Cardiac transplantation in New Zealand: eight years experience

Between December 1987 and December 1995, 62 patients underwent orthotopic cardiac transplantation at Green Lane Hospital. Their cardiac dysfunction resulted from dilated cardiomyopathy (32), coronary artery disease (21), rheumatic heart disease (7), congenitally corrected transposition of the great arteries (1) and hypertrophic cardiomyopathy (1). Before transplantation all patients were in New York Heart Association (NYHA) functional class III or IV. Eight patients (13%) died in the perioperative period and a further seven (11%) died 1 to 4 years after transplantation. Actuarial 1 and 3 year survival was 87% and 80% respectively. Forty-five of forty-seven surviving patients were in NYHA functional class I at the time of analysis. The results confirm that cardiac transplantation has a limited but valuable role in the treatment of end stage myocardial dysfunction.     

Cardiomyopathy induced by tachycardia: description of a typical clinical case

Different chronic tachyarrhythmias may cause a form of reversible myocardial dysfunction and left ventricular enlargement known as tachycardia-induced cardiomyopathy. Many authors in recent years observed that the control of heart rate or interruption of the arrhythmia were frequently associated with a significant improvement in ventricular function and a reduction of cardiac dimensions. We report a case of tachycardia-induced cardiomyopathy secondary to atrial fibrillation of unknown duration which occurred in a young patient with structurally normal heart. The regression of left ventricular enlargement and the recovery of left ventricular systolic function were complete few months after the restoration of sinus rhythm.     

Nonmetastatic accumulations in bone radionuclide scans in a patient with breast neoplasm

Left ventricular dilation and systolic dysfunction develop in 14-16% of patients with hypertrophic cardiomyopathy. Such findings may easily be misdiagnosed as dilated cardiomyopathy. It is unknown whether left ventricular dilatation and systolic dysfunction in patients with hypertrophic cardiomyopathy are reversible. A 35-year-old man had been a heavy drinker for 13 years and was abstinent for 1 year. Five years previously he suffered cardiac arrest and, based on echocardiographic, radionuclide, and cardiac catheterization findings, the diagnosis of alcohol-induced dilated cardiomyopathy was established. At presentation the heart was of normal size, with concentric left ventricular hypertrophy and only slightly reduced systolic function. Hypertrophic cardiomyopathy was diagnosed since no other cause for left ventricular hypertrophy could be detected. In hypertrophic cardiomyopathy, alcohol may induce reversible systolic dysfunction and left ventricular dilatation.     

An investigation into the interaction between drug efficacy and drug price of praziquantel in determining the cost-effectiveness of school-targeted treatment for Schistosoma mansoni using a population dynamic model

The data from animal and human in-vivo studies suggest that cardiac function is dependent in part on the normal function of the GH/IGF-1 axis (growth hormone/insulin-like growth factor-1). The syndrome of heart failure appears to be associated with a perturbation of the GH/IGF-1 axis. So far encouraging results from phase II clinical trials evaluating the effects of long-term growth hormone treatment in patients with moderate to severe chronic congestive heart failure due to dilated cardiomyopathy have been published. In these studies growth hormone (i.e., DNA-derived recombinant human growth hormone) was not used alone but in addition to standard optimal therapy for chronic heart failure. The following rationale is the basis of this new approach for the treatment of chronic congestive heart failure due to dilated cardiomyopathy. According to Laplace's Law, cardiac wall stress(i.e., the force acting per unit of cross-sectional area of the ventricular wall) is directly related to intraventricular pressure and ventricular radius and inversely related to ventricular wall thickness. Cardiac (ventricular) wall stress if increased in dilated cardiomyopathy (mainly because of the dilatation of the ventricles and to a minor extent because of the relative reduction in ventricular thickness). Growth hormone seems to be capable of increasing ventricular wall thickness in dilated cardiomyopathy, thus, reducing cardiac wall stress which in turn leads to an improvement in systolic cardiac performance. Recombinant human growth hormone as a pharmacologic treatment is not only an expensive but also risky therapeutic modality (e.g., potential risk of inducing colonic carcinoma, de-novo leukemias, relapses of leukemias and central nervous system tumors). Given these prerequisites and a receptivity for cost effectiveness and risk-benefit analyses, it seems as if subcutaneous recombinant human growth hormone-as an additional therapeutic substance in conjunction with one of the widely accepted drugs for end-stage chronic congestive heart failure due to dilated cardiomyopathy-e.g., angiotensin converting-enzyme inhibitors, diuretics, nitrates, digoxin, and beta-adrenergic receptor blockers (Carvedilol) could either become a bridge to transplantation (i.e., supporting patients awaiting transplantation) or an alternative to the very expensive cardiac transplantation. There are three reasons for this hypothesis. First, the fact that end-state dilated cardiomyopathy along with ischemic heart disease are the main indications for heart transplantation in adults; second, the worldwide small supply of human donor organs for heart transplantation; and, third, the urgent need to find alternative cost-effective and risk-beneficial therapeutic modalities.     

Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study

Although cardiac transplantation offers prolonged survival and improved quality of life to patients with end-stage heart failure, many patients with idiopathic dilated cardiomyopathy do not undergo this procedure. Possible barriers to cardiac transplantation were examined among 138 patients with idiopathic dilated cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow-up for approximately 5 years. The patients or a close family member were interviewed at baseline about socioeconomic factors and medical history. The patients or their next-of-kin were recontacted at 1-year intervals to determine patients' vital status and to obtain information about cardiac transplantation. Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%, respectively. Only 3.6% (5 of 138) of the patients underwent cardiac transplantation, and 19 (13.8%) patients had been placed on a waiting list for a heart transplant. Black race and nonmarried status were inversely associated with cardiac transplantation. Factors associated with not having been placed on a waiting list included older age, lower income, and lack of private health insurance. Black race was found to be significantly, but inversely associated with cardiac transplantation while older age was inversely associated with having been placed on a waiting list after adjusting for sex, race, education, and private insurance. These findings suggest that black patients with idiopathic dilated cardiomyopathy are less likely to undergo cardiac transplantation.     

The role of echocardiography in preoperative diagnosis of cardiac risk in patients before non-cardiac surgical interventions

Echocardiography is a noninvasive method for cardiac evaluation. A review of the current literature shows that the routine use of echocardiography for assessing perioperative cardiac risk in patients undergoing noncardiac surgery can not be supported. Only patients with suspected relevant heart valve diseases, acute heart failure, cardiomyopathy or condition after heart or heart-lung transplantation may benefit from preoperative echocardiography. In patients with suspected or proven coronary artery disease stress echocardiography offers the most relevant additional information for the anaesthesiologist. However, because of the high financial and personal implications it should be reserved to those patients who are not able to perform a normal stress test. Besides in patients in whom transthoracic echocardiography doesn't offer sufficient information or is not possible transesophageal echocardiography plays only a minor role in preoperative cardiac evaluation.     

Heart transplantation in children and young adults: early and intermediate-term results

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.     

Identification of two novel 5'' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts

OBJECTIVES: This study was performed to determine the degree and time course over 6 years of cardiomyocyte hypertrophy and myocardial fibrosis of the cardiac allograft in transplanted patients. BACKGROUND: Diastolic dysfunction and to a certain extent systolic dysfunction are common cardiac findings after heart transplantation. The development of posttransplant cardiomyocyte hypertrophy and myocardial fibrosis likely contributes to these derangements. METHODS: Cardiomyocyte diameter and percent fibrosis were determined in serial endomyocardial biopsy specimens obtained from 1 month up to 6 years following heart transplantation in 50 patients. Endomyocardial biopsy specimens from 40 patients with primary dilated cardiomyopathy and 11 normal subjects were similarly analyzed for control data. Analyses were performed in a blinded format using a validated computerized image analysis system (Optimas 5.2). RESULTS: Early (1 month) cardiomyocyte enlargement decreased to the smallest diameter 6 months posttransplant, but thereafter progressively increased by 10% to 20% over the subsequent 5- to 6-year period. Although not statistically established, principal stimuli may include a discrepancy in body size (recipient > donor), coronary allograft vasculopathy and posttransplant systemic hypertension. Percent myocardial fibrosis rose early (1 to 2 months) posttransplant and thereafter remained at the same modest level of severity. CONCLUSIONS: Cardiomyocyte diameter of the transplanted heart gradually increases over time, while percent myocardial fibrosis rises early and remains in a modestly elevated plateau after 2 months posttransplant. These histostructural changes likely contribute to the hemodynamic and cardiac functional alterations commonly observed posttransplant.     

