https://orcid.org/0000-0002-9295-9344
Abstract
We aim to evaluate the clinical relevance and the prognostic value of arterial and venous renal Doppler in acute decompensated precapillary pulmonary hypertension (PH).
The renal resistance index (RRI) and the Doppler-derived renal venous stasis index (RVSI) were monitored at admission and on Day 3 in a prospective cohort of precapillary PH patients managed in intensive care unit for acute right heart failure (RHF). The primary composite endpoint included death, circulatory assistance, urgent transplantation, or rehospitalization for acute RHF within 90 days following inclusion. Ninety-one patients were enrolled (58% female, age 58 ± 16 years). The primary endpoint event occurred in 32 patients (33%). In univariate logistic regression analysis, variables associated with RRI higher than the median value were non-variable parameters (age and history of hypertension), congestion (right atrial pressure and renal pulse pressure), cardiac function [tricuspid annular plane systolic excursion (TAPSE) and left ventricular outflow tract- velocity time integral], systemic pressures and NT-proBNP. Variables associated with RVSI higher than the median value were congestion (high central venous pressure, right atrial pressure, and renal pulse pressure), right cardiac function (TAPSE), severe tricuspid regurgitation, and systemic pressures. Inotropic support was more frequently required in patients with high RRI (P = 0.01) or high RVSI (P = 0.003) at the time of admission. At Day 3, a RRI value <0.9 was associated with a better prognosis after adjusting to the estimated glomerular filtration rate.
Renal Doppler provides additional information to assess the severity of patients admitted to the intensive care unit for acute decompensated precapillary PH.
Introduction
Precapillary pulmonary hypertension (PH) defines a group of disorders characterized by a progressive increase in pulmonary vascular resistance (PVR) that develops as a result of abnormal remodelling of the pulmonary microvasculature.1 The prognosis of these patients is mainly driven by the ability of the right ventricle to adapt to the progressive increase in afterload. The occurrence of an episode of acute right heart failure (RHF) in patients with chronic precapillary PH is characterized by a rapidly progressive syndrome with systemic congestion resulting from impaired right ventricular (RV) filling and reduced RV flow output.2–4 This condition can affect all organ system and is characterized by a very poor prognosis in the short-term.5–9 All observational studies have identified acute renal insufficiency as a major prognostic factor. The pathophysiological mechanisms leading to acute renal dysfunction during an episode of acute RHF are probably similar to those observed in type I cardiorenal syndrome. Both elevated venous pressures combined with circulatory insufficiency contribute to decreased renal perfusion.10
Intensive care for acute decompensated precapillary PH is based on the treatment of triggering factors, careful fluid management, and strategies to improve cardiac function and reduce RV afterload. In the case of refractory RHF despite maximal medical treatment, the use of mechanical support should now be considered in selected candidates for lung transplantation, or less commonly as a bridge to recovery in patients with a treatable cause of right-sided heart failure.2 Therefore, close monitoring of cardiac and other organ failure is mandatory to optimize the management of these patients in the intensive care unit (ICU). Early detection of the consequences of cardiac failure on systemic organs and more specifically on renal function appears to be a key factor to anticipate an evolution towards refractory RHF. Unfortunately, the early identification of worsening renal function is highly challenging as the use of serum creatinine and estimated glomerular filtration rate (eGFR) has several limitations.
Arterial and venous Doppler ultrasonography was recently proposed to evaluate renal perfusion and congestion.11 Previous studies have demonstrated the potential prognostic value of renal Doppler in chronic left12–14 and RHF15 in stable conditions. Moreover, in acute left heart failure, the renal perfusion assessed by the renal resistive index (RRI) at admission could predict worsening renal function16 and a change of intrarenal venous flow pattern from discontinuous to continuous pattern seems to be relevant to predict outcomes of patients.17 In contrast, the clinical significance and prognostic value of renal Doppler in acute decompensated precapillary PH have never been studied.
The aim of our study was to identify the parameters that lead to a perturbance of venous and arterial Doppler in acute decompensated precapillary PH and to evaluate the prognostic value of the arterial and venous renal Doppler at the time of admission in the ICU and three days after the initiation of medical support.
Methods
Study design
Patients who were referred to the ICU of the French Reference Center of PH for the management of acute decompensated precapillary PH were prospectively enrolled between 1 December 2019 and 31 July 2021. This monocentric non-interventional prospective study was approved by the institutional review board of the French Society of Respiratory Diseases (Reference CEPRO 2021-003) according to French regulations. All patients gave informed consent to participate. In addition, all were enrolled in the French PH Registry. The data collected were anonymized and complied with the requirements of the ‘Commission Nationale Informatique et Libertés’, the organization dedicated to privacy, information technology, and civil rights in France. The committee approved the methods used to collect and analyse the data on 24 May 2003 (approval number 842063).
Patient population
Patient inclusion in the present study required a baseline right heart catheterization (RHC) confirming precapillary PH due to pulmonary vascular disease, defined as a mean pulmonary arterial pressure >20 mmHg with mean pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and PVR ≥ 2 Wood units. In line with current PH guidelines, all patients with a diagnosis of precapillary PH underwent extensive investigations to detect causes or risk factors for PH.18 Patients included in the study exhibited acute clinical deterioration (within one month before ICU admission) associated with clinical and biological evidence of systemic congestion and/or low cardiac output due to RHF.2 Exclusion criteria were age fewer than 18, postcapillary PH, pregnancy, end-stage chronic kidney disease on renal replacement therapy, history of renal transplantation, shock related to a cause other than RHF (such as sepsis), and technical difficulties in imaging renal vessels by Doppler sonography. Management of RHF in the ICU is described in Supplementary data online, Materials and methods.
Monitoring and data collection
Data from all enrolled patients were prospectively collected at the time of admission and on Day 3. Baseline demographics were recorded. We analysed clinical data and biological data. Laboratory data included serum blood urea nitrogen (BUN), creatinine, sodium, and N-terminal B-type natriuretic peptide (NT-proBNP). The glomerular filtration rate (GFR) on admission to the hospital was estimated using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation.19 If a central venous catheter was required, central venous pressure (CVP) and venous oxygen saturation were collected. Renal perfusion pressure was defined as the mean arterial pressure (MAP)—central venous pressure (CVP). In a subgroup of patients, RHC was performed within two hours before ICU admission at the discretion of the physician. The cardiac index was calculated using the thermodilution method.
The intrarenal Doppler and transthoracic echocardiography were performed with a Vivid S70 system (GE Healthcare, Horton, Norway) before intravenous diuretic or any treatment initiation and at Day 3.
Renal Doppler ultrasonography was performed with the use of a convex transducer frequency range of 2.5–5 MHz and a simultaneous electrocardiogram was obtained to precisely identify the phases of the cardiac cycle. Resting images were obtained in the left semi-lateral decubitus position where the right kidney was recorded. Colour Doppler images were used to locate interlobar vessels. Pulsed Doppler waveforms of interlobar arteries and veins were recorded simultaneously during a breathing pause and patients were asked to avoid Valsalva. The RRI was obtained with the arterial Doppler while the intrarenal venous flow pattern (IRVF) and the Renal venous stasis index (RVSI) were obtained by the venous Doppler. All measurements were averaged over three cardiac cycles during sinus rhythm, or five cardiac cycles if patients were in atrial fibrillation. We determined the maximal systolic velocity (MSV) and end-diastolic velocity (EDV) (centimeters/second) to calculate the RRI as = [(MSV − EDV)/MSV]. If the EDV was not recordable because too low, the arbitrary value of RRI was 1.14 As previously published, the IRVF patterns were categorized into continuous (non-congestive, grade A) and discontinuous (nadir velocity = 0) flow patterns. We further classified the discontinuous IRVF patterns into three stages: pulsatile (grade B), biphasic (with venous peaks during systole and diastole: grade C), and monophasic (with a venous peak during diastole: grade D). RVSI indicates the proportion of the cardiac cycle during which there is no renal venous outlet flow and is calculated as follows: (cardiac cycle time venous flow time)/cardiac cycle time).15 Continuous renal venous flow with an RVSI value of 0 is considered normal (see Supplementary data online, Figure S1). Renal Doppler was blinded and reviewed by an experimental radiologist (Jonathan Cortese) and interobserver variability was analysed. The physicians were blinded to the intrarenal Doppler results.
