Animal models of pulmonary hypertension due to left heart disease

Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Characteristics of biochemical markers in patients with pulmonary hypertension related to left heart disease

Objective To investigate the differences of biochemical markers between the patients with pulmonary hypertension related to left heart disease(PH-LHD)and LHD;to explore the sensitive biomarkers which may predict PH in LHD patients.Methods A total of 355 LHD patients admitted to our hospital from 2014-01 to

Correlation analysis between lung ultrasound scores and pulmonary arterial systolic pressure in patients with acute heart failure admitted to the emergency intensive care unit

Background:No convenient,inexpensive,and non-invasive screening tools exist to identify pulmonary hypertension(PH)-left heart disease(LHD)patients during the early stages of the disease course.This study investigated whether different methods of lung ultrasound(LUS)could be used for the initial investigation of PH-LHD.Methods:This was a single-center prospective observational study which was performed in the Zigong Fourth People’s Hospital.We consecutively enrolled patients with heart failure(HF)admitted to the emergency intensive care unit from January 2018 to May 2020.Transthoracic echocardiography and LUS were performed within 24 h before discharge.We used the Spearman coefficient for correlation analysis between ultrasound scores and pulmonary arterial systolic pressure(PASP).Bland-Altman plots were generated to inspect possible bias,and receiver operating characteristic(ROC)curves were calculated to assess the relationship between ultrasound scores and an intermediate and high echocardiographic probability of PH-LHD.Results:Seventy-one patients were enrolled in this study,with an overall median age of 79(interquartile range:71.5–84.0)years.Among the 71 patients,36(50.7%)cases were male,and 26(36.6%)had an intermediate and high echocardiographic probability of PH.All four LUS scores in patients with an intermediate and high probability of PH were significantly higher than in patients with a low probability of PH(P<0.05).The correlation coefficient(r)between different LUS scoring methods and PASP was moderate for the 6-zone(r=0.455,P<0.001),8-zone(r=0.385,P=0.001),12-zone(r=0.587,P<0.001),and 28-zone(r=0.535,P<0.001)methods.In Bland-Altman plots,each of the four LUS scoring methods had a good agreement with PASP(P<0.001).The 8-zone and 12-zone methods showed moderately accurate discriminative values in differentiating patients with an intermediate and high echocardiographic probability of PH(P<0.05).