670
Ventricular arrhythmia and long-term survival with maintenance dialysis SIR,-Sforzini
et
all concluded that ventricular ectopy does
not
predict mortality in dialysis patients. Since our experience in a study of similar size showed an important impact of arrhythmia,2 we reanalysed the data of Sforzini et al. It seems clear that ventricular premature beats did represent an important univariate predictor (p=0047), but were a non-significant covariable in their multivariate analysis. In their group with higher levels of ventricular arrhythmia (Lown grade 4), the univariate probability level of 0-052 would reduce to 0-025 if one additional patient had died during the study, reflecting a small sample size in this subgroup. In the earlier report of the Gruppo Emodialisi, patients on anti-arrhythmic agents were excluded even if stable at the time of entry.3 Subsequently a small number of individuals required anti-arrhythmic agents (9 patients, 55 % mortality at 4 years).Since we did not exclude patients taking cardioactive drugs, we were able to study a larger group (65 patients, 29% first-year mortality), with results that did achieve statistical significance.2 Another instance of study group size differences occurred with cardiac ischaemic disease (18 patients vs 65 in our report). Efforts to determine impact of ventricular ectopy in the smaller group would again be thwarted by an inadequate number of observations. We did find a highly significant impact on survival for ventricular ectopy in patients with ischaemic heart disease (p < 0-005). An additional concern is whether the prevalence of ventricular arrhythmias is higher in the group over 55 years of age. Such a skewed distribution of cardiac complications in the older patients would, combined with small sample size, contribute to advanced age rather than ventricular ectopy emerging as the apparent critical risk factor in the multivariate analysis. The clinical lessons from Sforzini et aP include: (1) high-risk cardiac patients on dialysis have higher mortality than low-risk patients, (2) older patients on dialysis have a higher prevalence of cardiac problems than younger patients; and (3) there exists a low-risk group with a mortality of only 7% at 4 years, a group that would not benefit from monitoring because ventricular arrhythmias are rare. We feel that these valid observations do not effectively contradict the relation between high-grade ventricular arrhythmia and cardiac mortality found in both dialysis and non-dialysis
settings. John Cook Renal Unit, Joslin Diabetes Center,
Nephrology Division, Deaconess Hospital, Boston, Massachusetts 02215, USA
LARRY A. WEINRAUCH RAY E. GLEASON JOHN A. D’ELIA
S, Latini R, Mingardi G, et al. Ventncular arrhythmias and four-year mortality in haemodialysis patients. Lancet 1992, 339: 212-13 2. D’Elia JA, Weinrauch LA, Gleason RE, et al. Application of the ambulatory 24-hour electrocardiogram in the prediction of cardiac death in dialysis patients Arch Intern Med 1988, 148: 2381-85. 3. Gruppo Emodialisi e Patologie Cardiovasculari. Multicentre, cross-sectional study of ventricular arrhythmias in chronically haemodialysed patients. Lancet 1988; ii: 1. Sforzini
305-09.
Increased myocardial cAMP in patients with
transplant coronary vasculopathy SiR,—We have shown that in right ventricular biopsy specimens patients after heart transplantation the myocardial &bgr;1( &bgr;2 adrenoceptor ratio decreased because &bgr;2 numbers increased and pj numbers decreased.’ Furthermore, despite similar catecholamine concentrations, patients with coronary vasculopathy (CVP) complicating the transplantation had a lower total 0-receptor density and a greater decrease in &bgr;1 density than patients without CVP.2 To further characterise the &bgr;-adrenergic system in patients with CVP, we asked whether the reduced p-receptor density in patients with CVP is accompanied by a decreased myocardial content of the secondary messenger, cyclic adenosine monophosphate (cAMP) as has been described in failing human myocardium.3 For morphological examination and for assay of cAMP, right ventricular biopsy samples from different regions of the intraventricular septum were taken from 34 patients (mean age 41-7
[SD 51] years, range 31-59) during routine follow-up after orthotopic heart transplantation. Patients were clinically stable and biopsy did not reveal histological evidence of significant rejection. Haemodynamic measurements during routine catheterisation showed
no
differences between the groups studied. Selective
angiography revealed coronary vasculopathy’ in 9 patients. Immunosuppression consisted of cyclosporin, azathioprine, and corticosteroids. Cyclosporin concentrations in patients with or without CVP were not significantly different. According to clinical need, patients received anti-hypertensive agents, such as angiotensin-converting enzyme inhibitors, calcium antagonists, or diuretics. In 3-4 biopsy specimens (5-8 mg), cAMP content was measured by radioinununoassay:’ coronary
cAMP
(pmollmg net weight) 4-03 (0 96) 1.88 (0’19)
n
With CVP Without CVP Mean
9 25
01 between groups by analysis of
(SEM) p
