Insight into specific pro-arrhythmic triggers in Brugada and early repolarization syndromes: results of long-term follow-up

The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34–190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K⁺ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34–190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.     

Early repolarization pattern: its ECG characteristics,arrhythmogeneity and heritability

Early repolarization (ER) has been accepted as a benign ECG variant for decades. Two seminal studies challenged this notion and have demonstrated that ER pattern is associated with an increased risk of arrhythmic and cardiac mortality in patients with idiopathic ventricular fibrillation (IVF) and in the general population. Recent clinical studies demonstrate its varying impact as an arrhythmogenic substrate on different diseases. For example, in ER syndrome, a primary electrical disease, ER appears as a major arrhythmogenic substrate for development of VF whereas in patients with coronary artery disease, an ER pattern may exist as a silent substrate, increasing the risk of VF during episodes of cardiac ischaemia. Due to the high prevalence of an ER pattern in the general population and a low VF event rate, it remains challenging to differentiate a malignant ER pattern from a benign form. Recent research suggests that a J-wave amplitude of more than 0.1 mV combined with a descending/horizontal ST segment may constitute a malignant ER pattern. Further studies are however necessary to evaluate its prognostic value for cardiac and arrhythmic death in the general population as well as in cases with a malignant ER pattern. While genetic testing has revealed putative causal DNA variants in sporadic cases, the lack of co-segregation with the disease in affected families suggests that ER syndrome is not monogenic but is likely a complex disorder influenced by multiple genetic as well as environmental factors.     

Low serum eicosapentaenoic acid level is a risk for ventricular arrhythmia in patients with acute myocardial infarction: a possible link to J-waves

Eicosapentaenoic acid (EPA) has antiarrhythmic effects. The J-wave on an electrocardiogram is associated with a high incidence of ventricular tachycardia/fibrillation (VT/VF). We evaluated relationships between EPA and J-waves, and their involvement in the occurrence of VT/VF in acute myocardial infarction (AMI). Two hundred consecutive patients undergoing successful percutaneous coronary intervention within 12 h after AMI onset were enrolled. Serum EPA level and J-waves at admission were evaluated. The patients were divided into two groups according to the optimal cutoff value (2.94) of serum EPA level (% of total fatty acids): LOW (<2.94, 61 ± 11 years, n = 103) and HIGH groups (≥2.94, 70 ± 13 years, n = 81). J-waves were observed more frequently in the LOW (36/103, 35 %) than in HIGH group (16/81, 20 %) (P = 0.020). The 30-day incidence of VT/VF including those occurring before admission was higher in the LOW (19.5 %) than in HIGH group (6.2 %) (P = 0.009). The patients with J-waves showed a higher incidence of VT/VF (23.1 %) than those without J-waves (9.9 %) (P = 0.019). Kaplan–Meier analysis showed that the highest incidence of VT/VF was observed in the LOW with J-wave group (27.8 %), followed by the LOW without J-wave (15.0 %), HIGH with J-wave (12.5 %), and HIGH without J-wave (4.6 %) (P = 0.013). Cox proportional hazard analysis revealed that Killip grade and low serum EPA level or presence of J-waves were significantly associated with the incidence of VT/VF. Low serum EPA level is a risk for incidence of VT/VF in the acute phase of myocardial infarction. Involvement of the J-wave and its possible link with EPA in the pathogenesis of ischemia-induced VT/VF are suggested.     

急性冠脉综合征者缺血性J波的临床研究

目的 研究伴有缺血性J波急性冠脉综合征(ACS)者的临床情况,评价缺血性J波的临床价值.方法 回顾分析372例ACS患者的心电图及相关临床资料,根据心电图有无缺血性J波分为J波组、无J波组,比较两组临床情况、恶性心律失常发生率等.结果 J波组ST段抬高型心肌梗死(STEMI)的发生率明显高于无J波组,J波组恶性心律失常的发生率为25.8%,明显高于无J波组的4.2%,J波组终点事件的发生率明显高于无J波组,差异均有统计学意义(P＜0.05).结论 ACS伴有缺血性J 波患者临床情况差,预后不良.     

