Isaac R. Whitman

Safety of Selective Serotonin Reuptake Inhibitor in Adults Undergoing Coronary Artery Bypass Grafting

Selective serotonin reuptake inhibitors (SSRIs) are commonly used in patients with coronary artery disease and depression, but they have been reported to increase the risk for bleeding. However, data on the short-term outcomes comparing SSRI and non-SSRI antidepressant use after coronary artery bypass grafting (CABG) are limited. A retrospective analysis was conducted of 1,380 adults who received any antidepressants before CABG from 2003 to 2006 at academic medical centers participating in the University HealthSystem Consortium. The primary end point was defined as a composite of in-hospital mortality or any bleeding events, including postprocedural hemorrhage or hematoma, gastrointestinal hemorrhage, and reopening of surgical site. A total of 1,076 adults (78%) received SSRIs. After controlling for propensity of receiving SSRIs compared with non-SSRIs, no significant differences were found in the primary end point (9.4% vs 8.2%, adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 0.60 to 1.78), any bleeding events (6.5% vs 7.2%, OR 0.93, 95% CI 0.50 to 1.76), or in-hospital mortality (3.1% vs 2.3%, OR 0.88, 95% CI 0.47 to 1.65). There was no increased risk associated with SSRI use when the analysis was restricted to patients who received antiplatelet and anticoagulant therapy for acute coronary syndromes (OR 1.03, 95% CI 0.40 to 2.61) and when examined by age, gender, nonsteroidal anti-inflammatory drug use, and type of CABG (on pump or off pump). In conclusion, compared with non-SSRIs, the preoperative use of SSRIs does not seem to increase the risk for bleeding or in-hospital mortality after CABG.

Secondhand smoke and atrial fibrillation: Data from the Health eHeart Study.

BACKGROUND Cigarette smoking is a risk factor for atrial fibrillation (AF), but whether secondhand smoke (SHS) impacts the risk of AF remains unknown. OBJECTIVE To determine if SHS exposure is associated with an increased risk of AF. METHODS We performed a cross-sectional analysis of data from participants enrolled in the Health eHeart Study, an internet-based, longitudinal cardiovascular cohort study, who completed baseline SHS exposure and medical conditions questionnaires. SHS was assessed through a validated 22-question survey, and prevalent AF was assessed by self-report, with validation of a subset (n = 42) by review of electronic medical records. RESULTS Of 4976 participants, 593 (11.9%) reported having AF. In unadjusted analyses, patients with AF were more likely to have been exposed to SHS in utero, as a child, as an adult, at home, and at work. After multivariable adjustment for potential confounders, having had a smoking parent during gestational development (OR 1.37, 95% CI 1.08-1.73, P = .009) and residing with a smoker during childhood (OR 1.40, 95% CI 1.10-1.79, P = .007) were each significantly associated with AF. Both positive associations were more pronounced among patients without risk factors for AF (P values for interaction <.05). CONCLUSIONS SHS exposure during gestational development and during childhood was associated with having AF later in life. This association was even stronger in the absence of established risk factors for AF. Our findings indicate that SHS in early life may be an important, potentially modifiable risk factor for the development of AF.

Intense Implementation of a Strict Insulin Infusion Protocol Does Not Guarantee Postoperative Glycemic Control

