Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials.

OBJECTIVES: The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. METHODS: In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial was clinical status at 9 months (assessed by the hierarchical clinical composite); the primary outcome across the 2 trials was death from any cause or hospitalization for heart failure. RESULTS: Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. CONCLUSIONS: Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Value of CACS compared with ETT and myocardial perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic patients at low risk for coronary disease: clinical implications in a multimodality imaging world.

OBJECTIVES: This prospective, observational study in 988 asymptomatic or symptomatic low-risk patients without prior coronary artery disease was conducted to define the relative value of coronary artery calcium score (CACS), exercise treadmill testing (ETT), and stress myocardial perfusion single-photon emission computed tomography (SPECT) variables in predicting long-term risk stratification. BACKGROUND: CACS, ETT, and stress myocardial perfusion SPECT results predict patients' outcome. There are currently no data comparing their relative value in long-term risk stratification. METHODS: Patients were stratified by Framingham risk score (FRS), with a median follow-up of 6.9 years. Cardiac events were defined as a composite of cardiac death, nonfatal myocardial infarction, and the need for coronary revascularization. Most patients (87%) were considered appropriate candidates for functional testing as defined by current appropriate use criteria. RESULTS: The long-term cardiac event rate was 11.2% (1.6% per year). Multivariate risk predictors in all patients and in the appropriate use cohort were abnormal SPECT (hazard ratio [HR]: 1.83 and 1.99), ETT ischemia (HR: 1.70 and 1.76), decreasing exercise capacity (HR: 1.11 and 1.17), decreasing Duke treadmill score (HR: 1.07 for both), and CACS severity (HR: 1.29 for both), respectively. Throughout the 10-year follow-up, CACS improved risk prediction, with event rates ranging from 0.6% per year (CACS ≤10) to 3.7% per year (CACS >400) (p < 0.0001). CACS also improved risk prediction in all patients, in the appropriate use cohort and among those with low-risk ETT and SPECT results (all, p < 0.001). Area under the receiver-operating characteristic curve was increased when CACS variables (from 0.63 to 0.70; p = 0.01) but not ETT variables (from 0.63 to 0.65) were added to FRS. Moreover, net reclassification improvement was significantly increased when CACS was added to FRS + functional variables in all patients and in the appropriate use cohort (both, p < 0.0001). CONCLUSIONS: CACS significantly improved long-term risk stratification beyond FRS, ETT, and SPECT results across the spectrum of clinical risk and importantly even among those who are currently considered appropriate candidates for functional testing or have low-risk functional test results. Our findings support CACS as a first-line test over ETT or SPECT for accurately assessing long-term risk in such patients.

Case report: Severe hypercalcemia mimicking ST-segment elevation myocardial infarction.

The identification of ST-segment elevation on the electrocardiogram is an integral part of decision making in patients who present with suspected ischemia. Unfortunately, ST-segment elevation is nonspecific and may be caused by noncardiac causes such as electrolyte abnormalities. We present a case of ST-segment elevation secondary to hypercalcemia in a patient with metastatic cancer.

Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: a randomized controlled trial.

