7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Myocardial Disease Contents Myocardial Disease - Secondary Hypertension or valvular disease Ischemic cardiomyopathy Alcohol Metabolic cardiomyopathy Tako-tsubo cardiomyopathy Peripartum cardiomyopathy Tachycardia-induced cardiomyopathy Myocardial Disease - Primary Hypertrophic cardiomyopathy Genetics Epidemiology Pathophysiology Diastolic dysfunction Ischemia Arrhythmia Wall thinning and cavity dilation Clinical diagnosis Echocardiography Electrocardiography Medical treatment Invasive treatment of obstructive HCM Dual chamber pacing Prognosis and outcome Dilated cardiomyopathy Genetics Pathophysiology Clinical diagnosis Management of DCM Specific dilated cardiomyopathies Cardiomyopathy in muscular dystrophy Prognosis and outcome Restrictive cardiomyopathy Infiltrative cardiomyopathy Amyloidosis Types of amyloidosis Cardiac amyloidosis https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 1/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Clinical manifestations Clinical diagnosis Physical examination Electrocardiography Echocardiography Management Sarcoidosis Pathophysiology Clinical diagnosis Management Storage diseases Hemochromatosis Diagnostic features Management Fabry disease (angiokeratoma corporis diffusum universale) Gaucher Disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Hypereosinophilic syndrome: L ffler Endocarditis Arrythmic cardiomyopathy: Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosis Treatment Unclassified Cardiomyopathy: Left ventricular non-compaction Clinical Presentation and Diagnosis Treatment and Prognosis Myocardial Disease Overall, myocardial diseases can be subdivided into two types: primary and secondary myocardial diseases. Whereas the primary type most commonly has a genetic cause, secondary myocardial diseases are mostly acquired but may be precipitated by a genetic background. Overall, the dilated type is the most prevalent manifestation of cardiomyopathy, and may be induced by a multitude of precipitating factors, such as chronic ischemia or alcohol abuse. The most common primary myocardial disease is hypertrophic cardiomyopathy, which is associated with a wide variety of genetic abnormalities. In the light of their substantially larger prevalence, we will first describe the secondary myocardial diseases, after which the less frequently occurring primary myocardial diseases will be discussed. Myocardial Disease - Secondary Myocardial disease subsequent to a known origin is termed secondary myocardial disease. Timely correction of the originating disease may result in reversal of the cardiomyopathy. Nine different etiologies can be distinguished: https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 2/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Hypertension Ischaemia Valvular disease Alcohol Metabolic cardiomyopathy Takotsubo cardiomyopathy Peripartum cardiomyopathy Tachycardia Hypertension or valvular disease Inadequately treated hypertension or aortic stenosis results in adaptation of the left ventricle by means of hypertrophy. Although primarily considered an adaptive process to systolic overload, hypertrophy of the left ventricle is associated with ventricular dysfunction, arrhythmias, and sudden cardiac death. The process of hypertrophy involves enlargement and proliferation of myocytes, and interstitial fibrosis characterized by deposition of collagen type I and III. With increasing fibrosis, the compliance of the ventricle decreases resulting in loss of diastolic function before systolic function becomes impaired. Within this process of increasing myocardial mass, the coronary vasculature fails to adapt accordingly. In an attempt to accommodate to the increase in myocardial oxygen demand, coronary autoregulatory vasodilation results in an increase in coronary flow by during resting conditions. This partial exhaustion the coronary vasodilator reserve renders the myocardium at relative high risk for ischemia, and hence, patients may suffer from anginal complaints even in the absence of significant coronary artery disease. In patients with LVH, atrial fibrillation and ventricular arrhythmias, including multifocal ventricular extrasystoles, and short runs of ventricular tachycardia, are frequently found. The combination of myocardial fybrosis, maladaptation of the vasculature causing ischemia, autonomic imbalance and a prolongation of the action potential may serve as arrhythmogenic substrate in patients with LVH, resulting in an increased risk of sudden cardiac death. Adequate antihypertensive treatment can regress left ventricular mass. In patients with aortic stenosis, ultimate treatment is valvular replacement to relief the systolic overload of the ventricle. With regression of the ventricle, improved diastolic, and preserved systolic function result, as