|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2001; 38:421-428 © 2001 by the American College of Cardiology Foundation |
* Heart Failure Research Group and D. W. Reynolds Cardiovascular Research Center, Division of Cardiology, University of Texas Southwestern Medical School, Dallas, Texas, USA
Division of Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
Manuscript received November 1, 2000; revised manuscript received March 27, 2001, accepted April 27, 2001.
Reprint requests and correspondence: Dr. Daniel L. Dries, Heart Failure Research Group, Reynolds Cardiovascular Research Center, Room H8.116, 5323 Harry Hines Boulevard, Dallas, Texas 75309
daniel.dries{at}utsouthwestern.edu
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionReferences |
|---|
We sought to determine the relative impact of diabetes mellitus on prognosis in ischemic compared with nonischemic cardiomyopathy.
BACKGROUND
Ischemic myocardium is characterized by increased reliance on aerobic and anaerobic glycolysis. Because glucose utilization by cardiomyocytes is an insulin-mediated process, we hypothesized that diabetes would have a more adverse impact on mortality and progression of heart failure in ischemic compared with nonischemic cardiomyopathy.
METHODS
We performed a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) Prevention and Treatment trials.
RESULTS
In adjusted analyses, diabetes mellitus was strongly associated with an increased risk for all-cause mortality in patients with ischemic cardiomyopathy, (relative risk [RR] 1.37, 95% confidence interval [CI] 1.21 to 1.55; p < 0.0001), but not in those with nonischemic cardiomyopathy (RR 0.98, 95% CI 0.76 to 1.32; p = 0.98). The increased mortality in patients with ischemic cardiomyopathy compared with nonischemic cardiomyopathy was limited to those with ischemic cardiomyopathy and diabetes mellitus (RR 1.37, 95% CI 1.21 to 1.56; p < 0.0001). When patients with ischemic cardiomyopathy and diabetes mellitus were excluded, there was no significant difference in mortality risk between the ischemic and nonischemic cardiomyopathy groups after adjusted analysis (RR 0.99, 95% CI 0.86 to 1.15; p = 0.99). Previous surgical revascularization identified patients within the cohort with ischemic cardiomyopathy and diabetes mellitus, with improved prognosis.
CONCLUSIONS
The differential impact of diabetes on mortality and heart failure progression according to the etiology of heart failure suggests that diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction. Evaluation of the potential for revascularization may be particularly important in patients with ischemic cardiomyopathy and diabetes mellitus.
| ||||||
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Patients were eligible for either trial if they had a documented ejection fraction 
35%. Participants were randomized to the angiotensin-converting enzyme inhibitor, enalapril, or placebo. Exclusion criteria included active angina pectoris requiring surgical intervention, unstable angina, myocardial infarction within one month, renal failure (defined as a creatinine value >2.0 mg/dl) or severe pulmonary disease.
Defining etiology of left ventricular systolic dysfunction. In each enrolled participant, the SOLVD site investigator determined the most likely etiology of heart failure and indicated it on the baseline form. Choices included "ischemic," "nonischemic" and "other." This was based on the site investigator’s opinion after reviewing all of the available information. The subjects did not routinely undergo cardiac catheterization or noninvasive testing to make this determination. For the present analysis, we refined the definition of ischemic etiology to minimize misclassification. The present analysis defined a participant as having an ischemic etiology of heart failure if any of the following were present: 1) classification as ischemic etiology by original SOLVD investigator; 2) previous myocardial infarction; and 3) previous surgical revascularization.
Definition of diabetes. The baseline form, completed for all participants, included information on the presence or absence of a history of diabetes mellitus. Data on the duration of diabetes, severity of diabetes (i.e., glycosylated hemoglobin) and medications used to treat diabetes were not available. For the purposes of the present analysis, we studied the impact of diabetes mellitus by stratifying patients into those with and without a history of diabetes mellitus at baseline.