CONTEXT: Atrial fibrillation (AF) is common, yet there remains an unmet medical need for additional treatment options. Current pharmacological treatments have limited efficacy and significant adverse events. Limited data from small trials suggest omega-3 polyunsaturated fatty acids may provide a safe, effective treatment option for AF patients. OBJECTIVE: To evaluate the safety and efficacy of prescription omega-3 fatty acids (prescription omega-3) for the prevention of recurrent symptomatic AF. DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, double-blind, placebo-controlled, parallel-group multicenter trial involving 663 US outpatient participants with confirmed symptomatic paroxysmal (n = 542) or persistent (n = 121) AF, with no substantial structural heart disease, and in normal sinus rhythm at baseline were recruited from November 2006 to July 2009 (final follow-up was January 2010). INTERVENTIONS: Prescription omega-3 (8 g/d) or placebo for the first 7 days; prescription omega-3 (4 g/d) or placebo thereafter through week 24. MAIN OUTCOME MEASURES: The primary end point was symptomatic recurrence of AF (first recurrence) in participants with paroxysmal AF. Secondary analyses included first recurrence in the persistent stratum and both strata combined. Participants were followed up for 6 months. RESULTS: At 24 weeks, in the paroxysmal AF stratum, 129 of 269 participants (48%) in the placebo group and 135 of 258 participants (52%) in the prescription group had a recurrent symptomatic AF or flutter event. In the persistent AF stratum, 18 participants (33%) in the placebo group and 32 (50%) in the prescription group had documented symptomatic AF or flutter events. There was no difference between treatment groups for recurrence of symptomatic AF in the paroxysmal stratum (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90-1.46; P = .26), in the persistent stratum (HR, 1.64; 95% CI, 0.92-2.92; P = .09), and both strata combined (HR, 1.22; 95% CI, 0.98-1.52; P = .08). Other, secondary end points were supportive of the primary result. A total of 5% of those receiving placebo and 4% of those receiving prescription omega-3 discontinued due to adverse events. Eicosapentaenoic and docosahexaenoic acid blood levels were significantly higher in the prescription group than in the placebo group at weeks 4 and 24. CONCLUSION: Among participants with paroxysmal AF, 24-week treatment with prescription omega-3 compared with placebo did not reduce recurrent AF over 6 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402363.

Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation.

The objective of the present study was to assess the safety and effectiveness of vernakalant hydrochloride injection (RSD1235), a novel antiarrhythmic drug, for the conversion of atrial fibrillation (AF) or atrial flutter to sinus rhythm (SR). Patients with either AF or atrial flutter were randomized in a 1:1 ratio to receive vernakalant (n = 138) or placebo (n = 138) and were stratified by an arrhythmia duration of >3 hours to ≤7 days (short duration) and 8 to ≤45 days (long duration). The first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if the arrhythmia had not terminated. A total of 265 patients were randomized and received treatment. The primary end point was conversion of AF to SR for ≥1 minute within 90 minutes of the start of the drug infusion in the short-duration AF group. Of the 86 patients receiving vernakalant in the short-duration AF group, 44 (51.2%) demonstrated conversion to SR compared to 3 (3.6%) of the 84 in the placebo group (p <0.0001). The median interval to conversion of short-duration AF to SR in the responders given vernakalant was 8 minutes. Of the entire AF population (short- and long-duration AF), 47 (39.8%) of the 118 vernakalant patients experienced conversion of AF to SR compared to 4 (3.3%) of the 121 placebo patients (p <0.0001). Transient dysgeusia and sneezing were the most common adverse events in the vernakalant patients. One vernakalant patient who had severe aortic stenosis experienced hypotension and ventricular fibrillation and died. In conclusion, vernakalant demonstrated a rapid and high rate of conversion for short-duration AF and was well tolerated.

Practice patterns among United States cardiologists for managing adults with atrial fibrillation (from the AFFECTS Registry).

The Atrial Fibrillation: Focus on Effective Clinical Treatment Strategies (AFFECTS) Registry was designed to examine atrial fibrillation (AF) treatment by United States cardiologists in the context of the American College of Cardiology, American Heart Association, and European Society of Cardiology guidelines after recent landmark clinical trials. Most patients in AFFECTS had AF without clinically significant structural heart disease or only uncomplicated hypertension. Among the all-enrolled population (n = 1,461), initial treatment strategies assigned were rhythm control in 64% and rate control in 36%. Among patients with either paroxysmal (n = 1,165) or persistent (n = 273) AF, 67% and 55%, respectively, were assigned rhythm control. The trend to assign rhythm control as the initial treatment goal decreased with age. In the rhythm-control group, most patients (74%) also received a rate-control agent during the registry, while 25% of those assigned to rate control received antiarrhythmic drugs. Most first prescriptions of antiarrhythmic drugs were for first-line therapy compliant with 2001 (76%) and 2006 (86%) guidelines. Most second prescriptions were for first-line therapies as well. Rates of serious adverse events were low. In conclusion, data from this study provide insight into community treatment patterns in patients with AF, most without clinically significant structural heart disease or with only uncomplicated hypertension.

