Faculty Bibliography
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129
Initial Invasive or Conservative Strategy for Stable Coronary Disease
BACKGROUND:Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS:We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS:Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS:Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
PMID: 32227755
ISSN: 1533-4406
CID: 5451242
Journal of the American College of Cardiology. 2020:Conference:(ACC).DOI: 10.1016/S0735-2D1097-252820-252930657-2D4
SEX DIFFERENCES IN STRESS TEST AND CCTA FINDINGS AND SYMPTOMS IN THE RANDOMIZED ISCHEMIA TRIAL [Meeting Abstract]
Background Sex differences in ischemia, coronary anatomy and symptoms have not been investigated among patients who have moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary CT angiography (CCTA) was required to have obstructive CAD to undergo randomization. We describe sex differences in stress testing and CCTA findings as well as symptoms in the ISCHEMIA trial. Methods ISCHEMIA enrolled patients based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most participants. Stress tests and CCTAs were reviewed at core laboratories. Those with no obstructive coronary artery disease (CAD) or with left main CAD >=50% were excluded. Angina was assessed using the Seattle Angina Questionnaire (SAQ). Results Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA), 34% versus 11%, p<0.001, resulting in more women excluded after enrollment. Randomized women (n=1168) had more angina at baseline than randomized men (n=4011), despite less extensive CAD on CCTA and less severe ischemia in women vs. men with stress imaging (Figure). Conclusion Women randomized in the ISCHEMIA trial had more frequent angina despite less extensive CAD and less ischemia than men. Our findings likely reflect inherent sex differences in the complex relationships between angina, atherosclerosis and ischemia that may have implications for testing and treatment of patients with suspected ischemic heart disease. [Formula presented]
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EMBASE:2005031830
ISSN: 1558-3597
CID: 4325282
Journal of the American College of Cardiology. 2020:Conference:(ACC).DOI: 10.1016/S0735-2D1097-252820-252930679-2D3
PREDICTION OF LEFT MAIN DISEASE USING CLINICAL AND STRESS TEST PARAMETERS [Meeting Abstract]
Background Detection of flow-limiting left main (LM) coronary artery disease (CAD) has both prognostic and therapeutic implications. Stress testing is the most common method to detect obstructive CAD, however stress markers of LM CAD remain unclear. We set out to identify markers of LM CAD using clinical and stress testing parameters. Methods The population consisted of patients enrolled in the ISCHEMIA trial who underwent non-imaging exercise tolerance testing, stress nuclear imaging or stress echocardiography (SE) and who underwent coronary computed tomography angiography (CCTA). Patients were enrolled based on local determination of moderate or severe ischemia. Those with prior coronary artery bypass grafting were excluded. Multivariate modeling was used to identify predictors of >=50% LM diameter stenosis ("LM disease"), first without and then with stress testing parameters included in the model. Results Of the 5145 patients included (mean age: 63 years, male: 74%), 414 (8%) had LM disease. Predictors of LM disease are shown in the Table. The models were weakly predictive of LM disease (C index 0.643 for clinical model, 0.671 for clinical + stress model). Conclusion In patients with moderate or severe ischemia on stress testing, clinical and stress testing parameters were weakly predictive of LM disease on CCTA. SE-detected TID and ST depression during ETT provided incremental information independent of clinical and other stress modality specific parameters for the prediction of LM disease. [Figure presented]
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EMBASE:2005042841
ISSN: 1558-3597
CID: 4380862
CHRONIC KIDNEY DISEASE IN HEART FAILURE PATIENTS UNDERGOING NON-CARDIAC SURGERY [Meeting Abstract]
Background Heart failure (HF) and chronic kidney disease (CKD) commonly co-exist, and are associated with adverse postoperative cardiovascular outcomes. The impact of CKD in HF patients undergoing noncardiac surgery is uncertain. Methods Patients with HF undergoing non-cardiac surgery were identified from the National Surgical Quality Improvement Program between 2009-2015. Patients were classified into 5 groups based on estimated glomerular filtration rate (eGFR) and requirement of dialysis and were followed prospectively for the primary outcome of death and major adverse cardiovascular events (MACE; a composite of death, myocardial infarction (MI), and stroke) within 30-days post-operatively. Multivariable logistic regression models