William H. Sauer

HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.

David H. Birnie, MD (Chair), William H. Sauer, MD, FHRS, CCDS (Chair), Frank Bogun, MD, Joshua M. Cooper, MD, FHRS, Daniel A. Culver, DO,* Claire S. Duvernoy, MD, Marc A. Judson, MD, Jordana Kron, MD, Davendra Mehta, MD, PhD, FHRS, Jens Cosedis Nielsen, MD, Amit R. Patel, MD, Tohru Ohe, MD, FHRS, Pekka Raatikainen, MD, Kyoko Soejima, MD From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada, University of Colorado, Aurora, Colorado, University of Michigan, Ann Arbor, Michigan, Temple University Health System, Philadelphia, Pennsylvania, Cleveland Clinic, Cleveland, Ohio, VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor, Michigan, Albany Medical College, Albany, New York, Virginia Commonwealth University, Richmond, Virginia, Mount Sinai School of Medicine, New York, New York, Aarhus University Hospital, Aarhus, Denmark, University of Chicago, Chicago, Illinois, Sakakibara Heart Institute of Okayama, Okayama, Japan, Heart Center, Tampere University Hospital, Tampere, Finland, and Kyorin University School of Medicine, Mitaka City, Japan.

Selective Serotonin Reuptake Inhibitors and Myocardial Infarction

Background—Depression is an independent risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors (SSRIs) may reduce this risk through attenuation of serotonin-mediated platelet activation in addition to treatment of depression itself. Methods and Results—A case-control study of first MI in smokers 30 to 65 years of age was conducted among all 68 hospitals in an 8-county area during a 28-month period. Cases were patients hospitalized with a first MI. Approximately 4 community control subjects per case were randomly selected from the same geographic area using random digit dialing. Detailed information regarding use of antidepressant medication as well as other clinical and demographic data were obtained by telephone interview. A total of 653 cases of first MI and 2990 control subjects participated. After adjustment, using multivariable logistic regression, for age, sex, race, education, exercise, quantity smoked per day, body mass index, aspirin use, family history of MI, number of physician encounters, and history of coronary disease, diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current SSRI users compared with nonusers was 0.35 (95% CI 0.18, 0.68;P <0.01). Non-SSRI antidepressant users had a nonsignificant reduction in MI risk with wide confidence intervals (adjusted odds ratio 0.48, CI 0.17, 1.32;P =0.15). However, analysis of this group was limited by the small number of exposed subjects. Conclusions—The use of SSRIs may confer a protective effect against MI. This could be attributable to the inhibitory effect SSRIs have on serotonin-mediated platelet activation or possibly amelioration of other factors associated with increased risk for MI in depression.

Effect of Antidepressants and Their Relative Affinity for the Serotonin Transporter on the Risk of Myocardial Infarction

Background Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), attenuate platelet activation by depleting serotonin storage and may decrease risk of myocardial infarction (MI). These drugs differ in their affinity for the platelet serotonin transporter and therefore may vary in their effects on MI protection. Methods and Results A case‐control study of first MI in patients aged 40 through 75 years was conducted among 36 hospitals in a 5‐county area during a 3‐year period. Case subjects were patients hospitalized with a first MI, and control subjects were randomly selected from the same geographic area. Detailed information regarding medication use and other clinical and demographic data were obtained by telephone interview. Among the 1080 cases and 4256 controls who participated, there were 223 users of antidepressants with high serotonin transporter affinity, all of which were SSRIs (paroxetine, fluoxetine, and sertraline). After adjustment with multivariable logistic regression for age, gender, race, education, physical activity, quantity of cigarettes smoked per day, body mass index, aspirin use, family history of MI, and history of diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current users of antidepressants with high serotonin transporter affinity compared with nonusers was 0.59 (95% CI 0.39 to 0.91; P=0.02). Increasing serotonin transporter affinity was associated with reduced odds of MI among users of all SSRIs (P for trend <0.01) but not tricyclic (P=0.77) or atypical (P=0.70) antidepressants. There was no association detected between non‐SSRI antidepressant use and MI. Conclusions Increasing serotonin transporter affinity correlates with greater MI protection with SSRI but not other antidepressant exposure. (Circulation. 2003;108:32‐36.)

Genetic Variation in Titin in Arrhythmogenic Right Ventricular Cardiomyopathy–Overlap Syndromes

Background— Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias and sudden death. We evaluated the cardiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks. Methods and Results— All 312 titin exons known to be expressed in human cardiac titin and the complete 3′ untranslated region were sequenced in 38 ARVC families. Eight unique TTN variants were detected in 7 families, including a prominent Thr2896Ile mutation that showed complete segregation with the ARVC phenotype in 1 large family. The Thr2896IIe mutation maps within a highly conserved immunoglobulin-like fold (Ig10 domain) located in the spring region of titin. Native gel electrophoresis, nuclear magnetic resonance, intrinsic fluorescence, and proteolysis assays of wild-type and mutant Ig10 domains revealed that the Thr2896IIe exchange reduces the structural stability and increases the propensity for degradation of the Ig10 domain. The phenotype of TTN variant carriers was characterized by a history of sudden death (5 of 7 families), progressive myocardial dysfunction causing death or heart transplantation (8 of 14 cases), frequent conduction disease (11 of 14), and incomplete penetrance (86%). Conclusions— Our data provide evidence that titin mutations can cause ARVC, a finding that further expands the origin of the disease beyond desmosomal proteins. Structural impairment of the titin spring is a likely cause of ARVC and constitutes a novel mechanism underlying myocardial remodeling and sudden cardiac death.Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias and sudden death. We evaluated the cardiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks.

