19.9 Diabetes and arrhythmias

Cardiac arrhythmias are more common in subjects with diabetes mellitus (DM) than in their countetrparts without diabetes. Atrial fibrillation (AF) is present in 10–20% of the DM patients, but the association between DM and AF is mostly due to co-morbidities of DM patients increasing the vulnerability to AF. When type 2 DM and AF coexist, there is a substantially higher risk of cardiovascular mortality, stroke, and heart failure, which indicates screening of AF in selected patients with DM. Anticoagulant therapy either with vitamin K antagonists or non-vitamin K antagonist oral anticoagulants is recommended for DM patients with either paroxysmal or permanent AF, if not contraindicated. Palpitations, premature ventricular beats, and non-sustained ventricular tachycardia are common in patients with DM. The diagnostic work-up and treatment of these arrhythmias does not differ between the patients with or without DM. The diagnosis and treatment of sustained ventricular tachycardia, either monomorphic or polymorphic ventricular tachycardia, or resuscitated ventricular fibrillation is also similar between the patients with or without DM. The risk of sudden cardiac death is higher in DM patients with or without a diagnosed structural heart disease. Patients with diabetes and a left ventricular ejection fraction less than 30–35% should be treated with a prophylactic implantable cardioverter defibrillator according to current guidelines. Beta-blocking therapy is recommended for DM patients with left ventricular dysfunction or heart failure to prevent sudden cardiac death due to arrhythmia.

Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia in the world (see Chapter 41.2). Individuals with AF have an increased risk of stroke, and have twice the mortality rate from cardiovascular diseases compared with those in sinus rhythm. Diabetes mellitus (DM) is not infrequent in patients with AF. Community studies demonstrate the presence of DM in 10–20% of patients with AF.^1,2,3,4,5 DM and AF share common antecedents such as hypertension, heart failure, coronary artery disease, and obesity. However, the independent role of DM as a risk factor for AF has not been well established. In univariate models the association between DM and AF is evident, but the association is not significant after adjustment for age and other risk factors. Atrial premature beats are also common in patients with DM and may predispose to the development of AF. Patients with DM have an increased risk of acute heart failure at the time of new-onset AF due to loss of atrial kick and an impaired left ventricular filling in DM.

A large multicentre study confirmed that AF is relatively common in type 2 DM and demonstrated that when type 2 DM and AF coexist, there is a substantially higher risk of all-cause mortality, cardiovascular death, stroke, and heart failure (Figure 19.9.1 and Figure 19.9.2).⁶ These findings suggest that AF identifies DM subjects likely to obtain greater benefits from aggressive management of all cardiovascular risk factors. Because AF is asymptomatic, or mildly symptomatic, in a substantial proportion of patients, screening for AF can be recommended in selected patient groups with type 2 DM with any suspicion of paroxysmal or permanent AF, such as palpitations or presence of frequent atrial premature beats on routine 12-lead electrocardiogram (ECG), by pulse palpation, Holter recordings, or some other evolving techniques able to diagnose asymptomatic episodes of AF.

DM increases the risk of stroke of patients with paroxysmal or permanent AF. DM is one of the risk factors of stroke (1 point) in the CHA₂DS₂VASc score (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65–74, and sex category (female) see Chapter 41.20). It is based on a point system in which 2 points are assigned for a history of stroke or transient ischaemic attack, or age 75 years or over, and 1 point for the other variables.⁷

Since DM is a risk factor for stroke, current guidelines recommend that oral anticoagulant therapy, either with warfarin or with non-vitamin K antagonist oral anticoagulants (dabigatran, apixaban, rivaroxaban, or edoxaban) should be considered based upon an assessment of the risk of bleeding complications and patient preferences (class IIa indication, level B).⁷ If other risk factors are present, warfarin or novel anticoagulants are recommended, unless contraindicated (class I, level A).

Palpitations, premature ventricular beats, and non-sustained ventricular tachycardia are common in DM (see Chapter 42.1).⁸ Diagnostic work-up and treatment of ventricular arrhythmias does not differ between the DM and non-DM patients (see Chapter 42.2). The presence of few premature ventricular beats during 24 h ambulatory monitoring is extremely common and can be considered normal. In patients with DM and frequent symptomatic premature ventricular beats or episodes of non-sustained ventricular tachycardia, the presence of underlying structural heart disease should be examined by exercise ECG, echocardiography, coronary angiography, or by magnetic resonance imaging in selected cases. The risk of cardiac events is usually dictated by an underlying heart disease rather than the arrhythmia. In highly symptomatic patients with premature ventricular beats or non-sustained ventricular tachycardia, beta blockers, calcium antagonists, or class Ic drugs, such as flecainide or propafenone in cases without the presence of structural heart disease, can be used to suppress the arrhythmias.

