Prognostic value of myocardial lactate dehydrogenase subunit ratio in heart transplant recipients.

BACKGROUND: Allograft coronary artery disease (CAD) is a major long-term complication in heart transplant recipients. Unfortunately, methods for early estimation of the likelihood of development of the disease are not currently available. Lactate dehydrogenase (LDH) is composed of heart and muscle subunits. The prevalence of these subunits in LDH isoenzymes (LDH1 through LDH5) is an accurate indicator of myocardial metabolism and allows indirect estimation of oxygen availability to cardiocytes. This study investigated the prognostic value of myocardial LDH composition for the occurrence of morbid events in patients with severe allograft CAD. METHODS: Eighty-eight heart transplant recipients were followed up for a median of 4.3 years. The isoenzymes of LDH and the ratio of the heart and muscle subunits (H/M) were determined in 526 endomyocardial biopsy samples. RESULTS: Eleven patients (12%) died from allograft CAD during follow-up. They had significantly lower H/M ratios compared with event-free patients, with clear differences as early as 6 months after operation. A threshold value of 2.75 was derived from receiver operating characteristic curve analysis. Patients showing H/M values < or =2.75 had a significantly higher mortality rate than did those with higher values (p=.0003). Importantly, the H/M ratio emerged as the most powerful independent prognostic factor of death by allograft CAD (p=.001) in a multivariate model. CONCLUSIONS: Poor myocardial aerobic metabolism estimated through low H/M values was highly predictive of cardiac death resulting from severe allograft CAD. Analysis of LDH isoenzyme profile in routine endomyocardial biopsies might be of clinical value.

Myocardial lactate dehydrogenase subunit ratio in cardiac allograft recipients.

BACKGROUND: Allograft coronary artery disease (CAD) is a major long-term complication in heart transplanted patients. However, the metabolic basis of allograft CAD remains to be fully elucidated. We analyzed the lactate dehydrogenase heart (H) and muscle (M) isoenzyme pattern in endomyocardial biopsy specimens and the evolution of the H/M ratio to test whether changes in this ratio could be the earliest manifestation of allograft CAD. METHODS: Twenty-four heart transplant recipients were followed up for 12 months. Endomyocardial biopsy was performed at 1, 2, 3, 6, and 12 months after transplantation. Lactate dehydrogenase 1 through 5 isoenzymes were separated by electrophoresis, and the H/M ratio was calculated. Two groups of patients were identified: group 1 (n = 20), patients without allograft CAD; and group 2 (n = 4), patients with poor outcome (three deaths, 1 case of low cardiac output) and angiographic and histologic evidence of allograft CAD. RESULTS: Both groups had similar H/M baseline values. The H/M ratio was higher (p = 0.01) in group 1 at 6 months (3.48 +/- 0.64 versus 2.17 +/- 0.43) and 12 months (3.76 +/- 0.92 versus 2.18 +/- 0.45) when compared with group 2. The H/M ratio increased from 2.78 +/- 0.89 at 1 month to 3.76 +/- 0.92 at 12 months (p = 0.02) in group 1 and decreased in group 2 (2.86 +/- 0.49 versus 2.18 +/- 0.45; not significant). CONCLUSIONS: Changes in H/M ratio reflect an anaerobic shift in the lactate dehydrogenase isoenzyme composition and can be taken as an early indicator of allograft CAD.

Clinical insights on the use of highly sensitive cardiac troponin assays.

This review describes the pathophysiological and histopathological rationale for using the cardiac isoforms of troponin T and troponin I in congestive heart failure (CHF). It also focuses on the potential clinical usefulness of new generation highly sensitive and specific cardiac troponin assays with respect to histological monitoring, risk stratification and therapeutic follow-up of patients with CHF. The availability of more powerful analytical tools for these highly specific markers of myocardial injury offers a unique opportunity to expand the field of their application and to explore new disease processes. Because cardiac troponin T and cardiac troponin I provide useful clinical information unavailable through other diagnostic techniques, they appear as promising biochemical markers in patients with CHF.

Cardiac troponin I in patients with hematologic malignancies.

