The dilated cardiomyopathies: experimental aspects

Dilated cardiomyopathy is characterized by the primacy of systolic dysfunction. Experimental animal models have contributed greatly to our current knowledge and promise to continue to expand our understanding, especially as methods of cellular and molecular biology are increasingly applied. Although specific etiologies dominate in some forms of dilated cardiomyopathy, the cause is generally multifactorial--that is, the full expression results from the interplay of a number of etiologic and enhancing factors. Recognition of these factors paves the way for therapy as well as primary and secondary prevention. This article has focused chiefly on experimental models of dilated cardiomyopathy associated with congestive heart failure and on interventions producing or aggravating heart failure. Many factors associated with the production or aggravation of experimental myocardial necroses have not been considered here. Even so, this overview reaffirms the concept that dilated cardiomyopathies are pluricausal. In Table 3, the major processes identifies as pathogenetic in experimental dilated cardiomyopathy are listed. Table 4 presents a list of major categories of enhancing factors. The evidence offered in this article indicates that in most models many pathogenetic mechanisms and enhancing factors may be operative, and this is also believed to be the case in human dilated cardiomyopathy Recognition of the multifactorial etiologies of the dilated cardiomyopathies is an important first step in therapeutic and preventive interventions. Experimental work in human dilated cardiomyopathy has not been included in this article, but some recent studies provide challenging insights.     

Dilated cardiomyopathy due to endocrine dysfunction.

Dilated cardiomyopathy can be idiopathic or be caused by many potentially treatable conditions. We report a complex case of peripartum heart failure associated with hypothyroidism and hypoparathyroidism. Myocardial biopsy suggested that hypothyroidism was the main cause for the dilated pattern, but hypocalcemia played a critical role in acute decompensation of heart failure during hospitalization. After a long and clinically complicated hospital stay, correction of hypothyroidism and hypocalcemia resulted in near-normal cardiac function.     

A case of nemaline myopathy with associated dilated cardiomyopathy and respiratory failure

Nemaline myopathy is a representative form of congenital myopathy, and is characterized by nemaline bodies in muscle fibers. Here we report a 47-year-old man with congenital nemaline myopathy complicated with dilated cardiomyopathy-related heart failure, and restrictive respiratory failure. The complication of dilated cardiomyopathy in nemaline myopathy has rarely been reported. In this case, nemaline bodies were detected in the cardiac muscle fibers, demonstrating the presence of underlying disease-related myocardial degeneration. The patient responded to the combination of conventional therapy for heart failure including β-blocker and noninvasive continuous positive-pressure ventilation for respiratory failure. His general condition has been stable during a 10-month follow up period.     

Torsades de pointes and acute de novo heart failure in a young woman

Hypothyroidism is a rare metabolic cause of dilated cardiomyopathy that responds to substitution therapy. We report on a young woman who presented with torsades de pointes, severe heart failure and multiple organ failure due to longstanding untreated hypothyroidism. Administration of appropriate substitution therapy was followed by a cessation of ventricular arrhythmias and a complete recovery of the cardiac function.     

Therapy of dilated cardiomyopathy with digitalis, diuretics and vasodilators

The treatment of dilated cardiomyopathy is primarily concerned with that of congestive heart failure. Digitalis is widely use in dilated cardiomyopathy but an improvement in the prognosis has not yet been demonstrated. Furthermore, the effects of digitalis in patients with sinus rhythm are debatable. If dilated cardiomyopathy induces atrial fibrillation and tachyarrhythmia, digitalis should be used. Diuretics are helpful in the treatment of congestive heart failure associated with dilated cardiomyopathy. By reducing hypervolemia and by venous dilatation, diuretics lower preload and afterload. This leads to relief of congestion and termination of the vicious cycle of congestive heart failure. Accordingly, the prognosis of dilated cardiomyopathy might be improved by diuretics. There are numerous diuretics acting differently on the renal tubules, the choice of which depends on the renal function and serum electrolyte concentrations. Reduction of preload and afterload improves congestive heart failure as has been demonstrated repeatedly. Many substances have therefore been used for arterial and venous dilation with differing results. At least for short-term periods, congestion is reduced and cardiac output increases. Especially inhibitors of angiotensin II converting enzyme are very effective since they act both in the arterial and venous systems. Additionally, inhibition of the action of angiotensin may be regarded as causal therapy since the renin-angiotensin system is the trigger for vasoconstriction and fluid retention in congestive heart failure. Unlike other substances, ACE inhibitors have been demonstrated to improve prognosis of patients with congestive heart failure. At present, combined diuretic therapy and angiotensin conversion enzyme inhibition would seem the most reasonable treatment for patients with dilated cardiomyopathy and sinus rhythm. If atrial fibrillation and tachyarrhythmia develop, additional digitalis therapy is effective.     

