ECG diagnosis of native heart ventricular tachycardia in a heterotopic heart transplant recipient.
A case is reported of haemodynamic collapse in a 51 year old male heterotopic heart transplant recipient caused by native heart ventricular tachycardia. An accurate diagnosis was made by selective right and left sided electrocardiography. Synchronised electrical cardioversion of the native heart (200 J) resulted in restoration of sinus rhythm with prompt relief of symptoms and amelioration of the clinical situation. (+info
Reversal of severe pulmonary hypertension with beta blockade in a patient with end stage left ventricular failure.
A 52 year old man with severe chronic left ventricular failure (New York Heart Association class IV) was considered unsuitable for cardiac transplantation because of high and irreversible pulmonary vascular resistance (PVR). In an attempt to produce symptomatic improvement, metoprolol was cautiously introduced, initially at 6.25 mg twice daily. This was slowly increased to 50 mg twice daily over a two month period and continued thereafter. After four months of treatment the patient's symptoms had improved dramatically. His exercise tolerance had increased and diuretic requirements reduced to frusemide 160 mg/day only. Assessment of right heart pressures was repeated and, other than a drop in resting heart rate, there was little change in his pulmonary artery pressure or PVR. His right heart pressures were reassessed showing a pronounced reduction in pulmonary artery pressure and a significant reduction in PVR, which fell further with inhaled oxygen and sublingual nitrates. He was then accepted onto the active waiting list for cardiac transplantation. A possible mechanism of action was investigated by assessing responses to beta agonists during treatment. Not only was there pronounced improvement in PVR but it was also demonstrated that beta receptor subtype cross-regulation may have contributed to the mechanism of benefit. (+info
Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung, and bone marrow transplant recipients as determined by nucleic acid sequence-based amplification.
Human cytomegalovirus (HCMV) infection was monitored retrospectively by qualitative determination of pp67 mRNA (a late viral transcript) by nucleic acid sequence-based amplification (NASBA) in a series of 50 transplant recipients, including 26 solid-organ (11 heart and 15 lung) transplant recipients (SOTRs) and 24 bone marrow transplant recipients (BMTRs). NASBA results were compared with those obtained by prospective quantitation of HCMV viremia and antigenemia and retrospective quantitation of DNA in leukocytes (leukoDNAemia). On the whole, 29 patients were NASBA positive, whereas 10 were NASBA negative, and the blood of 11 patients remained HCMV negative. NASBA detected HCMV infection before quantitation of viremia did but after quantitation of leukoDNAemia and antigenemia did. In NASBA-positive blood samples, median levels of viremia, antigenemia, and leukoDNAemia were significantly higher than the relevant levels detected in NASBA-negative HCMV-positive blood samples. By using the quantitation of leukoDNAemia as the "gold standard," the analytical sensitivity (47.3%), as well as the negative predictive value (68. 3%), of NASBA for the diagnosis of HCMV infection intermediate between that of antigenemia quantitation (analytical sensitivity, 72. 3%) and that of viremia quantitation (analytical sensitivity, 28.7%), while the specificity and the positive predictive value were high (90 to 100%). However, with respect to the clinically relevant antigenemia cutoff of >/=100 used in this study for the initiation of preemptive therapy in SOTRs with reactivated HCMV infection, the clinical sensitivity of NASBA reached 100%, with a specificity of 68. 9%. Upon the initiation of antigenemia quantitation-guided treatment, the actual median antigenemia level was 158 (range, 124 to 580) in SOTRs who had reactivated infection and who presented with NASBA positivity 3.5 +/- 2.6 days in advance and 13.5 (range, 1 to 270) in the group that included BMTRs and SOTRs who had primary infection (in whom treatment was initiated upon the first confirmation of detection of HCMV in blood) and who presented with NASBA positivity 2.0 +/- 5.1 days later. Following antiviral treatment, the durations of the presence of antigenemia and pp67 mRNA in blood were found to be similar. In conclusion, monitoring of the expression of HCMV pp67 mRNA appears to be a promising, well-standardized tool for determination of the need for the initiation and termination of preemptive therapy. Its overall clinical impact should be analyzed in future prospective studies. (+info
Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure.
OBJECTIVES: We studied whether direct assessment of the hemodynamic response to exercise could improve the prognostic evaluation of patients with heart failure (HF) and identify those in whom the main cause of the reduced functional capacity is related to extracardiac factors. BACKGROUND: Peak exercise oxygen consumption (VO2) is one of the main prognostic variables in patients with HF, but it is influenced also by many extracardiac factors. METHODS: Bicycle cardiopulmonary exercise testing with hemodynamic monitoring was performed, in addition to clinical evaluation and radionuclide ventriculography, in 219 consecutive patients with chronic HF (left ventricular ejection fraction, 22 +/- 7%; peak VO2, 14.2 +/- 4.4 ml/kg/min). RESULTS: During a follow-up of 19 +/- 25 months, 32 patients died and 6 underwent urgent transplantation with a 71% cumulative major event-free 2-year survival. Peak exercise stroke work index (SWI) was the most powerful prognostic variable selected by Cox multivariate analysis, followed by serum sodium and left ventricular ejection fraction, for one-year survival, and peak VO2 and serum sodium for two-year survival. Two-year survival was 54% in the patients with peak exercise SWI < or = 30 g x m/m2 versus 91% in those with a SWI >30 g x m/m2 (p < 0.0001). A significant percentage of patients (41%) had a normal cardiac output response to exercise with an excellent two-year survival (87% vs. 58% in the others) despite a relatively low peak VO2 (15.1 +/- 4.7 ml/kg/min). CONCLUSIONS: Direct assessment of exercise hemodynamics in patients with HF provides additive independent prognostic information, compared to traditional noninvasive data. (+info
T cell repertoire alterations of vascularized xenografts.
