Even a low comorbidity burden predicts poor outcome in chronic heart failure.

BACKGROUND: Patients with heart failure (HF) often have multiple cardiovascular risk factors (CVRF) and comorbidities (CMB). We evaluated the impact of additive CMB and CVRF in HF prognosis. METHODS: We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up: until January 2021. Endpoint: all-cause death. CVRF analyzed: Arterial hypertension, Diabetes mellitus and smoking. CMB evaluated: coronary artery disease, non-coronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer and atrial fibrillation. Classification according to the number of CVRF and/or CMB: < 2 and ≥ 2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox-regression. RESULTS: Most patients had ≥ 2 CMB (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had one and 32.1% had two. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRF (56.1 vs 43.4% in those with <2) and in those with ≥2 CMB (57.7 vs 31.0%). While patients with one CMB had similar mortality than those with none. Patients with ≥2 CMB had higher long-term mortality risk: HR=2.47 (95% CI: 1.95-3.14). In patients with ≥2CVRF: HR of dying = 1.39 (1.14- 1.70). When taken together there was a clear survival disadvantage for patients with ≥ 2 CVRF/CMB - adjusted HR: 2.20 (1.45-3.34). CONCLUSION: The presence of only 2 CVRF/CMB more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management.

Eosinophilic Colitis, an Uncommon Cause of Diarrhea: Case Report and Literature Review.

Eosinophilic colitis and hypereosinophilic syndrome with colic involvement are rare diagnosis that are characterized by wide-ranging gastrointestinal symptoms and idiopathic infiltration of eosinophils in the colon. The diagnostic workup is challenging since there are no standardized criteria. We report a case of a man admitted to the hospital with a history of nonbloody chronic diarrhea. The detailed workup demonstrated blood eosinophilia, and the colonic biopsies revealed extensive eosinophilic infiltration. He was treated with steroids with clinical and analytical improvement. Due to relapsing colitis after therapy withdrawal, he was chronically medicated with 10 mg of prednisolone with ultimate symptom control. This case report describes the diagnostic workup and highlights the most important features of this often underdiagnosed entity.

A colite eosinofílica e síndrome hipereosinofílico com atingimento gastrointestinal é um diagnóstico raro caracterizado por uma grande variedade de sintomas gastrointestinais e pela evidência de infiltração por eosinófilos na mucosa cólica. A marcha diagnóstica é desafiante dado não haver até à data critérios de diagnóstico. Os autores apresentam um caso de um homem hospitalizado com história de diarreia crónica não sanguinolenta. Durante a investigação etiológica foi identificada eosinofilia periférica e as biópsias cólicas realizadas evidenciaram predominante infiltração eosinofílica. Foi iniciado tratamento com corticoterapia tendo-se verificado normalização da contagem de eosinófilos e resolução do quadro clínico. Dado o carácter recidivante da colite que pode ocorrer com o desmame de corticoterapia, o doente ficou medicado cronicamente com 10 mg de prednisolona. Destaca-se este caso pela sua raridade na literatura de forma a realçar aspetos particulares desta entidade incomum.

Benzodiazepine use and mortality in chronic heart failure.

INTRODUCTION: The prognostic implications of using benzodiazepines (BZD) in heart failure (HF) patients are still unknown. OBJECTIVES: This study aimed to assess the association of BZD use with all­cause death in ambulatory, chronic HF patients. PATIENTS AND METHODS: We investigated a retrospective cohort of ambulatory HF patients with left ventricular systolic dysfunction (LVSD). The patients were followed up from their first medical appointment until January 2021 and all­cause mortality was the primary end point. The Cox regression analysis was used to assess the association between BZD use and all­cause mortality. Subgroup analyses were performed considering age, sex, body mass index (BMI), respiratory disease, chronic kidney disease (CKD), and New York Heart Association (NYHA) class. Multivariable models were built to account for confounders. RESULTS: We studied 854 patients (69% men), of mean (SD) age 71 (13) years, of whom 51% had severe LSVD, and 242 (28.3%) regularly used BZD. During a median follow­up of 46 months, 443 patients (51.9%) died. BZD use predicted no crude survival disadvantage in the entire investigated group and in the subgroup analysis according to sex, respiratory disease, BMI, and NYHA class. BZD use was not mortality­associated among patients aged 75 years and younger. However, in those older than 75 years the hazard ratio (HR) of all­cause death was 1.3 (95% CI, 0.99-1.69; P = 0.06). BZD use seemed safe in the patients without CKD, but in those with CKD it was associated with worse survival (HR, 1.33; 95% CI, 1.02-1.73). In a multivariable­adjusted analysis, the use of BZD was independently associated with increased death risk (HR, 1.36; 95% CI, 1.06-1.75). CONCLUSIONS: The patients medicated with BZD presented a 36% higher risk of dying. BZD should probably be used with caution, particularly in older HF patients and in those with CKD.