Warfarin and aspirin use in atrial fibrillation among practicing cardiologist (from the AFFECTS Registry).

Among patients with atrial fibrillation (AF), the risk of thromboembolism is a significant concern. However, the reported use of warfarin among patients with AF at elevated risk of stroke remains low. In the present study, we have provided information on anticoagulation use reported during the recent Atrial Fibrillation: Focus on Effective Clinical Treatment Strategies (AFFECTS) Registry. Among patients identified by their physician at baseline to be at an increased risk of stroke, as determined from an assessment of the medical history, 74% received warfarin and 29% received aspirin. Post hoc analysis of warfarin use stratified by Congestive heart failure, Hypertension, Age, Diabetes, Stroke, (CHADS(2)) doubled score revealed that at the end of the study, warfarin use was 73% (155 of 213) and 66% (185 of 280) in the rate- and rhythm-control patients with a score of > or = 2, respectively, compared to 60% (183 of 306) and 49% (322 of 662) in the rate- and rhythm-control patients with a score of <2, respectively. The practicing cardiologists who participated in this registry initiated anticoagulation therapy in most of their patients with AF. However, warfarin use is not yet in line with the guidelines and evidence-based recommendations. Patients considered at no risk of stroke appear to have been overprescribed anticoagulant agents, and a considerable portion of high-risk patients did not receive warfarin. In conclusion, these results suggest that continued physician education of appropriate anticoagulation use in patients with AF is needed.

Coronary artery calcium scoring in the emergency department: identifying which patients with chest pain can be safely discharged home.

STUDY OBJECTIVE: Coronary artery calcium scoring (CACS) is a simple and readily available test for identifying coronary artery disease. Our objective is to evaluate whether a CACS of zero will identify chest pain patients who can be safely discharged home, without need for further cardiac testing. METHODS: This was a prospective observational cohort study conducted at an urban tertiary care hospital of stable patients presenting to the emergency department (ED) with chest pain of uncertain cardiac cause. Patients with a normal initial troponin level, nonischemic ECG, and no history of coronary artery disease had stress myocardial perfusion imaging (SPECT) and CACS within 24 hours of ED admission. Cardiac events were defined as an acute coronary syndrome during the index hospitalization or in follow-up. CACS results were assessed in relation to SPECT findings and cardiac events. RESULTS: The 1,031 patients enrolled (mean [SD] age 54 [13] years) had a median CACS of 0 (61% with CACS of 0). The frequency of an abnormal SPECT ranged from 0.8% (CACS of 0) to17% (CACS>400). Cardiac events occurred in 32 patients (3.1%) during the index hospitalization (N=28) or after hospital discharge (N=4) (mean 7.4 [3.3] months). Only 2 events occurred in 625 patients with a CACS of 0 (0.3%; 95% confidence interval 0.04% to 1.1%). Thus, 2 of 32 patients with a cardiac event had a CACS of 0 (6%; 95% confidence interval 0.8% to 21%). Both of these patients developed increased troponin levels during their index visit but had normal serial ECG and SPECT study results and no cardiac events at 6-month follow-up. CONCLUSION: A majority of patients (61% in our sample) evaluated for chest pain of uncertain cardiac cause have a CACS of 0, which predicts both a normal SPECT result and an excellent short-term outcome. Our results suggest that patients with a CACS of 0 can be discharged home, without further cardiac testing.

Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Postoperative atrial arrhythmias are common and are associated with considerable morbidity. This study was designed to evaluate the efficacy and safety of vernakalant for the conversion of atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery. METHODS AND RESULTS: This was a prospective, randomized, double-blind, placebo-controlled trial of vernakalant for the conversion of AF or AFL after coronary artery bypass graft, valvular surgery, or both. Patients were randomly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo. If AF or AFL was present after a 15-minute observation period, then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given. The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing. In patients with AF, 47 of 100 (47%) who received vernakalant converted to SR compared with 7 of 50 (14%) patients who received placebo (P<0.001). The median time to conversion was 12 minutes. Vernakalant was not effective in converting postoperative AFL to sinus rhythm. Two serious adverse events occurred within 24 hours of vernakalant administration (hypotension and complete atrioventricular block). There were no cases of torsades de pointes, sustained ventricular tachycardia, or ventricular fibrillation. There were no deaths. CONCLUSIONS: Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. Identifier: NCT00125320.

The coronary artery calcium score and stress myocardial perfusion imaging provide independent and complementary prediction of cardiac risk.

OBJECTIVES: This study sought to examine the relationship between coronary artery calcium score (CACS) and single-photon emission computed tomography (SPECT) results for predicting the short- and long-term risk of cardiac events. BACKGROUND: The CACS and SPECT results both provide important prognostic information. It is unclear whether integrating these tests will better predict patient outcome. METHODS: We followed-up 1,126 generally asymptomatic subjects without previous cardiovascular disease who had a CACS and stress SPECT scan performed within a close time period (median 56 days). The median follow-up was 6.9 years. End points analyzed were total cardiac events and all-cause death/myocardial infarction (MI). RESULTS: An abnormal SPECT result increased with increasing CACS from <1% (CACS < or =10) to 29% (CACS >400) (p < 0.001). Total cardiac events and death/MI also increased with increasing CACS and abnormal SPECT results (p < 0.001). In subjects with a normal SPECT result, CACS added incremental prognostic information, with a 3.55-fold relative increase for any cardiac event (2.75-fold for death/MI) when the CACS was severe (>400) versus minimal (< or =10). Separation of the survival curves occurred at 3 years after initial testing for all cardiac events and at 5 years for death/MI. CONCLUSIONS: The CACS and SPECT findings are independent and complementary predictors of short- and long-term cardiac events. Despite a normal SPECT result, a severe CACS identifies subjects at high long-term cardiac risk. After a normal SPECT result, our findings support performing a CACS in patients who are at intermediate or high clinical risk for coronary artery disease to better define those who will have a high long-term risk for adverse cardiac events.

Efficacy and safety of prescription omega-3-acid ethyl esters for the prevention of recurrent symptomatic atrial fibrillation: a prospective study.

BACKGROUND: Atrial fibrillation (AF) continues to be one of the most common cardiac problems, placing an expanding burden on the public health system. In several circumstances, AF can increase the risk of stroke and heart failure. Current pharmacologic treatment options are associated with the potential for significant adverse events, which often outweigh the benefits of achieving sinus rhythm. There is evidence to suggest antiarrhythmic benefits of omega-3 polyunsaturated fatty acids; however, the data are not conclusive. This study is designed to further assess the effect of prescription omega-3 ethyl esters (P-OM3) in the prevention of recurrent AF in patients with AF without (significant) structural heart disease. METHODS: This trial is a 6-month randomized, double-blind, placebo-controlled, parallel-study design. Patients with confirmed symptomatic paroxysmal or persistent AF (5:1 ratio) will be randomized to receive either 4 g/d P-OM3 (Lovaza; GlaxoSmithKline, Research Triangle Park, NC) or placebo. The primary end point is the first recurrence of symptomatic AF among patients with paroxysmal AF. Secondary end points include the first recurrence of symptomatic AF among all patients. Safety will be assessed regularly. CONCLUSION: This is the first randomized blinded trial to assess the antiarrhythmic effects of 4 g/d P-OM3 in paroxysmal AF.

Azimilide reduces emergency department visits and hospitalizations in patients with an implantable cardioverter-defibrillator in a placebo-controlled clinical trial.

