Summary
Background
The ageing graft frequently shows coronary lesions and a restrictive physiology.
Aims
To determine the presenting features and outcome of chronic heart failure in heart transplant recipients.
Methods
In this cohort study, we compared 44 consecutive heart transplant recipients who developed chronic heart failure more than 1 year after heart transplantation with 44 control heart transplant recipients who did not develop heart failure.
Results
We found that patients who developed heart failure had more frequently a history of hypertension or diabetes before transplantation. During the 12 months after transplantation, significantly more patients had moderate-to-severe acute rejections (≥ grade 2R) in the heart failure group than in the control group. At the time of heart failure diagnosis, systolic left ventricular function was preserved in 50% of patients and coronary angiography was normal or near normal in 36% of patients. Half of the 44 patients in the heart failure group died within 2 years of heart failure diagnosis. Ascites and end-stage renal failure requiring dialysis were significantly more frequent during follow-up in the heart failure group than in the control group (respectively, 10/44 vs 0/44 [ P = 0.001] and 18/44 vs 5/44 [ P = 0.003]).
Conclusion
In heart transplant recipients presenting with heart failure, systolic left ventricular function is frequently preserved and coronary angiography is frequently abnormal, but may be normal or near normal. During follow-up, the main features of these patients are a high mortality rate after heart failure diagnosis, a frequent need for renal dialysis and frequent ascites.
Résumé
Contexte
Le greffon cardiaque vieillissant présente souvent des lésions coronaires et une physiologie de type restrictif.
Objectif
Le but de cette étude est décrire la présentation et le devenir de l’insuffisance cardiaque chez le greffé cardiaque.
Méthodes
Dans cette étude de cohorte, nous avons comparé 44 transplantés cardiaques consécutifs ayant présenté une insuffisance cardiaque plus d’un an après la greffe à 44 greffés cardiaques témoins qui n’ont pas présenté d’insuffisance cardiaque.
Résultats
Les patients du groupe insuffisance cardiaque avaient plus fréquemment des antécédents d’hypertension ou de diabète avant la transplantation. Durant les 12 mois ayant suivi la transplantation, les patients du groupe insuffisance cardiaque ont présenté significativement plus de rejets de gravité moyenne à sévère (≥ 2R) que les témoins. Au moment du diagnostic d’insuffisance cardiaque, la fonction systolique ventriculaire gauche était conservée chez 50 % des patients et la coronarographie était normale ou subnormale chez 36 % des patients. Dans les deux ans suivant le diagnostic d’insuffisance cardiaque, 50 % des patients sont morts. Ascites et insuffisance rénale terminale nécessitant la dialyse étaient significativement plus fréquentes pendant le suivi dans le groupe insuffisance cardiaque que chez les témoins (respectivement, 10/44 contre 0/44 [ p = 0,001] et 18/44 contre 5/44 [ p = 0,003]).
Conclusion
Chez les greffés cardiaques présentant une insuffisance cardiaque, au moment du diagnostic, la fonction systolique ventriculaire gauche est souvent préservée et la coronarographie est souvent anormale mais peut être normale ou subnormale. Pendant le suivi, les principales caractéristiques de ces patients sont la survenue fréquente d’une ascite et d’un passage en dialyse rénale.
Background
In the years after heart transplantation, the cardiac graft frequently deteriorates at an accelerated rate. The predominant features of the ageing graft at pathology are a diffuse thickening of the arterial intima, named cardiac allograft vasculopathy (CAV), and myocardial fibrosis . Clinical manifestations are sudden death, ventricular and supraventricular arrhythmias, acute coronary syndromes and congestive heart failure (HF) . The full spectrum of presenting features and the outcome of HF in these patients have not yet been fully described. The purpose of this study was to report the characteristics of HF in a cohort of heart transplant recipients (HTRs).
Methods
In this cohort study, we included all the HTRs diagnosed with chronic HF after transplantation (HF group) at our institution between May 1994 and May 2014, who survived more than 1 year after heart transplantation. We compared these patients with HTRs who did not develop HF and survived more than 1 year after heart transplantation (control group). As the risk of developing HF is time dependent and may depend on the immunosuppressive era, each control was matched with one patient from the HF group with a close transplantation date. Each control was the next patient on the chronological list of transplanted patients at our centre who did not develop HF during the study period. Of the 164 HTRs followed at our institution during the study period, 44 met the inclusion criteria in the HF group and 44 controls were matched to these patients.
Criteria for the diagnosis of HF were symptoms associated with either left ventricular ejection fraction (LVEF) < 50% at rest echocardiography and/or elevated filling pressures at right-sided cardiac catheterization (pulmonary capillary wedge pressure > 15 mmHg or mean right atrial pressure > 8 mmHg) . Accepted symptoms were shortness of breath and/or signs of fluid retention, such as pulmonary congestion, ankle swelling or ascites. Exclusion criteria were as follows: age < 18 years at the time of the diagnosis of HF; chronic HF diagnosed less than 1 year after transplantation, as early graft failure may have different causes and outcome compared with late HF; acute heart rejection associated with transient symptoms of HF and subsequent recovery of normal ejection function and normal filling pressures on a modified immunosuppressive regimen.
