Measurement Of Pulmonary Artery Pressure Research Articles

Comparison of Repetitive Cardiac Output Measurements at Rest and End-Exercise by Direct Fick Using Pulse Oximetry vs. Blood Gases in Patients With Pulmonary Hypertension.

Background: Exact and simultaneous measurements of mean pulmonary artery pressure (mPAP) and cardiac output (CO) are crucial to calculate pulmonary vascular resistance (PVR), which is essential to define pulmonary hypertension (PH). Simultaneous measurements of mPAP and CO are not feasible using the direct Fick (DF) method, due to the necessity to sample blood from the catheter-tip. We evaluated a modified DF method, which allows simultaneous measurement of mPAP and CO without needing repetitive blood samples.Methods: Twenty-four patients with pulmonary arterial or chronic thromboembolic PH had repetitive measurements of CO at rest and end-exercise during three phases of a crossover trial. CO was assessed by the original DF method using oxygen uptake, measured by a metabolic unit, and arterial and mixed venous oxygen saturations from co-oximetry of respective blood gases served as reference. These CO measurements were then compared with a modified DF method using pulse oximetry at the catheter- and fingertip.Results: The bias among CO measurements by the two DF methods at rest was −0.26 L/min with limits of agreement of ±1.66 L/min. The percentage error was 28.6%. At the end-exercise, the bias between methods was 0.29 L/min with limits of agreement of ±1.54 L/min and percentage error of 16.1%.Conclusion: Direct Fick using a catheter- and fingertip pulse oximetry (DFp) is a practicable and reliable method for assessing CO in patients with PH. This method has the advantage of allowing simultaneous measurement of PAP and CO, and frequent repetitive measurements are needed during exercise.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02755259, identifier: NCT02755259.

The thromboxane receptor antagonist NTP42 improves haemodynamics, inhibits remodelling, and restores function within the cardiopulmonary system in preclinical pulmonary arterial hypertension models

Abstract Background Pulmonary arterial hypertension (PAH) is a rare and fatal disease characterised by a progressive increase of pulmonary artery pressure leading to right heart failure. While current PAH therapies provide symptomatic relief and some improvement in quality of life, they show limited benefit in preventing disease progression and often have severe side effects. Recent studies by us reported that a novel thromboxane A2 receptor (TP) antagonist NTP42 attenuated multiple disease hallmarks of PAH in two preclinical models of the disease. Purpose The aim of this study was to assess the efficacy of a novel oral formulation of NTP42 developed for pharmaceutical use on monocrotaline (MCT)-induced PAH in rats across a range of cardiopulmonary parameters, and when compared with standard of care (SOC) PAH therapies. It also aimed to evaluate the expression of the TP, the target receptor for NTP42, in tissues from the MCT-induced PAH model and related disease models. Methods PAH was induced by subcutaneous injection of 60 mg/kg MCT. Rats were randomly assigned to 7 groups: (1) No MCT; (2) MCT Only; (3) MCT+NTP42 Formulation (1 mg/kg); (4) MCT+Sildenafil (50 mg/kg); (5) MCT+Macitentan (30 mg/kg), (6) MCT+Selexipag (1 mg/kg), and (7) MCT+Riociguat (5 mg/kg), where in all cases twice-daily oral dosing was initiated 7 days post-MCT and continued for 22 days. Results The results show that the formulated NTP42 reduced the severity of MCT-induced PAH as determined from haemodynamic measurements of mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), Fulton's Index of cardiac hypertrophy and histological assessments of pulmonary vascular remodelling, pulmonary oedema, inflammation and fibrosis, and right ventricular fibrosis. In addition, these assessments showed that NTP42 inhibited these effects at least to a similar extent relative to the SOC drugs Sildenafil, Macitentan, Selexipag and Riociguat. Notably, unlike most of the PAH SOCs, NTP42 had no adverse effects on liver weight and or on hepatic histopathology. Importantly, NTP42 had no effects on either the systemic mean arterial pressure (mAP) or heart rate (HR). Furthermore, while abundant expression of the target TP was noted in numerous cell and tissue types of both cardiac and pulmonary tissue, there were highly significant upregulations of TP expression observed following PAH-induction (RV, >2-fold, p=0.0002). Conclusions Taken together, these data demonstrate that NTP42 significantly attenuates MCT-induced PAH and to a similar or greater extent relative to market leader PAH SOC drugs. Notably, we reveal that expression of the TP, the target receptor for NTP42, was shown to be highly significantly upregulated throughout the cardiopulmonary system, validating the potential importance of this largely ignored PAH target ripe for pharmaceutical intervention. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020 SME Instrument

Sensitivity and Specificity of Pulmonary Artery Pressure Measurement in Echocardiography and Correlation with Right Heart Catheterization.

