Certain heritable conditions (fortunately rare) can also cause arrhythmias. They are important to recognize because they may alert physicians to the need for intervention to prevent sudden cardiac death (discussed later) in the proband and their family members. Some of these disorders are associated with recognizable anatomic abnormalities (e.g., congenital anomalies, hypertrophic cardiomyopathy, mitral valve prolapse). However, other heritable disorders precipitate arrythmias and sudden death in the absence of structural cardiac pathology (so-called “primary electrical disorders”). These syndromes can only be diagnosed by genetic testing, which is performed in those with a positive family history or an unexplained nonlethal arrhythmia. The most important of these are the channelopathies, which are caused by mutations in genes that are required for normal function of Na+, K+, and Ca+ channels. Since ion channels are responsible for conducting the electrical currents that mediate contraction of the heart, it is not surprising that defects in these channels may provoke arrythmias. The prototype is the long QT syndrome, characterized by prolongation of the QT segment in ECGs and susceptibility to malignant ventricular arrhythmias. Mutations in several different genes account for the cases of long QT syndrome, with KCNQ1 being the most common; it results in decreased potassium currents.
Sudden cardiac death (SCD) is defined as unexpected death due to a lethal arrhythmia such as asystole or sustained ventricular fibrillation. Roughly 400,000 individuals are victims of SCD each year in the United States. Coronary artery disease is the leading cause of SCD, being responsible for 80% to 90% of cases. Unfortunately, SCD may be the first manifestation of IHD. Of interest, autopsy typically shows severe atherosclerotic disease without evidence of acute plaque disruption. Thus, in the vast majority of cases, there is no associated myocardial infarction; 80% to 90% of patients who suffer SCD but are successfully resuscitated do not show any enzymatic or ECG evidence of myocardial necrosis—even if the cause is IHD! Healed remote MIs are present in about 40% of cases.
In younger victims of SCD, nonatherosclerotic causes are more common, including the following:
Hereditary (channelopathies) or acquired abnormalities of the cardiac conduction system
Myocardial hypertrophy. Increased cardiac mass is an independent risk factor for SCD; thus, in some young individuals who die suddenly, including athletes, hypertensive hypertrophy or unexplained increased cardiac mass is the only pathologic finding.
Although ischemic injury (and other pathologic conditions) can directly affect the major components of the conduction system, most cases of fatal arrhythmia are triggered by electrical irritability of myocardium distant from the conduction system.
The prognosis of many patients at risk for SCD, including those with chronic IHD, is markedly improved by implantation of a pacemaker or an automatic cardioverter defibrillator, which senses and electrically counteracts an episode of ventricular fibrillation.
The relationship of coronary artery disease to the various clinical end points discussed earlier is depicted in
Fig. 11.15
Arrhythmiascanbecausedbyischemicorstructuralchangesintheconductionsystemorbymyocyteelectricalinstability.Instructurallynormalhearts,arrhythmiasmoreoftenareduetomutationsinionchannelsthatcauseaberrantrepolarizationordepolarization.
SCDmostfrequentlyisduetocoronaryarterydiseaseleadingtoischemia.Myocardialirritabilitytypicallyresultsfromnonlethalischemiaorfrompreexistingfibrosisfrompreviousmyocardialinjury.SCDlessoftenisduetoacuteplaquerupturewiththrombosisthatinducesarapidlyfatalarrhythmia.