Ventricular arrhythmia and long-term survival with maintenance dialysis SIR,-Sforzini
et
all concluded that ventricular ectopy does
not
predict mortality in dialysis patients. Since our experience in a study of similar size showed an important impact of arrhythmia,2 we reanalysed the data of Sforzini et al. It seems clear that ventricular premature beats did represent an important univariate predictor (p=0047), but were a non-significant covariable in their multivariate analysis. In their group with higher levels of ventricular arrhythmia (Lown grade 4), the univariate probability level of 0-052 would reduce to 0-025 if one additional patient had died during the study, reflecting a small sample size in this subgroup. In the earlier report of the Gruppo Emodialisi, patients on anti-arrhythmic agents were excluded even if stable at the time of entry.3 Subsequently a small number of individuals required anti-arrhythmic agents (9 patients, 55 % mortality at 4 years).Since we did not exclude patients taking cardioactive drugs, we were able to study a larger group (65 patients, 29% first-year mortality), with results that did achieve statistical significance.2 Another instance of study group size differences occurred with cardiac ischaemic disease (18 patients vs 65 in our report). Efforts to determine impact of ventricular ectopy in the smaller group would again be thwarted by an inadequate number of observations. We did find a highly significant impact on survival for ventricular ectopy in patients with ischaemic heart disease (p < 0-005). An additional concern is whether the prevalence of ventricular arrhythmias is higher in the group over 55 years of age. Such a skewed distribution of cardiac complications in the older patients would, combined with small sample size, contribute to advanced age rather than ventricular ectopy emerging as the apparent critical risk factor in the multivariate analysis. The clinical lessons from Sforzini et aP include: (1) high-risk cardiac patients on dialysis have higher mortality than low-risk patients, (2) older patients on dialysis have a higher prevalence of cardiac problems than younger patients; and (3) there exists a low-risk group with a mortality of only 7% at 4 years, a group that would not benefit from monitoring because ventricular arrhythmias are rare. We feel that these valid observations do not effectively contradict the relation between high-grade ventricular arrhythmia and cardiac mortality found in both dialysis and non-dialysis
settings. John Cook Renal Unit, Joslin Diabetes Center,
Nephrology Division, Deaconess Hospital, Boston, Massachusetts 02215, USA
LARRY A. WEINRAUCH RAY E. GLEASON JOHN A. D’ELIA
S, Latini R, Mingardi G, et al. Ventncular arrhythmias and four-year mortality in haemodialysis patients. Lancet 1992, 339: 212-13 2. D’Elia JA, Weinrauch LA, Gleason RE, et al. Application of the ambulatory 24-hour electrocardiogram in the prediction of cardiac death in dialysis patients Arch Intern Med 1988, 148: 2381-85. 3. Gruppo Emodialisi e Patologie Cardiovasculari. Multicentre, cross-sectional study of ventricular arrhythmias in chronically haemodialysed patients. Lancet 1988; ii: 1. Sforzini
305-09.
Increased myocardial cAMP in patients with
transplant coronary vasculopathy SiR,—We have shown that in right ventricular biopsy specimens patients after heart transplantation the myocardial &bgr;1( &bgr;2 adrenoceptor ratio decreased because &bgr;2 numbers increased and pj numbers decreased.’ Furthermore, despite similar catecholamine concentrations, patients with coronary vasculopathy (CVP) complicating the transplantation had a lower total 0-receptor density and a greater decrease in &bgr;1 density than patients without CVP.2 To further characterise the &bgr;-adrenergic system in patients with CVP, we asked whether the reduced p-receptor density in patients with CVP is accompanied by a decreased myocardial content of the secondary messenger, cyclic adenosine monophosphate (cAMP) as has been described in failing human myocardium.3 For morphological examination and for assay of cAMP, right ventricular biopsy samples from different regions of the intraventricular septum were taken from 34 patients (mean age 41-7
[SD 51] years, range 31-59) during routine follow-up after orthotopic heart transplantation. Patients were clinically stable and biopsy did not reveal histological evidence of significant rejection. Haemodynamic measurements during routine catheterisation showed
no
differences between the groups studied. Selective
angiography revealed coronary vasculopathy’ in 9 patients. Immunosuppression consisted of cyclosporin, azathioprine, and corticosteroids. Cyclosporin concentrations in patients with or without CVP were not significantly different. According to clinical need, patients received anti-hypertensive agents, such as angiotensin-converting enzyme inhibitors, calcium antagonists, or diuretics. In 3-4 biopsy specimens (5-8 mg), cAMP content was measured by radioinununoassay:’ coronary
cAMP
(pmollmg net weight) 4-03 (0 96) 1.88 (0’19)
n
With CVP Without CVP Mean
9 25
01 between groups by analysis of
(SEM) p
