mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Real-world validation of smartphone-based photoplethysmography for rate and rhythm monitoring in atrial fibrillation.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial.

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.

Arrythmia-Mediated Valvular Heart Disease.

The aging population is rising at record pace worldwide. Along with it, a steep increase in the prevalence of atrial fibrillation and heart failure with preserved ejection fraction is to be expected. Similarly, both atrial functional mitral and tricuspid regurgitation (AFMR and AFTR) are increasingly observed in daily clinical practice. This article summarizes all current evidence regarding the epidemiology, prognosis, pathophysiology, and therapeutic options. Specific attention is addressed to discern AFMR and AFTR from their ventricular counterparts, given their different pathophysiology and therapeutic needs.

Conceptions of the pathophysiology of happy hypoxemia in COVID-19.

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.

The pathophysiology of 'happy' hypoxemia in COVID-19.

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.

An evaluation of the influence of force- and weight bearing (a)symmetry on patient reported outcomes after total knee arthroplasty.

It has been reported that balance impairments and asymmetrical movement patterns occur in patients after total kne arthroplasty (TKA). The purpose of this study was to evaluate if force- and weight-bearing asymmetry correlate with patient-reported outcomes (PROMs). Twenty patients were prospectively analysed up to 6 months after TKA. Quadriceps- and hamstring force were measured using a hand-held dynamometer. Vertical ground reaction forces during sit-to-stand, stair descending and squatting were assessed by force plates. Patients were asked to complete the KOOS, OKS and 2011 KSS. The symmetry-ratios during sit-to-stand, squat and stair-descent improved significantly. Preopera-tive quadriceps-force was positively correlated with KOOS-Symptoms (r=0.583, p=0.037). The pre-operative load-symmetry ratio during STS was negatively correlated with improvement in KOOS Pain (r=-0.675, p=0.011) and Symptoms (r=-0.674, p=0.008). In deep flexion, preoperative bodyweight ratio was positively correlated with postoperative OKS (r=0.601, p=0.039), KSS-Satisfaction (r=0.675, p=0.011) and improvement in KSS-Satisfaction (r=0.684, p=0.029). Weight bearing and force asymmetry do exist before TKA and take up to at least 6-months to fully recover. The more symmetry in muscle-force and weight-bearing is found preoperatively, the better the PROMs will be at 6 months after surgery.

Improved walking distance and range of motion predict patient satisfaction after TKA.

PURPOSES: The focus in the evaluation of total knee arthroplasty has shifted from objective measures of implant position and knee function, to patient-reported outcome measures (PROMs). The relation between these two measures was investigated and the possibility of prediction of the patient satisfaction level was evaluated by defining thresholds for improvement of (1) range of motion (ROM), (2) 6-min walk test (6MWT), (3) sit-to-stand test (STS) and (4) quadriceps force after TKA? METHODS: Fifty-seven patients were prospectively tested at preoperative and 6 months postoperative intervals. The ROM, 6MWT, STS-test and quadriceps force were evaluated. Two clusters were created based on the postoperative KOOS, OKS and the satisfaction subscore of the new KSS, cluster 1 consisted of patients with good to excellent PROMs, cluster 2 of patients with poorer PROMs. Patients in each cluster were more similar to each other than to those in the other cluster. Receiver operating characteristic (ROC)-curve analysis was used to identify thresholds for the functional outcomes that established cluster allocation. Multiple logistic regression was used to define a model to predict cluster allocation. RESULTS: Patients with high postoperative PROMs (cluster 1 allocation) showed higher postoperative functional outcomes (p < 0.05). Thresholds for the improvement of ROM (≥ 5°, OR 6.3, 95% CI 1.23-31.84), 6MWT (≥ 50 m, OR 8.2, 95% CI 1.61-42.18) STS (≥ 1.05 s, OR 3, 95% CI 0.56-16.07) and normalized Q4 force (≥ 1.5 N/BMI, OR 2.5, 95% CI 0.49-12.89) were found to be predictors of cluster allocation. A model to predict the cluster allocation contained gender, ROM improvement and 6MWT improvement (sensitivity 91.1%, specificity 75%). CONCLUSIONS: Thresholds for improvement of functional parameters can predict the patient satisfaction cluster. Patients, who are male, improve on the 6-min walk test with 50 m or more and have an increased range of motion of 5° or more, compared to the preoperative situation, are 6-8 times more likely of being satisfied after TKA. These tests are easy to use in clinical practice and can predict the level of patient satisfaction after TKA. LEVEL OF EVIDENCE: Level II, prognostic study.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSION: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling.