adjusted for age, sex, race, surgery type, and clinical history and surgery type were generated to estimate the association between CKD stage and outcomes. Results Among 27,612 HF patients undergoing surgery, 65.1% had CKD (19.7% with eGFR 45-60, 20.3% eGFR 30-45, and 25.1% eGFR < 30 with or without dialysis). The incidence of postoperative death and MACE increased with worsening CKD (Table). After multivariable adjustment, eGFR <60 was associated with increased odds of MI and cardiac arrest and eGFR <45 was associated with postoperative mortality. No association was observed between CKD and stroke. Conclusion Among HF patients, the presence of CKD is common and is associated with increased risk for postoperative mortality and MACE. [Figure presented]
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EMBASE:2005039289
ISSN: 0735-1097
CID: 4367642
Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers: JACC State-of-the-Art Review
A new cardiometabolic-based chronic disease (CMBCD) model is presented that provides a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and mitigate the development and ravages of cardiovascular disease. In the first part of this JACC State-of-the-Art Review, a framework is presented for CMBCD, focusing on 3 primary drivers (genetics, environment, and behavior) and 2 metabolic drivers (adiposity and dysglycemia) with applications to 3 cardiovascular endpoints (coronary heart disease, heart failure, and atrial fibrillation). Specific mechanistic pathways are presented configuring early primary drivers with subsequent adiposity, insulin resistance, β-cell dysfunction, and metabolic syndrome, leading to cardiovascular disease. The context for building this CMBCD model is to expose actionable targets for prevention to achieve optimal cardiovascular outcomes. The tactical implementation of this CMBCD model is the subject of second part of this JACC State-of-the-Art Review.
PMID: 32029136
ISSN: 1558-3597
CID: 4300602
Cardiometabolic-Based Chronic Disease, Addressing Knowledge and Clinical Practice Gaps: JACC State-of-the-Art Review
In the second part of this JACC State-of-the-Art Review, an early and sustainable preventive care plan is described for cardiometabolic-based chronic disease. This plan can improve cardiometabolic health by targeting early mechanistic events to decrease the risk for certain cardiovascular diseases (e.g., coronary heart disease, heart failure, and atrial fibrillation). Included are various prevention modalities, intensive lifestyle interventions, pharmacotherapy and cardiovascular outcome trial evidence, and bariatric/metabolic procedures. A tactical approach of implementing published clinical practice guidelines/algorithms for early behavioral, adiposity, and dysglycemia targeting is emphasized, as well as relevant educational and research implications.
PMID: 32029137
ISSN: 1558-3597
CID: 4300612
Baseline Predictors of Low-Density Lipoprotein Cholesterol and Systolic Blood Pressure Goal Attainment After 1 Year in the ISCHEMIA Trial
BACKGROUND:Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described. METHODS AND RESULTS/RESULTS:The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy. The primary aim of this analysis was to determine predictors of meeting trial goals for LDL-C (low-density lipoprotein cholesterol, goal <70 mg/dL) or systolic blood pressure (SBP, goal <140 mm Hg) at 1 year post-randomization. We included all randomized participants in the ISCHEMIA trial with baseline and 1-year LDL-C and SBP values by January 28, 2019. Among the 3984 ISCHEMIA participants (78% of 5179 randomized) with available data, 35% were at goal for LDL-C, and 65% were at goal for SBP at baseline. At 1 year, the percent at goal increased to 52% for LDL-C and 75% for SBP. Adjusted odds of 1-year LDL-C goal attainment were greater with older age (odds ratio [OR], 1.11 [95% CI, 1.03-1.20] per 10 years), lower baseline LDL-C (OR, 1.19 [95% CI, 1.17-1.22] per 10 mg/dL), high-intensity statin use (OR, 1.30 [95% CI, 1.12-1.51]), nonwhite race (OR, 1.32 [95% CI, 1.07-1.63]), and North American enrollment compared with other regions (OR, 1.32 [95% CI, 1.06-1.66]). Women were less likely than men to achieve 1-year LDL-C goal (OR, 0.68 [95% CI, 0.58-0.80]). Adjusted odds of 1-year SBP goal attainment were greater with lower baseline SBP (OR, 1.27 [95% CI, 1.22-1.33] per 10 mm Hg) and with North American enrollment (OR, 1.35 [95% CI, 1.04-1.76]). CONCLUSIONS:In ISCHEMIA, older age, male sex, high-intensity statin use, lower baseline LDL-C, and North American location predicted 1-year LDL-C goal attainment, whereas lower baseline SBP and North American location predicted 1-year SBP goal attainment. Future studies should examine the effects of sex disparities, international practice patterns, and provider behavior on risk factor control.
