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Definition of pulmonary hypertension (PH) associated with left heart disease. mPAP: mean pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; DPG: diastolic pressure gradient. Information from [4, 26, 27].

Definition of pulmonary hypertension (PH) associated with left heart disease. mPAP: mean pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; DPG: diastolic pressure gradient. Information from [4, 26, 27].

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Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common type of PH, but its natural history is not well understood. PH-LHD is diagnosed by right heart catheterisation with a mean pulmonary arterial pressure ⩾25 mmHg and a pulmonary capillary wedge pressure >15 mmHg. The primary causes of PH-LHD are left ventricula...

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... of the disease, heterogeneity in the definitions and terminology, and variations in the different haemodynamic presentations. PH-LHD belongs to group 2 of the World Symposium on Pulmonary Hypertension PH clinical classification [26]. This group is defined as post-capillary PH, characterised by a mean PAP of ⩾25 mmHg and PAWP of >15 mmHg ( fig. 1) [26,27]. In contrast, the haemodynamic definition of pre-capillary PH differs from post-capillary PH in that PAWP is ⩽15 mmHg [27]. Pulmonary arterial hypertension (PAH) (group 1), PH due to pulmonary disease (group 3), chronic thromboembolic PH (group 4), and PH with unclear and/or multifactorial mechanisms (group 5) are all types of ...
Context 2
... This method takes into account the diastolic pressure gradient (DPG) (defined as the difference between diastolic PAP and mean PAWP), and defines patients with a low DPG (<7 mmHg) and PAWP >15 mmHg as having isolated post-capillary PH, but patients with DPG ⩾7 mmHg and PAWP >15 mmHg as having post-capillary PH with a pre-capillary component ( fig. 1) ...

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... Survival rates for patients with PH varies by type. The mortality rates at 12 months in patients of group 2 can be up to 32% (Farber and Gibbs 2015). One study reported that 1 year survival rates for patients of group 3 were 79%, 3-year survival rates were 48%, and 5-year survival rates were 31% (Rose et al. 2019). ...
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Pulmonary hypertension (PH) is a chronic progressive disease characterized by pulmonary vasoconstriction and remodeling. It causes a gradual increase in pulmonary vascular resistance leading to right-sided heart failure, and may be fatal. Chronic exposure to cigarette smoke (CS) is an essential risk factor for PH group 3; however, smoking continues to be prevalent and smoking cessation is reported to be difficult. A majority of smokers exhibit PH, which leads to a concomitant increase in the risk of mortality. The current treatments for PH group 3 focus on vasodilation and long-term oxygen supplementation, and fail to stop or reverse PH-associated continuous vascular remodeling. Recent studies have suggested that pulmonary vascular endothelial dysfunction induced by CS exposure may be an initial event in the natural history of PH, which in turn may be associated with abnormal alterations in connexin (Cx) expression. The relationship between Cx and CS-induced PH development has not yet been directly investigated. Therefore, this review will describe the roles of CS and Cx in the development of PH and discuss the related downstream pathways. We also discuss the possible role of Cx in CS-induced PH. It is hoped that this review may provide new perspectives for early intervention.
... In candidates for cardiac transplantation, reversibility of post-capillary PH and thus a better outcome post-transplantation is assumed if TPG decreases to <15 mmHg and/or pulmonary vascular resistance decreases to <3 WU. In other heart failure patients, VRT is currently not recommended, and a consistent protocol is lacking as well as the definition of a positive test result (22,23). Ghio et al. (24) conducted VRT using intravenous nitrates in 156 heart failure patients with a reduced LVEF and PH and found that survival was significantly reduced in non-responders in contrast to responders. ...
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Background: Pulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients. Methods: The primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome. Results: The cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30-3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25-0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34-3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis. Conclusions: In our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.
... Pre-capillary (mPAWP ≤ 15 mmHg) PH encompasses most of the WHO classification groups (1,3,4, and 5) while postcapillary PH (mPAWP > 15 mmHg) relates to left heart disease (group 2) (1-3). ...