Refractory hemophagocytic syndrome in systemic lupus erythematosus successfully treated with intermittent intravenous cyclophosphamide: three case reports and literature review

We experienced three patients with refractory or severe hemophagocytic syndrome associated with the activity of systemic lupus erythematosus, so-called acute lupus hemophagocytic syndrome (ALHS). All patients were successfully treated with intermittent intravenous injections of cyclophosphamide (IVCY). In each patient, hemophagocytosis was found during bone marrow examination, and infectious causes of hemophagocytic syndrome were carefully excluded. Patients 1 and 2 were refractory to combination therapy with a high-dose corticosteroid and rituximab or cyclosporine and were successfully treated with additive IVCY. Patient 3 had very severe ALHS that developed after cardiac surgery but was successfully treated with a high-dose corticosteroid and IVCY. We conducted a literature review of adult ALHS and analyzed 54 cases reported from 2006 to 2013. Although the clinical and laboratory features were diverse, fever, bicytopenia or pancytopenia, and hyperferritinemia were almost universal. Including our 3 patients, a total of 16 have reportedly been treated with IVCY-containing regimens, and ALHS was successfully controlled in most of them without switching or adding other therapies. We suggest that combination therapy with IVCY and corticosteroids may be useful to treat severe or refractory ALHS.     

Effects of Electrophysiologic-Guided Therapy with Class IA Antiarrhythmic Drugs on the Long-Term Outcome of Patients with Idiopathic Ventricular Fibrillation with or without the Brugada Syndrome

INTRODUCTION: Implantation of a implantable cardioverter defibrillator (ICD) is viewed universally as the "gold standard" therapy for patients with idiopathic ventricular fibrillation (VF). We sought to study the long-term value of electrophysiologic (EP)-guided therapy with Class IA antiarrhythmic drugs in patients with idiopathic VF with or without the Brugada syndrome. METHODS AND RESULTS: We performed EP studies in 34 consecutive patients who had idiopathic VF with (n = 5) or without (n = 29) the Brugada syndrome. All patients with inducible sustained polymorphic ventricular tachycardia (SPVT) or VF underwent repeated EP evaluation after oral administration of a Class IA antiarrhythmic drug (mainly quinidine). Patients rendered noninducible received this therapy on a long-term basis. SPVT/VF were induced in 27 (79.4%) patients at baseline studies. Class IA drugs effectively prevented induction of SPVT/VF in 26 (96%) patients. Of the 23 patients treated with these medications, no patient died or had a sustained ventricular arrhythmia during a mean follow-up period of 9.1 +/- 5.6 years (7 to 20 years in 15 patients). Two deaths occurred in patients without inducible SPVT/VF at baseline studies who had been treated empirically. CONCLUSION: Our results suggest that EP-guided therapy with Class IA agents is a reasonable, safe, and effective approach for the long-term management of patients with idiopathic VF. A randomized prospective study of EP-guided Class IA therapy in patients with ICDs seems warranted.     

Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy

OBJECTIVES: We sought to demonstrate the mode of spontaneous onset of ventricular fibrillation (VF) in patients with Brugada syndrome. BACKGROUND: The electrophysiologic mechanisms of VF in Brugada syndrome have not been fully investigated. METHODS: Nineteen patients (all male, mean age 47 +/- 12 years) with Brugada syndrome were treated with an implantable cardioverter defibrillator (ICD). The implanted devices were capable of storing electrograms during an arrhythmic event. We investigated the mode of spontaneous onset of VF according to the electrocardiographic features during the episode of VF, which were obtained from stored electrograms of ICDs and/or electrocardiographic (ECG) monitoring. RESULTS: During a follow-up of 34.7 +/- 19.4 months (range 14 to 81 months), 46 episodes of spontaneous VF attacks were documented in 7/19 (37%) patients. The event-free period between ICD implantation and the first spontaneous occurrence of VF was 14.6 +/- 12.1 months (range 3.7 to 27.4 months). We investigated 33/46 episodes of VF, for which electrocardiographic features (10 to 20 s before and during VF) were obtained from ICDs and/or ECG monitoring in five patients. A total of 22/33 episodes of VF were preceded by premature ventricular contractions (PVCs), which were almost identical to the initiating PVCs of VF. Furthermore, in three patients who had multiple VF episodes, VF attacks were always initiated by the same respective PVC. The coupling interval of the initiating PVCs of VF was 388 +/- 28 ms. CONCLUSIONS: Spontaneous episodes of VF in patients with Brugada syndrome were triggered by specific PVCs. These findings may provide important insights into the pathophysiological mechanisms causing VF in Brugada syndrome.     