ObjectiveEchocardiography is helpful in assessment of pulmonary hemodynamic, however its correlation with Right heart catheterization (RHC) is conflicting. We conducted a study to evaluate sensitivity and specificity of pulmonary hemodynamic parameters measured in echocardiography. Furthermore its correlation with the values measured in RHC was assessed.MethodRetrospective, cross-sectional study conducted at King Fahad medical City, Riyadh, Saudi Arabia. 95 adult patients referred for right heart catheterization were enrolled in the study. All the patients had echocardiography and RHC within one week of each other.ResultDiabetes mellitus, hypertension and dyslipidemia were present among 55%, 66% and 41% of patients respectively. 85% of the study participants were diagnosed to have pulmonary hypertension and 79% of the study participants had postcapillary pulmonary hypertension. Sensitivity of pulmonary artery systolic pressure (PAPs), mean pulmonary artery pressure (PAPm) using PAPs and pulmonary artery acceleration velocity (PAcT) were 86%, 93% and 89% respectively. Correlation of PAPs, PAPm using PAPs and PAcT on echo with invasive hemodynamic in RHC were 0.56, 0.43 and 0.24 respectively. Among patients with moderate to severe Tricuspid Regurgitation (TR) and tricuspid annular plane systolic excursion (TAPSE) <1.5cm correlation of PAPs, PAPm using PAPs and PAcT on echocardiography with right heart catheterization were 0.31, 0.24 and 0.42 respectively.ConclusionEchocardiographic assessment of PAPs and PAPm has high sensitivity and weak to moderate correlation with hemodynamic data in RHC. PAPs measurement on echocardiogram has best correlation with invasive measurement followed by PAPm measurement using PAPs. Among patients with moderate to severe TR and TAPSE <1.5cm PAPm measurement using PAcT has better correlation than using PAPs.

Morning pulmonary artery pressure measurements by CardioMEMS are most stable and recommended forpressure trends monitoring.

AimsThe CardioMEMS HF system is used to measure pulmonary artery (PA) pressures of patients with heart failure (HF). The goal of this study was to determine the impact of time in the daily PA pressure measurements, considering variance and influence of circadian rhythms on cardiovascular pathophysiology.Methods and resultsThe study included 10 patients with HF with reduced ejection fraction (LVEF < 40%; New York Heart Association class III). Individual daily PA pressures were obtained by CardioMEMS sensors, per protocol, measured up to six times throughout the day, for a period of 5 days. Differences between variation of morning versus evening PA pressures were compared with Wilcoxon signed-rank test.Mean PA pressures (mPAP) increased from a morning value of 19.1 ± 2 mm Hg (8 am; mean ± standard error of the mean [SEM]) to 21.3 ± 2 mm Hg late in the evening (11 pm; mean ± SEM). Over the course of 5 days, evening mPAP exhibited a significantly higher median coefficient of variation than morning mPAP (14.9 (interquartile range [IQR] 7.6–21.0) and 7.0 (IQR 5.0–12.8) respectively; p = 0.01). The same daily pattern of pressure variability was observed in diastolic (p = 0.01) and systolic (p = 0.04) pressures, with diastolic pressures being more variable than systolic at all time points.ConclusionsMorning PA pressure measurements yield more stable values for observing PA trends. Patients should thus be advised to consistently perform their daily PA pressure measurements early in the morning. This will improve reliability and interpretation of the CardioMEMS management, indicating true alterations in the patient’s health status, rather than time-of-day-dependent variations.Supplementary InformationThe online version of this article (10.1007/s12471-021-01590-7) contains supplementary material, which is available to authorized users.

Renal Function and Pulmonary Fluid Balance in Porcine Models of Acute Lung Injury

