Management of pulmonary hypertension from left heart disease in candidates for orthotopic heart transplantation.
Ontology highlight
ABSTRACT:
SUBMITTER: Koulova A
PROVIDER: S-EPMC5594194 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Management of pulmonary hypertension from left heart disease in candidates for orthotopic heart transplantation.
Koulova Anna A Gass Alan L AL Patibandla Saikrishna S Gupta Chhaya Aggarwal CA Aronow Wilbert S WS Lanier Gregg M GM
Journal of thoracic disease 20170801 8
Pulmonary hypertension in left heart disease (PH-LHD) commonly complicates prolonged heart failure (HF). When advanced, the PH becomes fixed or out of proportion and is associated with increased morbidity and mortality in patients undergoing orthotopic heart transplant (OHT). To date, the only recommended treatment of out of proportion PH is the treatment of the underlying HF by reducing the pulmonary capillary wedge pressure (PCWP) with medications and often along with use of mechanical circula ...[more]
Similar Datasets
Project description:Pulmonary hypertension (PH) is frequent in left heart disease (LHD), as a consequence of the underlying condition. Significant advances have occurred over the past 5 years since the 5th World Symposium on Pulmonary Hypertension in 2013, leading to a better understanding of PH-LHD, challenges and gaps in evidence. PH in heart failure with preserved ejection fraction represents the most complex situation, as it may be misdiagnosed with group 1 PH. Based on the latest evidence, we propose a new haemodynamic definition for PH due to LHD and a three-step pragmatic approach to differential diagnosis. This includes the identification of a specific "left heart" phenotype and a non-invasive probability of PH-LHD. Invasive confirmation of PH-LHD is based on the accurate measurement of pulmonary arterial wedge pressure and, in patients with high probability, provocative testing to clarify the diagnosis. Finally, recent clinical trials did not demonstrate a benefit in treating PH due to LHD with pulmonary arterial hypertension-approved therapies.
| S-EPMC6351334 | biostudies-literature
Project description:Metformin is ubiquitously used in the management of Type II Diabetes Mellitus (DMII). Over the years, our growing knowledge of its therapeutic potential has broadened its use to the treatment of infertility in polycystic ovarian syndrome, gestational diabetes, and even obesity. Recently, it has been suggested as a novel therapy in cardiovascular disease (CVD). Given that CVD is the leading cause of death in patients with DMII, with ~ 75% dying from a cardiovascular event, the intersection of DMII and CVD provides a unique therapeutic target. In particular, pulmonary hypertension (PH) related to CVD (Group II PH) may be an optimal target for metformin therapy. The objective of this review article is to provide an overview of the pathophysiology of PH related to left heart disease (PH-LHD), outline the proposed pathophysiologic mechanism of insulin resistance in heart failure and PH-LHD, and evaluate the role metformin may have in heart failure and PH-LHD.
| S-EPMC7466644 | biostudies-literature
Project description:Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet, pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to noncardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH. Whole rat genome microarray analyses were performed in lung homogenates of three rats with established PH following supracoronary aortic banding and in three sham-operated controls. Out of a total of 28,000 analysed genes, differential expression defined as 2-fold change with p<0.05 was evident for 120 genes. Of these, 76 were upregulated and 44 downregulated in aortic banding compared with control lungs gene. Enrichment analysis revealed regulation of mast cell specific genes - 13 out of 20 genes were significantly upregulated in aortic banding compared with control lungs. To test for a putative functional role of mast cells in lung vascular remodelling and PH in LHD, we applied a pharmacological approach by treatment of aortic banding rats with the mast cell stabiliser ketotifen. Microarray analysis then compared rats that were treated with untreated. In brief, congestive heart failure (CHF) was induced in juvenile rats by supracoronary aortic banding and rats were analyzed 9 weeks thereafter when they had established left heart failure with preserved ejection fraction and secondary pulmonary hypertension. Three heart failure rats were untreated, and 3 received the mast cell stabilizer ketotifen (1 mg/kg-1 bodyweight/day-1) with the drinking water. Sham rats underwent the same surgical procedure but without placement of a clip on the supracoronary aorta. Microarray analyses: Lungs from banded and control rats were excised and total RNA was extracted (Stratagene Absolutely RNA Miniprep Kit; Stratagene, La Jolla, USA). Three µg total RNA from three control and three banded rats each were processed according to the One-Cycle Target Labeling protocol (GeneChip Expression Analysis, Affymetrix, Santa Clara, USA). Before and after amplifications, the total RNA/complementary RNA concentrations were checked with NanoDrop ND-1000 (Thermo Scientific, Wilmington, USA) and quality was controlled (Experion electrophoresis station, BioRad; Hercules, USA). Samples were hybridized to GeneChip® Rat Genome 230 2.0 arrays (Affymetrix; Santa Clara, USA) containing 31,000 probe sets covering 28,000 rat genes.
