Successful reversal by chelation therapy of congestive cardiomyopathy due to iron overload

A patient who developed severe iron overload cardiomyopathy is described. Venesection could not be performed because the patient had chronic anemia. Deferoxamine mesylate, a chelating agent, was administered daily for more than 2 years and produced significant improvement in ventricular function which was associated with a biopsy-proven decrease in myocardial iron stores. This is the first reported case in which a severe cardiomyopathy due to iron overload was reversed by chelation therapy alone.     

Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine

It is believed that myocardial iron deposition and the resultant cardiomyopathy only occur in the presence of severe liver iron overload. Using cardiovascular magnetic resonance, it is now possible to assess myocardial and liver iron levels as well as cardiac function in the same scan, allowing this supposition to be examined. We describe a patient with progressive myocardial iron deposition and the development of early iron overload cardiomyopathy despite excellent compliance to standard subcutaneous desferrioxamine, minimal liver iron and well-controlled serum ferritin levels. These indirect markers remained far below the thresholds conventionally believed to be associated with increased cardiac risk.     

Dose-effect and structure-function relationships in doxorubicin cardiomyopathy

The cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (Adriamycin) provides a unique opportunity to analyze dose-effect and structure-function relationships during development of myocardial disease. We measured the degree of morphologic damage by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormality by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg/m². Performance abnormallties correlated weakly with dose, exhibited a curvillnear relationship, and had a “threshold” for expression. Catheterization abnormalitles correlated well with morphologic damage (r = 0.57 to 0.78) in a subgroup of patients in whom exercise hemodynamics were measured, and this relationship also exhibited a curvilinear, threshold configuration. In DXR-CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose) while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly.     

Early anthracycline cardiotoxicity

Eight patients in whom cardiac dysfunction developed within four weeks of receiving their first or second course of daunorubicin or doxorubicin are described. Four patients presented with pericarditis; three of these four had evidence of myocardial dysfunction. Histopathologic analysis of these patients was consistent with an acute myocyte damage and secondary inflammatory process. An additional group of four patients presented with symptoms and signs of heart failure. These patients were either elderly or had evidence of previous cardiac disease. One of these patients suffered a myocardial infarction 24 hours after receiving 60 mg/m² of daunorubicin; earlier doses in the same course had been associated with evidence of myocardial ischemia. We conclude that anthracycline antibiotics may manifest clinically significant cardiotoxicity at total cumulative doses much less than have been associated with chronic cardiomyopathy.     

Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries

Clinical and morphologic features of transmural myocardial infarction (associated with insignificant or absent atherosclerosis of the extramural coronary arteries) are described in seven patients with hypertrophic cardiomyopathy. Marked chronic congestive heart failure associated with supraventricular arrhythmias occurred in six of the seven patients, each of whom had no or mild left ventricular outflow tract obstruction under basal conditions. No patient had typical angina pectoris, and only one patient had clinically evident acute myocardial infarction. Infarction may have caused cardiac arrest in one other patient, but was “silent” in the remaining five patients.

At necropsy, six of the seven patients had extensive myocardial scarring involving the ventricular septum, left ventricular free wall and one or both left ventricular papillary muscles; in four patients portions of the right ventricular wall were also scarred. Six patients had dilated ventricular cavities, including two who were known to have nondilated ventricular cavities earlier in their clinical course.

It is concluded that transmural myocardial infarction in the absence of significant coronary atherosclerosis is a not uncommon finding (prevalence rate 15 percent) in a population of patients who had died from hypertrophic cardiomyopathy. Although transmural infarction is possibly a secondary event, it more likely contributes causally to the clinical deterioration of some patients with hypertrophic cardiomyopathy, leading to ventricular dilatation and progressive fatal cardiac failure.     

Hypothyroid dilated cardiomyopathy

Most patients with dilated cardiomyopathy have a poor prognosis due to progressive and irreversible myocardial dysfunction. Rarely, is a metabolic etiology responsive to specific therapy identified. Although many studies have confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. In this study, we report the case of a patient with severe hypothyroidism and a dilated cardiomyopathy complicated by heart failure, which has receded after recovery to euthyroidism with L-thyroxin therapy. This case suggests that hypothyroidism should be evoked systematically when a dilated cardiomyopathy is diagnosed.     

