Peter A. Brady

Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction

OBJECTIVES The purpose of this study was to examine the impact of sulfonylurea drug use on outcome in diabetic patients undergoing direct coronary angioplasty for acute myocardial infarction. BACKGROUND Sulfonylurea drugs impair ischemic preconditioning. Whether sulfonylurea drugs affect outcome adversely in diabetic patients undergoing direct angioplasty for acute myocardial infarction is unknown. METHODS Clinical outcomes after direct balloon angioplasty for acute myocardial infarction were evaluated in 67 diabetic patients taking oral sulfonylurea drugs and 118 diabetic patients not taking these drugs. RESULTS Hospital mortality was significantly higher among diabetics treated with sulfonylurea drugs at the time of myocardial infarction (24% vs. 11%). Univariate analysis identified sulfonylurea drug, age, ventricular function, ejection fraction less than 40%, prior bypass surgery and congestive heart failure as correlates of increased in-hospital mortality. Logistic regression found sulfonylurea drug use (odds ratio 2.77, p=0.017) to be independently associated with early mortality. Congestive heart failure, but not sulfonylurea drug use, was associated with an increased incidence of in-hospital ventricular arrhythmias. Congestive heart failure, prior bypass surgery and female gender, but not sulfonylurea drug use, were associated with late adverse events. CONCLUSIONS Sulfonylurea drug use is associated with an increased risk of in-hospital mortality among diabetic patients undergoing coronary angioplasty for acute myocardial infarction. This early risk is not explained by an increase in ventricular arrhythmias, but may reflect deleterious effects of sulfonylurea drugs on myocardial tolerance for ischemia and reperfusion. For surviving patients sulfonylurea drug use is not associated with an increased risk of serious late adverse events.

Syncope Evaluation in the Emergency Department Study (SEEDS) A Multidisciplinary Approach to Syncope Management

Background—The primary aim and central hypothesis of the study are that a designated syncope unit in the emergency department improves diagnostic yield and reduces hospital admission for patients with syncope who are at intermediate risk for an adverse cardiovascular outcome. Methods and Results—In this prospective, randomized, single-center study, patients were randomly allocated to 2 treatment arms: syncope unit evaluation and standard care. The 2 groups were compared with &khgr;2 test for independence of categorical variables. Wilcoxon rank sum test was used for continuous variables. Survival was estimated with the Kaplan-Meier method. One hundred three consecutive patients (53 women; mean age 64±17 years) entered the study. Fifty-one patients were randomized to the syncope unit. For the syncope unit and standard care patients, the presumptive diagnosis was established in 34 (67%) and 5 (10%) patients (P<0.001), respectively, hospital admission was required for 22 (43%) and 51 (98%) patients (P<0.001), and total patient-hospital days were reduced from 140 to 64. Actuarial survival was 97% and 90% (P=0.30), and survival free from recurrent syncope was 88% and 89% (P=0.72) at 2 years for the syncope unit and standard care groups, respectively. Conclusions—The novel syncope unit designed for this study significantly improved diagnostic yield in the emergency department and reduced hospital admission and total length of hospital stay without affecting recurrent syncope and all-cause mortality among intermediate-risk patients. Observations from the present study provide benchmark data for improving patient care and effectively utilizing healthcare resources.

The Sulfonylurea Controversy: More Questions From the Heart

Myocardial ischemia and infarction are associated with substantially increased morbidity and mortality among patients with diabetes mellitus. Although many factors contribute to the increased morbidity and mortality, in patients with non-insulin-dependent (type II) diabetes mellitus, one contributor may be the use of sulfonylurea drugs, the most widely used oral hypoglycemic agents. Such a possibility, which first arose over a 25 years ago when it was observed that patients taking sulfonylurea drugs had increased cardiovascular mortality, has recently resurfaced after the discovery that sulfonylureas act by inhibiting adenosine triphosphate (ATP)-sensitive potassium channels. In the pancreas, inhibition of ATP-sensitive potassium channels induces release of insulin; but in the heart, inhibition of these channels prevents ischemic preconditioning, an endogenous cardioprotective mechanism that protects the heart from lethal injury. This review outlines the current understanding of the molecular and cellular pharmacodynamics of sulfonylurea drugs and discusses the potential clinical consequences of inhibition of ATP-sensitive potassium channels in the heart of diabetic patients with cardiac disease in whom the use of sulfonylureas may be harmful.