AIMS: Sodium restriction was not associated with improved outcomes in heart failure patients in recent trials. The skin might act as a sodium buffer, potentially explaining tolerance to fluctuations in sodium intake without volume overload, but this is insufficiently understood. Therefore, we studied the handling of an increased sodium load in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Twenty-one ambulatory, stable HFrEF patients and 10 healthy controls underwent a 2-week run-in phase, followed by a 4-week period of daily 1.2 g (51 mmol) sodium intake increment. Clinical, echocardiographic, 24-h urine collection, and bioelectrical impedance data were collected every 2 weeks. Blood volume, skin sodium content, and skin glycosaminoglycan content were assessed before and after sodium loading. Sodium loading did not significantly affect weight, blood pressure, congestion score, N-terminal pro-brain natriuretic peptide, echocardiographic indices of congestion, or total body water in HFrEF (all p > 0.09). There was no change in total blood volume (4748 ml vs. 4885 ml; p = 0.327). Natriuresis increased from 150 mmol/24 h to 173 mmol/24 h (p = 0.024), while plasma renin decreased from 286 to 88 µU/L (p = 0.002). There were no significant changes in skin sodium content, total glycosaminoglycan content, or sulfated glycosaminoglycan content (all p > 0.265). Healthy controls had no change in volume status, but a higher increase in natriuresis without any change in renin. CONCLUSIONS: Selected HFrEF patients can tolerate sodium loading, with increased renal sodium excretion and decreased neurohormonal activation.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Reduced Left Atrial Appendage Flow Is Associated With Future Atrial Fibrillation After Cryptogenic Stroke.

BACKGROUND: Hemostasis within the left atrial appendage (LAA) is a common cause of stroke, especially in patients with atrial fibrillation (AF). Although LAA flow provides insights into LAA function, its potential for predicting AF has yet to be established. The aim of this study was to explore whether LAA peak flow velocities early after cryptogenic stroke are associated with future AF on prolonged rhythm monitoring. METHODS: A total of 110 patients with cryptogenic stroke were consecutively enrolled and underwent LAA pulsed-wave Doppler flow assessment using transesophageal echocardiography within the early poststroke period. Velocity measurements were analyzed offline by an investigator blinded to the results. Prolonged rhythm monitoring was conducted on all participants via 7-day Holter and implantable cardiac monitoring devices, with follow-up conducted over a period of 1.5 years to determine the incidence of AF. The end point of AF was defined as irregular supraventricular rhythm with variable RR interval and no detectable P waves lasting ≥30 sec during rhythm monitoring. RESULTS: During a median follow-up period of 539 days (interquartile range, 169-857 days), 42 patients (38%) developed AF, with a median time to AF diagnosis of 94 days (interquartile range, 51-487 days). Both LAA filling velocity and LAA emptying velocity (LAAev) were lower in patients with AF (44.3 ± 14.2 and 50.7 ± 13.3 cm/s, respectively) compared with patients without AF (59.8 ± 14.0 and 76.8 ± 17.3 cm/sec, respectively; P < .001 for both). LAAev was most strongly associated with future AF, with an area under the receiver operating characteristic curve of 0.88 and an optimal cutoff value of 55 cm/sec. Age and mitral regurgitation were independent determinants of reduced LAAev. CONCLUSIONS: Impaired LAA peak flow velocities (LAAev < 55 cm/sec) in patients with cryptogenic stroke are associated with future AF. This may facilitate the selection of appropriate candidates for prolonged rhythm monitoring to improve its diagnostic accuracy and implementation.

