Serelaxin: insights into its haemodynamic, biochemical, and clinical effects in acute heart failure

Treatment for acute heart failure (AHF) has not changed much in the last two decades.1 Intravenous drugs such as levosimendan, nesiritide, rolofylline and tezosentan have been studied in phase III randomized controlled trials (RCTs) with disappointing results. None of these drugs improved dyspnoea, worsening heart failure, readmissions to the hospital, cardiovascular mortality or all-cause mortality in AHF patients, mostly in the short-term follow-up.1 These drugs increased the probability of ventricular and atrial arrhythmias or symptomatic hypotension (levosimendan, nesiritide), or seizures and strokes (rolofylline). Ularitide, a novel natriuretic peptide, is undergoing a phase III RCT focused on symptoms and cardiovascular mortality. Several reasons for negative results are possible, including high heterogeneity of patients with AHF, several sources of bias in RCTs, scarcity of outcomes, and incomplete pre-clinical evaluation of drugs.
Authors: Hernandez, Adrian V.
Source: European Heart Journal
URL: http://hdl.handle.net/10757/322408

Global kidney disease

We read with interest the Lancet Series on Global Kidney Disease. Valerie Luyckx and colleagues describe the economics and medical management of chronic kidney disease in sub-Saharan Africa.1 We note clear similarities with patients in Peru. Indeed, in Peru, the Ministry of Health (MINSA)—which covers 70% of the population—does not have a comprehensive programme for the management of patients with chronic kidney disease, including renal replacement therapies. However, the Social Security System (Essalud)—which covers 20% of the population—has a chronic kidney disease programme.
Authors: Herrera Anazco, Percy; Mezones Holguin, Edward; Hernandez, Adrian V.
Source:  The Lancet

URL: http://hdl.handle.net/10757/322401

Inferior vena cava filters and postoperative outcomes in patients undergoing bariatric surgery: a meta-analysis

Background: Pulmonary embolism (PE) accounts for almost 40% of perioperative deaths after bariatric surgery. Placement of prophylactic inferior vena cava (IVC) filter before bariatric surgery to improve outcomes has shown varied results. We performed a meta-analysis to evaluate postoperative outcomes associated with the preoperative placement of IVC filters in these patients. Methods: A systematic review was conducted by three investigators independently in PubMed, EMBASE, the Web of Science and Scopus until February 28, 2013. Our search was restricted to studies in adult patients undergoing bariatric surgery with and without IVC filters. Primary outcomes were postoperative deep vein thrombosis (DVT), pulmonary embolism (PE), and postoperative mortality. Meta-analysis used random effects models to account for heterogeneity, and Sidik-Jonkman method to account for scarcity of outcomes and studies. Associations are shown as Relative Risks (RR) and 95% Confidence Intervals (CI). Results: Seven observational studies were identified (n=102,767), with weighted average incidences of DVT (0.9%), PE (1.6%), and mortality (1.0%) for a follow-up ranging from 3 weeks to 3 months. Use of IVC filters was associated with an approximately 3-fold higher risk of DVT and death that was nominally significant for the former outcome, but not the latter (RR 2.81, 95%CI 1.33-5.97, p=0.007; and RR 3.27, 95% CI 0.78-13.64, p=0.1, respectively); there was no difference in the risk of PE (RR 1.02, 95%CI 0.31-3.77, p=0.9). Moderate to high heterogeneity of effects was noted across studies. Conclusions: Placement of IVC filter before bariatric surgery is associated with higher risk of postoperative DVT and mortality. A similar risk of PE in patients with and without IVC filter placement cannot exclude a benefit, given the potential large imbalance in risk at baseline. Randomized trials are needed before IVC placement can be recommended.
Authors: Kaw, Roop; Pasupuleti, Vinay; Overby, D.Wayne; Deshpande, Abhishek; Craig I. Coleman Pharm; John P.A. Ioannidis;Hernandez, Adrian V.
Source: Surgery for Obesity and Related Diseases

URL: http://hdl.handle.net/10757/320268

Incidence, Predictors, and Impact on Survival of Left Ventricular Systolic Dysfunction and Recovery in Advanced Cancer Patients

Although left ventricular (LV) dysfunction occurs not uncommonly in the course of cancer therapy, little is known about its natural history and prognostic impact on patients. To investigate the incidence, predictors, and impact on survival of LV systolic dysfunction and recovery during cancer therapy, we conducted a retrospective cohort observational study over 1 year at the University of Texas MD Anderson Cancer Center. We enrolled patients with a decrease in ejection fraction by echocardiography to <50% while undergoing cancer therapy from January 2009 to December 2009.We collected and analyzed their chart data. Of 7,648 patients with echocardiograms in 2009, 366 (4.8%) had ejection fraction <50% and 104 met study criteria. LV systolic dysfunction was associated with cardiotoxic therapy in 53 patients (51%). Recovery occurred in 57 patients (55%) and was independently predicted by younger age, smaller left atrial volume index, and lower B-type natriuretic peptide. At last follow-up, 69 patients (66%) were dead, and 35 (34%) were alive. There was a 20% advantage in 2-year survival among patients with LV systolic recovery compared with those without (95% confidence interval 4% to 41%, p [ 0.02). In this retrospective study, LV systolic dysfunction recovery occurred in over half of the patients, appeared independent of cardiotoxic etiology, and associated with a 20% survival benefit at 2 years. Multivariable predictors of recovery are younger age, a small left atrial volume index, and lower B-type natriuretic peptide.
Authors: Oliveira, Guilherme H.; Mukerji, Siddarth; Hernandez, Adrian V.; Qattan, Marwan Y.; Banchs, Jose; Durand, Jean-Bernard;Iliescu, Cezar; Plana, Juan Carlos; Tang, W.H. Wilson
Source:  American Journal of Cardiology

URL:  http://hdl.handle.net/10757/320254

Association between Insulin Resistance and Breast Carcinoma: A Systematic Review and Meta-Analysis

Objective: This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. Study Design: We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. Results: Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD 20.03, 95%CI 20.32 to 0.27; p = 0.9). Similarly, non-fasting/ fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, 20.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMAIR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p, 0.00001). Conclusions: Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.
Authors: Hernandez, Adrian V.; Guarnizo, Mirella; Miranda, Yony; Pasupuleti, Vinay; Deshpande, Abhishek; Paico, Socorro; Lenti, Hosten; Ganoza, Silvia; Montalvo, Laritza; Thota, Priyaleela; Lazaro, Herbert
Source:  Public Library of Science (PLoS)

URL:  http://hdl.handle.net/10757/320267