Life-threatening Arrhythmias In Patients Research Articles

Delving into the issue of life-threatening arrhythmias in patients with Takotsubo syndrome

Delving into the issue of life-threatening arrhythmias in patients with Takotsubo syndrome

Early repolarization and positive T-wave alternans as risk markers for life-threatening arrhythmias in patients with vasospastic angina

BackgroundSeveral arrhythmogenic markers have been suggested as predictors for risk of life-threatening arrhythmias during symptom-free periods in vasospastic angina (VSA), but no definite conclusion has been drawn. ObjectiveTo investigate prevalence of fatal ventricular tachyarrhythmia in VSA and its relation to appearance of early repolarization (ER) and positive T wave alternans (p-TWA) in patients with VSA during symptom-free periods. MethodsWe studied 116 consecutive patients with chest pain who underwent an acetylcholine provocation test for VSA diagnosis. Patients were divided into two groups with positive (VSA group; 66 cases) and negative (control group; 50 cases) provocation test results. The presence of ER on electrocardiogram and the modified moving average analysis of TWA during symptom-free periods were explored. ResultsThe incidences of ER and p-TWA were higher in the VSA than in the control group (P=0.001 and P=0.006, respectively). Multivariate analysis revealed that ER and p-TWA were independent predictors of VSA (odds ratio, 5.65 and 4.94; 95% confidence interval: 1.11–28.9 and 1.22–19.9, respectively). The incidence of coexisting baseline ER and p-TWA was significantly higher in VSA patients with life-threatening arrhythmic events (3/3 vs. 6/38; P<0.001) than in those without. ConclusionsVSA patients with arrhythmic events showed a high incidence of ER and p-TWA during symptom-free periods. Therefore, baseline ER and p-TWA may help to identify VSA patients at high risk for life-threatening arrhythmias.

Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts.

Na(+) current (INa) results from the integrated function of a molecular aggregate (the voltage-gated Na(+) channel complex) that includes the β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including Brugada syndrome and sudden unexpected death in patients with epilepsy. We used Scn1b null mice to understand better the relation between Scn1b expression, and cardiac electrical function. Loss of Scn1b caused, among other effects, increased amplitude of tetrodotoxin-sensitive INa, delayed after-depolarizations, triggered beats, delayed Ca(2+) transients, frequent spontaneous calcium release events and increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM tetrodotoxin. We propose that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis. Na(+) current (INa) is determined not only by the properties of the pore-forming voltage-gated Na(+) channel (VGSC) α subunit, but also by the integrated function of a molecular aggregate (the VGSC complex) that includes the VGSC β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including cases of Brugada syndrome and sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null mouse models to understand better the relation between Scn1b expression, and cardiac electrical function. Using a combination of macropatch and scanning ion conductance microscopy we show that loss of Scn1b in juvenile null animals resulted in increased tetrodotoxin-sensitive INa but only in the cell midsection, even before full T-tubule formation; the latter occurred concurrent with increased message abundance for the neuronal Scn3a mRNA, suggesting increased abundance of tetrodotoxin-sensitive NaV 1.3 protein and yet its exclusion from the region of the intercalated disc. Ventricular myocytes from cardiac-specific adult Scn1b null animals showed increased Scn3a message, prolonged action potential repolarization, presence of delayed after-depolarizations and triggered beats, delayed Ca(2+) transients and frequent spontaneous Ca(2+) release events and at the whole heart level, increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM tetrodotoxin. Our results suggest that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis in ventricular myocytes.

Early repolarization and myocardial scar predict poorest prognosis in patients with coronary artery disease.

PurposeRecent studies show positive association of early repolarization (ER) with the risk of life-threatening arrhythmias in patients with coronary artery disease (CAD). This study was to investigate the relationships of ER with myocardial scarring and prognosis in patients with CAD.Materials and MethodsOf 570 consecutive CAD patients, patients with and without ER were assigned to ER group (n=139) and no ER group (n=431), respectively. Myocardial scar was evaluated using cardiac single-photon emission computed tomography.ResultsER group had previous history of myocardial infarction (33% vs. 15%, p<0.001) and lower left ventricular ejection fraction (57±13% vs. 62±13%, p<0.001) more frequently than no-ER group. While 74 (53%) patients in ER group had myocardial scar, only 121 (28%) patients had in no-ER group (p<0.001). During follow up, 9 (7%) and 4 (0.9%) patients had cardiac events in ER and no-ER group, respectively (p=0.001). All patients with cardiac events had ER in inferior leads and horizontal/descending ST-segment. Patients with both ER in inferior leads and horizontal/descending ST variant and scar had an increased adjusted hazard ratio of cardiac events (hazard ratio 16.0; 95% confidence interval: 4.1 to 55.8; p<0.001).ConclusionER in inferior leads with a horizontal/descending ST variant was associated with increased risk of cardiac events. These findings suggest that ER in patients with CAD may be related to myocardial scar rather than pure ion channel problem.