Definitions of end points. The cause of death was determined by the site investigators after a detailed review of the circumstances of death. Categories included "pump failure," "arrhythmia with antecedent worsening of heart failure" and "arrhythymia with no antecedent worsening of heart failure." For the present analysis, we defined pump failure death to include those deaths, attributed by the original SOLVD investigators, as due to "pump failure," as well as those attributed to "arrhythmia with antecedent worsening of heart failure." Consequently, the definition of "arrhythmic death" in the present analysis was limited to those deaths classified by the original SOLVD investigators as "arrhythmia with no antecedent worsening of heart failure." The definition of death due to myocardial infarction was not standardized, but was based on a detailed review of all information available on each death by the original SOLVD investigators.
Data collection, definitions and statistical analysis.
Baseline data were collected at the time of enrollment in either of the SOLVD trials. Group comparisons of continuous data were done using the Student t test, assuming unequal variances in the comparison groups when appropriate. Group comparisons of categorical data were done using the chi-square test. A p value 0.05 was considered statistically significant. Kaplan-Meier survival curves were formally compared by using the log-rank test.
Univariate and multivariate relationships were investigated using a Cox proportional hazards model. Two-sided 95% confidence intervals were constructed around each point estimate of relative risk, and a p value 0.05 was considered statistically significant. For multivariate analyses, participants in the Prevention and Treatment trials were combined to increase statistical power. In the adjusted analyses, age and left ventricular ejection fraction were analyzed as continuous variables. The following variables were analyzed as dichotomous variables: gender, SOLVD trial (Treatment vs. Prevention), self-reported race/ethnicity (African-American/black vs. white or other), baseline use of beta-blocker (yes vs. no), aspirin (yes vs. no), New York Heart Association (NYHA) functional class (III or IV vs. I or II) and randomization assignment (enalapril vs. placebo). Statistical analyses were conducted using the Statistical Analysis Software (SAS), version 8.0 (Cary, North Carolina).
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
|
|
Prognostic impact of diabetes is influenced by etiology of heart failure. Marked differences in the association between diabetes and mortality were demonstrated in participants stratified by etiology of heart failure. As demonstrated in multivariate analysis (Table 3), diabetes remained independently associated with an increased risk of all-cause mortality, pump failure death and the composite end point (death from any cause or hospital admission for heart failure) in the subjects with ischemic cardiomyopathy; however, there was no association between diabetes and outcomes in the nonischemic cohort. The p value for evidence of interaction between diabetes mellitus and the etiology of heart failure upon the risk for all-cause mortality was highly significant (p = 0.007).
|
|
|
|
Survival in revascularized diabetics with ischemic cardiomyopathy. The baseline characteristics of subjects with and without a history of coronary artery bypass graft surgery were compared in the diabetic and nondiabetic cohorts (Tables 5 and 6). The subjects without surgical revascularization were more likely to be female and African-American in the diabetic and nondiabetic cohorts. Of the patients with diabetes mellitus, those without surgical revascularization did not differ from those with surgical revascularization with regard to mean ejection fraction, severity of heart failure, as assessed by NYHA functional class, measures of vascular disease (pulse pressure and history of stroke) and baseline renal function, as assessed by the creatinine value. The unadjusted incidence of all-cause mortality (Table 7) in these groups demonstrates that previous surgical revascularization identifies a subgroup within the ischemic cardiomyopathy/diabetes mellitus cohort with improved survival, and the absolute magnitude of the unadjusted mortality reduction associated with previous surgical revascularization is greater in the patients with diabetes mellitus.
|
|
|
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Impact of diabetes on modes of death in ischemic cardiomyopathy. An interesting finding was the spectrum of risk associated with the various modes of death in the patients with ischemic cardiomyopathy stratified according to diabetes mellitus. Diabetes mellitus is associated with more diffuse and severe coronary artery disease and increased mortality from acute coronary syndromes and myocardial infarction (7–9). Therefore, the increased mortality in the patients with ischemic cardiomyopathy and diabetes mellitus might be expected. However, the increased risk of all-cause mortality in the subjects with ischemic cardiomyopathy and a history of diabetes mellitus, compared with those without a history of diabetes mellitus, was related to an increased risk of progression of heart failure, as suggested by the increased risk of pump failure death and the composite end point of death from any cause or hospital admission for heart failure. The risk of myocardial infarction did not reach statistical significance. There was a trend toward an increased risk of arrhythmic death in the patients with ischemic cardiomyopathy and diabetes, compared with those without diabetes mellitus. However, we know from a recent autopsy study that recurrent myocardial infarction accounts for many deaths in patients with ischemic cardiomyopathy (10). The trend toward greater arrhythmic death in the subjects with diabetes and ischemic cardiomyopathy, compared with those without diabetes mellitus, may suggest, based on published data (10), that many of the deaths attributed to a fatal arrhythmia may indeed have resulted from a myocardial infarction. Finally, nonfatal infarctions may have been more common in the subjects with diabetes mellitus and ischemic cardiomyopathy and resulted in acceleration of left ventricular dysfunction.