All transthoracic echocardiography measurements were made according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging.20,21 The right atrial (RA) area was quantified from the apical 4- chamber view. The RV function was quantified using the following parameters: Tricuspid annular plane systolic excursion (TAPSE), tissue Doppler-derived tricuspid lateral annular peak systolic velocity (S’), RV longitudinal strain. The mitral E/A ratio was obtained from the apical four-chamber view and the left ventricular outfow tract—velocity time integral (LVOT-VTI) from the apical five-chamber view. Tricuspid regurgitation was considered severe in the presence of at least two of these criteria: vena contracta with >0.7 cm, jet area >10 cm2 for central jets at a Nyquist limit of 50–60 cm/s with a relative jet to atrial size >40%.22
Outcomes
The primary endpoint of the study was a composite endpoint including death, extracorporeal life support, urgent transplantation, or re-admission for new episodes of acute RHF within the 90 days following inclusion.
Statistical analysis
Continuous variables were expressed as the mean ± SD or median [interquartile range, 25–75% (IQR)] according to data distribution. Categorical data are expressed as numbers (n) and percentages (%). Categorical variables were compared using the χ2 test. Differences in continuous variables were compared using the independent Student’s t-test for normally distributed variables and the Mann−Whitney U test for non-normally distributed variables. Changes from baseline to Day 3 were assessed using a paired Student’s t-test, Wilcoxon signed-rank test, or χ2 test as appropriate. The Kaplan–Meier method was used to estimate the cumulative incidence of the primary outcome and the log-rank test was used for distribution comparison. A P value < 0.05 was considered statistically significant. Interobserver reproducibility (agreement between readers) was determined by the corresponding intraclass correlation coefficients and their 95% confidence interval (CI) using Spearman correlation analysis. Univariable and multivariable forward stepwise Cox proportional hazards regression models were performed to determine the risk of the primary endpoint according to variables at baseline and Day 3 visit. A receiver operating characteristic (ROC) curve was used to assess the optimal point of RRI that allows the highest sensitivity and specificity associated with the primary endpoint.
Results
Patient characteristics and management in ICU
Ninety-one patients were enrolled in the study between 1 December 2019, and 31 July 2021. The characteristics at the time of ICU admission are shown in Table 1. The mean age at admission was 58 ± 16 years and 53 (58%) were female. PH diagnosis was revealed by the episode of acute decompensation in 26 patients (28%). All patients received intravenous diuretics. Loop diuretics were used in all cases combined with mineralocorticoid receptor antagonists in 31 (34%) and thiazide diuretics in 9 (10%). The use of dobutamine was required in 62 patients (68%) combined with norepinephrine in 25 (27%).
Characteristics at time of admission in ICU
| n = 91 | |
|---|---|
| Sex, female n (%) | 53 (58) |
| Age, years | 58 ± 16 |
| Etiology of precapillary PH, n (%) | |
| Idiopathic/heritable | 19 (21) |
| Connective tissue disease | 23 (25) |
| Porto-PH | 6 (7) |
| HIV-associated PAH | 1 (1) |
| Congenital heart disease | 2 (2) |
| Pulmonary veno-occlusive disease | 11 (12) |
| Chronic lung disease (group 3) | 7 (8) |
| Chronic thromboembolic PH (group 4) | 16 (17) |
| Multifactorial mechanisms (group 5) | 6 (7) |
| PAH therapies, n (%) | |
| – None | 33 (36) |
| – Monotherapy | 22 (24) |
| – Dual therapy | 26 (29) |
| – Triple therapy | 10 (11) |
| – PGI2 analogues alone or in combination | 11 (12) |
| Comorbidities, n (%) | |
| – Hypertension | 31 (36) |
| – Diabetes | 17 (20) |
| – Severe chronic renal insufficiency (eGFR < 45 mL/min/m2) | 10 (11) |
| Clinical characteristics | |
| – Systolic arterial pressure, mmHg | 112 ± 18 |
| – MAP, mmHg | 86 ± 13 |
| – Diastolic arterial pressure, mmHg | 74 ± 13 |
| – Heart rate, rpm | 90 ± 16 |
| – Supraventricular arrhythmia, n (%) | 13 (14%) |
| Biological variables | |
| – Na, mmol/L | 136 ± 4 |
| – BUN, mmol/L | 8 ± 3 |
| – Creatinine, umol/L | 109 ± 40 |
| – eGFR, mL/min/1.73 m2 | 63 ± 26 |
| – NT-proBNP, pg/mL | 3.744 [1.641–6.458] |
| – Lactate, mmol/L | 1.4 [1–1.9] |
| SAPS II | 24 [18–32] |
| Central catheter, n = 59 | |
| – CVP, mmHg | 15 [11–19] |
| – Renal perfusion pressure, mmHg | 71 ± 15 |
| – ScVO2, % | 57 [49–63] |
| Hemodynamics, n = 57 | |
| – mPAP, mmHg | 52 ± 13 |
| – PAWP, mmHg | 11 ± 5 |
| – RAP, mmHg | 15 ± 7 |
| – CI, l/min/m2 | 2.2 ± 0.8 |
| – PVR, UW | 11 ± 5 |
| – SVI, mL/m2 | 27 ± 9 |
| n = 91 | |
|---|---|
| Sex, female n (%) | 53 (58) |
| Age, years | 58 ± 16 |
| Etiology of precapillary PH, n (%) | |
| Idiopathic/heritable | 19 (21) |
| Connective tissue disease | 23 (25) |
| Porto-PH | 6 (7) |
| HIV-associated PAH | 1 (1) |
| Congenital heart disease | 2 (2) |
| Pulmonary veno-occlusive disease | 11 (12) |
| Chronic lung disease (group 3) | 7 (8) |
| Chronic thromboembolic PH (group 4) | 16 (17) |
| Multifactorial mechanisms (group 5) | 6 (7) |
| PAH therapies, n (%) | |
| – None | 33 (36) |
| – Monotherapy | 22 (24) |
| – Dual therapy | 26 (29) |
| – Triple therapy | 10 (11) |
| – PGI2 analogues alone or in combination | 11 (12) |
| Comorbidities, n (%) | |
| – Hypertension | 31 (36) |
| – Diabetes | 17 (20) |
| – Severe chronic renal insufficiency (eGFR < 45 mL/min/m2) | 10 (11) |
| Clinical characteristics | |
| – Systolic arterial pressure, mmHg | 112 ± 18 |
| – MAP, mmHg | 86 ± 13 |
| – Diastolic arterial pressure, mmHg | 74 ± 13 |
| – Heart rate, rpm | 90 ± 16 |
| – Supraventricular arrhythmia, n (%) | 13 (14%) |
| Biological variables | |
| – Na, mmol/L | 136 ± 4 |
| – BUN, mmol/L | 8 ± 3 |
| – Creatinine, umol/L | 109 ± 40 |
| – eGFR, mL/min/1.73 m2 | 63 ± 26 |
| – NT-proBNP, pg/mL | 3.744 [1.641–6.458] |
| – Lactate, mmol/L | 1.4 [1–1.9] |
| SAPS II | 24 [18–32] |
| Central catheter, n = 59 | |
| – CVP, mmHg | 15 [11–19] |
| – Renal perfusion pressure, mmHg | 71 ± 15 |
| – ScVO2, % | 57 [49–63] |
| Hemodynamics, n = 57 | |
| – mPAP, mmHg | 52 ± 13 |
| – PAWP, mmHg | 11 ± 5 |
| – RAP, mmHg | 15 ± 7 |
| – CI, l/min/m2 | 2.2 ± 0.8 |
| – PVR, UW | 11 ± 5 |
| – SVI, mL/m2 | 27 ± 9 |
Data are presented as median [first to third quartile], numbers (percentages), or mean ± Standard deviation.
Abbreviations: CI, cardiac index; mPAP, mean pulmonary arterial pressure; SVI, stroke volume index.