Abstract 183: Life-Threatening Arrhythmias in Patients Hospitalized with Acute Coronary Syndrome: Data from Latvian Registry 2008-2010

Purpose. Despite the major improvements in the care of patients with acute coronary syndrome (ACS), life - threatening arrhythmia (LTA) remains a common complication of myocardial infarction (MI). We have analyzed the rate of LTA in first hours after hospitalization in patients presenting with acute coronary syndrome and receiving different treatment strategies. Materials and methods. The data from Latvian registry of ACS in years 2008-2010 were analyzed. LTA was defined: complete AV block, unsustained/ sustained ventricular tachycardia (VT), ventricular fibrillation (VF). Results. In STEMI cohort, the incidence of LTA was significantly lower in PCI group after six hours (p&lt;0.05) than in patients receiving thrombolysis. In first two hours LTA incidence was higher in PCI patients, what we can be explained with earlier reperfusion changes and electrical instability. In non-STEMI cohort, the incidence of LTA was significantly lower than in STEMI patients (p&lt;0.01), but it was higher in non-invasive group compared to invasive treatment group. LTA rate was significantly reduced in statin users (p&lt;0.05). Conclusions. Despite the more aggressive treatment strategy, incidence of LTA remains high in ACS patients. Arrhythmias are often observed earlier in patients after PCI and later after thrombolysis. Earlier PCI can decrease late complication rate and potentially improve survival in STEMI patients.

Incidence and time frame of life-threatening arrhythmias in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Life-threatening arrhythmias may complicate the hospital course of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). The optimal duration of electrocardiographic monitoring in such patients is not well established. We aimed to determine the incidence and the time of occurrence of life-threatening arrhythmias in STEMI patients undergoing PPCI. Data of 382 consecutive patients with STEMI undergoing PPCI were analysed regarding the occurrence of ventricular fibrillation (VF), sustained ventricular tachycardia (sVT) or bradycardia necessitating temporary or permanent pacing. Of these patients, 55% had inferior STEMI, 41% anterior and 4% lateral STEMI. The infarct-related arteries were the right in 41%, the left anterior descending in 41%, the left circumflex in 16%, the left main stem in 1% and a vein graft in <1%. During hospitalisation, 27 (7.0%) patients developed 29 life-threatening arrhythmias (incidence 7.6%): 19 episodes occurred during PPCI (VF n = 11, bradycardia n = 8), 9 episodes during the first 24 hours after PPCI (VF n = 7, sVT n = 2), and 1 sVT episode in a hypokalemic patient on the 4th post-procedural day. A total of 17 patients (4.5%) died within the first 30 days, and 3 of these died during the PPCI procedure. Life-threatening arrhythmias occur in a considerable proportion of STEMI patients undergoing PPCI during hospitalisation. Most of these arrhythmias occur during the PPCI procedure. Post-procedural life-threatening arrhythmias are virtually limited to the first 24 hours after PPCI. Thus, routine electrocardiographic monitoring beyond the first 24 hours after PPCI might not be required in most patients with uncomplicated STEMI.

Cardiac resynchronization therapy to prevent life-threatening arrhythmias in patients with congestive heart failure

Various clinical data demonstrate that cardiac resynchronization therapy (CRT) provides a favorable structural as well as electrical remodeling. The CArdiac Resynchronization–Heart Failure study, which tested the pure effect of CRT (using CRT devices without the capability of defibrillation) clearly showed a significant reduction in the total mortality by partly preventing sudden cardiac death. The antiarrhythmic effects of CRT are explained, at least in part, by ionic and genetic modulation of ventricular myocytes. It has been revealed in animal experiments to mimic disorganized ventricular contraction that CRT reverses down-regulation of certain K+ channels and abnormal Ca2+ homeostasis in the failing heart. However, CRT can be proarrhythmic in some particular cases especially in the early phase of this therapy. According to our study, proarrhythmic effects after CRT can be observed in approximately 10% of patients. The relatively high incidence of the proarrhythmic effects of CRT may promote a trend toward selecting CRT-D rather than CRT-P.

