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Funding Acknowledgements Type of funding sources: None. Background Platypnea-orthodeoxia syndrome (POS) is an uncommon condition characterized by dyspnoea and hypoxemia in the upright position that improves with recumbency.1 Possible causes are intracardiac shunt, pulmonary arteriovenous shunt, and V/Q mismatch.1,2 Echocardiography is the cornerstone of POS diagnosis, with special focus on atrial septal defect (ASD) morphology and right-to-left shunt confirmation.3 Purpose To evaluate the clinical and echocardiographic features of patients presenting with POS due to a cardiac cause. Methods We performed a retrospective analysis of patients diagnosed with POS in our centre between 2015 January and 2021 August. Routine blood tests and transthoracic echocardiogram (TTE) were performed in all patients. Demographics, clinical presentation, blood test results, TTE information, and PFO closure procedure details were recorded. Results Seven patients were included, 85.7% female (n = 6). The median (IQR) age was 78 (72-85) years. The most prevalent cardiovascular risk factors were hypertension (100%; n = 7) and overweight/obesity (85.7%; n = 6). Two patients (28.6%) had chronic pulmonary disease. The most common symptoms were fatigue and exercise intolerance (n= 5; 71.4%) and the most frequent sign was persistent hypoxemia (n = 7; 100%), although 28.6% (n = 2) patients did not present the typical positional changes in peripheral oxygen saturation. Haemoglobin levels [14.1 (13.3-15.2)] were within the normal range and serum NTproBNP levels [656 (287-1196)] were slightly elevated. Left ventricle function was preserved in all patients; right ventricle morphology and function were normal in 85.7% (n = 6) patients, low probability of pulmonary hypertension in TTE was found in 85.7% (n = 6), and exuberant Eustachian valve was observed in 14.3% (n = 1). All patients presented atrial septal hypermobility, 87.5% (n = 6) meeting atrial septal aneurysm criteria. Patent foramen ovale was found in 85.7% of patients (n = 6) and ostium secundum ASD in 14.3% (n = 1). POS precipitating factors were aortic root dilation (28.6%; n = 2), chest trauma (14.3%; n = 1), right hip arthroplasty (14.3%; n = 1), atrial septal stretching regarding right volume overload (14.3%; n = 1). The underlying mechanism was unknown in 28.6% (n = 2) of patients. ASD closure was performed in 57.1% (n = 4) of patients: 75% (n = 3) showed residual shunt, but clinical improvement was reported by all. No acute complications were described, except for paroxysmal atrial fibrillation (14.3%; n = 1). Conclusion POS diagnosis depends on high clinical suspicion: the most common manifestations are fatigue and persistent hypoxemia. Typical positional changes in oxygen saturation are not present in all patients. Polycythaemia, right chambers dilation, and pulmonary hypertension are not common. Echocardiography is fundamental for diagnosis, allowing right-to-left shunt confirmation and ASD morphology evaluation to outline a successful closure procedure.

Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist that has been shown to reduce the urinary albumin-to-creatinine ratio in patients with CKD treated with a renin angiotensin system blocker, improving cardiovascular injury while having smaller effects on serum potassium levels than spironolactone. We aim to assess whether nonsteroidal mineralocorticoid receptor antagonists are effective in the treatment of patients with type 2 diabetes and chronic kidney disease using a systematic review approach. We searched PubMed and screened the resulting records on 10 September 2021. A total of 13026 participants were included in this analysis. Overall cardiovascular outcomes were significantly lower in the finerenone group (RR 0.88 (95% CI 0.81 to 0.96; I² = 0%; p = 0.004). Cardiovascular death had an RR of 0.88 (95% CI 0.76 to 1.02; I² = 0%), nonfatal myocardial infarction had an RR of 0.91 (95% CI 0.74 to 1.13; I² = 8%), and heart failure hospitalizations had an RR of 0.79 (95% CI 0.66 to 0.64; I² = 23%; p = 0.001). Overall renal outcomes were significantly lower in the finerenone group (RR 0.84 (95% CI 0.79 to 0.90; I² = 0%; p ≤ 0.00001). Death from renal causes had an RR of 0.86 (95% CI 0.73 to 1.01; I² = 0%). End-stage kidney disease was lower in the intervention arm (p = 0.05) (RR 0.79 (95% CI 0.63 to 1.00; I² = 10%). These results suggest that finerenone might have an additional protective effect on the cardiovascular and renal systems that is nonexistent with the use of spironolactone and eplerenone.

Funding Acknowledgements Type of funding sources: None. Introduction Hyperkalemia and negative chronotropic drugs are well known causes of reversible bradycardia. Their synergic combination may result in BRASH syndrome (Bradycardia, Renal failure, Atrioventricular blockade, Shock, and Hyperkalemia), a consequence of the vicious cycle between bradycardia, renal failure and worsening hyperkalemia, leading ultimately to multiorgan dysfunction. In potentially reversible bradycardia, drug discontinuation or metabolic correction is recommended before permanent pacemaker (PPM) implantation. Objectives To determine the long-term prognosis in patients with potentially reversible symptomatic bradycardia. Methods We retrospectively reviewed 176 patients who presented to the emergency department with symptomatic bradycardia, between January 2015 and August 2016. Patients without any reversible cause of bradycardia were excluded. Participants were stratified into three groups according to the reversible causes of bradycardia: patients with hyperkalemia, with or without acute renal injury (ARI) (group 1); patients taking negative chronotropic drugs, with or without ARI (group 2); patients with BRASH syndrome (combination of hyperkalemia and negative chronotropic drugs, with or without ARI) (group 3). The primary endpoint was PPM implantation after discharge. Secondary endpoints included: bradycardia-related rehospitalization, heart failure (HF) hospitalization, all-cause mortality and a composite of all the previous endpoints. Results A total of 105 patients were included (52.4% female; mean age 79.8±8.6 years). Group 1 was comprised by 15 patients (14.3%), group 2 by 69 patients (65.7%) and group 3 by 21 patients (20%, figure 1). The incidence of each event is presented in figure 2. During a mean follow-up of 3.2±2.1 years, PPM was implanted in 60 patients (57.1%) – 51 during hospital stay (85%) and 9 after discharge (15%). Across all groups, approximately 50% of the patients needed PPM implantation at some point, without significant differences between groups (p=0.508). Group 3 had the lowest need of in-hospital PPM (38.1%) but the highest bradycardia-related readmissions (9.5%). Nevertheless, post-discharge PPM implantation was still higher in group 1 (33.3%), followed by group 3 (22.2%). There were no significant differences in the post-discharge PPM implantation rate between groups (p=0.76). In groups 1 and 3 the composite endpoint (73.3% and 76.2%, respectively) was significantly more frequent than in group 2 (44.9%, p=0.046 and p=0.012, respectively). Conclusions Nearly half of the patients with an episode of reversible bradycardia needed a PPM at some point. Given the advanced age of most patients with bradycardia secondary to metabolic derangement and/or drug toxicity, it is possible that this unveils underlying conduction system disease, which is likely to recur without PPM implantation.