scholarly journals Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402094878
Author(s):  
Galo M. Sanchez Palacios ◽  
Cindy Schmidt ◽  
Tammy Wichman
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Left Heart ◽  
Phosphodiesterase 5 Inhibitors ◽  
Left Heart Disease ◽  
Phosphodiesterase 5

Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.

scholarly journals Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261753
Author(s):  
Yusuke Joki ◽  
Hakuoh Konishi ◽  
Hiroyuki Ebinuma ◽  
Kiyoshi Takasu ◽  
Tohru Minamino
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Mitral Regurgitation ◽  
Pulmonary Artery ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Severe Mitral Regurgitation ◽  
Left Heart ◽  
Right Heart ◽  
Left Heart Disease

Background Heart failure is a severe condition often involving pulmonary hypertension (PH). Soluble low-density lipoprotein receptor with 11 ligand-binding repeats (sLR11) has been associated with pulmonary artery hypertension. We examined whether sLR11 correlates with PH in left heart disease and can be used as a predictive marker. Method We retrospectively analyzed patients with severe mitral regurgitation who underwent right heart catheterization before surgery for valve replacement or valvuloplasty from November 2005 to October 2012 at Juntendo University. We measured sLR11 levels before right heart catheterization and analyzed correlations with pulmonary hemodynamics. We compared prognoses between a group with normal sLR11 (≤9.4 ng/ml) and a group with high sLR11 (>9.4 ng/ml). Follow-up was continued for 5 years, with end points of hospitalization due to HF and death due to cardiovascular disease. Results Among 34 patients who met the inclusion criteria, sLR11 correlated with mean pulmonary artery pressure (r = 0.54, p<0.001), transpulmonary pressure gradient (r = 0.42, p = 0.012), pulmonary vascular resistance (r = 0.36, p<0.05), and log brain natriuretic peptide (BNP). However, logBNP did not correlate with pulmonary vascular resistance (p = 0.6). Levels of sLR11 were significantly higher in the 10 patients with PH (14.4±4.3 ng/ml) than in patients without PH (9.9±3.9 ng/ml; p = 0.002). At 5 years, the event rate was higher in the high-sLR11 group than in the normal-sLR11 group. The high-sLR11 group showed 5 hospitalizations due to HF (25.0%) and 2 deaths (10.0%), whereas the normal-sLR11 group showed no hospitalizations or deaths. Analyses using receiver operating characteristic curves showed a higher area under the concentration-time curve (AUC) for sLR11 level (AUC = 0.85; 95% confidence interval (CI) = 0.72–0.98) than for BNP (AUC = 0.80, 95%CI = 0.62–0.99) in the diagnosis of PH in left heart disease. Conclusions Concentration of sLR11 is associated with severity of PH and offers a strong predictor of severe mitral regurgitation in patients after surgery.

scholarly journals Pulmonary Hypertension Due to Left Heart Disease

Hypertension ◽  
2020 ◽  
Vol 75 (6) ◽  
pp. 1397-1408 ◽  
Author(s):  
Mohammed S. Al-Omary ◽  
Stuart Sugito ◽  
Andrew J. Boyle ◽  
Aaron L. Sverdlov ◽  
Nicholas J. Collins
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Left Atrial ◽  
Left Atrial Pressure ◽  
Left Heart ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) due to left heart disease (LHD) is the most common type of PH and is defined as mean pulmonary artery systolic pressure of >20 mm Hg and pulmonary capillary wedge pressure >15 mm Hg during right heart catheterization. LHD may lead to elevated left atrial pressure alone, which in the absence of intrinsic pulmonary vascular disease will result in PH without changes in pulmonary vascular resistance. Persistent elevation in left atrial pressure may, however, also be associated with subsequent pulmonary vascular remodeling, vasoconstriction, and an increase in pulmonary vascular resistance. Hence, there are 2 subgroups of PH due to LHD, isolated postcapillary PH and combined post- and precapillary PH, with these groups have differing clinical implications. Differentiation of pulmonary arterial hypertension and PH due to LHD is critical to guide management planning; however, this may be challenging. Older patients, patients with metabolic syndrome, and patients with imaging and clinical features consistent with left ventricular dysfunction are suggestive of LHD etiology rather than pulmonary arterial hypertension. Hemodynamic measures such as diastolic pressure gradient, transpulmonary gradient, and pulmonary vascular resistance may assist to differentiate pre- from postcapillary PH and offer prognostic insights. However, these are influenced by fluid status and heart failure treatment. Pulmonary arterial hypertension therapies have been trialed in the treatment with concerning results reflecting disease heterogeneity, variation in inclusion criteria, and mixed end point criteria. The aim of this review is to provide an updated definition, discuss possible pathophysiology, clinical aspects, and the available treatment options for PH due to LHD.

