Measurement of respiratory function: gas exchange and its clinical applications

Gas exchange is the main function of the lungs. Lungs have a large reserve for gas exchange. Oxygen and carbon dioxide diffuse along their partial pressure gradient across the alveolar–capillary membrane. Alveolar ventilation and pulmonary circulation are closely matched to provide efficient gas exchange in the lungs. Hypoxaemia often results from mismatch in ventilation–perfusion. Gas exchange can be impaired in various disease states. Measurement of the diffusing capacity for carbon monoxide (DLCO) provides estimation of the gas exchange function. A low DLCO indicates an impairment of oxygen transfer across the alveolar–capillary membrane. Based on the lung function tests one can assess the risks of perioperative pulmonary complications. Anaesthesia and surgery adversely affect pulmonary function, many of which adverse effects can be prevented.     

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

BackgroundWorld Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.ObjectivesThe aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.MethodsPatients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.ResultsAmong 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by ?3.0 ± 0.3 WU after PADN and ?1.9 ± 0.3 WU after sham (adjusted difference ?1.4; 95% CI: ?2.6 to ?0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro–brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.ConclusionsIn patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)     

1H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication

BackgroundDiabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed due to lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated complication/comorbidities.MethodologyThe present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites in diabetes (DB = 38) vs. diabetes-related complication (DC = 35) along with the healthy control (HC = 50) subjects. A combined and pairwise analysis was performed to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites.ResultsThe DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline, and threonine).ConclusionThe ¹H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its complication on their onset or progression by determining the altered levels of the metabolites in serum.     

Defining Percutaneous Coronary Intervention Complexity and Risk: An Analysis of the United Kingdom BCIS Database 2006-2016

ObjectivesThe authors used the BCIS (British Cardiovascular Intervention Society) database to define the factors associated with percutaneous coronary intervention (PCI) procedural complexity.BackgroundComplex high-risk indicated percutaneous coronary intervention (CHIP-PCI) is an emerging concept that is poorly defined.MethodsThe BCIS (British Cardiovascular Intervention Society) database was used to study all PCI procedures in the United Kingdom 2006-2016. A multiple logistic regression model was developed to identify variables associated with in-hospital major adverse cardiac or cerebrovascular events (MACCE) and to construct a CHIP score. The cumulative effect of this score on patient outcomes was examined.ResultsA total of 313,054 patients were included. Seven patient factors (age ≥80 years, female sex, previous stroke, previous myocardial infarction, peripheral vascular disease, ejection fraction <30%, and chronic renal disease) and 6 procedural factors (rotational atherectomy, left main PCI, 3-vessel PCI, dual arterial access, left ventricular mechanical support, and total lesion length >60 mm) were associated with increased in-hospital MACCE and defined as CHIP factors. The mean CHIP score/case for all PCIs increased significantly from 1.06 ± 1.32 in 2006 to 1.49 ± 1.58 in 2016 (P < 0.001 for trend). A CHIP score of 5 or more was present in 2.5% of procedures in 2006 increasing to 5.3% in 2016 (P < 0.001 for trend). Overall in-hospital MACCE was 0.6% when the CHIP score was 0 compared with 1.2% with any CHIP factor present (P < 0.001). As the CHIP score increased, an exponential increase in-hospital MACCE was observed. The cumulative MACCE for procedures associated with a CHIP score 4+ or above was 3.2%, and for a CHIP score 5+ was 4.4%. All other adverse clinical outcomes were more likely as the CHIP score increased.ConclusionsSeven patient factors and 6 procedural factors were associated with adverse in-hospital MACCE and defined as CHIP factors. Use of a CHIP score might be a future target for risk modification.     

Effects of Diet and Sodium Reduction on Cardiac Injury,Strain, and Inflammation: The DASH-Sodium Trial

BackgroundThe DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.ObjectivesThe purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.MethodsDASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.ResultsOf the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: ?27% to ?7%) and hs-CRP by 13% (95% CI: ?24% to ?1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: ?24% to ?14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: ?31% to ?7%) and NT-proBNP by 23% (95% CI: ?32% to ?12%), whereas hs-CRP was not significantly changed (?7%; 95% CI: ?22% to 9%) compared with the high sodium-control diet.ConclusionsCombining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608)