Heart and Metabolism

Number 25, 2004
Heart failure in diabetes
Diabetes and heart failure

Stephen Wheatcroft
Department of Cardiology, King's College Hospital, London, UK
Correspondence: Dr Stephen Wheatcroft, Department of Cardiology, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
Tel: +442077374000, fax: +442073463489, e-mail: stephen.wheatcroft@kingsch.nhs.uk

Abstract

Diabetes is a major risk factor for the development of heart failure. This is partly explained by the association of diabetes with coronary heart disease and hypertension. However, diabetes-specific biochemical, structural, and functional abnormalities may exacerbate adverse remodeling and lead to progressive cardiac dysfunction. This case demonstrates the presentation and clinical management of heart failure in a patient with type 2 (non-insulin-dependent) diabetes. ▪ Heart Metab. 2004;25:26–29.

Keywords: Heart failure, diabetes, cardiomyopathy, pharmacotherapy, neurohumoral blockade

Case report
A 56-year-old man presented to hospital with an 8-hour history of lower chest and epigastric discomfort. He had a background of type 2 (noninsulin-dependent) diabetes, diagnosed 12 years earlier, and had been receiving treatment for hypertension for 8 years. His electrocardiogram on admission revealed ST-segment elevation in leads II, III, and aVF (Figure 1), consistent with an inferior ST-segment elevation myocardial infarction.

Figure 1. Electrocardiogram showing inferior ST-segment elevation myocardial infarction.

On assessment, the patient had a sinus tachycardia of 100 beats/min and an increased blood pressure of 170/80mm Hg. There were no cardiac murmurs, but inspiratory crackles were audible in both lung fields. He was taking an oral hypoglycemic agent and a thiazide diuretic before his admission to hospital.
The patient had never smoked; he consumed about 6 units of alcohol weekly. His mother and brother had diabetes, but there was no family history of premature cardiovascular disease.
The initial management comprised aspirin, oxygen, intravenous diuretics, and a nitrate infusion. Streptokinase was administered as a thrombolytic agent. The patient was transferred to the coronary care unit, where a sliding-scale insulin infusion was commenced in the short term, before being changed to a twice-daily subcutaneous regimen after 48hours. His progress in hospital was uneventful, with no further chest discomfort and no arrhythmias. Echocardiography revealed inferoapical akinesis with mural thrombus, prompting anticoagulation with warfarin. Coronary arteriography demonstrated diffuse left coronary artery disease. The right coronary artery was patent, with a severe stenosis at the crux and diffuse distal atheroma (Figure 2). An exercise electrocardiogram was satisfactory, with no inducible ischemia at a moderate workload, and the patient was discharged taking insulin, aspirin, a statin, an angiotensin-converting enzyme (ACE) inhibitor, a β-blocker, and warfarin.

Figure 2. Angiographic appearance of right coronary artery.

Over the next 18 months, the patient developed symptomatic heart failure, with progressive exertional breathlessness culminating in New York Heart Association class III symptoms. Repeat echocardiography demonstrated progressive left ventricular dilatation, significant impairment of systolic function, and dyssynchronous contraction. His functional status improved after optimization of pharmacotherapy with titration of the doses of β-blocker and ACE inhibitor and the initiation of spironolactone. The patient is currently under regular review in a dedicated heart failure clinic and, if limiting symptoms persist despite maximal medical treatment, he will be evaluated for cardiac resynchronization therapy with biventricular pacing.

