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 Amyloidosis is a disease that results from tissue deposition of fibrils that have a distinct secondary structure of a beta-pleated sheet configuration, leading to characteristic histological changes. Amyloid depositions can occur in almost any organ, but usually remains clinically undetected unless extensive depositions are present. Types of amyloidosis https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 16/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology The most frequent types of amyloidosis are the AL (primary) and AA (secondary) types. AL amyloidosis is a plasma cell dyscrasia, which can occur solitarily or in association with multiple myeloma. AA amyloidosis can be considered a complication of chronic inflammatory disease states such as rheumatoid arthritis, in which the depositions consist of fragments of serum amyloid A, which is an acute phase reactant. Hereditary amyloidosis has been increasingly recognized in the last decade, and results from mutations in the gene for thransthyretin. Some mutations are clinically limited to the myocardium. Its incidence increases with increasing age, with a predilection for men, but its prognosis is better than that of the AL type. Senile systemic amyloidosis results from deposition of normal wild-type transthyretin. This form of amyloidosis is clinically predominated by an infiltrative cardiomyopathy, but progression is slow and prognosis is better than of other acquired forms. Cardiac amyloidosis Cardiac amyloidosis is a progressive infiltrative cardiomyopathy. The primary form carries the highest cardiac involvement of approximately one third to half of patients, where deposits may be present even in the absence of clinical symptoms. Secondary amyloidosis is less frequently accompanied by cardiac infiltration, approximately 5% of cases, and is less likely associated with ventricular dysfunction due to a smaller size and more favourable location of the depositions. Familial amyloidosis is associated with clinical signs of cardiac involvement in a quarter of patients, typically presenting after the age of 35 with a distinct involvement of the cardiac conduction system. In senile amyloidosis, the extent of deposits may vary widely from solitarily atrial involvement up to extensive ventricular infiltration. Clinical manifestations Apart from the occurrence of cardiac disease in the presence of known AL amyloidosis or connective tissue disease or other chronic inflammatory disorders, cardiac amyloidosis should be considered in case of: Restrictive cardiomyopathy of unknown origin Left ventricular hypertrophy with a converse low-voltage ECG Congestive heart failure of unknown origin, not responding to contemporary medical management. Clinical diagnosis Diagnostic testing should include a 12-lead ECG, possibly with Holter monitoring, and routine echocardiography. Specific characteristics are a low-voltage 12-lead ECG with increase septal and posterior wall ventricular thickness. Physical examination https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 17/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology A physical examination may reveal an elevated jugular venous pressure, and signs of systemic edema. Auscultation frequently reveals an apical murmur due to mitral regurgitation, and a third heart sound, but the presence of a fourth heart sound may exclude amyloidosis, as atrial infiltration causes impaired atrial contraction. Electrocardiography Routine 12-lead ECG shows low voltage in the limb leads, and a pseudoinfarct pattern in approximately 50% of patients. Furthermore, conduction abnormalities occur frequently, as does atrial fibrillation. Echocardiography Thickening of the left ventricular wall with diastolic dysfunction are early echocardiografic features of the disease. In advancing disease, wall thickening increases, resulting in a restrictive cardiomyopathy. Sparkling myocardium is a distinct characteristic of cardiac amyloidosis, referring to an increased echogenicity of the myocardium. However, only a minority of patients has this pattern. Doppler evaluation shows a restrictive pattern with E dominance and a short deceleration time. Furthermore, intracardiac thrombus is common, which is associated with atrial fibrillation and left ventricular diastolic dysfunction. The thickening of the ventricular wall caused by amyloidosis may be misinterpreted as hypertrophy on echocardiography. An important distinctive characteristic of amyloidosis is the voltage-to-mass ratio. Unlike normal hypertrophic myocardium, the increased ventricular mass in amyloidosis is associated with a decrease in electrocardiographic voltage. Management Few treatments for cardiac amyloidosis exist, and those available are dependent on the type of amyloidosis present. Hence, typing of the disease is pertinent. AL amyloidosis may be treated with chemotherapy using alkylating agents alone or in combination with bone marrow transplantation. Heart transplantation in combination with bone marrow transplantation after high-dose