Risk prediction in pulmonary hypertension due to chronic heart failure: incremental prognostic value of pulmonary hemodynamics.

BACKGROUND: There is no generally accepted comprehensive risk prediction model cooperating risk factors associated with heart failure and pulmonary hemodynamics for patients with pulmonary hypertension due to left heart disease (PH-LHD). We aimed to explore outcome correlates and evaluate incremental prognostic value of pulmonary hemodynamics for risk prediction in PH-LHD. METHODS: Consecutive patients with chronic heart failure undergoing right heart catheterization were prospectively enrolled. The primary endpoint was all-cause mortality. Individual variable selection was performed by machine learning methods. Cox proportional hazards models were conducted to identify the association between variables and mortality. Incremental value of hemodynamics was evaluated based on the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores. RESULTS: A total of 276 PH-LHD patients were enrolled, with a median follow-up time of 34.7 months. By L1-penalized regression model and random forest approach, diastolic pressure gradient (DPG) and mixed venous oxygen saturation (SvO2) were the hemodynamic predictors most strongly associated with mortality (coefficient: 0.0255 and -0.0176, respectively), with consistent significance after adjusted for SHFM [DPG: HR 1.067, 95% CI 1.024-1.113, P = 0.022; SvO2: HR 0.969, 95% CI 0.953-0.985, P = 0.002] or MAGGIC (DPG: HR 1.069, 95% CI 1.026-1.114, P = 0.011; SvO2: HR 0.970, 95% CI 0.954-0.986, P = 0.004) scores. The inclusion of DPG and SvO2 improved risk prediction compared with using SHFM [net classification improvement (NRI): 0.468 (0.161-0.752); integrated discriminatory index (IDI): 0.092 (0.035-0.171); likelihood ratio test: P < 0.001] or MAGGIC [NRI: 0.298 (0.106-0.615); IDI: 0.084 (0.033-0.151); likelihood ratio: P < 0.001] scores alone. CONCLUSION: In PH-LHD, pulmonary hemodynamics can provide incremental prognostic value for risk prediction. CLINICAL TRIAL REGISTRATION: NCT02164526 at https://clinicaltrials.gov .

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients　- A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.

BACKGROUND: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).

Exercise Hemodynamics in the Prognosis of Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Assessment of prognosis is of major importance when deciding on a therapeutic strategy in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: The aim of this study was to investigate the prognostic value of pulmonary hemodynamics during exercise and changes during treatment in patients with PAH. METHODS: Consecutive incident patients (n = 49) with PAH undergoing right heart catheterization at rest and during a constant workload cycle exercise in supine position were included. Predictors of survival were identified at baseline using Cox proportional hazard regression models in a univariate analysis unadjusted and adjusted for age and gender. RESULTS: During a median follow-up period of 42 months, 13 (27%) of the 49 patients studied died. Two predictors of death were found: rest-to-exercise changes in heart rate and systolic pulmonary artery pressure. Adjusted hazard ratios were 0.92 (95% CI 0.86-0.99) and 0.93 (95% CI 0.88-0.99), respectively. These 2 variables were correlated with each other (r = 0.55, p < 0.001). CONCLUSIONS: Rest-to-exercise changes in heart rate and systolic pulmonary artery pressure measured at diagnosis are predictors of survival in patients with PAH. These measurements taken from an exercise test reflect right ventricular function.

Riociguat Improves Pulmonary Hemodynamics in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Few studies have investigated the effects of riociguat on pulmonary hemodynamics in Asian patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study, we evaluated the effects of riociguat on pulmonary hemodynamics in inoperable CTEPH patients. METHODS: We retrospectively collected the clinical data of 11 inoperable CTEPH patients. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-minute walk distance and World Health Organization (WHO) functional class were assessed at baseline and after riociguat treatment. RESULTS: The median duration of riociguat treatment was 12 months, and all 11 patients tolerated riociguat 7.5 mg/day well after titration. With regards to pulmonary hemodynamic data, both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 41 ± 8 mmHg to 38 ± 9 mmHg (p = 0.045) and 787 ± 417 dyn·s·cm-5 to 478 ± 267 dyn·s·cm-5 (p = 0.007), respectively. With regards to clinical symptoms, WHO functional class significantly improved in nine of the 11 patients, and there was no change in the other two patients (p = 0.004). In addition, the median level of N-terminal pro-brain natriuretic peptide also significantly decreased from 281 (117-5943) pg/ml to 226 (48-1276) pg/ml (p = 0.021). CONCLUSIONS: Riociguat treatment improved both clinical symptoms and pulmonary hemodynamics in the inoperative CTEPH patients in this study.

