Composition VendorNewgen KnowledgeWorks (P) Ltd.PLoS OneplosplosonePLOS One1932-6203Public Library of ScienceSan Francisco, CA USA10.1371/journal.pone.0341438PONE-D-25-33529Research ArticleMedicine and health sciencesVascular medicineBlood pressureMedicine and health sciencesPulmonologyPulmonary hypertensionMedicine and health sciencesVascular medicineBlood pressureSystolic pressureMedicine and health sciencesDiagnostic medicineDiagnostic radiologyUltrasound imagingEchocardiographyResearch and analysis methodsImaging techniquesDiagnostic radiologyUltrasound imagingEchocardiographyMedicine and health sciencesRadiology and imagingDiagnostic radiologyUltrasound imagingEchocardiographyBiology and life sciencesAnatomyCardiovascular anatomyHeartCardiac ventriclesMedicine and health sciencesAnatomyCardiovascular anatomyHeartCardiac ventriclesBiology and life sciencesAnatomyCardiovascular anatomyBlood vesselsArteriesPulmonary arteriesMedicine and health sciencesAnatomyCardiovascular anatomyBlood vesselsArteriesPulmonary arteriesMedicine and health sciencesSurgical and invasive medical proceduresCatheterizationPhysical sciencesPhysicsCondensed matter physicsMagnetismMagnetic resonanceComparison of pulmonary circulation parameters acquired by cardiovascular magnetic resonance with right heart catheterization and transthoracic echocardiography in patients with recent-onset dilated cardiomyopathyPulmonary transit time and cardiac function in recent-onset dilated cardiomyopathyhttps://orcid.org/0000-0002-5504-7370OpatřilLukášConceptualizationData curationFormal analysisInvestigationMethodologyProject administrationWriting – original draftWriting – review & editing1‡https://orcid.org/0000-0002-9827-1006Mojica-PisciottiMary LuzConceptualizationData curationMethodologySoftwareWriting – original draftWriting – review & editing2‡https://orcid.org/0000-0001-8489-132XPanovskýRomanConceptualizationFunding acquisitionInvestigationMethodologySupervisionWriting – review & editing1*MáchalJanData curationMethodologySoftwareWriting – review & editing3HolečekTomášInvestigationMethodologyProject administrationWriting – review & editing4FeitováVěraData curationFormal analysisInvestigationMethodologyVisualizationWriting – review & editing5GodavaJúliusConceptualizationFormal analysisInvestigationWriting – review & editing6PoloczkováHanaData curationFormal analysisFunding acquisitionSupervisionWriting – review & editing6KinclVladimírConceptualizationFormal analysisFunding acquisitionInvestigationWriting – review & editing1AndrejMichaelConceptualizationData curationInvestigationWriting – review & editing7KrejčíJanConceptualizationFormal analysisFunding acquisitionInvestigationMethodologySupervisionWriting – review & editing6First Department of Internal Medicine and Cardioangiology, International Clinical Research Centre, St. Anne´s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech RepublicInternational Clinical Research Centre, St. Anne´s University Hospital, Brno, Czech RepublicDepartment of Pathophysiology, International Clinical Research Centre, St. Anne´s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Medical Imaging, International Clinical Research Centre, St. Anne´s University Hospital, Department of Biomedical Engineering, Brno University of Technology, Brno, Czech RepublicDepartment of Medical Imaging, International Clinical Research Centre, St. Anne´s University Hospital, Brno, Czech RepublicFirst Department of Internal Medicine and Cardioangiology, St. Anne´s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech RepublicFaculty of Medicine, Masaryk University, Brno, Czech RepublicBauerWolfgang RudolfEditorUniversitatsklinikum Wurzburg, GERMANY
The authors have declared that no competing interests exist.
‡ LO and MLMP contributed equally to this work and are joint first authors on this work.
* E-mail: panovsky@fnusa.cz10220262026212e034143825620257120262026Opatřil et alThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction
Evaluating pulmonary circulation parameters (PCP) with cardiovascular magnetic resonance (CMR) is a relatively new approach with the potential for complex evaluation of the cardio-pulmonary system. Its impact might complement clinical assessment through right heart catheterization (RHC), the gold standard in evaluating pulmonary hypertension (PH) and hemodynamics, and transthoracic echocardiography (TTE). The study aims to examine the correlation between PCP and diastolic and systolic function, as well as PH, in patients with recent-onset dilated cardiomyopathy (RODCM).
Methods
Eighty-four patients with RODCM were retrospectively included. All patients had a CMR examination, RHC (including pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance (PVR)), and TTE. The pulmonary transit time (PTT), corrected pulmonary transit time (PTTc), systolic and diastolic function, and PH were assessed. Patients were divided into groups according to the PH and the diastolic function.
Results
PTT and PTTc correlated with PCWP, cardiac index, PVR, and E/e’. Patients with a restrictive filling pattern showed significantly longer PTT. The receiver operating characteristic curves for PTT, PTTc, and PH were assessed with areas under the curve of 72.7% for PTT and 75.3% for PTTc, and cut-off values of 8.62 s (PTT) and 8.52 s (PTTc).
Conclusion
To our knowledge, this is the first study focused on CMR-derived PCP in an RODCM group. Our findings show that PTT and PTTc are prolonged in patients with impaired systolic and diastolic function, and PH. Therefore, PCP might offer critical information to evaluate the cardio-pulmonary system comprehensively.
Pulmonary circulation parameters (PCP) are, in terms of cardiovascular magnetic resonance (CMR), a relatively new technique with the potential for complex evaluation of the cardio-pulmonary system as a whole [1–5]. While previously assessed by other modalities, such as radionuclide imaging [6], computed tomography [7], or contrast-enhanced transthoracic echocardiography (TTE) [8], CMR shows significant advantages and even allows retrospective analysis of these parameters [1,2].
Right heart catheterization (RHC) is the gold standard in evaluating pulmonary hypertension (PH) and hemodynamics [9]. In addition, compared to other PH evaluation methods, only RHC can differentiate between precapillary and postcapillary PH [9]. TTE, on the other hand, is the gold standard in diastolic function assessment [10,11].
A prolongation in PCP parameters has been documented by systolic dysfunction [3,12], diastolic dysfunction [2,13], and recently, PH as well [14,15]. Therefore, the data on the correlation between PCP, RHC, and TTE are crucial but limited. To our knowledge, no article including all three modalities and the PCP assessment in patients with recent-onset dilated cardiomyopathy (RODCM) has been published so far.
