Giulia Cernuschi

To anticoagulate or not to anticoagulate? That is the question: A Medline-based quantitative approach to share evidence on common clinical problems

Mr. P.C., an 81-year-old man, was admitted to our hospital for worsening of anemia of unknown origin (hemoglobin 7 g/dl, while the previous value was 10 g/dl 4 months earlier, recent negative gastroduodenoscopy and colonoscopy) and congestive heart failure. The medical history was significant for permanent atrial fibrillation, hypertension, ischemic stroke, peptic ulcer disease 10 years before and chronic renal failure (serum creatinine 2 mg/dl). The patient’s medication included warfarin, atorvastatin, omeprazole, amlodipine, furosemide and lorazepam. Considering the worsening of anemia on one hand and atrial fibrillation and comorbid conditions on the other, the clinical dilemma was to continue warfarin, to substitute warfarin with an antiplatelet drug such as aspirin or withdraw warfarin without taking any antithrombotic therapy [1]. How could we know which one is the best choice (Fig. 1)? Dr. Costantino First of all, we have to estimate the risk of cardio-embolic stroke in Mr. P.C., considering atrial fibrillation and the additional risk factors. In order to answer this question, I performed a search on PubMed to find a clinical risk score that was validated and userfriendly. The key words for this search were: [(scale) OR (rule) OR (risk prediction) OR (score)] AND (atrial fibrillation) AND (stroke). Every term was searched as text word or Medical Subject Headings (MeSH). 572 results were retrieved. I tried to limit to systematic reviews, but I obtained only 21 results, none of which regarded the validation of a clinical score. 572 results were then analyzed. Among them 16 were about the validation of at least one clinical risk score. 14 considered CHADS2 score, 2 CHADSVASC score, 2 NICE scale, 2 ACCP scale [1–16]. I decided to use the CHADS2 score [2] that is the most commonly used and validated score, granting a good prediction of the risk of cardio-embolic stroke in single patients. Moreover Poli et al. [11] have compared different risk scores and CHADS2 was the most accurate. This stroke risk scheme is based on five risk factors, assigning to each of them a score (1 point for Congestive heart failure, Hypertension, Age, Diabetes, 2 points for previous Stroke or transient ischemic attack). A CHADS2 score between 0 and 6 is computed for each patient, and a high score corresponds to a greater annual risk of stroke, while a low score corresponds to a lower annual risk of stroke. In our patient the result of the score was 5, and it was associated with an estimated annual risk of 12.5 % without antithrombotic therapy. Such a high risk virtually excludes the no antithrombotic therapy option (Table 1). Dr. Podda An integral part of anticoagulation treatment decision-making is the estimation of the risk of bleeding in a patient on anticoagulants, with iron deficiency anemia and other risk factors. I performed a search on PubMed similar to the previous one, to find a hemorrhagic prediction clinical score that could be applied to our patient. The keywords for my search were: (anticoagulants) AND [(scale) OR (rule) OR (risk prediction) OR (score)] On behalf of Gruppo di Autoformazione Metodologica (GrAM).

Eplerenone, an aldosterone antagonist, reduces hospitalization and death in heart failure patients with nyha class II and an ejection fraction of less than 30%

BackgroundThe renin-angiotensin-aldosterone system (RAAS) playsan important role in pathophysiology of heart failure (HF).RAAS blockade with angiotensin converting (ACE)inhibitor slows the progression of HF and improves thesurvival [1]. However, ACE inhibitors do not block themineralocorticoid receptors, which are usually overexpressed in patients with heart failure, and promote car-diac fibrosis in experimental models [2]. The latter hasbeen confirmed by clinical trials that show a reduction inmortality and hospitalization of patients with severe heartfailure in New York Heart Association class III–IV(NYHA III–IV) treated with spironolactone [3], or inpatients after a myocardial infarction complicated by areduced systolic function treated with eplerenone [4].Thus, it is reasonable to suppose that the use of aldoste-rone antagonists might also delay the progression of heartfailure in patients with mild failure symptoms (NYHA II).SummaryThe Eplerenone in Mild Patients Hospitalization and Sur-vival Study in Heart Failure (EMPHASIS-HF) trial [5]randomized 2,737 patients aged more than 55 years withNYHA II heart failure and an ejection fraction of not morethan 35%, to receive either eplerenone (up to 50 mg daily)or placebo, in addition to recommended therapy. The pri-mary outcome was a composite of death from cardiovas-cular causes or a first hospitalization for heart failure. Deathand hospitalization for any cause were secondary outcomes.The trial was planned to last 48 months, but it wasstopped prematurely, after a median follow-up period of21 months, because of an overwhelming benefit in theeplerenone group. The primary outcome occurred in 18.3%of patients in the eplerenone group as compared with25.9% in the placebo group (hazard ratio, 0.63, 95% con-fidence interval (CI), 0.54–0.74, P\0.001). A total of12.5% of patients receiving eplerenone and 15.5% of thosereceiving placebo died (hazard ratio, 0.76, 95% CI,0.62–0.93, P = 0.008); hospitalizations for heart failureand any other cause were also reduced with eplerenone.Among adverse events, only hyperkalemia showed a sig-nificant difference between the two groups: serum potas-sium level exceeding 5.5 mmol per litre occurred in 11.8%of patients in the eplerenone group and in 7.2% of those inthe placebo group (P\0.001). The estimated number ofpatients who would need to be treated to prevent one pri-mary outcome per year was 19 (95% CI 15–27), and theestimated number needed to treat to postpone one death peryear, was 51 (95% CI 32–180).Strength of the study– It addresses a relevant clinical issue (it’s the first trialconducted among the patients in class NYHA II).– Rationale of the study: there is a strong pathophysio-logic background for the utility of aldosterone antag-onists in heart failure patients, and the previous studyalready confirms this observation [3, 4];