OBJECTIVES: The goal of this study was to determine whether azimilide, as compared with placebo, will reduce the number of emergency department (ED) visits and hospitalizations caused by arrhythmias or cardiac events in patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Patients with an ICD may require ED visits and hospitalizations because of arrhythmias, which trigger ICD therapies. The effect of adjunctive antiarrhythmic therapy on these outcomes is not known. METHODS: A total of 633 patients with an ICD were randomized in the SHIELD (SHock Inhibition Evaluation with AzimiLiDe) trial, a blinded, placebo-controlled randomized trial of the investigational class III antiarrhythmic azimilide (75 and 125 mg/day), and, prospectively, cardiac and arrhythmic ED visits and hospitalization data were collected over 1 year. RESULTS: All patients had symptomatic sustained ventricular tachycardia (72%) or ventricular fibrillation (28%) before study entry. Overall, 44% (n = 276) experienced at least 1 cardiac ED visit or hospitalization. Among 214 patients assigned to placebo, 38.3% had at least 1 arrhythmic-related ED visit or hospitalization compared with 21.8% of 220 patients assigned to 75-mg azimilide (p < 0.001) and 27.6% of 199 patients assigned to 125 mg azimilide (p < 0.05). Symptomatic ventricular tachycardia treated by antitachycardia pacing, shocks, and shocks plus symptomatic arrhythmias were significant predictors of cardiac-related ED visits or hospitalizations (relative risk: 2.0, 3.0, and 3.1, respectively). In a stepwise logistic regression model, the presence of congestive heart failure (New York Heart Association functional class II/III) was the only additional independent predictor of cardiac ED visits or hospitalizations. CONCLUSIONS: Azimilide significantly reduces the number of ED visits and hospitalizations in patients with an ICD at high risk of arrhythmias.

Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial.

BACKGROUND: The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF). METHODS AND RESULTS: Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time, 11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<0.001). Overall, in the short- and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients (2.6%; P<0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. CONCLUSIONS: Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.

Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial.

BACKGROUND: Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. METHODS: We did a double-blind, placebo-controlled study of a device-based non-specific immunomodulation therapy (IMT) in patients with New York Heart Association (NYHA) functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting within the past 12 months. Patients were randomly assigned to receive IMT (n=1213) or placebo (n=1213) by intragluteal injection on days 1, 2, 14, and every 28 days thereafter. Primary endpoint was the composite of time to death from any cause or first hospitalisation for cardiovascular reasons. The study continued until 828 primary endpoint events had accrued and all study patients had been treated for at least 22 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00111969. FINDINGS: During a mean follow-up of 10.2 months, there were 399 primary events in the IMT group and 429 in the placebo group (hazard ratio 0.92; 95% CI 0.80-1.05; p=0.22). In two prespecified subgroups of patients--those with no history of previous myocardial infarction (n=919) and those with NYHA II heart failure (n=689)--IMT was associated with a 26% (0.74; 0.57-0.95; p=0.02) and a 39% (0.61; 95% CI 0.46-0.80; p=0.0003) reduction in the risk of primary endpoint events, respectively. INTERPRETATION: Non-specific immunomodulation may have a role as a potential treatment for a large segment of the heart failure population, which includes patients without a history of myocardial infarction (irrespective of their functional NYHA class) and patients within NYHA class II.