well as a relief of vascular maladaptation-induced ischemia; the combination of which results in a decrease in cardiovascular events. Ischemic cardiomyopathy Chronic myocardial ischemia due to diffuse coronary atherosclerosis can cause cardiomyopathy of the dilated type (DCM). This ischemic cardiomyopathy may occur following one or multiple (silent) myocardial infarction(s), but may also occur from chronic (silent) ischemic myocardial damage. As such, it may be a progressive course of ventricular dilatation and ventricular dysfunction, but may also be the first manifestation of ischemic heart disease. The extent of viable, or hibernating, myocardium determines the clinical relevance of revascularization of the ischemic myocardium. In patients with viable myocardial tissue, reperfusion improves symptoms, and supposedly prognosis. Several non-invasive tests may be used for this purpose, such as nuclear techniques, dobutamine echocardiography or contrast-enhanced cardiac MRI. However, the prognosis of https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 3/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology ischemic cardiomyopathy is worse than non-ischemic forms of DCM, mainly due to a high risk of major ventricular arrhythmias. Moreover, subsequent ischemic episodes have a high impact on ventricular function in ischemia-related DCM. As stated previously, revascularization may improve long-term prognosis in patients with objectively viable myocardium. In the absence of viability, routine heart failure therapy is the cornerstone of treatment including beta-blockade and ACE-inhibition (or angiotensine antagonists), and ICD implantation in a selection of patients. Alcohol Long-term alcohol abuse, >80g of alcohol per day (equivalent to 1 liter of wine) for more than 5 years, may lead to a dilated form of cardiomyopathy. Alcohol-induced dilated cardiomyopathy is the leading cause of non-ischemic dilated cardiomyopathy, some claim that it accounts for even up to 50% of cases. Most probably a genetic predisposition for DCM also plays an important role, as excess alcohol consumption itself prevails far more often than alcoholic cardiomyopathy (ACM). Both direct toxic effects of ethanol and its metabolites, as well as frequently occurring concomitant deficiencies of vitamins, minerals or electrolytes may adversely affect myocardial function. Two stages of ACM are recognized when the disease is left untreated. The first stage comprises asymptomatical ventricular dilatation in which diastolic dysfunction may be present, at least partly due to interstitial fibrosis of the myocardium. Fifty percent of asymptomatic patients have echocardiographic signs of LVH with preserved systolic function. The second stage is characterized by impairment of systolic function, and clinically overt heart failure. The prognosis of untreated ACM is comparable to DCM, but is far more favourable in patients that abstain from alcohol use, or dramatically reduce alcohol intake (to less than 60g of ethanol per day). Most of the improvement follows abstinence within 6 months, but ventricular function may improve for up to 2 years. Heart failure therapy may improve ventricular function, but has only been shown to benefit survival in patients that practise abstinence. Metabolic cardiomyopathy The group of metabolic cardiomyopathies comprises a heterogenous group of myocardial disease secondary to a disruption in metabolism. Metabolic cardiomyopathy associated with diabetes mellitus is most common. Independent of its influence on hypertension or coronary artery disease, high levels of plasma glucose are increasingly associated with a direct deteriorative effect on ventricular function. Other examples of metabolic disease able to induce cardiomyopathy are nutritional deficits such as thiamine deficiency, or storage diseases, and mutations in AMP kinase. Tako-tsubo cardiomyopathy The prevalence of tako-tsubo cardiomyopathy is largely unknown, but the syndrome predominantly affects women between 60 and 65 years of age. Patients with Tako-tsubo cardiomyopathy present with electrocardiographic features mimicking an acute coronary syndrome in association with elevated cardiac biomarkers, but in the absence of significant coronary artery disease. The disease has inherited its name from the distinct angiographic feature of apical ballooning, resembling an octopus-pot or "Tako-tsubo". Left ventricular function is typically impaired in the apical and mid ventricular regions, with preserved basal function, although reverse patterns may be seen. High levels of cathecholamines have been suggested to play an important role in the etiology of the syndrome, which can be associated with emotional or physical stress, or in extremes in case of subarachnoidal hemmorhage. This https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 