Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Conclusions and Relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Roles of accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, and attenuated nitric oxide synthase activity in endothelial cells for pulmonary hypertension in rats.

Nitric oxide (NO) has been suggested to play a key role in the pathogenesis of pulmonary hypertension (PH). To determine which mechanism exists to affect NO production, we examined the concentration of endogenous nitric oxide synthase (NOS) inhibitors and their catabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) activity and protein expression (DDAH1 and DDAH2) in pulmonary artery endothelial cells (PAECs) of rats given monocrotaline (MCT). We also measured NOS and arginase activities and NOS protein expression. Twenty-four days after MCT administration, PH and right ventricle (RV) hypertrophy were established. Endothelium-dependent, but not endothelium-independent, relaxation and cGMP production were significantly impaired in pulmonary artery specimens of MCT group. The constitutive NOS activity and protein expression in PAECs were significantly reduced in MCT group, whereas the arginase, which shares l-arginine as a common substrate with NOS, activity was significantly enhanced in PAECs of MCT group. The contents of monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), but not symmetric dimethylarginine (SDMA), were increased in PAECs of MCT group. The DDAH activity and DDAH1, but not DDAH2, protein expression were significantly reduced in PAECs of MCT group. These results suggest that the impairment of cGMP production as a marker of NO production is possibly due to the blunted endothelial NOS activity resulting from the downregulation of endothelial NOS protein, accumulation of endogenous NOS inhibitors, and accelerated arginase activity in PAECs of PH rats. The decreased overall DDAH activity accompanied by the downregulation of DDAH1 would bring about the accumulation of endogenous NOS inhibitors.

Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome.

BACKGROUND: The characteristics of unique ECG findings in the Brugada syndrome have not been well explained. METHODS: To clarify their characteristics and mechanisms, body surface maps (BSM) were recorded from patients with the Brugada syndrome (13 cases; a mean age of 48 years) before and after administration of isoproterenol (ISP) or Na channel blockers (12 cases). RESULTS: ST elevation in V1-V3 was decreased by 0.1 mV or more after ISP infusion in 8 of 11 cases and elevated after Na channel blockers in 8 of 12. In ventricular activation time (VAT) isochronal map, delayed conduction was noted on upper anterior chest in 11 and on anterior left chest in two. Delayed conduction areas were decreased by ISP and expanded by Na channel blockers. QRST isointegral map showed normal findings in baseline with minimal changes after ISP or Na channel blockers. Activation recovery interval (ARI) isochronal map showed prolonged area on upper anterior chest in baseline, being reduced by ISP and expanded by Na channel blockers. ARI dispersion (ARI-d), defined as difference between the maximum and minimum value of ARI, was larger in Brugada patients than that of normal subjects in baseline, and decreased after ISP and increased after Na channel blockers. CONCLUSION: ST elevation in the Brugada syndrome is primarily caused by abnormality in depolarization rather than in repolarization. BSM can provide better information to clarify a mechanism of ECG changes adding its diagnostic value for this unique syndrome.