chemotherapy was shown to be result in approximately a third of treated patients surviving over 5 years, but as the great majority of patients with AL amyloidosis has severe non-cardiac amyloidosis, most patients are not suitable transplant candidates. Patients with other types of amyloidosis frequently have less affected hearts, and progression of the disease is slow. AA amyloidosis may respond to anti-inflammatory and immunosupressive drugs that reduce production of the acute-phase reactant protein. If heart failure is present, it is usually more prone to routine medical treatment to reduce symptoms. If needed, heart transplantation can be performed successfully. In patients where transthyretine is the amyloidogenic protein, liver transplantation may be curative as tranthyretine is produced in the liver, but the cardiac disease may progress regardless in some patients. Overall, caution should be taken in prescribing digitalis, nifedipine, verapamil and ACE-inhibitors to cardiac amyloidosis patients. There is a high susceptibility to digitalis intoxication, nifedipine-induced hemodynamic deterioration, verapamil-induced left ventricular dysfunction, and ACE-inhibitor induced profound hypotension. If atrial fibrillation is present, or systolic ventricular function is severely impaired https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 18/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology anticoagulation is indicated to prevent intracardiac thrombi. In selected patients with conduction disorders, pacemaker implantation may be considered. If ventricular function is severely impaired, ICD implantation may be considered. Nonetheless, prognosis of especially AL amyloidosis is poor. Sarcoidosis Sarcoidosis is a multisystem inflammatory condition characterized by the formation of non-caseating granulomas, most frequently affecting the lungs and lymphatic system. Myocardial involvement is seen in one quarter of cases only. Genetic factors are suggested as there was found to be an aggregation of cases within families. Pathophysiology Non-caseating granulomas may infiltrate the myocardium, leading to fibrotic scarring of the myocardium. Involvement of the myocardium is usually patchy, resulting in a relatively high likelihood of false-negative results from biopsy. Cardiac sarcoidosis must be differentiated from chronic active myocarditis and giant cell myocarditis. Clinical diagnosis Patients may present with syncope, heart block or congestive heart failure. Sudden cardiac death may well be the initial manifestation of the disease due to malignant ventricular arrhythmias, but both atrial and ventricular arrhythmia is common at initial presentation. Symptoms of heart failure may result from direct myocardial involvement, but can also be due to extensive pulmonary fibrosis; cor pulmonale. Physical examination may include signs of extracardiac sarcoidosis, a right sided third heart sound, and both S3 and S4, as well as murmurs of tricuspid regurgitation or mitral regurgitation. Initial consideration of the diagnosis is often based on chest radiographs showing bilateral hilar lymfadenopathy. CMR is emerging as a highly sensitive and specific test for sarcoidosis, and nuclear imaging techniques may show regional perfusion defect due to the granulomatous inflammation on SPECT, or focal uptake on PET CT. electrocardiography is useful to assess the extent of conduction system involvement. Echocardiography shows left ventricular dilatation with hypokinesis, right ventricular enlargement and hypertrophy and possibly left ventricular aneurysm formation. Minimal evaluation of a patient suspected of cardiac sarcoidosis consists of a 12-lead ECG, Holter monitoring and echocardiography. Management Early detection of the disease is critical for its clinical course. Immunosuppression using corticosteroids to halt the progression of inflammation is the treatment of choice in sarcoidosis, to which myocardial dysfunction, conduction disturbances, and arrhythmias may all respond. Most important is the differentiation of sarcoidosis from giant cell myocarditis, which is a more aggressive disorder requiring https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 19/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology intensive medical and mechanical support and frequently necessitating heart transplantation. Pacemaker or ICD implantation is indicated in patients with conduction disorders or malignant arrhythmias, as medical treatment is usually ineffective in these cases. Storage diseases Hemochromatosis Hemochromatosis is defined as a disorder of the iron metabolism, resulting in accumulation of iron in parenchymal tissues. In particular cardiac, liver, gonadal and pancreatic involvements are typical for hemochromatosis, in which the toxicity of redox-active iron results in organ dysfunction. Typically, hemochromatosis leads to a combination of heart failure, cirrhosis, impotence, diabetes and arthritis. Although several organ systems are usually involved, cardiac complications predominate the initial presentation, which are dependent on the