Ultrasonic liposculpturing: extrapolations from the analysis of in vivo sonicated adipose tissue

BACKGROUND: A local renin-angiotensin system in the heart is often invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions. METHODS AND RESULTS: We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin. CONCLUSIONS: These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.     

Extracorporeal membrane oxygenation for cardiac support in children

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support for cardiac failure has been used in children since 1981 at the Children's Hospital in Pittsburgh. Most children required support after cardiac operations. Recently, however, a larger number of patients with decompensated cardiomyopathy or myocarditis have been supported with ECMO, which was used as a bridge to transplantation in most. METHODS: From 1981 to 1994, 68 children were placed on ECMO for cardiac support. RESULTS: The overall survival for the entire time period was 38%, with the more recent experience survival increased to 47%. In 14 children, ECMO was used as a bridge to transplantation, with 9 children receiving a heart transplant and 7 long-term survivors. Extracorporeal membrane oxygenation has also been used to resuscitate 11 children after sudden cardiac arrest, with a long-term survival of 53%. CONCLUSIONS: We conclude that ECMO support for severe cardiac failure is effective. Patient selection and the use of heart transplantation for intractable heart failure have improved the overall survival.     

Actin mutations in dilated cardiomyopathy, a heritable form of heart failure

To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that cosegregate with IDC were identified in two unrelated families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Coupled with previous data showing that dystrophin mutations also cause dilated cardiomyopathy, these results raise the possibility that defective transmission of force in cardiac myocytes is a mechanism underlying heart failure.     

Transient normalization of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy

A 19-year-old man who had fulminant heart failure caused by an idiopathic dilated cardiomyopathy was supported with a left ventricular assist device for 183 days as a bridge to heart transplantation. At the time of intended transplantation it was noted that the patient's heart had returned to normal size, had a normal ejection fraction, and was able to maintain normal pressures and flows. In view of the apparent recovery of cardiac properties, the left ventricular assist device was explanted and the transplantation was not performed. However, the heart dilated, ejection fraction worsened, and the patient died of heart failure exacerbated acutely by a systemic viral illness. Although such recovery of systolic function is uncommon, as use of the left ventricular assist devices becomes more widespread other physicians might encounter similar findings and, in this regard, they might find our experience useful as they contemplate their treatment options.     

Alternative surgical options to heart transplantation

Cardiac transplantation is the treatment of reference for refractory cardiac failure but the limited number of donors, the complications inherent to transplantation and the relative and absolute contra-indications has made it necessary to find alternative surgical solutions. The detection of myocardial viability by Thallium scintigraphy, Dobutamine echocardiography and/or position emission tomography in coronary disease, allows identification of zones which are capable of recovering contractile function after revascularisation. The authors report the results of a series of 91 operated patients with a 10 year follow-up having a 72% 5 year actuarial survival and improved ejection fraction. The other alternative which may improve symptoms and prognosis in patients with severe ischaemic heart disease with left ventricular dysfunction is apical remodelling or Dor's procedure. The results of a haemodynamic study at 1 year of 171 patients clearly show a functional improvement and an increase of the ejection fraction. The advantage of this method is that it can be used in patients with dyskinetic and akinetic plaques resulting from antero-septo-apical infarction. Finally, even if mitral regurgitation is relatively uncommon in chronic ischaemic heart disease, a simple procedure (annuloplasty) is often sufficient to correct the mitral regurgitation and reduce the afterload of a failing ventricle. On the other hand, in dilated cardiomyopathy, two new options have been developed; one, suggested by Steven Bolling, proposes simple mitral annuloplasty whatever the underlying cause (primary or ischaemic cardiomyopathy) with symptomatic improvement and better haemodynamics in terms of increased cardiac output and oxygen consumption on exercise and an actuarial survival much higher than that of cardiac transplantation at one and at two years. The most recent innovation is the Batista procedure which is a method of ventricular reduction associated with correction of mitral regurgitation. The authors have assessed 20 patients for this operation at the Foch Hospital by Dobutamine echocardiography and 5 patients underwent the procedure. All 5 patients reported symptomatic improvement but some had an unchanged haemodynamic status. Others improved at rest and some improved on exercise. The Cleveland Clinic series reported results in 57 cases. Whichever alternative method tested, there is a significant functional improvement but the cardiac output does not always increase. There are no comparative prospective randomised studies and strict selection of patients is required, a problem not yet resolved for all indications. The advantages of these procedures are certain as there is no waiting list, the functional results in good indications have been demonstrated and, if necessary, secondary orthotopic cardiac transplantation is always possible.     

Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.     

Renography before heart transplantation in patients with cardiomyopathy

In patients with ischemic cardiomyopathy (CM), abnormal renograms may result not only from circulatory failure (which should reverse after transplantation) but also from intrinsic renal disease (which contraindicates heart transplantation). Here, the outcome of heart transplantation was related to preoperative renograms, and the differentiating and prognostic value of renography was analyzed. METHODS: The study population consisted of 50 patients with ischemic CM expecting heart transplantation. Anatomical renal pathology was excluded in all patients. Dynamic renal scintigraphy was performed with 99mTc-mercaptoacetyltriglycine. Background-subtracted renograms were inspected visually and characterized numerically. Mean parenchymal transit time (mPTT), renal tracer content at 15 min (RTC15) and retention index (RI) were determined. The parametric renogram values were related to a normal reference group of 64 patients. The preoperative renograms were matched with the postoperative outcome. RESULTS: Three characteristic types of symmetrical findings in the kidneys were found: no pathological findings, mildly delayed peak and excretion phase and severely delayed peak and excretion phase. Pathological renograms were observed in 36 of 50 (72%) patients. The mean parametric renogram values in ischemic CM were as follows: Group A (normal kidney function), mPTT = 142+/-26.6 sec, RTC15 = 22.3%+/-4.6% and RI = 24.7+/-11.9; Group B (mild dysfunction), mPTT = 210+/-44.0 sec, RTC15 = 42.6%+/-10.3% and RI = 101.4+/-50.5; Group C (severe dysfunction), mPTT = 320+/-94.2 sec, RTC15 = 79.6%+/-15.9% and RI = 347.7+/-194.7; and reference patients (normal kidney function), mPTT = 137+/-31.1 sec, RTC15 = 22.8%+/-3.8% and RI = 24.6+/-7.9. Postoperative serum creatinine levels were <1.5 mg/dl in all Group A patients, between 1.5 and 2.5 mg/dl in 78% of Group B patients and >2.5 mg/dl in 75% of Group C patients. CONCLUSION: Renography revealed abnormal kidney function when structural pathology was excluded. The renographic abnormalities in ischemic CM did not reflect simply the circulatory failure. The numerical grading of renograms allowed patient stratification, suggestive of possible renal insufficiency after cardiac transplantation and immunosuppressive therapy. With further experience, renography may become a useful tool for predicting postoperative outcome in ischemic CM.     

Rate-dependent hemodynamic responses during incremental atrial pacing in chronic constrictive pericarditis before and after surgery

Chronic constrictive pericarditis is a frequent cause of diastolic dysfunction, and results in impaired ventricular filling. Unlike in normal subjects, ventricular filling in constrictive pericarditis occurs almost entirely in the initial one third of diastole, and cardiac output is dependent predominantly on heart rate. Tachycardia impairs ventricular filling in normal subjects, but its effects in patients with constrictive pericarditis have not been studied. The effect of increasing heart rate alone with atrial pacing on the central and peripheral hemodynamics of patients with untreated chronic constrictive pericarditis before and after pericardiectomy was evaluated. Increased heart rate with atrial pacing increased cardiac output, whereas stroke volume remained unchanged up to heart rates of 140 beats/min. Further increases in heart rate resulted in reductions of cardiac output and stroke volume. There were no significant changes in ventricular filling pressures. Infusion of 300 ml of saline solution at peak pacing rates did not improve cardiac output. After successful surgical pericardiectomy, the hemodynamic effects of atrial pacing returned to normal. It is concluded that moderate tachycardia improves the hemodynamic profile of patients with constrictive pericarditis.     

