The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient’s clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.

Background and Aims: In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear. Methods: This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms. Results: On admission, median estimated glomerular filtration rate (eGFR) was 40 (30–52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805). Conclusions: Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes. ClinicalTrials.gov Identifier: NCT03505788.

Pulmonary hypertension (PH) is present in an important proportion of patients with interstitial lung diseases (ILDs), encompassing a large, heterogeneous group of diffuse parenchymal lung diseases. Development of ILD-related PH is associated with reduced exercise capacity, increased need for supplemental oxygen, decreased quality of life and earlier death. Diagnosis of ILD-related PH is important and requires a high index of suspicion. Noninvasive diagnostic assessment can suggest the presence of PH, although right heart catheterisation remains the gold standard to confirm the diagnosis and to assess its severity. A comprehensive assessment is needed to make sure reversible causes of PH have been ruled out, including thromboembolic events, untreated hypoxaemia and sleep disordered breathing. The results of trials concerning pulmonary vasodilators in this particular patient group have been disappointing and, in some cases, were even associated with an increased risk of harm. Newer strategies such as medications administered through inhalation and combinations with antifibrotic drugs show encouraging results. Moreover, unravelling the role of the vasculature in the pathophysiology of pulmonary fibrosis and ILD-related PH may potentially unlock new therapeutic opportunities.

Photoplethysmography- (PPG) based smartphone applications facilitate heart rate and rhythm monitoring in patients with paroxysmal and persistent atrial fibrillation (AF). Despite an endorsement from the European Heart Rhythm Association, validation studies in this setting are lacking. Therefore, we evaluated the accuracy of PPG-derived heart rate and rhythm classification in subjects with an established diagnosis of AF in unsupervised real-world conditions. Fifty consecutive patients were enrolled, 4 weeks before undergoing AF ablation. Patients used a handheld single-lead electrocardiography (ECG) device and a fingertip PPG smartphone application to record 3907 heart rhythm measurements twice daily during 8 weeks. The ECG was performed immediately before and after each PPG recording and was given a diagnosis by the majority of three blinded cardiologists. A consistent ECG diagnosis was exhibited along with PPG data of sufficient quality in 3407 measurements. A single measurement exhibited good quality more often with ECG (93.2%) compared to PPG (89.5%; P < 0.001). However, PPG signal quality improved to 96.6% with repeated measurements. Photoplethysmography-based detection of AF demonstrated excellent sensitivity [98.3%; confidence interval (CI): 96.7–99.9%], specificity (99.9%; CI: 99.8–100.0%), positive predictive value (99.6%; CI: 99.1–100.0%), and negative predictive value (99.6%; CI: 99.0–100.0%). Photoplethysmography underestimated the heart rate in AF with 6.6 b.p.m. (95% CI: 5.8 b.p.m. to 7.4 b.p.m.). Bland–Altman analysis revealed increased underestimation in high heart rates. The root mean square error was 11.8 b.p.m. Smartphone applications using PPG can be used to monitor patients with AF in unsupervised real-world conditions. The accuracy of AF detection algorithms in this setting is excellent, but PPG-derived heart rate may tend to underestimate higher heart rates.

In their letter-to-the-editor entitled “Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19”, Tobin et al. (Respir Res 21:249, 2020) debated our views on happy hypoxemia in COVID-19 (Respir Res 21:198, 2020). We thank the authors for their interesting comments and alternative viewpoints, and we would like to clarify several important aspects raised.