The diagnosis and treatment of sustained ventricular tachycardia, either monomorphic or polymorphic ventricular tachycardia, or resuscitated ventricular fibrillation is similar between the patients with or without DM (see Chapter 42.4).⁸ Diagnosis of underlying structural heart disease with echocardiography, magnetic resonance or other imaging techniques, and coronary angiography are usually needed, if no obvious triggering factors, such as electrolyte imbalance or acute infarction, can definitely diagnosed as a cause of these malignant arrhythmias. Most of the patients with sustained ventricular tachycardia or resuscitated ventricular fibrillation without a diagnosed trigger need an implantable cardioverter defibrillator to prevent sudden death.

The published epidemiological studies in general population samples have shown that subjects with DM are at higher risk of sudden cardiac death (see Chapter 43.1). In the Framingham Study, DM was associated with an increased risk of sudden cardiac death in all ages (almost fourfold), and was consistently greater in women than in men.⁹ The Nurses’ Health Study¹⁰ reported that sudden cardiac death occurred as the first sign of heart disease in 69% of cases, even if almost all the women who died suddenly had at least one cardiac risk factor. DM was a very strong risk factor, associated with a nearly threefold increased risk of sudden death compared with hypertension, which was associated with a 2.5-fold increased risk, and obesity, with a 1.6-fold increased risk. The Honolulu Heart Programme¹¹ showed an increased risk for sudden cardiac death in subjects with DM and impaired glucose tolerance. The Paris Prospective Study demonstrated that the risk of sudden cardiac death, but not of fatal myocardial infarction, was increased in DM.¹² A report from the Atherosclerosis Risk in Communities (ARIC) investigators demonstrated that the magnitude of the relative increase in risk associated with DM was similar for sudden cardiac death and non-sudden cardiac death. In this study, DM attenuated the sex difference in cardiac death showing that DM increases the risk of SCD especially in females.¹³

DM increases the cardiovascular mortality in patients with heart failure and in survivors of myocardial infarction. In an analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) programme, DM was an independent predictor of mortality, including sudden cardiac death, in patients with heart failure independent of ejection fraction.¹⁴ In a series of post-infarction patients from Germany and Finland, the incidence of sudden cardiac death was higher in type 2 DM than in patients without diabetes.¹⁵ The incidence of sudden cardiac death in post-infarction patients with a left ventricular ejection fraction greater than 35% was equal to that of non-DM patients with an ejection fraction less than or equal to 35%. The incidence of sudden cardiac death was substantially increased among DM patients with an ejection fraction less than 35%, supporting the concept that a prophylactic implantable cardioverter defibrillator should be used in all DM patients with an ejection fraction less than 30–35% unless contraindicated. Patients with type 2 DM should be screened by echocardiography or some other method to measure the EF after acute myocardial infarction and in those with signs of congestive heart failure to identify the candidacy for the prophylactic implantable cardioverter defibrillator therapy.¹⁶ All post-infarction and heart failure patients should also be treated with beta-blocking drugs, which are well established in reducing the occurrence of sudden cardiac death, if not contraindicated.

The causes underlying the increased vulnerability of the electrical substrate in DM are unclear and it is likely to be the consequence of several concomitant factors: (i) the presence and extent of CAD; (ii) myocardial fibrosis resulting in impaired left ventricular filling (diastolic dysfunction) and systolic heart failure; (iii) microvascular disease and diabetic nephropathy; (iv) autonomic nephropathy due to diabetes; and (v) abnormalities in electrical propagation in the myocardium reflected in ECG repolarization and depolarization abnormalities.^17,18,19

Many reasons and mechanisms, such as nephropathy, autonomic neuropathy, prolonged QTc interval, and co-morbidities related to DM, have been proposed to increase the risk of sudden cardiac death in DM. On the basis of available evidence, it seems that glucose intolerance, even at a pre-diabetes stage, is associated with progressive development of a variety of abnormalities that adversely affect survival and predispose to sudden arrhythmic death.²⁰ The identification of independent predictors of sudden cardiac death in DM has not progressed to a stage where it is possible to devise an individualized risk stratification scheme for prevention.

Physicians treating patients with DM should be aware of the increased arrhythmic risk of subjects with DM. Arrhythmias and sudden cardiac death are more common in DM patients than in non-DM patients of same age and sex. Special attention should be paid to recognition of AF and adequate anticoagulation of the patients with DM with diagnosed AF. Left ventricular function should be measured from post-infarction patients and patients with heart failure and an implantable cardiac defibrillator should be considered for all DM patients with a left ventricular ejection fraction less than 30–35%.