A syndrome of congenital cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia

A distinctive syndrome of cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia was noted in four male patients aged 19 to 49 years. Each presented with cardiac enlargement and varying degrees of left ventricular failure. One patient was known to have had complete heart block from infancy and another patient from 13 years of age. Each had chronic atrial fibrillation or flutter, with a regular ventricular rhythm at 35 to 45/min. Hemodynamic studies showed dilatation and poor contractility of the left ventricle, considerable mitral regurgitation, reduced resting cardiac output and elevated left ventricular end-diastolic pressures. The clinical course in follow-up periods of up to 5 years has been one of relatively mild, slowly progressive congestive heart failure. Mitral valve replacement and permanent pacemaker installation in one patient had no effect on the clinical course. The mitral valve showed redundant leaflet tissue with mucoid degenerative changes. This syndrome appears to represent a form of congenital cardiomyopathy which involves degeneration or fibrotic changes in both the myocardium and the conduction system. Familial occurrence has not been recognized.     

Acute myocardial dysfunction after nasal infiltration with cocaine

We report the case of a patient with severe myocardial dysfunction after nasal infiltration of cocaine during septoplasty. Complete recovery of myocardial function was observed in twelve days. Several reports have described chronic cardiomyopathy in long-term cocaine users, but only one case of acute cardiomyopathy. None of these cases were related to the medical use of cocaine.     

Myocardial infarction in patients with coronary artery spasm demonstrated by angiography

Twelve cases of myocardial infarction (MI) were documented in 11 of 39 patients who had coronary artery spasm (CAS) that was observed by angiography either before MI (3 patients), after MI (5 patients), or both before and after MI (3 patients). MI corresponded in location to sites of ECG changes of myocardial ischemia during spontaneous angina pectoris in 7 of 7 patients and to the region of myocardium supplied by the vessel in which CAS was observed by angiography in each patient. MI occurred in the distribution of the right coronary artery in 8 patients and of the left coronary artery in 4 patients. Of 12 vessels that supplled infarcted regions of myocardium, 7 vessels had ≥50% diameter fixed coronary artery narrowing (CAN), but the remaining 5 vessels had minimal (10%) or no fixed CAN. In those patients who were studied after MI, coronary angiography demonstrated that only 3 of 9 vessels in the distribution of infarcted regions of myocardium were completely occluded. Clinical follow-up for an average of 1.3 years after MI showed that 7 patients continued to have chest pain, 2 patients were asymptomatic, and 2 patients died suddenly 9 weeks and 1 year, respectively, after MI. Therefore, among our patients with CAS demonstrated by angiography, Mis (1) were frequent (28%), (2) occurred in the distribution of observed coronary spasm, (3) were frequently (5 of 12 arteries) in the distribution of vessels having minimal or no fixed narrowing, and (4) were often (6 of 9 arteries) in the distribution of vessels that were demonstrated to be patent after MI.     

Ischemic cardiomyopathy

The term “ischemic cardiomyopathy” was used initially to describe a clinical syndrome that was indistinguishable from primary congestive cardiomyopathy but due to severe, diffuse coronary artery disease. The term has been expanded to include the larger category of myocardial disease secondary to coronary artery disease. Using this expanded definition, we have discussed the varied clinical preventations of congestive ischemic cardiomyopathy and restrictive ischemic cardiomyopathy (stiff heart syndrome and right ventricular infarction), and how the effects of ischemia on left ventricular systolic and diastolic performance may cause these varied presentations. The prognosis of any ischemic cardiomyopathy is related primarily to the degree of ventricular dysfunction and the extent of coronary artery disease. Therapy is aimed at preventing or ameliorating myocardial ischemia and halting the progression of, or even reversing, the deterioration in myocardial function.     