Myosin heavy chain gene expression in human heart failure

Two isoforms of myosin heavy chain (MyHC), alpha and beta, exist in the mammalian ventricular myocardium, and their relative expression is correlated with the contractile velocity of cardiac muscle. Several pathologic stimuli can cause a shift in the MyHC composition of the rodent ventricle from alpha- to beta-MyHC. Given the potential physiological consequences of cardiac MyHC isoform shifts, we determined MyHC gene expression in human heart failure where cardiac contractility is impaired significantly. In this study, we quantitated the relative amounts of alpha- and beta-MyHC mRNA in the left ventricular free walls (LVs) of 14 heart donor candidates with no history of cardiovascular disease or structural cardiovascular abnormalities. This group consisted of seven patients with nonfailing (NF) hearts and seven patients with hearts that exhibited donor heart dysfunction (DHD). These were compared with 19 patients undergoing cardiac transplantation for chronic end-stage heart failure (F). The relative amounts of alpha-MyHC mRNA to total (i.e., alpha + beta) MyHC mRNA in the NF- and DHD-LVs were surprisingly high compared with previous reports (33.3+/-18.9 and 35.4+/-16.5%, respectively), and were significantly higher than those in the F-LVs, regardless of the cause of heart failure (2.2+/-3.5%, P < 0.0001). There was no significant difference in the ratios in NF- and DHD-LVs. Our results demonstrate that a considerable amount of alpha-MyHC mRNA is expressed in the normal heart, and is decreased significantly in chronic end-stage heart failure. If protein and enzymatic activity correlate with mRNA expression, this molecular alteration may be sufficient to explain systolic dysfunction in F-LVs, and therapeutics oriented towards increasing alpha-MyHC gene expression may be feasible.     

Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement

BACKGROUND & AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia is common but often asymptomatic. However, in some cases, the vascular lesions that involve the liver may lead to high-output cardiac failure and pulmonary hypertension that is predominant over hepatobiliary manifestations. Liver transplantation and treatment of these complications are described and discussed in this article. METHODS: Three patients with hereditary hemorrhagic telangiectasia and hepatic involvement received transplants. They had pulmonary hypertension and chronic right-sided heart failure caused by disseminated intrahepatic telangiectasias with shunts between the hepatic artery and hepatic veins or portal vein. Left-to-right intrahepatic shunt output was estimated to range between 51% and 57.5% of cardiac output. RESULTS: Hyperdynamic circulation disappeared after liver transplantation in all patients. Results of computed tomography and right-sided heart catheterization performed 6 months later were normal. Follow-up periods currently are 65, 53, and 29 months, and each patient continues to be asymptomatic. CONCLUSIONS: This report suggests that liver transplantation can be considered as an alternative and successful curative treatment that may prevent the irreversible evolution of cardiopulmonary disease.     

Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Genomic structure and chromosomal localization of the murine LIM class homeobox gene Lhx1

Catecholamine-induced cardiomyopathy is a rare complication of pheochromocytoma. We present a case of pheochromocytoma that developed preoperative heart failure. Left ventricular dilation and severe hypokinesia were demonstrated by echocardiography. Heart failure was successfully treated with digitalis, diuretics and captopril. There were no surgical complications and the follow up showed and improvement on the systolic function evaluated by echocardiography and isotope ventriculography, 3 and 6 months after surgery. We review the pathophysiology and evolution of catecholamine induced cardiomyopathy. Preload reserve can be one of the adaptive mechanisms of the ventricle in catecholamine-induced cardiomyopathy. Conventional therapy of hypertension and heart failure can be effective to correct the symptoms of cardiac dysfunction.