Intracoronary administration of bone marrow-derived mononuclear cells and arrhythmic events in patients with chronic heart failure

There are continued debates on potential proarrhythmic effects of intracoronary bone marrow-derived progenitor cell (BMC) therapy for treatment of chronic heart failure. Implantable cardioverter-defibrillators (ICDs), a mainstay of heart failure therapy, provide the possibility of validly assessing arrhythmias in patients with chronic heart failure. The aim of this analysis was to assess the arrhythmogenic potential of intracoronary BMC therapy, continuously documented by ICD-stored intracardiac electrograms. Matched cohort study of 112 patients receiving intracoronary administration of autologous BMC and 224 heart failure patients, matched for age, gender, and left ventricular ejection fraction fitted with an ICD. Within a follow-up period of 2 years (total patient-years at risk: 595 years), no significant difference was detected for ICD-stored episodes of ventricular tachycardia (VT; 25.0 vs. 27.1%; P = 0.779), VT/ventricular fibrillation treated by antitachycardia pacing or ICD shock (15.6 vs. 15.5%; P = 0.956), or death from arrhythmic cause (4.2 vs. 1.0%; P = 0.667). Predictors of occurrence of major arrhythmic events were parameters of advanced heart failure and implantation of ICD for secondary prevention; no influence could be detected for BMC administration (odds ratio = 1.198; P = 0.440). There is no evidence that intracoronary administration of BMC aggravates life-threatening arrhythmias in patients with chronic heart failure.

Usefulness of T-wave alternans in sudden death risk stratification and guiding medical therapy.

Visible T-wave alternans (TWA), a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed for over a century to occur in association with life-threatening arrhythmias in patients with acute coronary syndrome, heart failure, and cardiac channelopathies. This compelling linkage prompted development of quantitative techniques leading to FDA-cleared commercial methodologies for measuring nonvisible levels of TWA in the frequency and time domains. The first aim of this review is to summarize evidence from more than a hundred studies enrolling a total of >12,000 patients that support the predictivity of TWA for cardiovascular mortality and sudden cardiac death. The second focus is on the usefulness of TWA in guiding therapy. Until recently, TWA has been used primarily in decision making for cardioverter-defibrillator implantation. Its potential utility in guiding pharmacologic therapy has been underappreciated. We review clinical literature supporting the usefulness of TWA as an index of antiarrhythmic effects and proarrhythmia for different drug classes. Beta-adrenergic and sodium channel-blocking agents are the most widely studied drugs in clinical TWA investigations, with both reducing TWA magnitude; the exception is patients in whom sodium channel blockade discloses the Brugada syndrome and provokes macroscopic TWA. An intriguing possibility is that TWA may help to detect beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which indirectly protects from arrhythmia through improving myocardial remodeling. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic intervention and thereby serve as a therapeutic target.

T-Wave Alternans as a Therapeutic Marker for Antiarrhythmic Agents

Over the course of more than a century, visible T-wave alternans (TWA), defined as a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed to occur in close association with life-threatening arrhythmias in patients with acute myocardial ischemia and infarction, heart failure, Prinzmetal's angina, and channelopathies, including Brugada and long QT syndromes. Over 100 studies enrolling a total of more than 12,000 patients support the predictivity of TWA testing for cardiovascular mortality and sudden cardiac death during both exercise and ambulatory electrocardiogram monitoring. To date, the main intended application has been to aid decision-making for cardioverter-defibrillator implantation. The prospect that TWA could be used to guide pharmacologic therapy has not received adequate attention. The literature supporting the utility of TWA as a therapeutic marker of antiarrhythmic effects and proarrhythmia is reviewed for each of the major antiarrhythmic drug classes. Beta-adrenergic and sodium channel blocking agents are the most widely studied drug classes in clinical TWA investigations, which report reductions in TWA magnitude. Patients with Brugada syndrome constitute a significant exception, because sodium channel blockade provokes the diagnostic electrocardiogram changes as well as macroscopic TWA. Calcium channel blockers have undergone extensive research in several animal models, but, surprisingly, no clinical studies on TWA with this class of drugs have been performed. Interestingly, TWA may help to detect the beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which exert their protective effects through putative indirect actions on myocardial remodeling. There is also suggestive evidence that the proarrhythmic effects associated with cardiovascular and noncardiovascular agents may be disclosed by elevated levels of TWA. Thus, the emerging collective evidence indicates the broad utility of TWA in estimating antiarrhythmic and proarrhythmic effects of diverse agents across differing pathologies. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic therapy.