Cardiac transplantation in man. Review of first three years' experience

A one year follow-up of the first 29 patients who underwent cardiac transplantation at Stanford University Medical Center from January 1968 to January 1971 is reported. Actuarial survival is 49 per cent at six months, 37 per cent at 12 and 18 months, and 30 per cent at two years. Recipient selection is important for the best long-term results; the ideal candidate is a relatively young patient with recent severe cardiac disability which has been unresponsive to optimal medical and surgical therapy.In our series, three patients died within 72 hours after transplantation secondary to severe fixed pulmonary hypertension. Nine additional patients died in the hospital; in seven of these death was related to unremitting rejection or infection.Thirteen patients were discharged from the hospital, with a 60 per cent actuarial chance of living two years. Evaluation has documented “normal denervated” cardiac function in eight patients one year, and in one of two patients two years after transplantation. Chronic rejection appears to be manifested by cardiac arrhythmias, coronary artery intimal hyperplasia, atherosclerosis and subsequent myocardial infarction.Improved diagnosis and treatment of acute rejection has resulted in yearly improvement in the short-term survival. These patients return to normal activities after hospital discharge and are not limited by their cardiac function. Their long-term survival appears to be limited by coronary arterial changes related to chronic rejection.     

Acute myocardial infarction complicating the clinical course of dilated cardiomyopathy in childhood.

An acute myocardial infarction occurred in a 6-year-old child with dilated cardiomyopathy. This caused severe hemodynamic deterioration that led to a fatal outcome. Autopsy revealed diffuse myocardial atrophy without cell infiltrate, normal epicardial coronary arteries, and a massive healed anteroapical infarction. Coronary embolism or spasm could not be ruled out as the cause of the infarction.     

Clinical and morphological features of human hypertensive-diabetic cardiomyopathy

The existence of a specific cardiomyopathy secondary to diabetes mellitus is controversial. During a 2-year period, we had the opportunity to examine nine diabetic patients at autopsy who had clinically severe congestive heart failure and minimal extramural coronary artery atherosclerosis. Unexpectedly, all nine patients were found to be hypertensive. Accordingly, we initiated a detailed study of the clinical and morphological features of this group, and compared the findings to age-matched autopsied subjects with either isolated hypertension, isolated diabetes mellitus, or no heart disease.The study of the hypertensive-diabetic hearts revealed severe interstitial fibrosis, focal or confluent scars, and extensive myocytolytic activity. Comparison with the diabetic, hypertensive, and normal groups showed statistically significant differences in regard to the degree of interstitial and focal scarring, and the presence of myocytolysis. Only the hypertensive group had minimal interstitial scarring. There were no statistical differences in the small vessel changes between the four groups, although subjectively the hypertensive and hypertensive-diabetic patients had more severe disease.It is concluded that the association of diabetes mellitus and hypertension in the absence of significant coronary artery atherosclerosis may lead to a severe cardiomyopathy. Although the etiology of myocardial failure in this syndrome is uncertain, the degree of myocardial fibrosis and the frequency of myocytolytic lesions possibly related to catecholamine hypersensitivity, are potential explanations. Several studies suggesting that hypertension has adverse consequences in diabetes, as well as an animal model of hypertensive-diabetic cardiomyopathy, support our conclusion that cardiomyopathy associated with diabetes mellitus is a specific entity which may be secondary to the combined effects of diabetes and hypertension on the myocardium.     

Coronary stenting for a muscular bridge in a patient with hypertrophic obstructive cardiomyopathy

A young woman with hypertrophic cardiomyopathy presented with intractable chest pain due to a myocardial bridge over the left anterior descending artery, producing severe compression during systole. Percutaneous intracoronary stenting was performed. The patient, however, developed severe and diffuse restenosis within 30 days of the procedure. Myotomy may provide a more effective treatment option for such patients with symptomatic myocardial bridging.     

Reversible severe congestive cardiomyopathy in three cases of hypophosphatemia.

