Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a condition characterized by disarray of myocardial fibers and myofibrils, producing excessive and inappropriate hypertrophy of the left ventricle (LV), most frequently of the interventricular septum. The hypertrophy interferes with ventricular relaxation and, in up to 25% of patients, causes dynamic obstruction across the left ventricular outflow tract. Early observational studies of right ventricular apical pacing suggested regression of ventricular hypertrophy and dramatic clinical improvement.¹ However, this benefit was not substantiated in subsequent randomized controlled clinical trials,¹ so this strategy has been largely abandoned, except when there is another indication for pacing, such as AV block after alcohol septal ablation (discussed later).

Neurocardiogenic Syncope

Neurocardiogenic syncope is a common problem that accounts for approximately 6% of hospital admissions in the United States annually. Despite improved diagnostic techniques, the cause of syncope remains undiagnosed in up to 50% of cases. It is likely that many of these cases are neurally mediated. The term neurocardiogenic syncope (also known as vasovagal syncope or neurally mediated syncope) is used to describe a group of related conditions that include carotid sinus hypersensitivity, post-tussive syncope, postmicturition syncope, and others. Because episodes are often accompanied by bradycardia, it was hypothesized that permanent pacing may be beneficial. Unfortunately, as with HCM, early uncontrolled studies suggested that permanent pacing offered major clinical benefits that have not been confirmed by subsequent randomized clinical trials.1,2 Currently, there is no clear clinical indication for permanent pacing in neurocardiogenic syncope. However, a subgroup of patients who experience very long pauses (>6 seconds) or marked bradycardia on ambulatory monitoring may benefit from pacing therapy.³

Long QT Syndrome

The long QT syndrome is a heterogeneous group of disorders characterized by QT prolongation and a tendency to develop torsades de pointes and sudden cardiac death. Congenital forms of this disorder have been linked to point mutations in specific genes associated with sodium or potassium channel activity. Acquired forms of the long QT syndrome are usually associated with use of QT-prolonging medications (e.g., sotalol, tricyclic antidepressants), the list of which continues to grow. It is also possible that congenital and acquired forms actually make up a continuum, with some individuals manifesting the abnormality in the baseline state and others requiring trigger factors to elicit QT prolongation. The pathogenesis of ventricular arrhythmias in this syndrome has not been completely elucidated but seems related to sympathetic activation and early afterdepolarizations.

Initial therapy for the long QT disorders traditionally has been pharmacologic (β-blockers), although left stellate ganglion ablation and permanent pacing have also been advocated. The exact mechanism by which pacing exerts its beneficial effect is unclear but probably is related to preventing pauses that characteristically precede episodes of torsade, with elimination of early afterdepolarizations and decreased dispersion of refractoriness. In addition, overdrive pacing to increase heart rate decreases the QT interval. Currently, it is standard to use an implantable cardioverter-defibrillator (ICD) in any individual with documented cardiac arrest, sustained ventricular tachycardia, or recurrent syncope refractory to β-blockers, with pacing reserved for symptomatic bradycardia.

Chronic Disorders of the Neuromuscular System

The muscular dystrophies are a diverse group of inherited, chronic degenerative conditions primarily affecting skeletal muscle. It has long been appreciated that these disorders can also affect cardiac muscle, resulting in fibrosis and fatty replacement of the myocardium. Awareness is growing that the prevalence of arrhythmias, conduction system disease, and sudden cardiac death in these patients may warrant early intervention.⁴ Because these conditions are infrequent, the therapeutic guidelines are necessarily nonspecific. In general, it can be recommended that unexplained syncope, presyncope, and other transient neurologic symptoms should be aggressively investigated using ambulatory electrocardiographic recordings, long-term event recorders and loop recorders, and, in more worrisome situations (e.g., unexplained sudden syncope precipitating a motor vehicle accident), hospitalization with inpatient monitoring. In most cases, the finding of second-degree atrioventricular block, even when asymptomatic, may warrant permanent pacemaker implantation. It should be noted that ventricular tachyarrhythmias are also common in this population, so, depending on the clinical scenario, an ICD should also be considered.

Infiltrative Diseases of the Myocardium

The myocardium is infiltrated and replaced by nonmyocardial tissue in a diverse variety of disorders. Although the prognosis is usually determined more by type and severity of the underlying disease, cardiac and conduction system involvement is not unusual and may be accompanied by potentially life-threatening bradyarrhythmias or tachyarrhythmias. In these situations, permanent pacemakers may be helpful symptomatically, although they may not necessarily prolong life.