4/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology cathecholamine storm may induce severe peripheral coronary spasm, leading to its clinical presentation. Treatment usually consists of aspirin, ACE-inhibitors or angiotensin receptor antogonists in case of preserved blood pressure, beta-blockers to to reduce heart counteract coronary spasms. LV function may restore rapidly within a few hours or days, even when admission ejection fraction was severely impaired, and clinical outcome is good although the disease may recur in approximately 5% of patients. rate, and nitrates Peripartum cardiomyopathy function Left impairment within 1 month of delivery, or during the first 5 months post partum, in the absence of pre-existing cardiac disease, and in the absence of another recognized cause for the cardiac dysfunction is termed peripartum cardiomyopathy. ventricular systolic Presentation is typically with features of left ventricular failure, although many features from normal changes in pregnancy, due to which mild forms may not even be recognized. An inflammatory component has been suggested, in addition to malnutrition, viral infection, an abnormal immune response, and familial predisposition. Recurrence of the disease in subsequent pregnancies is noted, and makes the previously mentioned etiologies hard to explain. Most probably, peripartum cardiomyopathy results from predisposition to DCM, triggered to uncover by the high cardiovascular burden of the pregnancy. are undistinguishable Tako-tsubo cardiomyopathy Standard heart failure therapy can be instituted in peripartum cardiomyopathy, but the use of ACE- inhibitors and angiotensin receptor antagonists is contraindicated during pregnancy after the first trimester due to their possible adverse effects on the fetus. In extreme cases, the potential risks for the fetus should however be balanced against the critical need for preservation of ventricular function in order to provide both the mother and the fetus the best chance for a favourable clinical outcome. Pregnancy is also associated with a high risk of thrombo-embolism, as it is a hypercoagulable state per definition, which is enhanced by the presence of an impaired ventricular function in case of peripartum cardiomyopathy, and prophylaxis is therefore recommended. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 5/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Despite optimal treatment, LV function may normalize in as less as 50% of patients, and may deteriorate to end-stage heart failure in 15%. Potential recurrence in future pregnancies requires counselling of patients to prevent subsequent episodes of symptomatic heart failure and progression of ventricular dysfunction. Tachycardia-induced cardiomyopathy Persistently high heart rates (above 110 beats per minute), such as in sustained ventricular tachycardia, or associated with atrial fibrillation, results in heart failure when left untreated. Normalization of the heart rate by means of beta-blockade subsequently leads to normalization of ventricular function, and is therefore the cornerstone in treatment of tachycardia-induced cardiomyopathy. Myocardial Disease - Primary Five different groups of primary myocardial disease exist; which are defined as diseases of the myocardium with impaired cardiac function, also referred to as cardiomyopathies. Hypertrophic cardiomyopathy (HCM) Dilated cardiomyopathy (DCM) Restrictive cardiomyopathy (RCM) Arrythmic cardiomyopathy (ACM) Unclassified cardiomyopathy (UCM) Hypertrophic cardiomyopathy The essential characteristics of hypertrophic cardiomyopathy (HCM) are unexplained hypertrophy of the left ventricle in the absence of causal cardiac or systemic disorders. Distinctive features further comprise myocyte disarray, familial occurrence, and an association with sudden cardiac death (SCD). Genetics The identification of the genetic background of HCM resulted in the hypothesis that HCM is a disease of the sarcomere; the contractile unit of the cell. First, mutations were found in the cardiac B-myosin heavy chain gene, while later on other sarcomeric proteins were found to play a role in HCM (Table 1). Table 1. Sarcomeric genes associated with HCM -tropomyosin cardiac troponin T troponin I myosin-binding protein C regulatory myosin light chain essential myosin light chain cardiac actin titin troponin C -myosin heavy chain https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 6/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology It was shown that macroscopic hypertrophy of the myocardium is not essential for neither diagnosis nor prognosis, as mutations for example in troponin T may lead to only minor or no hypertrophy, whereas it is associated with a high incidence of SCD. Nowadays HCM is considered a genetic disorder, inherited mainly autosomal dominant