The study aims to provide such data and examine the correlation between PCP and diastolic and systolic function, as well as PH, in patients with RODCM, defined as newly diagnosed dilated cardiomyopathy with heart failure symptoms appearing in the last six months.
Materials and methodsStudy design and population
This retrospective study was performed in accordance with the Declaration of Helsinki (2000) of the World Medical Association. The analysis used pseudonymized data from participants enrolled in a study approved by the Ethics Committee of the St. Anne´s University Hospital under No. 32V/2013, for which written informed consent was obtained. No minors were included. According to Czech legislation, no additional ethics approval was required for this retrospective analysis.
Eighty-four patients with RODCM already participating in a research project in our department were retrospectively included in this study. They had a CMR examination (including rest perfusion), RHC (including pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance (PVR)), and TTE (including diastolic function assessment). CMR and RHC were performed within 0–8 days of each other. Patients were divided into groups according to their PH and diastolic function.
CMR protocol
CMR studies were performed following our standard protocol [2,16] using a 1.5 T scanner (Ingenia, Philips Medical Systems, Best, The Netherlands) equipped with 5- and 32-element phased-array receiver coils, allowing for the use of parallel acquisition techniques in the supine position in repeated breath-holds. Functional imaging using balanced steady-state free precession (SSFP, b-TFE) cine sequences included four-chamber, two-chamber, and left ventricular outflow tract (LVOT) long-axis views, and a short-axis (SAX) stack from the cardiac base to the apex in the plane perpendicular to the LV long axis. LV functional and morphological parameters were calculated from the SAX stack using the summation-of-disc methods following the recommendations on post-processing evaluation from the Society for Cardiovascular Magnetic Resonance [17].
CMR first‐pass contrast‐enhanced myocardial perfusion images were acquired as described in previous studies [2]. Briefly, a b-TFE sequence acquired images in three SAX sections (basilar, midventricular, and apical) with these parameters: field of view 300 × 300 mm, reconstruction matrix 224, slice thickness 10 mm, acquisition voxel size 2.5 × 2.5 mm, time to repetition (TR) ≈ 2.2 ms, echo time (TE) ≈ 1.1 ms, flip angle 50°, SENSE factor 2.3, number of dynamics = 90, non-shared saturation prepulse. The images were acquired without breath-hold.
Pulmonary circulation biomarkers analyses
Data obtained allowed the assessment of the PCP in accordance with our previous studies [2]. PCP parameters included pulmonary transit time (PTT) and pulmonary transit beats (PTB). The PTT and PTB values were estimated from SAX rest and stress first-pass perfusion images using a custom script developed in Python 3.7.16 (Python Software Foundation). A motion correction algorithm was applied to optimize image registration and avoid potential contamination from pixels in the blood pool. The registration accuracy was visually assessed. Regions of interest (ROIs) in the RV and the LV were manually traced in a sample image for the mid-ventricular slice and, in case of repetitive misregistration, in a basal one. The ROIs propagated throughout the stack of images, their average was computed, and signal intensity (SI) curves vs time were obtained. The algorithm identified the onset SI values; PTT was defined as the difference between the LV and the RV onset time, and PTB was the number of frames between these times [2] (see Fig 1).
10.1371/journal.pone.0341438.g001
Pulmonary transit time analysis.
Regions of interest (not shown) are manually traced in the right ventricle (RV) and the left ventricle (LV) to create the signal intensity (SI) vs. time curves. The pulmonary transit time (PTT) corresponds to the difference between the onsets, selected as the points where the signal surpasses 10% of the maximum values.
In addition, to reduce the effect of the heart rate (HR) on the results, corrected pulmonary transit time (PTTc) was calculated using Bazett’s formula [18]. Likewise, PTTc (s) was defined as PTT (s)/⎷(RR interval/1 s), as shown previously [2,13].
Right heart catheterization
The RHC was performed following the European Society of Cardiology 2022 guidelines [9]. A fluid-filled catheter and pressure transducer were used to measure the pressure. PH was defined as the mean pulmonary arterial pressure (mPAP) over 20 mmHg in rest conditions. Transpulmonary gradient (TPG) was calculated as the difference between mPAP and pulmonary capillary wedge pressure (PCWP). Cardiac output (CO) was determined using the thermodilution method and indexed to BSA as cardiac index (CI). Finally, the pulmonary vascular resistance (PVR) was calculated as (mPAP - PCWP)/ CO.
Precapillary PH was defined as mPAP > 20 mmHg, PCWP ≤ 15 mmHg and PVR > 2 WU; isolated post-capillary pulmonary hypertension (IpcPH) as mPAP > 20 mmHg, PCWP > 15 mmHg and PVR ≤ 2 WU; and combined postcapillary and precapillary pulmonary hypertension (CpcPH) as mPAP > 20 mmHg, PCWP > 15 mmHg and PVR > 2 WU [9].
In addition, the Pulmonary Artery Pulsatility Index (PAPi), as a clinically validated hemodynamic parameter used to assess RV function was calculated. It was defined as:
All patients underwent the standard TTE exam, and all examinations were performed by experienced cardiologists in our center and according to the guidelines.
Diastolic function was evaluated in accordance with established recommendations [19,20] based on Doppler echocardiography. Patients were divided into subgroups depending on the diastolic dysfunction grade (grade I to IV).
Statistical analysis
PTT and PTB were correlated with echocardiographic and RHC markers using the Pearson correlation coefficient; logarithmic transformation was employed when needed to fit the normal distribution (including both PTB and PTT). The different patterns of diastolic dysfunction were compared using ANOVA with the Tukey post hoc test for unequal samples. The ability of PTT and PTTc to determine the presence of RHC-defined PH was expressed by the area under the receiver operating characteristic (ROC) curve, and a cut-off point was proposed based on the highest Youden index.
Intra- and inter-observer reproducibility were assessed using the intraclass correlation coefficient (ICC) (type C, two-way mixed-effects model with 95% confidence intervals (CI) from ten randomly selected cases. These cases were analyzed by two readers, one of whom repeated the analysis two weeks apart. The repeatability was classified as poor (<0.5), fair (0.50 to 0.75), good (0.75 to 0.90), and excellent (0.90 to 1). Statistica (version 14.0.0.15, TIBCO software) and R (version 3.6.1, R Foundation for Statistical Computing) were used for the analyses.