Impact of surgical revascularization. Previous surgical revascularization identified a subgroup within the diabetic cohort with ischemic cardiomyopathy with substantially lower mortality. The adverse prognosis in the nonrevascularized diabetic patients with systolic dysfunction may reflect the influence of selection bias in the determination of which diabetics with ischemic cardiomyopathy were offered surgical revascularization. Interestingly, the baseline characteristics of the diabetics with and without surgical revascularization did not identify obvious differences in comorbidities or measures of the severity of heart failure between the groups that might be expected to detract from their candidacy for surgical revascularization. However, it should be emphasized that surgical revascularization was not a randomized treatment, and we had little data on the completeness of revascularization in each subject. These patients were highly selected in an era when surgical revascularization was often not performed on the basis of a low ejection fraction, and the presence of diabetes may have created a selection bias explaining these results.
Potential explanations for the interaction between diabetes and etiology of heart failure. The differential impact of diabetes on mortality according to the etiology of heart failure suggests that diabetes mellitus and ischemic heart disease interact to accelerate the progression of myocardial dysfunction. As mentioned already, this may be partly explained by an increased risk of nonfatal myocardial infarctions, incomplete revascularization in those who had surgical revascularization or comorbidities resulting from diabetes. However, as hypothesis-generating, these data suggest that there may be additional mechanisms for a deleterious synergy between these two disease processes. For example, ischemic cardiomyopathy is characterized by a shift in myocardial substrate utilization from free fatty acids to increased reliance on glucose and glycolysis (2,3,11,12). This has been demonstrated in animal models mimicking the chronic decrease in coronary blood flow that is thought to characterize hibernating myocardium (2,3). Glucose uptake into cardiomyocytes requires insulin (4) and has been demonstrated to be impaired in an animal model of type II diabetes (13). In the presence of the greater reliance on glycolysis and decreased reliance of free fatty acid metabolism that occurs in chronic coronary artery disease, the impaired myocardial glucose uptake characteristic of diabetes may be particularly deleterious (2,3). In addition, the cumulative oxidative stress of chronic ischemia may be additive to the oxidative stress superimposed by diabetes. This oxidative stress results in myocardial subcellular remodeling, leading to abnormal intracellular calcium homeostasis (14).
Study limitations. The limitations of this retrospective study must be emphasized. The determination of the exact etiology of heart failure was not based on routine cardiac catheterization, and it is likely that there was some misclassification. Surgical revascularization was not randomized, but was determined by history at the time of randomization, and we did not have data on the severity of coronary disease or other factors that may have excluded some of the ischemic diabetic patients from receiving surgical revascularization. Classification of the causes of death in heart failure is imprecise and subject to misclassification. Therefore, the data relating each cohort’s relative risk according to the mode of death should be interpreted with caution.
Conclusions. The differential impact of diabetes on mortality and heart failure progression, based on the etiology of heart failure, suggests that diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction. Evaluation of the potential for revascularization may be particularly important in patients with coronary artery disease who have both diabetes and heart failure.