BACKGROUND The Surgical Care Improvement Project (SCIP) has benchmarked 6:00 AM blood sugars on postoperative days (PODs) 1 and 2 at <200 mg/dL as an indicator of overall glycemic control (GC) in postoperative cardiac surgery patients. However, even in demonstration hospitals that publicly report for incentive payments, only 10% are compliant with this benchmark. The objectives of this study were to validate that the SCIP indicator correlates with overall GC, and relate the intensity of implementation of an insulin infusion protocol (IIP) (goal, blood sugar 100 to 140 mg/dL) to effective GC. STUDY DESIGN All postoperative cardiac surgery patients for 12 consecutive months on the IIP were divided into 2 groups: group 1 included patients who were SCIP compliant (n = 98), and group 2 were patients who were not SCIP compliant (n = 10). For each patient, we determined average blood sugar, duration of hyperglycemia (percent of time with blood sugar >200mg/dL), and intensity of implementation of the IIP, defined as (number of blood sugar checks/hours on IIP), with 0.5 = minimum intensity of implementation dictated by the IIP, ie, an insulin adjustment every 2 hours. RESULTS The average blood sugar for each of the 110 patients was no different than the SCIP 6:00 AM blood sugar: 146 versus 154 mg/dL, p = 0.18. SCIP noncompliance correlated with more intense implementation of the IIP, 0.72 ± 0.03 versus 0.83 ± 0.06 blood sugar checks/hour. CONCLUSIONS The SCIP 6:00 AM blood sugar metric does correlate with average blood sugar on POD 1. Compliance with SCIP 6:00 AM blood sugar measurement is a valid surrogate for GC, though duration of hyperglycemia was still 14% in the compliant group. Use of an IIP does not guarantee GC, despite increased intensity of its application. Even intense use of an IIP may be ineffective when it fails to account for patient risk factors for hyperglycemia.

Brain Emboli After Left Ventricular Endocardial Ablation

Background: Catheter ablation for ventricular tachycardia and premature ventricular complexes (PVCs) is common. Catheter ablation of atrial fibrillation is associated with a risk of cerebral emboli attributed to cardioversions and numerous ablation lesions in the low-flow left atrium, but cerebral embolic risk in ventricular ablation has not been evaluated. Methods: We enrolled 18 consecutive patients meeting study criteria scheduled for ventricular tachycardia or PVC ablation over a 9-month period. Patients undergoing left ventricular (LV) ablation were compared with a control group of those undergoing right ventricular ablation only. Patients were excluded if they had implantable cardioverter defibrillators or permanent pacemakers. Radiofrequency energy was used for ablation in all cases and heparin was administered with goal-activated clotting times of 300 to 400 seconds for all LV procedures. Pre- and postprocedural brain MRI was performed on each patient within a week of the ablation procedure. Embolic infarcts were defined as new foci of reduced diffusion and high signal intensity on fluid-attenuated inversion recovery brain MRI within a vascular distribution. Results: The mean age was 58 years, half of the patients were men, half had a history of hypertension, and the majority had no known vascular disease or heart failure. LV ablation was performed in 12 patients (ventricular tachycardia, n=2; PVC, n=10) and right ventricular ablation was performed exclusively in 6 patients (ventricular tachycardia, n=1; PVC, n=5). Seven patients (58%) undergoing LV ablation experienced a total of 16 cerebral emboli, in comparison with zero patients undergoing right ventricular ablation (P=0.04). Seven of 11 patients (63%) undergoing a retrograde approach to the LV developed at least 1 new brain lesion. Conclusions: More than half of patients undergoing routine LV ablation procedures (predominately PVC ablations) experienced new brain emboli after the procedure. Future research is critical to understanding the long-term consequences of these lesions and to determining optimal strategies to avoid them.

Loss-of-Function KCNE2 Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

Background— Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2-encoded voltage-gated channel &bgr;-subunit, is limited. We sought to further characterize its clinical phenotype. Methods and Results— Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database. Clinical features were assessed, while reported KCNE2 mutations were evaluated for genotype–phenotype segregation and classified according to the contemporary American College of Medical Genetics guidelines. Twenty-seven probands possessed reported pathogenic KCNE2 mutations, while a MEDLINE search identified 17 additional LQT6 cases providing clinical and genetic data. Sixteen probands had normal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to QT-prolonging stressors, 10 had other LQTS pathogenic mutations, and 10 did not have an LQTS phenotype. Although the remaining 8 subjects had an LQTS phenotype, evidence suggested that the KCNE2 variant was not the underlying culprit. The collective frequency of KCNE2 variants implicated in LQT6 in the Exome Aggregation Consortium database was 1.4%, in comparison with a 0.0005% estimated clinical prevalence for LQT6. Conclusions— On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype–phenotype segregation, our findings suggest that many KCNE2 variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, KCNE2 variants may confer proarrhythmic susceptibility when provoked by additional environmental/acquired or genetic factors, or both.