CA-125 variation in acute heart failure: a single-centre analysis.

AIMS: A decrease in carbohydrate antigen 125 (CA-125) predicts survival advantage in chronic heart failure (HF); the impact of its variation in acute HF is unknown. We studied the association of CA-125 decrease with prognosis in acute HF. METHODS AND RESULTS: We studied acute hospitalized HF patients. Predictors of admission and discharge CA-125 were determined by linear regression. Follow-up was 1 year; endpoint was all-cause death. The association of admission and discharge CA-125 with mortality was assessed using a Cox-regression analysis. A Cox-regression analysis was also used to assess the prognostic impact of CA-125 decrease during hospitalization. Analysis was stratified by length of hospital stay (LOS). We studied 363 patients, 51.5% male, mean age 75 ± 12 years, 51.5% ischaemic, 30.0% with preserved ejection fraction, and 57.3% with reduced ejection fraction; patients presented elevated comorbidity burden. Median LOS was 7 (5-11) days. In the subgroup of 262 patients with CA-125 measured both at admission and at discharge, we reported a significant increase in its levels: 56.0 (26.0-160.7) U/mL to 74.0 (32.3-195.0) U/mL. Independent predictors of admission CA-125 were higher BNP and lower creatinine. Predictors of discharge CA-125 were higher discharge BNP, lower discharge albumin, and younger age. Both admission and discharge CA-125 predicted mortality. During follow-up, 75 (31.8%) patients died. A decrease in CA-125 predicted a 68% reduction in the 1 year death risk only in patients with LOS > 10 days. CONCLUSIONS: Our results suggest that an early re-evaluation (>10 days) with CA-125 measurement after an acute HF hospitalization may be of interest in patient management.

The prognostic impact of magnesium in acute heart failure is different according to the presence of diabetes mellitus.

Background: Hypermagnesemia predicts mortality in chronic heart failure (HF); however, in acute HF, magnesium does not seem to be outcome-associated. Diabetes mellitus (DM) frequently associates with altered magnesium status. We hypothesized that DM might influence the prognostic impact of magnesium in acute HF. Methods: This is a retrospective cohort study of hospitalized patients with acute HF. Patients without data on admission serum magnesium were excluded. Follow-up: 1 year from hospital admission. Primary end point: all-cause mortality. Patients were divided according to median serum magnesium (1.64 mEq/L). The Kaplan-Meier survival method was used to determine survival curves according to magnesium levels. The analysis was stratified according to the presence of DM. A multivariable Cox regression analysis was used to study the prognostic impact of magnesium. Results: We studied 606 patients. The mean age was 76 ± 12 years, 44.1% were male, 50.7% had DM, and 232 (38.3%) died during follow-up. Median magnesium was 1.64 (1.48-1.79) mEq/L. Patients with magnesium ≥1.64 mEq/L had higher 1-year mortality [141 (46.4%) vs 91 (30.1%), P < .001]. After adjustments for age, sex, history of atrial fibrillation, systolic blood pressure, heart rate, ischemic etiology, B-type natriuretic peptide, estimated glomerular filtration rate, alcohol consumption, antihyperglycaemic agents or glycated hemoglobin, admission glycemia, New York Heart Association class IV, and severe left ventricle systolic dysfunction, serum magnesium ≥1.64 mEq/L was associated with higher mortality only in patients with DM: HR 1.89 (95% confidence interval: 1.19-3.00), P = .007, and 1.27 (95% confidence interval: 0.83-1.94) and P = .26 for non-DM patients. The results were similar if magnesium was analyzed as a continuous variable. Per 0.1 mEq/L increase in magnesium levels, patients with DM had 13% increased risk of 1-year mortality. Conclusions: Higher magnesium levels were associated with worse prognosis only in HF patients with DM.

Cushing's Syndrome Behind Hypokalemia and Severe Infection: A Case Report.

Cushing's syndrome (CS) is a rare condition associated with increased morbidity and mortality. Complications derive from hypercortisolism and are mainly cardiovascular, infectious and thrombotic. Most manifestations are unspecific, and the diagnosis is frequently delayed and made only in the setting of complications. We present a woman in whom CS was investigated because of refractory hypokalemia, hypernatremia and metabolic alkalosis. The patient had many cardiovascular risk factors and was admitted to the hospital due to a serious bacterial infection - muscle abscesses evolving into osteomyelitis. The final etiological diagnosis was not possible because the acute event had a fatal outcome. Immunosuppression associated with hypercortisolism makes these patients predisposed to severe infection. Indeed, infectious complications are a relevant cause of death in CS. Diagnosing and treating CS early is paramount in preventing its dismal complications.

