Current status of heart assist and replacement in Taiwan

The first clinical application of intraaortic balloon pumps (IABP) in Taiwan was in 1976 to treat post-cardiotomy cardiogenic shock. It is now the most commonly used circulatory assist. From 1991 to 1995, 186 patients received IABP support with an overall mortality rate 41.9%. The male patients had the best survival rate, 67%, after coronary artery bypass grafting. The first extracorporeal membrane oxygenation (ECMO) was in 1987 to treat intractable heart failure caused by severe acute rejection after heart transplantation. Because of poor outcome, patients only received ECMO sporadically during the past years. From November 1994 to November 1995, 30 patients received ECMO support with 50% of them eventually weaned from ECMO and 27% discharged. For short-term support or emergency rescue, ECMO was a good choice. When long-term support was required, the ventricular assist device (VAD) was a more suitable assist. One patient who received Thermedics VAD developed right heart failure and finally died of sepsis and multiple organ failure. VAD should be implanted before the secondary organ failure. The first successful clinical heart transplantation in Taiwan was performed on July 17, 1987. From 1991 to 1995, 102 patients underwent heart transplantation. The operative mortality was 3.9%, and the 1 and 5 year actuarial survival rates were 86 +/- 3% and 77 +/- 5%, respectively. To improve the success rate of clinical heart transplantation, organ donation should be encouraged.     

Ambulatory therapy of multiple myeloma with vincristine, adriamycin and dexamethasone

BACKGROUND AND OBJECTIVE: If multiple myeloma (MM) progresses in patients after chemotherapy with alkylating agents, the combination of vincristine, adriamycin and dexamethasone (VAD) can achieve a response in 40-70% of cases. Because of its low toxicity for haematopoetic stem-cells this form of chemotherapy is often undertaken before high-dose blood stem-cell transplantation. It was the objective of this study to examine effectiveness and complications of ambulant VAD treatment. PATIENTS AND METHODS: Within four years VAD chemotherapy was given to 62 ambulant MM patients, administered by microprocessor-regulated pumps via intravenously polyurethane catheters with a safety valve. Response to treatment, treatment-associated complications and infections were documented prospectively and analysed. RESULTS: VAD treatment achieved tumour reduction of more than 25% in 50 of 62 patients. This treatment had to be discontinued in two of 192 pump-infusions because of irreversible catheter occlusion. Eight patients were hospitalised because of infections and two for noninfectious complications. Severe infectious complications (> or = WHO grade III) occurred in 4% of treatment cycles. CONCLUSION: VAD chemotherapy can be performed with a low rate of infection in ambulant patients despite the need for prolonged intravenously infusion of the drugs. But to avoid complications by intravenously catheters, random prospective tests should first be done with oral alkylating agents.     

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.     

Restrictive criteria for heart transplantation candidacy maximize survival of patients with advanced heart failure

