1Medizinische Hochschule Hannover Kardiologie und Angiologie Hannover, Deutschland; 2Medizinische Hochschule Hannover Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation Hannover, Deutschland; 3Medizinische Hochschule Hannover Klinik für Nieren- und Hochdruckerkrankungen Hannover, Deutschland; 4Medizinische Hochschule Hannover Klinik für Neurologie Hannover, Deutschland
Background: Right ventricular (RV) dysfunction has been reported as an independent prognostic parameter in patients with cardiac amyloidosis (CA). The afterload-adjusted parameters of RV function may provide a more comprehensive insight into RV performance. This study aims to assess the prognostic value of echocardiographic surrogates of RV-pulmonary artery (PA) coupling in cardiac immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis.
Methods: We retrospectively analyzed RV-PA coupling in consecutive patients with AL or ATTR-CA from our center diagnosed between 2014 and 2023. RV-PA coupling was assessed using three different echocardiographic surrogates: tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP), fractional area change/PASP (FAC/PASP), and RV free wall strain/PASP (RVFWS/PASP) ratios. Median values were determined to identify RV-PA uncoupling and stratify the population. The primary endpoint was all-cause mortality.
Results: 133 patients with CA (83% with ATTR-CA, 17% with AL-CA) were included in the study (median age 77 years, 87% male). During a median follow-up period of 23 months (IQR: 15-34) the primary endpoint of all-cause mortality occurred in 29 patients (22%). The median values of TAPSE/PASP, FAC/PASP, and RVFWS/PASP were 0.41 mm/mmHg (IQR: 0.32-0.60), 0.88 %/mmHg (IQR: 0.62-1.18), and 0.41 %/mmHg (IQR: 0.29-0.63), respectively. RV-PA uncoupling at the diagnosis of CA was observed in 52% of the study patients when using TAPSE/PASP and FAC/PASP, and 51% when using the RVFWS/PASP ratio. Patients exhibiting RV-PA uncoupling were older, more symptomatic, had worse systolic left ventricular (LV) and RV function as well as higher NT-proBNP levels and poorer laboratory parameters indicative of secondary organ damage (Table 1). Impaired RV-PA coupling was associated with an increased all-cause mortality as indicated by a TAPSE/PASP ratio <0.41 (hazard ratio (HR) 4.19, 95% confidence interval (CI) 2.02–8.69, p = 0.001; figure 1), and these findings remained consistent in both AL- and ATTR-CA patient cohorts. Receiver operating characteristic (ROC) analysis revealed that the TAPSE/PASP ratio exhibited the best predictive value for outcomes (area under the curve (AUC) = 0.700, 95% CI: 0.560–0.840) when compared to FAC/PASP (AUC = 0.676, 95% CI: 0.541–0.811) and RVFWS/PASP (AUC = 0.662, 95% CI: 0.532–0.793).
Conclusions: Early RV-PA uncoupling is linked to a higher risk of all-cause mortality in CA patients. TAPSE/PASP outperforms FAC/PASP and RVFWS/PASP in predicting long-term survival.
Table 1. Baseline characteristics of the study population stratified by RV-PA uncoupling (TAPSE/PASP <0.41 mm/mmHg)
| Variable | All N = 133 | Impaired RV-PA coupling N = 69 | Normal RV-PA coupling N = 64 | P value |
| Age, years | 77 (72-81) | 79 (75-84) | 76 (72-80) | 0.008 |
| NYHA class ≥3, n (%) | 39 (29) | 26 (37) | 13 (21) | 0.048 |
| LVEF, % | 48 ± 11 | 44 ± 12 | 52 ± 9 | <0.001 |
| LVGLS, % | -11.8 ± 4.2 | -10.4 ± 3.7 | -13.1 ± 4.3 | <0.001 |
| TAPSE, mm | 16 ± 5 | 13 ± 3 | 19 ± 4 | <0.001 |
| FAC, % | 34 ± 10 | 29 ± 9 | 39 ± 8 | <0.001 |
| RVFWS, % | -16.0 ± 5.8 | -12.6 ± 4.0 | -19.6 ± 5.2 | <0.001 |
| RVGLS, % | -12.1 ± 4.7 | -9.6 ± 3.1 | -15 ± 4.5 | <0.001 |
| NT-proBNP, ng/l | 2583 (1255-5728) | 5100 (2681-10279) | 1661 (729-3172) | <0.001 |
| Creatinine, μmol/l | 108 (93-143) | 117 (99-159) | 101 (84-118) | 0.003 |
| Bilirubin, mg/dl | 12 (9-18) | 15 (10-25) | 11 (8-15)
| 0.005 |
Figure 1. Kaplan-Meier survival analysis in CA patients with vs. without RV-PA uncoupling