2016-07-22 | E-GEOD-84704 | biostudies-arrayexpress
Project description:Pulmonary hypertension (PH) is common in advanced heart failure and often improves quickly after left ventricular assist device (VAD) implantation or orthotopic heart transplantation (OHT), but long-term effects and outcomes are not well-described. This study evaluated PH persistence after VAD as destination therapy (VAD-DT), bridge to transplant (VAD-OHT), or OHT-alone. The study constituted a retrospective review of patients who underwent VAD-DT (n = 164), VAD-OHT (n = 111), or OHT-alone (n = 138) at a single tertiary-care center. Right heart catheterization (RHC) data was collected pre-, post-intervention (VAD and/or OHT), and 1-year from final intervention (latest-RHC) to evaluate the longitudinal hemodynamic course of right ventricular function and pulmonary vasculature. PH (Group II and Group I) definitions were adapted from expert guidelines. All groups showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output, and pulmonary vascular resistance (PVR) at each RHC with greatest improvement at post-intervention RHC (post-VAD or post-OHT). PH was reduced from 98% to 26% in VAD-OHT, 92%-49% in VAD-DT, and 76%-28% in OHT-alone from preintervention to latest-RHC. At latest-RHC mPAP remained elevated in all groups despite normalization of PAWP and PVR. VAD-supported patients exhibited suppressed pulmonary artery pulsatility index (PaPi < 3.7) with improvement only posttransplant at latest-RHC. Posttransplant patients with PH at latest-RHC (n = 60) exhibited lower survival (HR: 2.1 [95% CI: 1.3-3.4], p < 0.001). Despite an overall significant improvement in pulmonary pressures and PH proportion, a notable subset of patients exhibited PH post-intervention. Post-intervention PH was associated with lower posttransplant survival.
| S-EPMC10614205 | biostudies-literature
Project description:Left heart failure is currently the most prevalent cause of pulmonary hypertension (PH) worldwide and this is due mainly to the increased left ventricular and pulmonary venous pressures seen in this condition. Still, a quota of patients with left heart failure will have a pulmonary arterial disease "disproportionate" to the initial increase of left-sided pressures. Whatever the mechanism involved, the appearance of PH is a powerful marker, as it determines decreased exercise tolerance and survival. To date, all trials using therapies approved for pulmonary arterial hypertension (PAH) failed to demonstrate a benefit in the context of heart failure (HF) without or with PH. In addition, the comparison among studies is limited by relevant differences in definitions, methodology, and timing of assessment. A novel rigorous hemodynamic classification based on the diastolic pulmonary gradient has been recently proposed to better characterize this form of PH. This will promote uniformity in patient populations and end-points for future clinical trials.
| S-EPMC4311271 | biostudies-literature
Project description:Pulmonary hypertension has high disability and mortality rates. Among them, pulmonary hypertension caused by left heart disease (PH-LHD) is the most common type. According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, PH-LHD is classified as group 2 pulmonary hypertension. PH-LHD belongs to postcapillary pulmonary hypertension, which is distinguished from other types of pulmonary hypertension because of its elevated pulmonary artery wedge pressure. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. The primary strategy in managing PH-LHD is optimizing treatment of the underlying cardiac disease. Recent clinical studies have found that mechanical unloading of left ventricle by an implantable non-pulsatile left ventricular assist device with continuous flow properties can reverse pulmonary hypertension in patients with heart failure. However, the specific therapies for PH in LHD have not yet been identified. Treatments that specifically target PH in LHD could slow its progression and potentially improve disease severity, leading to far better clinical outcomes. Therefore, exploring the current research on the pathogenesis of PH-LHD is important. This paper summarizes and classifies the research articles on the pathogenesis of PH-LHD to provide references for the mechanism research and clinical treatment of PH-LHD, particularly molecular targeted therapy.