Managing pulmonary edema is critical to maintaining blood oxygenation and perfusion for adequate tissue oxygen delivery after acute lung injury. While it is well recognized that renal failure often leads to complications of nephrogenic pulmonary edema, how the regulation of lung fluid is changed during altered renal function in conditions of traumatic injury is poorly understood. We hypothesized that control of lung water balance after a traumatic blunt force lung injury accompanied by a renal response to hemorrhage and hypotension would be different than after simple disruption of the alveolar-capillary liquid barrier interface. Hence, we compared the changes in effective lung water index (ELWI, measured by the Pulse Ion Contour Cardiac Output (PICCO), Getinge) method in a pig model of Traumatic Acute Lung Injury (TALI, n=9), and a model of diffuse alveolar-capillary barrier disruption with oleic acid (OA, n=5), versus a control group (n=10). Anesthetized, mechanically ventilated, Yorkshire cross male and female pigs (body weight 27.0 +/- 0.6 kg) were catheterized with a Swan Ganz catheter for measurement of pulmonary artery pressure and cardiac output determination by thermodilution. Pulmonary function, hemodynamics, and urinary output were examined before and after localized blunt right chest trauma (TALI), or oleic acid injection into the main pulmonary artery (OA 0.3 ml in 50% w/v ethanol). Pulmonary vasoconstriction was induced in the acute lung injury groups as indicated by an increase in pulmonary to systemic vascular resistance ratios in TALI (0.37 +/- 0.03) and OA (0.34 +/-0.08) compared to controls (0.21+/-0.02). TALI resulted in a decrease in mean arterial pressure (MAP, 46+/-4 mmHg) compared to controls (60 +/-2 mmHg) or OA (62+/-3 mm Hg). In all groups ELWI remained steady compared to pre-injury baseline. In the OA and control groups, circulating vasopressin decreased over the time course of the experiment (p<0.01) but did not decrease in the TALI group in accordance with the injury-induced hemorrhage and decreased MAP. Accordingly, urine flow decreased in the TALI group compared to OA and controls. Fractional excretion of water decreased in the OA and control groups, (p<0.01) but remained unchanged in TALI, indicating retention of water in OA and controls compared to TALI. The overall maintenance of ELWI despite differences in renal water handling in TALI compared to controls suggest that protection against pulmonary edema needs to be considered in treatment of hypotension with fluid resuscitation in traumatic lung injury.

Sequential Combination Diuretic-Therapy for Massive Fluid Overload in Furosemide-Refractory Patients with Diabetic Kidney Disease

Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of massive fluid overload in Furosemide-refractory renal patients. The added diuretics were Spironolactone 25 mg daily for 3 days, to those without risk of hyperkalemia, followed by Hydrochlorothiazide 25 mg/Metolazone 5 mg daily for 3 more days. Excluded patients were those with 1) acute renal disease, 2) echocardiographic evidence of: a) left ventricular ejection fraction < 40%, b) significant stenotic or incompetent valvular disease, c) ASD or VSD, d) significant pericardial disease, and 3) significant limb venous disease or on drugs likely to cause limb-oedema. To assess the extent of fluid overload; clinical examination was complemented with radiological imaging as well as echocardiographic measurement of systolic pulmonary arterial pressure (sPAP). SCDT led to significant symptomatic, clinical, and radiological improvement of fluid overload without significant side effects. The latter were limited to hyperkalemia and hyponatremia which improved with dietary compliance. Moreover, hyperkalemia improved after subsequent addition of Thiazide/Metolazone. SCDT led to significant (p < 0.001) increase in fractional excretion of sodium and decrease in body weight and sPAP. In conclusion; SCDT is a safe and efficacious measure to control fluid overload in patients with renal diseases.

CardioMEMS Pulmonary Artery Pressure Guided Management of Advanced HF Patients Supported with a HeartMate LVAD: INTELLECT 2-HF Study

