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Does heart transplantation confer additional benefit over medical therapy to patients who have waited > 6 months for heart transplantation?

OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.

Actuarial Analysis↗

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Adolescent↗

Altered inotropic and lusitropic responses to heart rate in conscious dogs with tachycardia-induced heart failure.

OBJECTIVES: The effects of increasing heart rate on left ventricular contraction and relaxation were examined in conscious dogs with tachycardia-induced heart failure under autonomically blocked conditions. BACKGROUND: Previous studies using isolated myocardium have shown attenuated positive inotropic responses to stimulation frequency in heart failure. However, these responses have not been well examined in intact preparations in the presence of heart failure with autonomic system blockade, where the intrinsic ventricular responses to increasing heart rate could be revealed. METHODS: Seven dogs were instrumented with a micromanometer and a conductance volume catheter. After autonomic blockade to eliminate neural reflexes, left ventricular contractile properties were quantified by the slope of the end-systolic pressure-volume relation (ventricular elastance), and left ventricular relaxation was assessed by the time constant of isovolumetric ventricular pressure decay. RESULTS: Increasing the heart rate by 60 beats/min enhanced ventricular elastance by 71 +/- 18% (mean +/- SD) and decreased end-systolic volume by 6 +/- 5% in normal hearts. In failing hearts, ventricular elastance increased by only 21 +/- 20%, and end-systolic volume did not change appreciably. Although the reduction in left ventricular end-diastolic and minimal pressures by tachycardia was smaller in the failing heart, ventricular relaxation rate remained unaltered both in the normal heart and in the failing heart. CONCLUSIONS: Under conscious but autonomically blocked conditions, effects of increasing heart rate on the failing left ventricle are characterized by a predominant attenuation of the inotropic response rather than of the lusitropic response.

Animals↗

A comparison of low versus high heart rate in patients with atrial fibrillation and advanced chronic heart failure: effects on clinical profile, neurohormones and survival.

BACKGROUND: Atrial fibrillation is common in chronic heart failure. Long-term restoration of sinus rhythm is generally unsuccessful. It may be speculated that higher heart rates are unfavorable, since this may lead to tachycardiomyopathy, but there are no data which have examined this. METHODS AND RESULTS: Seventy-seven patients with atrial fibrillation and advanced chronic heart failure, age 70 +/- 7 years, left-ventricular ejection fraction 0.23 +/- 0.08, 61% with ischemic etiology were included. Patients were dichotomized according to the median heart rate (80 bpm) at inclusion (39 patients with "low" heart rate and 38 patients with "high" heart rate). At baseline, both patient groups were remarkably comparable. After a mean follow-up of 3.3 +/- 0.9 years, mortality was comparable (62% versus 55%, p = non-significant). An independent relation was found between lower heart rate and survival, in addition to absence of hypertension, digoxin use, and higher N-ANP, dopamine, and renin levels. CONCLUSION: In the present analysis, patients with atrial fibrillation and advanced chronic heart failure with higher heart rates are comparable to those with lower heart rates. Not higher heart rates at baseline but, on the contrary, lower heart rates seem associated with a worse outcome.

Aged↗

Novel technique for isolated accessory right heart transplantation for congenital heart disease.

BACKGROUND: Our prior laboratory work has permitted adding a whole donor heart to a preserved recipient right heart, producing a heart-and-a-half preparation able to cope with pulmonary hypertension in the recipient. The experiments in the present study explore the feasibility of the converse operation: adding an isolated donor right heart to an entire preserved heart. METHODS: Eight adult mongrel dogs (4 donors and 4 recipients) were used in 4 transplant operations performed through a right thoracotomy without cardiopulmonary bypass (using side-biting control of recipient vessels). The donor heart underwent resection of the left atrium and left ventricle, leaving an isolated donor right heart. Blood supply to the donor right ventricle was preserved from the donor ascending aorta. Through a right thoracotomy, the donor right heart was transplanted in parallel to the native right heart of the recipient by using the following anastomoses: (1) donor superior vena cava to recipient superior vena cava (end-to-side anastomosis); (2) donor pulmonary artery to recipient pulmonary artery (end-to-side anastomosis); (3) donor ascending aorta to recipient aorta (through a great vessel [end-to-end anastomosis] to provide arterial inflow to donor coronary arteries). Animals were euthanized within 1 hour after completion of transplantation. RESULTS: Isolation of the right ventricle by excision of the left chambers was technically feasible. Transplantation without cardiopulmonary bypass was feasible in all cases. The isolated right heart beat well after transplantation in all animals, demonstrating sinus rhythm. Three of 4 animals were able to sustain good hemodynamics on support with epinephrine. Bleeding from the septum or aortic valve of the donor (now open to the pericardial space) was not problematic. Mean arterial pressure was 85 mm Hg (mean) at a right atrial pressure of 6 mm Hg (mean). In 2 animals the recipient superior vena cava was ligated to obligate upper body flow to pass through the accessory ventricle; hemodynamics were preserved under these circumstances. CONCLUSION: Transplantation of an isolated right heart is feasible. Such a technique has potential as a novel therapeutic alternative for obstructive or hypoplastic lesions of the right heart in human children.