FREEDOM FROM RECURRENT VENTRICULAR TACHYCARDIA AFTER CATHETER ABLATION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH STRUCTURAL HEART DISEASE: AN INTERNATIONAL VT ABLATION CENTER COLLABORATIVE GROUP STUDY

BACKGROUND The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.

Incidence and Predictors of Very Late Recurrence of Atrial Fibrillation After Ablation

Introduction: Radiofrequency catheter ablation can effectively treat patients with refractory atrial fibrillation (AF). Very late AF recurrence (≥12 months post‐ablation) is uncommon and may represent a unique patient cohort.

Implantable Cardioverter Defibrillator Therapy in Patients with Cardiac Sarcoidosis

ICD Shocks in Cardiac Sarcoidosis. Background: An implantable cardioverter defibrillator (ICD) is indicated for some patients with cardiac sarcoidosis (CS) for prevention of sudden death. However, there are little data regarding the event rates of ICD therapies in these patients. We sought to identify the incidence and characteristics of ICD therapies in this patient population.

Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis

AIMS Implantable cardiac defibrillator (ICD) implantation is a class IIA recommendation for patients with cardiac sarcoidosis (CS). However, little is known about the efficacy and safety of ICDs in this population. The goal of this multicentre retrospective data review was to evaluate the efficacy and safety of ICDs in patients with CS. METHODS AND RESULTS Electrophysiologists at academic medical centres were asked to identify consecutive patients with CS and an ICD. Clinical information, ICD therapy history, and device complications were collected for each patient. Data were collected on 235 patients from 13 institutions, 64.7% male with mean age 55.6 ± 11.1. Over a mean follow-up of 4.2 ± 4.0 years, 85 of 234 (36.2%) patients received an appropriate ICD therapy (shocks and/or anti-tachycardia pacing) and 67 of 226 (29.7%) received an appropriate shock. Fifty-seven of 235 patients (24.3%) received a total of 222 inappropriate shocks. Forty-six adverse events occurred in 41 of 235 patients (17.4%). Patients who received appropriate ICD therapies were more likely to be male (73.8 vs. 59.6%, P = 0.0330), have a history of syncope (40.5 vs. 22.5%, P = 0.0044), lower left ventricular ejection fraction (38.1 ± 15.2 vs. 48.8 ± 14.7%, P ≤ 0.0001), ventricular pacing on baseline electrocardiogram (16.1 vs. 2.1%, P = 0.0002), and a secondary prevention indication (60.7 vs. 24.5%, P < 0.0001) compared with those who did not receive appropriate ICD therapies. CONCLUSION Patients with CS and ICDs are at high risk for ventricular arrhythmias. This population also has high rates of inappropriate shocks and device complications.

Atrioventricular Nodal Reentrant Tachycardia in Patients Referred for Atrial Fibrillation Ablation Response to Ablation That Incorporates Slow-Pathway Modification

Background— Although the most common sites of atrial ectopy that trigger atrial fibrillation (AF) are in or around the pulmonary veins (PVs), atrioventricular nodal reentrant tachycardia (AVNRT) can also cause or coexist with AF. We sought to characterize patients with AF and AVNRT and assess clinical outcomes after ablation. Methods and Results— To determine the prevalence of concomitant AVNRT and AF, 629 consecutive patients referred for catheter ablation between November 1998 and March 2005 were studied. Electrophysiological studies with programmed stimulation during isoproterenol infusion identified atrial ectopy that initiated AF and the presence of inducible AVNRT. AF ablation consisted of proximal isolation of PVs and elimination of any non-PV trigger of AF, including AVNRT. There were 27 patients (4.3%) who had inducible AVNRT at the time of AF ablation. Of these, 13 underwent AVNRT ablation without PV isolation. Compared with the rest of the cohort, patients with AVNRT and AF were younger at the time of symptom onset (age 36.8±13.8 versus 48.2±11.7 years; P<0.01). Freedom from AF with or without previously ineffective antiarrhythmic medication was similar in both groups (96.3% versus 90.7%; mean follow-up 21.4±9.4 months); however, patients with AVNRT targeted for ablation were more likely to be AF free while not taking any antiarrhythmic medication after a single procedure during the follow-up period (87.5% versus 54.7%; P<0.01) and had fewer complications (0% versus 2.5%; P=0.30). Twelve of the 13 patients who underwent slow-pathway ablation without left atrial ablation remained AF free without the need for antiarrhythmic medication after a single procedure. Conclusions— AVNRT is an uncommon AF trigger seen more frequently in younger patients. Ablation of AVNRT in patients with AF was associated with improved outcomes compared with those with other triggers of AF.

Patient and Cardiologist Perceptions on Decision Making for Implantable Cardioverter‐Defibrillators: A Qualitative Study

Background:  Although implantable cardioverter‐defibrillators (ICDs) reduce mortality in selected patients, they are also associated with potential risks. Periprocedural decision making requires understanding both benefits and risks.