Takashi Noda

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

OBJECTIVESnThis study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers.nnnBACKGROUNDnThe LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance.nnnMETHODSnThe 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV).nnnRESULTSnThe mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients.nnnCONCLUSIONSnEpinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

Sex Hormone and Gender Difference—Role of Testosterone on Male Predominance in Brugada Syndrome

Introduction: The clinical phenotype is 8 to 10 times more prevalent in males than in females in patients with Brugada syndrome. Brugada syndrome has been reported to be thinner than asymptomatic normal controls. We tested the hypothesis that higher testosterone level associated with lower visceral fat may relate to Brugada phenotype and male predominance.

ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome.

OBJECTIVESnThe study examined whether patients with Brugada syndrome are sensitive to vagal stimulation or ischemia.nnnBACKGROUNDnExperimental studies have suggested that a prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of the action potential dome in the epicardium, but not in the endocardium, give rise to ST-segment elevation and subsequent ventricular fibrillation (VF).nnnMETHODSnWe evaluated the frequency of coronary spasm, augmentation (> or =0.1 mV) of ST-segment elevation in leads V(1) to V(3), and induction of VF by intracoronary injection of acetylcholine (ACh) and/or ergonovine maleate (EM) in 27 symptomatic patients with Brugada syndrome and 30 control subjects.nnnRESULTSnThe coronary spasm was induced in 3 (11%) of the 27 patients with Brugada syndrome and in 13 (43%) of the 30 control subjects. ST-segment elevation was augmented by 11 (33%) of the 33 right coronary injections (ACh: 6/11 [55%]; EM: 5/22 [23%]), without coronary spasm, but not by any of the left coronary injections in patients with Brugada syndrome. Ventricular fibrillation was induced by 3 (9%) of the 33 right coronary injections (ACh: 2/11 [18%]; EM: 1/22 [5%]), but not by any of the left coronary injections. In contrast, neither ST-segment elevation nor VF was observed in any of the control subjects.nnnCONCLUSIONSnOur results support the hypothesis that mild ischemia and vagal influences act additively or synergistically with the substrate responsible for the Brugada syndrome to elevate the ST-segment and precipitate VF. These observations suggest that Brugada patients may be at a higher risk for ischemia-related sudden death.

Prominent J wave and ST segment elevation: Serial electrocardiographic changes in accidental hypothermia

From the Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Suita, Japan; *Division of Cardiology, Department of Internal Medicine, Miyoshi General Hospital, Miyoshi, Japan; and †Division of Frontier Medical Science, Department of Medicine and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

High value of right ventricular to left ventricular interlead electrical delay during right ventricular pacing predict favorable response in patients with cardiac resynchronization therapy

Introduction: Anatomical and electrical separation of left ventricular (LV) and right ventricular (RV) electrodes is significant for successful cardiac resynchronization therapy (CRT). During bi-ventricular pacing, the electrical activation was composed by RV and LV pacing wavefronts. So the region with latest activation during intrinsic rhythm might not correspond to the optimal pacing site during CRT.nnHypothesis: We assess the hypothesis that interlead electrical delay measurements during RV and LV pacing besides intrinsic rhythm could predict favorable response to CRT.nnMethods and results: We evaluated 51 heart failure patients (age 64±13 years, LV ejection fraction 28±12%, QRS duration 155±37ms) who had successfully implanted CRT. The LV-RV interlead electrical delay (IED) during intrinsic rhythm, RV pacing (RV pacing-LV sensing: RVp-LVs) and LV pacing (LV pacing-RV sensing: LVp-RVs) were measured intraoperatively by utilizing intracardiac electrograms. After CRT implantation, 33 (65%) patients responded to CRT. The responders showed a significantly higher value of RVp-LVs compared with non-responders (166±42 vs. 141±36ms, respectively, p=0.04) and the absolute value of the difference between RVp-LVs and LVp-RVs was lower in responders than in non-responders (16±19 vs. 28±22ms, respectively, p=0.04). The IED during intrinsic rhythm (71±53 vs. 40±44ms, p=0.07) and LVp-RVs (170±47 vs. 146±35, p=0.06) showed higher tendency in responders, however they couldnt predict responders. Moreover, among narrow QRS patients (n=21; median QRS duration 118ms, 95 to 140ms), RVp-LVs was significantly higher in responders than in non-responders (159±32 vs. 121±32ms, p=0.01). Same as the entire cohort, the IED during intrinsic rhythm couldnt predict responders (59±24 vs. 35±36ms, p=0.11). At multivariate analysis, RVp-LVs was the only independent predictor of reverse remodeling in narrow QRS subgroup (p=0.03).nnConclusion: Interlead electrical delay during intrinsic rhythm couldnt predict LV reverse remodeling after CRT. However high value of RVp-LVs measured intraoperatively was associated with favorable response irrespective of QRS width, which implies an optimal LV lead position during CRT implantation.