BACKGROUND: The cardiac isoform of troponin I (cTnI) is a myofibrillar protein highly specific for myocardial injury. We used a recently developed new-generation immunoassay with high analytical sensitivity to measure cTnI in patients diagnosed with hematologic malignancies, before chemotherapy and after an intermediate cumulative dose of anthracyclines. We hypothesized that measurement of cTnI with this sensitive method would provide evidence of myocardial injury in these patients. METHODS: Sera from 115 individuals (60 healthy controls, 25 anthracycline-naive patients and 30 patients treated with intermediate cumulative doses of anthracyclines) were assessed for cTnI, creatine kinase MB (CKMB) mass and myoglobin. Radionuclide left ventricular ejection fraction (LVEF) was also determined. RESULTS: Using this sensitive assay, detectable concentrations of cTnl were measured in the healthy population [mean, 19.5 pg/ml, 95% confidence interval (CI) 13.5-25.5 pg/ml]. Anthracycline-naive patients had cTnI mean values (36.5 pg/ml, 95% CI 25.1-47.9 pg/ml) that were significantly (P < 0.01) greater than those in the control group. cTnI was significantly (P < 0.00001) increased in anthracycline-treated patients (76.4 pg/ml, 95% CI 67.0-85.8 pg/ml) compared with both the anthracycline-naive patients and the controls. CKMB, myoglobin and LVEF were within the normal range in all patients. CONCLUSIONS: These data provide evidence for cardiac involvement in patients with hematological malignancies before and during the course of anthracycline chemotherapy. They suggest that detection of myocardial injury may be facilitated by measurement of cTnI with a highly sensitive assay.

Epidemiology of heart failure.

The enormous impact of the growing epidemic of heart failure mandates the development of easily accessible registries for patients with all classes of CHF, particularly those with advanced heart failure. It also is important to compile data from patients not enrolled in randomized trials to truly appreciate the natural history of this disease. The continued aging of the United States population will surely lead to continual increase in the prevalence of heart failure and its impact on the health care economy. It also is important to develop methods to reliably identify patients with systolic versus primary diastolic dysfunction to better understand the demographics, risk factors, and natural history of diastolic dysfunction. Increased attention clearly is warranted to better understand the demographics and risk factors for development CHF and to help devise strategies to reduce the morbidity, mortality, and economic impact of this disease.

False aneurysm of the ascending aorta following aortic valve replacement.

False aneurysm of the ascending aorta is a rare and life-threatening complication of open heart surgery, usually occurring late after operation. Echocardiography, especially transesophageal echocardiography, is a non-invasive method of examination which can be very helpful in its diagnosis. Deep hypothermia and circulatory arrest allow a bloodless field during surgery and provide an adequate patient protection. Infection is a very well known predisposing factor, but cystic medial necrosis of the aortic wall also seems to play a role in this complication. We report three cases, two of them had cystic medial necrosis and the presence of infection could be proved in none.

Adult coronary aneurysms related to Kawasaki disease.

Kawasaki disease (KD) is an acute illness encountered in infancy and childhood. Cardiovascular complications of this syndrome are recognized as being part of the adult coronary artery disease population. Reported herein is the surgical treatment of multiple coronary artery aneurysms, severe stenotic lesions and thrombotic involvement of the coronary arterial tree that could be ascribed to childhood KD in two adult patients with no risk factors for atherosclerotic heart disease. Surgical management of such patients reveals safe and provides satisfactory quality of life.

[The troponin complex: a new biochemical approach to cardiac insufficiency]. / Le complexe des troponines: une nouvelle approche biochimique de l'insuffisance cardiaque.

The progression of cardiac failure is related to the loss of functional myocytes. The aim of these studies was to describe the structural degradation of the myocardium by the use of cardiac troponins as specific and sensitive markers of cardiac cell necrosis. The cardiac isoforms of troponin I and troponin T were measured in patients with NYHA class III-IV heart failure using second generation immunoassays without cross-reactivity with the skeletal isoforms of the two proteins. The results showed that the cardiac troponin I (72.1 +/- 15.8 vs 20.4 +/- 3.2 pg/mL; p < 0.01) and troponin T (0.21 +/- 0.6 vs 0.0005 +/- 0.002 ng/mL; p < 0.001) concentrations were significantly higher in patients with cardiac failure compared to a control population of healthy volunteers. These results suggest that troponin I and troponin T may have valuable clinical applications in the biological monitoring of cardiac failure and the appreciation of its progression.

Short-term development of transplant-related coronary artery disease in orthotopic cardiac allograft recipients.

Transplant-related coronary artery disease is the main cause of death in orthotopic heart transplant recipients one year or more after operation. We report our own experience with chronic vascular rejection occurring 4, 10, and 15 months after transplantation in 3 of 71 consecutive patients. Immunosuppressive regimen included perioperative lymphocyte antibody therapy, cyclosporine, azathioprine and methylprednisolone. All 3 patients received cardiac allografts from donors not the same ABO blood type and developed cytomegalovirus infection (one primary phase infection and two reactivations). Death occurred in all of them. Histologic signs of both cellular and vascular rejection were found in one patient and two had pure vascular rejection. These observations support the potential role of cytomegalovirus infection and donor-recipient partial ABO blood type group incompatibility in the development of allograft vasculopathy as a short-term complication in heart transplant recipients.