scholarly journals Diagnostic value of right heart and pulmonary artery catheterization in patients with suspected pulmonary hypertension. Part 1. Methodology of the procedure, nosology of the diseases and vasoreactivity testing

2020 ◽  
Vol 26 (6) ◽  
pp. 64-76
Author(s):  
Yu. M. Sirenko ◽  
I. O. Zhyvylo ◽  
G. D. Radchenko
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Index ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Pulmonary Artery Catheterization ◽  
Right Heart ◽  
The Mean

The aim – critical review of our own experience, its compliance with current recommendations and data from international registries, as also assessment of pulmonary and systemic hemodynamics obtained in patients with pulmonary arterial hypertension (PAH) in Ukraine. Materials and methods. 220 procedures of the right heart and pulmonary artery catheterization were performed in 195 patients with medium or high probability of PAH according to echocardiography in compliance with current recommendations. All patients were hospitalized at National Scientific Center “M.D. Strazhesko Institute of Cardiology” of NAMS of Ukraine with suspected PAH (primary) or with worsening of the disease course (repeatedly) or in order to confirm the status of vasoreactivity (repeated).Results and discussion. 220 successful catheterization procedures were performed. Primary (diagnostic) right heart catheterization was performed in 195 patients, and repeated – in 25. A diagnosis of pulmonary hypertension was confirmed in 178 patients. In 17 patients, according to the results of catheterization, the diagnosis of PAH was excluded: the mean pressure in the pulmonary artery was less than 20 mm Hg. The structure of nosology in patients who underwent right heart catheterization was as follows: idiopathic PAH was fixed in 68 (38 %) patients, of which 11 (6 %) were vasoreactive; PAH associated with connective tissue diseases – in 21 (12 %) patients; PAH associated with HIV infection in – 4 (2 %) patients; PAH associated with portal hypertension – in 4 (2 %) patients; PAH associated with congenital heart disease – in 26 (15 %) patients; chronic thromboembolic pulmonary hypertension – in 50 (28 %) patients. Vasoreactivity testing was performed in 33 patients with idiopathic PAH. In 11 of them it was positive (33 %). In patients with a positive vasoreactivity testing, the mean pulmonary artery pressure decreased by an average of 21.8 mm Hg to the level of 26.5 mm Hg (p 0.0001), while the cardiac index increased by 31 % and reached 3.8 l · min · m–2 (p<0.1). Pulmonary vascular resistance decreased by 6.4 Wood units to the level of 2.7 Wood units (p<0.0001). In patients with a negative vasoreactivity testing, the decrease in mean pulmonary artery pressure and pulmonary vascular resistance was not statistically significant (p>0.05), and no changes in the cardiac index were detected. Conclusions. Based on the experience of our center, hemodynamic assessment using catheterization is safe and remains the diagnostic standard for PAH. Catheterization is necessary to clarify 4 parameters that are critical for the clinical profile of patients with pulmonary hypertension: right atrium pressure, pulmonary vascular resistance, cardiac output, pulmonary wedge pressure. Patients with idiopathic PAH also need to have vasoreactivity evaluated in order to predict sensitivity to calcium channel blockers therapy, the presence of which is associated with better treatment and survival outcomes.

scholarly journals Therapeutic Challenges and Emerging Treatment Targets for Pulmonary Hypertension in Left Heart Disease

2021 ◽  
Author(s):  
Christelle Lteif ◽  
Ali Ataya ◽  
Julio D. Duarte
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Therapeutic Targets ◽  
Pulmonary Artery Hypertension ◽  
Left Heart ◽  
Genetic Associations ◽  
Mortality And Morbidity ◽  
Left Heart Disease ◽  
Underlying Mechanisms ◽  
Phosphodiesterase 5

Abstract Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and morbidity in this patient population. Specific therapies for PH‐LHD have not yet been identified and the use of pulmonary artery hypertension‐targeted therapies in PH‐LHD are not recommended. Endothelin receptor antagonists, phosphodiesterase‐5 inhibitors, guanylate cyclase stimulators, and prostacyclins have all been studied in PH‐LHD with conflicting results. Understanding the mechanisms underlying PH‐LHD could potentially provide novel therapeutic targets. Fibrosis, oxidative stress, and metabolic syndrome have been proposed as pathophysiological components of PH‐LHD. Genetic associations have also been identified, offering additional mechanisms with biological plausibility. This review summarizes the evidence and challenges for treatment of PH‐LHD and focuses on underlying mechanisms on the horizon that could develop into potential therapeutic targets for this disease.

