Reversible Heart Failure and Inflammation - Essay Example

Reversible Heart Failure and Inflammation Literature review has provided fairly good evidence of conditions that lead to heart failure on temporarybasis, which may revert on the removal of the sole cause which led to the failure in addition to the supportive treatment. More frequently reported or well-established conditions are: 1. Alcoholic cardiomyopathy 2. Tachycardia induced cardiomyopathy 3. Hyperthyroidism/Thyrotoxicosis associated cardiomyopathy 4. Peripartum cardiomyopathy 5. Pharmacological cardiomyopathy 1. Bortezomib 2. Clozapine 3. Dapsone 1. Alcoholic cardiomyopathy Association between alcohol intake and morbidity related to various systems in the body has been discussed for years. Literature supports the graded effect of alcohol utilization on the heart functioning. Response of alcohol drinkers varies depending upon the duration and quantity of intake. In chronic users, the response of heart is better as compared to those who take high volumes in shorter intervals. Direct effect of alcohol on heart is myocardial depression that results in diastolic dilatation, which manifests itself as, delayed or prolonged relaxation. The exact mechanism for these findings still needs to be explored. Another change in the cardiac anatomy and eventually in physiology is cardiomyopathy. For the alcoholic cardiomyopathy, it has been suggested that there is accumulation of triglycerides, which may alter the transport of various ions across the membrane. Calcium is an important ion in the contractility of heart muscle but in alcoholic cardiomyopathy its movement is disturbed; moreover, the Na/K ATPase is also inhibited in this type of cardiomyopathy. The mechanism of alcoholic and idiopathic cardiomyopathies has been found to be different. S survival analysis was carried out to compare the survival of the patients of these two types of cardiomyopathies. The response of patients was different and patients with alcoholic cardiomyopathy were found to be with better prognosis as compared to the other group. These findings suggest a different mechanism operating for the two types of conditions. The hallmark in the treatment of alcoholic cardiomyopathy is the cessation of alcoholic intake at a certain period when with the support of drugs the situation can be reverted; if alcoholic intake continues in specific quantities for a specific period of time then it may not revert to the normal function even after the abstinence of alcohol. 2. Cardiomyopathy secondary to tachycardia is a well known situation which results in chronic cardiomyopathy and presents with symptoms of heart failure. In this condition systolic function is compromised. If the tachycardia is controlled effectively then the heart failure is also controlled in majority of the cases (ref). There are multiple examples in the literature presented as case studies, like: an old man developed cardiomyopathy as a result of tachycardia with focus in tricuspid annulus. The arrhythmia was controlled with intervention on the tricuspid valve which resulted in the improvement of tachycardia and eventually the myocardial functions (ref). This situation may involve children also. An infant presented with persistent tachycardia, alongwith heart failure, due to posteroseptal pathway. Her problem as managed by surgical ablation and she recovered with no more persisting problem either related to tachycardia or heart failure (ref). 3. Hyperthyroidism/Thyrotoxicosis and heart failure Reversible heart failure has been associated with thyrotoxicosis as a rare but established fact. It is presented as low output congestive heart failure with dilated cardiomyopathy; the condition improves to normal by treating thyroid problem with antithyroid drugs. Thyrotoxicosis results in tachycardia alongwith other manifestations. This tachycardia in the form of atrial fibrillation results in dilated cardiomyopathy and eventually heart failure. The mechanism is similar to tachycardia induced heart failure due to any reason. When thyrotoxicosis is controlled with improvement of heart beat the heart failure is also improved (ref). In a similar situation, a male patient with atrial fibrillation, which was afterwards diagnosed as Graves's disease, presented with heart failure and cardiomyopathy. This patient's condition improved after hyperthyroidism and tachycardia was controlled (ref). 4. Peripartum cardiomyopathy This is a rare disorder of late pregnancy or early postpartum period. The etiology is not known very well but it develops in previously healthy women but some characteristics of these women predispose to them to this condition, like: women in older age groups, increased number of children, twins and gestational hypertension. When no apparent cause of heart failure is identified then this diagnosis is made and it is managed like any other heart failure and majority of the patients recovered completely but some proportion may develop persistent cardiomyopathy. 5. Pharmacological Preparations: Bortezomib is a drug utilized in multiple myeloma and non-small cell lung cancer. Because of the excellent response to this drug a patient was started on it for his tumor. After quite long time of the start, the patient symptoms of heart failure; the treatment was continued as its effect on tumor cells but when the patient condition deteriorated the medicine was discontinued and he recovered subsequently. Dapsone related hypersensitivity resulting in reversible heart failure A patient was treated with dapsone for malaria. After startin dapsone, the patient developed congestive heart failure. He was started on trh etreatment of heart failure alongwith steroids and dapsone was stopped, the patient recovered with good cardiac function very soon. Clozapine: A treatment of choice for schizophrenic patients who are resistant to neuroleptics. A patient of schizophrenia was started on Clozapine. After about 12 days the symptoms of psychosis were improved but new symptoms were developed related to infection and cardiac compromise. On histology, myocarditis was confirmed and the patient was started on steroids which resulted in reversal of the symptoms of cardiac failure. The syndrome of heart failure is the result of combined effect of multiple factors, like: anatomical, physiological and biochemical features which contribute to the situation individually but the result