ResultsPatient´s population
The mean age in our group was 50.5 ± 11.3 years, mean BMI 28.5 ± 5.4 kg/m2, and BSA 2.1 ± 5.4 m2. Patients had a reduced LV ejection fraction (LVEF) of 30.4 ± 11.2%, RV ejection fraction (RVEF) of 46.7 ± 15%, and an increased mPAP of 22.4 ± 8.6 mmHg. For a detailed list of basic clinical, CMR, RHC, and TTE parameters, see Table 1.
10.1371/journal.pone.0341438.t001
Baseline clinical, TTE, CMR, and RHC parameters.
Parameters
Value
n
Number of patients
84
84
Age (years)
50.5 ± 11.3
84
Gender (male), (%)
76.2
64
Body mass index (kg/m2)
28.5 ± 5.4
84
Body surface area (m2)
2.1 ± 0.2
84
Heart rate (BPM)
77.7 ± 17.1
84
TEE parameters
LVEF – Estimation (%)
24.4 ± 9.3
84
LVEF – Simpson (%)
26.6 ± 9.9
84
E/A
1.5 ± 1.1
72
E/e´
13.7 ± 7.6
82
TRPG (mmHg)
22.7 ± 13.4
84
TDI – IVS S (m/s)
0.05 ± 0.02
82
TDI – IVS E (m/s)
0.07 ± 0.13
82
TDI – IVS A (m/s)
0.07 ± 0.04
71
sPAP (mmHg)
26.4 ± 14.9
84
CMR parameters
LVEF (%)
30.4 ± 11.2
84
LVEDV (mL/m2)
254.6 ± 98.2
84
LVESV (mL/m2)
184.4 ± 93.5
84
PTB
10.1 ± 5.5
84
PTT (s)
8.10 ± 3.56
84
PTTc (s)
9.19 ± 4.41
84
PBVI (mL/m2)
317.9 ± 151.1
84
RHC parameters
mPAP (mmHg)
22.4 ± 8.6
84
PCWP (mmHg)
14.3 ± 7.6
84
PVR (dyn-s/cm5)
1.8 ± 0.8
84
CVP (mmHg)
5.4 ± 3.6
84
TP (mmHg)
8.3 ± 2.5
84
DPG (mmHg)
0.00 ± 2.73
84
PAPi
6.4 ± 5.6
84
RVSWI (gm/m2)
6.3 ± 2.4
84
CI (L/min/m2)
2.4 ± 0.6
84
Values are presented as mean ± SD unless otherwise indicated.
Transthoracic echocardiography and right heart catheterization
TTE assessment of diastolic function was based on Doppler echocardiography of transmitral velocities of transmitral flow and tissue Doppler imaging of mitral annular velocity. Seventeen patients had normal diastolic function, 35 had impaired relaxation, 13 had pseudonormalization, and 19 had restrictive filling patterns. In addition, E/A and E/e´ were also entered as separately analyzed parameters.
According to the RHC, the mean mPAP of the population was 22.4 ± 8.6, PVR 1.84 ± 0.8, CVP 5.4 ± 3.6, PCWP 14.25 ± 7.64, and CI 2.36 ± 0.62. The patients were divided into subgroups according to the signs of PH: 47 had signs of PH (PH group), and 37 had no signs (non-PH group). Among the 47 patients with PH, 6 had isolated precapillary PH, 18 had IpcPH, and 22 had CpcPH. In one particular case, the patient had elevated mPAP over 20 mmHg, therefore signs of PH, but neither elevated PCWP nor PVR; thus, the patient could not be assigned to any category.
Of the six patients with precapillary PH, three were diagnosed with underlying lung disease at the time of the RHC; one patient was a smoker with a high likelihood of undetected lung pathology, and in two cases the cause remained unknown.
Pulmonary circulation parameters
Intra-observer reproducibility was excellent for both PTB (ICC 0.992, 95% CI 0.970–0.998) and PTT (ICC 0.988, 95% CI 0.953–0.997). Likewise, inter-observer reproducibility was also excellent for PTB (ICC 0.982, 95% CI 0.934–0.996) and PTT (ICC 0.969, 95% CI 0.883–0.992).
All PTT, PTTc, and PTB had moderate correlations (ranging from approximately 0.37 to 0.61) with LVEF, PCWP, mean PAP, cardiac output, and E/A. All values are shown in Table 2.
PTB, PTT, PTTc, CVP, CO, CI and PVR denote variables with log-normal distribution; logarithmic transformation was applied in these cases.
In addition, only PTT and PTTc showed a moderate correlation with PVR and E/e’. Other parameters correlating with PCP included the peak systolic myocardial velocity (S’) of the interventricular septum (IVS) assessed by pulsed-wave tissue Doppler imaging (TDI) and the central venous pressure (CVP). All correlations are shown in Table 2.
Patients with restrictive filling pattern (diastolic dysfunction grade III) showed significantly longer PTT compared to subgroups without diastolic dysfunction and with impaired relaxation (p = 0.01; p < 0.01 resp.) (see Fig 2).
10.1371/journal.pone.0341438.g002
Box-plot comparison of subgroups with different diastolic function.
Patients with diastolic dysfunction grade III (restrictive filling pattern, group 3) showed significantly longer PTT compared to subgroups without diastolic dysfunction (group 0) and with diastolic dysfunction grade II (impaired relaxation, group 2).
Finally, the PTT, PTTc, and PH ROC curves were assessed. In the case of PTT, the area under the curve was 72.7%, and the Youden index-based cut-off value was 8.62 s, with a sensitivity of 53.2% and a specificity of 86.5%. For PTTc, the area under the curve was 75.3%, and the Youden index-based cut-off value was 8.52 s, with a sensitivity of 70.2% and a specificity of 81.5% (see Fig 3 and Fig 4).
10.1371/journal.pone.0341438.g003
Receiver operating characteristics for pulmonary transit time and pulmonary hypertension.
Receiver operating characteristics demonstrating the ability of pulmonary transit time (PTT) to determine pulmonary hypertension with a threshold of 8.62, sensitivity of 53.2%, specificity of 86.5%, and an area under the curve of 72.7%.
10.1371/journal.pone.0341438.g004
Receiver operating characteristics for corrected pulmonary transit time and pulmonary hypertension.
Receiver operating characteristics demonstrating the ability of corrected pulmonary transit time (PTTc) to determine pulmonary hypertension with a threshold of 8.52, sensitivity of 70.2%, specificity of 81.1%, and an area under the curve of 75.3%.
