Make a firm diagnosis. A firm arrhythmia diagnosis should be established. For example, the misuse of verapamil in patients with ventricular tachycardia mistakenly diagnosed as supraventricular tachycardia can lead to catastrophic hypotension and cardiac arrest. As increasingly sophisticated methods to characterize underlying arrhythmia mechanisms become available and are validated, it may be possible to direct certain drugs toward specific arrhythmia mechanisms.
3.
Determine the baseline condition. Underlying heart disease is a critical determinant of drug selection for a particular arrhythmia in a particular patient. A key question is whether the heart is structurally abnormal. Few antiarrhythmic drugs have documented safety in patients with congestive heart failure or ischemic heart disease. In fact, some drugs pose a documented proarrhythmic risk in certain disease states, eg, class 1C drugs in patients with ischemic heart disease. A reliable baseline should be established against which to judge the efficacy of any subsequent antiarrhythmic intervention. Several methods are now available for such baseline quantification. These include prolonged ambulatory monitoring, electrophysiologic studies that reproduce a target arrhythmia, reproduction of a target arrhythmia by treadmill exercise, or the use of transtelephonic monitoring for recording of sporadic but symptomatic arrhythmias.
A Cystic Fibrosis Link in the Heart?
Cystic fibrosis is a serious autosomal-recessive inherited disease that causes defective Cl− secretion in the lung. The defective Cl− secretion is caused by mutations of the CFTR (cystic fibrosis transmembrane conductance regulator) Cl− channel, resulting in the generation of thick and dehydrated mucus and chronic bacterial infections. Although more than 1600 types of muta-tions have been identified in the CFTR gene, most current therapies to treat cystic fibrosis lung disease target downstream consequences of the disease that are secondary to loss of CFTR Cl− channel function. Recently, the FDA approved the use of a new CFTR potentiator drug, ivacaftor, for treatment of a subset of cystic fibrosis patients (4%) with a specific (G551D) mutation. Ivacaftor improves CFTR channel function, resulting in better lung function. Another CFTR modulator, crofelemer, which inhibits CFTR Cl− channels, has recently been approved by the FDA for the treatment of diarrhea induced by antiviral drugs. Surprisingly, recent studies have demonstrated the expression of CFTR Cl− channels in the heart, where they appear to modulate action potential duration and membrane potential during sym-pathetic stimulation. Various animal models of cardiac disease have suggested that CFTR Cl− channels may play a role in hyper-trophy and heart failure and may be cardioprotective against ischemia and reperfusion damage. The physiologic and patho-physiologic roles of CFTR Cl− channels in human heart remain to be defined clearly. It is not known if there are significant cardiac alterations in cystic fibrosis patients, and the possible effects of the two new CFTR channel modulators, ivacaftor and crofelemer, on heart function remain to be determined.
4. Question the need for therapy. The mere identification of an abnormality of cardiac rhythm does not necessarily require that the arrhythmia be treated. An excellent justification for conservative treatment was provided by the Cardiac Arrhythmia Suppression Trial (CAST) referred to earlier.
The benefits of antiarrhythmic therapy are difficult to establish. Two types of benefits can be envisioned: reduction of arrhythmia-related symptoms, such as palpitations, syncope, or cardiac arrest; and reduction in long-term mortality in asymptomatic patients. Among drugs discussed here, only β blockers have been definitely associated with reduction of mortality in relatively asymptomatic patients, and the mechanism underlying this effect is not established (see Chapter 10).