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  U. Khanderia, R. Pop-Busui, and K. A Eagle Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective Ann. Pharmacother., October 1, 2008; 42(10): 1466 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shishido, C.-H. Woo, B. Ding, C. McClain, C. A. Molina, C. Yan, J. Yang, and J.-i. Abe Effects of MEK5/ERK5 Association on Small Ubiquitin-Related Modification of ERK5: Implications for Diabetic Ventricular Dysfunction After Myocardial Infarction Circ. Res., June 6, 2008; 102(11): 1416 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. MacDonald, M. C. Petrie, F. Varyani, J. Ostergren, E. L. Michelson, J. B. Young, S. D. Solomon, C. B. Granger, K. Swedberg, S. Yusuf, et al. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: An analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme Eur. Heart J., June 1, 2008; 29(11): 1377 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. MacDonald, M. C. Petrie, N. M. Hawkins, J. R. Petrie, M. Fisher, R. McKelvie, D. Aguilar, H. Krum, and J. J.V. McMurray Diabetes, left ventricular systolic dysfunction, and chronic heart failure Eur. Heart J., May 2, 2008; 29(10): 1224 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Berry, M Brett, K Stevenson, J J V McMurray, and J Norrie Nature and prognostic importance of abnormal glucose tolerance and diabetes in acute heart failure Heart, March 1, 2008; 94(3): 296 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Torp-Pedersen, M. Metra, A. Charlesworth, P. Spark, M. A. Lukas, P. A Poole-Wilson, K. Swedberg, J. G F Cleland, A. Di Lenarda, W. J Remme, et al. Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET) Heart, August 1, 2007; 93(8): 968 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Granberry, J. B. Hawkins, and A. M. Franks Thiazolidinediones in patients with type 2 diabetes mellitus and heart failure Am. J. Health Syst. Pharm., May 1, 2007; 64(9): 931 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. C. Hoppe, N. Freemantle, J. G.F. Cleland, M. Marijianowski, and E. Erdmann Effect of Cardiac Resynchronization on Morbidity and Mortality of Diabetic Patients With Severe Heart Failure Diabetes Care, March 1, 2007; 30(3): 722 - 724. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Horowitz and J. A. Kennedy Time to Address the Cardiac Metabolic "Triple Whammy": Ischemic Heart Failure in Diabetic Patients J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2232 - 2234. [Full Text] [PDF]
|
|
|
|
|
|
K. Siirila-Waris, J. Lassus, J. Melin, K. Peuhkurinen, M. S. Nieminen, V.-P. Harjola, and for the FINN-AKVA study group Characteristics, outcomes, and predictors of 1-year mortality in patients hospitalized for acute heart failure Eur. Heart J., December 2, 2006; 27(24): 3011 - 3017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gheorghiade, G. Sopko, L. De Luca, E. J. Velazquez, J. D. Parker, P. F. Binkley, Z. Sadowski, K. S. Golba, D. L. Prior, J. L. Rouleau, et al. Navigating the Crossroads of Coronary Artery Disease and Heart Failure Circulation, September 12, 2006; 114(11): 1202 - 1213. [Full Text] [PDF]
|
|
|
|
 |
|
 A. F.L. Schinkel, D. Poldermans, V. Rizzello, R. T. van Domburg, R. Valkema, A. Elhendy, E. Biagini, E. P. Krenning, M. L. Simoons, and J. J. Bax Impact of Diabetes Mellitus on Prediction of Clinical Outcome After Coronary Revascularization by 18F-FDG SPECT in Patients with Ischemic Left Ventricular Dysfunction J. Nucl. Med., January 1, 2006; 47(1): 68 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Pocock, D. Wang, M. A. Pfeffer, S. Yusuf, J. J.V. McMurray, K. B. Swedberg, J. Ostergren, E. L. Michelson, K. S. Pieper, C. B. Granger, et al. Predictors of mortality and morbidity in patients with chronic heart failure Eur. Heart J., January 1, 2006; 27(1): 65 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, K. Swedberg, Writing Committee:, J. Cleland, H. Dargie, H. Drexler, F. Follath, M. Komajda, L. Tavazzi, O. A. Smiseth, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology Eur. Heart J., June 1, 2005; 26(11): 1115 - 1140. [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kittleson, K. M. Minhas, R. A. Irizarry, S. Q. Ye, G. Edness, E. Breton, J. V. Conte, G. Tomaselli, J. G. N. Garcia, and J. M. Hare Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure Physiol Genomics, May 11, 2005; 21(3): 299 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kittleson, S. Q. Ye, R. A. Irizarry, K. M. Minhas, G. Edness, J. V. Conte, G. Parmigiani, L. W. Miller, Y. Chen, J. L. Hall, et al. Identification of a Gene Expression Profile That Differentiates Between Ischemic and Nonischemic Cardiomyopathy Circulation, November 30, 2004; 110(22): 3444 - 3451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M Shindler Nonischaemic heart failure and diabetes mellitus Eur. Heart J., April 2, 2004; 25(8): 629 - 630. [Full Text] [PDF]