Discussion
To our knowledge, this is the first study aimed to explore PCP parameters in RODCM patients involving three modalities (CMR, TTE, RHC) as gold standards for assessing systolic, diastolic function, and PH. Our findings suggest that the prolongation of PCP strongly correlates with parameters measured by CMR, RHC, and TTE, such as PVR, E/e´, LVEF, PCWP, CI, and grade III diastolic dysfunction, demonstrating the ability of PTT to differentiate patients with PH using CMR. Similarly to what we have described previously [1], although still limited, current data show a strong predictive value for the prolongation of PCP across various cardiac diagnoses, making this dynamically developing topic attractive for clinical applications today. From a pathophysiological point of view, longer times correspond to impairments of either the pumping function of the heart (systolic for both ventricles, diastolic for the LV) or the lungs‘response (foremost PH). This behaviour implies that these parameters have a unique potential to assess the cardiopulmonary system. To date, no CMR-based method reliably estimates markers of PH, and even the assessment of diastolic function remains highly limited. This approach, combined with the simplicity of their acquisition and the growing body of evidence supporting their predictive value, makes them a highly promising marker for the future of integrated cardiopulmonary diagnostics.
Expanding the available PCP data with correlations to RHC, which are currently severely limited, our results further demonstrate the potential of these fairly new parameters to contribute significantly to the assessment of pulmonary circulation as a whole, giving them great potential to complement existing diagnostic tools.
In addition, this is the first study to focus on CMR-based PCP assessment in patients with RODCM. The time between CMR and RHC in our cohort was only 8 days at most, while it was up to 30 days in previous works [14,15]. The mean time delay between CMR and RHC was 1.8 ± 2.1 days and in the case of CMR and TTE 4.7 ± 12.1 days. Since hemodynamics can be influenced by many different things, such as congestion, this approach reduces potential bias and ensures methodological consistency.
Finally, we also found that PTB showed less correlation with the studied parameters, while PTT and PTTc are comparable in their diagnostic ability, making them preferable for assessment, as they offer a more optimal option for differentiating PH using CMR.
This study has some limitations. Foremost, it is a retrospective single-centre study. Another limitation is our patient selection, RODCM. In them, isolated precapillary PH is rare; therefore, data on comparing precapillary with other types of PH are severely limited. One of the objectives of this study was to determine whether PCP can distinguish patients with isolated pre- or postcapillary PH. Although these parameters (particularly PTT and PTTc) correlate with PCWP, they also show a weaker correlation with PVR. In our dataset, the cohort consisted of patients with newly diagnosed HF referred to our center, and as expected, the largest subgroup was those with CpcPH. In contrast, the number of patients with isolated precapillary PH was very limited. Partly because of this, we were unfortunately unable to differentiate isolated pre- or postcapillary PH using PCP alone reliably. It would also be invaluable to study prognosis in RODCM patients based on PCP, but we were not able to do so based on our data. However, we plan to carry out such a study in the future.
Conclusion
To our knowledge, this is the first study focused on CMR-derived PCP in a RODCM group, including three diagnostic modalities as gold standards for assessing systolic function, diastolic function, and PH. Our findings show that PTT and PTTc are prolonged with impaired systolic and diastolic function as well as PH. Therefore, PTT and PTTc might offer critical information for a comprehensive evaluation of the cardio-pulmonary system as a whole.
Supporting information
PH subgroups.
(XLSX)
Source data file.
(XLSX)
Abbreviations:BMI
body mass index
BSA
body surface area
b-TFE
balanced turbo field echo
CO
cardiac output
CI
cardiac index
CMR
cardiovascular magnetic resonance
CpcPH
combined post- and pre-capillary pulmonary hypertension
CVP
central venous pressure
DPG
diastolic pulmonary artery pressure
HR
heart rate
IpcPH
isolated post-capillary pulmonary hypertension
LV
left ventricle
LVEF
left ventricular ejection fraction
LVEDV
left ventricle end-diastolic volume
LVESV
left ventricle end-systolic volume
LVOT
left ventricular outflow tract
LVSV
left ventricular stroke volume
mPAP
mean pulmonary artery pressure
MRI
magnetic resonance imaging
PAPi
pulmonary artery pulsatility index
PBVI
pulmonary blood volume index
PCP
pulmonary circulation parameters
PCWP
pulmonary capillary wedge pressure
PH
pulmonary hypertension
PTB
pulmonary transit beats
PTT
pulmonary transit time
PTTc
Bazett’s formula corrected pulmonary transit time
PVR
pulmonary vascular resistance
RHC
right heart catheterization
RODCM
recent-onset dilated cardiomyopathy
ROC
receiver operating characteristic
ROIs
regions of interest
RVSWI
right ventricular stroke work index
RV
right ventricle
RVEF
right ventricle ejection fraction
RVSV
right ventricular systolic volume
SAX
short-axis
SI
signal intensity
SSFP
steady-state free precession
TE
echo time
TP
transpulmonary gradient
TR
repetition time
TTE
transthoracic echocardiography
ReferencesOpatřilL, PanovskýR, Mojica-PisciottiM, KrejčíJ, MasárováL, KinclV, et al. Stress and rest pulmonary transit times assessed by cardiovascular magnetic resonance. Cardiol Rev. 2024;32(3):243–7. doi: 10.1097/CRD.000000000000049536728820OpatřilL, PanovskyR, Mojica-PisciottiM, MáchalJ, KrejčíJ, HolečekT, et al. Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant. Sci Rep. 2022;12(1):6130. doi: 10.1038/s41598-022-09739-z35414701HouardL, AmzulescuMS, ColinG, LangetH, MilitaruS, RousseauMF, 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.120.01168033438438CaoJJ, LiL, McLaughlinJ, PassickM. Prolonged central circulation transit time in patients with HFpEF and HFrEF by magnetic resonance imaging. Eur Heart J Cardiovasc Imaging. 2018;19(3):339–46. doi: 10.1093/ehjci/jex05128387860SeraphimA, KnottKD, MenachoK, et al. Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR. JACC:Cardiovascular Imaging. 2021;14(11):2107–19. doi: 10.1016/j.jcmg.2021.03.029SlutskyRA, BhargavaV, HigginsCB. 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):41–5.ColinGC, PouleurA-C, GerberBL, PonceletP-A, de MeesterC, D’HondtA-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):1291–8. doi: 10.1093/ehjci/jez29031808507HeroldIHF, Soliman HamadMA, van AssenHC, BouwmanRA, KorstenHHM, MischiM. 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/aeu554257535982022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension | European Heart Journal | Oxford Academic. Accessed February 17, 2024. https://academic.oup.com/eurheartj/article/43/38/3618/6673929DugoC, RigolliM, RossiA, WhalleyGA. Assessment and impact of diastolic function by echocardiography in elderly patients. J Geriatr Cardiol. 2016;13(3):252–60. doi: 10.11909/j.issn.1671-5411.2016.03.00827103921MottramPM, MarwickTH. Assessment of diastolic function: what the general cardiologist needs to know. Heart. 