Circulating Blood-Based Biomarkers in Pulmonary Hypertension

Pulmonary hypertension (PH) is a serious hemodynamic condition, characterized by increased pulmonary vascular resistance (PVR), leading to right heart failure (HF) and death when not properly treated. The prognosis of PH depends on etiology, hemodynamic and biochemical parameters, as well as on response to specific treatment. Biomarkers appear to be useful noninvasive tools, providing information about the disease severity, treatment response, and prognosis. However, given the complexity of PH, it is impossible for a single biomarker to be adequate for the broad assessment of patients with different types of PH. The search for novel emerging biomarkers is still ongoing, resulting in a few potential biomarkers mirroring numerous pathophysiological courses. In this review, markers related to HF, myocardial remodeling, inflammation, hypoxia and tissue damage, and endothelial and pulmonary smooth muscle cell dysfunction are discussed in terms of diagnosis and prognosis. Extracellular vesicles and other markers with complex backgrounds are also reviewed. In conclusion, although many promising biomarkers have been identified and studied in recent years, there are still insufficient data on the application of multimarker strategies for monitoring and risk stratification in PH patients.

Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a disease that progress over time and is defined as an increase in pulmonary arterial pressure and pulmonary vascular resistance that frequently leads to right-ventricular (RV) failure and death. Epigenetic modifications comprising DNA methylation, histone remodeling, and noncoding RNAs (ncRNAs) have been established to govern chromatin structure and transcriptional responses in various cell types during disease development. However, dysregulation of these epigenetic mechanisms has not yet been explored in detail in the pathology of pulmonary arterial hypertension and its progression with vascular remodeling and right-heart failure (RHF). Targeting epigenetic regulators including histone methylation, acetylation, or miRNAs offers many possible candidates for drug discovery and will no doubt be a tempting area to explore for PAH therapies. This review focuses on studies in epigenetic mechanisms including the writers, the readers, and the erasers of epigenetic marks and targeting epigenetic regulators or modifiers for treatment of PAH and its complications described as RHF. Data analyses from experimental cell models and animal induced PAH models have demonstrated that significant changes in the expression levels of multiple epigenetics modifiers such as HDMs, HDACs, sirtuins (Sirt1 and Sirt3), and BRD4 correlate strongly with proliferation, apoptosis, inflammation, and fibrosis linked to the pathological vascular remodeling during PAH development. The reversible characteristics of protein methylation and acetylation can be applied for exploring small-molecule modulators such as valproic acid (HDAC inhibitor) or resveratrol (Sirt1 activator) in different preclinical models for treatment of diseases including PAH and RHF. This review also presents to the readers the application of microfluidic devices to study sex differences in PAH pathophysiology, as well as for epigenetic analysis.

Hybrid extracorporeal membrane oxygenation (ECMO) cannulation following traumatic pneumonectomy: A case report

A 28-year-old man presented in extremis after a motorcycle crash. Following traumatic pneumonectomy, he developed right heart failure and was placed on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) only to transition to veno-arteriovenous (VAV) ECMO due to persistent hypoxemia. Resulting flow limitation caused distal ischemia of his left leg, requiring thrombectomy and fasciotomy. Potential loss of limb necessitated transitioning to veno-venous (VV) ECMO from which he was successfully decannulated thereafter. ECMO can bridge recovery following the most dire injuries, and hybrid strategies can ameliorate post-operative complications; however, ECMO itself carries significant risks that must be weighed against intended benefit.