Pulmonary capillary surface area in supine exercising humans: demonstration of vascular recruitment.

In exercising humans, cardiac output (CO) increases, with minor increases in pulmonary artery pressure (PAP). It is unknown if the CO is accommodated via distention of already perfused capillaries or via recruitment of nonconcomitantly perfused pulmonary capillaries. Ten subjects (9 female) performed symptom-limited exercise. Six had resting mean PAP (PAPm) <20 mmHg, and four had PAPm between 21 and 24 mmHg. The first-pass pulmonary circulatory metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) was measured at rest and at peak exercise, and functional capillary surface area (FCSA) was calculated. Data are means ± SD. Mean pulmonary arterial pressure rose from 18.8 ± 3.3 SD mmHg to 28.5 ± 4.6 SD mmHg, CO from 6.4 ± 1.6 to 13.4 ± 2.9 L/min, and pulmonary artery wedge pressure from 14 ± 3.3 to 19.5 ± 5 mmHg (all P ≤ 0.001). Percent BPAP metabolism fell from 74.7 ± 0.1% to 67.1 ± 0.1%, and FCSA/body surface area (BSA) rose from 2,939 ± 640 to 5,018 ± 1,032 mL·min-1·m-2 (all P < 0.001). In nine subjects, the FCSA/BSA-to-CO relationship suggested principally capillary recruitment and not distention. In subject 10, a marathon runner, resting CO and FCSA/BSA were high, and increases with exercise suggested distention. Exercising humans demonstrate pulmonary capillary recruitment and distention. At moderate resting CO, increasing blood flow causes principally recruitment while, based on one subject, when exercise begins at high CO, further increases appear to cause distention. Our findings clarify an important physiologic question. The technique may provide a means for further understanding exercise physiology, its limitation in pulmonary hypertension, and responses to therapy.

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

Extracorporeal CO2 removal and regional citrate anticoagulation in an experimental model of hypercapnic acidosis.

Low flow extracorporeal veno-venous CO2 removal (ECCO2 R) therapy is used to remove CO2 while reducing ventilation intensity. However, the use of this technique is limited because efficiency of CO2 removal and potential beneficial effects on pulmonary hemodynamics are not precisely established. Moreover, this technique requires anticoagulation that may induce severe complications in critically ill patients. Therefore, our study aimed at determining precise efficiency of CO2 extraction and its effects on right ventricular (RV) afterload, and comparing regional anticoagulation with citrate to systemic heparin anticoagulation during ECCO2 R. This study was performed in an experimental model of severe hypercapnic acidosis performed in two groups of three pigs. In the first group (heparin group), pigs were anticoagulated with a standard protocol of unfractionated heparin while citrate was used for ECCO2 R device anticoagulation in the second group (citrate group). After sedation, analgesia and endotracheal intubation, pigs were connected to a volume-cycled ventilator. Severe hypercapnic acidosis was obtained by reducing tidal volume by 60%. ECCO2 R was started in both groups when arterial pH was lower than 7.2. Pump Assisted Lung Protection (PALP, Maquet, Rastatt, Germany) system was used to remove CO2 . CO2 extraction, arterial pH, PaCO2 as well as systemic and pulmonary hemodynamic were continuously followed. Mean arterial pH was normalized to 7.37 ± 1.4 at an extracorporeal blood flow of 400 mL/min, coming from 7.11 ± 1.3. RV end-systolic pressure increased by over 30% during acute hypercapnic acidosis and was normalized in parallel with CO2 removal. CO2 extraction was not significantly increased in citrate group as compared to heparin group. Mean ionized calcium and MAP were significantly lower in the citrate group than in the heparin group during ECCO2 R (1.03 ± 0.20 vs. 1.33 ± 0.19 and 57 ± 14 vs. 68 ± 15 mm Hg, respectively). ECCO2 R was highly efficient to normalize pH and PaCO2 and to reduce RV afterload resulting from hypercapnic acidosis. Regional anticoagulation with citrate solution was as effective as standard heparin anticoagulation but did not improve CO2 removal and lead to more hypocalcemia and hypotension.