Pulmonary-renal syndrome in systemic sclerosis: a report of three cases and review of the literature

We describe three cases of acute renal failure with diffuse alveolar hemorrhage, which is designated pulmonary-renal syndrome (PRS), in systemic sclerosis (SSc) and review the literature to better define this rare but severe complication of SSc. The clinical course of three SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage are reported, and the literature published between 1967 and 2005 is reviewed following a PubMed search. Including our cases, a total of 19 SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage have been reported. Pulmonary-renal syndrome developing in SSc patients can be categorized clinicopathologically into three entities: PRS with thrombotic microangiopathy, PRS with small vessel vasculitides accompanied with SSc, and d-penicillamine-induced Goodpasture-like syndrome. Patients with scleroderma PRS with thrombotic microangiopathy, to which group our all patients belong, often developed diffuse alveolar hemorrhage after receiving high-dose corticosteroid therapy. Pulmonary-renal syndrome is a fatal complication of SSc and results from different pathogenic processes. Prompt differential diagnosis between the subsets is critical, because therapeutic strategy may differ in the use of high-dose corticosteroid and plasma exchange between the subsets of PRS. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy.     

HIV-1 gp41 antigen demonstration in esophageal ulcers with acquired immunodeficiency syndrome.

Esophageal ulcers associated with acquired immunodeficiency syndrome (AIDS) may be chronic, debilitating, and resistant to antifungal or antiviral therapy. The therapeutic management of these lesions remains controversial due to the difficulty in identifying pathogenic agent(s). We review previously published cases and describe three AIDS patients with esophageal ulcers that stained by immunoperoxidase techniques for human immunodeficiency virus (HIV)-1 surface glyloprotein (gp41). All three showed symptomatic resolution and healing of their ulcers with corticosteroid therapy. We believe this documentation of HIV-1 gp41 antigen within mononuclear cells of esophageal ulcers in AIDS supports a role of the HIV-1 virus in the pathophysiology of idiopathic esophageal ulcers in patients with AIDS. These cases further support a role for corticosteroid therapy in the treatment of esophageal ulcers resistant to antifungal and antiviral therapy in patients with AIDS.     

Alveolitis may persist during treatment that sufficiently controls muscle inflammation in myositis

Eight patients with dermato- and polymyositis (DM/PM) and two further cases with sclerodermamyositis overlap syndrome were investigated. These patients showed signs of lung manifestation by noninvasive methods. Bronchoalveolar lavage (BAL) was performed to detect alveolitis. Four of the eight DM/PM patients showed elevated neutrophil counts. All of these and one additional case had increased lymphocyte counts. Five of the DM/PM patients showed higher total cell numbers than five healthy controls. One of the cases with scleroderma-myositis overlap syndrome also developed lymphocyte alveolitis. We conclude that signs of alveolitis are often present in patients with myositis, even though the myositis was adequately controlled by corticosteroid therapy and, in four cases, with corticosteroid plus azathioprine. The need for further follow-up studies to determine the effectiveness of intensified corticosteroid/cytostatic treatment in these patients is emphasised.     

Churg Strauss syndrome after introducing oral steroid to inhaler: a report of three cases

The tetrad of bronchial asthma, severe sinusitis, nasal polyp, eosinophilia, and systemic vasculitis is the main feature of allergic granulomatosis and angitis (Churg- Strauss Syndrome). This vasculitis is usually seen idiopathic in patients with a long history of asthma; oral steroids using steroid inhalers, vaccination and desensitization might be triggering factors. Drugs such as leukotriene receptor antagonists (LTRAS), penicillin, sulphonamides, anticonvulsants and thiazides have also been implicated. By presenting the cases in this article, the authors suggest that some cases of CSS may be partially or totally suppressed by corticosteroid therapy of asthma for long periods and replacing oral steroid by inhaler will reveal a pathologic condition of CSS, called frustes CSS forms. We report three subjects with asthma who had been receiving previously multiple corticosteroid courses for control, but when systemic corticosteroids were discontinued or switched over to steroid inhaler, the patients developed a similar syndrome.     

