Search

Background The association between raised pulmonary artery pressures, pulmonary vascular resistance (PVR), and right‐sided heart dysfunction is well recognized. The added value of pulsatile indices, specifically pulmonary arterial compliance (PAC) and characteristic impedance, remains unclear. This study aimed to identify the optimal vascular afterload model for predicting right‐sided heart dysfunction in newly diagnosed pulmonary hypertension (PH). METHODS AND RESULTS This was a prospective cohort study of 86 patients with suspected PH (60±16 years; 66 women) who underwent right‐sided heart catheterization and cardiac magnetic resonance imaging. Right ventricular end‐diastolic volume index (RVEDVi) and right atrial (RA) volume index were measured using cardiac magnetic resonance imaging. Vascular resistance, PAC, and characteristic impedance were measured using pulmonary artery pressure from right‐sided heart catheterization and pulmonary artery flow from cardiac magnetic resonance imaging. Optimal model fit was determined by the lowest Akaike Information Criterion value. A total of 58% of patients had a right ventricular ejection fraction

Abstract Background Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results Pulmonary pressures increased after the initial PE administration (p

Background: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. Conclusion: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden. [ABSTRACT FROM AUTHOR]

Aims: A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and haemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH‐LHD) and chronic lung disease (PH‐CLD). Methods and results: Eight patients with PH‐LHD and 10 patients with PH‐CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas‐filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Haemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. No complications or investigational device‐related serious adverse events occurred. Device activation in PH‐LHD and PH‐CLD patients decreased pulmonary arterial pulse pressure by 5.6 ± 4.2 mmHg (−12%; p = 0.003) and 4.2 ± 2.2 mmHg (−11%; p < 0.001), increased CPA by 0.4 ± 0.2 ml/mmHg (+23%; p = 0.004) and 0.4 ± 0.3 ml/mmHg (+25%; p = 0.001), and increased right ventricular‐to‐pulmonary vascular (RV‐PV) coupling by 0.24 ± 0.18 (+40%; p = 0.012) and 0.11 ± 0.07 (+21%; p = 0.001), respectively. Conclusions: Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV‐PV coupling. [ABSTRACT FROM AUTHOR]

Background Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge‐to‐edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge‐to‐edge repair. Methods and Results We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge‐to‐edge repair. The end points were all‐cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve–derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

The pulmonary and cardiovascular systems have profound effects on each other. Overall cardiac function is determined by heart rate, preload, contractility, and afterload. Changes in lung volume, intrathoracic pressure (ITP), and hypoxemia can simultaneously change all of these four hemodynamic determinants for both ventricles and can even lead to cardiovascular collapse. Intubation using sedation depresses vasomotor tone. Also, the interdependence between right and left ventricles can be affected by lung volume-induced changes in pulmonary vascular resistance and the rise in ITP. An increase in venous return due to negative ITP during spontaneous inspiration can shift the septum to the left and cause a decrease in left ventricle compliance. During positive pressure ventilation, the increase in ITP causes a decrease in venous return (preload), minimizing ventricular interdependence and will decrease left ventricle afterload augmenting cardiac output. Thus, positive pressure ventilation is beneficial in acute heart failure patients and detrimental in hypovolemic patients where it can cause a significant decrease in venous return and cardiac output. Recently, this phenomenon has been used to assess patient's volume responsiveness to fluid by measuring pulse pressure variation and stroke volume variation. Heart–lung interaction is very dynamic and changes in lung volume, ITP, and oxygen level can have various effects on the cardiovascular system depending on preexisting cardiovascular function and volume status. Heart failure and either hypo or hypervolemia predispose to greater effects of ventilation of cardiovascular function and gas exchange. This review is an overview of the basics of heart–lung interaction. [ABSTRACT FROM AUTHOR]