Characteristics at time of admission in ICU
| n = 91 | |
|---|---|
| Sex, female n (%) | 53 (58) |
| Age, years | 58 ± 16 |
| Etiology of precapillary PH, n (%) | |
| Idiopathic/heritable | 19 (21) |
| Connective tissue disease | 23 (25) |
| Porto-PH | 6 (7) |
| HIV-associated PAH | 1 (1) |
| Congenital heart disease | 2 (2) |
| Pulmonary veno-occlusive disease | 11 (12) |
| Chronic lung disease (group 3) | 7 (8) |
| Chronic thromboembolic PH (group 4) | 16 (17) |
| Multifactorial mechanisms (group 5) | 6 (7) |
| PAH therapies, n (%) | |
| – None | 33 (36) |
| – Monotherapy | 22 (24) |
| – Dual therapy | 26 (29) |
| – Triple therapy | 10 (11) |
| – PGI2 analogues alone or in combination | 11 (12) |
| Comorbidities, n (%) | |
| – Hypertension | 31 (36) |
| – Diabetes | 17 (20) |
| – Severe chronic renal insufficiency (eGFR < 45 mL/min/m2) | 10 (11) |
| Clinical characteristics | |
| – Systolic arterial pressure, mmHg | 112 ± 18 |
| – MAP, mmHg | 86 ± 13 |
| – Diastolic arterial pressure, mmHg | 74 ± 13 |
| – Heart rate, rpm | 90 ± 16 |
| – Supraventricular arrhythmia, n (%) | 13 (14%) |
| Biological variables | |
| – Na, mmol/L | 136 ± 4 |
| – BUN, mmol/L | 8 ± 3 |
| – Creatinine, umol/L | 109 ± 40 |
| – eGFR, mL/min/1.73 m2 | 63 ± 26 |
| – NT-proBNP, pg/mL | 3.744 [1.641–6.458] |
| – Lactate, mmol/L | 1.4 [1–1.9] |
| SAPS II | 24 [18–32] |
| Central catheter, n = 59 | |
| – CVP, mmHg | 15 [11–19] |
| – Renal perfusion pressure, mmHg | 71 ± 15 |
| – ScVO2, % | 57 [49–63] |
| Hemodynamics, n = 57 | |
| – mPAP, mmHg | 52 ± 13 |
| – PAWP, mmHg | 11 ± 5 |
| – RAP, mmHg | 15 ± 7 |
| – CI, l/min/m2 | 2.2 ± 0.8 |
| – PVR, UW | 11 ± 5 |
| – SVI, mL/m2 | 27 ± 9 |
| n = 91 | |
|---|---|
| Sex, female n (%) | 53 (58) |
| Age, years | 58 ± 16 |
| Etiology of precapillary PH, n (%) | |
| Idiopathic/heritable | 19 (21) |
| Connective tissue disease | 23 (25) |
| Porto-PH | 6 (7) |
| HIV-associated PAH | 1 (1) |
| Congenital heart disease | 2 (2) |
| Pulmonary veno-occlusive disease | 11 (12) |
| Chronic lung disease (group 3) | 7 (8) |
| Chronic thromboembolic PH (group 4) | 16 (17) |
| Multifactorial mechanisms (group 5) | 6 (7) |
| PAH therapies, n (%) | |
| – None | 33 (36) |
| – Monotherapy | 22 (24) |
| – Dual therapy | 26 (29) |
| – Triple therapy | 10 (11) |
| – PGI2 analogues alone or in combination | 11 (12) |
| Comorbidities, n (%) | |
| – Hypertension | 31 (36) |
| – Diabetes | 17 (20) |
| – Severe chronic renal insufficiency (eGFR < 45 mL/min/m2) | 10 (11) |
| Clinical characteristics | |
| – Systolic arterial pressure, mmHg | 112 ± 18 |
| – MAP, mmHg | 86 ± 13 |
| – Diastolic arterial pressure, mmHg | 74 ± 13 |
| – Heart rate, rpm | 90 ± 16 |
| – Supraventricular arrhythmia, n (%) | 13 (14%) |
| Biological variables | |
| – Na, mmol/L | 136 ± 4 |
| – BUN, mmol/L | 8 ± 3 |
| – Creatinine, umol/L | 109 ± 40 |
| – eGFR, mL/min/1.73 m2 | 63 ± 26 |
| – NT-proBNP, pg/mL | 3.744 [1.641–6.458] |
| – Lactate, mmol/L | 1.4 [1–1.9] |
| SAPS II | 24 [18–32] |
| Central catheter, n = 59 | |
| – CVP, mmHg | 15 [11–19] |
| – Renal perfusion pressure, mmHg | 71 ± 15 |
| – ScVO2, % | 57 [49–63] |
| Hemodynamics, n = 57 | |
| – mPAP, mmHg | 52 ± 13 |
| – PAWP, mmHg | 11 ± 5 |
| – RAP, mmHg | 15 ± 7 |
| – CI, l/min/m2 | 2.2 ± 0.8 |
| – PVR, UW | 11 ± 5 |
| – SVI, mL/m2 | 27 ± 9 |
Data are presented as median [first to third quartile], numbers (percentages), or mean ± Standard deviation.
Abbreviations: CI, cardiac index; mPAP, mean pulmonary arterial pressure; SVI, stroke volume index.
Variables of renal Doppler and transthoracic echocardiography at admission and on Day 3
Renal Doppler and transthoracic echocardiography were performed in all enrolled patients at admission. Among them, 82 were assessed on Day 3. Measurements were not performed on Day 3 in nine patients because of death (n = 1), urgent transplantation (n = 2), ICU discharge (n = 2), and non-available data (n = 4).
The interobserver reproducibility of RRI and RVSI measurements were found to be reliable (ρ = 0.93; 95% CI 0.85–0.97 and ρ = 0.85; 95% CI 0.70–0.96, respectively) (see Supplementary data online, Table S1).
At the time of admission, the median value of RRI was 0.77 (0.7–1). Renal venous Doppler was discontinuous in 86 patients (94%). The venous flow was pulsed, biphasic, and monophasic in 15 (14%), 42 (46%), and 29 patients (32%), respectively. The median value of RVSI was 0.52 (0.30–0.67). No significant correlation was observed between RRI and RVSI (ρ = 0.41; 95%CI 0.22–0.56).
The values of renal Doppler parameters, transthoracic echocardiography, CVP, and central venous oxygen saturation (ScVO2) of patients assessed at admission and Day 3 (n = 82) are detailed and compared in Table 2. The CVP significantly decreased 3 days after ICU admission (P < 0.001). While no significant change in RRI in the overall population was observed, venous Doppler showed a significant decrease in RVSI as well as a significant decrease in the proportion of patients with monophasic pattern on Day 3.
Renal Doppler and transthoracic echocardiography parameters of patients assessed at admission and on Day 3
| Day 0 | Day 3 | P value | |
|---|---|---|---|
| Renal Doppler, n = 82 | |||
| RRI | 0.78 [0.69–1] | 0.79 [0.70–1] | 0.843 |
| RVSI | 0.52 [0.30–0.67] | 0.37 [0.14–0.52] | <0.001 |
| Monophasic pattern, n (%) | 30 (33) | 12 (13) | <0.001 |
| Echocardiography, n = 86 | |||
| TAPSE, mm | 14 [11–16] | 14 [11–16] | 0.101 |
| RV longitudinal strain, % | −11 [14–8] | −10 [12–8] | 0.161 |
| Severe TR | 32 (37) | 22 (28) | 0.143 |
| LVOT-VTI, cm | 15 [13–18] | 15 [13–19] | 0.047 |
| Mitral E/A ratio | 0.8 [0.6–1] | 0.7 [0.6–0.9] | 0.589 |
| Central catheter, n = 53 | |||
| CVP, mmHg | 15 [11–19] | 9 [7–12] | <0.001 |
| ScVO2, % | 57 [49–63] | 59 [51–64] | 0.177 |
| Day 0 | Day 3 | P value | |
|---|---|---|---|
| Renal Doppler, n = 82 | |||
| RRI | 0.78 [0.69–1] | 0.79 [0.70–1] | 0.843 |
| RVSI | 0.52 [0.30–0.67] | 0.37 [0.14–0.52] | <0.001 |
| Monophasic pattern, n (%) | 30 (33) | 12 (13) | <0.001 |
| Echocardiography, n = 86 | |||
| TAPSE, mm | 14 [11–16] | 14 [11–16] | 0.101 |
| RV longitudinal strain, % | −11 [14–8] | −10 [12–8] | 0.161 |
| Severe TR | 32 (37) | 22 (28) | 0.143 |
| LVOT-VTI, cm | 15 [13–18] | 15 [13–19] | 0.047 |
| Mitral E/A ratio | 0.8 [0.6–1] | 0.7 [0.6–0.9] | 0.589 |
| Central catheter, n = 53 | |||
| CVP, mmHg | 15 [11–19] | 9 [7–12] | <0.001 |
| ScVO2, % | 57 [49–63] | 59 [51–64] | 0.177 |
Data are presented as median [first to third quartile], numbers (percentages).
Abbreviations: TR, tricuspid regurgitation.
Renal Doppler and transthoracic echocardiography parameters of patients assessed at admission and on Day 3
| Day 0 | Day 3 | P value | |
|---|---|---|---|
| Renal Doppler, n = 82 | |||
| RRI | 0.78 [0.69–1] | 0.79 [0.70–1] | 0.843 |
| RVSI | 0.52 [0.30–0.67] | 0.37 [0.14–0.52] | <0.001 |
| Monophasic pattern, n (%) | 30 (33) | 12 (13) | <0.001 |
| Echocardiography, n = 86 | |||
| TAPSE, mm | 14 [11–16] | 14 [11–16] | 0.101 |
| RV longitudinal strain, % | −11 [14–8] | −10 [12–8] | 0.161 |
| Severe TR | 32 (37) | 22 (28) | 0.143 |
| LVOT-VTI, cm | 15 [13–18] | 15 [13–19] | 0.047 |
| Mitral E/A ratio | 0.8 [0.6–1] | 0.7 [0.6–0.9] | 0.589 |
| Central catheter, n = 53 | |||
| CVP, mmHg | 15 [11–19] | 9 [7–12] | <0.001 |
| ScVO2, % | 57 [49–63] | 59 [51–64] | 0.177 |
| Day 0 | Day 3 | P value | |
|---|---|---|---|
| Renal Doppler, n = 82 | |||
| RRI | 0.78 [0.69–1] | 0.79 [0.70–1] | 0.843 |
| RVSI | 0.52 [0.30–0.67] | 0.37 [0.14–0.52] | <0.001 |
| Monophasic pattern, n (%) | 30 (33) | 12 (13) | <0.001 |
| Echocardiography, n = 86 | |||
| TAPSE, mm | 14 [11–16] | 14 [11–16] | 0.101 |
| RV longitudinal strain, % | −11 [14–8] | −10 [12–8] | 0.161 |
| Severe TR | 32 (37) | 22 (28) | 0.143 |
| LVOT-VTI, cm | 15 [13–18] | 15 [13–19] | 0.047 |
| Mitral E/A ratio | 0.8 [0.6–1] | 0.7 [0.6–0.9] | 0.589 |
| Central catheter, n = 53 | |||
| CVP, mmHg | 15 [11–19] | 9 [7–12] | <0.001 |
| ScVO2, % | 57 [49–63] | 59 [51–64] | 0.177 |
Data are presented as median [first to third quartile], numbers (percentages).
Abbreviations: TR, tricuspid regurgitation.
Parameters associated with high RRI and RVSI values at admission
In univariate analysis, variables associated with RRI higher than the median value at the time of admission, were non-variable parameters (age and history of hypertension), congestion (RA pressure and renal pulse pressure), cardiac systolic function (TAPSE and LVOT-VTI), systemic pressures, NT-proBNP, and supraventricular arrhythmia. Variables associated with RVSI higher than the median value were congestion (high CVP, RA pressure, and renal pulse pressure), right cardiac function (TAPSE), severe tricuspid regurgitation, and systemic pressures. Both RRI and RVSI were associated with higher levels of BUN and lower level of eGFR. All univariate analysis data are detailed in Table 3. Inotropic support was more frequently required in patients with an RRI higher than the median value (80% vs. 55%, P = 0.01) and in patients with an RVSI higher than the median value (82% vs. 53%, P = 0.003) at the time of admission.
Parameters associated with high value of RRI and RVSI at time of admission in univariate analysis
| RRI ≥ median value | RVSI ≥ median value | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.066 (1.031–1.102) | 0.0002 | 1.022 (0.995–1.049) | 0.1108 |
| Female, yes | 1.661 (0.717–3.853) | 0.2367 | 0.804 (0.349–1.851) | 0.6075 |
| Hypertension, yes | 2.604 (1.039–6.529) | 0.0413 | 1.131 (0.469–2/727) | 0.7847 |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 6.968 (0.825–58.85) | 0.0745 | 1.250 (0.317–4.930) | 0.7499 |
| Diabetes, yes | 1.349 (0.461–3.948) | 0.5845 | 1.003 (0.347–2.901) | 0.9950 |
| CVP, mmHg | 1.096 (0.997–1.206) | 0.0581 | 1.269 (1.106–1.456) | 0.0007 |
| Heart rate, bpm | 0.995 (0.970–1.021) | 0.7187 | 0.987 (0.961–1.013) | 0.3161 |
| Supraventricular arrhythmia, yes | 4.095 (1.026–15.52) | 0.0393 | 2.493 (0.675–7.741) | 0.2305 |
| Cardiac index, l/min/m2 | 1.178 (0.628–2.210) | 0.6097 | 0.624 (0.314–1.238) | 0.1773 |
| RAP, mmHg | 1.088 (1.000–1.163) | 0.0495 | 1.212 (1.082–1.358) | 0.0009 |
| TAPSE, mm | 0.830 (0.729–0.945) | 0.0050 | 0.819 (0.717–0.935) | 0.0032 |
| Severe TR, yes | 2.466 (0.999–6.086) | 0.0502 | 8.211 (2.881–23.40) | <0.0001 |
| LVOT-VTI, cm | 1.108 (1.004–1.224) | 0.0423 | 0.995 (0.909–1.089) | 0.9120 |
| RV longitudinal strain, % | 0.913 (0.811–1.027) | 0.1299 | 0.903 (0.801–1.018) | 0.0941 |
| MAP, mmHg | 0.928 (0.892–0.996) | 0.0003 | 0.946 (0.912–0.981) | 0.0026 |
| Renal perfusion pressure, mmHg | 0.931 (0.890–0.974) | 0.0018 | 0.911 (0.865–0.959) | 0.0004 |
| NT-proBNP, pg/mL per 100 | 1.011 (1.002–1.022) | 0.0295 | 1.005 (0.996–1.014) | 0.2752 |
| eGRF, mL/min/1.73 m2 | 0.969 (0.951–0.988) | 0.0016 | 0.974 (0.956–0.992) | 0.0052 |
| Na, mmol/L | 0.913 (0.824–1.011) | 0.0795 | 0.915 (0.827–1.013) | 0.0878 |
| BUN, mmol/L | 1.243 (1.109–1.394) | 0.0002 | 1.106 (1.017–1.203) | 0.0180 |
| RRI ≥ median value | RVSI ≥ median value | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.066 (1.031–1.102) | 0.0002 | 1.022 (0.995–1.049) | 0.1108 |
| Female, yes | 1.661 (0.717–3.853) | 0.2367 | 0.804 (0.349–1.851) | 0.6075 |
| Hypertension, yes | 2.604 (1.039–6.529) | 0.0413 | 1.131 (0.469–2/727) | 0.7847 |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 6.968 (0.825–58.85) | 0.0745 | 1.250 (0.317–4.930) | 0.7499 |
| Diabetes, yes | 1.349 (0.461–3.948) | 0.5845 | 1.003 (0.347–2.901) | 0.9950 |
| CVP, mmHg | 1.096 (0.997–1.206) | 0.0581 | 1.269 (1.106–1.456) | 0.0007 |
| Heart rate, bpm | 0.995 (0.970–1.021) | 0.7187 | 0.987 (0.961–1.013) | 0.3161 |
| Supraventricular arrhythmia, yes | 4.095 (1.026–15.52) | 0.0393 | 2.493 (0.675–7.741) | 0.2305 |
| Cardiac index, l/min/m2 | 1.178 (0.628–2.210) | 0.6097 | 0.624 (0.314–1.238) | 0.1773 |
| RAP, mmHg | 1.088 (1.000–1.163) | 0.0495 | 1.212 (1.082–1.358) | 0.0009 |
| TAPSE, mm | 0.830 (0.729–0.945) | 0.0050 | 0.819 (0.717–0.935) | 0.0032 |
| Severe TR, yes | 2.466 (0.999–6.086) | 0.0502 | 8.211 (2.881–23.40) | <0.0001 |
| LVOT-VTI, cm | 1.108 (1.004–1.224) | 0.0423 | 0.995 (0.909–1.089) | 0.9120 |
| RV longitudinal strain, % | 0.913 (0.811–1.027) | 0.1299 | 0.903 (0.801–1.018) | 0.0941 |
| MAP, mmHg | 0.928 (0.892–0.996) | 0.0003 | 0.946 (0.912–0.981) | 0.0026 |
| Renal perfusion pressure, mmHg | 0.931 (0.890–0.974) | 0.0018 | 0.911 (0.865–0.959) | 0.0004 |
| NT-proBNP, pg/mL per 100 | 1.011 (1.002–1.022) | 0.0295 | 1.005 (0.996–1.014) | 0.2752 |
| eGRF, mL/min/1.73 m2 | 0.969 (0.951–0.988) | 0.0016 | 0.974 (0.956–0.992) | 0.0052 |
| Na, mmol/L | 0.913 (0.824–1.011) | 0.0795 | 0.915 (0.827–1.013) | 0.0878 |
| BUN, mmol/L | 1.243 (1.109–1.394) | 0.0002 | 1.106 (1.017–1.203) | 0.0180 |
Abbreviations: TR, Tricuspid regurgitation. Bold value : P <0.05.
Parameters associated with high value of RRI and RVSI at time of admission in univariate analysis
| RRI ≥ median value | RVSI ≥ median value | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.066 (1.031–1.102) | 0.0002 | 1.022 (0.995–1.049) | 0.1108 |
| Female, yes | 1.661 (0.717–3.853) | 0.2367 | 0.804 (0.349–1.851) | 0.6075 |
| Hypertension, yes | 2.604 (1.039–6.529) | 0.0413 | 1.131 (0.469–2/727) | 0.7847 |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 6.968 (0.825–58.85) | 0.0745 | 1.250 (0.317–4.930) | 0.7499 |
| Diabetes, yes | 1.349 (0.461–3.948) | 0.5845 | 1.003 (0.347–2.901) | 0.9950 |
| CVP, mmHg | 1.096 (0.997–1.206) | 0.0581 | 1.269 (1.106–1.456) | 0.0007 |
| Heart rate, bpm | 0.995 (0.970–1.021) | 0.7187 | 0.987 (0.961–1.013) | 0.3161 |
| Supraventricular arrhythmia, yes | 4.095 (1.026–15.52) | 0.0393 | 2.493 (0.675–7.741) | 0.2305 |
| Cardiac index, l/min/m2 | 1.178 (0.628–2.210) | 0.6097 | 0.624 (0.314–1.238) | 0.1773 |
| RAP, mmHg | 1.088 (1.000–1.163) | 0.0495 | 1.212 (1.082–1.358) | 0.0009 |
| TAPSE, mm | 0.830 (0.729–0.945) | 0.0050 | 0.819 (0.717–0.935) | 0.0032 |
| Severe TR, yes | 2.466 (0.999–6.086) | 0.0502 | 8.211 (2.881–23.40) | <0.0001 |
| LVOT-VTI, cm | 1.108 (1.004–1.224) | 0.0423 | 0.995 (0.909–1.089) | 0.9120 |
| RV longitudinal strain, % | 0.913 (0.811–1.027) | 0.1299 | 0.903 (0.801–1.018) | 0.0941 |
| MAP, mmHg | 0.928 (0.892–0.996) | 0.0003 | 0.946 (0.912–0.981) | 0.0026 |
| Renal perfusion pressure, mmHg | 0.931 (0.890–0.974) | 0.0018 | 0.911 (0.865–0.959) | 0.0004 |
| NT-proBNP, pg/mL per 100 | 1.011 (1.002–1.022) | 0.0295 | 1.005 (0.996–1.014) | 0.2752 |
| eGRF, mL/min/1.73 m2 | 0.969 (0.951–0.988) | 0.0016 | 0.974 (0.956–0.992) | 0.0052 |
| Na, mmol/L | 0.913 (0.824–1.011) | 0.0795 | 0.915 (0.827–1.013) | 0.0878 |
| BUN, mmol/L | 1.243 (1.109–1.394) | 0.0002 | 1.106 (1.017–1.203) | 0.0180 |
| RRI ≥ median value | RVSI ≥ median value | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.066 (1.031–1.102) | 0.0002 | 1.022 (0.995–1.049) | 0.1108 |
| Female, yes | 1.661 (0.717–3.853) | 0.2367 | 0.804 (0.349–1.851) | 0.6075 |
| Hypertension, yes | 2.604 (1.039–6.529) | 0.0413 | 1.131 (0.469–2/727) | 0.7847 |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 6.968 (0.825–58.85) | 0.0745 | 1.250 (0.317–4.930) | 0.7499 |
| Diabetes, yes | 1.349 (0.461–3.948) | 0.5845 | 1.003 (0.347–2.901) | 0.9950 |
| CVP, mmHg | 1.096 (0.997–1.206) | 0.0581 | 1.269 (1.106–1.456) | 0.0007 |
| Heart rate, bpm | 0.995 (0.970–1.021) | 0.7187 | 0.987 (0.961–1.013) | 0.3161 |
| Supraventricular arrhythmia, yes | 4.095 (1.026–15.52) | 0.0393 | 2.493 (0.675–7.741) | 0.2305 |
| Cardiac index, l/min/m2 | 1.178 (0.628–2.210) | 0.6097 | 0.624 (0.314–1.238) | 0.1773 |
| RAP, mmHg | 1.088 (1.000–1.163) | 0.0495 | 1.212 (1.082–1.358) | 0.0009 |
| TAPSE, mm | 0.830 (0.729–0.945) | 0.0050 | 0.819 (0.717–0.935) | 0.0032 |
| Severe TR, yes | 2.466 (0.999–6.086) | 0.0502 | 8.211 (2.881–23.40) | <0.0001 |
| LVOT-VTI, cm | 1.108 (1.004–1.224) | 0.0423 | 0.995 (0.909–1.089) | 0.9120 |
| RV longitudinal strain, % | 0.913 (0.811–1.027) | 0.1299 | 0.903 (0.801–1.018) | 0.0941 |
| MAP, mmHg | 0.928 (0.892–0.996) | 0.0003 | 0.946 (0.912–0.981) | 0.0026 |
| Renal perfusion pressure, mmHg | 0.931 (0.890–0.974) | 0.0018 | 0.911 (0.865–0.959) | 0.0004 |
| NT-proBNP, pg/mL per 100 | 1.011 (1.002–1.022) | 0.0295 | 1.005 (0.996–1.014) | 0.2752 |
| eGRF, mL/min/1.73 m2 | 0.969 (0.951–0.988) | 0.0016 | 0.974 (0.956–0.992) | 0.0052 |
| Na, mmol/L | 0.913 (0.824–1.011) | 0.0795 | 0.915 (0.827–1.013) | 0.0878 |
| BUN, mmol/L | 1.243 (1.109–1.394) | 0.0002 | 1.106 (1.017–1.203) | 0.0180 |
Abbreviations: TR, Tricuspid regurgitation. Bold value : P <0.05.
Outcomes and prognostic value of renal Doppler at the time of ICU admission and on Day 3
The primary endpoint occurred on Day 90 in 32 patients (33%). Among them, 17 patients died, venous-arterial extracorporeal membrane oxygenation (ECMO) was implanted in two patients, five underwent urgent transplantation and eight were readmitted for a new episode of RHF. Comparison of characteristics at baseline and Day 3 between patients with (E+) and without the occurrence of primary endpoints (E–) is detailed in the Supplementary data online, Tables S2 and S3.
Univariate logistic regression for clinical variables, including RRI, RVSI, and other common prognostic biomarkers at the time of admission and on Day 3, are presented for the overall cohort in Table 4. In the overall cohort, a high RRI or RVSI at the time of admission was not identified as prognostic factors. At Day 3, a high level of RRI as well as a decrease in RRI in comparison to baseline value were associated with the primary endpoint. ROC curve analysis was performed to determine the best RRI threshold at Day 3 of event-free survival (<0.9) (see Supplementary data online, Figure S2). Kaplan–Meier curves of the cumulative incidence of death, transplantation, ECMO, or new RHF episode according to the value of RRI < or ≥ 0.9 and changes in RRI at Day 3 are illustrated in Figure 1. In univariable analysis, the hazard ratio of RRI at Day 3 expressed as dichotomous variables (according to thresholds previously determined) at diagnosis was 9.54 (95% CI 2.96–28). The relationship between RRI and the occurrence of primary endpoint persisted in multivariable models adjusted for low eGFR ≤ 45 mL/min/1.73 m2 (Table 5). The prognostic value of RRI according to the level of eGFR at Day 3 is illustrated in Figure 2.
Cumulative incidence of death, ECMO, urgent transplantation, or new episode of RHF according to RRI on Day 3.
Cumulative incidence of death, ECMO, urgent transplantation, or new episode of RHF according to RRI in patients with low eGFR ≤ 45 mL/min/1.73 m2 and patients with eGFR patients > 45 mL/min/1.73 m2 at time of admission and on Day 3.
Identification of parameters associated with the occurrence of the primary endpoint (death, ECMO, transplantation, or re-admission for acute RHF) at the time of admission and on Day 3
| At the time of admission | At Day 3 | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.015 (0.987–1.004) | 0.29 | — | — |
| Female, yes | 1.134 (0.475–2.709) | 0.7767 | — | — |
| Hypertension, yes | 0.632 (0.246–1.623) | 0.3406 | — | — |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 1.079 (0.272–4.279) | 0.9134 | — | — |
| Diabetes, yes | 0.705 (0.223–2.228) | 0.5517 | — | — |
| RRI, per 0.1 | 1.250 (0.921–1.712) | 0.1552 | 1.923 (1.315–2.922) | 0.0012 |
| Decrease in RRI on Day 3, yes | — | — | 0.256 (0.096–0.759) | 0.0123 |
| RVSI, per 0.1 | 1.087 (0.901–1.323) | 0.3917 | 1.217 (0.996–1.506) | 0.0596 |
| Decrease in RVSI at Day 3, yes | — | — | 0.411 (0.1445–1.196) | 0.0942 |
| CVP, mmHg | 1.018 (0.931–1.113) | 0.7978 | 1.013 (0.923–1.112) | 0.7828 |
| Cardiac index, l/min/m2 | 0.171 (0.038–0.778) | 0.0223 | — | — |
| TAPSE, mm | 0.902 (0.794–1.025) | 0.1133 | 0.933 (0.830–1.050) | 0.2498 |
| Tricuspid S wave, cm/s | 0.928 (0.803–1.073) | 0.3142 | 0.928 (0.803–1.073) | 0.3142 |
| RA area, cm2 | 1.016 (0.975–1.060) | 0.4475 | 1.031 (0.978–1.087) | 0.2530 |
| Severe TR yes | 1.668 (0.668–4.162) | 0.2730 | 2.933 (1.105–7.786) | 0.0351 |
| LVOT-VTI, cm | 0.900 (0.809–1.002) | 0.0540 | 0.908 (0.815–1.012) | 0.0812 |
| RV longitudinal strain, % | 1.080 (0.969–1.203) | 0.1649 | 1.053 (0.933–1.188) | 0.4018 |
| MAP, mmHg | 0.963 (0.929–0.998) | 0.0382 | 0.976 (0.937–1.016) | 0.2306 |
| NT-proBNP, pg/mL, per 100 | 1.010 (1.001–1.019) | 0.0388 | 1.011 (1.003–1.021) | 0.0198 |
| eGRF, mL/min/1.73m2 | 0.976 (0.957–0.995) | 0.0158 | 0.978 (0.961–0.996) | 0.0183 |
| Na, mmol/L | 0.953 (0.862–1.055) | 0.3533 | 0.946 (0.843–1.062) | 0.3474 |
| Urea, mmol/L | 1.055 (0.981–1.135) | 0.1468 | 1.078 (0.992–1.172) | 0.0756 |
| At the time of admission | At Day 3 | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.015 (0.987–1.004) | 0.29 | — | — |
| Female, yes | 1.134 (0.475–2.709) | 0.7767 | — | — |
| Hypertension, yes | 0.632 (0.246–1.623) | 0.3406 | — | — |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 1.079 (0.272–4.279) | 0.9134 | — | — |
| Diabetes, yes | 0.705 (0.223–2.228) | 0.5517 | — | — |
| RRI, per 0.1 | 1.250 (0.921–1.712) | 0.1552 | 1.923 (1.315–2.922) | 0.0012 |
| Decrease in RRI on Day 3, yes | — | — | 0.256 (0.096–0.759) | 0.0123 |
| RVSI, per 0.1 | 1.087 (0.901–1.323) | 0.3917 | 1.217 (0.996–1.506) | 0.0596 |
| Decrease in RVSI at Day 3, yes | — | — | 0.411 (0.1445–1.196) | 0.0942 |
| CVP, mmHg | 1.018 (0.931–1.113) | 0.7978 | 1.013 (0.923–1.112) | 0.7828 |
| Cardiac index, l/min/m2 | 0.171 (0.038–0.778) | 0.0223 | — | — |
| TAPSE, mm | 0.902 (0.794–1.025) | 0.1133 | 0.933 (0.830–1.050) | 0.2498 |
| Tricuspid S wave, cm/s | 0.928 (0.803–1.073) | 0.3142 | 0.928 (0.803–1.073) | 0.3142 |
| RA area, cm2 | 1.016 (0.975–1.060) | 0.4475 | 1.031 (0.978–1.087) | 0.2530 |
| Severe TR yes | 1.668 (0.668–4.162) | 0.2730 | 2.933 (1.105–7.786) | 0.0351 |
| LVOT-VTI, cm | 0.900 (0.809–1.002) | 0.0540 | 0.908 (0.815–1.012) | 0.0812 |
| RV longitudinal strain, % | 1.080 (0.969–1.203) | 0.1649 | 1.053 (0.933–1.188) | 0.4018 |
| MAP, mmHg | 0.963 (0.929–0.998) | 0.0382 | 0.976 (0.937–1.016) | 0.2306 |
| NT-proBNP, pg/mL, per 100 | 1.010 (1.001–1.019) | 0.0388 | 1.011 (1.003–1.021) | 0.0198 |
| eGRF, mL/min/1.73m2 | 0.976 (0.957–0.995) | 0.0158 | 0.978 (0.961–0.996) | 0.0183 |
| Na, mmol/L | 0.953 (0.862–1.055) | 0.3533 | 0.946 (0.843–1.062) | 0.3474 |
| Urea, mmol/L | 1.055 (0.981–1.135) | 0.1468 | 1.078 (0.992–1.172) | 0.0756 |
Abbreviations: TR, Tricuspid regurgitation. Above value : P <0.05.