Cardiopulmonary Adaptation During First Day of Life in Human Neonates.

OBJECTIVE: To characterize the natural history of cardiopulmonary physiology in the first 24 hours after birth. STUDY DESIGN: A prospective observational study of healthy newborns was conducted at a large tertiary perinatal center. Echocardiography was performed at <0.5, 2-3, 7-10, and 22-24 hours of age. Specifically, assessment of pulmonary vascular resistance (PVR) (pulmonary artery acceleration time [PAAT], right ventricular ejection time, right ventricular ejection time:PAAT [PVR index], and PAAT indexed to heart rate [PAATi]), ventricular outputs (right and left), and ventricular function (tricuspid annular planar excursion, right ventricular [RV] fractional area change [FAC], RV/left ventricular [LV] global peak longitudinal strain, and LV ejection fraction) were performed. One-way repeated-measures ANOVA analysis was performed for time-dependent variables. RESULTS: In total, 15 neonates (9 males), born at 40 ± 0.8 weeks and 3.5 ± 0.5 kg, respectively, were studied. We observed increased PAATi (P < .05) by 2-3 hours, followed by a subsequent decline in all indices of PVR (PVR index, PAATi, midsystolic notching, and right-to-left ductal flow [P < .0001]). Although right and left ventricular stroke volume increased over the study interval (P < .001), LV output remained stable. All indices of RV function (tricuspid annular planar excursion, RV fractional area change 4-chamber, and RV global peak longitudinal strain-3 chamber [P < .001]) increased during the study interval. CONCLUSION: The immediate transition after birth is characterized by lower PVR, reversal of the transductal shunt, and increased biventricular stroke volume. The differential adaptive response of the RV and LV is novel and may relate to loading conditions and patent ductus arteriosus closure.

Sex differences in hemodynamic responses and long-term survival to optimal medical therapy in patients with pulmonary arterial hypertension.

It is widely known that the incidence of pulmonary arterial hypertension (PAH) is higher in female, whereas prognosis is poorer in male patients. However, sex differences in hemodynamic response to and long-term prognosis with PAH-targeted treatment in the modern era remain to be fully elucidated. We examined the long-term prognosis of 129 consecutive PAH patients (34 males and 95 females) diagnosed in our hospital from April 1999 to October 2014, and assessed hemodynamic changes in response to PAH-targeted therapy. Female patients had better 5-year survival compared with male patients (74.0 vs. 53.4%, P = 0.003); however, higher age quartiles in females were associated with poor outcome. Follow-up examination after medical treatment showed significant decreases in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and pulmonary arterial capacitance (PAC) in both sexes (both P < 0.05), whereas only females had a significant improvement in right ventricular end-diastolic pressure (RVEDP), right atrial pressure (RAP), cardiac index, and mixed venous oxygen saturation (SvO2) (all P < 0.05). Baseline age significantly correlated with the hemodynamic changes only in female patients; particularly, there were significant sex interactions in RVEDP and RAP (both P < 0.10). The multivariable analysis showed that SvO2 at baseline and mPAP and SvO2 at follow-up were significant prognostic factors in males, whereas the changes in mPAP, PVR, and PAC and use of endothelin-receptor antagonist in females. These results indicate that female PAH patients have better long-term prognosis than males, for which better improvements of right ventricular functions and hemodynamics may be involved.

Relationship between Mean Airways Pressure, Lung Mechanics, and Right Ventricular Output during High-Frequency Oscillatory Ventilation in Infants.