PurposeHemodynamic-guided management with a pulmonary artery pressure (PAP) sensor (CardioMEMS) is effective in reducing HF hospitalization (HFH) in chronic HF patients. We sought to determine the utility of managing patients on continuous-flow LVAD support using the CardioMEMSTM HF system.MethodsIn this multi-center observational study, we enrolled patients with a HeartMate 2 (HM2) (n=52) or HM3 (n=49) LVAD who either already had a CardioMEMS sensor (n=53) or were clinically implanted after enrollment for residual HF (n=48). Patients underwent assessments at baseline, 1, 3 and 6 months for endpoints: 6-minute walk distance (6MWD), change in PAP, quality of life score (EQ-5D-5L scores), and HFH rates. Patients were stratified post-hoc as clinical responders (cR) if there was a reduction in PA diastolic pressure (PAD) of at least 1 mmHg at 6 months, and the remainder were deemed non-responders (cNR).ResultsOf 101 patients enrolled, 88 patients completed 6-month follow-up. PAP measurement was feasible with excellent weekly patient compliance (91.1% ± 19.8%). There were no clinically relevant differences between cR (n=37) and cNR (n=46) patients at baseline (data not shown). PAD at 6 months was 3.5 ± 4.6 mmHg lower than baseline within the cR group (20.8 to 17.3 mmHg, p=0.0002) (Figure-panel A). While there were no observed differences in QoL or HFH between cR and cNR, significant increases in 6MWD occurred among cR (286 vs 332 meters, p=0.03, Figure-panel B). Those individuals who maintained a PAD < 20mmHg had significantly reduced HFH (Figure-panel C).ConclusionThe use of CardioMEMS system in HeartMate LVAD patients is feasible. Significant reduction in PAD at 6 months was associated with improvements in 6MWD and achieving a PAD < 20 mmHg was associated with lower HFH events. These findings provide justification and guidance for prospective investigations utilizing the CardioMEMS system to improve the management and outcomes of LVAD patients. Hemodynamic-guided management with a pulmonary artery pressure (PAP) sensor (CardioMEMS) is effective in reducing HF hospitalization (HFH) in chronic HF patients. We sought to determine the utility of managing patients on continuous-flow LVAD support using the CardioMEMSTM HF system. In this multi-center observational study, we enrolled patients with a HeartMate 2 (HM2) (n=52) or HM3 (n=49) LVAD who either already had a CardioMEMS sensor (n=53) or were clinically implanted after enrollment for residual HF (n=48). Patients underwent assessments at baseline, 1, 3 and 6 months for endpoints: 6-minute walk distance (6MWD), change in PAP, quality of life score (EQ-5D-5L scores), and HFH rates. Patients were stratified post-hoc as clinical responders (cR) if there was a reduction in PA diastolic pressure (PAD) of at least 1 mmHg at 6 months, and the remainder were deemed non-responders (cNR). Of 101 patients enrolled, 88 patients completed 6-month follow-up. PAP measurement was feasible with excellent weekly patient compliance (91.1% ± 19.8%). There were no clinically relevant differences between cR (n=37) and cNR (n=46) patients at baseline (data not shown). PAD at 6 months was 3.5 ± 4.6 mmHg lower than baseline within the cR group (20.8 to 17.3 mmHg, p=0.0002) (Figure-panel A). While there were no observed differences in QoL or HFH between cR and cNR, significant increases in 6MWD occurred among cR (286 vs 332 meters, p=0.03, Figure-panel B). Those individuals who maintained a PAD < 20mmHg had significantly reduced HFH (Figure-panel C). The use of CardioMEMS system in HeartMate LVAD patients is feasible. Significant reduction in PAD at 6 months was associated with improvements in 6MWD and achieving a PAD < 20 mmHg was associated with lower HFH events. These findings provide justification and guidance for prospective investigations utilizing the CardioMEMS system to improve the management and outcomes of LVAD patients.

Right Atrial Function Index in Chronic Thromboembolic Pulmonary Hypertension before and after Pulmonary Thromboendarterectomy

Purpose Chronic thromboembolic pulmonary hypertension (CTEPH) can be effectively treated with pulmonary thromboendarterectomy (PTE). The standard for assessing postoperative success is through right heart catheterization measurements of mean pulmonary arterial pressure (mPAP) and peripheral vascular resistance (PVR). Recently, a novel echocardiographic parameter (right atrial function index, RAFi) was shown to predict clinical outcomes in patients (pts) with precapillary PH. In this study, we assessed the utility and predictive value of this novel index in CTEPH patients before and after PTE. Methods 50 consecutive CTEPH pts with pre- and post-PTE echocardiograms (echos) were studied. RA volumes were assessed in the apical 4 chamber view. RA end-systolic volume (ESV) was measured just before tricuspid valve opening; RA end diastolic volume (EDV) was assessed at tricuspid valve closure. RV outflow tract velocity time integral (VTI) was also obtained in all pts. Calculations RAEF = ([RAESV-RAEDV]/RAESV)*100RAESVi = RAESV(mL)/BSA(m2)RAFi = (RAEF (%)*VTI (cm))/RAESVi (mL/m2) Results The mean pre-op RAFi was 24.1 ± 23.5; mean post-op RAFi was 20.2 ± 17.7 (p=0.27). Before PTE, there was a modest correlation between RAFi & mPAP (R= -0.399, p Conclusion In our patient population, RAFi was surprisingly unchanged statistically (and trended downward) after successful PTE. This trend may be due to sudden changes in RAESV and RAEDV or postoperative RV stunning, which could have caused the minimal change in RVOT VTI. Thus, RAFi cannot be used as a noninvasive parameter of post-PTE success. However, there is a significant correlation between pre-op RAFi and traditional invasive measurements that may be useful in the noninvasive assessment of pts with CTEPH.