site and amount of cardiac depositions. DCM is the typical phenotype of cardiac involvement, but a restrictive pattern may be present. The most frequent, adult-onset, form of hemochromatosis was found arise from mutations in the HFE- gene, coding for a transmembrane protein involved in iron uptake in the liver and the intestine. Less frequently, mutations in the transferrine 2-encoding gene may result in hemochromatosis. The juvenile form of hemochromatosis results from mutations in the genes encoding hepcidin and hemojuvelin. The disease may also be acquired and result from ineffective erythropoiesis secondary to a defect in haemoglobin synthesis, chronic liver disease, chronic excessive oral or parenteral intake of iron, or from multiple blood transfusions. Three stages of the natural history of adult-onset hemochromatosis can be differentiated. The first stage, the biochemical stage, is characterized by an iron overload which remains confined to the plasma compartment. Transferrin saturation is increased. The second phase, the deposition phase, is characterized by iron accumulation in parenchymal tissues, accommodated by an increase in serum ferritine levels. The third and final stage is that of organ dysfunction. Juvenile hemochromatosis is a more rapidly progressing disease, which leads to early organ dysfunction, around the age of 30, and is frequently characterized by premature death due to severe cardiac complications. The invariably present symptoms of heart failure may frequently be accompanied by arrhythmias, especially ventricular extrasystoles, supraventricular tachycardia, and atrial fibrillation or flutter; either due to atrial iron depositions, or ventricular dysfunction resulting in increased ventricular pressure. Furthermore, conduction system involvement may lead to AV block or sick sinus syndrome. Diagnostic features Symptoms at initial presentation may vary. Echocardiography may show increased left ventricular wall thickness, ventricular dilatation, and ventricular dysfunction. CMR imaging represents a sensitive mean and may aid in early detection of the disease. Electrocardiographic characteristics include ST-segment https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 20/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology and T-wave abnormalities as well as supraventricular arrhythmias, but occur as the disease advances. Biochemical testing reveals increased elevated transferrine saturation, increase plasma iron levels with low or normal iron binding capacity. Management Repeated phlebotomy is the cornerstone of hemochromatosis treatment, although chelating agents such as deferoxamine may be considered. Early detection of the disease is critical, as depletion of iron overload may result in complete reversal of symptoms at this stage. Evidence was found that a threshold exists beyond which iron depletion does not result in recovery of function. At end-stage disease, heart transplantation is a viable option with good survival rates. Importantly, screening of first degree relatives is important to ensure early detection of hereditary forms of hemochromatosis. Fabry disease (angiokeratoma corporis diffusum universale) Fabry disease is an X-linked inheritable deficiency of the lysosomal alpha-galactosidase A, resulting in an accumulation of glycosphingolipids in the lysosomes. There is a wide variety of know mutations, which all result in a different level of alpha-galactosidase inactivity, and hence, clinical manifestation may range from isolated myocardial disease to systemic involvement. Patients may suffer from angina pectoris and myocardial infarction due to the accumulation of the aforementioned lipids in the endothelium of the coronary arteries, but the epicardial vessels show no abnormalities on angiography. Ventricular function is hampered due to thickening of the ventricular walls, which results in impaired diastolic compliance with a preserved systolic function, and may even precede myocardial hypertrophy. Other common features of the disorder include systemic hypertension, congestive heart failure, and mitral valve prolapse. The surface electrocardiogram may reveal a short P-R interval, atrioventricular block, and ST-segment and T wave abnormalities. Echocardiography may be inconclusive, but CMR imaging may differentiate Fabry disease from other infiltrative processes. Definite diagnosis is made on endomyocardial biopsy. Treatment of Fabry is safe and effective, and consists of enzyme-replacement therapy. Gaucher Disease Gaucher disease is an inheritable deficiency of beta-glucosidase, resulting in accumulation of cerebrosides. Cardiac involvement results in impaired cardiac function due to reduced ventricular compliance. Treatment of Gaucher disease consists of enzyme replacement therapy, or liver transplantation as a last resort. Response to treatment with respect to recovery of symptoms is heterogeneous. Glycogen storage disease https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 21/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Glycogen storage disease may result in cardiac