Three patients presented with severe congestive cardiomyopathy of unknown cause. All three had a profound depression of serum phosphorus levels resulting from the chronic ingestion of large quantities of a phosphorus-binding antacid. Results of physical examination and echocardiograms were consistent with cardiomegaly and severe myocardial dysfunction, and chest films showed enlargement of the cardiac silhouette with interstitial pulmonary edema. Serum phosphorus was restored to normal levels, and within 2 to 5 weeks the results of physical examination and echocardiogram of each patient returned to normal. We conclude that these patients had reversible hypophosphatemic cardiomyopathy and show the importance of inorganic phosphorus in myocardial metabolism and function. Serum phosphorus measurements should be a part of the routine evaluation of patients with congestive cardiomyopathy because, at least in some patients, hypophosphatemia appears to be a reversible cause of this disorder.     

Left ventricular hypertrophy in coronary artery disease. A cardiomyopathy syndrome following myocardial infarction

Eighty-five patients with ventricular dysfunction due to coronary disease and to nonobstructive cardiomyopathy were studied by biplane angiocardiography (12/sec) to determine the extent of hypertrophy and the distinguishing features between primary myocardial and coronary disease. Patients with cardiomyopathy and equally severe dysfunction due to coronary disease had identical end-diastolic, end-systolic and stroke volume and work per square meter, stroke work per gram of ventricular mass, end-diastolic pressure, peak equatorial wall stress, ejection fraction, peak circumferential shortening velocity, peak ventricular ejection rate, peak external pump power, left ventricular mass and mass to diastolic volume ratio. Hypertrophy develops after myocardial infarction in proportion to ventricular dilatation and may result in a syndrome of massive hypertrophy, hypokinesis and congestive failure quantitatively identical to that found in primary cardiomyopathy except for etiology. Hypertrophy is associated with normalization of wall stress in both coronary and primary myocardial disease and is thus not dependent on the type of insult to the contractile mechanism.     

Left bundle branch block with right axis deviation: A marker of congestive cardiomyopathy

Three patients with primary congestive cardiomyopathy (COCM), complete left bundle branch block (LBBB) and right axis deviation in the standard leads are described. Review of 50 additional patients from the literature since 1950 indicates that the uncommon combination of LBBB and RAD is a marker of severe myocardial disease, especially COCM. The mechanism of production of this electrocardiographic pattern appears to be diffuse conduction system involvement in advanced myocardial disease.     

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload.

AIMS: To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops. METHODS AND RESULTS: We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0.93, P<0.0001). Inter-study cardiac reproducibility was 5.0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0.61, P<0.001). All patients with ventricular dysfunction had a myocardial T2* of <20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0.79, P<0.002). CONCLUSIONS: Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.     

Afterload reduction in the management of postinfarction ventricular septal defect

The primary goal in the medical management of ventricular septal defect complicating myocardial infarction is to support cardiac function and control symptoms, if possible, for a period of 4 to 6 weeks. If the patient survives this period, surgical correction of the defect is technically easier and safer. In many cases, however, cardiac function is severely compromised, intractable biventricular failure develops, early operation is necessary and the likelihood of successful repair is diminished.

We recently treated two such patients by means of afterload reduction with nitroprusside. In one patient, sublingually administered isosorbide dinitrate was later used, and prolonged survival was achieved after surgery. Hemodynamic investigations in both cases demonstrated that nitroprusside improved cardiac output without necessarily decreasing mean arterial pressure. The effect of nitroprusside on pulmonary blood flow and left to right shunt was variable: One patient demonstrated a decrease in the ratio of pulmonary to systemic blood flow, and the other did not. We conclude that afterload reduction with either intravenous or oral agents is a potentially useful measure in the management of patients with ventricular septal defect complicating myocardial infarction.     

Rapid reversal of heart failure in a patient with phaeochromocytoma and catecholamine-induced cardiomyopathy who was treated with captopril

A patient with a phaeochromocytoma and severe left ventricular heart failure caused by a catecholamine-induced cardiomyopathy is described. The clinical signs of congestive heart failure resolved rapidly on treatment with captopril and myocardial performance became normal within two weeks of medical treatment with captopril for one week and with captopril in combination with phenoxybenzamine for another week.