BACKGROUND: The shortage of organ donors and the amelioration of medical management of advanced heart failure mandate strict selection of heart transplant candidates on the basis of the need and probability of success of transplantation, with the aim of maximizing survival of patients with advanced heart failure, both with and without transplantation. This study analyzes the impact of restricting the criteria for heart transplantation candidacy on the outcome of patients with advanced heart failure referred for transplantation. METHODS: Survival and freedom from major cardiac events (death, resuscitated cardiac arrest, transplantation while supported with inotropes or mechanical devices) were compared between patients listed during 1990 to 1991, when standard criteria were applied (group 1, n = 118), and patients listed during 1993 to 1994, when only patients requiring continuous/recurrent intravenous inotrope therapy in spite of optimized oral medications and outpatients showing actual progression of the disease were admitted to the waiting list (group 2, n = 88). Survival and freedom from cardiac events (defined as above plus listing in urgent status) were also calculated in stable outpatients evaluated in 1993 to 1994, who were potential heart transplant candidates according to standard criteria but were not listed because of restrictive criteria (group 3, n = 52, New York Heart Association functional class > or = III, mean echocardiographic ejection fraction 0.22 +/- 0.05, mean peak oxygen consumption 12.3 +/- 1.5 ml/kg/min, mean follow-up 19 +/- 10 months). RESULTS: Thirty-one percent, 40%, and 50% of group 1 patients versus 58%, 65%, and 77% of group 2 patients underwent transplantation within 3, 6, and 12 months after listing (p < 0.0007). The 1- and 2-year survival rates after listing were 80% and 71% in group 1 versus 85% and 84% in group 2 (p < 0.0001). Freedom from death/urgent transplantation was lower in group 2 than in group 1 (55% and 48% versus 72% and 59% at 6 and 12 months, respectively; p < 0.0001). In patients undergoing transplantation, the postoperative survival rate was similar (87% and 91% at 2 years in group 1 and group 2, respectively). Two years after heart transplantation candidacy was denied, 86% of group 3 patients were alive, and 74% were event-free. CONCLUSIONS: Restricting the admissions to the waiting list to patients with refractory/progressive heart failure improved survival rates after listing by increasing the probability to undergo transplantation in a short time. Selection of most severely ill candidates did not affect postoperative survival. Survival and freedom from cardiac events were good in patients with advanced but stable heart failure, in spite of their severe functional limitation. Thus restrictive criteria for heart transplantation candidacy allows maximal survival benefit from both medical therapy and transplantation.     

The pharmacokinetics and steady state pharmacodynamics of mivacurium in children

BACKGROUND: The main causes of allograft failure after cardiac transplantation are primary graft dysfunction, intractable acute rejection, and coronary graft disease. Despite the important progress in the last several years in graft preservation, surgical techniques, immunosuppression, and treatment of coronary graft disease, retransplantation in selected cases is the only way to achieve long-term recipient survival. METHODS: We compare here in a case-control study 24 retransplantations with 47 first transplants in patients matched for date of transplantation. RESULTS: Between 1973 and 1996, 1,063 patients underwent cardiac transplantation in our institution. In this cohort, 22 patients had a total of 24 retransplantations (2 second-time retransplantations). The causes of retransplantations were primary graft failure (n=4), acute rejection (n=7), coronary graft disease (n=11), and miscellaneous (n=2). Survival at 1 and 5 years of patients with retransplantations is 45.5% and 31.2%, and survival of control patients is 59.4% and 38.8% (p=0.07). An interval between first transplantation and retransplantation shorter (n=11) or longer (n=13) than 1 year is associated with a 1-year survival of 27.3% and 61.5% and a 4-year survival of 27.3% and 46%, respectively (not significant). Intervals shorter than 1 year between first transplantation and retransplantation were exclusively secondary to primary graft failure or intractable acute rejection. CONCLUSIONS: In the face of lack of donor grafts, these and other data indicate that retransplantation should be considered cautiously, especially when the interval between the first transplantation and retransplantation is short.     

The continuing evolution of mechanical ventricular assistance

A great number of patients suffer and die of the sequelae of acute and chronic heart failure each year. Although advances in medical and surgical therapy have benefited many of these patients, most have disease that is refractory to any definitive therapy. For these patients cardiac transplantation is the only remaining hope. Unfortunately, because of the increasing demand for donor organs in the face of a fixed and limited supply, this option is available to only a small percentage of these patients. Even in patients accepted for transplantation, a significant waiting list mortality has been observed. A variety of VADs have been developed since the first successful case of mechanical cardiac assistance more than 30 years ago. These devices differ in basic mechanical function, method of insertion, and degree of implantability and thus have different indications and potential applications. Whereas the intraaortic balloon pump and centrifugal pumps are effective short-term support modalities, extracorporeal and implantable pulsatile devices have been used successfully for long-term support of patients with reversible and nonreversible cardiac failure. Although these pumps have most commonly been used as bridges to transplantation, increasing clinical experience has supported the notion of long-term mechanical assistance as a definitive therapy for patients with end-stage heart disease. Although complications, particularly infection and thromboembolism, pose significant challenges and long-term device reliability remains to be fully determined, available implantable devices appear to be capable of providing effective long-term support. As data are obtained from currently ongoing trials comparing VAD support with medical therapy for end-stage heart failure, ethical and economic issues will assume increasing importance.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

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.     