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease that progresses to right ventricular (RV) failure and death if left untreated. Little is known regarding the progression of RV failure in this disease, greatly limiting effective prognoses, and therapeutic interventions. Large animal models enable the use of clinical techniques and technologies to assess progression and diagnose failure, but the existing large animal models of CTEPH have not been shown to replicate the functional consequences of the RV, i.e., RV failure. Here, we created a canine embolization model of CTEPH utilizing only microsphere injections, and we used a combination of right heart catheterization (RHC), echocardiography (echo), and magnetic resonance imaging (MRI) to quantify RV function. Over the course of several months, CTEPH led to a 6-fold increase in pulmonary vascular resistance (PVR) in four adult, male beagles. As evidenced by decreased cardiac index (0.12 ± 0.01 v. 0.07 ± 0.01 [L/(min*kg)]; p < 0.05), ejection fraction (0.48 ± 0.02 v. 0.31 ± 0.02; p < 0.05), and ventricular-vascular coupling ratio (0.95 ± 0.09 v. 0.45 ± 0.05; p < 0.05), as well as decreased tricuspid annular plane systolic excursion (TAPSE) (1.37 ± 0.06 v. 0.86 ± 0.05 [cm]; p < 0.05) and increased end-diastolic volume index (2.73 ± 0.06 v. 2.98 ± 0.02 [mL/kg]; p < 0.05), the model caused RV failure. The ability of this large animal CTEPH model to replicate the hemodynamic consequences of the human disease suggests that it could be utilized for future studies to gain insight into the pathophysiology of CTEPH development, following further optimization.

Relevant pressure recovery (PR) has been shown to increase functional stenotic aortic valve orifice area and reduce left ventricular load. However, little is known about the relevance of PR in the pulmonary artery. The study examined the impact of PR using 2D‐echocardiography in the pulmonary artery distal to the degenerated homograft in patients after Ross surgery. Ninety‐two patients with pulmonary homograft were investigated by Doppler echocardiography (mean time interval after surgery 31 ± 26 months). PR was measured as a function of pulmonary artery diameter determined by computed tomography angiography. Homograft orifice area, valve resistance, and transvalvular stroke work were calculated with and without considering PR. PR decreased as the pulmonary artery diameter increased (r = −0.69, p < 0.001). Mean PR was 41.5 ± 7.1% of the Doppler‐derived pressure gradient (Pmax), which resulted in a markedly increased homograft orifice area (energy loss coefficient index [ELCOI] vs. effective orifice area index [EOAI], 1.3 ± 0.4 cm2/m2 vs. 0.9 ± 0.4 cm2/m2, p < 0.001). PR significantly reduced homograft resistance and transvalvular stroke work (822 ± 433 vs. 349 ± 220 mmHg × ml, p < 0.0001). When PR was considered, the correlations of the parameters used were significantly better, and 11 of 18 patients (61%) in the group with severe homograft stenosis (EOAI <0.6 cm2/m2) could be reclassified as moderate stenosis. Our results showed that the Doppler measurements overestimated the degree of homograft stenosis and thus the right ventricular load, when PR was neglected in the pulmonary artery. Therefore, Doppler measurements that ignore PR can misclassify homograft stenosis and may lead to premature surgery. [ABSTRACT FROM AUTHOR]

Background: The association between raised pulmonary artery pressures, pulmonary vascular resistance (PVR), and right-sided heart dysfunction is well recognized. The added value of pulsatile indices, specifically pulmonary arterial compliance (PAC) and characteristic impedance, remains unclear. This study aimed to identify the optimal vascular afterload model for predicting right-sided heart dysfunction in newly diagnosed pulmonary hypertension (PH)., Methods and Results: This was a prospective cohort study of 86 patients with suspected PH (60±16 years; 66 women) who underwent right-sided heart catheterization and cardiac magnetic resonance imaging. Right ventricular end-diastolic volume index (RVEDVi) and right atrial (RA) volume index were measured using cardiac magnetic resonance imaging. Vascular resistance, PAC, and characteristic impedance were measured using pulmonary artery pressure from right-sided heart catheterization and pulmonary artery flow from cardiac magnetic resonance imaging. Optimal model fit was determined by the lowest Akaike Information Criterion value. A total of 58% of patients had a right ventricular ejection fraction <50%, 63% had an increased RVEDVi, and 56% had an increased RA volume index. Overall, PVR was the best predictor of right ventricular ejection fraction <50% ( P <0.01), increased RVEDVi ( P <0.01), and RA volume index ( P =0.02). However, for patients with a PVR <240 dynes.s.cm -5 , PAC clinical outperformed PVR in predicting right ventricular ejection fraction <50% ( P =0.02) and increased RVEDVi ( P =0.05). A 3-component model (PVR, PAC clinical , and characteristic impedance) best predicted RA dilatation ( P =0.05). In paired analysis, alternative methods of PAC quantification better predicted increased RVEDVi (PAC decay P =0.02) and RA volume index (PAC area P =0.02). PAC clinical <2.3 mL/mm Hg optimally predicted right-sided heart dysfunction (area under the curve, 0.768) and increased the AUC for PVR in undifferentiated/left-sided PH (0.89 versus 0.72)., Conclusions: Pulsatile vascular afterload measurement improves right-sided heart dysfunction prediction in undifferentiated/left-sided PH. More accurate PAC measurement methods could further enhance prognostic accuracy, while a PVR ≥240 dynes.s.cm -5 remains a valuable threshold for precapillary PH.