同种原位心脏移植二例报告

目的报告2例原位心脏移植的初步体会。方法2003年8月与2004年12月进行了2例原位心脏移植,1例为瓣膜型心肌病,另1例是扩张型心肌病。采用冷晶体停跳液顺灌进行供心保护,中度低温体外循环下行双腔静脉法原位心脏移植手术。免疫抑制方案采用环孢素A、骁悉、甲基泼尼松龙三联。结果1例术后52h右心衰竭至全心衰竭死亡;另1例围术期无急性排斥反应及感染发生。心功能恢复至Ⅰ级,术后存活8个月。结论合理选择受体,良好的心肌保护、术后合理的监测与抗排异治疗是心脏移植成功的关键。     

Lyme carditis--rare cause of dilated cardiomyopathy and rhythm disturbances

Case report of young woman presents involvement of dilated cardiomyopathy and rhythm disturbances in 18 months after infection of tick, with direct assessment of spirochetes in myocardial tissue. Cardial decompensation occured after asthma exacerbation, complicated by bronchopneumonia. Rhythm disturbances and heart failure gradually subside after parenteral antibiotic treatment and peroral treatment of heart failure. Nevertheless there is a long-lasting persistence of dilated cardiomyopathy with significant systolic dysfunction, which is supposedly last consequence of Borrelia infection. Resynchronic therapy combinated with cardioverter-defibrilator primary considering was postponed for improvement clinical condition and myocardial electric stability. There is demonstrating complicated serologic diagnostics of Lyme disease in discussion. Lyme carditis would be part of differential diagnosis in rhythm disturbances and cardiomyopathy of unknown etiology, including serious or fatal events.     

Reversible dilated cardiomyopathy associated with glucagonoma

An association between dilated cardiomyopathy and glucagonoma has not previously been described. A case of a 54 year old woman with tachycardia and congestive heart failure is described. Initial evaluation included an echocardiogram, which showed dilated cardiomyopathy with an ejection fraction of 15%. Coronary angiography and endomyocardial biopsy did not identify a secondary cause of her cardiomyopathy. She subsequently developed necrolytic migratory erythema, and imaging of her pancreas identified a pancreatic mass with a major increase of her serum glucagon concentration. Tachycardia persisted despite treatment with beta blockers. After resection of her tumour, her heart rate normalised and subsequently her heart returned to normal size and function. Glucagon is used to treat overdoses of beta blockers and calcium channel blockers, increasing heart rate by increasing myocardial cyclic AMP concentrations. Although rare, in the appropriate clinical setting, glucagonoma should be considered in the differential diagnosis for tachycardia and dilated cardiomyopathy.     

Dual etiology of dilated cardiomyopathy: The synergistic role of vitamin D deficiency

Dilated cardiomyopathy is the commonest form of cardiomyopathy in pediatric patients. Various causal factors have been identified, including ionic imbalance. Calcium ions play an essential role in regulating myocardial contractile function, and the harmful role of hypocalcemia as a coadjuvant or even precipitating factor of worsening heart failure has been described in rare case reports. Multiple causative factors may occasionally be present. We describe the first case, to our knowledge, of dilated cardiomyopathy in an infant with severe hypocalcemia and viral myocarditis.     

Rheumatoid arthritis and myocardiopathy. A patient awaiting a heart transplant

Cardiovascular pathology is common in rheumatoid arthritis. However, myocardial affection is unusual and clinical disease is rare. We report a case of dilated cardiomyopathy in a patient with rheumatoid arthritis and progressive heart failure that required inclusion into a heart transplantation list.     

Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy: one simulates hypertrophic and the other dilated cardiomyopathy]

Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy were presented. In case 1 (a 68 year-old woman), moderate pericardial effusion and myocardial hypertrophy were observed on admission. In case 2 (a 69 year-old woman), dilation of the left ventricle, hypokinesis of the interventricular septum and the left ventricular free wall, and reduced left ventricular systolic function were observed on admission. These echocardiographic findings were similar to hypertrophic or dilated cardiomyopathy. In the two cases, after recovery to euthyroid state, these echocardiographic abnormalities returned to normal. We concluded that hypothyroidism led to a reversible hypertrophic or dilated cardiomyopathy, and that echocardiographic study was useful for diagnosis and for following up cardiac manifestations of hypothyroidism.     

Dilated cardiomyopathy: an unusual presentation of aortic coarctation in an infant

Coarctation of the aorta commonly presents in infancy as congestive heart failure, or later in childhood as hypertension or as a heart murmur. However, we experienced a unique infant case of isolated coarctation presenting with acute decompensation of a dilated cardiomyopathy, which recovered completely 8 months postoperatively. Our report highlights the previously unreported presentation of coarctation in infancy as a dilated cardiomyopathy. It also implies that before we label any patient presenting with a dilated cardiomyopathy as an idiopathic cardiomyopathy, we must exclude all possible specific causes of myocardial dysfunction because many such specific cardiomyopathies are curable and very rewarding, just like our patient.     

Cardiac Resynchronization Therapy in Children

Cardiac Resynchronization therapy has become an important management tool in adults with heart failure and dilated cardiomyopathy. The role of CRT in children with CHF is still unclear. Evidence is slowly emerging in the pediatric cardiology literature that CRT may have an important and useful role in certain select populations with CHF. These include patients with complete heart block who develop pacing-induced cardiomyopathy, certain forms of congenital heart disease associated with systemic ventricular failure (even if the systemic ventricle is a morphologic RV) and in patients with idiopathic dilated cardiomyopathy. Studies in children supporting the use of CRT include many case reports, a few studies of CRT in post-operative patients, and one multi-center registry reporting the use of CRT in children. These papers will be summarized.     

Dilated cardiomyopathy and myocardial infarction secondary to congenital generalized lipodystrophy

Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is a very rare hereditary syndrome that is characterized by an almost complete absence of adipose tissue from birth. Cardiac involvement seems to have substantial influence in the long-term prognosis. Herein, we report an apparently unique case of congenital generalized lipodystrophy with cardiac sequelae. A 17-year-old woman, diagnosed in childhood with Berardinelli-Seip syndrome, presented with severe epigastric pain that was secondary to previous myocardial infarction. The patient had ischemia, dilated cardiomyopathy, and congestive heart failure, but no coronary artery disease. She was discharged from the hospital in stable condition after 3 days of medical treatment. To our knowledge, this is the 1st reported case of congenital generalized lipodystrophy with dilated cardiomyopathy, congestive heart failure, severe mitral regurgitation, and inferior myocardial infarction as cardiac sequelae of this syndrome--but without evidence of coronary artery disease or cardiac hypertrophy. In addition to discussing this patient's case, we present diagnostic and therapeutic approaches to Berardinelli-Seip syndrome.     

Acute effects of adaptive servo ventilation on hemodynamics, coronary flow, and flow reserve in a patient with idiopathic dilated cardiomyopathy

Adaptive servo ventilation (ASV) is reported to be effective for the treatment of heart failure. We treated a patient with idiopathic dilated cardiomyopathy using ASV and assessed the effects on hemodynamics, coronary flow, and flow reserve before and after ASV therapy. This case suggests that ASV might decrease myocardial oxygen demand, which was represented by the decreased resting coronary flow velocity (the improvement of coronary flow velocity reserve) on ASV.     

Cardiomyopathy: How far have we come in 25 years,how far yet to go?