OBJECTIVE: To characterize changes in lung mechanics and right ventricular output (RVO) during incremental/decremental continuous distending pressure (CDP) maneuvers in newborn infants receiving high-frequency oscillatory ventilation, with the aim of evaluating when open lung maneuvers are needed and whether they are beneficial. STUDY DESIGN: Thirteen infants on high-frequency oscillatory ventilation were studied with a median (IQR) gestational age of 261 (253-291) weeks and median (IQR) body weight of 810 (600-1020) g. CDP was increased stepwise from 8 cmH2O to a maximum pressure and subsequently decreased until oxygenation deteriorated or a CDP of 8 cmH2O was reached. The lowest CDP that maintained good oxygenation was considered the clinically optimal CDP. At each CDP, the following variables were evaluated: oxygenation, respiratory system reactance (Xrs), and RVO by Doppler echocardiography. RESULTS: At maximal CDP reached during the trial, 19 [1] cmH2O (mean [SEM]), oxygenation markedly improved, and Xrs and RVO decreased. During deflation, oxygenation remained stable over a wide range of CDP settings, Xrs returned to the baseline values, and RVO increased but the baseline values were not readily restored in all patients. CONCLUSION: These results suggest that Xrs and RVO are more sensitive than oxygenation to overdistension and they may be useful in clinical practice to guide open lung maneuvers.

Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 µg twice daily and titrated up to 1,600 µg by increments of 200 µg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683.2±237.3 to 560.3±238.7 dyn·s/cm5(P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD) increased from 445.0±102.2 to 459.1±112.8 m (P=0.0324); World Health Organization functional class improved in 4 patients (12.1%), and was maintained in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor antagonist. Most of the commonly reported adverse events were consistent with those reported for other PGI2formulations. Thirty-four patients attained the individual maximum tolerated dose (maintenance dose). CONCLUSIONS: The efficacy and tolerability of selexipag in Japanese PAH patients was confirmed by improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is an efficacious treatment option for Japanese PAH patients. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111532].).

Major contribution of central pulmonary reservoir discharge to increased pulmonary arterial diastolic blood flow after birth in near-term lambs.

Recent fetal lamb data have suggested that the pulmonary trunk (PT) region displays a reservoir function and that a pharmacologically induced fall in pulmonary vascular resistance (PVR) increases and redistributes diastolic discharge from this central pulmonary reservoir toward the lungs, thereby producing a positive diastolic offset in the pulmonary arterial (PA) blood flow profile. As a similar offset in PA flow characteristically occurs after birth, this study tested the hypotheses that 1) central pulmonary reservoir discharge is both redistributed toward the lungs and increased in magnitude during the birth transition and 2) discharge from this reservoir constitutes a major component of increased PA diastolic blood flow after birth. Six anesthetized near-term fetal lambs were instrumented with PT, ductal and left PA transit-time flow probes, and aortic, PT and left atrial catheters. Hemodynamic data were recorded in fetuses and at regular intervals during 2-h mechanical ventilation following cesarean section delivery. Diastolic PA blood flow rose from near zero in fetuses to 468 ± 188 ml/min by 15 min (P < 0.001). Central pulmonary reservoir discharge in fetuses (99 ± 44 ml/min) passed primarily right-to-left across the ductus. However, this reservoir discharge redistributed entirely to the lungs by 1 min after birth, and then doubled to a peak of 214 ± 167 ml/min at 15 min (P < 0.001). Reservoir discharge subsequently stabilized at 151 ± 60 ml/min at 30-120 min, which comprised ∼50% of diastolic and ∼20% of mean PA blood flow. These findings suggest that enhanced diastolic central pulmonary reservoir discharge plays a major role in supporting an increased pulmonary perfusion after birth.

At high cardiac output, diesel exhaust exposure increases pulmonary vascular resistance and decreases distensibility of pulmonary resistive vessels.

