These results provide the first evidence that Rho-kinase is substantially involved in coronary microvascular dysfunction associated with myocardial ischemia in patients with effort angina, suggesting that Rho-kinase can be a novel therapeutic target in ischemic heart disease.

Clinical benefits of deep sedation with a supraglottic airway while monitoring the bispectral index during catheter ablation of atrial fibrillation

Pulmonary vein antrum isolation (PVAI) under sedation has proven to be a useful strategy for catheter ablation of atrial fibrillation (AF).

Acute heart failure caused by mechanical valve leaflet dislodgment at the mitral position.

A 46-year-old woman was transferred to the hospital by ambulance for sudden dyspnoea and frothy blood-streaked sputum with cardiogenic shock, who has taken mitral valve replacement (MVR) using a mechanical valve (Edward TEKNA, 29 mm) at the age of 34 due to severe mitral regurgitation. Chest radiography revealed marked blood congestion ( Panel A ). Because her vital sign was …