Loud P2 on Cardiac Auscultation: A Useful Clinical Clue to Fluid Overload

Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the increase in the intensity of the second heart sound generated by its pulmonary component (P2) and its correlation with fluid overload in such patients. To confirm its potentials and avoid interference with patients with cardiac disease; we included only those who lacked echocardiographic evidence of (a) ASD or VSD, (b) primary cardiac defects associated with high P2 viz pulmonary aneurysm, mitral stenosis and myocardial disease, (c) primary cardiac defects associated with soft P2 viz pulmonary stenosis, pulmonary atresia and tetralogy of Fallot, (d) primary cardiac defects associated with low A2 viz mitral regurgitation, aortic regurgitation, low diastolic arterial pressure, severe immobile aortic valve disease. To assess the extent of fluid overload; the clinical examination was complemented with radiological imaging as well as the echocardiographic measurement of systolic pulmonary arterial pressure. There was a significant correlation between P2 intensity and fluid changes. In conclusion; load P2 is a useful clinical clue to fluid overload and decline in its intensity correlates with the extent of fluid removal.

283 Heterosis and its potential influence on pulmonary arterial pressure in beef cattle

Abstract High altitude disease (HAD) is a hypoxia-influenced pathologic condition experienced by cattle raised at high elevations (&amp;gt; 1,524 m). Pulmonary arterial pressure (PAP) is a common diagnostic tool used as an indicator of susceptibility to develop HAD. Given PAP is moderately heritable, possibilities to genetically reduce the incidence of HAD are feasible. However, an alternative strategy could be given by heterosis, since non-additive genetic effects have been related to survivability and environmental fitness. Therefore, objectives of this study were to determine heterosis and breed percentage effects on PAP measurements. A total of 1,083 cattle with varying percentages of Simmental, Angus, Hereford and Red Angus breeds were used for the study. Such animals’ available information included PAP records, PAP test date, PAP technician, sex, herd of origin and breed percentages of parents. A general linear model was utilized to estimate the effect of heterosis on PAP. Contemporary group (defined as a combination between herd, PAP date, PAP technician and sex) was included as a categorical fixed effect; whereas the age at PAP measurement and the degree of outcross were included as linear covariates. Similarly, breed effects were estimated by including breed percentages of Simmental, Angus, Hereford, Red Angus and “Other” breeds as linear covariates in the model. The general average for PAP measurements in the entire dataset was 41.29 ± 0.22, with range of 26 and 108 mmHg. The estimated regression coefficient for PAP on heterosis was -1.834 ± 1.676 mmHg/percent of outcross (P = 0.276), whereas, the range of breed effects on PAP was 15.08 mmHg. These results suggested that heterosis had no significant effects on PAP measurements. However, further research including other multibreed populations is required in order to better understand if increased levels of heterozygosity could potentially be related to lower PAP scores.

265 Evaluation of the genetic relationship amongst high elevation pulmonary arterial pressure, feedlot and carcass performance traits

Abstract The objective of the study was to evaluate if a genetic relationship exists between pulmonary arterial pressure (PAP) measured at high elevation with traits associated with moderate elevation feedlot and carcass traits. For this analysis, PAP, feed intake, and carcass data were taken from 6,898, 558, and 1,627 animals, respectively. At an elevation of 2,115 m, PAP measurements were collected, then a selective group of steers was relocated to a moderate elevation feedlot (1,500 m) where feed intake data were collected. Genetic relationships were evaluated with 5-trait animal models using REML statistical analysis. For all traits in the analysis, fixed effects and contemporary groups were assigned as well as a direct genetic random effect. For weaning weight, a maternal permanent environmental effect was applied in the analysis. For PAP, the heritability estimate was 0.29 ± 0.03. Genetic correlations between PAP with feedlot traits was positive, with estimates of 0.34 ± 0.20 (average dry matter intake) and 0.05 ± 17 (average daily gain). The strongest genetic correlation between PAP and carcass performance traits were those of rib eye area (-0.30 ± 0.12) and calculated yield grade (0.29 ± 0.13). Genetic correlations between PAP and marbling score, back fat, or hot carcass weight were 0.00 ± 0.13, -0.07 ± 0.13, and 0.14 ± 0.10, respectively. These results suggest a favorable genetic relationship exists between PAP with feedlot and carcass traits.

Pulmonary hemodaynamic in obesity

Abstract Background Higher prevalence of pulmonary hypertension exist in obesity subjects. Little known about pulmonary hemodynamics during exercise in obesity population. Purpose To assess and compare the response of pulmonary vascular resistance during exercise in obese subjects vs healthy controls. Methods Seventeen obesity subjects (gender: 25%men, age: 44±11 years, height: 1.7±0.1 m, weight: 111±17 kilogram, BMI: 38±4 kg/m2) were compared to twenty gender-, age-, height- and race-matched healthy control subjects (age: 46±12 years, height: 1.7±0.1 m, weight: 64±11 kilogram, BMI: 22±2 kg/m2). All subjects underwent an incremental exercise stress echocardiography with measurements of pulmonary artery pressure (PAP), cardiac output (CO), cardiac index (CI) and tricuspid annular plane systolic excursion (TAPSE) at rest and at increasing exercise intensities. Total pulmonary vascular resistance index (PVRi) was calculated as mean PAP/CI and right ventricular-arterial coupling as TAPSE/systolic PAP. Results The results are described in the table 1. Pulmonary hemodynamic was not different at rest between two groups, but lower at maximal exercise in obesity subjects. In obesity subjects, identical exercise level was associated with a higher mean PAP and PVRi, and a lower TAPSE/systolic PAP ratio. Conclusion While pulmonary hemodynamic seems preserved at rest in obesity patients, pulmonary vascular resistance is increased and right ventricular coupling is decreased, particularly at exercise. Funding Acknowledgement Type of funding source: None