Abstract Relevant pressure recovery (PR) has been shown to increase functional stenotic aortic valve orifice area and reduce left ventricular load. However, little is known about the relevance of PR in the pulmonary artery. The study examined the impact of PR using 2D‐echocardiography in the pulmonary artery distal to the degenerated homograft in patients after Ross surgery. Ninety‐two patients with pulmonary homograft were investigated by Doppler echocardiography (mean time interval after surgery 31 ± 26 months). PR was measured as a function of pulmonary artery diameter determined by computed tomography angiography. Homograft orifice area, valve resistance, and transvalvular stroke work were calculated with and without considering PR. PR decreased as the pulmonary artery diameter increased (r = −0.69, p

Pulmonary arterial capacitance or compliance (PAC) has been reported as an independent predictor of mortality in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension secondary to left heart disease (PH-LHD). We conducted a literature search of PubMed/Medline, Google Scholar, and Cochrane library databases from July 30th to September 4th, 2020, and identified all the relevant studies reporting mortality outcomes in patients with PAH and PH-LHD. Pooled data from these studies were used to perform a meta-analysis to identify the role of PAC in predicting all-cause mortality in this subset of patients. Pooled data on 4997 patients from 15 individual studies showed that the mortality risk in patients with PAH and PH-LHD varies significantly per unit change in PAC either from baseline or during follow-up. A reduction in PAC per 1 ml/mmHg was associated with a 4.25 times higher risk of all-cause mortality (95% CI 1.42–12.71; p = 0.021) in PAH patients. Among patients with PH-LHD, mortality risk increased by ~30% following a unit decrease in PAC (HR, 1.29; p = 0.019), whereas an increase in PAC by 1 ml/mmHg lowered the mortality risk by 30% (HR, 0.70). PAC is a strong and independent predictor of all-cause mortality in both patients with PAH and PH-LHD. A decrease in PAC by 1 ml/mmHg from baseline or during follow-up significantly increases the risk of all-cause mortality among both patients with PAH and PH-LHD. Treatment modalities targeted at PAC improvement can affect the overall survival and quality of life in such patients. • PAC predicts mortality in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to left heart disease (PH-LHD). • A decrease in PAC by 1ml/mmHg from baseline or during follow-up significantly increases mortality risk in PAH and PH-LHD patients & vice-versa. • Treatment modalities targeted at PAC improvement can affect the overall survival and quality of life in such patients. [ABSTRACT FROM AUTHOR]