Wilson's Disease and Cardiac Myopathy

Wilsons disease is a well-characterized disorder known to cause liver and brain disease due to abnormal copper deposition. Data regarding copper infiltration of the heart is conflicting, and the risk of heart disease has not been well described. We aimed to determine whether Wilsons disease is associated with cardiac myopathy, clinically evident in the atria as atrial fibrillation (AF) and in the ventricles as heart failure (HF). We longitudinally assessed 14.3 million patients in the California Healthcare Cost and Utilization Project database from 2005 through 2009 for diagnoses of Wilsons disease, AF, HF, and covariates using International Classification of Diseases-9th Edition codes. Cirrhosis and appendicitis diagnoses were assessed for positive and negative validation, respectively. We identified 463 patients with Wilsons disease. As expected in validation analyses, patients with Wilsons disease had a threefold greater risk of cirrhosis (hazard ratio [HR] 2.85, 95% confidence interval [CI] 2.81 to 2.90, p <0.0001) and no increased risk of appendicitis (HR 0.24, 95% CI 0.04 to 1.71, p = 0.16). Patients with Wilsons disease exhibited a 29% higher risk of AF after adjusting for age, gender, race, income, hypertension, diabetes, renal disease, hyperlipidemia, obesity, coronary disease, and obstructive sleep apnea (HR 1.29, 95% CI 1.15 to 1.45, p <0.0001). After adjusting for the same covariates, patients with Wilsons disease had a 55% higher risk of incident HF (HR 1.55, 95% CI 1.41 to 1.71, p <0.0001). Patients with Wilsons disease have an increased risk of AF and HF, supporting the need for careful surveillance for heart disease. These findings also suggest that the role of copper metabolism in heart disease should be more broadly investigated.

Atrial Fibrillation Associated Genetic Variants and Left Atrial Histology: Evaluation for Molecular Sub-Phenotypes.

Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF), but the mechanisms underlying these relationships have not yet been elucidated. Inflammation and fibrosis have been posited as important mechanisms responsible for AF. We sought to investigate the impact of SNP carrier status on inflammation and fibrosis in left atrial appendage tissue.

Compliance with surgical care improvement project blood glucose--a marker for euglycemia, but does it put our patients at risk?

To improve outcomes in open heart surgery (OHS) patients, the Surgical Care Improvement Project (SCIP) requires 6 am postoperative day (POD) 1 and 2 blood glucose (BG) to be ≤200mg/dL. This study examined risk factors for SCIP noncompliance when using an insulin infusion protocol (IIP) and evaluated this SCIP metric as a surrogate for glycemic control. The authors divided 99 consecutive OHS patients, all subjected to 1 uniform IIP, into 2 groups: Group 1-SCIP compliant (n=79) and Group 2-SCIP noncompliant (n=20). They determined mean BG for the first 48 postoperative hours, percent of total time with hyperglycemia (% time BG >200mg/dL) for each group, and assessed risk of SCIP noncompliance as relates to multiple risk factors including intensity of IIP application, and switching to subcutaneous (SQ) insulin prior to 6 am on POD 2. Group 1 had lower mean BG than Group 2 and percent of total time with hyperglycemia, P<0.0001. Multivariate analysis showed diabetes, obesity in nondiabetics, and switching to SQ insulin prior to 6 am on POD 2 to be risk factors for SCIP noncompliance. The 6 am BG values on POD 1 or POD 2 each correlated with average postoperative BG, and compliance with the SCIP BG metric was associated with virtually uniform BG ≤200mg/dL. IIP application was not significantly different between groups (P=0.2). Only patients who had been switched to SQ insulin prior to 6 am POD 2 were noncompliant at 6 am on POD 2. There were hypoglycemic events (BG <70mg/dL) in 15 of 99 patients (15%), 12 of whom (80%) were in Group 1. Noncompliance with this SCIP measure occurred more frequently in patients with diabetes or, if nondiabetic, in those patients with obesity. A trend toward increased insulin assessments in the SCIP noncompliant group suggests that 1 uniform IIP for all patients may not be effective. By not requiring the reporting of hypoglycemia, SCIP may inadvertently be exposing patients to harm.