Myocardial Disease: Difference between revisions

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=====

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.

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.  

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=====Electrocardiography=====

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).

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.

=====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.

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.  

====Management of DCM====

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|'''''Noninfiltrative'''''

*Drugs causing fibrous endocarditis(serotonin, methysergide, ergotamine, mercurial agents, busulfan)

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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.  

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

*Congestive heart failure of unknown origin, not responding to contemporary medical management.

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.

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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.

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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.

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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.

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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 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 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.

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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.

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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.

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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 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 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.

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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 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.

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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.

====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.

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.

The hypereosinophilic syndrome is a systemic disease, involving several organ systems. Cardiac involvement, Löffler endocarditis, is usually present when eosinophil counts are high for a longer period of time. The eosinophilia itself may occur from several different causes.

====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.

====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.