2005;91(5):681–95. doi: 10.1136/hrt.2003.02941315831663SegerothM, WinkelDJ, StrebelI, YangS, van der StouweJG, FormambuhJ, et al. Pulmonary transit time of cardiovascular magnetic resonance perfusion scans for quantification of cardiopulmonary haemodynamics. Eur Heart J Cardiovasc Imaging. 2023;24(8):1062–71. doi: 10.1093/ehjci/jead00136662127RicciF, AungN, ThomsonR, BoubertakhR, CamaioniC, DoimoS, et al. Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy. Eur Heart J Cardiovasc Imaging. 2019;20(12):1368–76. doi: 10.1093/ehjci/jez21331504370GongC, GuoX, WanK, ChenC, ChenX, GuoJ, et al. Corrected MRI pulmonary transit time for identification of combined precapillary and postcapillary pulmonary hypertension in patients with left heart disease. J Magn Reson Imaging. 2023;57(5):1518–28. doi: 10.1002/jmri.2838637021578CaoJJ, LiL, McLaughlinJ, PassickM. Prolonged central circulation transit time in patients with HFpEF and HFrEF by magnetic resonance imaging. Eur Heart J Cardiovasc Imaging. 2018;19(3):339–46. doi: 10.1093/ehjci/jex05128387860PanovskýR, PešlM, HolečekT, MáchalJ, FeitováV, MrázováL, 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/s13023-018-0986-030626423Schulz-MengerJ, BluemkeDA, BremerichJ, FlammSD, FogelMA, FriedrichMG, 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;15(1):35. doi: 10.1186/1532-429X-15-3523634753IshidaM, SchusterA, MortonG, ChiribiriA, HussainS, PaulM, 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-13-2821609423NaguehSF, AppletonCP, GillebertTC, MarinoPN, OhJK, SmisethOA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10(2):165–93. doi: 10.1093/ejechocard/jep00719270053NaguehSF, SmisethOA, AppletonCP, Byrd BF3rd, DokainishH, EdvardsenT, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the american society of echocardiography and the European association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging. 2016;17(12):1321–60. doi: 10.1093/ehjci/jew0822742289910.1371/journal.pone.0341438.r001Decision Letter 0BauerWolfgangAcademic Editor2026Wolfgang BauerThis is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Submission Version0
27 Oct 2025
Dear Dr. Panovský,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.
Please submit your revised manuscript by Dec 11 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.
A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.
If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .
We look forward to receiving your revised manuscript.
Kind regards,
Wolfgang Rudolf Bauer, M.D., Ph.D.
Academic Editor
PLOS ONE
Journal Requirements:
When submitting your revision, we need you to address these additional requirements.
1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf
2. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.
3. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.
Before we proceed with your manuscript, please address the following prompts:
a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.
b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible.
Please update your Data Availability statement in the submission form accordingly.
4. In the online submission form, you indicated that data cannot be shared publicly - eventough it is pseudoanonymized, it still contains potentially confident data about our patients and therefore we cannot share it publicly. Data are available from the Internationa Clinical Research Center Institutional Data Access (contact via corresponding author - ass. prof. Panovský) for researchers who meet the criteria for access to confidential data.
All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information.
This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval.
5. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.
When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.
6. Thank you for stating the following financial disclosure:
Supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU and by AZV grant project undert Ministry of Health of the Czech Republic, grant nr. NU22-02-00418.
Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."
If this statement is not correct you must amend it as needed.
Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.
7. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.
[Note: HTML markup is below. Please do not edit.]
Reviewers' comments:
Reviewer's Responses to Questions
Comments to the Author
1. Is the manuscript technically sound, and do the data support the conclusions?
Reviewer #1: Yes
Reviewer #2: Yes
**********
2. Has the statistical analysis been performed appropriately and rigorously? -->?>
Reviewer #1: Yes
Reviewer #2: Yes
**********
3. Have the authors made all data underlying the findings in their manuscript fully available??>
The PLOS Data policy
Reviewer #1: Yes
Reviewer #2: Yes
**********
4. Is the manuscript presented in an intelligible fashion and written in standard English??>
Reviewer #1: Yes
Reviewer #2: Yes
**********
Reviewer #1: systolic and diastolic function and pulmonary hypertension in 84 patients with recent-onset dilated cardiomyopathy. All patients had a CMR examination, RHC (including pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance 42 (PVR)), and TTE. The pulmonary transit time (PTT) and corrected pulmonary transit time 43 (PTTc) correlated with PCWP, cardiac index, PVR, and E/e’. ROC AUC was of 72.7% for PTT and 75.3% for PTTc, with cut-off values of 8.62 s (PTT) and 8.52 s (PTTc). The authors conclude that CMR-derived PCP might offer critical information to evaluate the cardio-pulmonary system comprehensively in patients with DCM.
The manuscript deals with an interesting topic and is based on sound methodology,
There are some points the authors might wish to address to further improve the manuscript.
1) Patients were divided in groups according to their PH and diastolic function. What was the respective rationale? Please specify.
2) Please provide quality assurance measures for CMR parameters (inter- and intra-observer agreement)
3) Is the software and algorithms used in this project freely available/transferable to other centers/machines?
4) What was the time delay between the different assessments (CMR, Echo, RHC)?
5) Table 1: gender: the n is missing
6) Table 1: “TEE” might rather the “TTE”
7) Table 1: the number of decimals should be equal for all numbers. One decimal might be sufficient
8) Table 1: for consistency, please also provide TTE LVEF and TR Vmax or TRmaxPG
9) Since you report a correlation with IVS, please provide the respective value in table 1
10) What parameters was the diagnosis of RODCM based on? Signs/Symptoms, NT-proBNP, Imaging markers??
Reviewer #2: General comments
The manuscript presents a retrospective cohort study analyzing pulmonary circulation parameters (Pulmonary Transit Beats [PTB], Pulmonary Transit Time [PTT], and corrected PTT [PTTc]) derived from cardiovascular magnetic resonance (CMR) imaging in comparison with right heart catheterization (RHC) and echocardiographic parameters, in 84 patients with recent-onset dilated cardiomyopathy. The authors demonstrate that PTT and PTTc correlate with systolic and diastolic cardiac function as well as hemodynamic indices from RHC, and that these metrics predict pulmonary hypertension (PH).