Hydroquinidine therapy in Brugada syndrome

OBJECTIVES: We sought to assess hydroquinidine (HQ) efficacy in selected patients with Brugada syndrome (BrS). BACKGROUND: Management of asymptomatic patients with BrS and inducible arrhythmias remains a key issue. Effectiveness of class Ia antiarrhythmic drugs, which inhibit the potassium transient outward current of the action potential, has been suggested in BrS. METHODS: From a cohort of 106 BrS patients, we studied 35 who received HQ (32 men; mean age 48 +/- 11 years). Patients had asymptomatic BrS and inducible arrhythmia (n = 31) or multiple appropriate shocks from an implantable cardioverter-defibrillator (ICD) (n = 4). Asymptomatic patients with inducible arrhythmia underwent electrophysiologic (EP)-guided therapy. When ventricular tachycardia (VT)/ventricular fibrillation (VF) inducibility was not prevented, or in case of HQ intolerance, an ICD was placed. RESULTS: Hydroquinidine prevented VT/VF inducibility in 76% of asymptomatic patients who underwent EP-guided therapy. Syncope occurred in two of the 21 patients who received long-term (17 +/- 13 months) HQ therapy (1 syncope associated with QT interval prolongation and 1 unexplained syncope associated with probable noncompliance). In asymptomatic patients who received an ICD (n = 10), one appropriate shock occurred during a follow-up period of 13 +/- 8 months. In patients with multiple ICD shocks, HQ prevented VT/VF recurrence in all cases during a mean follow-up of 14 +/- 8 months. CONCLUSIONS: Hydroquinidine therapy prevented VT/VF inducibility in 76% of asymptomatic patients with BrS and inducible arrhythmia, as well as VT/VF recurrence in all BrS patients with multiple ICD shocks. These preliminary data suggest that preventive treatment by HQ may be an alternative strategy to ICD placement in asymptomatic patients with BrS and inducible arrhythmia.     

缺血性J波预测急性心肌梗死后恶性室性心律失常的临床价值

目的:分析急性心肌梗死J波与恶性心律失常的关系,探讨J波预测急性心肌梗死后恶性室性心律失常的临床价值。方法:将126例急性心肌梗死患者根据心电图是否存在J波分为观察组和对照组。结果:两组患者心律失常情况差异总体无显著性(P0.05),但是个别指标有显著性差异(P0.05)。J波呈顿挫型、振幅高、持续时间长者提示发生心脏事件危险性增加。结论:心电图中对J波综合征的诊断可以早期发现高危人群,提高对心源性猝死的防范,临床预测价值大。     

Ventricular fibrillation in acute myocardial infarction before and during primary PCI

BACKGROUND: There are scarce and sometimes contradictory data about ventricular fibrillation (VF) during the acute phase of MI. In-hospital VF most often occurs with inferior MI, when treated with fibrinolytics. Out-of-hospital VF seems to be associated with anterior MI. We studied characteristics of patients with VF during reperfusion therapy by primary angioplasty (PCI) versus patients with VF before PCI. METHODS: From January 1995 until December 2001, we treated 2826 patients for acute MI and reviewed clinical records of all patients who developed VF and classified the patients according to the first episode of VF: either before or during the angioplasty procedure. RESULTS: VF developed in 219 (8%) patients. Patients with VF during reperfusion therapy (n=74, 3%) were older (p=0.03), more frequently female (0.04), less often had heart failure (p=0.04), when compared with patient with VF before PCI (n=145, 5%). Patients with VF during PCI experienced more often preinfarction angina (p=0.009) and suffered more often from inferior MI (p=0.001), when compared with patients with VF before PCI. CONCLUSIONS: Patients with early VF before reperfusion have different characteristics when compared with patients with VF during reperfusion. Infarct location is a major determinant of timing of VF, when both groups are compared (p<0.001).     

A case of sjögren's syndrome associated with sweet's syndrome

Summary We report a case of Sjögren's syndrome whose clinical course had been indolent until the patient presented with Sweet's syndrome (acute febrile neutrophilic dermatosis). This patient showed renal failure and renal tubular acidosis. Sweet's syndrome resolved within 3 weeks without corticosteroid therapy. Renal biopsy findings were consistent with interstitial nephritis. His renal manifestations responded to corticosteroid therapy and the renal function remained stable during 6 years follow-up without recurrence of Sweet's syndrome. Although close association of both syndromes is already known, in our case Sjögren's syndrome may have been exacerbated by occurrence of Sweet's syndrome.     

