Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.

1st Department of Internal Medicine and Cardioangiology International Clinical Research Centre Faculty of Medicine Masaryk University St Anne's University Hospital Brno Czech Republic

1st Department of Internal Medicine and Cardioangiology St Anne's University Hospital Pekarska 53 656 91 Brno Czech Republic

Department of Medical Imaging St Anne's University Hospital Brno Czech Republic

Department of Paediatric Oncology University Hospital Brno Brno Czech Republic

Department of Pathophysiology Faculty of Medicine Masaryk University Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

International Clinical Research Centre St Anne's University Hospital Brno Czech Republic

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Slutsky RA, Bhargava V, Higgins CB. Pulmonary circulation time: Comparison of mean, median, peak, and onset (appearance) values using indocyanine green and first-transit radionuclide techniques. Am. Heart J. 1983;106(1 Pt 1):41–45. doi: 10.1016/0002-8703(83)90436-2. PubMed DOI

de Lepper AGW, Herold IHF, Saporito S, Bouwman RA, Mischi M, Korsten HHM, et al. Noninvasive pulmonary transit time: A new parameter for general cardiac performance. Echocardiography. 2017;34(8):1138–1145. doi: 10.1111/echo.13590. PubMed DOI

Herold IHF, Soliman Hamad MA, van Assen HC, Bouwman RA, Korsten HHM, Mischi M. Pulmonary blood volume measured by contrast enhanced ultrasound: A comparison with transpulmonary thermodilution. Br. J. Anaesth. 2015;115(1):53–60. doi: 10.1093/bja/aeu554. PubMed DOI

Colin GC, Pouleur A-C, Gerber BL, Poncelet P-A, de Meester C, D’Hondt A-M, et al. Pulmonary hypertension detection by computed tomography pulmonary transit time in heart failure with reduced ejection fraction. Eur. Heart J. Cardiovasc. Imaging. 2020;21(11):1291–1298. doi: 10.1093/ehjci/jez290. PubMed DOI

Shors SM, Cotts WG, Pavlovic-Surjancev B, François CJ, Gheorghiade M, Finn JP. Heart failure: Evaluation of cardiopulmonary transit times with time-resolved MR angiography. Radiology. 2003;229(3):743–748. doi: 10.1148/radiol.2293021363. PubMed DOI

Houard L, Amzulescu MS, Colin G, Langet H, Militaru S, Rousseau MF, et al. Prognostic value of pulmonary transit time by cardiac magnetic resonance on mortality and heart failure hospitalization in patients with advanced heart failure and reduced ejection fraction. Circ. Cardiovasc. Imaging. 2021;14(1):e011680. doi: 10.1161/CIRCIMAGING.120.011680. PubMed DOI

Ricci F, Aung N, Thomson R, Boubertakh R, Camaioni C, Doimo S, et al. Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy. Eur. Heart J. Cardiovasc. Imaging. 2019;20(12):1368–1376. doi: 10.1093/ehjci/jez213. PubMed DOI PMC

Ricci F, Barison A, Todiere G, Mantini C, Cotroneo AR, Emdin M, et al. Prognostic value of pulmonary blood volume by first-pass contrast-enhanced CMR in heart failure outpatients: The PROVE-HF study. Eur. Heart J. Cardiovasc. Imaging. 2018;19(8):896–904. doi: 10.1093/ehjci/jex214. PubMed DOI

Cao JJ, Li L, McLaughlin J, Passick M. Prolonged central circulation transit time in patients with HFpEF and HFrEF by magnetic resonance imaging. Eur. Heart J. Cardiovasc. Imaging. 2018;19(3):339–346. doi: 10.1093/ehjci/jex051. PubMed DOI

Meluzin J, Hude P, Leinveber P, Krejci J, Spinarova L, Bedanova H, et al. High prevalence of exercise-induced heart failure with normal ejection fraction in post-heart transplant patients. Biomed. Pap. 2014;158(2):295–302. doi: 10.5507/bp.2013.095. PubMed DOI

Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: Retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009;339:b4606. doi: 10.1136/bmj.b4606. PubMed DOI PMC

Yeh ETH, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy. Circulation. 2004;109(25):3122–3131. doi: 10.1161/01.CIR.0000133187.74800.B9. PubMed DOI

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension | European Heart Journal | Oxford Academic [Internet]. https://academic.oup.com/eurheartj/article/37/1/67/2887599. Accessed 28 Mar 2021.