The ratio of furosemide dosage to urinary sodium concentration predicts mortality in patients with chronic stable heart failure.

INTRODUCTION: The urinary sodium (UNa) concentration is associated with outcomes in patients with acute heart failure (HF). Its impact in individuals with chronic HF is unknown. OBJECTIVES: This study examined the combined effect of diuretic dosage and UNa concentration in chronic HF. PATIENTS AND METHODS: The research sample for this retrospective cohort study consisted of ambulatory patients receiving optimized therapy and followed in an HF clinic. The patients were recruited between 2009 and 2012. The exclusion criteria were therapeutic adjustments or hospital admissions in the previous 2 months and renalreplacement therapy. The patients were followed for 5 years; the endpoint was all­cause mortality. The association between the ratio of furosemide dosage to UNa concentration and 5­year mortality was studied using a receiver operating characteristic (ROC) curve. The  patients were cross­classified according to daily furosemide dosage (with the cutoff set at 80 mg) and UNa concentration (80 mEq/l). Multivariable Cox regression analysis was used to assess the prognostic impact of the ratio. RESULTS: We analyzed 283 patients with chronic HF (70.3% male; mean age, 69 years). During follow­up, 134 patients died. The median furosemide dosage was 80 mg/day and the mean UNa concentration was 85 mEq/l. Based on the ROC curve, the best cutoff for the ratio of daily furosemide dosage to UNa concentration was 0.8. Patients with a ratio of 0.8 or higher had an adjusted hazard ratio for 5­year mortality of 2.85 (95% CI, 1.78-4.58). Patients with a UNa excretion rate of less than 80 mEq/l who wereadministered 80 mg or more of furosemide per day were found to have a worse prognosis (HR, 4.15; 95% CI, 2.31-7.45) when compared with those with a UNa excretion rate of 80 mEq/l or more and less than 80 mg furosemide per day. CONCLUSIONS: Combining the diuretic dosage and measurement of UNa excretion can be used to refine risk stratification in chronic HF. The furosemide­to­UNa ratio can be a surrogate marker for diuretic resistance and has a prognostic impact in chronic HF.

The prognostic impact of uric acid in acute heart failure according to coexistence of diabetes mellitus.

BACKGROUND AND AIMS: Increased uric acid levels predict higher mortality in heart failure (HF) patients. Patients with diabetes mellitus (DM) appear to have increased xanthine oxidase activity. We aimed to study if the association between uric acid and mortality in acute HF was different according to the coexistence of DM. METHODS AND RESULTS: We studied a cohort of patients hospitalized due to acute HF in 2009-2010. Patients with no uric acid measurement upon admission were excluded from the analysis. FOLLOW-UP: 2 years; endpoint: all-cause mortality. Patients with elevated uric acid (>80.0 mg/L) were compared with those with lower values. We used a multivariate Cox-regression analysis to assess the prognostic impact of uric acid (both continuous and categorical variable: cut-off 80.0 mg/L). The analysis was stratified according to coexistence of DM. We studied 569 acute HF patients, 44.6%male, mean age 76 years, 290 were diabetic. Median admission uric acid: 81.2 mg/L and 52.2%had uric acid >80.0 mg/L. Elevated uric acid predicted all-cause mortality in acute HF only in patients with DM. The multivariate-adjusted HR of 2-year mortality was 1.68 (95 % CI: 1.15-2.46) for diabetic HF patients with uric acid>80.0 mg/L compared to those with lower levels (p = 0.008) and 1.10 (95 % CI: 1.03-1.18) per each 10 mg/L increase in uric acid (p = 0.007). In non-diabetic HF patients, uric acid was not associated with mortality. CONCLUSIONS: Increased uric acid predicts ominous outcome in acute HF patients with diabetes, however, it is not prognostic associated in non-diabetics. Uric acid may play a different role in acute HF depending on DM status.

Rhabdomyolysis Following Administration of Comirnaty®.