The role of T cells in the rejection of vascularized xenografts has been little explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterations in molecular interactions could impair the T cell response. Because the analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipients treated with a combination of cobra venom factor and cyclosporin A (CsA), to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rejected xenografts, compared with allografts. After withdrawal of CsA (on day 40), the analysis of V beta family expression and corresponding complementarity-determining region 3 lengths in rejected xenografts revealed a Gaussian pattern, in contrast to a much more restricted pattern in rejected allografts (p = 0.002), suggesting that, after withdrawal of CsA, all the underrepresented T cell clones are rapidly expanded in xenografts. These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high number of T cells, the rapid expression of markers of activation (IL-2 receptor alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts. Taken together, these results suggest that the intensity and diversity of the T cell response to xenografts could be stronger than the response to allografts in vivo. (+info
Sympathetic rhythmicity in cardiac transplant recipients.
BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects. (+info
High and low pulmonary vascular resistance in heart transplant candidates. A 5-year follow-up after heart transplantation shows continuous reduction in resistance and no difference in complication rate.
BACKGROUND: In heart transplantation candidates, high pulmonary vascular resistance has been found to decrease promptly after heart transplantation without any further reduction during follow-up. Pulmonary hypertension has been described as associated with an increased peri- and postoperative complication rate and mortality. This study describes the evolution of pulmonary vascular resistance and the outcome for patients during 5 years following heart transplantation. METHODS AND RESULTS: Haemodynamic data, complication rate and mortality have been analysed during 5-year follow-up in all patients (n = 80) who were heart transplanted at Sahlgrenska University Hospital from 1988 through 1990. We found a significant and continuous reduction in pulmonary vascular resistance both in patients with a pre-operative high (> 3 Wood Units; n = 36), but reversible on nitroprusside, and pre-operative low (< or = 3 Wood Units; n = 44) pulmonary vascular resistance. A multivariate analysis showed that a pre-operative high mean pulmonary artery and low mean pulmonary capillary wedge pressure predicted the decline in pulmonary vascular resistance during 5 years after heart transplantation. The need for a postoperative assist device, complication rate, and early and late mortality were independent of the pre-operative level of pulmonary vascular resistance. CONCLUSIONS: A continuous reduction in pulmonary vascular resistance during 5 years following heart transplantation was found in patients with both high, but reversible, and low pre-operative resistance levels. The outcome and survival were independent of the pre-operative pulmonary vascular resistance level. (+info
Incidence and clinical relevance of coronary calcification detected by electron beam computed tomography in heart transplant recipients.
BACKGROUND: Patients treated by cardiac transplantation who survive beyond one year are at significant risk from fatal coronary artery disease. The development of coronary artery calcification in these patients is discussed and methods available to detect it are reviewed. OBJECTIVES: To assess the clinical importance of coronary artery calcium in heart transplant recipients. METHODS: In a cohort of 102 cardiac transplant recipients, electron beam computed tomography was used to measure calcium in the coronary arterial wall 63 days to 9.1 years (median 4.6 years) after transplantation. The results were compared with angiographic findings and with conventional coronary disease risk factors. The patients were followed for a mean of 2.12 years (1.2-4.02 years) to assess the relationship between these findings and future cardiac events. RESULTS: Forty-one (40.2%) had a stenosis of > 24% in one or more major coronary artery at angiography. Forty-six (45%) had a coronary calcium score > 0. The absence of calcium had a negative predictive value with respect to angiographic disease in any vessels of 87.5%. Logistic regression revealed that dyslipidaemia, systemic hypertension and organ ischaemic time were significant predictors of calcification. At follow-up, both an abnormal coronary angiogram and coronary calcium were found to be the only significant predictors of late events. Multivariate analysis suggested that the detection of coronary calcium did not offer any additional predictive information over that provided by the angiogram itself. CONCLUSION: Electron beam computed tomography is well suited to the assessment of calcium in the coronary arteries of heart transplant recipients, although the mechanisms of this calcification remain poorly understood. Calcium is detected more frequently than would be suggested by studies using intravascular ultrasound. It is associated with the presence of angiographic disease, and with some conventional risk factors for coronary disease. At follow-up the presence of coronary calcium was associated with an adverse clinical outcome, as it is in conventional ischaemic heart disease. (+info