Identification of parameters associated with the occurrence of the primary endpoint (death, ECMO, transplantation, or re-admission for acute RHF) at the time of admission and on Day 3
| At the time of admission | At Day 3 | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.015 (0.987–1.004) | 0.29 | — | — |
| Female, yes | 1.134 (0.475–2.709) | 0.7767 | — | — |
| Hypertension, yes | 0.632 (0.246–1.623) | 0.3406 | — | — |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 1.079 (0.272–4.279) | 0.9134 | — | — |
| Diabetes, yes | 0.705 (0.223–2.228) | 0.5517 | — | — |
| RRI, per 0.1 | 1.250 (0.921–1.712) | 0.1552 | 1.923 (1.315–2.922) | 0.0012 |
| Decrease in RRI on Day 3, yes | — | — | 0.256 (0.096–0.759) | 0.0123 |
| RVSI, per 0.1 | 1.087 (0.901–1.323) | 0.3917 | 1.217 (0.996–1.506) | 0.0596 |
| Decrease in RVSI at Day 3, yes | — | — | 0.411 (0.1445–1.196) | 0.0942 |
| CVP, mmHg | 1.018 (0.931–1.113) | 0.7978 | 1.013 (0.923–1.112) | 0.7828 |
| Cardiac index, l/min/m2 | 0.171 (0.038–0.778) | 0.0223 | — | — |
| TAPSE, mm | 0.902 (0.794–1.025) | 0.1133 | 0.933 (0.830–1.050) | 0.2498 |
| Tricuspid S wave, cm/s | 0.928 (0.803–1.073) | 0.3142 | 0.928 (0.803–1.073) | 0.3142 |
| RA area, cm2 | 1.016 (0.975–1.060) | 0.4475 | 1.031 (0.978–1.087) | 0.2530 |
| Severe TR yes | 1.668 (0.668–4.162) | 0.2730 | 2.933 (1.105–7.786) | 0.0351 |
| LVOT-VTI, cm | 0.900 (0.809–1.002) | 0.0540 | 0.908 (0.815–1.012) | 0.0812 |
| RV longitudinal strain, % | 1.080 (0.969–1.203) | 0.1649 | 1.053 (0.933–1.188) | 0.4018 |
| MAP, mmHg | 0.963 (0.929–0.998) | 0.0382 | 0.976 (0.937–1.016) | 0.2306 |
| NT-proBNP, pg/mL, per 100 | 1.010 (1.001–1.019) | 0.0388 | 1.011 (1.003–1.021) | 0.0198 |
| eGRF, mL/min/1.73m2 | 0.976 (0.957–0.995) | 0.0158 | 0.978 (0.961–0.996) | 0.0183 |
| Na, mmol/L | 0.953 (0.862–1.055) | 0.3533 | 0.946 (0.843–1.062) | 0.3474 |
| Urea, mmol/L | 1.055 (0.981–1.135) | 0.1468 | 1.078 (0.992–1.172) | 0.0756 |
| At the time of admission | At Day 3 | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age, years | 1.015 (0.987–1.004) | 0.29 | — | — |
| Female, yes | 1.134 (0.475–2.709) | 0.7767 | — | — |
| Hypertension, yes | 0.632 (0.246–1.623) | 0.3406 | — | — |
| eGFR < 45 mL/min/1.73 m2 at the last evaluation | 1.079 (0.272–4.279) | 0.9134 | — | — |
| Diabetes, yes | 0.705 (0.223–2.228) | 0.5517 | — | — |
| RRI, per 0.1 | 1.250 (0.921–1.712) | 0.1552 | 1.923 (1.315–2.922) | 0.0012 |
| Decrease in RRI on Day 3, yes | — | — | 0.256 (0.096–0.759) | 0.0123 |
| RVSI, per 0.1 | 1.087 (0.901–1.323) | 0.3917 | 1.217 (0.996–1.506) | 0.0596 |
| Decrease in RVSI at Day 3, yes | — | — | 0.411 (0.1445–1.196) | 0.0942 |
| CVP, mmHg | 1.018 (0.931–1.113) | 0.7978 | 1.013 (0.923–1.112) | 0.7828 |
| Cardiac index, l/min/m2 | 0.171 (0.038–0.778) | 0.0223 | — | — |
| TAPSE, mm | 0.902 (0.794–1.025) | 0.1133 | 0.933 (0.830–1.050) | 0.2498 |
| Tricuspid S wave, cm/s | 0.928 (0.803–1.073) | 0.3142 | 0.928 (0.803–1.073) | 0.3142 |
| RA area, cm2 | 1.016 (0.975–1.060) | 0.4475 | 1.031 (0.978–1.087) | 0.2530 |
| Severe TR yes | 1.668 (0.668–4.162) | 0.2730 | 2.933 (1.105–7.786) | 0.0351 |
| LVOT-VTI, cm | 0.900 (0.809–1.002) | 0.0540 | 0.908 (0.815–1.012) | 0.0812 |
| RV longitudinal strain, % | 1.080 (0.969–1.203) | 0.1649 | 1.053 (0.933–1.188) | 0.4018 |
| MAP, mmHg | 0.963 (0.929–0.998) | 0.0382 | 0.976 (0.937–1.016) | 0.2306 |
| NT-proBNP, pg/mL, per 100 | 1.010 (1.001–1.019) | 0.0388 | 1.011 (1.003–1.021) | 0.0198 |
| eGRF, mL/min/1.73m2 | 0.976 (0.957–0.995) | 0.0158 | 0.978 (0.961–0.996) | 0.0183 |
| Na, mmol/L | 0.953 (0.862–1.055) | 0.3533 | 0.946 (0.843–1.062) | 0.3474 |
| Urea, mmol/L | 1.055 (0.981–1.135) | 0.1468 | 1.078 (0.992–1.172) | 0.0756 |
Abbreviations: TR, Tricuspid regurgitation. Above value : P <0.05.
Multivariable logistic regression analysis of RRI and eGFR at Day 3
| Odds-ratios | 95%CI | P | |
|---|---|---|---|
| Model 1 | |||
| eGFR, mL/min/1.73 m2 | 0.989 | 0.968–1.011 | 0.3529 |
| RRI, per 0.1 | 1.788 | 1.167–2.852 | 0.0101 |
| Model 2 | |||
| eGFR > 45 mL/min/1.73 m2 | 0.454 | 0.138–1.534 | 0.1931 |
| RRI ≥ 0.9 | 8.741 | 2.773–30.53 | 0.0003 |
| Odds-ratios | 95%CI | P | |
|---|---|---|---|
| Model 1 | |||
| eGFR, mL/min/1.73 m2 | 0.989 | 0.968–1.011 | 0.3529 |
| RRI, per 0.1 | 1.788 | 1.167–2.852 | 0.0101 |
| Model 2 | |||
| eGFR > 45 mL/min/1.73 m2 | 0.454 | 0.138–1.534 | 0.1931 |
| RRI ≥ 0.9 | 8.741 | 2.773–30.53 | 0.0003 |
Multivariable logistic regression analysis of RRI and eGFR at Day 3
| Odds-ratios | 95%CI | P | |
|---|---|---|---|
| Model 1 | |||
| eGFR, mL/min/1.73 m2 | 0.989 | 0.968–1.011 | 0.3529 |
| RRI, per 0.1 | 1.788 | 1.167–2.852 | 0.0101 |
| Model 2 | |||
| eGFR > 45 mL/min/1.73 m2 | 0.454 | 0.138–1.534 | 0.1931 |
| RRI ≥ 0.9 | 8.741 | 2.773–30.53 | 0.0003 |
| Odds-ratios | 95%CI | P | |
|---|---|---|---|
| Model 1 | |||
| eGFR, mL/min/1.73 m2 | 0.989 | 0.968–1.011 | 0.3529 |
| RRI, per 0.1 | 1.788 | 1.167–2.852 | 0.0101 |
| Model 2 | |||
| eGFR > 45 mL/min/1.73 m2 | 0.454 | 0.138–1.534 | 0.1931 |
| RRI ≥ 0.9 | 8.741 | 2.773–30.53 | 0.0003 |
Discussion
An optimal monitoring of patients admitted to ICU for acute decompensated PH is required to detect evolution towards refractory RHF needing specific management. In this study, we present the first analysis of the clinical relevance and the prognostic value of intrarenal arterial and venous Doppler in acute decompensated PH. While RRI is partially influenced by age and comorbidities (hypertension), RVSI seems to be independent of non-variables parameters. RRI and RVSI are associated with parameters reflecting cardiac function, congestion, and systemic arterial pressure. Even though both arterial and venous Doppler at the time of ICU admission are not prognostic factors, the use of inotropic and/or vasopressors supports was more frequently required in patients with high levels of RRI and RVSI at baseline. Value of RRI parameters 3 days after initiation of medical support seems to be relevant to predict outcomes more specifically in patients with eGFR lower than 45 mL/min/1.73 m2.
