Kengo Kusano

Risk stratification in patients with brugada syndrome without previous cardiac arrest – Prognostic value of combined risk factors

BACKGROUND Risk stratification in patients with Brugada syndrome for primary prevention of sudden cardiac death is still an unsettled issue. A recent consensus statement suggested the indication of implantable cardioverter defibrillator (ICD) depending on the clinical risk factors present (spontaneous type 1 Brugada electrocardiogram (ECG) [Sp1], history of syncope [syncope], and ventricular fibrillation during programmed electrical stimulation [PES+]). The indication of ICD for the majority of patients, however, remains unclear. METHODS AND RESULTS A total of 218 consecutive patients (211 male; aged 46 ± 13 years) with a type 1 Brugada ECG without a history of cardiac arrest who underwent evaluation for ICD including electrophysiological testing were examined retrospectively. During a mean follow-up period of 78 months, 26 patients (12%) developed arrhythmic events. On Kaplan-Meier analysis patients with each of Sp1, syncope, or PES+ suffered arrhythmic events more frequently (P=0.018, P<0.001, and P=0.003, respectively). On multivariate analysis Sp1 and syncope were independent predictors of arrhythmic events. When dividing patients according to the number of these 3 risk factors present, patients with 2 or 3 risk factors experienced arrhythmic events more frequently than those with 0 or 1 risk factor (23/93 vs. 3/125; P<0.001). CONCLUSIONS Syncope, Sp1, and PES+ are important risk factors and the combination of these risks well stratify the risk of later arrhythmic events.

Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations

BACKGROUND Andersen-Tawil syndrome (ATS) is an autosomal dominant genetic or sporadic disorder characterized by ventricular arrhythmias (VAs), periodic paralyses, and dysmorphic features. The optimal pharmacological treatment of VAs in patients with ATS remains unknown. OBJECTIVE We evaluated the efficacy and safety of flecainide for VAs in patients with ATS with KCNJ2 mutations. METHODS Ten ATS probands (7 females; mean age 27 ± 11 years) were enrolled from 6 institutions. All of them had bidirectional VAs in spite of treatment with β-blockers (n = 6), but none of them had either aborted cardiac arrest or family history of sudden cardiac death. Twenty-four-hour Holter recording and treadmill exercise test (TMT) were performed before (baseline) and after oral flecainide therapy (150 ± 46 mg/d). RESULTS Twenty-four-hour Holter recordings demonstrated that oral flecainide treatment significantly reduced the total number of VAs (from 38,407 ± 19,956 to 11,196 ± 14,773 per day; P = .003) and the number of the longest ventricular salvos (23 ± 19 to 5 ± 5; P = .01). At baseline, TMT induced nonsustained ventricular tachycardia (n = 7) or couplets of premature ventricular complex (n = 2); treatment with flecainide completely (n = 7) or partially (n = 2) suppressed these exercise-induced VAs (P = .008). In contrast, the QRS duration, QT interval, and U-wave amplitude of the electrocardiogram were not altered by flecainide therapy. During a mean follow-up of 23 ± 11 months, no patients developed syncope or cardiac arrest after oral flecainide treatment. CONCLUSION This multicenter study suggests that oral flecainide therapy is an effective and safe means of suppressing VAs in patients with ATS with KCNJ2 mutations, though the U-wave amplitude remained unchanged by flecainide.

Risk stratification based on nutritional screening on admission: Three-year clinical outcomes in hospitalized patients with acute heart failure syndrome

BACKGROUND Several blood tests are commonly used to assess nutritional status, including serum albumin levels (SAL) and lymphocyte counts (LC). The aim of this study is to investigate whether nutritional screening on admission can be used to determine risk levels for adverse clinical events in acute heart failure syndrome (AHFS) patients. METHODS In 432 consecutive AHFS patients, we measured SAL and LC and prospectively followed the patients for their combined clinical events (all-cause death and re-hospitalization for heart failure) for three years from admission. The classification and regression tree (CART) tool identified the cut-off criteria for SAL and LC to differentiate among patients with different risks of clinical events as 3.5g/dl and 963/mm3, respectively. RESULTS The CART tool classified 15.5% patients as high risk, 15.7% as intermediate risk, and 68.8% as low risk. The CART for nutritional status (CART-NS) values were strongly correlated with combined clinical events [hazard ratio of 2.13 (low vs high risk), 95% confidence interval of 1.42-3.16, p<0.001], even after adjusting for plasma brain natriuretic peptide levels. The CART-NS analysis improved the specificity (89.5%) of predictions of clinical outcomes with the comparable sensitivity (36.3%) compared with the use of a single criterion (SAL <3.5g/dl: 70.2, 42.4% or LC <963/mm3: 73.4, 41.7%, respectively). CONCLUSION A substantial proportion of AHFS patients are at risk of malnutrition, and this risk is associated with poor clinical outcomes. We demonstrate that this algorithm for nutritional screening, even in emergency clinical settings, can determine risk levels for further adverse events in AHFS patients.

