Porth's Essentials of Pathophysiology, 4e

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Disorders of Cardiac Function

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outflow obstruction that is caused by systolic anterior motion of the mitral valve and midsystolic contact with the ventricular septum. The obstruction is worsened by factors that increase myocardial contraction (e.g., sympa- thetic stimulation or exertion) or decrease left ventricular filling (e.g., Valsalva maneuver, peripheral vasodilation). Clinical Manifestations. The clinical manifestations of HCM are highly variable and may progress to end-stage heart failure with left ventricular remodeling and sys- tolic dysfunction. The most frequent symptoms of HCM are dyspnea and chest pain in the absence of coronary artery disease. Syncope (fainting) is also common and is typically post-exertional, when diastolic filling dimin- ishes and outflow obstruction increases. Atrial fibrilla- tion can occur as a long-term consequence of elevated left atrial pressures. Ventricular arrhythmias are also common and sudden death may occur, often in athletes after extensive exertion. Risk factors for sudden cardiac death among patients with HCM include a family his- tory of syncope or sudden cardiac death, certain gene mutations, and extreme hypertrophy of the left ventricle. Diagnosis and Treatment. Diagnosis of HCM is fre- quently established with 2D echocardiography, ECG, and continuous ambulatory monitoring. Cardiac MRI can also be helpful. Genetic testing, through bidirectional deoxyribonucleic acid (DNA) sequence analysis, is impor- tant for identifying gene mutations and making diagno- ses, although with some limitations. 48 In many patients with HCM, physical examination results are normal. Medical management of HCM is primarily focused on symptom management. The first-line approach to relief of symptoms is pharmacologic therapy designed to block the effects of catecholamines that exacerbate outflow obstruction and to slow heart rate to enhance diastolic filling. In the majority of cases of symptomatic HCM, beta blockers are the initial choice for therapy. Calcium channel blockers, especially verapamil, can also be used in patients who do not respond to beta block- ers. Calcium channel blockers can, however, exacerbate left ventricular outflow obstruction and are not recom- mended for persons with severe outflow obstruction and pronounced symptoms. Dual-chamber and biventricular pacing may be used to prevent progression of hypertrophy and obstruction. In obstructive HCM that is refractory to drug therapy, septal myotomy–myectomy (surgical excision of part of the outflow myocardial septum) or alcohol ablation of the interventricular septum can be used. An implant- able cardioverter–defibrillator should be considered for persons with HCM who have sustained ventricular tachycardia or ventricular fibrillation and are receiving optimal medical therapy. 46 Arrhythmogenic Right Ventricular Dysplasia Arrhythmogenic right ventricular dysplasia (ARVD) also called arrhythmogenic right ventricular cardio- myopathy (ARVC), is a heart muscle disease that pri- marily affects the right ventricle, leading to various

rhythm disturbances, particularly ventricular tachycar- dia, and potentially to heart failure. 49 It ranks second, after HCM, as the leading cause of sudden cardiac death in young athletes. The incidence of ARVD varies from about 1 in 2000 to 1 in 5000, affecting men more fre- quently than women. 49 Arrhythmogenic right ventricular dysplasia is inherited as an autosomal dominant trait in greater than 50% of cases, although often with incomplete penetrance and vari- able expression. Although multiple gene mutations have been identified (mapping to chromosomes 1, 2, 3, 14, and 17), 50 the pathogenesis of the disorder remains undefined. Clinical Manifestations. The disorder is characterized by progressive loss of myocytes, with partial or complete replacement of the right ventricular muscle with adi- pose or fibrofatty tissue. These changes are associated with reentrant ventricular tachyarrhythmias of right ventricular origin that are often precipitated by an exer- cise-induced discharge of catecholamines. Clinical mani- festations include palpitations, syncope, or cardiac arrest, usually in young or middle-aged men. Other symptoms may include abdominal pain and mental confusion. Diagnosis andTreatment. Diagnosis of ARVD is based on clinical, ECG, echocardiographic, and histologic find- ings. Personal and family history, including first- and second-degree relatives, is important. Treatment for ARVD is aimed at prevention of sudden cardiac death, prevention or delay. Although ARVD cannot be cured, the goal of treatment is to prevent and control the arrhyth- mias with antiarrhythmic agents. 49 Radiofrequency abla- tion may be used in cases that are refractory to drug therapy, although it is completely successful in only 30% to 65% of cases, with multiple ablations some- times needed. An implantable cardioverter–defibrillator is also indicated for drug-refractory cases and for those who have survived a sudden cardiac death episode. Final options for treatment include ventriculotomy and heart transplantation. 49 There are no randomized trials evalu- ating ARVD treatment modalities at this time. Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is a common cause of heart failure and the leading indication for heart trans- plantation. Up to 35% of cases are reported as familial; however, that proportion may be even higher, but due to incomplete penetrance it is difficult to identify early or latent disease in family members. 6,51 Most familial cases appear to be transmitted as an autosomal dominant trait, but autosomal recessive, X-linked recessive, and mitochondrial inheritance patterns have been identified. Other causes include infections (i.e., viral, bacterial, fungal, mycobacterial, parasitic), toxins, alcoholism, chemotherapeutic agents, metals, and multiple other disorders. Often no cause is found, in which case it is often referred to as idiopathic DCM. Dilated cardiomyopathy is characterized by pro- gressive cardiac dilation and contractile (systolic) dysfunction, usually with concurrent hypertrophy. 6,51