Noninvasive Arrhythmia Risk Assessment in Guiding Pharmacologic Therapy for Prevention of Sudden Cardiac Death: Where Do We Stand? Where Do We Go?

Noninvasive Arrhythmia Risk Assessment in Guiding Pharmacologic Therapy for Prevention of Sudden Cardiac Death: Where Do We Stand? Where Do We Go?

Ventricular fibrillation triggered by marijuana use in a patient with ischemic cardiomyopathy: a case report

BackgroundA 60-year-old man presented to the emergency department with a left eye orbital rupture sustained during a fall due to syncope shortly after smoking more than his usual amount of marijuana.Case presentationThe patient reported experiencing a shock from his implantable cardioverter-defibrillator (ICD) device prior to the loss of consciousness. There was no biochemical, electrocardiographic, or clinical evidence of ischemia. ICD interrogation revealed one episode of ventricular fibrillation which was appropriately sensed and treated with a single shock of 35 Joules.ConclusionAlthough the cardiovascular effects of marijuana are usually well tolerated in young healthy users, its use may trigger life-threatening arrhythmias in patients with structural heart disease. To the best of our knowledge, this is the first report on a case of ventricular fibrillation triggered by marijuana use in a patient with an ICD.

Implantable cardioverter defibrillators and Chagas' disease: results of the ICD Registry Latin America

Chagas' disease is an endemic parasitic affliction in Latin America. It is frequently associated with ventricular tachyarrhythmia and sudden death. The aim of this study is to assess the evolution of patients with Chagas' disease treated with an implantable cardioverter defibrillator (ICD). Eighty-nine chagasic patients with ICD were included for analysis from the Medtronic ICD Registry Latin America. At implant, mean age was 59 +/- 10 years, and 72% were male. Eighty-one patients (91%) had secondary prevention indications. Mean left ventricular ejection fraction was 40 +/- 11%, and mean follow-up was 12 +/- 7 months. During follow-up, six patients died (6.7%); three due to congestive heart failure, one due to sudden death, and two due to non-cardiac cause. Hospitalization occurred in seven patients. Thirty-eight patients (42%) received appropriate ICD therapies. A total of 737 episodes were detected by the ICD. The mean period between ICD implantation and the first appropriate therapy was 104 days. Electrical storms were observed in 14 of the 89 patients (15.7%). Inappropriate therapies were observed in seven patients. This registry confirms that ICD therapy provides protection by effectively terminating life-threatening arrhythmias in patients with Chagas' disease. This is especially so when patients receive the device for secondary prevention.

Clinical trials update from the American College of Cardiology 2008: Carisma, Trends, meta‐analysis of Cox‐2 studies, Hat, on‐Target, Hyvet, Accomplish, Momentum, Protect, Horizon‐hf and Reverse

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. CARISMA investigated the use of implantable loop recorders for detecting life-threatening arrhythmias in patients with LVSD after MI and found that brady- and ventricular tachy-arrhythmias predicted an adverse prognosis. The TRENDS study showed that the burden of atrial fibrillation detected by pacemakers or defibrillators predicted the risk of embolic events but not with sufficient precision to justify changes in anti-thrombotic management. A meta-analysis of six trials reported an increased cardiovascular risk associated with celecoxib, particularly for heart failure, which was related to dose and baseline cardiovascular risk. The HAT study failed to show a benefit of providing post-MI patients with a home defibrillator. MOMENTUM, a study of a device designed to augment aortic blood flow, was stopped early due to increased bleeding risk. Results from PROTECT support the use of rolofylline 30 mg/day in acute heart failure, a definitive study is now underway. Istaroxime, an agent that appears to have both inotropic and lusitropic effects, improved haemodynamics when added to standard therapy in patients stabilised after admission with heart failure in HORIZON-HF. The REVERSE study suggested that CRT improves ventricular function and reduces morbidity even in patients with few or no symptoms of heart failure and may delay or prevent worsening heart failure.

