Myocardial Disease: Difference between revisions

{{DevelopmentPhase}}

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:

*Tachycardia

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.

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.

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.

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.

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.

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 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 reduce heart rate, and nitrates to 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.

Left ventricular systolic function 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.

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.

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.  

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)

*Unclassified cardiomyopathy (UCM)

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).  

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

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.

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.

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 :

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 :

|}

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.  

[[Image:Myocardi1.jpg|400px|thumb|Treatment strategy in HCM]]

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 death, which may even be its initial presentation, in particular 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 relatively low prevalence, 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.

|-

!Table 4. Risk factors for SCD

*Fibrosis on CMR

|}

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.  

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.

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.

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 the physical examination is a gallop 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.

''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. 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 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.

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.

Is described under ‘Secondary Myocardial Disease’

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.

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.

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 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.  

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.

|-

|-

|'''Myocardial'''

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

|-

|}

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.  

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.

{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="100%"

|-

|}

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

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.  

{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="100%"

|-

Routine care applies to these patients. Diuretics and neurohumoral blockade are appropriate, as is anticoagulation. Corticosteroids and cytotoxic drugs increase survival in patients with Löffler endocarditis, and interferon may be used as a last option in refractory patients.  Surgical therapy may be considered as palliative treatment in the fibrotic fase of the disease.

Arrhythmogenic Right Ventricular Cardiomyopathy, (ARVC, or ARVD: Arrhythmogenic Right Ventricular Disease) 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.  

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 [http://www.arvc.ca/pdg/public.php?rep=arvc_cri online calculator] can help in assessing the risk in an individual patient.  

|-

! Table 6. The Revised Task Force Criteria for ARVD / ARVC Revised Task Force Criteria

*Radiofrequency ablation can be useful as adjunctive therapy in management of patients with ARVC with recurrent ventricular tachycardia, despite optimal anti-arrhythmic drug therapy.  

Left ventricular non-compaction (LVNC) is characterized by distinct structural abnormalities: