Prognostic impact of neurohormonal modulation in very old patients with chronic heart failure.

BACKGROUND: A gap in evidence exists concerning the survival-benefit of neurohormonal blockade in older patients with chronic heart failure (HF). The purpose of our study was to investigate the neurohormonal modulation therapy in older HF patients. METHODS: We retrospectively analysed data on chronic HF patients with systolic dysfunction from January 2012 to May 2018 at a central tertiary academic hospital in Porto, Portugal. Very old (VO) patients were those ≥80 years. Endpoint under analysis: all-cause mortality; patients were followed until January 2021. The prognostic impact of beta-blockers (BBs) and renin-angiotensin system inhibitors (RASi) use was assessed with a Cox-regression analysis adjusting for confounders. RESULTS: We studied 934 patients, 65.5% male; 45.3% had ischemic HF. BBs were used in 92.2% and RASi in 83.5%; 255 (27.3%) were VO patients. VO more often presented co-morbidities, were more symptomatic, presented worse renal function and higher BNP levels. BB prescription was similar in VO and non-VO patients, however RASi were less used in VO: 74.9% versus 86.7%, respectively. During a median follow-up of 47 months, 479 (51.3%) patients died: 71.4% among VO versus 43.7% in non-VO. BBs increased survival both in non-VO and VO-multivariate adjusted HRs of 0.57 (95% CI: 0.38-0.85) and 0.59 (0.36-0.97), respectively. A survival-benefit was also observed with RASi-adjusted HR of 0.71 (0.50-1.01) and 0.59 (0.42-0.83) in non-VO and VO. CONCLUSIONS: VO patients with chronic HF with systolic dysfunction have a very ominous outcome. Neurohormonal modulation therapy appears to portend survival-benefit also in this particularly vulnerable subgroup of patients.

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.

Predictors of severity and in-hospital mortality in patients with influenza.

Influenza virus is a common agent of acute respiratoty infections during epidemic periods. It is a major cause of morbidity and mortality and represent a significant burden on the healthcare system. We aimed to evaluate predictors of severity and of in-hospital mortality in patients hospitalized with influenza infection. We performed a retrospective cohort study of hospitalized, laboratory confirmed cases of influenza disease in Centro Hospitalar de São João between October 2016-May 2017 and October 2017-May 2018. The endpoints being analysed were severity and in-hospital mortality. A multivariate logistic regression analysis was used to determine independent predictors of severity and of in-hospital mortality. We studied 221 hospitalized influenza infection cases. Mean age 66±16 years, 57.9% were male, thirty-seven patients (16.7%) died in-hospital and 101 patients (45.7%) met severity criteria. C-reactive protein (CRP) was the only independent predictor of severity as well as the only independent predictor of higher in-hospital mortality in patients admitted due to influenza infection. Multivariate-adjusted CRP OR for severity was 1.10, 95% CI 1.06-1.15 per each 10 mg/L increase in CPR and for in-hospital mortality risk the OR was of 1.05, 95% CI 1.01-1.09, p=0.01, per each 10 mg/L increase. Concluding, in patients' hospital-admitted due to influenza infection CRP was the only predictor of severity with a 10% increased risk of inotropic support/ventilatory support/prolonged hospitalization needs and a 5% increase risk of in-hospital death per each 10 mg/l increase.

Is there a C-reactive protein value beyond which one should consider infection as the cause of acute heart failure?

BACKGROUND: Heart Failure (HF) is a low grade inflammatory condition. High sensitivity C-reactive protein (hsCRP) is an established marker of inflammation. A cut-off value of hsCRP beyond which an infection should be sought has never been studied in HF. We aimed to determine the best hsCRP cut-off for infection prediction in acute HF. METHODS: We analyzed patients included in an acute HF registry - EDIFICA (Estratificação de Doentes com InsuFIciência Cardíaca Aguda). Admission hsCRP measurement was available as part of the registry's protocol. Patients with acute coronary syndrome as the cause of acute HF were excluded from the registry. Infection was considered according to the diagnosis registered in the discharge record. A receiver-operating characteristic (ROC) curve was used to determine the best hsCRP cut-off for infection prediction. RESULTS: We studied 615 patients. Mean age was 76 years, 45.2% were male, 60.3% had systolic dysfunction. Median admission hsCRP was 20.3 (9.5-55.5)mg/L; in 41.6% the cause of decompensation was an infection. The area under the ROC curve for admission hsCRP in the prediction of infection was 0.79 (0.76-0.83); the best hsCRP cut-off was 25 mg/L with a sensitivity of 72.7%, specificity 77.2%, positive predictive value 69.4% and negative predictive value 79.9%. Age and elevated hsCRP independently associated with an infection as the precipitant of acute HF. CONCLUSIONS: We suggest 25 mg/L as a cut-off beyond which an infection should be sought underlying acute HF. Almost 80% of the patients with hsCRP< 25 mg/L are not infected and 69.4% of those with higher hsCRP have a concomitant infection.

Prognostic Effect of the Dose of Loop Diuretic Over 5 Years in Chronic Heart Failure.

BACKGROUND: High diuretic doses in chronic heart failure (HF) are potentially deleterious. We assessed the effect of dynamic furosemide dose on all-cause mortality among HF ambulatory patients. METHODS AND RESULTS: A cohort of 560 ambulatory patients from an outpatient clinic specialized in HF, with median age 70 years, 67% male, and 89% with moderate-severely reduced ejection fraction, was retrospectively followed for up to 5 years. Dynamic furosamide exposure was categorized as low (0-59 mg/d), medium (60-119 mg/d), high (120-159 mg/d), and very high (≥160 mg/d). Extended Cox models were used to estimate the association between time-varying diuretic dose and mortality. A dose-dependent crude association between higher doses of furosemide and death (hazard ratio [HR] = 1.34, 95% confidence interval (CI): 1.06-2.16; HR = 2.09, 95% CI: 1.54-2.84, for high and very high dose, respectively) was totally explained by patients' characteristics and disease severity indicators (adjusted HR = 0.94, 95% CI: 0.63-1.38; HR = 1.10, 95% CI: 0.79-1.55, for high and very high dose, respectively). CONCLUSION: In this context, higher doses of diuretic did not impair survival, but rather indicated greater severity of the patient's condition.

Prognostic prediction in acute heart failure patients with extreme BNP values.

BACKGROUND: Some patients have good prognosis despite elevated B-type natriuretic peptide (BNP), while others have ominous outcome with low BNP. We aimed at characterising these groups of patients. METHODS: We analysed patients prospectively included in an acute HF registry. Vital status within 1-year post discharge was ascertained. A receiver-operating characteristic curve was used to define discharge BNP cut-offs for 1-year death prediction. Among survivors, we compared patients with low and not-low BNP (cut-off 400 pg/mL); and among non-survivors those with high vs not-high BNP (cut-off 2000 pg/mL). In the specific subgroups of patients with low and high BNP, mortality predictors were assessed with multivariate Cox-regression analysis. RESULTS: We studied 584 patients, median age 78 years, 62.5% had HF with reduced ejection fraction; and 199 (34.1%) died during the first year. Non-survivors were very homogeneous irrespective of BNP, survivors were substantially different. In patients discharged with BNP <400 pg/mL, increasing age independently predicted death; when BNP ≥2000 pg/mL death predictors were higher NYHA class, and non-use of evidence-based therapy. BNP was outcome associated in both groups. CONCLUSIONS: Different prognostic predictors may play a role in different BNP levels. We suggest that risk stratification in HF would probably be more accurate if made on top of BNP knowledge.

Quality of nutritional uptake of community-dwelling, care-dependent older adults in Zurich.

OBJECTIVE: This study evaluated the quality of nutritional uptake of the care-dependent, community-dwelling older adults. METHODS: Community-dwelling care-dependent elders were recruited in this study. The food items along with their nutritional content were extracted from the participants' refrigerators and categorized according to the NOVA classification (G1: unprocessed/minimally processed; G2: processed culinary ingredients; G3: processed; G4: ultra-processed). The nutritional information of the food items was entered into a dietary analysis software that analyzed the content. Data was verified for a normal distribution and non-parametric tests were applied for statistical analysis (p < 0.05). RESULTS: 100 subjects (mean age = 81.1±9.5 y; mean MMSE: 26.6±6.8) participated in this study. The participants had significantly more G1 than G2, G3 or G4 (p < 0.001) foods. Women had more G1 items in their refrigerators than men (rs = 0.372, p < 0.001). Higher socio-economic status indicated a presence of more G1 (rs = 0.313, p = 0.002), G2 (rs = 0.342, p < 0.001) and G4 (rs = 0.237, p = 0.024) foods. Higher cognitive scores revealed an increase in presence of G4 (rs = 0.238, p = 0.023) items. Participants with an increased need for assistance had less G2 (rs = -0.332, p = 0.001), and G4 (rs = -0.215, p = 0.041) foods; age had no influence. CONCLUSION: The findings of this study confirm that the majority of care-dependent, community-dwelling adults procured healthy dietary aliments for their daily living; however, whether this correlated to the actual nutritional state of these older adults needs to be further investigated. This highlights the need for further investigation and tailored interventions to ensure good nutrition, emphasizing regular assessments and comprehensive support beyond just food access. CLINICAL RELEVANCE: Clinicians must recognize that access to healthy food alone may not ensure good nutrition in older adults. Regular nutritional assessments, personalized dietary interventions, and additional support services like meal preparation assistance, nutritional counseling, and tailored programs are essential to address specific dietary needs and preferences.

Oral health and nutritional status in care-dependent, community-dwelling older adults in Zurich, Switzerland.

The aim of this study was to assess the oral health status (OHS), Oral health impact profile (OHIP-G-14), and the nutritional status (NS) in community-dwelling, dependent older adults. Information on OHS including DMF(T), plaque (PI) and gingival (GI) indices, community-periodontal-index-for-treatment-needs (CPITN), OHIP-G-14, maximum bite force (MBF), chewing efficiency [subjective (SA) and quantitative (VoH) assessments] were collected. NS was obtained by Mini-nutritional assessment (MNA) and body mass index (BMI). Cognitive status was evaluated by the mini-mental state examination (MMSE). 240 elders (mean-age = 81.5 ± 8.9y; men =85, women =155) were recruited. Average number of teeth, functional occlusal units and DMF(T), were 18.8 ± 8.9, 7.7 ± 3.5, and 22.3 ± 5.3 respectively. Mean PI, GI, CPITN and OHIP-G-14 were 1.8 ± 0.8, 1.2 ± 0.8, 1.9 ± 1.1, and 8.0 ± 12.0, respectively. MBF, VoH, SA were 219.6 ± 193.6, 0.3 ± 0.2, and 3.3 ± 1.4, respectively. MNA and BMI were 22.9 ± 4.7 and 25.5 ± 5.3, respectively. Number of teeth reduced significantly with age (P < 0.001), cognitive decline (P < 0.001). Oral hygiene significantly deteriorated with cognitive decline (P < 0.001). OHIP scores were negatively affected by increasing cognitive decline (P < 0.001). MNA deteriorated in women (P = 0.026), with increasing age (P = 0.015), and advancing cognitive decline (P < 0.001). BMI reduced with advancing age (P = 0.003) and in women (P = 0.016). Based on the findings of this study, it may be concluded that advancing age and cognitive decline, negatively impacted the oral health, oral function, oral health-related quality of life, and the nutritional state of care-dependent community-dwelling older adults.

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.

Prognostic association of circulating relaxin-2 in acute heart failure.

BACKGROUND: Despite the increasing interest in the study of the endogenous relaxin system in heart failure (HF), its role as a prognostic marker in acute HF remains unclear. We aimed to evaluate the association of relaxin-2 circulating levels with 6 months' mortality in acute HF. METHODS: We evaluated relaxin-2 serum levels at admission in a cohort of patients with acute HF (n = 202) using an enzyme immunoassay. The ability of relaxin-2 to predict all-cause death (primary outcome) and HF-specific death (secondary outcome) at 6 months was assessed using Cox-regression analysis. RESULTS: The median age was 79 (70-85) years old, 44% of the patients were male, and 43% had preserved ejection fraction (≥50%). Median serum relaxin-2 level was 25 pg/mL. Patients with higher relaxin-2 levels had more peripheral oedemas, higher sodium retention score, higher pulmonary artery pressures, higher prevalence of right ventricle dysfunction and lower inferior vena cava collapse at inspiration. Conversely, there was no association with left chambers parameters or with B-type natriuretic peptide (BNP). Higher relaxin-2 concentrations were associated with a higher risk of all-cause death [HR 1.15; 95%CI 1.01,1.30; P = 0.030] and HF-specific death [HR 1.21; 95% CI 1.03-1.42; P = 0.018], after adjustment for classical prognostic factors such as age, sex and BNP. CONCLUSIONS: In our acute HF population, relaxin-2 circulating levels were associated with clinical and echocardiographic markers of systemic congestion and with 6-months' mortality, independently of BNP. These results lay the groundwork for future investigations on the potential of relaxin-2 as an auxiliary biomarker in HF.

Dipeptidyl peptidase IV and mortality after an acute heart failure episode.

BACKGROUND: Dipeptidyl peptidase IV (DPP IV) is a key enzyme in B-type natriuretic peptide processing. DPP IV was never studied in human heart failure (HF). We aimed to measure DPP IV concentration in acute HF and determine its association with mortality. METHODS AND RESULTS: Patients hospitalized with acute HF were eligible. We excluded patients with acute coronary syndromes. A discharge blood sample was collected from all patients and they were followed for a 6-month period. Outcome was HF death. Patients were compared across DPP IV quartiles. A Cox regression analysis was used to assess the prognostic power of DPP IV. We studied 164 patients. Median age was 78 years, 48.8% were men, and 63 had type 2 diabetes and 59.1% had left ventricular systolic dysfunction. Quartiles of DPP IV were <215.2; ≥ 215.2 and <269.3; ≥ 269.3 and <348.6; and ≥ 348.6 ng/mL; groups were homogenous between them. Seventeen patients died. Patients with DPP IV in the last quartile had a hazard ratio of HF death up to 6 months of 2.89, 95% confidence interval, 1.11-7.46. Association was B-type natriuretic peptide independent. CONCLUSIONS: Discharge DPP IV ≥ 348.6 ng/mL conferred an approximately 3-fold higher risk of 6-month HF death. Further studies would be important to understand the role of DPP IV in HF.

Low stress hyperglycemia ratio predicts worse prognosis in diabetic acute heart failure patients.

INTRODUCTION: Acute blood glucose but not glycated hemoglobin (HbA1c) predicts poor outcome in acute heart failure (HF). The stress hyperglycemia ratio (SHR) has been proposed as a prognostic predictor in various clinical settings. OBJECTIVES: We assessed the prognostic implications of the SHR in acute HF patients with and without diabetes. METHODS: We performed a retrospective analysis of an acute HF registry conducted between 2009 and 2010. Estimated average glucose (eAG) was calculated as (28.7×HbA1c)-46.7 and SHR as acute blood glucose divided by eAG. The primary endpoint was all-cause mortality. Follow-up was three months. Patients were grouped by SHR tertiles (≤0.88, 0.89-1.16, and >1.16). Cox regression analysis was used to test the association of SHR (cut-off 0.88) with all-cause mortality. Analysis was stratified according to the presence of diabetes. Multivariate models were built accounting for acute blood glucose and for eAG (models 1 and 2, respectively). RESULTS: We studied 599 patients, mean age 76±12 years, of whom 62.1% had reduced ejection fraction and 50.9% had diabetes. Median acute blood glucose, eAG and SHR were 136 (107-182) mg/dl, 131 (117-151) mg/dl, and 1.02 (0.20-3.34), respectively. During follow-up 102 (17.0%) died. In patients with diabetes, those in the lowest SHR tertile had a hazard ratio (HR) of 2.24 (95% CI: 1.05-5.22) (model 1) and 2.34 (1.25-4.38) (model 2). In patients without diabetes, the HR of three-month death in the lowest SHR tertile was 0.71 (95% CI: 0.36-1.39) and 1.02 (0.58-1.81). Significant interaction was observed between diabetes and SHR. CONCLUSIONS: In HF patients with diabetes, a SHR ≤0.88 was associated with a more than twofold higher three-month mortality risk. No such association was found in non-diabetic patients. The presence of diabetes influences the association of the SHR with mortality.

Prognostic impact of red blood cell distribution width in chronic heart failure patients with left ventricular dysfunction.

AIMS: Red blood cell (RBC) distribution width (RDW) measures RBC variations in size. Higher RDW values have been associated with poor outcome in acute heart failure (HF). We aimed to assess the prognostic impact of the RDW in chronic HF. METHODS: We retrospectively analysed a cohort of chronic HF patients with left ventricular systolic dysfunction followed in our HF clinic between January 2012 and May 2018. Patients with missing data concerning RDW were excluded. Patients were categorized according to RDW tertiles: ≤13.5%; between 13.5 and 14.7%; and >14.7%. Patients were followed until January 2021; all-cause mortality was the end point analysed. The association of RDW with all-cause mortality was assessed with a Cox-regression analysis. Two multivariate models were built. RESULTS: We studied 860 chronic HF patients, 66.4% males, mean age 70 (standard deviation, SD 13) years. Patients were followed for a median of 49 (29-82) months. During this period, 423 (49.2%) patients died. Mortality increased with increasing RDW tertiles. Patients with RDW >14.7% had a HR of mortality of 1.95 (1.47-2.58), p < 0.001 (model 1) and of 1.81 (1.35-2.41), p < 0.001 (model 2) when compared with those with RDW ≤13.5. Patients in the second RDW tertile had an all-cause death HR of 1.47 (1.12-1.93) and of 1.44 (1.09-1.90) in models 1 and 2, respectively. CONCLUSIONS: Chronic HF patients with RDW values >14.7% presented an almost 2-fold higher risk of dying in the long term than those with RDW <13.5%. RDW is a widely available and easily measured parameter that can help clinicians in the risk stratification of chronic HF patients.

Predictors of cancer in patients with acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) can occur as a manifestation of an underlying cancer and be of paraneoplastic aetiology. A previously unknown cancer is sometimes diagnosed after the acute PE diagnosis. The identification of a group of patients with elevated probability of having an occult cancer underlying PE was never performed. We aimed to determine predictors of occult cancer in acute PE. Our hypothesis was that the D-dimer levels would be a predictor of cancer. PATIENTS AND METHODS: We retrospectively analysed a cohort of patients hospitalized with acute PE. EXCLUSION CRITERIA: <18 years, venous embolism only of veins other than pulmonary territory or when the embolism was considered chronic, and no image confirmation of acute PE. Patients were grouped according to the timing of cancer diagnosis: 1) known concomitant active cancer, 2) cancer diagnosed during acute PE admission or in the following 2 years and, 3) no known cancer during the 2-year follow-up since PE diagnosis. Predictors of concomitant cancer were determined using a logistic regression analysis. Multivariate models were built. RESULTS: We studied 562 patients; median age was 72 years and 219 (39.0 %) were men. In 223 (39.7 %) of the patients the PE was of central arteries and 61.4 % presented with bilateral PE. PE was considered unprovoked at time of discharge in 47.7 %. Median (interquartile range) D-dimer level was 7.98 (3.30-14.99) µg/mL. A total of 126 (22.4 %) patients were in group 1, 47 in group 2 (cancer diagnosed after the diagnosis of acute PE and up to 2 years) and 389 patients were in group 3. Elevated D-dimer levels were independently associated with already known cancer. D-dimer were independent predictors of future cancer diagnosis: OR = 1.07 ((95 % CI: 1.01-1.14) per each 5 ng/mL increase; for patients with D-dimer >15.0 µg/mL the OR of future cancer was 2.10 (1.05-4.18). If only patients with unprovoked PE upon admission (n = 307) were to be considered results were similar considering D-dimer; anaemia also predicted unknown cancer [OR = 2.13 (1.08-4.16)]. CONCLUSIONS: Patients with D-dimer >15 µg/mL presented a >2-fold higher risk of being diagnosed with a cancer condition in the upcoming 2 years. D-dimer may help clinicians in identifying which patients are at higher risk of occult cancer.

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.

Influence of weight variation on long-term mortality of patients with heart failure.

BACKGROUND: In heart failure, weight loss predicts dismal prognosis. Weight variations have not been addressed in obese patients with heart failure. AIM: To study the impact of weight variation on heart failure mortality according to body mass index strata. METHODS: Retrospective study of patients with chronic heart failure with left ventricular ejection fraction<50%. Only patients with ≥1 year of follow-up were included. Patients with missing data for body mass index at the index and 1-year appointments were excluded. Patients were classified into three groups according to weight variation: weight gain>5%; weight loss>5%; and weight stability. Follow-up was set from the 1-year appointment. Cox-regression analysis was used to assess the prognostic impact of weight variation. RESULTS: We studied 589 patients: 69.8% male; mean age, 69 years. Over 1 year, 148 patients (25.1%) gained>5% weight, 97 (16.5%) lost>5% weight and the remaining 344 were weight-stable. During 49 months of median follow-up, 248 patients died. Patients who lost>5% of their weight presented a higher death risk than the others (hazard ratio 1.61, 95% confidence interval 1.18-2.19). After multivariable adjustment, the hazard ratio for death for low/normal-weight patients who lost>5% of their weight was 1.81 (95% confidence interval 1.02-3.21; P=0.04) compared with the others. Among the overweight, those who lost>5% of their weight had a hazard ratio of 2.34 (95% confidence interval 1.32-4.12). In the initially obese subgroup, weight loss>5% was not associated with prognosis (hazard ratio 1.08, 95% confidence interval 0.53-2.19). CONCLUSIONS: Weight loss predicted mortality in low/normal-weight and overweight patients with heart failure. However, in obese patients, significant weight loss did not predict poorer survival. Weight loss should not be discouraged in obese patients with heart failure.

Acute Kidney Injury Requiring Dialysis in McArdle Disease: A Case Report of a Rarely Seen Presentation.

McArdle disease is a genetic disorder that leads to impaired glycogenolysis in the muscle, resulting in exercise intolerance, fatigue, myalgias, and basal elevation of creatine kinase (CK). We report a case of a young woman with McArdle disease who had an episode of acute kidney injury (AKI) requiring temporary hemodialysis (HD), with subsequent complete recovery of renal function. We aim to report a rare clinical presentation of an already rare disease and discuss the possible causes involved; therefore, contributing to a better knowledge of the disease.

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.

Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia Syndrome due to Amlodipine: A Case Report of an Underdiagnosed Medical Condition.

We report the case of an 89-year-old female patient who presented to the emergency department with BRASH syndrome, an acronym that stands for bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia, which is an underdiagnosed and recently described clinical entity. Contrary to either hyperkalemia or atrioventricular nodal blockade alone, this syndrome represents the synergistic combination of both together, creating a vicious cycle. Conservative treatment of each component, avoiding invasive measures like dialysis or pacing, usually leads to complete resolution. Recognizing the existence of this syndrome is important for an integrative approach and to avoid its recurrence. The association between BRASH syndrome and amlodipine, a dihydropyridine calcium channel blocker, is not commonly described in literature.

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.