Hepatocyte growth factor gene therapy reduces ventricular arrhythmia in animal models of myocardial ischemia.

It was recently reported that gene therapy using hepatocyte growth factor (HGF) has the potential to preserve cardiac function after myocardial ischemia. We speculated that this HGF gene therapy could also prevent ventricular arrhythmia. To investigate this possibility, we examined the antiarrhythmic effect of HGF gene therapy in rat acute and old myocardial infarction models. Myocardial ischemia was induced by ligation of the left descending coronary artery. Hemagglutinating virus of Japan (HVJ)-coated liposome containing HGF genes were injected directly into the myocardium fourteen days before programmed pacing. Ventricular fibrillation (VF)was induced by programmed pacing. The VF duration was reduced and the VF threshold increased after HGF gene therapy ( p&#60; 0.01). Histological analyses revealed that the number of vessels in the ischemic border zone was greatly increased after HGF gene injection. These findings revealed that HGF gene therapy has an anti-arrhythmic effect after myocardial ischemia.</p

Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome.

We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.</p

Brugada syndrome: 12 years of progression.

Brugada syndrome is increasingly being recognized in clinical medicine. What started as an electrocardiographic curiosity has become an important focus of attention for individuals working in the different disciplines related to sudden cardiac death, from basic scientists to clinical cardiac electrophysiologists. In just 12 years, since the description of the disease, clinically relevant information is continuously being provided to physicians to help protect the individuals with Brugada syndrome to the best of our ability. And this information has been gathered thanks to the effort of hundreds of basic scientists, physicians and patients who continue to give their time, effort and data to help understand how the electrocardiographic pattern may cause sudden cardiac death. There are still many unanswered questions, both at the clinical and basic field. However, with the further collection of data, the longer follow-up and the continued interest from the basic science world we will have the necessary tools to the successful unraveling of the disease.</p

Risk factors for the first and second inappropriate implantable cardioverter-defibrillator therapy

Introduction: Various risk factors for the first inappropriate implantable cardioverter-defibrillator (ICD) therapy event have been reported, including a history of atrial fibrillation/atrial flutter (AF/AFL), younger age, and multiple zones. Nonetheless, which factors are concordant with real-world data has not been clarified, and risk factors for the second inappropriate ICD therapy event have not been well examined. This study aimed to clarify the risk factors for the first and second inappropriate ICD therapy events. Methods: We conducted a post-hoc secondary analysis of data from a multicenter, prospective observational study (the Nippon Storm Study) designed to clarify the risk factors for electrical storm. Results: The analysis included data from 1549 patients who received ICD or cardiac resynchronization therapy with defibrillator (CRT-D). Over a median follow-up of 28 months, 293 inappropriate ICD therapy events occurred in 153 (10.0%) patients. On multivariate Cox regression analysis, the risk factors for the first inappropriate ICD therapy event were younger age (hazard ratio [HR], 0.986; p = 0.028), AF/AFL (HR, 2.324; p = 0.002), ICD without CRT implantation (HR, 2.377; p = 0.004), and multiple zones (HR, 1.852; p = 0.010). "No-intervention" after the first inappropriate ICD therapy event was the sole risk factor for the second inappropriate ICD therapy event. Conclusions: Risk factors for the first inappropriate ICD therapy event were similar to those previously reported. Immediate intervention after the first inappropriate ICD therapy event could reduce the risk of the second inappropriate event

Continuous positive airway pressure ameliorated severe pulmonary hypertension associated with obstructive sleep apnea.

A 52-year-old obese woman was admitted to our institution for evaluation of dyspnea and pulmonary hypertension (PH). Polysomnography revealed severe obstructive sleep apnea (OSA) with an apnea hypopnea index of 99.8. Treatment with nocturnal continuous positive airway pressure (CPAP) resulted in correction of daytime hypoxemia, hypercapnia, and near-normalization of pulmonary artery pressure. To our knowledge, this is the most severe case of OSA-associated PH (approximately70 mmHg) reported to date, and it was successfully treated with nocturnal CPAP. This case demonstrates that OSA should be considered and polysomnography performed in all patients with PH, irrespective of severity, and that nocturnal CPAP has therapeutic effects on both OSA and daytime PH.</p

926-24 Clinical and Electrophysiological Characteristics in Patients with Exercise Induced Idiopathic Multiform Ventricular Tachycardia. Differential Effects of Atrial Pacing and Isoproterenol Infusion on QTc Interval and Induction of Ventricular Arrhythmia

Idiopathic multiform ventricular tachycardia (VT) is characterized by normal QT interval at restand 3 or more distinct QRS configuration during VT, which has been distinguished from torsade de pointes in long QT syndrome. Facilitation by exercise and suppression by β-antagonist of this VT suggest that it may depend on rapid heart rate (HR) or increased sympathetic tone. To determine which factors is responsible, we performed atrial pacing (120/min) and isoproterenol (ISP) infusion (0.5 or 1.0μg to attain HR 120/min) in 6 patients (2 males/4 females, mean 15.8 years) and 10 control (4 males/6 females, mean 22.8 years). Inducibility of premature ventricular contraction (PVC) or VT, and response of QTc interval (QT/√RR) were evaluated during the procedures.controlmultiform VTp valuePVCNT inductionAtrial pacing0/71/6n.s.Isoproterenol0/86/60.001OTc (secl/2)Rest0.40±0.02 (n=10)0.40±0.03n.s.Atrial pacing0.43±0.02 (n=7)0.47±003&lt;0.01Isoproterenol0.44±0.01 (n=8)0.50±0.05&lt;0.001ConclusionAlthough both rapid HR and increased sympathetic tone may be responsible for this VT, contribution of the latter is predominant. Differential response of QT interval to atrial pacing and isoproterenol infusion may have a possible role for the occurrence of this VT

High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarction

Aims Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST-segment (STEMI) and nonST-segment elevation (NSTEMI). Methods and results This prospective, single-centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 +/- 3 months after discharge). LVR was defined as a relative >= 20% increase in left ventricular end-diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 +/- 61.5 and 213.1 +/- 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut-off value of platelet reactivity for discriminating LVR was >= 245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (= d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85-9.79). Conclusions High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research

Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome

Objectives This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). Background Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. Methods Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 +/- 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/ genetic and electrocardiographic parameters were compared with VF/SCD events. Results On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration >= 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/ absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01). Conclusions The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high-and low-risk BrS patients