A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether gated adenosine Tc-99m sestamibi single-photon emission computed tomography (ADSPECT) could accurately define risk and thereby guide therapeutic decision making in stable survivors of acute myocardial infarction (AMI). BACKGROUND: Controversy continues as to the role of noninvasive stress imaging in stratifying risk early after AMI. METHODS: The INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) trial is a prospective multicenter trial which enrolled 728 clinically stable survivors of AMI who had gated ADSPECT within 10 days of hospital admission and subsequent 1-year follow-up. Event rates were assessed within prospectively defined INSPIRE risk groups based on the adenosine-induced left ventricular perfusion defect size, extent of ischemia, and ejection fraction. RESULTS: Total cardiac events/death and reinfarction significantly increased within each INSPIRE risk group from low (5.4%, 1.8%), to intermediate (14%, 9.2%), to high (18.6%, 11.6%) (p < 0.01). Event rates at 1 year were lowest in patients with the smallest perfusion defects but progressively increased when defect size exceeded 20% (p < 0.0001). The perfusion results significantly improved risk stratification beyond that provided by clinical and ejection fraction variables. The low-risk INSPIRE group, comprising one-third of all enrolled patients, had a shorter hospital stay with lower associated costs compared with the higher-risk groups (p < 0.001). CONCLUSIONS: Gated ADSPECT performed early after AMI can accurately identify a sizeable low-risk group who have a <2% death and reinfarction rate at 1 year. Identifying these low-risk patients for early hospital discharge may improve utilization of health care resources at considerable cost savings.

An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown. METHODS: A prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (> or =20%) and ischemic (> or =10%) adenosine-induced left ventricular perfusion defects and an ejection fraction > or =35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics. RESULTS: Both intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (-16.2 +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function.

Electrical storm in patients with an implantable defibrillator: incidence, features, and preventive therapy: insights from a randomized trial.

AIMS: The purpose of this study was to assess the incidence, features, and clinical sequelae of 'electrical storm' (ES). METHODS AND RESULTS: This study is a prospectively designed secondary analysis of SHIELD; a randomized trial of azimilide for suppression of ventricular tachycardia/fibrillation (VT/VF) leading to implanted cardioverter defibrillator (ICD) therapies. Systematic and rigorous follow-up and blinded adjudication of ICD therapy allowed identification of all ESs (>/=3 separate VT/VF episodes leading to ICD therapies within 24 h). Of 633 ICD recipients, 148 (23%) experienced at least one ES over 1-year follow-up. No clinical predictors of ES were identified. Frequent VT episodes accounted for 91% of all ESs, with the remaining being VF alone or both VT plus VF. ES led to a 3.1-fold increase in arrhythmia-related hospitalization (95% CI 2.3-4.3; P<0.0001) compared with patients with isolated VT/VF, and to a 10.2-fold increase (95% CI 6.4-16.3; P<0.0001) compared with patients without VT/VF. Compared with placebo, azimilide (75 and 125 mg/day) reduced the risk of recurrent ES by 37% (HR=0.63, 95% CI 0.35-1.11, P=0.11) and 55% (HR=0.45, 95% CI 0.23-0.87, P=0.018), respectively. However, the reduction in time-to-first ES did not reach statistical significance by both doses (75 and 125 mg) of azimilide (HR=0.82, 95% CI 0.56-1.19, P=0.29 and HR=0.69, 95% CI 0.46-1.04, P=0.07), respectively. CONCLUSION: ES is common and unpredictable in ICD recipients and it is a strong predictor of hospitalization.

Cumulative experience of azimilide-associated torsades de pointes ventricular tachycardia in the 19 clinical studies comprising the azimilide database.

OBJECTIVES: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. BACKGROUND: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. METHODS: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients with a left ventricular ejection fraction < or =35%. RESULTS: The TdP occurred in 56 patients assigned to azimilide, was dose-related, and tended to occur earlier with an azimilide-loading regimen. Forty-three percent of TdP patients had a QT interval corrected by Bazett's formula, for heart rate, (QTc) > or =500 ms at the time of or before the TdP occurrence. Significant risk factors using logistic regression were increasing age, female gender, diuretic use, and lack of aspirin use. CONCLUSIONS: Azimilide-associated TdP has characteristics and risk factors similar to other Ikr blockers. However, there is a distinctive temporal profile. The TdP events are not concentrated in the first week. The azimilide-associated TdP rate is 1% (95% confidence interval 0.78 to 1.35) and is not increased in patients with low left ventricular ejection fraction, even in women.

Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database).

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were <65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (<65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.