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Aims Pulmonary hypertension (PH) is dichotomized into pre- and post-capillary physiology by invasive catheterization. Imaging, particularly strain assessment, may aid in classification and be helpful with ambiguous hemodynamics. We sought to define cardiac MRI (CMR) feature tracking biatrial peak reservoir and biventricular peak systolic strain in pre- and post-capillary PH and examine the performance of peak left atrial strain in distinguishing the 2 groups compared to TTE. Methods and Results Retrospective cross-sectional study from 1 Jan 2015 to 31 Dec 2020; 48 patients (22 pre- and 26 post-capillary) were included with contemporaneous TTE, CMR and catheterization. Mean pulmonary artery pressures were higher in the pre-capillary cohort (55 ± 14 vs. 42 ± 9 mmHg; p < 0.001) as was pulmonary vascular resistance (median 11.7 vs. 3.7 WU; p < 0.001). Post-capillary patients had significantly larger left atria (60 ± 22 vs. 25 ± 9 ml/m ² ; p < 0.001). There was no difference in right atrial volumes between groups (60 ± 21 vs. 61 ± 29 ml/m ² ; p = 0.694), however peak RA strain was lower in post-capillary PH patients (8.9 ± 5.5 vs. 18.8 ± 7.0%; p < 0.001). In the post-capillary group, there was commensurately severe peak strain impairment in both atria (LA strain 9.0 ± 5.8%, RA strain 8.9 ± 5.5%). CMR LAVi and peak LA strain had a multivariate AUC of 0.98 (95% CI 0.89–1.00; p < 0.001) for post-capillary PH diagnosis which was superior to TTE. Conclusion CMR volumetric and deformation assessment of the left atrium can highly accurately distinguish post- from pre-capillary PH.
... 7,8 The 12-month mortality for patients with PH-LHD may be as high as 32%. 9 In patients with heart failure with reduced ejection fraction (HFrEF), the presence of PH (PH-LHD) has a significant impact on their prognosis. RV-PA coupling assessed by measuring the tricuspid annular plane systolic excursion (TAPSE)/systolic PAP (sPAP) ratio has been recently proposed as an early marker of RV dysfunction in patients with HFrEF, 10 the TAPSE/sPAP ratio has been proposed as the best echocardiographic method to evaluate it. ...
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The purpose of this study was to investigate the effects of sacubitril/valsartan on right ventricular (RV) function in patients with pulmonary hypertension (PH) due to heart failure with reduced ejection fraction(HFrEF). We prospectively enrolled patients with HFrEF‐induced PH admitted to the Department of Cardiology between August 2018 and December 2019. Patients were randomized to receive oral treatment with sacubitril/valsartan or enalapril. Epidemiological data were recorded before treatment. Echocardiography was performed at admission and 6 months follow‐up, and all parameters were compared. Major adverse cardiac events (MACE) were compared between baseline and 6 month follow up. There were no significant differences in the baseline characteristics between the two groups. After 6‐ months of treatment, both treatment groups improved the following parameters from baseline (mean ± SD): left atrium, left ventricle, the left ventricular ejection function (LVEF), right ventricular systolic function (the tricuspid annular plane systolic excursion [TAPSE], the systolic pulmonary artery pressure [sPAP] and TAPSE/sPAP). After 6‐months, sacubitril/valsartan improved significantly the following parameters compared with enalapril (all p<0.05): LVEF (47.07±6.93% vs. 43.47±7.95%); TAPSE (15.33±1.31 mm vs. 14.78±1.36 mm); sPAP (36.76±14.32 mmHg vs.42.26±12.07 mmHg; and TAPSE/sPAP ratio (0.50±0.23 vs.0.39±0.14), respectively. There was no difference in readmissions due to recurrent heart failure. Sacubitril/valsartan seems to provide more beneficial effects among patients with HFrEF‐induced PH to improve RV function, along with a decrease in pulmonary pressure. This article is protected by copyright. All rights reserved.
... Pre-capillary (mPAWP ≤ 15 mmHg) PH encompasses most of the WHO classi cation groups (1, 3, 4 and 5) while post-capillary PH (mPAWP > 15 mmHg) relates to left heart disease (group 2) [1][2][3]. ...
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... (Figure 1). 5 It is our opinion that a DPG < 7 mm Hg or ≥ 7 mm Hg is also a simple and effective way to differentiate isolated postcapillary PH and mixed pre-and postcapillary PH, respectively, but use of the DPG is not part of the 6th World Symposium definitions. Finally, pulmonary arterial hypertension (PAH) is a subclassification of PH and on RHC is defined as precapillary PH with a PVR ≥ 3 WU (Table 1). 4 This is also seen with mixed pre-and postcapillary PH. ...
