Linda K. Shaw

Relation of frequency and severity of mitral regurgitation to survival among patients with left ventricular systolic dysfunction and heart failure.

The goal of this study was to examine the frequency of mitral regurgitation (MR) in patients with left ventricular (LV) systolic dysfunction and to relate its presence and severity to long-term survival. Remodeling of the left ventricle after myocyte injury leads to a progressive change in LV size and shape, and it may lead to the development of MR. The frequency of MR and its relation to survival in patients with LV systolic dysfunction has not been completely characterized. We analyzed the histories, coronary anatomy, and degree of MR in patients with symptomatic heart failure and LV ejection fraction <40% who underwent cardiac catheterization between 1986 and 2000. Coxs proportional hazards modeling was used to assess the independent effect of MR on survival. Two thousand fifty-seven patients met study criteria; MR was common in this cohort (56.2%). Of patients with MR, 811 (70.1%) had mild (grades 1+ or 2+) and 345 (29.8%) had moderate or severe (grades 3+ or 4+) regurgitation. Survival rates at 1, 3, and 5 years were significantly lower in patients with moderate to severe MR versus those with mild or no MR (p <0.001). MR was found to be an independent predictor of mortality after multivariable analysis (hazards ratio 1.23, 95% confidence interval 1.13 to 1.34, p = 0.0001). This relation of MR and survival was present in those with ischemic and nonischemic cardiomyopathies. MR is common in patients with LV systolic dysfunction and heart failure. After adjusting for other clinical variables, the presence of MR independently predicted worsened survival.

Racial variation in the use of coronary-revascularization procedures. Are the differences real? Do they matter?

BACKGROUND Studies have reported that blacks undergo fewer coronary-revascularization procedures than whites, but it is not clear whether the clinical characteristics of the patients account for these differences or whether they indicate underuse of the procedures in blacks or overuse in whites. METHODS In a study at Duke University of 12,402 patients (10.3 percent of whom were black) with coronary disease, we calculated unadjusted and adjusted rates of angioplasty and bypass surgery in blacks and whites after cardiac catheterization. We also examined patterns of treatment after stratifying the patients according to the severity of disease, angina status, and estimated survival benefit due to revascularization. Finally, we compared five-year survival rates in blacks and whites. RESULTS After adjustment for the severity of disease and other characteristics, blacks were 13 percent less likely than whites to undergo angioplasty and 32 percent less likely to undergo bypass surgery. The adjusted black:white odds ratios for receiving these procedures were 0.87 (95 percent confidence interval, 0.73 to 1.03) and 0.68 (95 percent confidence interval, 0.56 to 0.82), respectively. The racial differences in rates of bypass surgery persisted among those with severe anginal symptoms (31 percent of blacks underwent surgery, vs. 45 percent of whites, P<0.001) and among those predicted to have the greatest survival benefit from revascularization (42 percent vs. 61 percent, P<0.001). Finally, unadjusted and adjusted rates of survival for five years were significantly lower in blacks than in whites. CONCLUSIONS Blacks with coronary disease were significantly less likely than whites to undergo coronary revascularization, particularly bypass surgery - a difference that could not be explained by the clinical features of their disease. The differences in treatment were most pronounced among those predicted to benefit the most from revascularization. Since these differences also correlated with a lower survival rate in blacks, we conclude that coronary revascularization appears to be underused in blacks.

A standardized definition of ischemic cardiomyopathy for use in clinical research.

OBJECTIVES We sought to evaluate the association between the extent of coronary artery disease (CAD) and survival in patients with symptomatic heart failure (HF) and to create the most prognostically powerful clinical definition of ischemic cardiomyopathy. BACKGROUND An ischemic etiology of HF is known to be a predictor of adverse outcome; however, there is no uniform definition for ischemic cardiomyopathy. METHODS We assessed the clinical history and coronary anatomy of patients with symptomatic HF and ejection fraction < or = 40% undergoing diagnostic coronary angiography between 1986 and 1999 (n = 1,921). Five classification schemes were tested to identify the most prognostically powerful method for defining the extent of CAD and to develop the best definition of ischemic cardiomyopathy for prognostic purposes. RESULTS A more extensive CAD was independently associated with shorter survival. When the various classification schemes were compared, a modified number-of-diseased-vessels classification, in which patients with single-vessel disease and no prior history of revascularization or myocardial infarction (MI) were classified as nonischemic, provided the most prognostic power. A definition of ischemic cardiomyopathy that incorporated this definition had more prognostic power than the traditional definition. CONCLUSIONS Angiographically diagnosed ischemic HF is associated with shorter survival than nonischemic HF. A more extensive CAD is independently associated with shorter survival, and patients with single-vessel disease and no history of MI or revascularization should be classified as nonischemic for prognostic purposes. Standardization of the definition of ischemic cardiomyopathy will be useful in the conduct and interpretation of clinical research in HF.

