BackgroundInflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology.ObjectiveWe sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.MethodsMice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.ResultsMice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release.ConclusionsMitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD.

ObjectivesThe clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK.MethodsWe retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention.ResultsMean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.ConclusionHypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

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AimsPulmonary hypertension (PH) is dichotomized into pre- and post-capillary physiology by invasive catheterization. Imaging, particularly strain assessment, may aid in classification and be helpful with ambiguous hemodynamics. We sought to define cardiac MRI (CMR) feature tracking biatrial peak reservoir and biventricular peak systolic strain in pre- and post-capillary PH and examine the performance of peak left atrial strain in distinguishing the 2 groups compared to TTE.Methods and ResultsRetrospective cross-sectional study from 1 Jan 2015 to 31 Dec 2020; 48 patients (22 pre- and 26 post-capillary) were included with contemporaneous TTE, CMR and catheterization. Mean pulmonary artery pressures were higher in the pre-capillary cohort (55 ± 14 vs. 42 ± 9 mmHg; p &lt; 0.001) as was pulmonary vascular resistance (median 11.7 vs. 3.7 WU; p &lt; 0.001). Post-capillary patients had significantly larger left atria (60 ± 22 vs. 25 ± 9 ml/m2; p &lt; 0.001). There was no difference in right atrial volumes between groups (60 ± 21 vs. 61 ± 29 ml/m2; p = 0.694), however peak RA strain was lower in post-capillary PH patients (8.9 ± 5.5 vs. 18.8 ± 7.0%; p &lt; 0.001). In the post-capillary group, there was commensurately severe peak strain impairment in both atria (LA strain 9.0 ± 5.8%, RA strain 8.9 ± 5.5%). CMR LAVi and peak LA strain had a multivariate AUC of 0.98 (95% CI 0.89–1.00; p &lt; 0.001) for post-capillary PH diagnosis which was superior to TTE.ConclusionCMR volumetric and deformation assessment of the left atrium can highly accurately distinguish post- from pre-capillary PH.

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