Air pollution has recently been associated with the development of acute decompensated heart failure, but the underlying biological mechanisms remain unclear. A pulmonary vasoconstrictor effect of air pollution, combined with its systemic effects, may precipitate decompensated heart failure. The aim of the present study was to investigate the effects of acute exposure to diesel exhaust (DE) on pulmonary vascular resistance (PVR) under resting and stress conditions but also to determine whether air pollution may potentiate acquired pulmonary hypertension. Eighteen healthy male volunteers were exposed to ambient air (AA) or dilute DE with a particulate matter of <2.5 µm concentration of 300 µg/m(3) for 2 h in a randomized, crossover study design. The effects of DE on PVR, on the coefficient of distensibilty of pulmonary vessels (α), and on right and left ventricular function were evaluated at rest (n = 18), during dobutamine stress echocardiography (n = 10), and during exercise stress echocardiography performed in hypoxia (n = 8). Serum endothelin-1 and fractional exhaled nitric oxide were also measured. At rest, exposure to DE did not affect PVR. During dobutamine stress, the slope of the mean pulmonary artery pressure-cardiac output relationship increased from 2.8 ± 0.5 mmHg · min · l (-1) in AA to 3.9 ± 0.5 mmHg · min · l (-1) in DE (P < 0.05) and the α coefficient decreased from 0.96 ± 0.15 to 0.64 ± 0.12%/mmHg (P < 0.01). DE did not further enhance the hypoxia-related upper shift of the mean pulmonary artery pressure-cardiac output relationship. Exposure to DE did not affect serum endothelin-1 concentration or fractional exhaled nitric oxide. In conclusion, acute exposure to DE increased pulmonary vasomotor tone by decreasing the distensibility of pulmonary resistive vessels at high cardiac output.

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease.

Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

Cardiopulmonary exercise testing as a diagnostic tool for the detection of left-sided pulmonary hypertension in heart failure.

BACKGROUND: Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly ominous consequence of left-sided heart failure (HF). The primary aim of this investigation was to assess the ability of key cardiopulmonary exercise testing (CPX) variables to detect elevated pulmonary pressures in a HF cohort. METHODS: This was a retrospective analysis of a prospectively collected database. Two hundred ninety-three subjects with HF (63 ± 10 years old, 79% male) underwent Doppler echocardiography to estimate resting pulmonary artery systolic pressure (PASP). Peak oxygen consumption (VO2), the minute ventilation/carbon dioxide production (VE/VCO2) slope, peak partial pressure of end-tidal CO2 (PETCO2) and exercise oscillatory ventilation (EOV) were determined. RESULTS: Forty-six percent (n = 134) of the subjects presented with a PASP ≥ 40 mm Hg. A VE/VCO2 slope

Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a clinical entity where there is a potential for reversibility of hepatic dysfunction once the acute hepatic insult resolves. The portal and systemic hemodynamics in ACLF patients to study its relevance in determining the clinical outcomes was studied. METHODS: Clinical, laboratory, portal, and systemic hemodynamic assessments were done at admission and after 3 months. Standard medical care was given to all the patients. RESULTS: Fifty-seven patients with ACLF were enrolled, and they underwent baseline hepatic venous pressure gradient (HVPG) measurement. Twenty-six (46%) patients died during the 3-month follow-up. Presence of high HVPG and hepatic encephalopathy were found to be independent baseline predictors of mortality. Of the 31 surviving patients, 24 consented for a repeat HVPG. The baseline HVPG reduced from 16 (range 12-30) to 13 (range 6-21) mmHg; (P < 0.05). The reduction in HVPG correlated with clinical and biochemical recovery, and reduction in Child-Turcotte-Pugh score score (P < 0.05), while the aortic mean arterial pressure, cardiac index and systemic vascular resistance index improved significantly (< 0.05). Six (25%) patients developed upper gastrointestinal bleed; the median HVPG between bleeders and non-bleeders was not different possibly because of early onset of bleed (median 20 [15-45 days]). CONCLUSIONS: Baseline HVPG is an independent predictor of mortality in ACLF patients. The portal and systemic circulatory anomalies regress substantially by 90 days and correlate with clinical recovery. However, in the initial phase, the raised portal pressure predisposes these patients to high risk of variceal bleeding.

Cardiac magnetic resonance imaging-derived septum swing index detects pulmonary hypertension: A diagnostic study.