Device complications and inappropriate implantable cardioverter defibrillator shocks in patients with hypertrophic cardiomyopathy

Background: Although the benefit of implantable cardioverter defibrillator (ICD) therapy in patients with hypertrophic cardiomyopathy (HCM) at risk for sudden cardiac arrest is well established, there may be a higher risk for device complications and inappropriate shocks. Objectives: To determine the incidence of inappropriate ICD shocks and device complications in HCM patients and the impact of young age at ICD implant and atrial fibrillation. Methods: HCM patients who underwent ICD implantation between January 1988 and December 2005 were included. The frequency of device complications, including pneumothorax, pericardial effusion, haematoma, lead revisions, infection and rate of inappropriate shocks, was determined. ICD shocks were characterised as inappropriate if triggered by sinus tachycardia, atrial fibrillation or device malfunction. Results: A total of 181 patients were included (mean age 44 (SD 17) years; 62% males). During a mean follow-up of 59 (42) months (4.92 years; 830.75 patient-years), 65 patients (36%) had a total of 88 device complications, including 42 (23%) patients with inappropriate shocks. The rate of inappropriate shocks was 5.3% per year (vs 4% risk of appropriate shocks), and the likelihood of inappropriate ICD shocks per 100 patient-years was 5.1. Younger age and atrial fibrillation were associated with an increased risk of inappropriate ICD discharges. Conclusions: The rate of inappropriate ICD shocks and frequency of device complications in HCM patients are not insignificant and are most common in younger patients and those with atrial fibrillation. Inappropriate ICD shocks are the most common device complication and should be accounted for when counselling high-risk HCM patients for ICD implantation.

Isolated Left Ventricular Noncompaction Syndrome

Isolated left ventricular noncompaction (ILVNC) is a rare congenital cardiomyopathy characterized by prominent trabeculae, deep intertrabecular recesses, and thickened myocardium with 2 distinct layers (compacted and noncompacted). Clinical characteristics, outcomes, and appropriate therapies remain poorly defined. Data were collected on patients diagnosed with ILVNC by echocardiographic criteria at the Mayo Clinic from 2001 through 2006. These data were entered prospectively into a clinical database and retrospectively analyzed. All-cause mortality, stroke, and development of atrial fibrillation (AF) were compared to community and nonischemic dilated cardiomyopathic (DC) controls. Implantable cardioverter-defibrillator (ICD) therapies were examined. Thirty patients with confirmed ILVNC were included in analyses (mean age at diagnosis 39 +/- 19.5 years, 60% men). Three patients with ILVNC died during follow-up (mean 2.5 +/- 1.2 years) compared to 5 DC and 1 community controls. No mortality difference was observed among these groups (p = 0.42 and 0.054, respectively). No ILVNC deaths were observed in patients with normal LV ejection fraction. New-onset AF was diagnosed in 2 patients with ILVNC, and none was observed in DC controls. Stroke occurred in 2 DC controls and none was observed in patients with ILVNC. ICDs were implanted in 11 patients with ILVNC. No appropriate therapies were identified during follow-up, but 2 patients underwent inappropriate therapies related to AF. In conclusion, mortality in patients with ILVNC is similar to that in DC patients. Deaths were observed only in patients with decreased LV ejection fraction, suggesting that ICD therapy may be reserved for this subgroup. New-onset AF may lead to inappropriate ICD discharges.

Inappropriate Sinus Tachycardia, Postural Orthostatic Tachycardia Syndrome, and Overlapping Syndromes

Background: Inappropriate sinus tachycardia (IAST) and postural orthostatic tachycardia syndrome (POTS) are syndrome complexes with some distinctive features, overlapping clinical manifestations, and potential common mechanisms. Pathogenesis of these overlapping syndromes is poorly understood. Diagnostic and therapeutic approaches have not been standardized.

Substrate and Procedural Predictors of Outcomes After Catheter Ablation for Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) due to diastolic dysfunction, elevated left atrial pressure, and enlargement. Although catheter ablation for drug‐refractory AF is an effective treatment, the efficacy in HCM remains to be established.

Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert.

BACKGROUND Acute decreases in intrathoracic impedance monitoring have been shown to precede heart failure hospitalization in a limited population of heart failure patients. We evaluated the relationship between changes in intrathoracic impedance with hospitalizations associated with acute decompensated heart failure (ADHF) in patients with cardiac resynchronization therapy plus defibrillator (CRT-D) devices. METHODS AND RESULTS The study enrolled 326 heart failure patients who had received CRT-D with impedance-monitoring capabilities (InSync Sentry, Medtronic). The date and duration of ADHF hospitalizations were retrospectively identified before device interrogation to obtain device diagnostic information. During 333 +/- 96 days of device monitoring, 228 patients experienced 540 intrathoracic impedance fluid index threshold crossings events (TCE) at the nominal threshold value (60 Omega. days). During the initial 4-month evaluation period, 17 subjects experienced 22 ADHF hospitalizations. In the subsequent monitoring period (206 +/- 95 days), 18 patients experienced 24 hospitalizations. The occurrence of TCEs during the monitoring period was independently correlated with the subsequent rate of ADHF hospitalization such that each TCE event during the risk stratification period was associated with a 35% increased risk for ADHF hospitalization in the remaining study period (P = .001). Poisson regression indicated that the subgroup of patients with an annual average rate of more than 3 threshold crossings per year during the monitoring period were significantly more likely to be hospitalized for ADHF than those patients with no TCE during the monitoring period (0.76 [0.20-1.325] vs. 0.14 [0.05-0.23] hospitalizations/subject/y [95%CI]; P = .02). Likewise, Kaplan-Meier analysis revealed that subsets of patients with more than 3 TCEs per year or with more than 30 days per year above threshold during the risk stratification period had significantly higher rates of ADHF hospitalization during the post risk stratification period than subjects with no TCE events, respectively. CONCLUSIONS In this multicenter retrospective cohort study, serial decreases in intrathoracic impedance sufficient to generate a fluid index threshold crossing as well as the net duration that the index remained above threshold during a 4-month monitoring period were associated with subsequent risk of ADHF hospitalization.

Catheter Ablation for Atrial Fibrillation in Patients With Obesity

Background— Obesity is a risk factor for atrial fibrillation and other cardiovascular conditions. Our objective was to determine whether catheter-based ablation effectively treated atrial fibrillation in obese patients. Methods and Results— Five hundred twenty-three consecutive patients with symptomatic, medication-refractory atrial fibrillation underwent catheter ablation. Patients were grouped by body mass index (lean, <25 kg/m2; overweight, 25 to 29.9 kg/m2; obese, ≥30 kg/m2). Outcome and quality of life were measured with a general health survey (Medical Outcomes Study 36-item Short-Form General Health Survey [SF-36]); patients were assessed before ablation and at 3 and 12 months after the procedure. Two hundred twenty-eight study patients (44%) were overweight, and 201 (38%) were obese. Twelve months after curative ablation, 72% of patients were free of atrial fibrillation without the use of antiarrhythmic agents; 84% were arrhythmia free when those receiving medication were included. Atrial fibrillation was eliminated in 75%, 72%, and 70% of the lean, overweight, and obese patients, respectively, at 12 months (P=0.41, trend test). SF-36 scores were lower for patients with higher body mass index (P<0.05) at baseline. SF-36 scores improved in every functional domain for all body mass index groups after ablation. The mean SF-36 total physical score increased from 59±20 at baseline to 77±19 in 12 months (P<0.001). The total mental health score improved from 66±18 to 79±16 in 12 months (P<0.001). Conclusions— Catheter ablation of atrial fibrillation was effective in obese patients. Coexistence of atrial fibrillation and obesity indicated lower SF-36 scores, but the improvement in quality of life was consistent across all body mass index categories.

Implantable Cardioverter Defibrillators in Patients with Cardiac Amyloidosis

Cardiac amyloidosis (CA) is associated with increased risk of sudden cardiac arrest. Although ICD therapy improves survival in patients with cardiomyopathy due to other etiologies, the benefit of ICD therapy in patients with CA is unclear in large part due to limited data on the precise mechanism of sudden cardiac arrest and selection of patients with cardiac amyloidosis for ICD therapy.