A novel biochemical approach to congestive heart failure: cardiac troponin T.

BACKGROUND: The major structural characteristic of congestive heart failure is myocardial cell death. The aim of our study was to determine whether the level of cardiac troponin T, a protein specific for cardiac necrosis, was increased in patients with congestive heart failure. METHODS AND RESULTS: Plasma samples were obtained from 33 patients and 47 healthy control subjects. Quantitative determination of cardiac troponin T was achieved with a second-generation enzyme immunoassay without cross-reactivity with the skeletal muscle troponin T. The mean circulating level of cardiac troponin T was 0.140 +/- 0.439 ng/mL in patients with heart failure and 0.0002 +/- 0.001 ng/mL in the healthy controls (P =. 0001). To evaluate the relation between structural degradation and functional impairment, patients in heart failure were categorized according to their radionuclide left ventricular ejection fraction (LVEF). In the 23 patients with LVEF 45% (P =.04). There was also a negative correlation between cardiac troponin T and LVEF (R = -0.41, P =.01). CONCLUSIONS: These data show that cardiac troponin T is increased in patients with congestive heart failure and that the level parallels the severity of the disease. We conclude that cardiac troponin T is a suitable candidate-marker molecule to monitor congestive heart failure from a structural perspective.

Cytokine inhibitors in patients with heart failure and impaired functional capacity.

Cytokines are proteins with pleiotropic biological effects, but the pathophysiologic role of cytokine inhibitors in advanced cardiac disease remains unclear. We assessed the levels of tumor necrosis factor (TNF)-alpha and its soluble receptors I (sTNF-RI) and II (sTNF-RII), soluble interleukin-1 receptor antagonist (sIL-1 Ra), and interleukin-6 soluble receptor (IL-6 sR) in sera from 11 patients with severe chronic congestive heart failure (mean left ventricular ejection fraction 19 +/- 6%; mean symptom-limited oxygen consumption 13 +/- 4 ml/min per kg) and 11 healthy volunteers. The serum concentrations of TNF, sTNF-RI, and sIL-1 Ra, but not of sTNF-RII and IL-6 sR, were significantly increased in heart failure patients. Importantly, their symptom-limited oxygen consumption was strongly associated with both sTNF-RI (R = -0.68, p = 0.04) and sIL-1 Ra (R = -0.77, p = 0.01). These results suggest that cytokine inhibitors from different receptor families may be involved in functional disability, a characteristic feature in patients with severe congestive heart failure. Understanding the response of cytokine inhibitors to heart failure might have therapeutic value as interventions against cytokines become available.

Circulating cardiac troponin I in severe congestive heart failure.

BACKGROUND: Spontaneous progression of severe congestive heart failure is structurally characterized by cellular degeneration and multiple foci of myocardial cell death. The cardiac muscle isoform of troponin I is uniquely expressed in the adult human myocardium, and an increase in its circulating levels is highly indicative of myocardial injury. Accordingly, we addressed the usefulness of cardiac troponin I as a sensitive and specific molecular marker of congestive heart failure in patients with severely reduced left ventricular performance. METHODS AND RESULTS: A new generation single-step immunoenzymoluminometric assay with high analytical sensitivity was used to assess cardiac troponin I in patients with severe congestive heart failure, healthy blood donors, and hospitalized control subjects without known cardiac disease. The cardiac troponin I concentration (mean+/-SEM) was 72.1+/-15.8 pg/mL in heart failure patients and 20.4+/-3.2 and 36.5+/-5.5 pg/mL in healthy and hospitalized control subjects, respectively (P<.01 versus heart failure patients). When both control groups were considered, the mean cardiac troponin I level was 25.4+/-2.9 pg/mL (P<.01 versus heart failure patients). Creatine kinase MB mass and myoglobin concentrations remained within the normal range in all groups. CONCLUSIONS: These data (1) provide the first evidence for ongoing myofibrillar degradation and increased cardiac troponin I levels in patients with advanced heart failure and (2) show potential usefulness of cardiac troponin I as a specific and sensitive new serum marker molecule in severe congestive heart failure.

Idiopathic Cardiomyopathy.

Idiopathic cardiomyopathy is a very common cause of heart failure today. It is a diagnosis of exclusion, and careful attention should be paid to the patient history to exclude all other causes. ACE inhibitors have become the first line therapy for all classes of left ventricular dysfunction. Doses of all therapeutic drugs for CHF should be up-titrated to maximum targeted dosages. New agents are being developed that offer increasing hope for therapies that will alter the natural history of heart failure.