Anastomosis, Surgical↗

Outcome while awaiting heart transplantation in children: a comparison of congenital heart disease and cardiomyopathy.

BACKGROUND: Outcomes for children who undergo heart transplantation differ for children with congenital heart disease as compared to those with structurally normal hearts. Similar data have not been reported for these groups of patients for the morbidity and mortality associated with waiting for a donor. We report these data. METHODS: A retrospective review was performed for all pediatric patients who were listed for heart transplantation at Stanford from 1977 to 1996, comparing mortality and major morbidity for patients with congenital heart disease and those with cardiomyopathy and structurally normal hearts. RESULTS: There were 96 patients who met study criteria, of whom 67 were successfully transplanted. The median waiting time was 23 days. Survival at 30 days was 93% and at 90 days was 81%, with no difference between groups. Major complications were identified in 38% of patients with structurally normal hearts, vs 9% of patients with congenital heart disease (p < 0.001). CONCLUSIONS: Overall mortality is similar for patients with congenital heart disease and those with structurally normal hearts while listed for heart transplantation, but patients with congenital heart disease have fewer episodes of major morbidity during this time.

Actuarial Analysis↗

Heart rate variability analysis in the assessment of autonomic function in heart failure.

Heart rate is not static, but rather changes continuously in response to physical and mental demands. In fact, an invariant heart rate is associated with disease processes such as heart failure. Heart rate variability analysis is a noninvasive technique used to quantify fluctuations in heart rate. In this article, the authors review neural control of heart rate, briefly describe heart rate variability, and summarize research data demonstrating that heart failure is associated with altered heart rate variability. In addition, the authors present evidence that heart failure patients with decreased heart rate variability are at risk for future cardiac events, heart transplantations, and death.

Baroreflex↗

Recovery kinetics of oxygen uptake and heart rate in patients with coronary artery disease and heart failure.

BACKGROUND: Patients with congestive heart failure exhibit a prolonged period of recovery to baseline levels of oxygen consumption, but the decline of heart rate during recovery from exercise has been shown to be similar to that in healthy subjects, and the results of studies on the response of ventilation in recovery have been mixed. Patients with coronary artery disease have a reduced exercise capacity, but it is unknown whether the patterns of the decline in oxygen uptake (VO2), ventilation, or heart rate are similar to those in patients with heart failure. METHODS: We performed a cardiopulmonary exercise test with a ramping protocol in 18 healthy subjects, 18 patients with coronary artery disease, 19 patients with class A or B congestive heart failure, and 19 patients with class C congestive heart failure, according to the Weber classification. Peak oxygen uptake and the kinetics of oxygen uptake, ventilation, and heart rate were calculated and expressed as the slope of a single exponential relation between VO2 levels and time during the first 3 min of recovery as y(VO2) = y0Ae(-x/t). RESULTS: A difference in time of recovery of VO2 was found only between healthy subjects and patients with more severe heart failure (class C) (p < 0.05); no significant differences were observed among any of the groups in ventilation or heart rate recovery responses. CONCLUSION: VO2 recovery time is prolonged only in the presence of more severe heart failure. The presence and degree of heart disease has no effect on ventilation or heart rate recovery time.

Coronary Disease↗

Decreased heart rate recovery in patients with heart failure: effect of fluvastatin therapy.

Heart rate recovery is the difference in heart rate at peak exercise and at a specific time interval following the onset of recovery. Attenuated heart rate recovery is an independent predictor of mortality in patients with a history of coronary artery disease. The aim of the present study was to evaluate the effect of a statin on heart rate recovery, particularly in patients with ischemic heart failure and hyperlipidemia. Twenty-nine consecutive hyperlipidemic, stable coronary artery disease patients with heart failure and 19 healthy subjects were enrolled. Heart rate recovery values at the 1st and 3rd minutes and lipid profiles of the patients were evaluated at baseline and following 3 months of treatment with fluvastatin. Compared with healthy subjects, the heart rate recovery values were significantly lower in the heart failure patients in both the 1st and 3rd minutes, respectively (31 +/- 6 versus 19 +/- 7, P < 0.0001; 66 +/- 7 versus 47 +/- 8, P < 0.0001). Heart rate recovery in the 1st and 3rd minutes increased from 19 +/- 7 to 24 +/- 9 and 47 +/- 8 to 57 +/- 11, respectively, following treatment (P < 0.001, P < 0.001). There were no significant correlations among the changes in lipid parameters or HRR in the first and third minutes in the recovery period. The results revealed an improvement in heart rate recovery in heart failure patients by fluvastatin treatment. If this association can be confirmed by other studies, it would be interesting to perform further studies into the mechanism underlying this finding.

Aged↗

[Experimental heart transplantation in dogs--preservation of isolated hearts for 36 hours by retrograde coronary sinus microperfusion].