Specific comments
1. Table 1 Formatting
- Please avoid reporting unnecessarily precise values, e.g., heart rate of 77.67 ± 17.08. Rounding should be applied where appropriate.
- Add a column indicating the number of available data points for each parameter. If all values are complete, mention this briefly in the Methods section.
- Present mean and systolic pulmonary artery pressure as well as cardiac index (CI) in Table 1. The data for mPAP and CI are already presented on page 11, line 183.
- Define “pulmonary artery pressure index” in the Methods section.
- DPG refers to “diastolic pressure gradient,” not “Diastolic Pulmonary Artery Pressure” (page 11, line 174). DPG is the difference between pulmonary artery diastolic pressure and pulmonary capillary wedge pressure. Please provide this definition in the Methods.
2. Subgroup Division and Classification (Page 11, lines 184–187)
The numbers cited for PH subgroups do not add up to the total of 84 patients. Please verify and correct the classification.
- Remove the 28 “precapillary” entry; do not sum isolated precapillary patients with combined post- and precapillary PH.
- One patient remains unclassified; please clarify.
The correct breakdown should be:
- 37 patients without PH
- 47 patients with PH
--6 with precapillary PH.
--40 with postcapillary PH
---18 isolated postcapillary PH (IpcPH)
---22 combined post- and precapillary PH (CpcPH)
3. Please provide a more detailed characterization of the patients classified as having precapillary pulmonary hypertension. Specifically, did these individuals have underlying lung disease or other identifiable etiologies for precapillary PH? Alternatively, did they exhibit features typical of postcapillary PH, apart from the absence of PAWP elevation? Additionally, please report the average pulmonary artery wedge pressure (PAWP) for this subgroup.
4. Can you provide a table divided by patients with no PH, pcPH and prePH illustrating all CMR and RHC parameters?
5. Completeness of Table 1 (Page 11, line 188)
Table 1 does not present a complete list of evaluated parameters. Please ensure all relevant variables are included or adjust the related text accordingly.
6. Discussion
- The first two discussion paragraphs are repetitive. Please streamline and avoid using nearly identical sentences.
- The discussion is brief. Please elaborate on the clinical advantage of assessing PTB, PTT and PTTc by CMR compared to standard echocardiographic evaluation of PH.
State whether PTT or PTTc can predict increased pulmonary artery wedge pressure (PAWP), as this would markedly increase the clinical utility of your results.
**********
what does this mean? ). If published, this will include your full peer review and any attached files.
If you choose “no”, your identity will remain anonymous but your review may still be made public.
Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy
Reviewer #1: No
Reviewer #2: No
**********
[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]
To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures
You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.
NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.
10.1371/journal.pone.0341438.r002Author response to Decision Letter 1Submission Version1
16 Dec 2025
Review Comments to the Author
Reviewer #1:
systolic and diastolic function and pulmonary hypertension in 84 patients with recent-onset dilated cardiomyopathy. All patients had a CMR examination, RHC (including pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance 42 (PVR)), and TTE. The pulmonary transit time (PTT) and corrected pulmonary transit time 43 (PTTc) correlated with PCWP, cardiac index, PVR, and E/e’. ROC AUC was of 72.7% for PTT and 75.3% for PTTc, with cut-off values of 8.62 s (PTT) and 8.52 s (PTTc). The authors conclude that CMR-derived PCP might offer critical information to evaluate the cardio-pulmonary system comprehensively in patients with DCM.
The manuscript deals with an interesting topic and is based on sound methodology,
There are some points the authors might wish to address to further improve the manuscript.
Thank you very much for your review and valuable input. We will address each of your comments below.
1) Patients were divided in groups according to their PH and diastolic function. What was the respective rationale? Please specify.
Thank you for the question. Our rationale for dividing patients into two groups based on pulmonary hypertension (PH) status and diastolic function was based on the distinct physiological mechanisms through which these conditions influence pulmonary transit time (PTT) and pulmonary circulation parameters (PCP).
For pulmonary hypertension, right-heart catheterization represents the gold standard for diagnosis, and the elevated pulmonary artery pressure values determined by this method (>20 mmHg) officially define PH. Separating patients into PH and non-PH groups allowed us to assess whether PTT and PTTc could discriminate between patients with and without elevated pulmonary pressures using an established gold-standard reference. This grouping was therefore essential to evaluate the diagnostic utility of these CMR-derived parameters.
For diastolic dysfunction, transthoracic echocardiography remains the most reliable noninvasive method for grading diastolic function. Diastolic function is the ability of the myocardium to relax and adjust its compliance to allow adequate and pressure-efficient ventricular filling during diastole. It is essential for maintaining optimal hemodynamic stability; therefore, it affects PCP in another way. Grouping patients by diastolic dysfunction grade allowed us to examine whether PCP and related measurements reflect these known pathophysiological differences.
Our approach enabled us to study the link between CMR-derived parameters and established echocardiographic markers across clinically relevant categories of dysfunction.
2) Please provide quality assurance measures for CMR parameters (inter- and intra-observer agreement)
Thank you for bringing this crucial point to our attention. While the automated algorithm for onset detection is deterministic (ensuring that signal intensity curve generation and onset identification are fully reproducible for any given ROI placement), variability in manual ROI placement contributes to measurement variability between observers and repeated measurements. Therefore, we randomly selected 10 cases (12% of the study population) and assessed the inter- and intra-observer reproducibility for pulmonary circulation parameters (PTB and PTT) using the intraclass correlation coefficient (ICC) (type C, two-way mixed-effects model). We added this description to the "statistical methods" section:
"Intra- and inter-observer reproducibility were assessed using the intraclass correlation coefficient (ICC) (type C, two-way mixed-effects model with 95% confidence intervals (CI) from ten randomly selected cases. These cases were analyzed by two readers, one of whom repeated the analysis two weeks apart. The repeatability was classified as poor (<0.5), fair (0.50 to 0.75), good (0.75 to 0.90), and excellent (0.90 to 1)."
