Abstract
Metabolic cardiomyopathy is a heterogeneous disease that often develops due to a genetic mutation on the mitochondrial DNA. The prevalence of mitochondrial cardiomyopathy has been approximated to be more than 1 in 5,000 infants. However, diagnosis and management of the disease are not often emphasized in most adult-cardiology curricula. Since metabolic cardiomyopathy usually occurs as a syndrome due to resultant multi-organ dysfunction, which might immediately appear to be precise to the cardiovascular system. Metabolic cardiomyopathy is a myocardial condition characterized by the abnormal structure of the heart muscles, the heart function as well as the genetic effect involving the mitochondrial respiratory system due to lack of concomitant coronary artery defect, valvar defect, or congenital heart disease. The common manifestation of metabolic cardiomyopathy can become worse especially during a metabolic crisis. The most appropriate way of managing the condition necessitates the involvement of multidisciplinary team, proper evaluation of the patients as well as the anticipation of iatrogenic and non-iatrogenic complication. In this report, we discuss the complex pathophysiology of metabolic cardiomyopathy together with its clinical features. The report will mainly focus on diagnosis and management of persons with metabolic cardiomyopathy which include optimal therapeutic management and regular monitoring.
Keywords: metabolic cardiomyopathy, mitochondrial cardiomyopathy, mitochondrial respiratory system.
Introduction
Metabolic cardiomyopathy is a myocardial disorder which occurs due myocardial disorder or as a result of a secondary genetic defect which brings about the weakening of the mitochondrial respirational series. The condition is approximated to affect 20-40% of infants with mitochondrial illnesses (El-Hattab, 2016).Therefore screening, for cardiomyopathy is a normal procedure for managing children as well as an adult with a suspected condition. Metabolic cardiomyopathy can have a different level of severity from a crisis status to severe manifestation such as cardiac arrest, heart failure among other serious conditions. Cardiac manifestation can become worse during metabolic decompensation usually triggered by conditions such as febrile illness and can go together with heart failure.Mortality in children due to metabolic disease is usually high in those with cardiomyopathy compared to those without. The manifestation of metabolic cardiomyopathies is usually accompanied by a manifestation of multi-organ involvement of mitochondrial complications. Moreover, mitochondrial cardiomyopathy can occur due to lack of known components of the mitochondria, of which it might be the first manifestation.
Discussion
Metabolic defects account for very little of the leading bases of cardiomyopathy. Nevertheless, detecting metabolic as the main cause for cardiomyopathy might result in extrapolative and positive implications. Most categories of metabolic illnesses linked to cardiomyopathy are fatty acid oxidation disorder, lysosomal disorder, glycogen disorder, congenital disease as well as mitochondrial disorder. Mitochondrial cardiomyopathy is a genetic and clinical disorder that occurs due to the dysfunction of the respiratory chain of the mitochondria, responsible for a generation of cellular energy .Since cardiac muscle requires a high amount of energy to function correctly, cardiac involvement occurs in numerous mitochondrial complications. The typical cardiac manifestation of mitochondrial complications is cardiomyopathies. Other diseases such as arrhythmias, pulmonary hypertension and pericardial effusion and coronary heart failure can also be viewed as mitochondrial diseases. The structure and function of the mitochondrial play a huge role in the development of the condition. Some of the important aspects to focus on in order mitochondrial diseases include clinical manifestation of cardiovascular cardiomyopathy, mitochondrial diseases, ethology of the condition, diagnosis, management, parthenogenesis of mitochondrial cardiomyopathies.
Etiology
Metabolic cardiomyopathies with hypertrophic phenotype have a common genetic etiology. However, the inroads to the expression of the phenotype as well as the clinical, morphological features greatly defer to the gene involved. One of the common lab findings in increased ventricular thickness of the sarcomere HCM, metabolic diseases, and familial transthyretin amyloidosis as well as leopard syndrome. Signs of the diagnosis include a pattern of inheritance, clinical manifestation, hypertrophy pattern, laboratory tests and finding the histopathologic concentration. The helps in identifying red flags that can help in guiding the genetic analysis of premises cardiomyopathies subsets.