Aims Right ventricular (RV) failure causes death from acute pulmonary embolism (PE), due to a mismatch between RV systolic function and increased RV afterload. We hypothesized that an echocardiographic ratio of this mismatch [RV systolic function by tricuspid annular plane systolic excursion (TAPSE) divided by pulmonary arterial systolic pressure (PASP)] would predict adverse outcomes better than each measurement individually, and would be useful for risk stratification in intermediate-risk PE. Methods and results This was a retrospective analysis of a single academic centre Pulmonary Embolism Response Team registry from 2012 to 2019. All patients with confirmed PE and a formal transthoracic echocardiogram performed within 2 days were included. All echocardiograms were analysed by an observer blinded to the outcome. The primary endpoint was a 7-day composite outcome of death or haemodynamic deterioration. Secondary outcomes were 7- and 30-day all-cause mortality. A total of 627 patients were included; 135 met the primary composite outcome. In univariate analysis, the TAPSE/PASP was associated with our primary outcome [odds ratio = 0.028, 95% confidence interval (CI) 0.010–0.087; P  < 0.0001], which was significantly better than either TAPSE or PASP alone (P  = 0.017 and P  < 0.0001, respectively). A TAPSE/PASP cut-off value of 0.4 was identified as the optimal value for predicting adverse outcome in PE. TAPSE/PASP predicted both 7- and 30-day all-cause mortality, while TAPSE and PASP did not. Conclusion A combined echocardiographic ratio of RV function to afterload is superior in prediction of adverse outcome in acute intermediate-risk PE. This ratio may improve risk stratification and identification of the patients that will suffer short-term deterioration after intermediate-risk PE. [ABSTRACT FROM AUTHOR]

Introduction: The occurrence of death from acute pulmonary embolism (PE) is often linked to right ventricular (RV) failure, arising from an imbalance between RV systolic function and heightened RV afterload. In our study, we posited that an echocardiographic ratio derived from this disparity [RV systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) divided by pulmonary arterial systolic pressure (PASP)] could offer superior predictive value for adverse outcomes compared to individual measurements of TAPSE and PASP alone., Methods: We conducted a retrospective analysis using data from a University Hospital Centre spanning from 2017 to 2023. All individuals with confirmed PE and a formal transthoracic echocardiogram within 7 days of diagnosis were included. The primary endpoint was a composite outcome of death, hemodynamic deterioration needing introduction of inotropes or thrombolysis within 30 days. Secondary endpoints included 6 months all-cause mortality and onset of right-sided heart failure., Results: Thirty-eight patients were included. Mean age was 58 ±15 years old. A male predominance was noted: 23 male patients (60.5%) and 15 female patients (39.5%). Eight patients met the primary composite endpoint while nine patients met the secondary composite endpoint. In multivariate analysis, the TAPSE/PASP ratio was independently associated with the primary outcome (OR=2.77, 95% CI 1.101-10.23, P=0.042). A TAPSE/PASP ratio <0.3 was independently associated with the secondary outcome (OR=3.07, 95% CI 1.185-10.18, P=0.034)., Conclusion: This study suggests that a combined echocardiographic ratio of RV function to afterload is effective in predicting adverse outcomes in acute PE.

Background: Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge-to-edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge-to-edge repair., Methods and Results: We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge-to-edge repair. The end points were all-cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve-derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea <0.6/mean pulmonary artery pressure (mPAP)) <35; High Elastance with No/Mild PH (HE-): Ea ≥0.6/mPAP <35; and HE with Moderate/Severe PH (HE+): Ea ≥0.6/mPAP ≥35) and MR pathogenesis (Primary MR [PMR])/low elastance, PMR/HE, and secondary MR). The association between this classification and clinical outcomes was examined using Cox regression. Among 114 patients included, 50.9% had PMR. Mean±SD age was 74.7±10.6 years. Patients with Ea ≥0.6 were more likely to have diabetes, atrial fibrillation, New York Heart Association III/IV status, and secondary MR (all P <0.05). Overall, 2-year cumulative survival was 71.1% and was lower in patients with secondary MR and mPAP ≥35. Compared with patients with low elastance, cumulative 2-year event-free survival was significantly lower in HE- and HE+ patients (85.5% versus 50.4% versus 41.0%, respectively, P =0.001). Also, cumulative 2-year event-free survival was significantly higher in patients with PMR/low elastance when compared with PMR/HE and patients with secondary mitral regurgitation (85.5% versus 55.5% versus 46.1%, respectively, P =0.005)., Conclusions: Assessment of the preprocedural cardiopulmonary profile based on mPAP, MR pathogenesis, and Ea guides patient selection by identifying hemodynamic features that indicate likely benefit from mitral-transcatheter edge-to-edge repair in PH or lack thereof.