with an incomplete and age-related penetrance. Pathological findings may include myocardial hypertrophy, small-vessel disease and myocyte disarray with or without fibrosis. The prevalence of HCM in the adult population is approximately 1 in 500. But as in only 60% of HCM patients mutations in the abovementioned known sarcomeric genes are present, non-sarcomeric variants of HCM or mutations in regulatory genes, have gained interest. Left ventricular hypertrophy in young children is known most often not to be caused by sarcomeric HCM, but rather by inherited metabolic disorders and syndromes with extracardiac features. These diseases may cause to non-sarcomeric HCM as they include Fabry disease and Danon disease. Recognition and diagnosis of HCM may involve familial counselling, which also helps to find the presence of extracardiac features, and may influence treatment. Epidemiology The prevalence of the HCM phenotype was found to be approximately 0.2%, or 1 in 500, in several epidemiological studies. This frequency is notably higher than its occurrence in daily clinical practice. Hence, a large amount of patients remains undiagnosed, most probably without symptoms of inferences for their prognosis. Pathophysiology Left ventricular outflow tract obstruction (LVOTO) The subdivision of HCM into obstructive and non-obstructive forms is clinically important, and is based on the presence or absence of a LV outflow tract gradient during rest and/or after provocation. The presence of such a gradient typically results in a loud apical systolic ejection murmur. The obstruction leads to an increase in intraventricular pressures, impairing LV function by increasing myocardial wall stress and oxygen demand. The obstruction is located either sub-aortic or mid-cavity, where the sub- aortic location is most common and is caused by systolic anterior motion (SAM) of the mitral valve and mid-systolic contact with the ventricular septum. SAM is thought to be facilitated by either an abnormal valvular apparatus loose enough to allow movement, or a hemodynamic force with an anterior component during systole. A drag-effect probably attributes to SAM, which refers to the force exerted by a fluid in the direction of the flow. Apart from its role in sub-aortic obstruction, SAM also results in concomitant mitral regurgitation. The sub-aortic gradient and associated LV pressure increase are pathophysiologically significant and may worsen outcome. LVOTO is an independent predictor for HCM-related death, progression of the disease in terms of New York Heart Association (NYHA) class III or IV, and death due to heart failure or stroke. A gradient threshold of 30 mmHg is prognostically important, but a further increase is not associated with further increased risk. Chronic outflow tract obstruction results in an increase in LV wall stress, myocardial ischemia and fibrosis, and justifies intervention in severely symptomatic patients when optimal medical management is insufficient. HCM patients can be divided into hemodynamic subgroups based on the representative obstructive gradient: 1. Obstructive - gradient under resting conditions equal to or greater than 30 mm Hg (2.7 m/s by Doppler) 2. Provocable obstructive (latent) - gradient less than 30 mm Hg under resting conditions and equal to or greater than 30 mm Hg with provocation https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 7/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology 3. Nonobstructive - less than 30 mm Hg under both resting and provocated conditions. LV outflow gradients are routinely measured noninvasively with continuous wave Doppler echocardiography. To define provocable gradients, treadmill or bicycle exercise testing is the preferred stress test, given that HCM-related symptoms are typically elicited with exertion. Pharmacological induction of stress by intravenous infusion of dobutamine is considered contra-indicated. Diastolic dysfunction HCM is, in contrast to other cardiomyopathies, characterized by early occurrence of diastolic dysfunction (both active and passive phases), while systolic function is typically preserved, even before signs of hypertrophy. The passive relaxation during filling of the ventricle is hampered by increased chamber stiffness, increasing filling pressures and decreasing myocardial blood flow. Isovolumetric relaxation in early diastole is prolonged in HCM. Diastolic dysfunction may well lie at the basis of heart failure in non- obstructive HCM with preserved systolic function. Ischemia Myocardial hypertrophy disrupts the subtle equilibrium of blood flow throughout the myocardial layers. Patients with HCM show an increase in coronary blood flow velocity compared to healthy individuals reflecting an autoregulatory decrease in microvascular resistance to adapt to an increase in oxygen demand during