Effect of long-term azathioprine administration in adults with minimal-change glomerulonephritis and nephrotic syndrome resistant to corticosteroids

Thirteen adult patients with nephrotic syndrome resistant to corticosteroid administration were treated with azathioprine daily for four years. Progressive improvement occurred in all 13 patients so that they were in complete remission after one to three years. The onset of apparent improvement was earlier and the rate of progressive improvement more rapid in patients who had selective proteinuria before therapy than in those whose proteinuria was nonselective. One patient who stopped therapy after 20 months suffered relapse but again responded when azathioprine treatment was restarted. Observation after the four-year therapeutic period ranges from three to 15 years; there have been no relapses during this time.     

Ventricular Fibrillation Associated With J-Wave Manifestation Following Pericarditis After Catheter Ablation for Paroxysmal Atrial Fibrillation

We present a patient with ventricular fibrillation (VF) associated with J-wave manifestation following pericarditis after catheter ablation of paroxysmal atrial fibrillation (AF). The premature ventricular contraction induced VF with J-waves in the inferior leads 2 days after the procedure. The patient's juvenile onset of AF and a family history of sudden cardiac death strongly suggested an underlying hereditable channelopathy. The late gadolinium enhancement in the posterior wall, viewed by cardiac magnetic resonance imaging, matched the leads of the J-waves. VF might develop in juvenile onset of AF especially in individuals with a family history of sudden cardiac death.     

Out-of-hospital cardiac arrest in patients with no overt heart disease: electrophysiologic observations and clinical outcome

Electrophysiologic studies were performed in nine survivors of out-of-hospital cardiac arrest who had no overt heart disease on clinical, hemodynamic and angiographic evaluation. Cardiac arrest occurred during sedentary activity in seven patients and during exercise in two; no patient was on antiarrhythmic drugs at the time of cardiac arrest. Twenty-four hour ambulatory electrocardiographic monitoring demonstrated premature ventricular beats in four patients (44%). Electrophysiologic stimulation induced sustained ventricular tachycardia (VT) or fibrillation (VF) in five patients, nonsustained VT in one patient and less than five ventricular beats in the remaining three patients. Of five patients with inducible sustained VT or VF, four had complete suppression of inducible VT with antiarrhythmic therapy, and none of these four patients died suddenly or had clinical VT after an average follow-up of 27 months (range 12 to 41 months). The remaining patient with inducible sustained VT refused serial electropharmacologic testing, was treated empirically with amiodarone (400 mg/day) and died suddenly eight months later. Of the four patients with noninducible sustained VT or VF, three received no antiarrhythmic therapy and one was given a beta-blocker. None had recurrent cardiac arrest or symptomatic VT after an average follow-up of 17 months (range 13 to 20 months). Thus, inducibility of sustained VT or VF provided a reliable end point for long term antiarrhythmic therapy and noninducibility identified a subset of patients that had an excellent prognosis without specific antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone

The determinants of long-term clinical outcome were studied in 42 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) who were treated with amiodarone as the sole antiarrhythmic agent. Of the 42 patients, 11 (26%) either died suddenly or had recurrent, symptomatic, sustained VT during a mean follow-up period of 10 months (range 0.3 to 45). Of the 19 patients without inducible VT/VF during electrophysiologic study while receiving amiodarone, 1 patient died suddenly but no patient had recurrent VT/VF. Ten of the 23 patients (43%) with persistently inducible arrhythmia have died suddenly or have had recurrent VT/VF. Using survival and stepwise logistic regression analyses, 2 significant independent predictors of recurrent arrhythmia were identified; persistently inducible VT during electrophysiologic testing in patients receiving amiodarone therapy (p < 0.002) and the left ventricular ejection fraction at rest (p < 0.05). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 67%, the sensitivity was 58% and the specificity was 91%. Thus, serial electrophysiologic testing is useful for determining the prognosis in patients with inducible VT/VF treated with amiodarone.     

Infant case with a malignant form of Brugada syndrome

We report a 6-month-old Japanese infant with a malignant form of Brugada syndrome, who had frequent episodes of ventricular fibrillation (VF) and nonsustained polymorphic ventricular tachycardia (VT). To the best of our knowledge, this infant is the youngest patient reported to have Brugada syndrome. Continuous infusion of a beta-adrenergic agonist and intravenous injection of a parasympathetic antagonist suppressed the electrical storm of polymorphic VT and VF. Combined oral administration of a beta1-adrenergic agonist, a parasympathetic antagonist, and quinidine has successfully suppressed recurrences of VT or VF for 6 months, and the combination may have the potential to decrease the incidence of VT or VF as an adjunctive therapy with prophylactic placement of an implantable cardioverter defibrillator.