|
|
|
|
|
|
P. de Groote, N. Lamblin, F. Mouquet, D. Plichon, E. McFadden, E. Van Belle, and C. Bauters Impact of diabetes mellitus on long-term survival in patients with congestive heart failure Eur. Heart J., April 2, 2004; 25(8): 656 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gustafsson, B. Brendorp, M. Seibaek, H. Burchardt, P. Hildebrandt, L. Kober, C. Torp-Pedersen, and DIAMOND Study Group Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure J. Am. Coll. Cardiol., March 3, 2004; 43(5): 771 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Levy and I. B. Hirsch Diabetes and heart failure: is insulin therapy the answer? J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1051 - 1053. [Full Text] [PDF]
|
|
|
|
|
|
M. Domanski, H. Krause-Steinrauf, P. Deedwania, D. Follmann, J. K. Ghali, E. Gilbert, S. Haffner, R. Katz, J. Lindenfeld, B. D. Lowes, et al. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial J. Am. Coll. Cardiol., September 3, 2003; 42(5): 914 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kittleson, S. Hurwitz, M. R. Shah, A. Nohria, E. Lewis, M. Givertz, J. Fang, J. Jarcho, G. Mudge, and L. W. Stevenson Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2029 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Wang, D. Levy, E. J. Benjamin, and R. S. Vasan The Epidemiology of "Asymptomatic" Left Ventricular Systolic Dysfunction: Implications for Screening Ann Intern Med, June 3, 2003; 138(11): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F.L. Schinkel, J. J. Bax, R. Valkema, A. Elhendy, R. T. van Domburg, E. C. Vourvouri, M. A. Bountioukos, E. P. Krenning, J. R.T.C. Roelandt, and D. Poldermans Effect of Diabetes Mellitus on Myocardial 18F-FDG SPECT Using Acipimox for the Assessment of Myocardial Viability J. Nucl. Med., June 1, 2003; 44(6): 877 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Borghi, S. Bacchelli, D. D. Esposti, and E. Ambrosioni Effects of the Early ACE Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction Diabetes Care, June 1, 2003; 26(6): 1862 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Shekelle, M. W. Rich, S. C. Morton, Col. S. W. Atkinson, W. Tu, M. Maglione, S. Rhodes, M. Barrett, G. C. Fonarow, B. Greenberg, et al. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: A meta-analysis of major clinical trials J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1529 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Vaur, P. Gueret, M. Lievre, S. Chabaud, and P. Passa Development of Congestive Heart Failure in Type 2 Diabetic Patients With Microalbuminuria or Proteinuria: Observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study Diabetes Care, March 1, 2003; 26(3): 855 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Silverberg, D. Wexler, M. Blum, J. Z. Tchebiner, D. Sheps, G. Keren, D. Schwartz, R. Baruch, T. Yachnin, M. Shaked, et al. The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron Nephrol. Dial. Transplant., January 1, 2003; 18(1): 141 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Cardiovascular Disease and Diabetes Diabetes Care, January 1, 2003; 26(1): 230 - 237. [Full Text] [PDF]
|
|
|
|
|
|
D. L. Dries, M. H. Strong, R. S. Cooper, and M. H. Drazner Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients J. Am. Coll. Cardiol., July 17, 2002; 40(2): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Bonow, W. E. Mitch, R. W. Nesto, P. T. O'Gara, R. C. Becker, L. T. Clark, S. Hunt, I. Jialal, S. E. Lipshultz, and E. Loh Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group V: Management of Cardiovascular-Renal Complications Circulation, May 7, 2002; 105 (18): e159 - e164. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nohria, E. Lewis, and L. W. Stevenson Medical Management of Advanced Heart Failure JAMA, February 6, 2002; 287(5): 628 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Diabetes and Heart Failure: What's the Prognosis? Journal Watch Cardiology, November 9, 2001; 2001(1109): 11 - 11. [Full Text]
|
|
|
|
 |
|
 |