... 11 The 12-month mortality for patients with PH-LHD may be as high as 32%. 13 Predictors of worse prognosis include renal dysfunction, anemia, older age, RV dysfunction, and the presence of combined postcapillary and precapillary PH rather than isolated postcapillary PH. 13,14 A cohort study in patients with PH-CLD reported 1-, 3-, and 5-year survival rates of 79%, 48%, and 31%, respectively. 15 Patients with more severe lung disease and severe PH have a poor prognosis. ...
... 11 The 12-month mortality for patients with PH-LHD may be as high as 32%. 13 Predictors of worse prognosis include renal dysfunction, anemia, older age, RV dysfunction, and the presence of combined postcapillary and precapillary PH rather than isolated postcapillary PH. 13,14 A cohort study in patients with PH-CLD reported 1-, 3-, and 5-year survival rates of 79%, 48%, and 31%, respectively. 15 Patients with more severe lung disease and severe PH have a poor prognosis. ...
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Pulmonary hypertension (PH) is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms. A range of underlying conditions can lead to these disorders. Overall, PH affects approximately 1% of the global population, and over half of patients with heart failure may be affected. Cardiologists are therefore likely to encounter PH in their practice. Routine tests in patients with symptoms and physical findings suggestive of PH include electrocardiography, chest radiography, and pulmonary function tests. Transthoracic echocardiography is used to estimate the probability of PH. All patients with suspected or confirmed PH, without confirmed left-sided heart or lung diseases, should have a ventilation-perfusion scan to exclude CTEPH. Right-sided heart catheterization is essential for accurate diagnosis and classification. All patients with PAH or CTEPH must be referred to a specialist center. Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH. Targeted treatments (phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists) are licensed for patients with PAH. The soluble guanylate cyclase stimulator riociguat is the only licensed targeted therapy for patients with inoperable or persistent/recurrent CTEPH. Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition.
... Congruously, several HF studies have demonstrated that PH is a direct consequence of left ventricular systolic dysfunction and is an ominous clinical condition leading to tremendously increased morbidity and mortality. 23,24 Often, secondary PH is diagnosed in patients with extremely severe or-long-lasting cardiac systolic dysfunction. Hence, PH can also be considered as a reliable hemodynamic risk marker to estimate severity as well as reversibility of systolic HF. ...
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Aims Atrial fibrillation (AF) and heart failure (HF) are the most common cardiac diseases and often coexist leading to increased mortality and morbidity compared with AF patients without HF. As shown previously, AF ablation using radio frequency (RF) in HF patients leads to a reduction of AF burden, an increase of left ventricular ejection fraction (LVEF) and consequently to reduced hospitalization and mortality. Previous AF ablation studies on HF patients have been liberal about additional targets beyond pulmonary vein isolation (PVI). Thus, the aim of this study was to assess systematically the impact of a straightforward PVI‐only strategy on LVEF, NYHA functional class, and cardiovascular hospitalization rate in HF patients. Methods and results Out of 414 consecutive patients undergoing PVI, only with the cryoballoon 113 patients with reduced LVEF [mean: 38.4 ± 10.8%, reduced ejection fraction (rEF) group] and 301 patients with normal LVEF (>55%) at baseline were identified [normal ejection fraction (nEF) group]. Remarkably, even though freedom from arrhythmia recurrence after 1 year was significantly lower in the rEF group (64.9%) compared with the nEF group (71.2%, P = 0.036), mean LVEF improved from 38.4 ± 10.8% to 52.5 ± 17.2% (P < 0.001) after cryoballoon ablation in the rEF group. Accordingly, HF‐related symptoms as well as hospitalization rate declined significantly in the rEF group during follow‐up compared with baseline. Conclusions The results of the present study suggest that catheter ablation restricted to a straightforward PVI‐only strategy using the cryoballoon leads to improved left ventricular ejection fraction as well as improvement of NYHA functional class and increased freedom from cardiovascular rehospitalization.
... 4 In AS, PH initially develops as a consequence of passive backwards transmission of filling pressures because of impaired LV relaxation and distensibility. 21 Then, RV dysfunction develops as a direct consequence of the increased pulmonary pressure. However, PH is not the only determinant of RV dysfunction in AS. ...