Is magnetic resonance safe in implanted cardiac devices patients

Nazarian et al. [1] evaluate in a prospective non-randomized trial the safety of a 1.5 T MRI protocol for patients with implanted cardiac devices (ICD and PM). 438 participants (54 % with PM and 46 % with ICD implanted, respectively,after the 1998 and 2000) were enrolled and underwent 555MRI examinations. Patients with a recent implant(\6 weeks), those with abandoned or epicardiac leads, and PM-dependent patients with an ICD were excluded.According to the experimental protocol, an asynchronous pacing mode (VOO/DOO) was programmed in the pacemaker-dependent patients, while an inhibited pacing mode(VVI/DDI) was used for the other patients. The ICD function of non-PM-dependent patients was disabled. During the MRI examination, blood pressure, electrocardiography, pulse oximetry and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had an immediate backup from an electrophysiologist.Device variables including sensing, impedance, capture threshold and battery voltage were evaluated before MRI examination, immediately after MRI and after 3–6 months.Variations exceeding 30, 40 and 50 %for, respectively, lead impedance, sensing and capture threshold were considered as significant changes in lead performance.Baseline and immediate follow-up interrogations were performed in all 438. Long-term follow-up device variables were available for 266 patients (61 %). 3 of 438 patients(0.7 %) experienced acute power-on-reset events. None of them had device dysfunction during long-term follow-up(3–6 months). Right ventricular sensing and atrial, right and left ventricular impedances were reduced immediately after MRI. At long-term follow-up in 61 % of the patients,decreased right ventricular (RV) sensing and lead impedance,increased RV capture threshold and decreased battery voltage were noted. The observed changes did not require device revision or reprogramming. The distributions of changes in device variables were within the 20 % at baseline for most participants. Thoracic MRI sequences had a greater effect on device variables and were more likely to result in artifacts (for instance, image distortion,signal voids or bright areas and poor fat suppression).

Diagnostic accuracy of transthoracic echocardiography to identify native valve infective endocarditis: a systematic review and meta-analysis

Infective endocarditis (IE) is a serious and potentially life-threatening disease, and accurate diagnosis is essential. We performed a systematic review and meta-analysis to assess the diagnostic accuracy of transthoracic echocardiography (TTE), with transesophageal echocardiography (TEE) as the reference standard, in patients with suspected IE of the native valves. We performed a systematic search in MEDLINE, EMBASE and Cochrane Library searching for studies that enrolled adult patients with suspected native valves IE where data about both TTE and TEE could be extracted. We included 11 studies, for a total of 2209 patients. The overall sensitivity, specificity, negative and positive likelihood ratios (LR) of TTE are 0.71 (95% CI 0.56–0.82), 0.80 (95% CI 0.58–0.92), 0.37 (95% CI 0.20–0.68) and 3.56 (95% CI 1.3–9.72), respectively. The subgroup analyses of the studies considering different cut-off levels show that the strict negative criteria (i.e., managing indeterminate results as positive) have the highest sensitivity and the lowest LR−. On the contrary, when managing indeterminate results as negative (standard criteria), the specificity and LR+ are the highest. We observed no differences between the studies performed with older and more recent technologies. In conclusion, our study results support the use of a negative TTE as a single rule-out test in patients with a low pre-test probability. In selected cases, the use of strict negative criteria might exclude IE in intermediate-risk patients, and a positive TTE might be considered as a single rule-in test with no need for TEE if TEE results would not change the patient’s management.

Adjunct prednisone therapy for patients with community-acquired pneumonia

Pneumonia is one of the principal causes of morbidity and mortality worldwide, despite the advances in antibiotic therapies and in preventive measures [1]. The intense inflammatory response that was of fundamental importance in the pre-antibiotics era nowadays might be excessive. In fact, it can lead to multiple organ failure, thus causing more harm than benefit [2]. Corticosteroids have a strong antiinflammatory effect; therefore, their use in pneumonia has been studied for a long time. One of the most important trials was recently published by Meijvis [3]. A 4-day course of 5 mg of dexamethasone was compared to placebo, showing a 1-day reduction in hospital stay, but no difference in mortality. A meta-analysis by Nie [4] does not find any significant reduction in pneumonia overall mortality; however, a subgroup analysis shows a significant reduction in mortality in both studies considering patients with severe pneumonias and treating subjects for more than 5 days. Therefore, the authors conclude that adequately powered double-blind randomized controlled trials (RCTs) are warranted to give recommendations for the use of steroids in pneumonia. Summary

Would apixaban be a good option for extended anticoagulation in venous thromboembolism

The treatment and the long-term management of deep vein thrombosis and pulmonary embolism are a delicate challenging topic. A thoughtful evaluation is warranted to balance the possible risks and benefits of antithrombotic therapy. While there is evidence that anticoagulation can be discontinued after 3 months in most of the patients who experience thromboembolism provoked by precise risk factors [1], conclusive data are still lacking concerning the best treatment regimen for patients with unprovoked venous thromboembolism (VTE), which has a higher rate of recurrence [2]. Some trials address the issue of the possible use in these patients of new anticoagulants, which might be valid alternatives to warfarin due to similar efficacy and administration in fixed doses, without the need for laboratory monitoring. Apixaban is an oral factor Xa inhibitor, which has already been shown to be useful for the prevention of stroke in patients with atrial fibrillation (at a dose of 5 mg twice daily) [3] and for thromboprophylaxis after major orthopedic surgery (at a lower dose of 2.5 mg twice daily) [4]. Summary