PMID: 31718297
ISSN: 1941-7705
CID: 4186842
Review of cardiovascular outcomes trials of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists
PURPOSE OF REVIEW/OBJECTIVE:In recent years, there have been several cardiovascular outcomes trials (CVOT) of two new classes of glucose-lowering medications: sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). It is important examine their potential for cardiovascular benefit and possible side effects among patients with type 2 diabetes (T2D) mellitus. RECENT FINDINGS/RESULTS:The current article reviews the findings of recent CVOT of SGLT2-i and GLP-1 RA, including their impact on cardiovascular events and relevant side effects. SUMMARY/CONCLUSIONS:For all T2D patients, with or without established cardiovascular disease, the SGLT2-i have demonstrated impressive reductions in hospitalization for heart failure and renoprotection. For T2D patients with established cardiovascular disease, SGLT2-i demonstrated an additional benefit of reduced major adverse cardiac events, on top of reductions in hospitalizations for heart failure, renoprotection, and in some instances, mortality. Similarly, all GLP-1 RA CVOTs demonstrated noninferiority compared with placebo for safety. In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.
PMID: 31436559
ISSN: 1531-7080
CID: 4046912
Association of Thrombocytopenia, Revascularization, and In-Hospital Outcomes in Patients with Acute Myocardial Infarction
BACKGROUND:The impact of thrombocytopenia on revascularization and outcomes in patients presenting with acute myocardial infarction remains poorly understood. We sought to evaluate associations between thrombocytopenia, in-hospital management, bleeding, and cardiovascular outcomes in patients hospitalized for acute myocardial infarction in the United States. METHODS:Patients hospitalized from 2004 to 2014 with a primary diagnosis of acute myocardial infarction were identified from the National Inpatient Sample. Management of acute myocardial infarction was compared between patients with and without thrombocytopenia. Multivariable logistic regression models were used to estimate odds of in-hospital adverse events stratified by thrombocytopenia and adjusted for demographics, cardiovascular risk factors, comorbidities, and treatment. RESULTS:A total of 6,717,769 patients were hospitalized with a primary diagnosis of acute myocardial infarction and thrombocytopenia was reported in 219,351 (3.3%). Patients with thrombocytopenia were older, more likely to have other medical comorbidities, were more likely to undergo coronary artery bypass grafting (28.8% vs. 8.2%, p<0.001), and were less likely to receive a drug eluting stent (15.5% vs. 29.5%, p<0.001). After multivariable adjustment, thrombocytopenia was independently associated with nearly two-fold increased odds of in-hospital mortality (aOR 1.91, 95% CI 1.86-1.97). Thrombocytopenia was also independently associated with ischemic stroke, cardiogenic shock, cardiac arrest and bleeding complications. CONCLUSIONS:Patients with thrombocytopenia in the setting of acute myocardial infarction had increased odds of bleeding, cardiovascular outcomes, and mortality compared with patients without thrombocytopenia. Future investigations to mitigate the poor prognosis of patients with acute myocardial infarction and thrombocytopenia are warranted.
PMID: 31034804
ISSN: 1555-7162
CID: 3854442
Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes
CONTEXT/BACKGROUND:For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the pre-specified subgroup of diabetic patients. EVIDENCE ACQUISITION/METHODS:We review the published literature focusing on the atherogenic nature of diabetes, and available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in diabetic patients. EVIDENCE SYNTHESIS/RESULTS:The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in diabetic patients. CONCLUSIONS:The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.
PMID: 30869793
ISSN: 1945-7197
CID: 3733362