Comparison of various instantaneous pulmonary arterial wedge pressure measurements with prognostic validation

Abstract Background Current recommendations on the diagnosis of pulmonary hypertension due to left heart disease (PH-LHD) emphasize the need for standardization of pulmonary arterial wedge pressure (PAWP) measurement. Instead of mean PAWP values instantaneous mid-A wave pressures or, in case of atrial fibrillation (AF), measurement 130–160 ms after the QRS onset is recommended. Recently, PAWP at the QRS onset has also been proposed. Our aim was to compare the various instantaneous PAWP measurements and assess the prognostic value of the derived diastolic pressure gradients (DPG) in heart failure (HF) patients. Methods and results PAWP and pulmonary arterial pressure (PAP) tracings of 116 patients with PH-LHD were manually analyzed offline. PAWP was measured in 4 different ways: 1. mean value [PAWPM]; 2.mid-A wave value in sinus, and at 10 ms intervals 130–160 ms following QRS onset in AF [PAWPR]; 3. at the onset of the QRS complex [PAWPQRS]; 4. pre C-wave point value [PAWPC]. The pre C-wave point was chosen as a reference for truly end-diastolic pressures. The corresponding DPGM, DPGR, DPGQRS and DPGC were calculated. The patients were followed for 17 (8–27) months and the prognostic value of the various DPG measurements for predicting all-cause mortality was assessed. The pre C-wave point was identifiable in 35 patients (30%); on average it occurred 171 ms after the QRS-onset whereas the A wave-onset and A-wave peak happened on average 62 and 149 ms after the QRS-onset, respectively. All three instantaneous PAWP measurements gave significantly lower values than PAWPM [19.3 (15.4–25.0)]. PAWPR did not differ from PAWPC [18.1 mmHg (14–22) vs. 19.2 mmHg (13–22.8), p=0.9], whereas PAWPQRS was lower [15.8 mmHg (12.2–19.9), p&amp;lt;0.001]. Accordingly, all instantaneous DPG measurements were higher than DPGM, yielding lower prevalence of negative DPG (29%, 17% and 45%, for DPGR, DPGQRS and DPGM, respectively). In AF (n=30), DPGR values at 130–140–150–160 ms demonstrated increasing scatter and progressively overestimated DPGQRS. For prognostic assessment, in case of both DPGQRS and DPGR, 6 mmHg was identified as a best cut-off value for predicting all-cause mortality, at which both indices provided superior prognostic information than DPGM [DPGR: HR 2.7; CI 1.1–6.9, p=0.029; DPGQRS: HR 2.6; CI 1.1–6.4, p=0.037, high-risk cases 17 for both; DPGM: HR 2.8; CI 1.0–7.6, p=0.045, high-risk cases 10]. Conclusions PAWP measured at the mid-A wave provides a reliable assessment of the end-diastolic PAWP in sinus rhythm. On the other hand, ECG-gated measurements yield more robust evaluation of PAWP in AF. Finally, both approaches carry significant and similar prognostic information in PH-LHD. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIN was supported by the János Bolyai Scholarship of the Hungarian Academy of Sciences

A closer look at physiological indicators of cardiovascular function post‐transplantation

A closer look at physiological indicators of cardiovascular function post‐transplantation

In Response.

We thank Dr A. K. Jha1 for his valuable comments regarding our article.2 Although there is a correlation between the relative perfusion to the operative lung as assessed by lung scans and the partial pressure of oxygen in arterial blood (Pao2), it is unclear whether this variable is clinically relevant for patients undergoing thoracic surgery.3 Because not all the patients enrolled in our trial underwent lung perfusion scans, we did not perform a between-group comparison. We also did not measure Pao2 levels by arterial blood gas analysis during 2-lung ventilation (TLV). Because the Pao2 level during 1-lung ventilation (OLV) strongly and positively correlates with Pao2 during TLV, we were able to predict hypoxemia during OLV for patients in both groups that presented with an average room air saturation of 93% before general anesthesia. Nonetheless, we acknowledge that the TLV parameters and preoperative perfusion scans may give more insight on the impact of OLV, peak inspiratory pressure (PIP) and Pao2/fractional inspiration of oxygen (Fio2) (P/F) ratio. Hypoxic pulmonary vasoconstriction (HPV) during OLV mitigates the shunt fraction. HPV is blunted by sevoflurane and suppressed by the pathologic effects of chronic obstructive pulmonary disease (COPD). Although we did measure sevoflurane concentrations, we administered balanced anesthesia that included a remifentanil infusion. Thus, the actual concentration of sevoflurane was probably less than 1 minimum alveolar concentration (MAC), a concentration thought to have limited impact on HPV.4 Also, the treatment of OLV-induced increase in pulmonary hypertension may have been beneficial, as Dr A. K. Jha1 commented in the letter. Unfortunately, as we mentioned in the limitation section, we can only speculate there was an OLV-induced rise in pulmonary artery pressure because it was not possible to obtain accurate measurements of pulmonary arterial pressure in our clinical practice. We agree with the view that iloprost-induced pulmonary arteriolar vasodilation in the ventilated lung resulted in blood diversion from nonventilated lung to the ventilated lung with physiological dead space reduction and P/F ratio augmentation. Indeed, as our study results indicate, inhaled iloprost improves oxygenation and dead space ventilation during OLV in COPD patients with poor lung oxygenation. Considering that atelectasis in the operated lung persists in the postoperative period,5 it can be deduced that the difference in P/F ratio in the postanesthetic care unit in both groups may be due to the residual intrapulmonary shunt fraction and the residual effects of iloprost inhalation, which ameliorates the ventilation/perfusion matching. In this regard, we speculate that the beneficial effects of iloprost during OLV may persist even after TLV or spontaneous ventilation is restored, but this needs to be clarified. We think that the comments provided by Dr A. K. Jha1 are valuable and should be considered when planning further studies. Namo Kim, MD, PhDDepartment of Anesthesiology and Pain MedicineAnesthesia and Pain Research InstituteYonsei University College of MedicineSeoul, Republic of Korea Su Hyun Lee, MDDepartment of Anesthesiology and Pain MedicineYonsei Sarang HospitalSeoul, Republic of Korea Young Jun Oh, MD, PhDDepartment of Anesthesiology and Pain MedicineAnesthesia and Pain Research InstituteYonsei University College of MedicineSeoul, Republic of Korea[email protected]

Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization

The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15mmHg. The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20mmHg and ≤20mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.

Continuous real-time monitoring of pulmonary arterial pressure using a tip deflecting microcatheter in an infant with pulmonary arterial hypertension

We present the case of a 3-month-old boy with pulmonary arterial hypertension after corrective repair of total anomalous pulmonary venous connection. The patient developed severe pulmonary arterial hypertension with a high mean pulmonary arterial pressure of 45 mmHg. We performed continuous monitoring of pulmonary arterial pressure using a tip deflecting microcatheter in the intensive care unit. We successfully managed this patient based on real-time pulmonary arterial pressure measurements. Continuous real-time monitoring of pulmonary arterial pressure using this microcatheter enables individualized targeted therapy for infants with pulmonary arterial hypertension.

Impaired Endothelial Caveolin‐1‐TRPV4 Channel Signaling Contributes to Endothelial Dysfunction in Pulmonary Hypertension