Background: Assessing right ventricular overload in children is challenging. We conducted this study involving children with pulmonary valvular stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS) to evaluate the potential of a new endogenous ligand of apelin receptor, Elabela (ELA), as a potential biomarker for right heart overload.Methods: In this prospective cohort study, a total of 118 congenital heart diseases patients with right ventricle outflow tract obstruction were recruited from 2018 to 2019. Among them, 44 isolated PS and 7 PA/IVS patients were selected. Their venous blood was collected, and all patients underwent an echocardiographic examination. Among them, post-operative blood was collected from 24 patients with PS after percutaneous balloon pulmonary valvuloplasty. The plasma ELA concentration was measured using enzyme-linked immunosorbent assay.Results: The ELA was significantly associated with the peak transvalvular pulmonary gradient (r = −0.62; p = 0.02), thus reflecting the severity of PS or PA/IVS. The ELA significantly increased at 3 days after intervention, when mechanical obstruction of the right outflow tract was relieved. Based on the receiver-operator characteristic curve results, ELA could be a risk factor for duct dependence in patients with critical PS or PA/IVS who are younger than 6 months (AUC: 0.82).Conclusion: ELA concentration and severity of PS or PA/IVS had a significant negative correlation, indicating that ELA might be a novel biomarker for right ventricular afterload and reflect the immediate pressure changes in the right heart. Furthermore, ELA could predict duct-dependency in PS and PA/IVS patients, as valuable as classical echocardiographic indexes.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease that progresses to right ventricular (RV) failure and death if left untreated. Little is known regarding the progression of RV failure in this disease, greatly limiting effective prognoses, and therapeutic interventions. Large animal models enable the use of clinical techniques and technologies to assess progression and diagnose failure, but the existing large animal models of CTEPH have not been shown to replicate the functional consequences of the RV, i.e., RV failure. Here, we created a canine embolization model of CTEPH utilizing only microsphere injections, and we used a combination of right heart catheterization (RHC), echocardiography (echo), and magnetic resonance imaging (MRI) to quantify RV function. Over the course of several months, CTEPH led to a 6-fold increase in pulmonary vascular resistance (PVR) in four adult, male beagles. As evidenced by decreased cardiac index (0.12 ± 0.01 v. 0.07 ± 0.01 [L/(min*kg)]; p < 0.05), ejection fraction (0.48 ± 0.02 v. 0.31 ± 0.02; p < 0.05), and ventricular-vascular coupling ratio (0.95 ± 0.09 v. 0.45 ± 0.05; p < 0.05), as well as decreased tricuspid annular plane systolic excursion (TAPSE) (1.37 ± 0.06 v. 0.86 ± 0.05 [cm]; p < 0.05) and increased end-diastolic volume index (2.73 ± 0.06 v. 2.98 ± 0.02 [mL/kg]; p < 0.05), the model caused RV failure. The ability of this large animal CTEPH model to replicate the hemodynamic consequences of the human disease suggests that it could be utilized for future studies to gain insight into the pathophysiology of CTEPH development, following further optimization.

Background: We aimed to study whether pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) could be predicted by conventional echo Doppler and novel tissue Doppler imaging (TDI) in a population of chronic obstructive pulmonary disease (COPD) free of LV disease and co-morbidities.Methods: Echocardiography and right heart catheterization was performed in 100 outpatients with COPD. By echocardiography the time-integral of the TDI index, right ventricular systolic velocity (RVSmVTI) and pulmonary acceleration-time (PAAcT) were measured and adjusted for heart rate. The COPD patients were randomly divided in a derivation (n = 50) and a validation cohort (n = 50). Results: PH (mean pulmonary artery pressure (mPAP) ≥ 25mmHg) and elevated PVR ≥ 2Wood unit (WU) were predicted by satisfactory area under the curve for RVSmVTI of 0.93 and 0.93 and for PAAcT of 0.96 and 0.96, respectively. Both echo indices were 100% feasible, contrasting 84% feasibility for parameters relying on contrast enhanced tricuspid-regurgitation. RVSmVTI and PAAcT showed best correlations to invasive measured mPAP, but less so to PVR. PAAcT was accurate in 90- and 78% and RVSmVTI in 90- and 84% in the calculation of mPAP and PVR, respectively. Conclusions: Heart rate adjusted-PAAcT and RVSmVTI are simple and reproducible methods that correlate well with pulmonary artery pressure and PVR and showed high accuracy in detecting PH and increased PVR in patients with COPD. Taken into account the high feasibility of these two echo indices, they should be considered in the echocardiographic assessment of COPD patients. [ABSTRACT FROM AUTHOR]

