Heart transplantation remains the most effective long-term intervention for patients with end-stage heart failure. Despite advances in immunosuppressive therapy, acute cellular rejection (ACR) remains common, with a prevalence up to 35% to 40%, and approximately 22% of patients require admission to the hospital for treatment within the first year after transplantation. ACR is also among the leading causes of death after heart transplantation. The gold-standard surveillance test to detect ACR is based on the histologic analysis of right ventricular (RV) myocardial tissue obtained at endomyocardial biopsy (EMB). Although this intervention is relatively safe in experienced hands, with a complication rate of approximately 0.5% to 1.5%, many of these complications, including myocardial perforation, pericardial tamponade, tricuspid valve injury causing significant tricuspid regurgitation, and access-site complications, create significant challenges for patients and physicians. In addition, the EMB procedure is expensive, is prone to sampling error due to the patchy nature of ACR, and, importantly, is disliked by many patients. Consideration of these reasons is important given that the current standard of care for ACR surveillance is to perform periodic EMBs during the first 6 to 12 postoperative months, which equates to more than several procedures during the first year of follow-up alone. For these reasons, noninvasive screening to detect significant ACR remains highly desirable.
ACR is a T cell–mediated process resulting in myocardial inflammation, and it can cause different severities of myocyte damage. It is postulated that this process should result in some degree of subclinical cardiac dysfunction that can possibly be detected by different imaging techniques, including echocardiography. Several studies have suggested that myocardial strain and strain rate are more sensitive measures than those derived from conventional echocardiography. Two recent reports, one published in a recent issue and the other in the current issue of JASE , have further examined the role of speckle-tracking echocardiography to detect ACR to monitor heart transplantation patients.
In the April 2015 issue of JASE , Ambardekar et al . reported an examination of myocardial strain and strain rate from speckle-tracking echocardiography to differentiate asymptomatic biopsy-proven cellular rejection in the first year after transplantation. Using Velocity Vector Imaging software from echocardiograms identified retrospectively at three time points in heart transplant recipients—at baseline (no rejection), during ACR, and after resolution of rejection—speckle-tracking strain and strain rate measurements were obtained from 30 patients. Asymptomatic biopsy-proven rejection was compared with a control cohort without ACR. There were three major findings. First, there were no significant differences in circumferential and longitudinal strain or strain rate among the baseline, rejection, and resolution studies. Second, there were also no significant differences in strain and strain rate in control transplantation patients during the first year (within the first month and at 6 and 12 months after transplantation). Third, in a prespecified subgroup analysis, there were no differences in any of the speckle-tracking echocardiographic parameters when limiting the analysis to those patients with mild (14 patients) versus moderate (16 patients) rejection over the course of the study time points. These investigators concluded that speckle-tracking analysis was unable to detect changes on serial studies from patients with asymptomatic rejection and thus cannot replace EMB.
The strength of the study by Ambardekar et al . relates to the investigators’ examining the diagnostic value of changes in left ventricular (LV) strain and strain rate longitudinally in the same patient, which mirrors clinical practice, as opposed to cross-sectional studies comparing average strains in a group of patients with rejection versus those without rejection. Unfortunately, the latter approach has been used in most of the studies examining this topic. It is important to place the observations and conclusions made in this study into clinical context and to keep in mind the EMB grading nomenclature and how the histologic grade is used to guide treatment of ACR. In 2004, under the direction of the International Society for Heart and Lung Transplantation, a multidisciplinary review of the EMB grading system was undertaken to address challenges and inconsistencies in its use. The revised categories of ACR were defined as follows: grade 0R, no rejection (no change from 1990); grade 1R, mild rejection (1990 grades 1A, 1B, and 2); grade 2R, moderate rejection (1990 grade 3A); and grade 3R, severe rejection (1990 grades 3B and 4). Knowing the revised category is important to understand how ACR is defined and to interpret published studies ( Table 1 ) that incorporate EMB readings using the 1990 grading system (typically retrospective studies with EMB data before 2006).
| Study | Total patients (prevalence of ACR) ∗ | Method and parameters (cutoff values) | Gold-standard EMB grade | Sensitivity | Specificity | PPV | NPV |
|---|---|---|---|---|---|---|---|
| Marcinak et al . (2007) | 31 (32%) | Color DTI | |||||
| ≥1B | 85% | 90% | 80% | 92.7% | ||
| 80% | 86% | 72.8% | 90.1% | |||
| Kato et al . (2010) | 35 (11%) | Color DTI | |||||
| ≥1B | 82.2% | 82.3% | 36.4% | 97.3% | ||
| 75.6% | 74.9% | 27.1% | 96.1% | |||
| Roshanali et al . (2010) | 38 (38%) | DTI | |||||
| [(PWT + LVMI) − (LV peak systolic strain + Sep-TS)] (≤0) | ≥3A | 100% | 71.0% | 67.9% | 100% | ||
| Eleid et al . (2010) | 51 (35%) § | 2D speckle-tracking | |||||
| ≥2R | NR | NR | NR | NR | ||
| |||||||
| |||||||
| Sato et al . (2011) | 32 (9%) | 2D speckle-tracking | |||||
| % change of LV torsion † (<25%) | ≥2R | 73.7% | 95.1% | 59.7% | 97.3% | ||
| Sera et al . (2014) | 59 (16%) | 2D speckle-tracking | |||||
| ≥1B ‡ | 64% | 63% | 24.2% | 90.4% | ||
| Ambardekar et al . (2015) | 98 (45%) § | 2D speckle-tracking | |||||
| ≥2/1R || | NR | NR | NR | NR | ||
| |||||||
| Mingo-Santos et al . (2015) | 34 (5.1%) | Speckle-tracking | |||||
| ≥2R | 85.7% | 91.1% | 42.9% | 98.8% | ||
| 85.7% | 81.4% | 25.0% | 98.8% | |||
| 100% | 77% | 25.9% | 100% |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