is somewhat synergism of these individual effects or combination in some other proportions. Due to difficulty in supporting the hypothesis of haemodynamic disorders, the scientists have started to explore other reasons and chain of events for the progression of heart failure. In the recent past the focus has been shifted towards neuro-hormones and the agents of inflammation, cytokine, which seem to be closely related in the progression of the heart failure. The neuro hormonal mechanism is comparatively older one as compared to the cytokines hypothesis. Cytokines is a group of protein molecule with smaller molecular weights and secreted by some cells on some type of stimulus (ref). It has been given the name of cytokine hypothesis. Cytokines are of various types and participate in the progression of heart failure in different forms. It is important that distinction be made between the effects of cytokines in setting a stage for starting heart failure or facilitating the already started process of heart failure towards more severity. In fact, cytokines either depress the functions of the heart through some toxic effect or aggravate the haemodynamic disturbance resulting from heart failure. Although, these two types of agents belong to biologically active classes of molecules but the mechanisms, which initiate the process and further on develop the process are different. Cytokines Endothelin I: Endothelin-1 is a cytokine which is present in heart in both the situations: failing or non-failing (ref) In both the scenarios this cytokine has got some link with the heart which helps in responding to any insult produce to heart (ref). In fact this mediator is a response from the body. When the response of cytokine is more intense at some latter stage it supports production of focal vasospasm, myocytolysis and myocardial fibrosis. It has been well established that the Endothelin-1 and its precursor big-ET-1 are present in the peripheral circulation during the period of haemodynamic instability around the time of heart failure (ref ). Therefore, these both chemical agents may act as the therapeutic and prognostic markers (ref). Tumor Necrosis Factor (TNF) - Alpha: During the last decade fairly good amount of research dissemination was carried out which focused on finding circulation of high levels of tumor necrosis factor alpha (TNF-alpha) in patients with advanced chronic heart failure (ref1-8). High levels of TNF-alpha in heart failure may support the cytokine hypothesis by mediating various changes which are hallmark of heart failure; for example: left ventricular dysfunction, pulmonary oedema, ventricular remodeling and cardiomyopath (ref 1-3). It has been proposed that some biochemical mechanism is involved in bringing in these changes. Currently, it is still under debate whether TNF-alpha is merely present during the period of heart failure or they have got some role in promoting changes, which appear after the failure. Literature review suggests that the link established between TNF-alpha and advanced heart failure through the publications was found in one third of the patients (ref). While a recent research work, the Studies of Left Ventricular Dysfunctions (SOLVD), carried out to make distinctions between the patients with symptomatic and asymptomatic ventricular dysfunctions as well as those who are the candidates for transplantation found that those patients who were with functional New York Heart Association (NYHA) class III and IV heart failure showed eight fold increase in the circulating levels of TNF-alpha as compared to the control or asymptomatic group (ref). It was further explored to look for any correlation between the TNF-alpha with neurohormones and atrial natriuretic peptide and this enquiry informed that no correlation there was no correlation between TNF-alpha and neurohormones but at the same time significant level correlation was between TNF-alpha and atrial natriuretic peptide.. Due to the strong association between the presence of TNF-alpha and heart failure, efforts have been made to look for any association of TNF-alpha with survival of the patient so that the role of TNF-alpha as a prognostic factor which was discussed earlier could be supported with more evidence. For this purpose, a Kaplan-Meier analysis was carried out on the SOLVD data for patients who could show high levels of cytokines (ref). After a follow up period of 48 months it was found that levels of TNF-alpha more than 6.5 pg/ml were associated with increased mortality as compared to the patients with levels less than that amount as shown in figure 2(ref). Interleukin-6 Interleukin-6 is one of the various cytokine mediators of immune and inflammatory responses. Its effects are similar to that of TNF-alpha in heart failure like, myocardial dysfunction and muscle wasting (ref). These effects are supported by the fact that these mediators are found in increasingly high quantities when inpatients who come under the functional classification of NYHA. It has been tested out that interleukin-6 releases when TNF-alpha is released; this association is further strengthened by significant correlation found between these two mediators. On the other hand, no correlation was found between interleukin-6 and neurohormones (ref); this again supports the hypothesis of cytokine as individual mechanism of heart failure progression if not the sole mechanism. So far we have tried to elaborate the role of cytokines in the progression of heart failure through a fairly good source of evidence. The evidence suggesting the role of cytokines in heart failure is the knowledge added to our earlier understanding on the subject of heart failure. It could be a fact that this is a multi factors issue because of the important and complex nature of task, which this organ has to carry out. With the addition of this hypothesis we propose the need of a multi-hit hypothesis till we reach to a single explanation. So if we add the role of cytokines in the progression of the heart failure then: suppression of cytokine should lead to the prolonged period of asymptomatic heart failure and at the same time should attenuate the symptoms of advanced heart failure; cytokines suppression should prolong the life in symptomatic heart failure; and more exploration should be carried out to detect the mechanisms which trigger the continuous release of cytokines in heart failure. Read More