Impact of Right Heart Failure on Clinical Outcome of Left Ventricular Assist Devices (LVAD) Implantation: Single Center Experience

The aim of this study was to examine the incidence and significance of right heart failure (RHF) in the early and late phase of left ventricular assist device (LVAD) implantation with the identification of predictive factors for the development of RHF. This was a prospective observational analytical cohort study. The study included 92 patients who underwent LVAD implantation and for whom all necessary clinical data from the follow-up period were available, as well as unambiguous conclusions by the heart team regarding pathologies, adverse events, and complications. Of the total number of patients, 43.5% died. The median overall survival of patients after LVAD implantation was 22 months. In the entire study population, survival rates were 88.04% at one month, 80.43% at six months, 70.65% at one year, and 61.96% at two years. Preoperative RHF was present in 24 patients, 12 of whom died and 12 survived LVAD implantation. Only two survivors developed early RHF (ERHF) and two late RHF (LRHF). The most significant predictors of ERHF development are brain natriuretic peptide (BNP), pre-surgery RHF, FAC < 20%, prior renal insufficiency, and total duration of ICU stay (HR: 1.002, 0.901, 0.858, 23.554, and 1.005, respectively). RHF following LVAD implantation is an unwanted complication with a negative impact on treatment outcome. The increased risk of fatal outcome in patients with ERHF and LRHF after LVAD implantation results in a need to identify patients at risk of RHF, in order to administer the available preventive and therapeutic methods.

Optimal Ambulatory Vital Sign Targets in Pulmonary Hypertension Pregnant Women via Time-Dependent Survival Analysis

Background: Pulmonary hypertension (PH) can cause complications in pregnant women due to significant hemodynamic fluctuation or right heart failure as well as death during pregnancy and postpartum. Those in critical condition would be sent to the intensive care unit (ICU) for observation and treatment. However, evidence to suggest the safe target vital signs is limited and none specific to pregnancy with PH.Methods: This retrospective study of consecutive obstetric patients with PH admitted to ICU of the First Affiliated Hospital of Air Force Military Medical University of China, from January 2011 to May 2020, consisted of 92 cases analyzed using time-dependent Cox regression to consider the dynamic features of vital signs. Results: 7/92 maternal deaths occurred. Most of these deaths occurred within the first three days of admission to the ICU. The vital signs for survival were stable and normal compared to death. Three vital signs were identified as risk factors in the maternal in-hospital mortality model via backward selection: SpO2（HR，0.93；95%CI，0.88-0.97；P=0.003）, heart rate（HR，0.94；95%CI，0.90-0.99；P=0.027）, and mean arterial pressure (MAP) （HR，1.09；95%CI，1.00-1.18；P=0.045）. Log of relative hazard ratios of mortality is linearly negatively related to SpO2 value with a U-shaped correlation with heart rate and MAP (both lower and higher values were associated with high mortality). The optimal range of SpO2 <73%, MAP was 65–95 mmHg, and heart rate was 59–125 beats per minute (bpm). Further exploration showed that the cumulative and the longest consecutive time of abnormal vital signs also affect the outcome. For example, SpO2<73% accumulated for 5 h or continuously up to 2 h increases mortality.Conclusions: Pregnant women with PH who died in the hospital experienced long-term abnormal fluctuations in MAP, heart rate, and SpO2 during ICU stay. Maintaining SpO2>73%, MAP at 65–95mmHg, and heart rate at 59–125 bpm can significantly reduce in-hospital maternal mortality. The effects of the abnormal SpO2, heart rate, and MAP on in-hospital maternal mortality should be combined with the cumulative time and the longest duration.Trial Registry: ChiCTR2100046637.

Unguarded Tricuspid Orifice with Congenitally Corrected Transposition of the Great Arteries and Aortic Atresia- A Highly Unusual Case

Unguarded tricuspid orifice is a very rare anomaly. It is characterised by the absence of one or more of the tricuspid valve leaflets resulting in severe tricuspid regurgitation and right heart failure. It is rarely an isolated anomaly but more often associated with pulmonary atresia and intact ventricular septum. When the ventricles are inverted however, the result of outflow tract obliteration is not pulmonary atresia, but aortic atresia. This anomaly has been described in the literature in only 2 cases so far. We present a case of a neonate with unguarded tricuspid orifice with absence of all tricuspid leaflets, congenitally corrected transposition of the great arteries and aortic atresia. The severe tricuspid regurgitation and right ventricular enlargement would have required a Norwood-like procedure combined with a right ventricular plication. Due to the complexity of this lesion no surgical therapy was attempted in consent with the parents.