The prognosis of acute decompensated RHF in PH has been mainly described by retrospective cohorts with a limited number of patients and relative heterogeneity of the population studied, in terms of severity at admission. However, all these clinical studies have demonstrated the very strong impact of acute decompensated PH on short-term prognosis.5–7,23,24 As in our study, the prognostic factors identified are mainly biomarkers of RHF, systemic pressure, and the occurrence of systemic disorders, in the first place of cardiorenal syndrome. The urgent transplantation and the use of extracorporeal life support contributed to improve the survival of eligible patients with end-stage PH.2,8 Thus, a better understanding of prognostic factors is of major interest in this population to develop new techniques of non-invasive monitoring that could contribute to improving the management and the survival of these patients.
Invasive monitoring using RHC, although very informative and safe in patients with stable PH is not routinely used in the ICU because of the risk of complications due to its invasive nature.25 During the last world symposium on PH, it was stipulated that RHC, preferably with continuous cardiac output measurement, is not always necessary, but should be considered in severe and complex cases.2 In our study, many patients had a RHC at the time of admission (61%) with a short delay between renal Doppler and haemodynamic measurement allowing us to establish a relationship between right atrial pressure (RAP) and altered arterial and venous Doppler. However, most procedures were performed in the catheterization room and few of the devices were left in place.
While transthoracic echocardiography is routinely used in the ICU, its prognostic value in acute decompensated PH is limited. Haddad et al. reported that tricuspid regurgitation severity was the only parameter of RV function associated with a worse prognosis in this specific clinical setting.5 This is in accordance with our results. Similarly, we found that neither right heart chamber size nor the parameters for assessing RV systolic function (including RV longitudinal strain) were associated with outcome. Our study seems to demonstrate that renal Doppler could be an interesting alternative non-invasive monitoring tool that integrates the important components of RV failure including congestion, circulatory failure, and cardiac function.
Intrarenal Doppler ultrasound is a non-invasive bedside tool useful to assess the arterial and venous blood flow in ICU.26 The RRI and RVSI were easily measured at the end of the echocardiographic examination by using the abdominal probe. In addition, the evaluation was not time consuming and our results demonstrate its high interobserver reproducibility as previously observed in stable condition12,14 and in ICU.27
In our study, RRI assessed by the arterial Doppler was influenced by both the intrinsic condition of the episode of acute decompensated PH and non-variable parameters such as age and systemic hypertension as previously described.28,29 RRI reflects the alteration of renal function by a complex pathophysiological mechanism, the substratum of which is the increase in intrarenal vascular resistance leading to a decrease in renal blood flow and therefore in GFR.30 It is important to emphasize that renal congestion is also an important component of the elevation of RRI values in our study as suggested by other previous studies. Indeed, Kirkpatrick et al showed that RRI was influenced by the increase in renal venous pressure induced by intra-abdominal hypertension.31 In the same study, diuretic treatment reduced RRI. In a retrospective cohort of PH patients in a stable condition, Husain et al.15 reported that RRI significantly increased with rising renal venous congestion defined by RVSI tercile.
It has been previously demonstrated that renal venous Doppler can be influenced by extrinsic factors (interstitial pressure, hydronephrosis, intra-abdominal pressure),15,32 RA hemodynamics, and right ventricle filling properties.33 Under physiological conditions, intrarenal veins exhibit continuous flow independent of renal function.34 The intrarenal venous flow can be affected and interrupted by an elevation and variation of the RAPs during the cardiac cycle leading to a pulsed, then biphasic, and finally monophasic flow. In our study, TAPSE and tricuspid regurgitation severity were both associated with renal congestion as previously observed in other studies.15,33 Indeed, severe tricuspid insufficiency can reverse the x-dip with marked elevation of the v-wave.35 Therefore, due to a continuously elevated RAP from tricuspid end closing to end systole, the intrarenal venous flow is more severely interrupted.
While neither RRI nor RVSI at the time of admission were identified as prognostic factors in our study, the use of dobutamine and norepinephrine was more frequently needed in patients with high values of these two parameters. This underlines that these two parameters are influenced by all components of severe RHF, including as expected, the occurrence of cardiorenal syndrome. In contrast, a dynamic analysis of RRI 3 days after the initiation of medical support seems to be more relevant to identify patients at risk of developing refractory RHF. Similarly, the prognostic value of RRI in addition to eGFR has been recently observed in chronic left heart failure.36 In acute heart failure a decrease of RRI during the stay is correlated to the increase of eGFR.37
We assume that our study has some limitations including its monocentric nature. However, it should be highlighted that the French PAH Reference Centre hosts a dedicated pulmonary vascular disease ICU working in close partnership with a nationwide network of 25 centres. Therefore, this single-centre characteristic allowed a similar management approach to be performed by the same team and offered to the patients all modern treatment options in the modern management era of RHF.
In conclusion, our data suggest that renal Doppler seems to be an interesting tool to monitor patients managed in the ICU for acute decompensated precapillary PH. Both venous and renal Doppler allowed us to identify patients needing inotropic support at admission, and the evolution of the arterial RRI seemed to be a relevant prognostic parameter. Our results need to be evaluated in a validation cohort.
Acknowledgements
The authors acknowledge Laurence Rottat (AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France) for her help in obtaining the data for this study and her hard work in managing data in the French PH Registry. They also thank all participants of the French PH Network.
Supplementary data
Supplementary data are available at European Heart Journal - Cardiovascular Imaging online.
Contributors
Jérémie Pichon is the guarantor of the content of the manuscript, including the data and analysis.
All the undersigning authors have substantially contributed to the paper: design and data analysis were made by Jérémie Pichon and Laurent Savale whereas all the authors have contributed to the acquisition of funding as well as writing the manuscript. All authors declare that the submitted work is original and has not been published before (neither in English nor in any other language) and that the work is not under consideration for publication elsewhere.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Author notes
The study was done in the intensive care unit of the French reference center for pulmonary hypertension, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France.
Guillaume Voiriot and Marc Humbert contributed equally to this work.
Conflict of interest: Over the last 3 years, J. Pichon declares no conflicts of interest. A. Roche declares no conflicts of interest. C. Fauvel reports grants or contracts from Pfizer and Novartis, consulting fees from Janssen and Payment or honoraria for lectures from Pfizer outside the submitted work. A. Boucly reports grants or contracts from Acceleron, Janssen, and MSD and Payment or honoraria for lectures from Janssen, Merck, and AOP Orphan outside the submitted work. O. Mercier reports grants or contracts from Edwards Lifescience, and consulting fees from MSD outside the submitted work. N. Ebstein declares no conflicts of interest. A. Beurnier declares no conflicts of interest. J. Cortese declares no conflicts of interest. M. Jevnikar declares no conflicts of interest. X. Jais declares grants or contracts from Acceleron, Janssen, Bayer, Merck, and payment or honoraria for lectures from Janssen and Merck outside the submitted work. M. Fartoukh reports grants or contracts from Funding: Fondation du Souffle (Profil COV), Funding: Fondation de l’AP-HP (Multicov trial), BioMérieux, and Payment or honoraria for lectures from Fisher & Paykel, BioMérieux, and Other financial or non-financial interests forme Pfizer outside the submitted work. E. Fadel declares no conflicts of interest. O. Sitbon reports honoraria for speaking, steering committees, and scientific advisory boards from Janssen, Bayer, Merck, Gossamer Bio, Ferrer, and United Therapeutics. D. Montani reports grants and personal fees from Acceleron, Janssen, Merck, and consulting fees from Accelron, Merck, Janssen, and payment or honoraria for lectures from Bayer, Janssen, and Merck outside the submitted work. G. Voiriot declares no conflicts of interest. M. Humbert reports grants and personal fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX, and United Therapeutics and payment or honoraria from Janssen and Merck outside the submitted work. L. Savale reports personal fees from Janssen and Janssen and MSD outside the submitted work.