Also, we report now in the "Pulmonary circulation parameters" subsection from the "results" section in the revised manuscript this information, i.e.,
"Pulmonary circulation parameters intra-observer reproducibility was excellent for both PTB (ICC 0.992, 95% CI 0.970-0.998) and PTT (ICC 0.988, 95% CI 0.953-0.997). Likewise, inter-observer reproducibility was also excellent for PTB (ICC 0.982, 95% CI 0.934-0.996) and PTT (ICC 0.969, 95% CI 0.883-0.992)."
3) Is the software and algorithms used in this project freely available/transferable to other centers/machines?
We thank the reviewer for the comment. The PTB and PTT analyses were performed using a custom Python script, which is not publicly available and not for commercial use. However, our approach is entirely transferable and can be reproduced on other systems and scanners by following the methodology described in the manuscript: motion correction of first-pass perfusion images, manual ROI placement in the RV and LV with automatic propagation across frames, extraction of signal intensity curves, onset detection, and calculation of PTB and PTT as the difference between LV and RV onset points (frame number or time, respectively). Our algorithm uses standard image processing techniques and readily available peak-detection methods in Python libraries. Centers with basic programming capabilities can implement this workflow using the detailed methodology provided.
4) What was the time delay between the different assessments (CMR, Echo, RHC)?
Thank you for the question. In the case of CMR and RHC, as stated in the discussion, the time between the two modalities was at most 8 days, which we consider essential, as hemodynamics can change significantly depending on factors such as the patient’s cardiac compensation, volume status, etc. As part of the statistical analysis, we also tested a subgroup with a maximum interval of only 3 days between the examinations; the results were comparable. Therefore, in the final version of the article, we kept the larger cohort with examinations performed within 8 days.
The mean time delay between CMR and RHC was 1.8 ± 2.1 days, and between CMR and ECHO, 4.7 ± 12.1 days. We updated the discussion section accordingly.
5) Table 1: gender: the n is missing
Thank you for this point and we apologize for the omission. We updated the table to include the number of available values for each parameter, and also specified the number of male patients.
6) Table 1: “TEE” might rather the “TTE”
Thank you for noticing this typo. The table has been updated accordingly.
7) Table 1: the number of decimals should be equal for all numbers. One decimal might be sufficient
Thank you for pointing this out. We updated the corresponding values in the tables to retain the proper number of significant digits.
8) Table 1: for consistency, please also provide TTE LVEF and TR Vmax or TRmaxPG
Thank you for your detailed point. Indeed, it improves consistency. Therefore, we updated Table 1 to include other TTE parameters, such as LVEF (%), TRPG (mmHg) (representing “TRmaxPG”), and sPAP (mmHg) as well..
9) Since you report a correlation with IVS, please provide the respective value in table 1
Thank you for this insightful point. In the "Pulmonary circulation parameters" subsection from the "results" section, we previously stated that “Other parameters correlating with PCP included the interventricular septum (IVS) from the tissue Doppler imaging (TDI).” This sentence meant the correlation of PCP with the TDI-derived peak systolic myocardial velocity S”, which was already shown in Table 1. To clarify this point, we updated the respective part of the results section to: “Other parameters correlating with PCP included the peak systolic myocardial velocity (S') of the interventricular septum (IVS) assessed by pulsed-wave tissue Doppler imaging (TDI).” In addition, since we listed the correlations in Table 2, we also included the correlation of this parameter in the table.
10) What parameters was the diagnosis of RODCM based on? Signs/Symptoms, NT-proBNP, Imaging markers??
Thank you for raising this relevant point. The definition of the RODCM throughout the literature is not standardized and lacks unification. In our article, we included patients with newly diagnosed dilated cardiomyopathy with heart failure symptoms appearing in the last six months, referred to our center based on the results from other hospitals. This is the most common definition. We updated the introduction section accordingly to include this definition.
Review Comments to the Author
Reviewer #2:
General comments
The manuscript presents a retrospective cohort study analyzing pulmonary circulation parameters (Pulmonary Transit Beats [PTB], Pulmonary Transit Time [PTT], and corrected PTT [PTTc]) derived from cardiovascular magnetic resonance (CMR) imaging in comparison with right heart catheterization (RHC) and echocardiographic parameters, in 84 patients with recent-onset dilated cardiomyopathy. The authors demonstrate that PTT and PTTc correlate with systolic and diastolic cardiac function as well as hemodynamic indices from RHC, and that these metrics predict pulmonary hypertension (PH).
Thank you very much for your review and valuable input. In addition to your comments, we also addressed those from the editor and another reviewer to our updated manuscript.
Specific comments
1. Table 1 Formatting
- Please avoid reporting unnecessarily precise values, e.g., heart rate of 77.67 ± 17.08. Rounding should be applied where appropriate.
Thank you for your suggestion. We updated the tables to include only the proper number of significant digits..
- Add a column indicating the number of available data points for each parameter. If all values are complete, mention this briefly in the Methods section.
Thank you for mentioning this point. We added the information to the table where possible. In some cases, the data points werenot available for all patients. For example, E/A data were not available for all patients because patients with atrial fibrillation lack an “A” wave.
- Present mean and systolic pulmonary artery pressure as well as cardiac index (CI) in Table 1. The data for mPAP and CI are already presented on page 11, line 183.
Thank you for this valuable suggestion. We updated Table 1 and added information on systolic pulmonary artery pressure (sPAP) and CI.
- Define “pulmonary artery pressure index” in the Methods section.
Thank you very much for noticing this omission. In Table 1, “PAPi” is defined as the “pulmonary artery pressure index,” but instead it should have been “Pulmonary Artery Pulsatility Index.” We are a transplantation + LVAD center, and PAPi is a clinically validated hemodynamic parameter used to assess the RV function, which is crucial in patients before LVAD implantation. It is defined as: PAPI = (Pulmonary artery systolic pressure – Pulmonary artery diastolic pressure) / Right atrial pressure. The methods section and table have been updated accordingly. We apologize for this oversight.
- DPG refers to “diastolic pressure gradient,” not “Diastolic Pulmonary Artery Pressure” (page 11, line 174). DPG is the difference between pulmonary artery diastolic pressure and pulmonary capillary wedge pressure. Please provide this definition in the Methods.
Thank you for noticing this oversight. We have added the definition in the methods section.
2. Subgroup Division and Classification (Page 11, lines 184–187)
The numbers cited for PH subgroups do not add up to the total of 84 patients. Please verify and correct the classification.
- Remove the 28 “precapillary” entry; do not sum isolated precapillary patients with combined post- and precapillary PH.
- One patient remains unclassified; please clarify.
The correct breakdown should be:
- 37 patients without PH
- 47 patients with PH
--6 with precapillary PH.