resting conditions. The coronary reserve is therefore partly exhausted. Apart from the changes in the coronary microcirculation, systolic extravascular compression might play a role. Most importantly, HCM results in a progressive mismatch between muscle tissue and vascular growth, resulting in a high risk of myocardial ischemia especially for the subendocardial layers. The presence of myocardial ischemia is an important determinant of progression of the disease as it promotes scarring and remodelling of the ventricle. Arrhythmia Myocardial fibrosis associated with HCM is an important arrhythmogenic substrate. Functional consequences of HCM may therefore provide a trigger for ventricular arrhythmias, i.e. ischemia and LVOTO, resulting in non-sustained ventricular tachycardia in approximately 20% of patients. Other functional consequences as diastolic dysfunction, mitral regurgitation, as well as LVOTO are associated with atrial fibrillation (AF) which is observed in 20-25% of HCM patients. Wall thinning and cavity dilation https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 8/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Over time, thinning of the hypertrophic LV wall may occur in patients with severe LVH which may account for the lack of marked echocardiographic LVH in the elderly. While mechanisms of LV remodelling in HCM are still to be defined, cavity dilation and hampered systolic function occur in less than 5% of patients. Clinical diagnosis The cornerstone of HCM diagnosis is represented by echocardiography and electrocardiography. In the overall population, the diagnostic criterion of HCM is a maximal wall thickness greater or equal to 15 mm. However, virtually any wall thickness may be associated with the presence of an HCM mutant gene, including wall thickness well within the normal range. Therefore, for both echocardiography and electrocardiography, criteria have been established for the diagnosis of HCM in patients with high risk for HCM. Specificity of these criteria relies significantly on the a-priori chance of HCM, and is therefore only pertinent in first-degree relatives of index cases with confirmed HCM, whom therefore all have a 50% a-priori chance of carrying an HCM mutation. HCM is confirmed in a first-degree relative when either 1 major or 2 minor echocardiographic criteria (Table 2), or 1 minor echocardiographic and 2 minor electrocardiographic criteria (Table 3) are present. Echocardiography Two-dimensional echocardiography is the easiest diagnostic modality for detection of HCM, (Table 2) but cardiac magnetic resonance imaging (CMR) may be used when echocardiography is inconclusive, acoustic windows are insufficient, or when more detailed anatomic information is needed for clinical decision making. Echocardiographic characteristics include thickening of the left ventricular wall without cavity dilatation, and a normal or hyperdynamic left ventricle. Left ventricular outflow tract obstruction is not mandatory for the diagnosis of HCM. Moreover, as mentioned previously, although the diagnosis of HCM is based on a cut-off value for maximal wall thickness of 15 mm in the overall population, multiple HCM-linked mutations are associated with only minor LVH, but represent a high risk of sudden cardiac death. Table 2. Echocardiographic diagnostic criteria for HCM in first-degree relatives of index cases with HCM : Major: LV wall thickness =13 mm in the anterior septum or =15 mm in the posterior septum or free wall Severe SAM (septum leaflet contact) Minor: LV wall thickness of 12mm in the anterior septum or posterior wall or of 14mm in the posterior septum or free wall Moderate SAM (no septum leaflet contact) Redundant mitral valve leaflets Electrocardiography https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 9/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Electrocardiographic signs of HCM are typical as the increase in myocardial tissue increases the size of the QRS complexes. Therefore, a typical ECG characteristic of HCM is that it meets voltage criteria for LVH, and shows changes in repolarization (Table 3). Table 3. Electrocardiographic diagnostic criteria for HCM in first-degree relatives of index cases with HCM : Major: Left ventricular hypertrophy and repolarization changes T-wave inversion in leads I and aVL (=3mm) (with QRS T wave axis difference =30 ), V3 V6 (=3mm) or II and III and aVF (=5mm) Abnormal Q (>40 ms or >25% R wave) in at least two leads from II, III, aVF (in absence of left anterior hemiblock), V1 V4; or I, aVL, V5 V6 Minor: Complete bundle branch block or (minor) interventricular conduction defect (in LV leads) Minor repolarization changes in LV leads Deep S V2 (>25mm) Medical treatment Asymptomatic HCM patients should only receive drugs when symptoms of diastolic dysfunction are present. Verapamil is the treatment