Pathophysiology
Even though numerous biochemical pathways involve mitochondria, the term mitochondrial diseases have been utilized to describe diseases where production of energy is impaired through the alteration of oxidative phosphorylation. Mitochondrial diseases can be categorized functionally or biochemically. Classification through genetics involves the location of the mutation in the nDNA or the mtDNA. Mitochondrial cardiomyopathy occurring as a result of mtDNA are common in adult while mitochondrial diseases from the nDNA are often common in young children. Mitochondrial diseases can be categorized the function of the proteins involved. Mutation originated from the genes that encode subunits of the electron transport chain complexes within the genes encoding ancillary proteins required for the transportation and function of the electron chain complexes or in a gene controlling mitochondria activities. Moreover, the mutation has been viewed as a gene encoding proteins responsible for the synthesis of cardiolipin, an important part of the mitochondrial membrane. Some of the most frequently identified biochemical anomalies are NADH-coenzyme deficiencies, and cytochrome –c oxidase.
Pathophysiology
Metabolic Cardiomyopathy has often been characterized enlargement of ventricular chambers, as well as dysfunctioning of the systolic rhythm with a bigger, left ventricular with little or no wall hypertrophy. Hypertrophy can be described as the ratio between the mass of the left ventricular and the size of the cavity. The ratio decreases in people with cardiomyopathy. Enlargement of the other chambers is primarily caused by the failure of the left ventricular. However, it might be secondary to the primary process of cardiomyopathy (Chinnery, 2012).Mitochondrial Cardiomyopathy is often associated with the dysfunctioning of the diastolic and systolic functioning. A decrease in systolic function is mainly a primary abnormality as a result of adverse myocardial remodeling, leading to an increase in the volume of the systolic and diastolic functioning.
The progress of the condition can cause significant tricuspid regurgitation, which might further reduce the output of the cardiac muscles and increase the stress on the ventricular wall. The compensation of systolic dysfunctioning and reducing the cardiac output is achieved by increasing the stroke volume and the heart rate or both. This can also be achieved by increasing the tone of the peripheral vascular system. Increasing the peripheral tone assists in maintaining the required blood pressure. To decompensate the systolic heart failure, the entire left ventricular shift to the right with an increase in diastolic pressure as well as the diastolic volume. Hypertension might impair coronary blood flow and increased stress on the ventricular walls. The premise of compensation of reduced cardiac output is the increase in muscle length, thus generating a larger amount of stress and the muscle stretches. Overstretching leads to failure of the myocardial contractile unit. The mechanisms of compensation are often blunted in people with different types of cardiomyopathy. Moreover, these mechanisms result in further injury of the myocardial contractile unit as well as geometrical remodeling.
Manifestation
. The manifestation of mitochondrial cardiomyopathy hypertrophic dilated and non-compaction of the left ventricular. The severity of the condition might range from no signs to severe multisystem disease.The representation of severe cardiomyopathy includes heart failure and ventricular tachyarrhythmia which can become more devastating during the metabolic crisis and can finally result in sudden death due to cardiac arrest. The mitochondrial crisis is usually triggered by physiological stressors such as febrile illness and can also go together with devastating heart failure. Multisystem complications usually accompany the clinical manifestation of mitochondrial cardiomyopathy. A majority of individuals with neuromuscular symptoms present with normal or high creative Kinase levels and the normal results of nerve conduction.
Laboratory Outcome
As a general rule, all mitochondria in a zygote a derived from the ovum. Therefore a mother with mtDNA mutation passes it to her children. However, it is only her daughter who will pass it to their children. Recent studies of paternal transmission of mtDNA in a patient with mitochondrial cardiomyopathy serve as the best warning that inheritance of mitochondrial cardiomyopathy is not an absolute rule. However, this does not negate the significance of maternal inheritance in mt-DNA associated diseases. Heteroplasmy and the threshold effect thousands of mtDNA molecules in the cells as well as pathogenic mutations of mtDNA of these genomes. As a result body cells and tissues Harbor wild-type and mutant mtDNA. The process can also be experienced in an organelle level where a single mitochondrion harbours both the wild-type and normal mtDNA. In a normal subject, all the mtDNA are identical. It is important to mention that, a small number of mutant mtDNA must be present prior to oxidative dysfunction to occur and clinical symptoms to become evident. This is known as the threshold effect. The threshold for the diseases is lower in tissues that depend heavily on oxidative metabolisms such as skeletal muscle, retina and endocrine glands. Therefore, these tissues are susceptible to pathogenic mutations in mtDNA (Frerichs, 2002).Mitotic segregation and random redistribution of organelles at time of cell division can affect the number of mutant mtDNA passed to the daughter cell, especially if the unaffected tissues are unaffected. The phenotype can also change. This explains why age-related variabilities of clinical symptoms is frequently observed in mtDNA-related disorder.