In this study, the method of preserving isolated canine hearts for transplantation was established. The newly-developed method is named retrograde coronary sinus microperfusion technique. Canine hearts were arrested and cooled to 4 degrees C by means of normograde coronary perfusion with Collins' solution containing 10% fluorocarbon (FC) in order to avoid myocardial damage during warm ischemic time. Then, the hearts, immersed in Collins' solution, were retrogradely perfused through a coronary sinus at a rate of 60 ml/hr or 30 ml/hr with above-mentioned solution. After preservation for 36 hours, heterotopic heart transplantation was performed in an abdominal cavity of a recipient dog. The 36 hour-preserved hearts restored their cardiac beat after reperfusion with recipient blood. Histological observation did not show any abnormal findings in these preserved hearts. In order to evaluate the cardiac functions of preserved hearts for 24 to 36 hours, left ventricular end-systolic pressure-volume ratio (Emax) and end-diastolic pressure-volume relation were measured. Both were well restored in 24 hour-preserved hearts. The 36 hour-preserved hearts resulted in Emax within a satisfactory range, while end-diastolic pressure was elevated in all cases. This was markedly impaired with infusion of isoproterenol. These results strongly suggested that transplantation using 24 hour-preserved hearts could be performed well. On the other hand, the 36 hour-preserved hearts were considered to function satisfactorily under careful management after grafting. The retrograde coronary sinus microperfusion method developed here was found to be useful for a distant heart procurement.

Animals↗

[Analysis of cardiac function of discordant heart xenografts using a blood-perfused, isolated, supported heart model].

UNLABELLED: Changes in cardiac function during hyperacute rejection are not fully understood because of lack of appropriate models. In this study, a blood-perfused, isolated, supported heart model was employed for the analysis of cardiac function in discordant heart xenografts. METHODS: Experiment 1: Changes in left ventricular end-systolic pressure (LVESP) and coronary perfusion pressure (CPP) were measured for 120 min. Dry heart weight after perfusion was measured in the following 4 groups: group A; isolated rat heart perfused with blood from support rat, group B; guinea pig heart, support guinea pig, group C; guinea pig heart, support rat, and group D; guinea pig heart, support rat with cobra venom factor (CVF) pretreatment. Complement C3 of support rat serum in group C and group D was measured by single radial immunodiffusion (SRID). Experiment 2: Fifteen guinea pig hearts perfused with blood from untreated support rats were analyzed for correlation between survival time and LVESP, and CPP as well. RESULTS: In groups A and B, LVESP and CPP was stable up to 120 min. In group C, 4 out of 6 hearts were stopped beating within 120 min. The difference between LVESP at 10 min in group C and that in group B was not obtained, possibly due to high variation of values in group C, whereas CPP in group C was higher than that in group B (p < 0.05). In group D, CVF was shown to deplete complement C3. Group D showed constant LVESP and CPP, similar to non-xenograft groups. Dry heart weight of group C was larger than those of group B and D. There were positive correlations between survival time and LVESP at 10 min, and increasing rate of LVESP after 10 min as well. A negative correlation between survival time and CPP at 10 min was observed, while no correlation was obtained between survival time and increasing rate of CPP after 10 min. CONCLUSIONS: 1) Decreases in LVESP and increases in CPP in xenograft group are considered to be due to hyperacute rejection. 2) These changes can be abolished by depletion of C3. 3) Guinea pig hearts can work well in xenograft condition as in allograft condition in certain circumstances, i.e. depletion of C3. 4) The blood-perfused, isolated, supported heart model is useful for the analysis of cardiac function in discordant xenografts.

Animals↗

Comparison of four methods of assessing heart rate variability in patients with heart failure.

BACKGROUND: Heart rate variability reflects autonomic tone and is used to assess progression and prognosis in a variety of illnesses. However, multiple heart rate variability methods exist and are not necessarily equivalent. OBJECTIVES: To compare four methods of heart rate variability in heart failure patients and healthy subjects. METHODS: Twenty-four-hour Holter recordings were obtained in 50 heart failure patients and 50 age- and gender-matched control patients. From these recordings, heart rate variability was assessed by histograms, standard deviation, Poincaré plots, and spectral analysis. RESULTS: For R-R interval histograms, standard deviation, and Poincaré plots, diminished heart rate variability was identified in 65% to 100% of heart failure patients versus 0% to 8% of controls. Agreement among these tests ranged from 69% to 96%. Spectral values varied greatly over the recording period, even in the same subject, possibly because of variations in activity. Only 16% of heart failure patients had spectral values that were identified as abnormal. Agreement between spectral analysis and the other methods ranged between 58% and 67%. CONCLUSIONS: Heart rate variability assessed over a 24-hour period with different techniques yields similar but not identical results. Heart rate variability assessed from spectral analysis of short periods of data varied markedly in a 24-hour period and should not be compared with measures obtained from 24-hour methods. Standardization of subject activity and recording time is necessary for comparison of spectral analysis of brief periods. Further research is required to determine if differences among methods assessing 24-hour heart rate variability yield complementary information.

Arrhythmias, Cardiac↗