Twenty-five years ago clinical investigators began to appreciate that cardiomyopathy is an important and reasonably common form of heart disease. Since then, several functional classifications have been proposed, the specific myocardial diseases have been classified and chronic ischemic ventricular failure has been described. The boundary separating myocarditis from dilated cardiomyopathy remains hazy and, despite intensive research, the causes of dilated cardiomyopathy remain obscure. In particular, we still do not understand the role that may be played by viral infection and alcohol. Myocardial biopsy has proved useful in patients with specific myocardial disorders, heart transplant recipients and patients receiving Adriamycin, but is disappointing in patients with dilated cardiomyopathy.It has become increasingly evident that exercise capacity does not correlate with ventricular function, being highly dependent on peripheral factors. Measurements of oxygen consumption during exercise promise to be useful in assessing treatment of dilated cardiomyopathy. True restrictive cardiomyopathy is uncommon, and the term should be reserved for cardiomyopathies that meet strict criteria. A restrictive component to filling is common to many cardiac disorders, including some cases of cardiac amyloidosis.The concept of hypertrophic cardiomyopathy has evolved rapidly over the past 25 years, and continues to evolve. The importance of arrhythmia as a cause of sudden death is becoming increasingly clear. The place of calcium channel blocking agents in the treatment of hypertrophic cardiomyopathy will probably emerge soon. Amiodarone is finding an increasing role in the treatment of dilated and hypertrophic cardiomyopathy. Surgical treatment is still required for some patients despite unanswered questions on how it works.     

Is myocardial impairment in idiopathic dilated hypertrophic cardiomyopathy reversible by carvedilol?: a case report

A 64-year-old woman with dilated hypertrophic cardiomyopathy was treated by beta-blocker, because of recurrent episodes of congestive heart failure. Carvedilol administration was started with a dose of 2.5 mg/day, and gradually increased to the dose of 20 mg/day 3 months later. Her functional class recovered from New York Heart Association stage IV to stage II. Thallium-201 scintigraphy demonstrated advanced myocardial damage: defect/low perfusion in the anteroseptal, infero-posterior and apical regions. Iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid scintigraphy confirmed these findings. However, the scintigraphic abnormalities had reversed to near normal perfusion and metabolism similar to those of stunned myocardium after an ischemic episode. This case demonstrates the recovery of myocardial impairment during beta-blocker therapy in a patient with dilated hypertrophic cardiomyopathy.     

Dilated cardiomyopathy and cocaine abuse. Report of two cases

Two young patients with dilated cardiomyopathies associated with long-term use of cocaine are described. A 42-year-old male cocaine abuser with normal coronary arteries experienced recurrent myocardial infarction, with development of a dilated, globally hypocontractile left ventricle. The second patient, a 28-year-old woman with a prominent history of inhaling vaporized cocaine ("free-basing"), presented with symptoms and signs of biventricular heart failure and was found to have a dilated cardiomyopathy. The clinical spectrum of cocaine cardiotoxicity is reviewed, and pathophysiologic mechanisms of cocaine-induced cardiomyopathy are discussed. Long-term cocaine use may cause dilated cardiomyopathy and recurrent myocardial infarction, even in the absence of atherosclerotic epicardial coronary artery disease.     

Immunadsorption als Therapieverfahren der dilatativen Kardiomyopathie

Abnormalities of the cellular and humoral immune system have been described in patients with dilated cardiomyopathy (DCM). For patients with DCM, immunochemical analyses of myocardial biopsies have demonstrated myocardial inflammation. Various circulating cardiac antibodies have been detected among DCM patients. Circulating antibodies are extractable by immunoadsorption. Recent open controlled pilot studies showed that removal of antibodies by immunoadsorption induces improvement of cardiac function in DCM. Furthermore, it decreases myocardial inflammation. This may offer a new therapeutic option for patients with severe heart failure due to dilated cardiomyopathy.     

Prevention of hereditary cardiomyopathy in the Syrian hamster with chronic verapamil therapy

The cardiomyopathic Syrian hamster develops genetically determined cardiac necrosis that invariably leads to premature death from congestive heart failure or arrhythmia. This hamster is a valuable model of human disease because it has many features in common with clinical dilated, congestive cardiomyopathy. Previous studies have shown that therapy for several weeks with the calcium channel blocking drug verapamil or the alpha-1 adrenoceptor blocking drug prazosin can prevent myocardial necrosis due to microvascular spasm. Other investigations have demonstrated the positive effects of verapamil in the early stages of disease. It is not clear, however, whether continued treatment can prevent the long-term expression of the cardiomyopathy or whether the disease is genetically predetermined. To address this question, hamsters were treated with oral verapamil for 7 to 8 months during the necrotizing, compensatory hypertrophy and early failure stages of disease. Analysis of myocardial pathologic and biochemical variables demonstrated that continuously treated animals were generally similar to unaffected control hamsters; discontinuous therapy led to partial protection. These findings demonstrate that virtually complete prevention of this hereditary disease is feasible; these results may have important implications for the treatment of human cardiomyopathy.