Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

Carbon monoxide (CO) poisoning is one of the most common types of poisoning and the leading cause of death by poisoning worldwide. Cardiac injury caused by CO poisoning has been little described despite being a predictor of poor prognosis. We present the case of a healthy 24-year-old woman, admitted to our emergency room due to an episode of lipothymia without loss of consciousness. She reported holocranial headache for the previous two weeks associated with nausea and vomiting. Laboratory tests revealed blood gas analysis: pH 7.392, pCO2 32 mmHg, pO2 101 mmHg, lactate 3.5 mmol/l, HCO3 20.8 mmol/l; COHb 29.2%; serial troponin I 1.21 → 5.25 → 6.13 → 3.65 μg/l; myoglobin 1378 → 964 → 352 μg/l; and NT-proBNP 1330 pg/l. The electrocardiogram showed sinus rhythm, heart rate 110 bpm, and ST-segment depression of 2 mm in V4 and 1 mm in V5. Transthoracic echocardiography revealed a left ventricle with normal wall motion and preserved ejection fraction. Given the clinical and epidemiological context, myocardial and central nervous system ischemia due to prolonged CO exposure was assumed and normobaric oxygen therapy was immediately started. In view of evidence of injury to two major organ systems the indication for hyperbaric oxygen therapy was discussed with a specialist colleague, who suggested maintaining conservative treatment with oxygen therapy and in-hospital monitoring for 72 h. The patient was discharged on the third day and was still asymptomatic at 400 days of follow-up. Besides symptoms and signs of central nervous system dysfunction, myocardial damage should also always be considered in the context of CO poisoning. Hyperbaric therapy is still controversial and the lack of objective data highlights the need for new randomized studies.

Hypercalcaemia is an emergency with severe consequences. Dehydration can be an uncommon cause of hypercalcaemia, as seen in this case. A 63-year-old woman with type 2 diabetes mellitus, hypothyroidism and osteoporosis, was admitted to the emergency room with abdominal distension and vomiting for 24 h. Initial evaluation was Hg 18.5 g/dL, Htc 56.2%, creatinine 2 mg/dL, metabolic acidaemia, lactate 8.3 mmol/L, anion gap 19, total Ca(2+) 17.7 mg/dL and PO4+ 6.6 mg/dL. CT revealed colonic distension without obstruction or ischaemia. Renal replacement therapy and pamidronate were initiated. The patient's clinical condition deteriorated with septic shock in the context of toxic megacolon and she underwent an emergency subtotal colectomy (10 kg). Hypercalcaemia was corrected in 24 h with aggressive fluid replacement (8 L NaCl 0.9% first 12 h), with a reduction of total Ca(2+) to 8.2 mg/dL. Other causes of hypercalcaemia were excluded. 'Hypercalcaemic crisis' secondary to severe acute dehydration is not mentioned in the literature.

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Objective To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

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Background: Severe metformin-associated lactic acidosis (MALA) is a rare but potentially fatal side effect of metformin. The clinical presentation is often unspecific, thus hindering early recognition. We aimed to assess the prevalence of MALA in an intensive care unit (ICU) and describe the demographic and clinical characteristics according to patient outcome. Methods:We conducted a 13-year single-center retrospective study, including all patients admitted in ICU with a high anion-gap metabolic acidosis and hyperlactatemia secondary to therapeutic use of metformin, after excluding other medical causes of acidosis.Results: Twenty one patients were admitted in ICU due to severe MALA (less than 1% of all admissions) with an ICU mortality rate of 23.8% (N=5). The baseline clinical characteristics were similar in survivors and nonsurvivors, both with a high prevalence of cardiovascular comorbidities as well as frequent concomitant therapy with angiotensin-converting-enzyme inhibitors and diuretics. All patients were treated with continuous renal replacement therapy (CRRT) and other organ failure support. Normal acid-base balance was achieved in all survivors in the first 24 hours. At baseline, the clinical and laboratory features of nonsurvivors were undistinguishable from survivors. Conclusions:Severe MALA is a rare cause of admission in the ICU.Although early institution of supportive therapy, MALA can progress to severe multiple-organ failure, especially when diagnosis and CRRT are delayed. Clinicians should suspect of MALA in all diabetic patients taking metformin with unexplained high anion-gap metabolic acidosis and hyperlactatemia.