involvement in case of type II, III, IV and V, but survival until adulthood is rare except for type III disease. Cardiac involvement is characterized by left ventricular hypertrophy, electrographically and echocardiographically, but cardiac symptoms are frequently absent. Endomyocardial Endomyocardial fibrosis Endomyocardial fibrosis is an important cause of congestive heart failure in equatorial Africa. Prevalence up to 20% has been reported, mostly familial in children or young adults, although symptoms occurred only in a minority of detected cases. The disease predominantly occurs in black individuals, but may rarely present in white subjects. The fibrous lesions hamper cardiac function by impairing the inflow of the ventricles, affecting the left or both ventricles most commonly. Solitaire right-sided involvement is less frequent, occurring in approximately 10% of cases. Symptoms are concordant with the ventricles involved, an atrial fibrillation and ascites are known factors associated with a poor prognosis. Clinical diagnosis is based upon clinical presentation, lab testing, and angiography. Left-sided myocardial biopsy is relatively contraindicated, as it may result in systemic emboli. Endomyocardial fibrosis is a relentless disease, half of patients not making it beyond 2 years after detection, depending on the extent of symptoms at presentation. Medical management is only effective in the early stages of the disease, and is aimed at relief of symptoms. Surgical correction of the clinical consequences of the disease, i.e. valve replacement, improves hemodynamic characteristics, but mortality is high, and fibrosis may reoccur. Hypereosinophilic syndrome: L ffler Endocarditis The hypereosinophilic syndrome is a systemic disease, involving several organ systems. Cardiac involvement, L ffler endocarditis, is usually present when eosinophil counts are high for a longer period of time. The eosinophilia itself may occur from several different causes. Histopathology shows eosinophilic myocarditis extending into the subendocardium, endocardial thickening, and inflammation of the small intramural coronary vessels. Clinical features of the disease are weight loss, cough, fever, and a rash. Cardiac involvement may not induce clinical symptoms in the early stages of the disease, but as the disease progresses as much as 50% of patients develop cardiomegaly or congestive heart failure. Cardiomegaly may be suspected on chest radiography, and the electrocardiogram shows non-specific abnormalities of the ST-segment and T-waves. Conduction defects may also occur. Echocardiography often shows a normal systolic function, and may show apical obliteration by thrombus. Obliteration of the apex with a preserved systolic function is a key characteristic of the disease on angiography. Endomyocardial biopsy can provide the diagnosis, but may be false-negative. Routine care applies to these patients. Diuretics and neurohumoral blockade are appropriate, as is anticoagulation. Corticosteroids and cytotoxic drugs increase survival in patients with L ffler endocarditis, and interferon may be used as a last option in refractory patients. Surgical therapy may be https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 22/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology considered as palliative treatment in the fibrotic fase of the disease. Arrythmic cardiomyopathy: Arrhythmogenic Right Ventricular Cardiomyopathy Arrhythmogenic Right Ventricular Cardiomyopathy, (ARVC, or ARVD: Arrhythmogenic Right Ventricular Disease, also AC Arrhythmogenic Cardiomyopathy) is characterized by fatty replacement and fibrosis of the heart. Most commonly, the right ventricle apex and outflow tract are involved. However, the left ventricle can be affected too. As a result of the fatty replacement and fibrosis, ventricular arrhythmias are common in this disease and can lead to palpitations, syncope and sudden death. At more advanced ages, right ventricular failure can occur. ARVC is a progressive disease, and its incidence is estimated to be 1:3.000-1:10.000. The disease usually manifests at adolescence. Although the diagnosis is more often confirmed in athletes, physical activity is not thought to have a causal relationship with the disease. ARVC can occur in families; more than 9 different chromosomal defects have been described, most often with autosomal dominant inheritance. One unique form of ARVC, called Naxos disease (after the Greek island where it was first diagnosed), has an autosomal recessive pattern of inheritance. A section throughout the heart of an ARVC patient. (A) Transmural fatty replacement of the right ventricular free wall. (B) Myocardial atrophy is confined to the right ventricle and substantially spares the interventricular septum as well as the left ventricular free wall. [1] Reproduced with permission from BMJ Publishing Group Ltd. Diagnosis ARVC is a difficult diagnosis to make. Therefore, the European Society of Cardiology has created a list of diagnostic criteria for the diagnosis of ARVC, which were updated in 2009 (Table 6). An online