Polypharmacy and cumulative anticholinergic burden in older adults hospitalized with fall.

Introduction: Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. Methods: A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Key Results: Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug-related orthostatic hypotension, 24.7% had drug-related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Conclusion: Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Role of open access echocardiography in detection of cardiac structural and functional abnormalities.

PURPOSE: To evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist. DESIGN: Data were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4-6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves. RESULTS: Echocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses. CONCLUSION: Major structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Role of open access echocardiography in detection of cardiac structural and functional abnormalities.

PURPOSE: To evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist. DESIGN: Data were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4-6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves. RESULTS: Echocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses. CONCLUSION: Major structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Comparison of the Effect of Sacubitril/Valsartan on Left Ventricular Systolic Function in Patients with Non-ischaemic and Ischaemic Cardiomyopathy.

PURPOSE: Sacubitril/valsartan has been demonstrated to improve prognosis and outcomes in heart failure with reduced ejection fraction (HFrEF) patients. We sought to compare the improvement in cardiac function between non-ischaemic and ischaemic cardiomyopathy for patients receiving sacubitril/valsartan. METHODS: We conducted a single centre prospective cohort survey of patients reviewed in the Heart Function Clinic between February 2017 and January 2018. Functional evaluation and measurement of biochemical and echocardiographic parameters occurred before the initiation of sacubitril/valsartan, and after 3 months of treatment. RESULTS: We identified 52 patients (26 non-ischaemic and 26 ischaemic cardiomyopathy) suitable for treatment with sacubitril/valsartan. Treatment was followed by a significant decrease in a New York Heart Association (NYHA) class in both patients with non-ischaemic (2.3 ± 0.6 vs. 1.6 ± 0.7, P < 0.001) and ischaemic cardiomyopathy (2.3 ± 0.5 vs. 1.5 ± 0.6, P < 0.001), along with an increase in ejection fraction in both patients with non-ischaemic (26.2% ± 6.5% vs. 37.2% ± 13.8%, P < 0.001) and ischaemic cardiomyopathy (28.1% ± 5.7% vs. 31.5% ± 8.4%, P = 0.007). The improvement in ejection fraction was significantly greater in the patients with non-ischaemic cardiomyopathy compared to those with ischaemic cardiomyopathy (10.7% ± 13.0% vs. 3.9% ± 6.0%, P = 0.023). CONCLUSION: Our study suggests that treatment with sacubitril/valsartan in patients with non-ischaemic cardiomyopathy is followed by a greater improvement in ejection fraction than in patients with ischaemic cardiomyopathy.

Sepsis Unmasking Fahr's Disease.

Fahr's disease is a sporadic or familial neurodegenerative disorder characterized by symmetrical calcification of cerebral structures, particularly the basal ganglia, cerebellar dentate nuclei and surrounding white matter, in the absence of metabolic causes of calcification. We report the case of a previously fit, high functioning 58-year-old man who developed catastrophic irreversible neuropsychiatric collapse after sepsis despite appropriate antimicrobial treatment. Cranial computed tomography revealed extensive diffuse calcifications located in unusual areas. Laboratory studies excluded the presence of other pathologic processes leading to secondary intracranial calcification and a multigene panel failed to confirm mutations in the genes currently known to be associated with the disorder, supporting a diagnosis of sporadic Fahr's disease or idiopathic brain calcification. Important diagnostic considerations in the septic patient who develops neurological complications, namely sepsis-associated encephalopathy and antibiotic-associated encephalopathy, are discussed. The patient remains severely handicapped 6 months after the acute event. Patients with clinically silent neurodegenerative/neuropsychiatric conditions, such as Fahr's disease, may present with florid and unpredicted neurological features in the context of systemic illness.

A Syndrome of Apparent Renal Failure.

Pseudo-azotemia is the syndrome of hypercreatininemia and hyperkaliemia without a change in glomerular filtration rate or structure of the kidney. A 57-year-old vulnerable woman with learning difficulties experienced an intraperitoneal bladder rupture in the absence of a pelvic fracture after a fall. It is suspected that the blunt force compression of a distended bladder situated above the bony protection of the pelvis resulted in delayed intraperitoneal bladder rupture. Urinary ascites resulted in pseudo-azotemia because of urinary creatinine reabsorption across the peritoneum. This "apparent" renal failure is fully reversible when diagnosis and treatment are prompt, with normalization of abnormal laboratory-investigation results often within 24 hours.

Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice.

PURPOSE OF THE STUDY: Iron deficiency anaemia (IDA) is associated with increased morbidity and mortality in heart failure patients. The aim of our audit was to evaluate the current practice in diagnosis and assessment of IDA in patients admitted with heart failure. STUDY DESIGN: We conducted a retrospective audit of patients admitted to our hospital between January 2017 and June 2017 with a diagnosis of heart failure, and obtained data regarding each patient's demographics and anaemic status. We also conducted a qualitative survey to assess healthcare professionals' ability to diagnose IDA, and their knowledge of iron replacement in heart failure patients. RESULTS: Our audit identified 218 heart failure patients, nearly two-thirds (n=138, 63.3%) of which were anaemic. Of the 138 anaemic patients, only 40 had a full haematinic screen compared with 98 who had incomplete investigations (29% vs 71%, p=0.007). Iron studies were the most commonly performed haematinic investigation (n=87, 63%), and over half of these patients were iron deficient (n=49, 56.3%). Only 12 (24.5%) iron deficient patients were prescribed oral iron therapy, while 37 (75.5%) were left without iron replacement (X2=12.8, p=0.0003). Our survey demonstrated a lack of awareness among healthcare professionals with only 19.7% of participants being able to correctly define anaemia and 9.1% being aware of guidelines regarding treatment of IDA. CONCLUSION: Many patients admitted to hospital with heart failure also have a concomitant diagnosis of anaemia. The aetiology of the underlying anaemia is often poorly investigated, and where IDA is identified it is poorly treated.