of choice, improving diastolic filling and relaxation of the ventricle, decreasing diastolic filling pressures. In symptomatic patients, first line medical treatment consists of a calcium-channel blocker or a betablocker. Verapamil is the first choice, but diltiazem may be used as an alternative. Second, beta- blockers may be used when symptoms prevail, and can be used solitarily or in combination with a calcium-channel blocker. In severely symptomatic patients, diuretics may be used, but with high caution as a small drop in ventricular filling pressure may reduce stroke volume and cardiac output dramatically in HCM patients. A combination can be made with either calcium-channel blockers or beta-blockers. Patients presenting with ventricular tachyarrhythmia or supraventricular atrial fibrillation, amiodarone may be used, and may even improve symptoms and prognosis. Disopyramide has negative inotropic action and results in peripheral vasoconstriction and may improve symptoms when diastolic dysfunction is most prominent (i.e. with preserved ejection fraction). Invasive treatment of obstructive HCM In patients where maximal medical treatment does not control the symptoms, invasive debulking of the myocardial septum may be considered when a marked outflow gradient is present. Treatment options comprise percutaneous alcohol septal ablation, or surgical septal myectomy. Surgical myectomy has shown excellent long-term result, but 15-20% of patients may suffer from ventricular remodelling and dilatation of the left ventricle. Since the introduction of alcohol ablation, surgical myectomy is reserved for patients with HCM with concomitant disease that independently https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 10/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology warrants surgical correction, such as coronary artery bypass grafting of valve repairs, in whom surgical myectomy can be performed as part of the operation. Septal ablation may be considered in patients with outflow tract gradients of more than 30 50 mmHg at rest or 60-100 mmHg after provocation. By injection of 1-3 mL of pure alcohol over 5 minutes into the first or second septal branch, a small myocardial infarction is created. Furthermore, the alcohol induces septal hypokinesis, adding to a reduction of the outflow tract gradient. The gradient may resolve immediately, but this process may take weeks to months. When the outflow tract obstruction persists, patients can be treated a second time. Dual chamber pacing In patients with medically refractory symptoms, whom are suboptimal candidates for invasive treatment, permanent dual chamber pacing may be considered. Pacing may alleviate symptoms by decreasing the outflow tract pressure gradient. However, maintaining a reduction in gradient requires pre-exitation of the right ventricular apex and distal septum, and complete ventricular caption. For optimal results, this should therefore be performed in highly experienced centers only. Prognosis and outcome In general, symptoms of HCM increase with age. Mortality rates have been reported to account between 2 and 3% per year. Most importantly, patients with HCM may be at high risk of sudden cardiac initial death, which may even be presentation, in asymptomatic or mildly symptomatic young patients. HCM is the most common cause of SCD in young people, including athletes. The pathophysiological basis for this predilection is unclarified, and although SCD is most frequent in young people less than 30 to 35 years old, an increased risk for SCD extends thereafter. Although HCM presentation and clinical manifestation is heterogeneous, and it has a clinical markers as shown in Table 4 may identify patients at high risk for SCD. Patients at high risk of SCD are eligible candidates for ICD implantation. its particular in Treatment strategy in HCM relatively low prevalence, https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 11/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 4. Risk factors for SCD Major Cardiac arrest (ventricular fibrillation) Spontaneous sustained ventricular *tachycardia Family history of premature sudden cardiac death Unexplained syncope LV thickness = 30mm Abnormal exercise blood pressure (increase in systolic blood pressure =20 mmHg) Nonsustained ventricular tachycardia (Holter) Minor Atrial fibrillation Myocardial ischemia LV outflow tract obstruction High-risk mutation Intense (competitive) physical exertion Fibrosis on CMR Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by ventricular dilatation (one or both ventricles) and impaired myocardial contractility. The impairment of myocardial function cannot be explained by abnormal loading conditions alone, such as valve disease or systemic hypertension. The prevalence of DCM is approximately 36 per 100 000; in at least 50% of patients