Detecting Paroxysmal Atrial Fibrillation From an Electrocardiogram in Sinus Rhythm: External Validation of the AI Approach.

BACKGROUND: Atrial fibrillation (AF) may occur asymptomatically and can be diagnosed only with electrocardiography (ECG) while the arrhythmia is present. OBJECTIVES: The aim of this study was to independently validate the approach of using artificial intelligence (AI) to identify underlying paroxysmal AF from a 12-lead ECG in sinus rhythm (SR). METHODS: An AI algorithm was trained to identify patients with underlying paroxysmal AF, using electrocardiographic data from all in- and outpatients from a single center with at least 1 ECG in SR. For patients without AF, all ECGs in SR were included. For patients with AF, all ECGs in SR starting 31 days before the first AF event were included. The patients were randomly allocated to training, internal validation, and testing datasets in a 7:1:2 ratio. In a secondary analysis, the AF prevalence of the testing group was modified. Additionally, the performance of the algorithm was validated at an external hospital. RESULTS: The dataset consisted of 494,042 ECGs in SR from 142,310 patients. Testing the model on the first ECG of each patient (AF prevalence 9.0%) resulted in accuracy of 78.1% (95% CI: 77.6%-78.5%), area under the receiver-operating characteristic curve of 0.87 (95% CI: 0.86-0.87), and area under the precision recall curve (AUPRC) of 0.48 (95% CI: 0.46-0.50). In a low-risk group (AF prevalence 3%), the AUPRC decreased to 0.21 (95% CI: 0.18-0.24). In a high-risk group (AF prevalence 30%), the AUPRC increased to 0.76 (95% CI: 0.75-0.78). This performance was robust when validated in an external hospital. CONCLUSIONS: The approach of using an AI-enabled electrocardiographic algorithm for the identification of patients with underlying paroxysmal AF from ECGs in SR was independently validated.

Sodium and potassium changes during decongestion with acetazolamide - A pre-specified analysis from the ADVOR trial.

AIMS: Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide. METHODS AND RESULTS: This is a pre-specified sub-analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (<3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non-significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (<3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels. CONCLUSIONS: Acetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels.

The use of cardiac troponins and B-type natriuretic peptide in COVID-19.

Coronavirus disease 2019 (COVID-19) is still challenging health care systems worldwide. Over time, it has become clear that respiratory disease is not the only important entity as critically ill patients are also more prone to develop complications, such as acute cardiac injury. Despite extensive research, the mainstay of treatment still relies on supportive care and targeted therapy of these complications. The development of a prognostic model which helps clinicians to diverge patients to an appropriate level of care is thus crucial. As a result, several prognostic markers have been studied in the past few months. Among them are the cardiac biomarkers, especially cardiac troponins T/I and brain natriuretic peptide, which seem to have important prognostic values as several reports have confirmed their strong association with adverse clinical outcomes and death. The use of these biomarkers as part of a prognostic tool could potentially result in more precise risk stratification of COVID-19 patients and divergence to an adequate level of care. However, several caveats persist causing international guidelines to still recommend in favour of a more conservative approach to cardiac biomarker testing for prognostic purposes.

Pulmonary hypertension in interstitial lung disease: an area of unmet clinical need.

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.

An eye-opening case report of constrictive pericarditis.

Background: Constrictive pericarditis is characterized by the encasement of the heart by a stiff pericardium leading to impaired diastolic function, which ultimately leads to congestive heart failure. Case summary: We report a case of a young woman, who first presented to the ophthalmologist with the sudden appearance of floaters and vision reduction. Eventually, invasive haemodynamic assessment led to the diagnosis of constrictive pericarditis leading to venous congestion. Conclusion: Understanding the pathophysiology and integrating the results of invasive and non-invasive diagnostic work up is important in making this challenging diagnosis.