High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. We studied 34 HAPH+ and 54 HH at Aksay (3250 m), and 34 LL at Bishkek (760 m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean ± SD 34 ± 3, 22 ± 5, 16 ± 4 mmHg, respectively (p < 0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG-derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. Pulse oximetry in HAPH+, HH and LL was, mean ± SD, 88 ± 4, 92 ± 2 and 95 ± 2%, respectively (p < 0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422 ± 24, 405 ± 27, 400 ± 28 ms (p < 0.05 HAPH+ vs. others); corresponding SI was 10.5 ± 1.9, 8.4 ± 2.6, 8.5 ± 2.0 m/s, heart rate was 75 ± 8, 68 ± 8, 70 ± 10 bpm (p < 0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling.
We investigated whether nocturnal oxygen therapy (NOT) mitigates the altitude-induced increase of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD) when staying overnight at moderate altitude. Patients with COPD living below 800m, underwent examinations at 490m and during 2 sojourns at 2048m (with a washout period of 2 weeks <800m between altitude sojourns). During nights at altitude patients received either NOT (3 l/min) or placebo (ambient air 3 l/min) via nasal cannula according to a randomized cross-over design. The main outcome was the difference of the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the 2nd day at altitude (performed under ambient air) between sojourns with NOT and placebo. Additional outcomes were other echocardiographic measures of the right and left heart function. Twenty-three COPD-patients (70% GOLD II / 30% GOLD III, mean±SD age 66±5years, FEV1 54±13% predicted) were included. TRPG significantly increased when patients travelled from 490m to 2048m (21.7±5.2mmHg; 2048m placebo 27.4±7.3mmHg; and 2048m NOT 27.8±8.3mmHg) without difference between interventions. The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo (2.6±0.6 vs. 2.3±0.4cm, mean difference (95% confidence interval) 0.3(0.1 to 0.5)cm, p=0.005). NOT did not mitigate the acute effect of altitude on the TRPG in COPD lowlanders travelling to altitude compared to placebo. Whether NOT during prolonged altitude sojourns affects right heart function remains to be studied.
Introduction: Patients with cardiopulmonary disorders may be at risk of malignant arrhythmia due to long-QT syndrome. A large proportion of these patients undergo sleep studies including overnight ECG. The purpose of this study was to compare an automated algorithm versus manual scoring of QT-intervals in patients with COPD undergoing sleep studies. Methods: We collected 62 overnight ECG recordings in 28 patients with COPD. All one-minute QT-intervals corrected for heart rate (QTc) were quantified, both by the automated algorithm and by manual cursor-assisted measurements of a mean ECG curve computed for each 1-min epoch. Manual scoring was done blinded for the results from the algorithm. Agreement of the two methods was calculated using Bland-Altman statistics. To quantify the accuracy for clinically relevant QT prolongations, we used confusion matrixes for 3 thresholds (460, 480, and 500ms). Results: 32944 one-minute intervals were analysed. Mean difference between manual and algorithm-based QTc-intervals was -1.4ms, with limits of agreement of -18.3, 15.5ms. A total of 2587, 357 and 0 QTc-intervals exceeding the threshold 460, 480, and 500ms, respectively, were identified by manual scoring. Using the automated algorithm, diagnostic classification revealed an accuracy of 0.98 (95%CI 0.98/0.98), 1.00 (1.00/1.00), and 1.00 (1.00/1.00) for 460, 480, and 500ms, respectively. Conclusion: Clinically relevant QTc-prolongations were accurately identified by the automated algorithm. The implementation of this tool in hospital sleep laboratories may identify asymptomatic patients with long-QT at risk for malignant arrhythmia, allowing them to consult a cardiologist before an eventual cardiac event.
To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH). We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method. The process was undertaken in parallel with the writing of the 2022 ESC/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension and involved the Task Force chairs, experts in PAH, Heart Failure Association (HFA) members and patient representatives. We identified five domains of care for patients with PAH: structural framework, diagnosis and risk stratification, initial treatment, follow-up, and outcomes. In total, 23 main and one secondary QIs for PAH were selected. This document presents the ESC QIs for PAH, describes their development process and offers scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and improve patient outcomes.
In patients with chronic obstructive pulmonary disease (COPD), oxygen delivery to the heart may be impaired during travel at altitude. We assessed electrocardiogram (ECG)-derived signs of cardiac ischemia and the effects of preventive acetazolamide therapy in COPD patients traveling to high altitudes. Patients with COPD [Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) grades 2-3] and a predicted forced expiratory volume in 1 s (FEV1) of 66 ± 11% (mean ± SD), aged 57 ± 8 years, and living <1,000 m were included in this analysis of secondary outcomes from a randomized placebo-controlled double-blind trial (www.clinicaltrials.gov, NCT03156231). Exercise electrocardiograms were recorded at the National Center of Internal Medicine and Cardiology, Bishkek (760 m) and on the day of arrival at the Tuja Ashu high-altitude clinic (3,100 m), Kyrgyzstan. Acetazolamide (375 mg/day) or placebo was administered 24 h before the ascent and during the stay at 3,100 m. The incidence of a post-exercise ST elevation (STE) ≥0.3 mm in aVR (J + 80 ms) was the main outcome. At 760 m, 3 of 49 (6%) patients randomized to placebo and 3 of 50 (6%) randomized to acetazolamide showed a post-exercise STE. At 3,100 m under placebo, two (4%) new STEs developed and one (2%) disappeared compared to 760 m (P = 0.564, McNemar's test). At 3,100 m under acetazolamide, one (2%) new STE developed and two (4%) disappeared compared to 760 m (P = 0.564). No treatment effect was detected (P = 0.242, Fisher's exact test). The mean difference (95% CI) in STE between post-peak exercise between 3,100 m and 760 m was 0.22 mm (0.06 to 0.39) and 0.09 mm (-0.06 to 0.24) under placebo and acetazolamide therapy [treatment effect, -0.13 mm (-0.35 to 0.08, P = 0.230)], respectively. In lowlanders with moderate to severe COPD ascending to 3,100 m, no ECG-derived signs of cardiac ischemia emerged neither at rest nor post-exercise and this was not modified by preventive acetazolamide therapy.
Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, chronic illness, characterized by bilateral pathological thickening of the intima layer of the pulmonary arteries (PA). The underlying molecular and pathogenic mechanisms are still largely unexplored. Methods: We analysed the expression of microRNAs let-7b and let-7d in PEA specimens of 45 CTEPH patients and in PA tissue from explanted lungs of 10 lung transplantation patients (reference PA). Spearman's correlation was performed to investigate possible relationships between microRNA expression and clinical parameters, and Mann-Whitney-U test to investigate differences in microRNA expression between CTEPH and reference PA. Results: Both let-7b and let-7d were successfully quantified in PEA-derived tissue. Expression levels of let-7b and let-7d were positively correlated between left and right side (r=0.403, p=0.016, and r=0.615, p<0.001, respectively). Moreover, let-7b expression of both sides was positively correlated with let-7d expression of the same side (right: r=0.377, p=0.020; left: r=0.615, p<0.001). Unlike our observations for other microRNAs on which we previously reported, there was no significant correlation between let-7b/7d expression and clinical parameters, and no statistically significant differences between CTEPH and reference PA samples. Conclusions: This is one of the first studies evaluating microRNAs in PEA-derived tissue. While we did not detect marked associations between expression levels of let-7b/7d and clinical presentation, the successful detection and quantification of let-7b/7d in CTEPH tissue is a first step towards the study of the possible involvement of microRNAs in pathogenic mechanisms leading to CTEPH.
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