with DCM, its cause cannot be determined which is referred to as idiopathic DCM. DCM is a condition of which causes and presentations are highly heterogeneous. The diagnosis of idiopathic DCM should only be made after exclusion of the specific cardiomyopathies with a dilated phenotype. Genetics The genetic background of DCM is not as clear as in HCM. Although previously thought to be sporadic, genetic transmission is now thought to account for 30-40% of cases. Multiple genes have been identified that are linked with the occurrence of DCM. Genetic disease may account in part for the primary forms of DCM, but importantly, genetic predisposure may well lead to DCM in case of exposure to precipitating factors such as (emotional) stress, excessive alcohol use or stress upon the cardiovascular system; secondary DCM. The expression of DCM in the familial form is frequently incomplete, and hence its prevalence is supposedly underestimated to a large extent. Even minor abnormalities may progress into overt DCM, and accurate clinical screening of (asymptomatic) relatives is therefore mandatory for early identification of familial DCM cases. Pathophysiology https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 12/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology In general, a wide variety of factors can induce or contribute to the development of DCM including arterial hypertension, myocarditis, alcohol abuse or tachyarrhythmias. A subsequent increase in wall stress combined with activation of neurohumoral pathways induces complex cellular and molecular maladaptation, and programmed cell death finally leads to a decrease in the number of functioning cardiomyocytes. This process of cardiac remodelling itself results in systolic and/or diastolic dysfunction, leading to increased wall stress, and thereby creating a vicious circle of progressive systolic dysfunction (Figure 1). The failing myocardium has several distinct factors promoting apoptosis of cardiomyocytes in vitro; cathecholamines, wall stress, angiotensin II, nitric oxide and inflammatory cytokines. Hence, medical management of DCM aims at antagonizing these pathways, reducing stress signalling in, and remodelling of the failing heart. Clinical diagnosis The most common initial manifestation of DCM is heart failure, in which clinical symptoms do not differ from heart failure of other causes. An important feature of is a gallop the physical examination rhythm of S3 and S4. S3 and S4 may fuse in tachycardic patients with new onset of heart failure. Special attention should focus upon excluding valvular heart disease as a cause, and excluding right- sided involvement. Figure 1. Process of cardiac remodelling Diagnostic testing in DCM focuses on identification of reversible causes, which focuses on the history (alcohol use) but also includes plasma biomarker evaluation, non-invasive imaging, electrocardiography, and exercise testing. Echocardiography is an important diagnostic modality in DCM, as it can be used to assess both the size and shape of the LV, but also to determine LV function by assessing the LV ejection fraction (LVEF). Furthermore, valvular heart disease or pericardial abnormalities can be excluded. CMR evaluation may contribute to identification of specific cardiomyopathic conditions, especially when acoustic windows are suboptimal. The cardiac response to exertion is an established risk factor in DCM patients, which may be evaluated by cardiopulmonary exercise testing. Dilatation of the ventricular cavity results in myocyte stretch. In response, B-type natriuretic peptide is released, which is a well-known neurohormone that can be used to evaluate progression of DCM and to guide medical treatment. High plasma concentrations (twice the ULN) are strongly associated with increased long-term mortality. Electrocardiography does not provide an accurate diagnostic mean in DCM, but can identify several characteristics associated with unfavourable prognosis, or identify factors contributing to DCM, and therefore is an important modality in the evaluation of DCM patients. Sinus tachycardia is frequently present, and non-specific ST-segment or T-wave changes as well as changes in P-wave morphology may well be present. AF is an important feature associated with high mortality; its control may contribute to improve cardiac performance. Furthermore, the presence of AF may indicate tachycardia-induced DCM. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 13/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology 24-hour Holter monitoring can reveal decreased heart rate variability or complex ventricular arrhythmias which are associated with a high risk for mortality. Finally, prolonged QTc intervals are associated with high mortality. Management of DCM Management of symptoms and progression of DCM accord to those described in the management of heart failure. Hence, also in DCM, diuretics and neurohumoral antagonists provide the basis for management of symptoms, and preventive ICD or pacemaker implantation is indicated in selected patients. Most importantly, surgical or percutaneous correction of underlying conditions facilitating progression of DCM, such as coronary artery disease, valvular heart disease or congenital abnormalities is warranted. Specific dilated cardiomyopathies It is important to note that there are several causes of secondary DCM. A foursome of these is of utmost importance to recognize early on, as accurate diagnosis influences the patients treatment strategy and chance for complete recovery. Tako-tsubo Is described under Secondary Myocardial Disease Peripartum cardiomyopathy Is described under Secondary Myocardial Disease Tachycardia-induced cardiomyopathy Is described under Secondary Myocardial Disease Alcoholic cardiomyopathy Is described under Secondary Myocardial Disease Cardiomyopathy in muscular dystrophy Defined as primary disorders of skeletal and/or cardiac muscles of genetic etiology, muscular dystrophies were primarily described based upon the distribution and extent of skeletal muscle involvement. The involvement of the heart was commonly attributed to processes extrinsic to the heart, resulting in restrictive lung disease, subsequent pulmonary hypertension, and secondary myocardial dysfunction. Intrinsic dysfunction is increasingly recognized as an important etiology for myocardial function impairment in the presence of muscular dystrophy. Typical forms of dystrophy are based on deficiency of dystrophin, of which mutations have been described in X-linked DCM. Furthermore, histological changes were found in the myocardium similar to those in skeletal muscles, which suggest a common etiology, and moreover cardiac manifestations may be present even in the absence of myopathic symptoms. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 14/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Treatment of cardiac dysfunction is treated according to the nature of cardiac involvement. Conduction disorders may present which require pacing, and standard heart failure therapy may be instituted in case of ventricular dilatation and functional impairment. Ventricular tachyarrhythmias may be found in particular in myotonic dystrophia, and require the implantation of an internal cardiac defibrillator to prevent its associated sudden cardiac death. Prognosis and outcome DCM has a highly variable clinical course. Approximately half of DCM patients respond well to routine heart failure medication, and a minority of patients even shows an improving clinical course. Conversely, a subgroup can be identified with a highly unfavourable clinical course, not responsive to heart failure medication and rapidly progressing to inotropy- or LVAD-dependency. Overall, 5-year survival rates approximate 30%. Restrictive cardiomyopathy Restrictive cardiomyopathy is characterized by an increase in ventricular wall stiffness, impairing its diastolic function. Systolic function is usually preserved in early stages of the disease, but may deteriorate with progression of the disease. RCM is less frequent in the developed world than the previously described HCM and DCM, but is an important cause of death in Africa, India, South and Central America, and Asia due to the high endemic incidence of endomyocardial fibrosis. The spectrum of restrictive cardiomyopathies can be classified as shown in Table 5, according to its cause. The most important specific causes of RCM will be discussed in detail below. An important differentiation is that between RCM and constrictive pericarditis. Constrictive pericarditis is similarly characterized by impaired ventricular filling with preserved systolic function, but may be adequately treated by pericardiectomy, which makes this distinction of major clinical importance. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 15/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 5 - Classification of Restrictive Cardiomyopathy Myocardial Noninfiltrative Idiopathic cardiomyopathy Familial cardiomyopathy Hypertrophic cardiomyopathy Scleroderma Pseudoxanthoma elasticum Diabetic cardiomyopathy Infiltrative Amyloidosis Sarcoidosis Hurler disease Fatty infiltration Storage Disease Hemochromatosis Fabry disease Gaucher disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Hypereosinophilic syndrome Carcinoid heart disease Metastatic cancers Radiation Toxic effects of anthracycline Drugs causing fibrous endocarditis(serotonin, methysergide, ergotamine, mercurial agents, busulfan) Adapted from Kushwaha S, Fallon JT, Fuster V: Restrictive cardiomyopathy. N Engl J Med 336:267, 1997. Copyright 1997, Massachusetts Medical Society. Infiltrative cardiomyopathy Amyloidosis