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Background: Pulmonary hypertension is an established outcome predictor in patients with aortic stenosis (AS), but the prognostic impact of right ventricular dysfunction has not been well studied. Methods: We included 2181 patients (50.4% men; mean age, 77 years) with aortic valve area <1.3 cm2 and analyzed the occurrence of all-cause death during follow-up according to tricuspid annular plane systolic excursion (TAPSE) quartiles. Results: Patients in the lowest quartile (TAPSE <17 mm) were at a high risk of death, whereas survival was comparable for the 3 other quartiles. Five-year survival was 55±2% for TAPSE <17 mm, 72±2% for TAPSE of 17 to 20 mm, 71±2% for TAPSE of 20 to 24 mm, and 73±2% for TAPSE >24 mm (overall P<0.001). TAPSE <17 mm was associated with increased mortality after adjustment for established prognostic factors (adjusted hazard ratio [HR], 1.55 [95% CI, 1.21–1.97]) and after further adjustment for aortic valve replacement (AVR; adjusted HR, 1.47 [95% CI, 1.15–1.87]). The excess mortality risk associated with TAPSE <17 mm was noticed in both patients managed initially conservatively (adjusted HR, 1.46 [95% CI, 1.20–1.76]) and patients who underwent early (within 3 months after diagnosis) AVR (adjusted HR, 1.61 [95% CI, 1.03–2.52]). In asymptomatic patients with severe AS and preserved ejection fraction, TAPSE <17 mm was independently predictive of mortality (adjusted HR, 2.14 [95% CI, 1.31–3.51]). Early AVR was associated with similar survival benefit in TAPSE <17 and ≥17 mm (adjusted HR, 0.23 [95% CI, 0.16–0.34] for TAPSE <17 mm, adjusted HR, 0.26 [95% CI, 0.19–0.35] for TAPSE ≥17 mm; P for interaction, 0.97). Conclusions: Right ventricular dysfunction is an important and independent predictor of mortality in AS. TAPSE <17 mm at the time of AS diagnosis is a marker of poor survival under conservative management and after AVR even in asymptomatic patients with severe AS. AVR was associated with a pronounced reduction in mortality independent of TAPSE suggesting that AVR should be discussed before right ventricular dysfunction occurs in severe AS.
... [2,3] PH-HFrEF is characterized by backwards transmission of filling pressures due to impaired left ventricular systolic function with increased pulmonary artery wedge pressure (PAWP), which may further lead to right ventricle overload and right ventricular failure. [4] At present, treatments for pulmonary artery pressure (PAP) of PH-HFrEF patients are lacking. ...
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Beraprost is used to treat peripheral chronic arterial occlusive disease. However, the efficacy and safety of beraprost in patients with pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) remains unknown. The primary objective of this study was to determine the effects of beraprost on PH-HFrEF.We prospectively recruited patients with PH-HFrEF as determined by echocardiography and right cardiac catheterization. Beraprost sodium was given orally (1 μg/kg/d) added to the usual treatment, and patients were evaluated at 1-year follow-up.Twenty-five patients were recruited with baseline systolic pulmonary artery pressure (PAP) of 49.5 ± 10.8 mm Hg. Systolic PAP results at 3, 6, 9, and 12 months were 39.1 ± 8.1, 30.4 ± 5.2, 27.7 ± 3.0, and 27.0 ± 4.7 mm Hg, respectively, which were all significantly lower than systolic PAP at baseline (P < .05). Left ventricular ejection fraction results at 6 months (43.5 ± 7.0%), 9 months (47.0 ± 5.5%), and 12 months (48.2 ± 4.8%) were significantly higher than at baseline (34.7 ± 9.2%) (P < .05). Six-minute walking distance at 3 months (282.8 ± 80.6 m), 6 months (367.1 ± 81.2 m), 9 months (389.8 ± 87.1 m), and 12 months (395.7 ± 83.4 m) increased with time, and all were significantly higher than baseline (190.1 ± 75.5 m) (P < .05). One patient developed atrial fibrillation and recovered to sinus rhythm after intravenous administration of amiodarone. There were no instances of cardiac-related death, severe bleeding, or severe impairment of liver function.Routine oral administration of beraprost sodium added to the usual treatment may improve cardiopulmonary hemodynamics and exercise capacityin patients with PH-HFrEF.