Discussion
Diabetes is a potent risk factor for the development of heart failure. The Framingham study revealed that heart failure is twice as common in diabetic men, and five times as common in diabetic women, than in age-matched nondiabetic controls [1]. This is largely explained by the close association between diabetes and coronary heart disease or hypertension, as illustrated by the present case. However, heart failure may develop in the absence of these factors, when complex diabetes-specific biochemical, morphological, and functional changes in cardiac cells lead ultimately to the development of diabetic cardiomyopathy.
The presence of diabetes substantially increases the risk of development of cardiac failure in individuals presenting with acute coronary syndromes [2], and diabetic individuals who do develop heart failure have a significantly increased mortality [3]. Angiographic studies confirm more diffuse, extensive coronary disease, with poor collateral development. Despite this, infarct size is not consistently greater in diabetic than in nondiabetic individuals, suggesting that cellular metabolic derangement, autonomic dysfunction, increased neurohumoral activation, and the presence of microvascular disease may collectively contribute to adverse cardiac remodeling.
Patients with diabetes who suffer acute myocardial infarction derive more benefit from thrombolysis or primary angioplasty than do nondiabetic patients, emphasizing the importance of early delivery of reperfusion strategies to this group. The findings of the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study highlighted the beneficial effects of tight glycemic control, with postinfarction administration of glucose/insulin and subsequent intensive insulin treatment leading to a 30% reduction in mortality at 1 year [4]. Subgroup analysis of other postmyocardial infarction trials confirmed that, compared with patients without diabetes, those with the condition derive similar, if not more, benefit from the introduction of aspirin, ACE inhibitors, statins, and β-blockers [5].
Despite optimal peri-infarction care, however, the patient presented here illustrates the increased risk of adverse cardiac remodeling in diabetes, characterized by left ventricular dilatation, myocardial fibrosis, neurohumoral activation, and eventual progression to overt heart failure.
Table I summarizes the factors contributing to the progression of heart failure in diabetes. Although metabolic derangements, including hyperglycemia, hyperinsulinemia, and increased free fatty acids, may contribute to cardiac dysfunction, the effects of optimal metabolic control on chronic heart failure have not been tested in a large clinical trial. Instead, modern drug therapy focuses on achieving complete neurohumoral blockade.

Table 1. Factors contributing to heart failure progression in diabetes.

Abundant evidence supports the beneficial effects of ACE inhibition in patients with symptomatic heart failure. A recent meta-analysis confirmed that ACE inhibitors confer a reduction in mortality in patients with diabetes and heart failure similar to that in their nondiabetic counterparts [6]. ACE inhibition can also reduce the risk of development of heart failure in at-risk diabetic individuals without heart failure at the outset [7,8].
The findings of recent trials suggest that angiotensin II receptor blockers (ARBs) exert a benefit similar to that of ACE inhibitors in postinfarction and chronic heart failure, supporting the use of ARBs when ACE inhibitors are not tolerated. Whether ARBs should be used in combination with an ACE inhibitor and β-blocker in the treatment of heart failure remains controversial. However, the recent Candesartan in Heart Failure – Assessment of Reduction in Mortality and Morbidity (CHARM)-Added study, in which almost a 33% of those studied had diabetes, showed that the addition of an ARB to an ACE inhibitor and, in most cases, a β-blocker, led to a significant reduction in cardiovascular death or admission to hospital with heart failure [9]. Interestingly, treatment of diabetic individuals without overt heart failure with an ARB may prevent the subsequent development of heart failure [10,11].
Aldosterone contributes to cardiac dysfunction in heart failure, largely by promoting myocardial fibrosis. In the Randomized Aldactone Evaluation Study (RALES) of patients with severe heart failure, aldosterone blockade with spironolactone reduced mortality by 30% [12]. Subgroup analysis of the more recent Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), in which mortality was reduced by 15% by the aldosterone antagonist, eplerenone, confirmed the benefit of aldosterone blockade in diabetic individuals with postinfarction heart failure [13].
Insulin resistance and hyperinsulinemia exacerbate the deleterious effects of the sympathetic nervous system in heart failure. β-Blockers improve left ventricular function and partially reverse the remodeling process, reducing left ventricular mass and favorably altering ventricular geometry. Although β-blockers may potentially promote glucose intolerance, inhibit insulin release, and adversely effect the lipid profile, these concerns should not limit the use of these drugs in diabetic individuals in clinical practice. Several large-scale trials have confirmed significant reductions of mortality by β-blockade in chronic heart failure and this effect is consistent in subgroups with diabetes [14].

Summary
Patients with diabetes are at high risk of developing heart failure. The cellular, metabolic, and neurohumoral abnormalities associated with diabetes contribute to the progression of heart failure and ultimately lead to impaired long-term survival. Pharmacological intervention, with effective antagonism of the renin–angiotensin system, sympathetic nervous system, and aldosterone, has been shown to decrease the morbidity and mortality associated with heart failure, particularly in those with diabetes. Dedicated heart failure clinics enhance the focused delivery of care to such patients. However, despite optimal pharmacotherapy, the prognosis of chronic heart failure remains impaired in patients with diabetes, emphasizing the importance of continued research in this area. ▪

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REFERENCES

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Number 25, 2004Heart failure in diabetes Diabetes and heart failure

Number 25, 2004Heart failure in diabetes

Number 25, 2004
Heart failure in diabetes
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Number 25, 2004
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