Plasma N-terminal pro-B-type natriuretic peptide (BNP) in mesalazine-induced myopericarditis.

Mesalazine (5-aminosalicylic acid)-based products are a widely used treatment for inflammatory bowel disease in children and adults. Associated myopericarditis is an uncommon but recorded phenomenon related to drug hypersensitivity. Unless recognised, this important complication may culminate in the development of dilated cardiomyopathy and severe heart failure. We report the case of a boy with Crohn's disease who developed myopericarditis 14 days after starting treatment with mesalazine. Discontinuation of the drug rapidly led to normalisation of left ventricular structure and function, and a parallel improvement in the levels of plasma N-terminal pro-B-type natriuretic peptide and other markers of myocardial damage. Clinicians should be aware of this potentially life-threatening adverse effect of mesalazine therapy, which is quickly and fully reversible on cessation of the agent.

Complete Regression of Primary Cardiac Lymphoma With Dose-Attenuated R-CVP Chemotherapeutic Regimen.

An elderly man was found to have a large right atrioventricular mass and pericardial effusion. He was diagnosed and treated as having primary cardiac lymphoma. A dose-attenuated chemotherapy regimen of rituximab, cyclophosphamide, vincristine, and prednisolone, with a cytoreductive pre-phase, afforded complete regression of disease with resolution of the patient's symptoms, and without deterioration in cardiac function or immunosuppression. The patient remains well 12 months after presentation. (Level of Difficulty: Advanced.).

Pericardial Cyst: Never Too Late to Diagnose.

Pericardial cysts are uncommon benign lesions of the middle mediastinum, making up less than 6% of all mediastinal masses. They are often detected as incidental findings on chest imaging and some can resolve spontaneously. Rarely, however, they may cause symptoms of chest pain, right ventricular outflow obstruction, and persistent cough. Furthermore, they may affect cardiac tamponade after acute rupture or cyst haemorrhage resulting in sudden death. We report the case of a 102-year-old woman presenting with urosepsis, in whom routine chest radiography was initially suspicious of advanced bronchial carcinoma. Further imaging supported a diagnosis of one of the largest pericardial cysts described in the literature located in the right parahilar space. The patient was appropriately managed conservatively.

Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival.

OBJECTIVES: The aim of this study was to comprehensively delineate iron metabolism and its implications in patients with chronic heart failure (CHF). BACKGROUND: Iron deficiency is an emerging therapeutic target in CHF. METHODS: Iron and clinical indexes were quantified in 157 patients with CHF. RESULTS: Several observations were made. First, iron homeostasis was deranged in anemic and nonanemic subjects and characterized by diminished circulating (transferrin saturation) and functional (mean cell hemoglobin concentration) iron status in the face of seemingly adequate stores (ferritin). Second, while iron overload and elevated iron stores were rare (1%), iron deficiency (transferrin saturation <20%) was evident in 43% of patients. Third, disordered iron homeostasis related closely to worsening inflammation and disease severity and strongly predicted lower hemoglobin levels independently of age, sex, erythrocyte sedimentation rate, New York Heart Association (NYHA) functional class, and creatinine. Fourth, the etiologies of anemia varied with disease severity, with an iron-deficient substrate (anemia of chronic disease and/or iron-deficiency anemia) evident in 16%, 72%, and 100% of anemic NYHA functional class I or II, III, and IV patients, respectively. Although anemia of chronic disease was more prevalent than iron-deficiency anemia, both conditions coexisted in 17% of subjects. Fifth, iron deficiency was associated with lower peak oxygen consumption and higher ratios of ventilation to carbon dioxide production and identified those at enhanced risk for death (hazard ratio: 3.38; 95% confidence interval: 1.48 to 7.72; p = 0.004) independently of hemoglobin. Nonanemic iron-deficient patients had a 2-fold greater risk for death than anemic iron-replete subjects. CONCLUSIONS: Disordered iron homeostasis in patients with CHF relates to impaired exercise capacity and survival and appears prognostically more ominous than anemia.

Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial.

OBJECTIVES: We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency. BACKGROUND: Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance. METHODS: We randomized 35 patients with CHF (age 64 +/- 13 years, peak oxygen consumption [pVO2] 14.0 +/- 2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/ml, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dl [anemic group] vs. 12.5 to 14.5 g/dl [nonanemic group]). The observer-blinded primary end point was the change in absolute pVO2. RESULTS: The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p < 0.0001), 0.1 (-0.8 to 0.9) g/dl for hemoglobin (p = 0.9), 96 (-12 to 205) ml/min for absolute pVO2 (p = 0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg (p = 0.01), 60 (-6 to 126) s for treadmill exercise duration (p = 0.08), -0.6 (-0.9 to -0.2) for New York Heart Association (NYHA) functional class (p = 0.007), and 1.7 (0.7 to 2.6) for patient global assessment (p = 0.002). In anemic patients (n = 18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute pVO2 (p = 0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p = 0.01). In nonanemic patients, NYHA functional class improved (p = 0.06). Adverse events were similar. CONCLUSIONS: Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).