Disorder in the mitochondrial protein used for systolic pressure have mitochondria targeting signals that enable them to be routed to the appropriate compartment within the organelle where they are placed in an active configuration. Even though the number of mutations targeting signals can be identified, few errors in the importation are known, since they are lethal. However. At least one of the symptoms can easily be identified. As a result, encoding the problem in the inter-membrane disorder is simplified. According to recent studies, the autosomal form is usually associated with mutation in the mitochondria. The mechanisms that are responsible for the association between syncope and death due to cardiomyopathy are obscure. Syncope might be an indicator of the end-stage of a cardiomyopathy process in a patient. Therefore, it might provide a poor prognosis. The death of patients with the condition might be caused by the sudden collapse of the hemodynamic system rather that arrhythmia. Therefore it is important to administer the optimal dose of angiotensin enzyme inhibitors together with other standards of intervention for cardiomyopathy.
Diagnosis
Primary mitochondrial cardiomyopathy is clinically or biomechanically heterogeneous. Due to the curious state of heteroplasmy, not all individuals with mtDNA mutation will present the symptoms of the diseases. Moreover, if DNA is present, multisystem symptoms and the disease may not be present early in the course of the disease. Some of the proposed diagnostic frameworks include histologic, functional as well as molecular factors. These factors have helps in improving the detection of mitochondrial cardiomyopathies. However, most of these criteria are not subject to interpretation and correction. Electron microscopy can sometimes be used to show the subsarcolemmal, inflated mitochondria with irregular cristae (DiMauro, 2003).Examination of electron respiratory chain using polarographic and spectrophotometric assays are usually conducted in muscle tissue. However, there are no standards for cardiac tissue evaluation. Mitochondrial genome screening is usually conducted on the muscle sample. Any abnormalities in the nuclear DNA are traditionally challenging to diagnose since it is only a small proportion of the nDNA mutation that can be identified. Regardless of using the optimal diagnostic tools, the outcomes can be ambiguous and pose a considerable challenge for clinicians.
Treatment
A mitochondrial crisis can be associated with an unusual elevation in the levels of lactate. Cardiac diseases during a mitochondrial crisis often involve cardiogenic shock, dilated cardiomyopathy and eventually death. Treatment of the condition should be directed towards the underlying cause of the crisis and focus on the appropriate care that would optimise proper mitochondrial function. The general manager of the condition should include laboratory testing and recommend the appropriate steps and precautions to consider.
Management of Mitochondrial cardiomyopathy is almost similar to the treatment of chronic heart failure. This is a syndrome in which various treatment methods have emerged. Comprehensive research on the biomedical alterations that occur in a subject with cardiomyopathy had resulted in a development of numerous management options designed to impact the alterations. Some therapeutic frameworks help to treat the symptoms while others help in managing factors of survival. As indicated earlier managing cardiomyopathy is similar to the treatment of chronic heart failure. When treating subject with cardiomyopathy, it is necessary to administer oxygen together with regular pulse oximetry. Cardiac monitoring is also necessary. In a severe condition initiation of continuous positive airway pressure might obviate the intubation.
Conclusion
Mitochondrial Cardiomyopathy is a progressive heart condition with common elements such as remodeling of the cardiac chambers. The secondary mitral regurgitation is often the end-stage of cardiomyopathy. Therefore it is important for an individual to be checked as early as possible before the condition goes out of hand. Mitochondrial cardiomyopathy is a diverse clinical condition often manifested in the subject with underlying genetic disorders that involve mitochondrial respiratory chain. Because, diagnosing the condition is difficult, the first step towards safety is maintaining a high level of suspicion. It is essential for patients to be regularly checked by mitochondrial specialists whenever the disease is suspected. Individuals with mitochondrial cardiomyopathy should be advised about the complications associated with cardiomyopathies and the appropriate medications. Physicians should be aware of the appropriate ways of establishing supportive strategies for the long term care of crisis status of various patients. The current pharmacologic strategies are still effective, and randomized trials are often warranted to direct future therapy.
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