Abstract: Awareness has grown in recent years that right ventricular (RV) function is equally important as left ventricular (LV) function in the setting of left-sided heart disease. RV dysfunction can be the consequence of an increased afterload imposed by the failing LV. The concept of “afterload” is physically most correctly described by vascular input impedance. However, for clinical purposes, afterload is most often modeled to consist of 3 components; pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), and characteristic impedance. Whereas PVR is historically most described, PAC (which represents the distensibility of the vasculature) has rapidly gained recognition for its prognostic ability in both pulmonary arterial hypertension and left-sided heart disease. Owing to the specific anatomy of the pulmonary circulation, PVR and PAC have an inverse hyperbolic relationship, which position can be shifted by varying wedge pressures. Knowledge of the afterload components helps one to understand how elevated left-sided filling pressures increase pulsatile load on the RV. An increase in resistive load (known as “reactive” or “out-of-proportion” pulmonary hypertension) ultimately complements the increase in pulsatile load. Perturbations in nitric oxide metabolism are thought to be crucial in this evolution and have therefore been sought as a major therapeutic target. [Copyright &y& Elsevier]

Background: Sepsis-induced cardiac dysfunction may limit fluid responsiveness and the mechanism thereof remains unclear. Since cardiac function may affect the relative value of cardiac filling pressures, such as the recommended central venous pressure (CVP), versus filling volumes in guiding fluid loading, we studied these parameters as determinants of fluid responsiveness, according to cardiac function. Methods: A delta CVP-guided, 90 min colloid fluid loading protocol was performed in 16 mechanically ventilated patients with sepsis-induced hypotension and three 30 min consecutive fluid loading steps of about 450 mL per patient were evaluated. Global end-diastolic volume index (GEDVI), cardiac index (CI) and global ejection fraction (GEF) were assessed from transpulmonary dilution. Baseline and changes in CVP and GEDVI were compared among responding (CI increase ≥10% and ≥15%) and non-responding fluid loading steps, in patient with low (<20%, n = 9) and near-normal (≥20%) GEF (n = 7) at baseline. Results: A low GEF was in line with other indices of impaired cardiac (left ventricular) function, prior to and after fluid loading. Of 48 fluid loading steps, 9 (of 27) were responding when GEF <20% and 6 (of 21) when GEF ≥20. Prior to fluid loading, CVP did not differ between responding and non-responding steps and levels attained were 23 higher in the latter, regardless of GEF (P = 0.004). Prior to fluid loading, GEDVI (and CI) was higher in responding (1007 ± 306 mL/m2) than non-responding steps (870 ± 236 mL/m2) when GEF was low (P = 0.002), but did not differ when GEF was near-normal. Increases in GEDVI were associated with increases in CI and fluid responsiveness, regardless of GEF (P < 0.001). Conclusions: As estimated from transpulmonary dilution, about half of patients with sepsis-induced hypotension have systolic cardiac dysfunction. During dysfunction, cardiac dilation with a relatively high baseline GEDVI maintains fluid responsiveness by further dilatation (increase in GEDVI rather than of CVP) as in patients without dysfunction. Absence of fluid responsiveness during systolic cardiac dysfunction may be caused by diastolic dysfunction and/or right ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: Chronic hypoxia causes pulmonary vasoconstriction and pulmonary hypertension, which lead to pulmonary vascular remodeling and right ventricular hypertrophy. To determine the effects of hypoxia-induced pulmonary vascular remodeling on pulmonary vascular impedance, which is the right ventricular afterload, we exposed C57BL6 mice to 0 (control), 10 and 15 days of hypobaric hypoxia (, each) and measured pulmonary vascular resistance (PVR) and impedance ex vivo. Chronic hypoxia led to increased pulmonary artery pressures for flow rates between 1 and 5ml/min (), and increased PVR, 0-Hz pulmonary vascular impedance and the index of wave reflection () as well as a more negative impedance phase angle for low frequencies (). The increases in resistance and 0-Hz impedance correlated with increased muscularization of small arterioles measured with quantitative immunohistochemistry (). The increases in wave reflection and decreases in phase angle are likely due to increased proximal artery stiffness. These results confirm that chronic hypoxia causes significant changes in steady and pulsatile pressure–flow relationships in mouse lungs and does so via structural remodeling. They also provide important baseline data for experiments with genetically engineered mice, with which molecular mechanisms of pulmonary vascular remodeling can be investigated. [Copyright &y& Elsevier]