Pronounced Shortening of QT Interval With Mexiletine Infusion Test in Patients With Type 3 Congenital Long QT Syndrome

BACKGROUND Mexiletine is often used for medical therapy in LQT3 patients, however, the usefulness of mexiletine infusion test for LQT3 patients has not been reported. The aim of this study was to evaluate the usefulness of mexiletine infusion test for detecting LQT3 patients. METHODSANDRESULTS We analyzed response in 12-lead electrocardiogram parameters measured in II or V5 to i.v. mexiletine infusion (2 mg/kg) during sinus rhythm among 31 genotype-positive LQT patients (29 ± 18 years, 12 male). Change in QTc interval after mexiletine was compared between LQT3 (n=15, 24 ± 21 years, 9 male) and other LQT patients (4 LQT1 and 12 LQT2; 34 ± 14 years, 3 male). Baseline RR, QT, and QTc interval were not different between the 2 groups (981 ± 182 vs. 1,023 ± 192 ms; 550 ± 94 vs. 524 ± 75 ms; 556 ± 66 vs. 520 ± 62 ms, respectively). While QTc interval was shortened with mexiletine in both groups (P<0.0001 vs. baseline), degree of QTc shortening (∆QTc) was significantly larger in LQT3 than in LQT1/LQT2 patients (99 ± 39 vs. 48 ± 32 ms; P=0.0004). The sensitivity, specificity and predictive accuracy of mexiletine infusion test for differentiating LQT3 from LQT1/LQT2 were 86.7%, 81.3% and 81.3%, respectively, and the optimal cut-off for ∆QTc was 69 ms on receiver operating characteristic analysis. No pro-arrhythmic event was observed. CONCLUSIONS Pronounced shortening of QT interval with mexiletine may facilitate genetic testing in patients with LQT3 syndrome.

Utility of High-Resolution Magnetocardiography to Predict Later Cardiac Events in Nonischemic Cardiomyopathy Patients With Normal QRS Duration

BACKGROUND Nonischemic dilated cardiomyopathy (NIDCM) patients, even those with a narrow QRS, are at increased risk for major adverse cardiac events (MACE). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect prognostic left intraventricular disorganized conduction (LiDC) by overcoming the limitations of fragmented QRS (fQRS, qualitative definitions, low specificity) and late potential (abnormality undetectable in earlier QRS).Methods and Results:We evaluated LiDC on MCG, defined as significant deviation from a global clockwise left ventricular (LV) activation pattern, and conventional noninvasive predictors of MACE, including fQRS and late potential, in 51 NIDCM patients with narrow QRS (LV ejection fraction, 22±7%; QRS duration, 99±11 ms). MACE was defined as cardiac death, lethal ventricular arrhythmias, or LV assist device (LVAD) implantation. LiDC was present in 22 patients. Baseline characteristics were comparable between patients with and without LiDC, except for the ratio of positive late potential. During a mean follow-up of 2.9 years, MACE developed in 16 NIDCM patients (3 cardiac deaths, 9 lethal ventricular arrhythmias, and 4 LVAD). MACE was more incident in patients with LiDC (13/22) than in those without (3/29, P<0.001). Multivariate analysis revealed LiDC, but not fQRS or late potential, as the strongest independent predictor of MACE (hazard ratio 4.28, 95% confidence interval 1.30-19.39, P=0.015). CONCLUSIONS MCG accurately depicts LiDC, a promising noninvasive predictor of MACE in patients with NIDCM and normal QRS.

Diagnostic Value of Right Ventricular Dysfunction in Tachycardia-Induced Cardiomyopathy Using Cardiac Magnetic Resonance Imaging.

BACKGROUND Predicting tachycardia-induced cardiomyopathy (TIC) in patients presenting with left ventricular (LV) dysfunction and tachyarrhythmias remains challenging. We assessed the diagnostic value of early right ventricular (RV) dysfunction to predict TIC using cardiac magnetic resonance (CMR) imaging. METHODSANDRESULTS A total of 102 consecutive patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias were examined. Patients whose LV ejection fraction (EF) improved to ≥50% during a 1-year follow-up were diagnosed with TIC, and with dilated cardiomyopathy (DCM) in those whose did not improve. CMR was performed at a median of 23 days after admission, and the TIC and DCM patients exhibited different distributions of EF and end-diastolic volume (EDV) between the LV and RV (both P<0.001, ANCOVA). TIC patients had significantly lower RVEF/LVEF ratio (1.01±0.23 vs. 1.36±0.31, P<0.001) and higher RVEDV/LVEDV ratio (0.96±0.21 vs. 0.73±0.19, P<0.001) compared with DCM patients, suggesting that RV systolic dysfunction and RV dilatation were observed in TIC. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were significant predictors of TIC, and RVEF/LVEF ratio of <1.05 most highly predicted TIC with a sensitivity of 69.1% and specificity of 91.5% (area under the curve 0.860). CONCLUSIONS Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, age and coexistence of RV dysfunction was a strong predictor of TIC. (Circ J 2016; 80: 2141-2148).