All patients had routine follow-up visits at our institution at least every 4 months, including physical examination, laboratory evaluation, electrocardiography, echocardiography and chest X-ray. From 1992 to 1998, most patients were treated using a protocol comprising cyclosporine and prednisolone, with or without additional azathioprine. In 1999, mycophenolate mofetil was introduced to replace azathioprine. In addition, tacrolimus was used instead of cyclosporine in patients with significant rejection or severe side effects. Since 2004, tacrolimus has been used as the calcineurin inhibitor of choice.
At presentation with HF symptoms, the patients had a clinical evaluation, laboratory measurements, standard 12 lead electrocardiography and echocardiography, and were referred, in the absence of contra-indication, for right cardiac catheterization and coronary angiography. Chronic microvoltage was defined as maximum QRS amplitude < 0.5 mV in each limb lead, observed in more than three consecutive electrocardiograms. All Doppler echocardiography studies were performed by an experienced cardiologist (P.A. or G.H.). LVEF was measured using the Simpson’s biplane method or by a visual estimate associated with the Teicholz method. Systolic dysfunction was defined as LVEF < 55%. Significant valve regurgitation was defined as moderate or severe mitral or tricuspid regurgitation. Conventional coronary angiography was performed using either the femoral or radial approach. Right catheterization and endomyocardial biopsies were performed using the femoral approach with the Judkins technique with local anaesthesia. Right ventricular pressures were measured using a 4F National Institute of Health catheter. Coronary angiographies were interpreted by two independent reviewers; if the reviewers disagreed, a third reviewer was consulted and consensus was achieved. Abnormalities at coronary angiography were classified according to the International society for heart and lung transplantation (ISHLT) classification from CAV0 (no detectable angiographic lesion) to CAV3 . Cardiac allograft rejection was classified according to the revised ISHLT consensus .
Statistical analysis
Intergroup comparisons were made using the unpaired Student’s t test or χ 2 analysis. Multivariable logistic regression analysis was applied to determine independent predictors of HF. We analysed mortality using the Kaplan-Meier model. The log-rank test was used to compare subgroup survival. Statistical analyses were performed using Statview, version 5.0 (SAS Institute Inc., Cary, NC, USA). A value of P < 0.05 was considered as statistically significant in all analyses.
Results
Table 1 shows the baseline characteristics of the 44 HTRs with HF and the 44 controls. Patients who subsequently developed HF had more frequently a history of hypertension or diabetes before transplantation. In a multivariable logistic regression model, including sex, age, hypertension, diabetes and primary cardiac disease, hypertension remained the only significant predictor of HF ( P = 0.02). The main primary heart disease was dilated cardiomyopathy in both groups. During the 12 months after transplantation, significantly more patients had moderate to severe acute rejections (≥ grade 2R) in the HF group than in the control group (23% vs 7%; P = 0.03). Body mass index measured 1 year after transplantation did not differ significantly between the HF and control groups (23.8 ± 3.6 vs 24.4 ± 3.2 kg/m 2 ; P = 0.4).
| Heart failure ( n = 44) | Controls ( n = 44) | P | |
|---|---|---|---|
| Men | 33 (75) | 38 (86) | 0.3 |
| Age (years) | 45.8 ± 16 | 49.6 ± 14 | 0.2 |
| Primary cardiac disease | |||
| Ischaemic | 15 (34) | 14 (32) | 0.8 |
| Idiopathic dilated cardiomyopathy | 22 (50) | 26 (59) | 0.4 |
| Other | 7 (16) | 4 (9) | 0.3 |
| History of hypertension | 10 (23) | 3 (7) | 0.04 |
| Diabetes | 6 (14) | 1 (2) | 0.04 |
| History of alcohol abuse | 6 (14) | 10 (23) | 0.3 |
| History of smoking | 24 (55) | 24 (55) | 0.9 |
| Chronic obstructive pulmonary disease | 2 (5) | 3 (7) | 0.7 |
| Heart/kidney transplantation | 2 (5) | 2 (5) | 0.9 |
Table 2 shows the presenting features in the HF group at the time of HF diagnosis . The first symptoms of chronic HF were noted as early as 1 year in some cases. However, time since transplantation was 7 years or more in most patients. Ankle oedema and exertional dyspnoea were the more frequent symptoms, and were both present in 15 patients. The type of presentation was progressive HF in 38 patients and acute pulmonary oedema or cardiogenic shock in six patients. In four of these six patients, acute HF was associated with an acute coronary syndrome.