Expression of collagenase and stromelysin in skin fibroblasts from recessive dystrophic epidermolysis bullosa

OBJECTIVE: To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. PATIENTS AND DESIGN: 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. METHODS: Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. RESULTS: Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. CONCLUSION: Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.     

Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.     

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.     

Local relation between oxidative metabolism and perfusion in leg muscles of patients with heart failure studied by magnetic resonance imaging and spectroscopy

BACKGROUND: We studied the local relation of muscle perfusion and metabolism in patients with severe chronic heart failure. Alterations of skeletal muscle blood flow and oxidative capacity contribute to exercise intolerance in these patients. The interdependence of both parameters has often been questioned. METHODS AND RESULTS: With the use of nuclear magnetic resonance, we quantified leg and muscle perfusion during reactive hyperemia in 7 patients with heart failure (New York Heart Association class III and IV) and 7 age-matched control subjects from the difference in longitudinal relaxation rate (1/T1). By using 31P nuclear magnetic resonance spectroscopy, we assessed oxidative metabolism from the creatine rephosphorylation time constant after a short ischemic exercise. Phosphocreatine recovery is slowed (74.6 +/- 11.3 vs 49.9 +/- 13.9 seconds, p = .002) and reactive hyperemic flow is reduced (48.5 +/- 24.9 vs 113 +/- 30.4 mL/100 mL per minute, p = .0005). CONCLUSIONS: By using a totally noninvasive protocol, we demonstrated that reactive hyperemic flow correlates with oxidative capacity in calf muscles from patients with heart failure, showing that exercise performance and local circulatory dysfunction are decreased in parallel in severe heart failure.     

Infections during extended circulatory support: University of Alabama at Birmingham experience 1989 to 1994

BACKGROUND: The University of Alabama at Birmingham experience with investigational ventricular assist devices (VADs) used as a bridge to transplantation has increased over the past several years; it now includes 27 VAD implantations with 13 VAD runs lasting for extended periods (ie, > 30 days). A review of complications experienced by patients during extended VAD runs is warranted before the further development and testing of chronically implanted mechanical circulatory support devices. METHODS: This study focuses on the infectious complications of extended VAD support; it includes 13 patients who were supported by either a Thoratec or HeartMate VAD for longer than 30 days pending cardiac transplantation. Infection was defined as any positive culture. The infections were classed according to site and severity as follows: class I were patient-related non-blood-borne infections, class II were blood-borne infections, class III were VAD percutaneous site infections, and class IV were infections of the blood-contacting surfaces or intracorporeal components of the VAD. RESULTS: The 8 Thoratec and 5 HeartMate patients were supported for a total of 1,648 days with a range of 33 to 279 days per patient. Every patient had at least one infection; however, there were 6 patients who had no class II or IV infections during the period of support. One of these 6 patients died of a stroke, whereas the other 5 patients survived VAD support. No trends were identified for a change in the incidence of bacterial compared with fungal infections during the course of VAD support. There was no trend for a greater number of infections in patients who died during VAD support compared with those who survived. Neither class II nor IV infections precluded transplantation. Three patients died during VAD support; 1 died as a direct consequence of fungal infection. Eight patients received transplants. One patient had an unanticipated recovery of cardiac function and the VAD was removed. Support in 1 patient is ongoing. CONCLUSIONS: Infection during VAD support pending cardiac transplantation is an important cause of morbidity and mortality in patients maintained for longer than 30 days by circulatory assist. Infectious complications will probably be a prominent component of the risk associated with the use of chronically implanted mechanical circulatory assist devices and will likely have an important effect on the quality of life experienced by these patients.     