To determine the effects of exercise with expiratory flow-limitation (EFL) on systemic O2 delivery, seven normal subjects performed incremental exercise with and without EFL at ~0.8 l s−1 (imposed by a Starling resistor in the expiratory line) to determine maximal power output under control ( W′max,c) and EFL ( W′max,e) conditions. W′max,e was 62.5% of W′max,c, and EFL exercise caused a significant fall in the ventilatory threshold. In a third test, after exercising at W′max,e without EFL for 4 min, EFL was imposed; exercise continued for 4 more minutes or until exhaustion. O2 consumption $$(V'_{{\text{O}}_{2}})$$ was measured breath-by-breath for the last 90 s of control, and for the first 90 s of EFL exercise. Assuming that the arterio-mixed venous O2 content remained constant immediately after EFL imposition, we used $$V'_{{\text{O}}_{2}} $$ as a measure of cardiac output ( Q′c). Q′c was also calculated by the pulse contour method with blood pressure measured continuously by a photo-plethysmographic device. Both sets of data showed a decrease of Q′c due to a decrease in stroke volume by 10% $$(p<0.001\;\hbox{for}\;V'_{{\text{O}}_{2}})$$ with EFL and remained decreased for the full 90 s. Concurrently, arterial O2 saturation decreased by 5%, abdominal, pleural and alveolar pressures increased, and duty cycle decreased by 43%. We conclude that this combination of events led to a decrease in venous return secondary to high expiratory pressures, and a decreased duty cycle which decreased O2 delivery to working muscles by ~15%. [ABSTRACT FROM AUTHOR]

Objective: To determine the presence of tricuspid regurgitation (TR) in patients affected by acute lung injury (ALI) and the adult respiratory distress syndrome (ARDS) during mechanical ventilation with positive end-expiratory pressure (PEEP).Design: A prospective clinical study.Setting: 10-bed general intensive care unit in a University Hospital.Patients: 7 consecutive patients an age 44.7 +/- 8.6 years with a diagnosis of ALI or ARDS were studied. All were on mechanical ventilation with PEEP.Interventions: PEEP was increased in steps of 5 cm H2O until the appearance of TR or up to a limit of 20 cm H2O.Measurements and Results: Right atrial pressure, pulmonary artery pressure, and wedge pressure were measured and cardiac output was determined by thermodilution. TR was graded from 0 to 3. Standard 2D echocardiographic and pulsed-wave images were obtained at each level of PEEP. PEEP was increased from 4 +/- 3 to 17 +/- 2 cm H2O. Mean PAP increased from 27.7 +/- 2.9 to 36.7 +/- 3.5 mm Hg (p < 0.02) when PEEP was increased. Five patients had competent valves and two had mild TR at baseline. In six out of the seven, TR either developed or increased when PEEP was increased.Conclusions: Our study demonstrated the development of TR after the use of PEEP in patients with ALI and ARDS as a consequence of pulmonary hypertension and right ventricular overloading. Since TR may randomly affect cardiac output values and derived parameters, the assessment of cardiac performance by some techniques such as thermodilution should be used with caution. [ABSTRACT FROM AUTHOR]