| S-EPMC10020203 | biostudies-literature
Project description:Development of pulmonary hypertension (PH) in patients with left side heart disease (LHD) is a predictor of poor prognosis. The use of pulmonary vasodilators in PH associated with LHD (PH-LHD) is controversial. In this study, we describe the practice patterns regarding the use of pulmonary vasodilators in PH-LHD among a group of international pediatric PH specialists. A survey was distributed to the members of three pediatric PH networks: PPHNet, PVRI, and REHIPED. The survey queried participants on the rationale, indications, and contraindications of the use of pulmonary vasodilators in children with PH-LHD. Forty-seven PH specialists from 39 PH centers completed the survey. Participants included PH specialists from North America (57%), South America (15%), and Europe (19%). The majority of participants (74%) recommended the use of pulmonary vasodilators only in patients with combined pre-capillary and post-capillary pulmonary hypertension. Participants required the presence of clinical symptoms or signs of heart failure (68%) or right ventricular dysfunction by echocardiography (51%) in order to recommend pulmonary vasodilator therapy. There was no agreement regarding hemodynamic criteria used to recommend pulmonary vasodilators or the etiologies of LHD considered contraindications for using pulmonary vasodilators to manage PH-LHD. Of the available PH-targeted drugs, most participants preferred the use of phosphodiesterase-5-inhibitors for this indication. In conclusion, the practice of recommending pulmonary vasodilators in PH-LHD is highly variable among international pediatric PH specialists. Most specialists of those surveyed (57% in North America) would consider the use of pulmonary vasodilators in PH-LHD only if pre-capillary pulmonary hypertension and right ventricular dysfunction are present.
| S-EPMC7879002 | biostudies-literature
Project description:Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet, pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to noncardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH. Whole rat genome microarray analyses were performed in lung homogenates of three rats with established PH following supracoronary aortic banding and in three sham-operated controls. Out of a total of 28,000 analysed genes, differential expression defined as 2-fold change with p<0.05 was evident for 120 genes. Of these, 76 were upregulated and 44 downregulated in aortic banding compared with control lungs gene. Enrichment analysis revealed regulation of mast cell specific genes - 13 out of 20 genes were significantly upregulated in aortic banding compared with control lungs. To test for a putative functional role of mast cells in lung vascular remodelling and PH in LHD, we applied a pharmacological approach by treatment of aortic banding rats with the mast cell stabiliser ketotifen. Microarray analysis then compared rats that were treated with untreated.
2016-07-22 | GSE84704 | GEO
Project description:In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.
| S-EPMC4800173 | biostudies-literature
Project description:Kidney transplantation (KT) is controversial in patients with pretransplant pulmonary hypertension (PtPH). We aimed to quantify post-KT graft and patient survival as well as survival benefit in recipients with PtPH.MethodsUsing UR Renal Data System (2000-2018), we studied 90 819 adult KT recipients. Delayed graft function, death-censored graft failure, and mortality were compared between recipients with and without PtPH using inverse probability weighted logistic and Cox regression. Survival benefit of KT was determined using stochastic matching and stabilized inverse probability treatment Cox regression.ResultsAmong 90 819 KT recipients, 2641 (2.9%) had PtPH. PtPH was associated with higher risk of delayed graft function (odds ratio, 1.23; 95% CI, 1.10-1.36; P < 0.01), death-censored graft failure (hazard ratio [HR], 1.23; 95% CI, 1.11-1.38; P < 0.01), and mortality (HR, 1.56; 95% CI, 1.44-1.69; P < 0.01). However, patients with PtPH who received a KT had a 46% reduction in mortality (HR, 0.54; 95% CI, 0.48-0.61; P < 0.01) compared with those who remained on the waitlist.ConclusionsAlthough PtPH is associated with inferior post-KT outcomes, KT is associated with better survival compared with remaining on the waitlist. Therefore, KT is a viable treatment modality for appropriately selected patients with PtPH.
| S-EPMC9276173 | biostudies-literature