Abstract 17912: Importance of Acute Hemodynamic Effects of Inhaled Nitric Oxide in Optimization of Heart Failure Treatment in Patients with Pulmonary Hypertension due to Left Heart Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shunsuke Tatebe ◽  
Koichiro Sugimura ◽  
Kotaro Nochioka ◽  
Tatsuo Aoki ◽  
Masanobu Miura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Inhaled Nitric Oxide ◽  
Left Heart ◽  
Hemodynamic Effects ◽  
Left Heart Disease

Background: Pulmonary hypertension (PH) due to left heart disease (LHD) is a major category of the disorder. We have recently reported that elevated pulmonary vascular resistance (PVR) in patients with post-capillary PH (pc-PH: defined as mean pulmonary arterial pressure (mPAP)≥25mmHg and pulmonary capillary wedge pressure (PCWP)>15mmHg) is associated with poor prognosis compared with those with no PH or pc-PH without elevated PVR. Although new treatment is required for targeting pulmonary vascular disease (PVD), thereis a concern about raising PCWP. In this study, we thus examined acute hemodynamic effects of inhaled nitric oxide (iNO) in patients with PH due to LHD and whether optimal heart failure (HF) treatment ameliorates pc-PH. Methods: We examined 60 consecutive pc-PH patients with chronic heart failure (63±14[SD] years, M/F 38/22, NYHA≥2) who underwent acute vasoreactivity test by iNO (40 ppm for 10 min) under right heart catheterization at our hospital from June 2011 to May 2014. Among them, 25 had valvular heart disease (VHD) and 35 had non-VHD. PVD (defined as PVR> 240dynes/s/cm -5 ) was noted in 18. We also evaluated right ventricular systolic pressure (RVSP) by echocardiography after optimization of HF treatment such as medications and valvular surgery. Results: iNO significantly decreased mPAP (-1.7±0.5 mmHg; P<0.01) and PVR (-66 ±14dyne/s/cm -5 , P<0.01) without altering cardiac output. iNO significantly increased PCWP (1.3±0.5 mmHg, P=0.01) only in non-VHD patients, while it significantly increased mean arterial pressure and systemic vascular resistance in VHD patients than in non-VHD patients (both P<0.05). Pc-PH patients with PVD were re-classified as having pc-PH without PVD in 9 and no PH in 1. Eight patients remained pc-PH with PVD. After the optimal medical treatment for 7.6 months, RVSP was significantly decreased in both non-VHD and VHD patient (-8±3mmHg, P=0.04, -19±8mmHg, P=0.01, respectively). However, in non-VHD group, significant reduction in RVSP was noted only in pc-PH patients without PVD (-8±3mmHg, P=0.03). Conclusions: These results indicate that elevated PVR in patients with pc-PH and non-VHD could be a novel therapeutic indication for NO-related pulmonary vasodilators in the current practice of HF.

scholarly journals Role of echocardiography to avoid misclassification of pulmonary hypertension associated with left heart disease as precapillary pulmonary hypertension

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
B Janssen ◽  
P Trujillo ◽  
J Grignola Rial
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Pretest Probability ◽  
Youden Index ◽  
Heart Catheterization ◽  
Left Heart ◽  
Left Heart Disease ◽  
Better Than