Sex and left ventricular volume predict survival in heart transplant candidates with peak oxygen uptake between ten and fourteen milliliters per kilogram per minute

BACKGROUND: The purpose of this study was to identify predictors of survival in patients referred for heart transplantation evaluation who had a peak oxygen uptake of 10 to 14 ml/kg/min measured during initial cardiopulmonary exercise testing. METHODS: Seventy-two patients were identified retrospectively from a database of 304 patients who underwent heart transplantation evaluations at our center from 1985 to 1995. All 72 patients underwent right-sided heart catheterization and first-pass right and left ventricular radionuclide ventriculography during cardiopulmonary exercise testing. RESULTS: There were 14 women and 58 men in the study (mean age 52 +/- 9 years, 80% male, 79% New York Heart Association class III/IV, left ventricular ejection fraction of 0.24 +/- 0.9, and left ventricular end-diastolic volume index of 144 +/- 59 ml). During a mean follow-up of 19 +/- 23 months, two women and 32 men (47%) reached the combined end point of death (n = 20) or pretransplantation admission for inotropic or mechanical support (n = 14). For the entire cohort, analysis of clinical, ventriculographic, and exercise parameters identified female sex, younger age, and age/ sex-adjusted peak oxygen uptake as independent predictors of survival. In men only, age, left ventricular end-diastolic volume index, and age/sex adjusted peak oxygen uptake were independent predictors of survival. CONCLUSIONS: Among patients referred for heart transplantation evaluation with a peak oxygen uptake between 10 to 14 ml/kg/min, younger age, female sex, and higher age/ sex-adjusted peak oxygen uptake predict longer survival to the combined end point of death or pretransplantation admission for inotropic or mechanical support. These measures may be useful in additional risk stratification of such patients.     

Improvement in quality of life in patients with heart failure who undergo transplantation

BACKGROUND: Very few studies have examined quality of life longitudinally in heart failure patients from before or after heart transplantation. The purpose of this study was to compare quality of life of patients with heart failure at the time of listing for a heart transplant with that 1 year after the operation. Major dimensions of quality of life measured in this study were health, physical and emotional functioning, and psychosocial functioning. METHODS: A convenience sample of 148 patients (80% male and mean age 52 years) was recruited from a midwestern and southern medical center. Data were collected from chart review and six patient-completed instruments: the Heart Transplant Symptom Checklist, Sickness Impact Profile, Heart Transplant Stressor Scale, Jalowiec Coping Scale, Quality of Life Index, and Rating Question Form. Informed consent was obtained, and patients who agreed to participate in the study completed the booklet of self-administered instruments. Statistical analyses included frequencies, measures of central tendency, paired t-tests, and Wilcoxon signed-ranks tests. RESULTS: Total symptom distress decreased significantly overall from before to after heart transplantation (before = 0.19 versus after = 0.15, p < 0.0001). Patients rated themselves as having significantly poorer health while listed as a heart transplant candidate than at 1 year after surgery (before = 4.5 versus after = 7.5, p < 0.0001). Although the overall level of functional disability was fairly low before and 1 year after transplantation, patients still reported significant improvement after surgery (before = 0.21 versus 1 year after = 0.13, p < 0.0001). No significant differences were found in total stress, which was low to moderate (before = .026 versus 1 year after = 0.26, p = not significant), coping use (before = 0.48 versus 1 year after = 0.48, p = not significant), or coping effectiveness (before = 0.40) versus 1 year after = 0.42, p = not significant), from before to 1 year after heart transplantation. However, changes in types of symptoms, functional disability, stressors, and coping were noted over time. Overall satisfaction with life, which was fairly high at both time periods, increased significantly from the time of listing for a transplant to 1 year after surgery (before = 0.72 versus 1 year after = 0.82, p <0.0001), and overall quality of life improved significantly from before to after heart transplantation (before = 5.5 versus after = 7.8, p < 0.0001). CONCLUSIONS: End-stage heart failure patients had improved quality of life from before to 1 year after heart transplant due to less total symptom distress, better health perception, better overall functional status, more overall satisfaction with life, and improved overall quality of life. However, post-transplant patients still experienced some symptom distress, functional disability, and stress, but were coping well.     

