||Name and Degree:
|Thomas Bigger, M.D.
Professor of Medcine & Pharmacology
|10/01/91 Dean's Distinguished Lecturer in the Clinical Sciences, College of Physicians and Surgeons of
Columbia University, New York, NY, Conquering Sudden Cardiac Death: How Close Are We?
5/09/98 Distinguished Scientist Award, Presented at the Annual Scientific Session of the North American
Society of Pacing and Electrophysiology in San Diego, CA.
3/19/02 Distinguished Scientist Award, Presented at the Annual Scientific Session of the American College
of Cardiology in Atlanta, GA.
4/26/02 Distinguished Alumnus Award, Medical College of Georgia, Augusta, GA.
|Education and Training
1952- 1955 , Psychology, Emory University
1957-1958 , Cardiovascular Physiology, National Heart Institute
1955-1960 , Medicine, Medical College of Georgia,
1960-1962 , Medicine, Columbia Division, Bellevue Hospital
1963-1964 , Medicine, New York-Presbyterian Hospital
1964-1967 , Cardiology, Pharmacology, Columbia University Medical Center
||National Board of Medical Examiners, 1961
American Board of Internal Medicine (#24559), 1970
Subspecialty Board of Cardiovascular Diseases, 1973
|Clinical Electrophysiology and Arrhythmias,Epidemiology and Clinical Trials,Diabetes and Cardiovascular Outcomes,Depression and Cardiovascular Outcomes,Prevention of Sudden Cardiac Death
|Sudden cardiac death - selection of patients for ICD prophylaxis (stratification of risk)
Depression and cardiovascular outcomes
Diabetes and cardiovascular outcomes
|Willian Hamilton, M.D. |
Andre Cournand, M.D.
Dickinson Richards, M.D.
Irene Ferrer, M.D.
Brian Hoffman, M.D.
1. Bloomfield DM, Bigger JT, Namerow PN, Steinman RC, Parides MJ, Curtis AB, Kaufman ES, Davidenko JM, Shinn TS, Fontaine JM. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006; 47:456-463.
OBJECTIVES: This study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit.
BACKGROUND: Many patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection.
METHODS: Our study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) ≤0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias.
RESULTS: Ischemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested.
CONCLUSIONS: Among patients with heart disease and LVEF ≤0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis.
2. Glassman AH, Bigger JT, Gaffney M, Shapiro PA, Swenson R. Onset of major depression associated with acute coronary syndromes. Relationship of onset, prior history, and episode severity to sertraline benefit. Arch Gen Psychiatry 2006; 63:1-6.
Context: Depression observed following acute coronary syndromes (ACS) is common and associated with an increased risk of death. The Sertraline Antidepressant Heart Attack Trial (SADHART) tested the safety and efficacy of an SSRI in this population. No evidence of harm was seen and sertraline had an overall beneficial effect on mood that occurred primarily in patients with a history of previous episodes of major depressive disorder (MDD).
Objective: To determine how frequently the major depressive disorder started before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline.
Design, Settings, and Participants: A randomized, double blind, placebo-controlled treatment of 369 ACS patients with MDD was conducted in 40 outpatient clinics in 10 countries between April 1997 and April 2001.
Primary Outcome Measures: Diagnosis of MDD, number of previous episodes of depression, and episode onset before or after hospitalization, were established using the Diagnostic Interview Schedule. Treatment response, measured with the Clinical Global Impression, Improvement scale.
Results: 53% of MDD episodes began before hospitalization for the index episode of ACS (197/369) and 94% of these episodes began more than 30 days before the ACS. Episodes of MDD that began before ACS had a significantly greater response to sertraline than to placebo (63% vs 46%, OR = 2.0, 95% CI = 1.13-3.55), whereas depression with onset beginning after hospitalization showed a high placebo response rate and low sertraline/placebo response ratio (1.15, 69% vs 60%). Multivariate analysis indicated that time of onset of the current episode, prior history of MDD, and baseline severity all independently predicted sertraline-placebo response ratio, .
Conclusion: Half of the episodes of major depression associated with ACS began long before the ACS and therefore were not caused by the ACS. Patients whose current episode of MDD begins before their ACS, those with a history of MDD, and those whose episode is severe should be treated because they will have significant benefit from sertraline. Since these three predictors of sertraline response are independent, having more than one of them substantially increases the benefit of sertraline.
3. Chan PS, Stein K, Chow T, Fendrick M, Bigger JT, Vijan S. Cost-effectiveness of a microvolt T-wave alternans screening strategy for Implantable Cardioverter-Defibrillator placement in the MADIT-II Eligible Population. J Am Coll. Cardiol 2006; 48:112-121.
OBJECTIVES: This study was designed to compare the cost-effectiveness of implantable cardioverter-defibrillator (ICD) placement with and without risk stratification with microvolt T-wave alternans (MTWA) testing in the MADIT-II (Second Multicenter Automatic Defibrillator Implantation Trial) eligible population.
BACKGROUND: Implantable cardioverter-defibrillators have been shown to prevent mortality in the MADIT-II population. Microvolt T-wave alternans testing has been shown to be effective in risk stratifying MADIT-II–eligible patients.
METHODS: On the basis of published data, cost-effectiveness of three therapeutic strategies in MADITII–eligible patients was assessed using a Markov model: 1) ICD placement in all; 2) ICD placement in patients testing MTWA non-negative;, and 3) medical management. Outcomes of expected cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness
were determined for patient lifetime.