Abstract Background The proportion of patients (pts) diagnosed with pulmonary arterial hypertension (PAH) at a more advanced age and/or with more risk factors for left ventricular diastolic dysfunction is increasing. Therefore, it can be challenging to differentiate PH associated with left heart disease (PH-LHD, PHpost) from other precapillary forms of PH (PHpre). Purpose We analyzed the performance of the Opotowsky (OS), D'Alto (DS), and simplified D'Alto (sDS) echocardiographic scores according to the pretest probability (before right heart catheterization – RHC) of PH-LHD in pts with suspected PH submitted to RHC to identify the hemodynamic phenotype. Methods 37 consecutive stable pts (3/2018–3/2020) with a tricuspid regurgitation peak velocity &gt;2.8 m/s were prospectively included (21F, 49±17 yrs). Blinded transthoracic echocardiography was performed within 2 hours of RHC. We assessed OS (−2 to 2 points) and DS/sDS (0 to 34/7 points). We estimated cardiac index (thermodilution) and hemodynamic parameters using standard formulas. If PA occlusion pressure (PAOP) cannot properly be measured at end-expiration, we assessed left ventricular end-diastolic pressure (LVEDP). PH was defined as a mean PA pressure (mPAP) ≥25 mmHg. PAOP/LVEDP &gt;15 mmHg defined PHpost. If the PAOP/LVEDP was between 13–15 mmHg in an I pt, a volume challenge was done. We categorized pts according to the pretest probability of PH-LHD proposed in the 6th WSPH based on the combination of 7 noninvasive variables (age, presence of CV comorbidities, presence of current or paroxysmal atrial fibrillation, prior cardiac intervention, presence of structural LHD, presence of left bundle branch/LV hypertrophy or RV strain in ECG, presence of left atrial dilatation/grade &gt;2 mitral flow in Echo). The individual average probability was calculated by assigning a score of 1, 2, and 3 for each variable (1 = low (L), 2 = intermediate (I), and 3 = high (H) probability) rounding the average of the sum of values allocated for each variable to the nearest integer. Nonparametric ROC plots assessed the performance of echo-scores. Results All pts had PH. 19 pts showed PHpost, 10/19 with PVR &gt;3Wu (Combined PHpost). All scores were lower in PHpost compared to PHpre pts (p&lt;0.05) (Table 1). ROC area was &gt;0.9 with a similar Youden index (0.83) among the three scores (p&lt;0.05) (Figure 1). 17 PHpost with H pts were correctly identified by all scores (94–100%). In 15 PHpre with L pts OS performed better than DS/sDS (93 vs. 80%). In 3 PHpre and 2 PHpost with I pts, DS/sDS performed better than OS (100 vs. 80%). Conclusion The use of simple echo-scores could facilitate the screening of the hemodynamic phenotype in pts with PH, regardless of the pretest probability of PH-LHD. D'Alto scores might have some advantage compared to OS to classify the intermediate pretest probability of PH pts correctly. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Centro Cardiovascular Universitario. Hospital de Clínicas. Facultad de Medicina. Universidad de la República Table 1. Echo & Hemodynamic Data Figure 1. ROC curves of Echo scores

scholarly journals Impact of left heart disease risk factors on risk stratification and treatment response in pulmonary arterial hypertension

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Kearney ◽  
J Anderson ◽  
R Cordina ◽  
M Lavender ◽  
D Celermajer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Risk Stratification ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Similar Response ◽  
Left Heart ◽  
Left Heart Disease ◽  
C Statistic

Abstract Background Contemporary registries have documented a change in the epidemiology of PAH patients displaying increasing co-morbidities associated with left heart disease (LHD). These patients are often excluded from randomized clinical trials. It is unclear whether the presence of LHD comorbidities may adversely impact the accuracy of risk stratification and response to PAH therapy. Method Data was extracted from the Pulmonary Hypertension Society of Australia and New Zealand registry for incident patients with a diagnosis with idiopathic/heritable/toxin-induced (I/H/D)-PAH and connective tissue disease (CTD) associated PAH from 2011 - 2020. Patients without available medication and follow up data were excluded. We used the AMBITION trial exclusion criteria to define the subpopulation with LHD risk factors and haemodynamic phenotype (PAH-rLHD). Results 489 patients (I/H/D-PAH=251, CTD-PAH=238) were included in our analysis, with 103 (21.0%) fulfilling the definition of PAH-rLHD (34 had ≥3 risk factors for left heart disease (rLHD-hypertension, diabetes, obesity or ischaemic heart disease) and 76 had borderline haemodynamics (mean capillary wedge pressure 13–15 with pulmonary vascular resistance &lt;500 dynes sec/cm5) including 7 who met both criteria). Compared to classical PAH, patients with PAH-rLHD were older at diagnosis (66±13 vs 58±19, p&lt;0.001), had lower pulmonary vascular resistance (PVR: 393±266 vs 708±391, p=0.031) but worse exercise capacity (6MWD: 286±130m vs 327±136m, p=0.005). PAH-rLHD were more likely to be started on initial monotherapy, compared with “classical” PAH (73% vs 56%, p=0.002). In the monotherapy groups, endothelin receptor antagonists (ERA) were used in 73% PAH-rLHD, compared with 66% in classical PAH group. Both groups exhibited similar response to both mono- and combination therapy with commensurate improvements in WHO functional class (mean change 0.3±0.6 vs 0.3±0.8, p=0.443) and 6-minute walk distance (mean change 44±82 vs 48±101, p=0.723). There was no difference in survival between classical PAH and PAH-rLHD (log rank, p=0.29). The REVEAL 2.0 risk score effectively discriminated risk in both populations at baseline and first follow up (classical PAH: baseline C statistic 0.750, follow up 0.774 and PAH-rLHD: baseline C statistic 0.756, follow up 0.791). Conclusion Despite lower PVR at diagnosis, PAH-rLHD patients and “classical” PAH demonstrate similar response to first-line therapy with similar long term survival. The REVEAL 2.0 risk score can be effectively applied to the subpopulation of PAH-rLHD in real life clinical practice. FUNDunding Acknowledgement Type of funding sources: None.

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