Impaired endothelium‐dependent vasodilation is a key contributor to elevated pulmonary arterial pressure (PAP) in pulmonary hypertension (PH). While the mechanisms of pathogenesis of PH remain elusive, recent studies show that spatially localized Ca2+ influx via endothelial transient receptor potential vanilloid 4 (TRPV4EC) channels promotes vasodilation in resistance‐sized pulmonary arteries (PAs) by activating endothelial nitric oxide synthase (eNOS) and releasing nitric oxide (NO). Caveolin‐1 (Cav‐1EC) is an essential structural protein within the pulmonary endothelium, where it has been found to associate with TRPV4EC channels in cultured endothelial cells. We hypothesized that Cav‐1EC regulates TRPV4EC channel activity and PAP, and that impaired Cav‐1EC‐TRPV4EC signaling contributes to elevated PAP in PH. To test these hypotheses, we used right ventricular systolic pressure (RVSP) and PAP measurements in normoxic or chronic hypoxic Cav‐1EC−/− and TRPV4EC−/− mice, and pressure myography and high‐speed Ca2+ imaging studies in PAs from these mice. TRPV4EC channel activity and TRPV4EC‐mediated vasodilation were significantly impaired in PAs from Cav‐1EC−/− mice, suggesting that Cav‐1EC enhances TRPV4EC channel activity in PAs. Purinergic signaling plays an important role in pulmonary circulation, and we recently identified adenosine triphosphate (ATP) as a novel physiological activator of TRPV4EC channels in PAs. ATP activation of TRPV4EC channels was abolished by protein kinase C (PKC) inhibition, and was absent in the arteries from Cav‐1EC−/− mice, supporting a Cav‐1EC‐PKC‐TRPV4EC signaling that enables ATP activation of TRPV4‐EC channels. Resting RVSP and PAP were elevated in Cav‐1EC−/− and TRPV4EC−/− mice supporting the concept that Cav‐1EC‐TRPV4EC signaling lowers resting PAP. Moreover, exposure to chronic hypoxia (CH, 3 weeks) resulted in higher increases in RVSPs in Cav‐1EC−/− and TRPV4EC−/− mice when compared to the respective wild‐type control mice, suggesting that Cav‐1EC‐TRPV4EC channel signaling is protective against CH‐induced PH. We further used two well‐established models of PH— CH and sugen 5416 injection + CH. TRPV4EC channel activity, and ATP‐ and PKC‐activation of TRPV4EC channels were impaired in PAs from both the models of PH, suggesting that Cav‐1EC‐PKC‐TRPV4EC signaling may be impaired in PH. Taken together, these results suggest that Cav‐1EC‐PKC‐TRPV4EC signaling lowers resting PAP, and is impaired in PH. Deciphering the mechanisms that impair the Cav‐1EC‐PKC‐TRPV4EC signaling in PH may lead to novel therapeutic strategies to restore endothelium‐dependent vasodilation in PH.Support or Funding InformationHL121484‐01, HL‐138496

Cardiovascular magnetic resonance 4D flow analysis has a higher diagnostic yield than Doppler echocardiography for detecting increased pulmonary artery pressure

BackgroundPulmonary hypertension is definitively diagnosed by the measurement of mean pulmonary artery (PA) pressure (mPAP) using right heart catheterization. Cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow analysis can estimate mPAP from blood flow vortex duration in the PA, with excellent results. Moreover, the peak systolic tricuspid regurgitation (TR) pressure gradient (TRPG) measured by Doppler echocardiography is commonly used in clinical routine to estimate systolic PA pressure. This study aimed to compare CMR and echocardiography with regards to quantitative and categorical agreement, and diagnostic yield for detecting increased PA pressure.MethodsConsecutive clinically referred patients (n = 60, median [interquartile range] age 60 [48–68] years, 33% female) underwent echocardiography and CMR at 1.5 T (n = 43) or 3 T (n = 17). PA vortex duration was used to estimate mPAP using a commercially available time-resolved multiple 2D slice phase contrast three-directional velocity encoded sequence covering the main PA. Transthoracic Doppler echocardiography was performed to measure TR and derive TRPG. Diagnostic yield was defined as the fraction of cases in which CMR or echocardiography detected an increased PA pressure, defined as vortex duration ≥15% of the cardiac cycle (mPAP ≥25 mmHg) or TR velocity > 2.8 m/s (TRPG > 31 mmHg).ResultsBoth CMR and echocardiography showed normal PA pressure in 39/60 (65%) patients and increased PA pressure in 9/60 (15%) patients, overall agreement in 48/60 (80%) patients, kappa 0.49 (95% confidence interval 0.27–0.71). CMR had a higher diagnostic yield for detecting increased PA pressure compared to echocardiography (21/60 (35%) vs 9/60 (15%), p < 0.001). In cases with both an observable PA vortex and measurable TR velocity (34/60, 56%), TRPG was correlated with mPAP (R2 = 0.65, p < 0.001).ConclusionsThere is good quantitative and fair categorical agreement between estimated mPAP from CMR and TRPG from echocardiography. CMR has higher diagnostic yield for detecting increased PA pressure compared to echocardiography, potentially due to a lower sensitivity of echocardiography in detecting increased PA pressure compared to CMR, related to limitations in the ability to adequately visualize and measure the TR jet by echocardiography. Future comparison between echocardiography, CMR and invasive measurements are justified to definitively confirm these findings.

NON-INVASIVE SEISMOCARDIOGRAPHY CAN ACCURATELY TRACK CHANGES IN PULMONARY ARTERY PRESSURES DURING VASODILATOR CHALLENGE AT THE TIME OF RIGHT HEART CATHETERIZATION

Intervening in response to ambulatory pulmonary artery pressure (PAP) measurements has been shown to improve outcomes in heart failure (HF) patients. A low cost non-invasive alternative to commercially available implantable devices for monitoring ambulatory PAP can improve HF management and reduce