Prognostic value of pulmonary transit time and pulmonary blood volume in dilated cardiomyopathy

Abstract

Background: Pulmonary transit time (PTT) has a prognostic role; however, this has not been specifically studied in dilated cardiomyopathy (DCM) (1). Objective: To assess whether pulmonary transit time estimated from stress-perfusion CMR in patients with DCM is associated with major adverse cardiovascular events (MACE). Methods: Patients with dilated cardiomyopathy phenotype who underwent clinical quantitative stress perfusion MRI at two centres were included. Inclusion criteria were left ventricular (LV) dilatation, left ventricular ejection fraction (LVEF) < 50%. Automated sampling of the right ventricular (RV) and LV was used to estimate PTT (centroid) that was normalized to RR interval i.e., nPTT (2). A group of healthy volunteers (HV; normal MRI and no known cardiovascular disease or risk factors; n= 27) and a group of age-matched patients with preserved LV function and size (HC; n= 40) were used for defining reference values for PTT. Follow up for occurrence of incident MACE was done by review of electronic health records. The primary outcome was composite of HF hospitalisation or death, analysis was on based on time to first event. Results: Of 320 patients, 199 had no significant CAD or VHD i.e., nonischemic DCM (NIDCM), and 121 had either CAD or VHD with a dilated impaired phenotype. 23 patients with DCM had recovered LVEF on subsequent imaging (from LVEF< 50% on echo to LVEF >50% on CMR). Rest PTT was significantly longer in DCM patients compared to HV (median 9.5[IQR7.5-12.2] versus 7.3[6.5-8.9]; p< 0.0001) and age matched HC (9.5[7.5-12.2] versus 7.0[6.3-7.8]; p< 0.0001). iPBV was significantly higher in DCM phenotype compared to age-matched HC (391[299-503] versus 370 [305-409]; p=0.029). On adenosine stress PTT shortened, and the stress-PTT in DCM remained significantly longer than age-matched HC (7.6[5.8-9.9] versus 5.6[4.7-6.6]; p=0.029). Rest PTT was associated with age (R=0.388, p=0.037), RVEF (R=-0.472, p< 0.0001), LVEF (R= -0.425, p= 0.022), and PCWP (R=0.328, p< 0.0001). Stress PTT was associated with age (R=0.482, p=0.007), LVEF (R=-0.467, p< 0.0001), RVEF (R=-0.472, p< 0.0001), rest PTT (R=0.604, p< 0.0001), PCWP (R=0.242, p< 0.0001) and NT pro BNP (R=0.656, p< 0.0001). Whereas PBV was significantly associated with PCWP (R=0.370, p< 0.0001), this was not significantly associated with age, LVEF or RVEF. Over a median follow-up of 3.06 years/1119 (IQR641-1359) days, MACE occurred in 37 (12.5%) patients (first event death, n=19). DCM with recovered LV function had no events. On Cox regression analysis, higher stress PTT stress associated with MACE (aHR 1.96, 95%CI 1.25 - 3.06, p=0.003), independent of LVEF, RVEF, rest PTT and myocardial blood flow. While higher rest PTT associated with mortality initially, this lost significance when adjusted for confounders. Kaplan Meier curve analysis showed higher rest nPTT rest (p=0.042), stress nPTT (p=0.047) and iPBV (p=0.07) were associated with lower MACE free survival rates. Conclusion: In dilated cardiomyopathy, pulmonary transit times are longer and pulmonary blood volume higher than in controls, and correlate with age and imaging markers of adverse cardiac remodeling. Both are associated with adverse cardiac events. The association of stress PTT with adverse events may represent transiently induced pulmonary congestion in DCM and requires further mechanistic studies.