calculator (http:// www.arvc.ca/pdg/public.php?rep=arvc_cri) can help in assessing the risk in an individual patient. ECG with an epsilon wave in V1 https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 23/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 6. The Revised Task Force Criteria for ARVD / ARVC Revised Task Force Criteria I. Global or regional dysfunction and structural alterations Major By 2D echo: Regional RV akinesia, dyskinesia, or aneurysm and 1 of the following (end diastole): PLAX RVOT =32 mm (corrected for body size [PLAX/BSA] =19 mm/m2) PSAX RVOT =36 mm (corrected for body **[PSAX/BSA] =21 mm/m2) or fractional area change =33% By MRI: Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and 1 of the following: Ratio of RV end-diastolic volume to BSA =110 mL/m2 (male) or =100 mL/m2 (female) or RV ejection fraction =40% By RV angiography: Regional RV akinesia, dyskinesia, or aneurysm Minor By 2D echo: Regional RV akinesia or dyskinesia and 1 of the following (end diastole): PLAX RVOT =29 to <32 mm (corrected for body size [PLAX/BSA] =16 to <19 mm/m2) PSAX RVOT =32 to <36 mm (corrected for body size [PSAX/BSA] =18 to <21 mm/m2) or fractional area change >33% to =40% By MRI: Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and 1 of the following: Ratio of RV end-diastolic volume to BSA =100 to <110 mL/m2 (male) or =90 to <100 mL/m2 (female) or RV ejection fraction >40% to =45% II. Tissue characterization of wall Major Residual myocytes <60% by morphometric analysis (or <50% if estimated), with fibrous replacement of the RV free wall myocardium in =1 sample, with or without fatty replacement of tissue on endomyocardial biopsy Minor Residual myocytes 60% to 75% by morphometric analysis (or 50% to 65% if estimated), with fibrous replacement of the RV free wall myocardium in =1 sample, with or without fatty replacement of tissue on endomyocardial biopsy III. Repolarization abnormalities Major https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 24/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in individuals >14 years of age (in the absence of complete right bundle-branch block QRS =120 ms) Minor Inverted T waves in leads V1 and V2 in individuals >14 years of age (in the absence of complete right bundle-branch block) or in V4, V5, or V6 Inverted T waves in leads V1, V2, V3, and V4 in individuals >14 years of age in the presence of complete right bundle-branch block IV. Depolarization/conduction abnormalities Major Epsilon wave (reproducible low-amplitude signals between end of QRS complex to onset of the T wave) in the right precordial leads (V1 to V3) Minor Late potentials by SAECG in =1 of 3 parameters in the absence of a QRS duration of =110 ms on the standard ECG Filtered QRS duration (fQRS) =114 ms Duration of terminal QRS <40 V (low-amplitude signal duration) =38 ms Root-mean-square voltage of terminal 40 ms =20 V Terminal activation duration of QRS =55 ms measured from the nadir of the S wave to the end of the QRS, including R , in V1, V2, or V3, in the absence of complete right bundle-branch block V. Arrhythmias Major Nonsustained or sustained ventricular tachycardia of left bundle-branch morphology with superior axis (negative or indeterminate QRS in leads II, III, and aVF and positive in lead aVL) Minor Nonsustained or sustained ventricular tachycardia of RV outflow configuration, left bundle- branch block morphology with inferior axis (positive QRS in leads II, III, and aVF and negative in lead aVL) or of unknown axis >500 ventricular extrasystoles per 24 hours (Holter) VI. Family history Major ARVC/D confirmed in a first-degree relative who meets current Task Force criteria ARVC/D confirmed pathologically at autopsy or surgery in a first-degree relative Identification of a pathogenic mutation categorized as associated or probably associated with ARVC/D in the patient under evaluation Minor History of ARVC/D in a first-degree relative in whom it is not possible or practical to determine whether the family member meets current Task Force criteria Premature sudden death (<35 years of age) due to suspected ARVC/D in a first-degree relative ARVC/D confirmed pathologically or by current Task Force Criteria in second-degree relative https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 25/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology PLAX indicates parasternal long-axis view; RVOT, RV outflow tract; BSA, body surface area; PSAX, parasternal short-axis view; aVF, augmented voltage unipolar left foot lead; and aVL, augmented voltage unipolar left arm lead. Diagnostic terminology for original criteria: This diagnosis is fulfilled by the presence of 2 major, or 1 major plus 2 minor criteria or 4 minor criteria from different groups. Diagnostic terminology for revised criteria: definite diagnosis: 2 major or 1 major and 2 minor criteria or 4 minor from different categories; borderline: 1 major and 1 minor or 3 minor criteria from different categories; possible: 1 major or 2 minor criteria from different categories. Hypokinesis is not included in this or subsequent definitions of RV