Background and Objectives: Because of pressure differences between the pulmonary artery and aorta, the ventricular septum moves in a swinging motion that is commonly observed on cardiac MR (CMR) cine sequences in patients with pulmonary hypertension (PH). We aimed to assess the use of septum swing index (SSI) derived by CMR for detecting PH. Methods: We retrospectively identified consecutive patients with suspected PH who underwent right heart catheterization (RHC) and CMR at a PH referral center between July 2019 and December 2020. The diagnostic accuracy of SSI for identifying PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) was assessed by receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values. Results: A total of 105 patients (mean age: 47.8 ± 15.0 years; 68 females) were included in the final analysis. SSI and mPAP were negatively correlated in the total study population and patients with PH, but not in patients without PH. SSI was an independent predictor of PH (adjusted odds ratio: 12.9, 95% confidence interval: 3.6 to 45.5, P = 0.003). The area under the curve for SSI was 0.91, with a cut-off value of 0.9673 yielding the best balance of sensitivity (86.4%), specificity (88.2%), positive predictive value (97.4%), negative predictive value (55.6%), and accuracy (86.7%) for detecting PH. Conclusions: Septum swing index was lower in patients with PH and is a simple, reliable method for detecting PH.

Quantification of pulmonary perfusion using LSIM-CT correlates with pulmonary hemodynamics in patients with CTEPD.

Background: Lung subtraction iodine mapping (LSIM)-CT is a clinically useful technique that can visualize pulmonary mal-perfusion in patients with chronic thromboembolic pulmonary disease (CTEPD). However, little is known about the associations of LSIM images with hemodynamic parameters of patients with CTEPD. This study investigates a parameter of LSIM images associated with mean pulmonary arterial pressure (mPAP) and validates the association between pulmonary vascular resistance, right atrial pressure, cardiac index, and exercise capacity in patients with CTEPD. Methods: This single-center, prospective, observational study involved 30 patients diagnosed with CTEPD using lung perfusion scintigraphy. To examine the correlation of decreased pulmonary perfusion area (DPA) with mPAP, areas with 0-10, 0-15, 0-20, and 0-30 HU in lung subtraction images were adopted in statistical analysis. The DPA to total lung volume ratio (DPA ratio, %) was calculated as the ratio of each DPA volume to the total lung volume. To assess the correlation between DPA ratios of 0-10, 0-15, 0-20, and 0-30 HU and mPAP, Spearman's rank correlation coefficient was used. Results: The DPA ratio of 0-10 HU had the most preferable correlation with mPAP than DPA ratios of 0-15, 0-20, and 0-30 HU (ρ = 0.440, P = 0.015). The DPA ratio of 0-10 HU significantly correlates with pulmonary vascular resistance (ρ = 0.445, P = 0.015). The receiver operating characteristic curve analysis indicated that the best cutoff value of the DPA ratio of 0-10 HU for the prediction of an mPAP of ≥30 mmHg was 8.5% (AUC, 0.773; 95% CI, 0.572-0.974; sensitivity, 83.3%; specificity, 75.0%). Multivariate linear regression analysis, which was adjusted for the main pulmonary arterial to ascending aortic diameter ratio and right ventricular to left ventricular diameter ratio, indicated that the DPA ratio of 0-10 HU was independently and significantly associated with mPAP (B = 89.7; 95% CI, 46.3-133.1, P < 0.001). Conclusion: The DPA ratio calculated using LSIM-CT is possibly useful for estimating the hemodynamic status in patients with CTEPD.

The hemodynamic characteristics of severe chronic lung disease referred for lung transplantation.

Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p < 0.001). The area under curve (AUC) of PAPs, PAPm, and PVR were excellent, 0.973, 0.970, and 0.938, respectively for discrimination between CLD and PAH on receiver operator characteristics curve analysis. Optimal cutoff values were 55.5 mmHg, 35.5 mmHg, and 6.1 Wood Units for PAPs, PAPm, and PVR with Youden Index 0.85, 0.80, and 0.82, respectively. There were distinct hemodynamic characteristics between the CLD group and the PAH group. Systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance are useful to discriminate between the phenotype of severe CLD and PAH.

Virtual Transcatheter Interventions for Peripheral Pulmonary Artery Stenosis in Williams and Alagille Syndromes.

Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and "extensive" interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient-specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention-induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long-segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.