Clinical Determinants of Mortality in Patients With Angiographically Diagnosed Ischemic or Nonischemic Cardiomyopathy

OBJECTIVES We sought to characterize the clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. BACKGROUND Patients with ischemic cardiomyopathy may have a worse prognosis than patients with nonischemic cardiomyopathy. Few studies have assessed the effect of ischemic versus nonischemic etiology on outcomes. METHODS We analyzed prospectively collected data on 3,787 patients with a left ventricular ejection fraction < or = 40% who underwent coronary angiography. Patients were considered to have ischemic cardiomyopathy (n = 3,112) if they had a history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or at least one major epicardial coronary artery with > or = 75% stenosis; all others were considered to have nonischemic cardiomyopathy (n = 675). RESULTS The median age, ejection fraction and proportion of patients with New York Heart Association functional class III or IV symptoms for the nonischemic and ischemic groups were 55 years versus 63 years, 27% versus 32% and 57% versus 25%, respectively. After adjustment for baseline clinical risk factors and presenting characteristics, ischemic etiology remained an important independent predictor of 5-year mortality (p < 0.0001). The extent of coronary artery disease was a better predictor of survival than ischemic or nonischemic etiology (log likelihood chi-square 700 vs. 675, respectively). CONCLUSIONS Ischemic etiology is a significant independent predictor of mortality in patients with cardiomyopathy. However, the extent of coronary artery disease contributes more prognostic information than the clinical diagnosis of ischemic or nonischemic cardiomyopathy. Further research is needed to refine the clinical definition of ischemic cardiomyopathy so that physicians can appropriately prescribe treatment and accurately predict outcome.

Use of a Prognostic Treadmill Score in Identifying Diagnostic Coronary Disease Subgroups

BACKGROUND Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined. METHODS AND RESULTS A logistic regression model was used to predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75% and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk patients (score <-11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001). CONCLUSIONS The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease.

Chronic Kidney Disease, Mortality, and Treatment Strategies among Patients with Clinically Significant Coronary Artery Disease

Cardiovascular disease is an important cause of mortality among patients with chronic kidney disease (CKD). This study describes associations between CKD, cardiac revascularization strategies, and mortality among patients with CKD and cardiovascular disease. All patients undergoing cardiac catheterization at Duke University Medical Center (1995 to 2000) with documented stenosis > or =75% of at least one coronary artery and available creatinine data were included. CKD was staged using creatinine clearance (CrCl) derived from the Cockcroft-Gault formula (normal, > or = 90 ml/min; mild, 60 to 89 ml/min; moderate, 30 to 59 ml/min; severe, 15 to 29 ml/min). Cox proportional-hazard regression estimated the relationship between clinical variables, including CrCl and percutaneous coronary artery intervention (PCI), coronary artery bypass grafting (CABG), medical management, and patient survival. There were 4584 patients included, and 24% had CrCl <60 ml/min. Each 10-ml/min decrement in CrCl was associated with an increase in mortality (hazard ratio, 1.14; P < 0.0001). CABG was associated with a survival benefit among patients with both normal renal function and patients with CKD compared with medical management. In patients with normal renal function, CABG was not associated with survival benefit over PCI. However, in patients with CKD, CABG was associated with improved survival. PCI was associated with a survival benefit compared with medical management among patients with normal, mildly, and moderately impaired renal function. Among patients with severe CKD, PCI was not associated with improved survival. CABG is associated with greater mortality reduction than PCI in severe CKD.

Survival After Coronary Revascularization, With and Without Mitral Valve Surgery, in Patients With Ischemic Mitral Regurgitation