--40 with postcapillary PH
---18 isolated postcapillary PH (IpcPH)
---22 combined post- and precapillary PH (CpcPH)
Thank you for raising this valuable comment. The PH and non-PH subgroups consisted of 47 and 37 patients, respectively, for a total of 84 patients. We believe the issue arises from a lack of clarity in the description we provided previously. Therefore, we revised the sentence for greater clarity. Including the “precapillary” category was indeed confusing; the original rationale was primarily statistical, but from a clinical perspective, it added ambiguity, so we removed it. The same applied to patients with postcapillary PH; therefore, we excluded this category as well. We retained only “isolated precapillary PH,” “isolated postcapillary PH,” and “combined pre- and postcapillary PH”, which also better reflects the guideline-based classification. Regarding the numbers, one patient had an mPAP of 21 mmHg, a PCWP of 13 mmHg, and a PVR of 1.8 WU, and thus could not be assigned to any category. In the literature, such cases are described as either “unclassified pulmonary hypertension” or “borderline/mildly elevated mPAP without a confirmed pre-capillary or post-capillary component.” The updated description is:
“The patients were divided into subgroups according to the signs of PH: 47 had signs of PH (PH group), and 37 had no signs (non-PH group). Among the 47 patients with PH, 6 had isolated precapillary PH, 18 had IpcPH, and 22 had CpcPH. In one particular case, the patient had elevated mPAP over 20 mmHg, therefore signs of PH, but neither elevated PCWP nor PVR; thus, the patient could not be assigned to any category.”
3. Please provide a more detailed characterization of the patients classified as having precapillary pulmonary hypertension. Specifically, did these individuals have underlying lung disease or other identifiable etiologies for precapillary PH? Alternatively, did they exhibit features typical of postcapillary PH, apart from the absence of PAWP elevation? Additionally, please report the average pulmonary artery wedge pressure (PAWP) for this subgroup.
Thank you for the opportunity to explain these details better. There were 6 patients classified as having precapillary PH in total. They showed a little bit higher LVEF than the whole population (27.1% ± 9.4 vs. 24.4% ± 9.3), comparable mPAP (23 mmHg ± 1.2 mmHg vs. 22.4 ± 8.6 mmHg) and lower PCWP (12.83 ± 0.9 mmHg vs. 14.3 ± 8.6 mmHg). The average pulmonary artery wedge pressure for subgroups with isolated postcapillary PH was even higher - 20.3 ± 5.1 mmHg. Additionally, from the 6 patients with precapillary PH, 3 were diagnosed with lung diseases at the time of the RHC; one patient was a smoker and drug user with high probability of underlying lung disease and in 2 cases the cause was unknown; therefore, idiopathic. Apart from the heart failure itself, they did not exhibit features typical of postcapillary PH.
We updated the results section to clarify this:
Of the six patients with precapillary PH, three were diagnosed with underlying lung disease at the time of the RHC; one patient was a smoker with a high likelihood of undetected lung pathology, and in two cases the cause remained unknown.”
4. Can you provide a table divided by patients with no PH, pcPH and prePH illustrating all CMR and RHC parameters?
Thank you for this suggestion. Yes, we can provide this table as a supplementary file. It illustrates the main CMR and RHC parameters for our cohort, and we hope it strengthens our findings.
5. Completeness of Table 1 (Page 11, line 188)
Table 1 does not present a complete list of evaluated parameters. Please ensure all relevant variables are included or adjust the related text accordingly.
Thank you for this suggestion. We updated the table with more evaluated parameters - including parameters such as LVEF (%), TRPG (mmHg) (representing “TRmaxPG”), sPAP (mmHg), mPAP (mmHg), and CI (L/min/m^2).
6. Discussion
- The first two discussion paragraphs are repetitive. Please streamline and avoid using nearly identical sentences.
- The discussion is brief. Please elaborate on the clinical advantage of assessing PTB, PTT and PTTc by CMR compared to standard echocardiographic evaluation of PH.
State whether PTT or PTTc can predict increased pulmonary artery wedge pressure (PAWP), as this would markedly increase the clinical utility of your results.
Submitted filename: Response to Reviewers.docx
10.1371/journal.pone.0341438.r003Decision Letter 1BauerWolfgangAcademic Editor2026Wolfgang BauerThis is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Submission Version1
7 Jan 2026
Comparison of pulmonary circulation parameters acquired by cardiovascular magnetic resonance with right heart catheterization and transthoracic echocardiography in patients with recent-onset dilated cardiomyopathy
PONE-D-25-33529R1
Dear Dr. Panovský,
We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.
Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.
An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .
If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.
Kind regards,
Wolfgang Rudolf Bauer, M.D., Ph.D.
Academic Editor
PLOS One
Additional Editor Comments (optional):
Reviewers' comments:
Reviewer's Responses to Questions
Comments to the Author
Reviewer #2: All comments have been addressed
**********
2. Is the manuscript technically sound, and do the data support the conclusions??>
Reviewer #2: Yes
**********
3. Has the statistical analysis been performed appropriately and rigorously? -->?>
Reviewer #2: Yes
**********
4. Have the authors made all data underlying the findings in their manuscript fully available??>
The PLOS Data policy
Reviewer #2: Yes
**********
5. Is the manuscript presented in an intelligible fashion and written in standard English??>
Reviewer #2: Yes
**********
Reviewer #2: Thank you for the thorough revision and happy new Year!
All my comments were addressed. I have only one further recommendation. The column “number” in table 1 illustrates the total number of participants to acknowledge the number of missings. The lign “ male gender” however shows the number of male participants (N=64). I doubt that the gender was unknown in 20 individuals. Please correct the number.
**********
what does this mean? ). If published, this will include your full peer review and any attached files.
If you choose “no”, your identity will remain anonymous but your review may still be made public.
Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy
Reviewer #2: No
**********
10.1371/journal.pone.0341438.r004Acceptance letterBauerWolfgangAcademic Editor2026Wolfgang BauerThis is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
27 Oct 2025
PONE-D-25-33529R1
PLOS One
Dear Dr. Panovský,
I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team.
At this stage, our production department will prepare your paper for publication. This includes ensuring the following:
* All references, tables, and figures are properly cited
* All relevant supporting information is included in the manuscript submission,
* There are no issues that prevent the paper from being properly typeset
You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.
Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.
You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing.
If we can help with anything else, please email us at customercare@plos.org.
Thank you for submitting your work to PLOS ONE and supporting open access.