INTRODUCTION: Vaccination against COVID-19 is essential to control the pandemic. The vaccines developed so far have good safety profiles but full knowledge of adverse effects will only be acquired with time and through case reports. CASE DESCRIPTION: We present the case of a man admitted with rhabdomyolysis 3 days after receiving his first dose of the Pfizer coronavirus vaccine Comirnaty® Other traumatic, infectious, endocrine, electrolyte disturbance and autoimmune causes of rhabdomyolysis were excluded. The temporal relationship between vaccine administration and disease onset indicated possible causality. The patient had a favourable evolution after receiving fluids and completely recovered. To our knowledge, there have been only 69 reports of rhabdomyolysis following Comirnaty® administration in Europe, as stated by the European Medicines Agency, and this is the first case report in Portugal. DISCUSSION: When a patient presents with rhabdomyolysis without an obvious traumatic or exertional cause, other aetiologies need to be excluded. Drug use is one of the most common causes of rhabdomyolysis in adults. CONCLUSION: We present a case compatible with an adverse effect of Comirnaty® in order to raise awareness of this condition in vaccinated patients. LEARNING POINTS: Rhabdomyolysis is frequently due to pharmacological causes.COVID-19 vaccines are safe but their adverse effects have not yet been fully elucidated and more case reporting would be beneficial.Rhabdomyolysis secondary to administration the Pfizer anti-COVID-19 vaccine Comirnaty® can be a severe adverse effect and should be considered in the relevant clinical scenario.

Glucose variability predicts 6-month mortality in patients hospitalized with acute heart failure.

In diabetes mellitus (DM), glycaemic fluctuations associate with higher oxidative stress than sustained chronic hyperglycaemia and glucose variability increases the risk of chronic diabetic complications. Our hypothesis was that higher glucose variability would associate with mortality after an acute heart failure (HF) episode. We retrospectively analysed patients with DM hospitalized with acute HF between 2009 and 2010. Patients with < 2 point-of-care glucose values/day were excluded. Glucose coefficient of variation (GCV) was defined as (glucose standard deviation/mean glucose) × 100. Patients were categorized according GCV ≤ 30.0 and > 30.0%. Follow-up: 6-months. Endpoint: all-cause mortality. A Cox-regression analysis was used to study the association of glucose variability with 6-month mortality. We studied 214 diabetic patients with acute HF, 49.1% male, mean age 76 years. Mean glycaemia during hospitalization was 187 ± 50 mg/dL, hypoglycaemia (< 70 mg/dL) was reported in 21 patients and mean GCV was 28.3 ± 7.6%. Patients with GCV > 30.0% had higher mean glycaemia, more hypoglycaemic episodes and higher HbA1c; they were also more often treated with insulin. Patients were similar concerning age, gender, comorbidities, left ventricular systolic dysfunction and ischemic heart disease. During the 6-month follow-up, 38 (17.8%) patients died. Patients with GCV > 30.0% had a HR of 6-month mortality of 2.21 (95% CI: 1.16-4.21), p = 0.02. This association with more than twofold higher short-term mortality was independent of main confounders. Elevated glycaemic variability in acute HF admissions of patients with DM predicts short-term mortality. Patients with GCV > 30.0% have an independent more than twofold higher risk of 6-month death after an acute HF hospitalization.

The Influence of Gender in The Prognostic Impact of Diabetes mellitus in acute Pulmonary Embolism.

Diabetes mellitus (DM) predicts ominous outcomes in acute pulmonary embolism (PE). The influence of gender on the prognostic impact of DM in PE is unknown. We did a retrospective analysis of a cohort of patients hospitalized with PE between 2006 and 2013. The exclusion criteria were age <18, non-pulmonary veins thromboembolism, recurrent PE, chronic thromboembolic pulmonary hypertension, no radiologic confirmation of PE, and active neoplasia. The primary endpoint was all-cause mortality. The follow-up was from diagnosis until October 2017. We assessed the prognostic impact of DM using a multivariate Cox regression analysis. The analysis was stratified according to gender. The interaction between gender and DM in the outcome of patients with PE was tested. We studied 577 PE patients (median age 65 years, 36.9% men, 19.8% diabetic). The genders were similar regarding the prevalence of DM, the extension and location of PE, and the thrombolytic therapy or brain natriuretic peptide (BNP) value. Diabetics presented higher all-cause mortality (Hazard ratio (HR) = 2.33 (95% confidence Interval (CI) 1.513.61)) when compared with non-diabetics. However, when analysis was stratified according to gender, DM was independently associated with a worse prognosis only in women (HR = 2.31 (95% CI 1.453.65)), while in men the HR was 1.10 (95% CI 0.592.04). The interaction between gender and DM was significant (p = 0.04). Gender influences the prognostic impact of DM in acute PE. Diabetic women with PE have twice the long-term mortality risk, while DM is not mortality-associated in men.