Background—The most appropriate treatment for patients with ischemic mitral regurgitation (IMR) is often debated. We compared the survival rates of patients with IMR undergoing different treatment strategies, namely: medical therapy, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and CABG + mitral valve (MV) surgery. Methods and Results—Patients undergoing catheterization between 1986 and 2001 were included. IMR was defined as: ≥grade 2+ mitral regurgitation (MR) and significant coronary artery disease (CAD) without primary mitral valve disease. Patients undergoing catheterization for the evaluation of congenital or other valvular heart disease were excluded. Multivariable Cox proportional hazards modeling was utilized to assess the independent relation between treatment and survival. Propensity score methods were used to correct for the nonrandom assignment of treatment. Of the 2,757 patients who met study criteria: 1,305 were treated medically, 537 underwent PCI, 687 underwent CABG, and 228 underwent CABG + MV surgery. The median duration of follow-up was 3.2 (0.9, 7.1) years. Patients undergoing CABG + MV surgery had more severe MR and more severe heart failure than those treated by other modalities. After adjusting for differences in baseline characteristics, patients undergoing PCI, CABG, and CABG + MV surgery had a 31% (hazards ratio [HR]=0.69; P =0.0001), 42% (HR=0.58; P =0.0001), and 42% (HR=0.58; P =0.0001) reduction in the risk of death, respectively, compared with those undergoing medical therapy. The performance of mitral valve surgery with CABG was not associated with improved survival versus CABG alone (P =0.258). Conclusions—Among patients with IMR, treatment with PCI, CABG, or CABG + MV surgery is associated with improved survival compared with medical therapy.

Chronic kidney disease is associated with increased risk of sudden cardiac death among patients with coronary artery disease

Sudden cardiac death is the most common cause of mortality among patients with end-stage kidney disease maintained on hemodialysis. To examine whether this increased risk is also seen with less advanced kidney disease, we studied the relationship between glomerular filtration rate and risk of sudden cardiac death in patients with moderate kidney disease and known coronary artery disease. This retrospective longitudinal study encompassed 19,440 consecutive patients who underwent cardiac catheterization at a single academic institution. There were 522 adjudicated sudden cardiac death events, yielding an overall rate of 4.6 events per 1000 patient years. This figure reflected rates of 3.8 events in 14,652 patients with estimated glomerular filtration rates (eGFR) > or =60 (stage 2 CKD or better) and 7.9 events in 4788 patients with glomerular filtration rates <60 (stage 3-5 CKD), all normalized to 1000 patient-years. After adjusting for differences in known cardiac risk factors and other covariates in a multivariate Cox proportional hazards model, the eGFR was independently associated with sudden cardiac death (hazard ratio (HR)=1.11 per 10 ml/min decline in the eGFR). Our analysis found that reductions in the eGFR in CKD stages 3-5 are associated with a progressive increase in risk of sudden cardiac death in patients with coronary artery disease. Additional studies are needed to better characterize the mechanisms by which reduced kidney function increases this risk.

Galectin-3 in Ambulatory Patients with Heart Failure: Results from the HF-ACTION Study

Background— Galectin-3 is a soluble s-galactoside–binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results— HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P <0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions— Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. Clinical Trial Registration— URL: . Unique identifier: [NCT00047437][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00047437&atom=%2Fcirchf%2F5%2F1%2F72.atomBackground— Galectin-3 is a soluble ß-galactoside–binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results— HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions— Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Thrombolysis and counterpulsation to improve survival in myocardial infarction complicated by hypotension and suspected cardiogenic shock or heart failure: results of the TACTICS Trial.

Background: Sustained hypotension, cardiogenic shock, and heart failure all imply a poor prognosis in acute myocardial infarction (MI). We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation (IABP) to standard treatment for MI, in an international trial among hospitals without primary angioplasty capabilities.Methods: We randomized 57 patients with MI complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure to receive either fibrinolytic therapy and IABP or fibrinolysis alone. The primary end point was all-cause mortality at 6 months.Results: In all, IABP was inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis began and continued for a median 34 hours. Of the 27 patients assigned to fibrinolysis alone, 9 deteriorated such that IABP was required. The IABP group was at slightly higher risk at baseline, but the incidence of the primary end point did not differ significantly between groups (34% for combined treatment versus 43% for fibrinolysis alone; adjusted P = 0.23). Patients with Killip class III or IV showed a trend toward greater benefit from IABP (6-month mortality 39% for combined therapy versus 80% for fibrinolysis alone; P = 0.05).Conclusions: While early IABP use was not associated with a definitive survival benefit when added to fibrinolysis for patients with MI and hemodynamic compromise in this small trial, its use suggested a possible benefit for patients with the most severe heart failure or hypotension.Abbreviated Abstract. We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation to fibrinolytic therapy among 57 patients with acute myocardial infarction complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure. The primary end point, mortality at 6 months, did not differ between groups (34% for combined treatment versus 43% for fibrinolysis alone [n = 27]; adjusted P = 0.23), although patients with Killip class III or IV did show a trend toward greater benefit from IABP (39% for combined therapy versus 80% for fibrinolysis; P = 0.05).