UVB induces atypical melanocytic lesions and melanoma in human skin

OBJECTIVES: The purpose of the present study was to examine the expression of the endothelial-type nitric oxide synthase (NOS III) and the inducible-type NOS (NOS II) in human myocardium and their regulation in heart failure from patients with different etiologies. BACKGROUND: In heart failure, plasma levels of nitrates were found to be elevated. However, data on myocardial NOS expression in heart failure are conflicting. METHODS: Using RNase protection analysis and Western blotting, the expression of NOS III and NOS II was investigated in ventricular myocardium from nonfailing (NF) hearts (n=5) and from failing hearts of patients with idiopathic dilated cardiomyopathy (dCMP, n=14), ischemic cardiomyopathy (iCMP, n=9) or postmyocarditis cardiomyopathy (mCMP, n=7). Furthermore, immunohistochemical studies were performed to localize NOS III and NOS II within the ventricular myocardium. RESULTS: In failing human hearts, NOS III mRNA levels were increased to 180% in dCMP, 200% in iCMP and to 210% in mCMP as compared to NF hearts. Similarly, in Western blots (using constitutively expressed beta-tubulin as a reference) NOS III protein expression was increased about twofold in failing compared to NF hearts. Immunohistochemical studies with a selective antibody to NOS III showed no obvious differences in the staining of the endothelium of cardiac blood vessels from NF and failing human hearts. However, NOS III-immunoreactivity in cardiomyocytes was significantly more intense in failing compared to NF hearts. Low expression of NOS II mRNA was detected in only 2 of 30 failing human hearts and was not found in NF hearts. Inducible-type NOS protein was undetectable in either group. CONCLUSIONS: We conclude that the increased NOS III expression in the ventricular myocardium of failing human hearts may contribute to the contractile dysfunction observed in heart failure and/or may play a role in morphologic alterations such as hypertrophy and apoptosis of cardiomyocytes.     

Prognostic value of plasma catecholamines, plasma renin activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure: comparison with clinical evaluation, ejection fraction, and exercise capacity

Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest and during maximal exercise in congestive heart failure, and to compare it to clinical and exercise test variables and left ventricular ejection fraction. One hundred ninety consecutive patients (136 men and 54 women; median age, 66 years; range, 42-75 years) with clinically stable congestive heart failure were included. Sixteen patients were in New York Heart Association class I, 87 in class II, 83 in class III, and 4 in class IV. Left ventricular ejection fraction was 0.30 (range, 0.06-0.74). Total survival after 1 year was 79%, after 2 years, it was 68%. Prognostic variables at univariate analysis were: plasma noradrenaline at rest (P < .0001), plasma adrenaline at rest (P = .049), and atrial natriuretic peptide at rest (P = .016). During exercise, plasma catecholamines and plasma atrial natriuretic peptide increased significantly; the change, however, was not related to survival. Six variables carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exercise < or = 35 min-1 (P < .0001), serum creatinine > 121 mumol/L (P = .004), and serum urea > 7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase, however, is not related to mortality. Plasma noradrenaline at rest contributes with further prognostic information despite knowledge of clinical and exercise variables and was the only neurohormonal variable with independent, significant prognostic information on survival.     

Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles

Plasma levels of erythropoietin (mU/ml) were measured in patients with congestive heart failure (CHF) (n = 108) and in a control group of normal subjects (n = 45). In normal subjects, plasma levels of erythropoietin were 1.9 +/- 0.2. In patients with CHF, plasma levels of erythropoietin increased progressively according to New York Heart Association (NYHA) class (I: 1.4 +/- 0.2, n = 28; II: 5.4 +/- 0.8, n = 27; III: 9.6 +/- 2, n = 32; IV: 34 +/- 8, n = 21; F = 57.7, p < 0.001) and were significantly higher in NYHA classes II, III, and IV than in normal subjects. Plasma erythropoietin significantly decreased (from 43 +/- 14 to 12 +/- 3 mU/ml, p < 0.01) in patients with severe CHF (n = 9) when enalapril (20 mg/day administered orally) was added to long-term treatment for 3 weeks. Finally, in a subgroup of patients with NYHA class IV CHF (n = 9) and high plasma erythropoietin levels (37 +/- 9 mU/ml), packed red blood cell volume, assessed by the iodine-125-albumin dilution method, was higher than that in normal subjects (n = 11) (2,616 +/- 235 vs 2,028 +/- 119 ml, p < 0.05). The present study demonstrates that plasma erythropoietin levels are elevated in a large cohort of patients with CHF of varying etiology, and that this increase is related to the progression of the disease. The increase in circulating erythropoietin is associated with augmented packed red blood cell volume in patients with severe CHF. These results suggest a participation of erythropoietin in the complex neurohormonal response that occurs in CHF.     

Molecular executors of cell death--differential intrarenal expression of Fas ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of human renal allografts

BACKGROUND: Changes in peripheral thyroid hormone concentration and metabolism can occur in euthyroid patients suffering from severe non-thyroidal illnesses. Recently, sick euthyroid syndrome has been reported in patients suffering from advanced heart failure. AIM: This study was to evaluate prospectively the presence and pathophysiological implications of sick euthyroid syndrome in moderate-to-severe chronic heart failure patients. METHODS: The study population were 199 chronic heart failure patients admitted over a 2-year period to our heart failure unit for assessment of cardiac transplantation. They were closely followed up with clinical and instrumental examinations (including clinical, hormonal, nutritional and cardiac function evaluations). Sick euthyroid syndrome was defined as a serum total triiodothyronine value of less than the lowest normal limit (< 1.23 nmol.l-1) in the presence of a normal serum thyroid stimulating hormone concentration. RESULTS: Sick euthyroid syndrome was found in 36/199 patients (18%). According to the New York Heart Association (NYHA) classification of severity of heart failure, sick euthyroid syndrome patients appear in higher NYHA classes (31% of classes III and IV, vs 7% of class I and II). Such patients also weigh less and are more frequently malnourished. Alterations in cardiac index, ventricular filling pressures, functional impairment, and the liver function parameters, were more significant in sick euthyroid syndrome than in non-sick euthyroid syndrome patients. Serum norepinephrine and atrial natriuretic factor were significantly higher, and insulin significantly lower in the sick euthyroid syndrome group. During follow-up, deaths were significantly more frequent in sick euthyroid syndrome patients (13/27, 48%) than in non-sick euthyroid syndrome (30/141, 21%; P < 0.005). In six sick euthyroid syndrome patients who underwent heart transplantation, mean total triiodothyronine values increased from 0.9 +/- 0.1 before to 1.96 +/- 0.3 nmol.l(-1)post-transplantation (P < 0.05). CONCLUSIONS: In a large and representative population of patients with moderate-to-severe heart failure, sick euthyroid syndrome shows a prevalence of 18%. Its occurrence was related to the degree of functional cardiac impairment, but was not an independent negative prognostic factor. Preliminary results indicate that heart transplantation is associated with reversibility of sick euthyroid syndrome.     

Exercise-related ventilatory abnormalities and survival in congestive heart failure

This retrospective study of 104 New York Heart Association class 1 to 4 heart failure patients undergoing exercise stress testing with gas exchange analysis demonstrated that the ventilatory equivalent for carbon dioxide at anaerobic threshold is useful in determining prognosis in patients with severe congestive heart failure, particularly when used in combination with peak exercise oxygen consumption. A ventilatory equivalent for carbon dioxide >50 and peak oxygen consumption < or =15.0 ml/kg/min defines a very high-risk patient group who should be prioritized for transplantation.