RESULTS: Under base-case assumptions, providing ICDs only to those who test MTWA non-negative produced a gain of 1.14 QALYs at an incremental cost of $55,700 when compared to medical therapy, resulting in an incremental cost-effectiveness ratio (ICER) of $48,700/QALY.
When compared with a MTWA risk-stratification strategy, placing ICDs in all patients resulted in an ICER of $88,700/QALY. Most (83%) of the potential benefit was achieved by implanting ICDs in the 67% of patients who tested MTWA non-negative. Results were most sensitive to the effectiveness of MTWA as a risk-stratification tool, MTWA negative screen rate, cost and efficacy of ICD therapy, and patient risk for arrhythmic death.
CONCLUSIONS: Risk stratification with MTWA testing in MADIT-II–eligible patients improves the cost-effectiveness of ICDs. Implanting defibrillators in all MADIT-II–eligible patients, however, is not cost-effective, with one-third of patients deriving little additional benefit at great expense.
4. The DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial. Lancet 2006; 368:1096-1105.
Background: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug’s ability to prevent type 2 diabetes in individuals at high risk of developing the condition.
Methods: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat.
Findings: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11•6%) individuals given rosiglitazone and 686 (26•0%) given placebo developed the composite primary outcome (hazard ratio 0•40, 95% CI 0•35–0•46; p<0•0001); 1330 (50•5%) individuals in the rosiglitazone group and 798 (30•3%) in the placebo group became normoglycaemic (1•71, 1•57–1•87; p<0•0001). Cardiovascular event rates were much the same in both groups, although 14 (0•5%) participants in the rosiglitazone group and two (0•1%) in the placebo group developed heart failure (p=0•01).
Interpretation: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.
5. Kaufman ES, Bloomfield DM, Steinman RC, Namerow PB, Costantini O, Cohen RJ, Bigger JT. “Indeterminate” Microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006; 48:1399-1404.
OBJECTIVES: This study tested the hypothesis that an “indeterminate” microvolt T-wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise heart rate (HR), has prognostic significance similar to a positive MTWA test.
BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in patients with structural heart disease, has been limited by a substantial number of “indeterminate” tests. Indeterminate tests are due to patient factors— excessive ventricular ectopy during exercise, unsustained MTWA, or failure to achieve a HR of 105 beats/min for 1 min—or technical factors such as a noisy recording or an exercise protocol that causes an excessively rapid rise in HR.
METHODS: Patients in sinus rhythm with left ventricular ejection fraction ≤0.40 underwent MTWA exercise tests, analyzed with the spectral method and classified by a computerized interpretation algorithm. The primary end point was all-cause mortality or documented non-fatal sustained ventricular arrhythmia (SVA). “Indeterminate” tests were reviewed jointly by 2 readers blinded to subsequent events to determine the primary reason for indeterminacy.
RESULTS: Participants (N _ 549) were 56 _ 13 years and 71% male; 49% had ischemic cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%) indeterminate results were due to patient factors. The 2-year rate for death or SVA was 17.8% in patients with an “indeterminate” MTWA test compared with 12.3% in those with a positive test.
CONCLUSIONS: In patients with left ventricular dysfunction, an “indeterminate” MTWA test due to patient factors predicted death or SVA at least as well as a positive test.
6. Glassman AH, O'Conner CM, Califf RM, Swedberg K, Schwartz P, Bigger JT, Krishnan KRR, van Zyl LT, Swenson JR, Finkel MS, Landau C, Shapiro PA, Pepine CJ, Mardekian J, Harrison W, for the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Group. Sertraline treatment of major depression in patients with acute myocardial infarction or unstable angina. JAMA 2002; 288:701-709.
Context: Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.
Objective: To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.
Design and Setting: Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.
Patients A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).
Intervention: After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.
Main Outcome Measures: The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.
Results: Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P >.05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P = .049), but not the HAM-D (P = .14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P = .01), in the group with at least 1 prior episode of depression (72% vs 51%; P = .003), and in the more severe MDD group (78% vs 45%; P = .001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.
Conclusion Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.
1. Glassman AH, O'Conner CM, Califf RM, Swedberg K, Schwartz P, Bigger JT, Krishnan KRR, van Zyl LT, Swenson JR, Finkel MS, Landau C, Shapiro PA, Pepine CJ, Mardekian J, Harrison W: Sertraline treatment of major depression in patients with acute myocardial infarction or unstable angina. J Am Med Assn 2002;288: 701-709
2. Bloomfield DM, Bigger JT, Namerow PN, Steinman RC, Parides MJ, Curtis AB, Kaufman ES, Davidenko JM, Shinn TS, Fontaine JM: Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006;47: 456-463
3. Glassman AH, Bigger JT, Gaffney M, Shapiro PA, Swenson R: Onset of major depression associated with acute coronary syndromes. Arch Gen Psychiatry 2006;63: 1-6
4. The DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators: Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial. Lancet 2006;368: 1096-1105
5. Kaufman ES, Bloomfield DM, Steinman RC, Namerow PB, Costantini O, Cohen RJ, Bigger JT: “Indeterminate” Microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006;48: 1399-1404
6. Bigger JT, Kleiger RE: Individualizing decisions for patients with prophylactic implantable cardiac defibrillators subject to device advisories: A commentary. Am J Cardiol 2006;98: 1291-1293