Panovský R, Pešl M, Holeček T, Máchal J, Feitová V, Mrázová L, et al. Cardiac profile of the Czech population of Duchenne muscular dystrophy patients: A cardiovascular magnetic resonance study with T1 mapping. Orphanet J. Rare Dis. 2019;14(1):10. doi: 10.1186/s13023-018-0986-0. PubMed DOI PMC

Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J. Cardiovasc. Magn. Reson. 2013;1(15):35. doi: 10.1186/1532-429X-15-35. PubMed DOI PMC

Ishida M, Schuster A, Morton G, Chiribiri A, Hussain S, Paul M, et al. Development of a universal dual-bolus injection scheme for the quantitative assessment of myocardial perfusion cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 2011;13(1):28. doi: 10.1186/1532-429X-13-28. PubMed DOI PMC

Styner M, Brechbuhler C, Szckely G, Gerig G. Parametric estimate of intensity inhomogeneities applied to MRI. IEEE Trans. Med. Imaging. 2000;19(3):153–165. doi: 10.1109/42.845174. PubMed DOI

Pluim JPW, Maintz JBA, Viergever MA. Mutual-information-based registration of medical images: A survey. IEEE Trans. Med. Imaging. 2003;22(8):986–1004. doi: 10.1109/TMI.2003.815867. PubMed DOI

Bazett HC. An analysis of the time-relations of electrocardiogram. Heart. 1920;7:353.

Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation. 1990;82(5):1595–1606. doi: 10.1161/01.CIR.82.5.1595. PubMed DOI

Salerno M, Taylor A, Yang Y, Kuruvilla S, Ragosta M, Meyer CH, et al. Adenosine stress cardiovascular magnetic resonance with variable-density spiral pulse sequences accurately detects coronary artery disease. Circ. Cardiovasc. Imaging. 2014;7(4):639–646. doi: 10.1161/CIRCIMAGING.113.001584. PubMed DOI PMC

Monahan TS, Sawmiller DR, Fenton RA, Dobson JG. Adenosine A2a-receptor activation increases contractility in isolated perfused hearts. Am. J. Physiol. Heart Circ. Physiol. 2000;279(4):H1472–H1481. doi: 10.1152/ajpheart.2000.279.4.H1472. PubMed DOI

Hori M, Kitakaze M. Adenosine, the heart, and coronary circulation. Hypertension. 1991;18(5):565–574. doi: 10.1161/01.HYP.18.5.565. PubMed DOI

Chandrasekera PC, McIntosh VJ, Cao FX, Lasley RD. Differential effects of adenosine A2a and A2b receptors on cardiac contractility. Am. J. Physiol. Heart Circ. Physiol. 2010;299(6):H2082–H2089. doi: 10.1152/ajpheart.00511.2010. PubMed DOI PMC

Costa MA, Matsumoto JPP, Carrettiero DC, Fior-Chadi DR. Adenosine A1 and A2a receptors modulate the nitrergic system in cell culture from dorsomedial medulla oblongata. Auton. Neurosci. 2020;229:102737. doi: 10.1016/j.autneu.2020.102737. PubMed DOI

Tian L, Tang G, Liu Q, Yin Y, Li Y, Zhong Y. Blockade of adenosine A1 receptor in nucleus tractus solitarius attenuates baroreflex sensitivity response to dexmedetomidine in rats. Brain Res. 2020;1743:146949. doi: 10.1016/j.brainres.2020.146949. PubMed DOI

Ellenbogen KA, Thames MD, DiMarco JP, Sheehan H, Lerman BB. Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. Circulation. 1990;81(3):821–828. doi: 10.1161/01.CIR.81.3.821. PubMed DOI

Flyer JN, Zuckerman WA, Richmond ME, Anderson BR, Mendelsberg TG, McAllister JM, et al. Prospective study of adenosine on atrioventricular nodal conduction in pediatric and young adult patients after heart transplantation. Circulation. 2017;135(25):2485–2493. doi: 10.1161/CIRCULATIONAHA.117.028087. PubMed DOI PMC

Jiménez-Jaso JM, Ezponda A, Sáenz-Diez JM, Caballeros M, Rábago G, Bastarrika G. Valoración del índice de reserva de perfusión miocárdica por resonancia magnética en pacientes con trasplante cardíaco. Radiologia. 2020;62(6):493–501. doi: 10.1016/j.rx.2020.04.004. PubMed DOI

Stress and Rest Pulmonary Transit Times Assessed by Cardiovascular Magnetic Resonance