regional wall motion abnormalities for the proposed modified criteria. A pathogenic mutation is a DNA alteration associated with ARVC/D that alters or is expected to alter the encoded protein, is unobserved or rare in a large non ARVC/D control population, and either alters or is predicted to alter the structure or function of the protein or has demonstrated linkage to the disease phenotype in a conclusive pedigree. E.g.: in TMEM43, DSP, PKP2, DSG2, DSC2, JUP. Arvd ecg1.png Arvd ecg2.png Arvd ecg3.png An ECG of a patient with ARVD Onset of a VT from right inferior the ventricle, typical for ARVD Sustained VT with LBBB pattern and superior in ARVD axis Treatment Treatment focuses on avoiding complications. Medication: Anti-arrhythmics: Sotalol better than Amiodarone. ACE-inhibitors to prevent cardiac remodelling ICD implantation is recommended for the prevention of sudden cardiac death in patients with ARVC with documented sustained VT or VF who are receiving chronic optimal medical therapy. ICD implantation can be considered for the prevention of sudden cardiac death in patients with ARVC with extensive disease, including those with left ventricular involvement, 1 or more affected family member with SCD, or undiagnosed syncope when ventricular tachycardia or ventricular Fibrillation has not been excluded as the cause of syncope, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. Radiofrequency ablation can be useful as adjunctive therapy in management of patients with ARVC https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 26/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology with recurrent ventricular tachycardia, despite optimal anti-arrhythmic drug therapy. Unclassified Cardiomyopathy: Left ventricular non-compaction Left ventricular non-compaction (LVNC) is characterized by distinct structural abnormalities: A two-layered structure of the myocardium, with a thin compacted epicardial band and a thick non- compacted endomyocardial part, overall resulting in a thickened myocardium. LVNC is diagnosed by the ratio between the maximal non-compacted and compacted myocardial layer thickness measured during end-systole. In adults, a non-compacted/compacted thickness ratio of =2 confirms the diagnosis, whereas a ratio of =1.4 is considered diagnostic in children. The non-compacted layer is further characterized by prominent trabeculations, with intertrabecular spaces in direct connection with the left ventricular cavity. The non-compacted regions are predominantly found in the lateral, apical or inferior wall of the left ventricle. Where normal myocardium, originally consisting of a sponge-like structure of myocardial fibres, shows a pattern of basal to apical, and epicardial to endocardial compaction of the myocardial fibres during the 5th to 8th week of embryonal development, non-compaction supposedly originates from halting of this process due to a genetic defect. Clinical Presentation and Diagnosis Age of onset may be highly variable, with cyanosis, failure to thrive or dysmorphic features described in the neonatal period, to adult patients presenting with LV failure or ventricular arrhythmia. Possibly, sudden cardiac death entails one of the manifestations of LVNC, although evidence is only limited at this moment. Owing to technical advances in the field of echocardiography, predominantly an increase in image resolution, LVNC has only recently been recognized as an independent entity in the spectrum of cardiomyopathies, which supposedly has frequently been misdiagnosed as HCM in the past. Two-dimensional echocardiography entails the cornerstone of LVNC diagnostics, enhanced by intravenous contrast agents if necessary. Magnetic resonance imaging may pose an option in case acoustic windows are insufficient. ECG abnormalities in patients with LVNC are mostly non-specific. Considering the genetic background of LVNC, inheriting most commonly autosomal dominant, echocardiographic evaluation of family members of LVNC patients is pertinent. Treatment and Prognosis Treatment strategies are mainly extrapolated from other cardiomyopathies: standard heart failure therapy in case of LV dysfunction, beta-blockade and/or amiodarone in non-sustained VT in the absence of LV dysfunction, and ICD placement indicated in patients with LVEF <35%, sustained VT or recurrent unexplained syncope. Routine anticoagulation in not indicated, but anticoagulation may be instituted in case of ventricular dilatation or systolic LV function impairment. The prognosis of LVNC has currently not yet been defined. One small report indicates a high mortality risk, owing to a high prevalence of sudden death, but community-based populations may well show a different prognosis as many patients with LVNC are non-symptomatic at the initial diagnosis. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Myocardial_Disease&oldid=2363" https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 27/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology This page was last edited on 9 May 2013, at 12:59. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 28/28