Short-term day-time periodic breathing is not a risk factor for life-threatening arrhythmias in patients with heart failure

Short-term day-time periodic breathing is not a risk factor for life-threatening arrhythmias in patients with heart failure

Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure

Statins are associated with decreased incidence of life-threatening arrhythmias in patients with cardiomyopathy and reduce death and hospitalization in congestive heart failure (CHF). We hypothesized that statin use will reduce incident atrial fibrillation (AF) in patients with coronary heart disease (CHD), including those with CHF. A cohort of 17,741 patients with CHD examined between 1994 and 1997 at 5 Veterans Affairs medical facilities was assembled. Patients with known AF, warfarin treatment, liver disease, or no follow-up visits were excluded. The final cohort included 13,783 patients. The primary outcome was time to development of AF. Propensity scores were used to balance statin-treated and untreated patients with respect to baseline characteristics. Time from the initial visit to development of AF was analyzed with a Cox regression model, using statin treatment as a time-varying covariate. Among the 13,783 patients, 5417 (39%) received statin treatment. Statin-treated patients were younger with fewer comorbid conditions. After propensity adjustment, the baseline characteristics of the statin-treated and untreated patients were similar. During an average follow-up of 4.8 years, 1979 (14%) patients developed AF. In the overall study population there was no difference in AF incidence with statin treatment (hazard ratio 1.0, 95% CI 0.88-1.14, P = .9). However, AF was less common among statin-treated patients with CHF (hazard ratio 0.57, 95% CI 0.33-1.00, P = .04). We did not find any effect of statin treatment on AF incidence in patients with CHD; however, AF was reduced in a subset of patients with CHF.

Full Length Article

The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha “spontaneous” baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from −0.09 ± 0.01 to −0.16 ± 0.01 mm Hg · mm Hg−1, p < 0.01, and from 1.25 ± 0.9 to 1.76 ± 1.1 ms · mm Hg−1, p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 ± 1.4 to 12.2 ± 1.2 ms · mm Hg−1, p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.

Enhanced Baroreceptor Control of the Cardiovascular System by Polyunsaturated Fatty Acids in Heart Failure Patients

The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha "spontaneous" baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from -0.09 +/- 0.01 to -0.16 +/- 0.01 mm Hg x mm Hg(-1), p < 0.01, and from 1.25 +/- 0.9 to 1.76 +/- 1.1 ms x mm Hg(-1), p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 +/- 1.4 to 12.2 +/- 1.2 ms x mm Hg(-1), p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.

Effects of Statin Therapy on Arrhythmic Events and Survival in Patients With Nonischemic Dilated Cardiomyopathy

We sought to evaluate whether statins were associated with a survival benefit and significant attenuation in life-threatening arrhythmias in patients with nonischemic dilated cardiomyopathy. Statins are associated with a reduction in appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease and improved clinical status in nonischemic dilated cardiomyopathy. The effect of statin use on time to death or resuscitated cardiac arrest and time to arrhythmic sudden death was evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on time to first appropriate shock was analyzed only in the 229 patients who were randomized to ICD therapy. The unadjusted hazard ratio (HR) for death among patients on versus those not on statin therapy was 0.22 (95% confidence interval [CI] 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p = 0.04). There was one arrhythmic sudden death in the 110 patients receiving statin therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04). The unadjusted HR for arrhythmic sudden death among patients on versus those not on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for appropriate shocks among patients on versus those not on statin therapy was 0.78 (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two groups. Statin use in the DEFINITE study was associated with a 78% reduction in mortality. This reduction was caused, in part, by a reduction in arrhythmic sudden death. These findings should be confirmed in a prospective, randomized clinical trial.

Clinical trials update from the European Society of Cardiology meeting 2005: CARE‐HF extension study, ESSENTIAL, CIBIS‐III, S‐ICD, ISSUE‐2, STRIDE‐2, SOFA, IMAGINE, PREAMI, SIRIUS‐II and ACTIVE

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.