Non-Cardiac Surgery in Developing Countries: Epidemiological Aspects and Economical Opportunities – The Case of Brazil

Background: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. Methods and Findings: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than$1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near$98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). Conclusion: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.Scholarship Program of Cardiology Society of Sao Paulo (SOCESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

The Ankle-Brachial Index is Associated With Cardiovascular Complications After Noncardiac Surgery

Background: This study evaluated the association of the ankle-brachial index (ABI) and cardiovascular complications after noncardiac surgery. Methods: We prospectively evaluated patients referred for noncardiac surgery. The ABI was performed before surgery. Patients with abnormal ABI (≤0.9) were included in the peripheral artery disease (PAD) group and the remaining constituted the control group. Cardiac troponin and electrocardiogram were obtained 72 hours after surgery. Patients were followed up to 30 days, and primary end point was the occurrence of any cardiovascular event: cardiovascular death, acute coronary syndrome, isolated troponin elevation (ITE), decompensated heart failure, cardiogenic shock, unstable arrhythmias, nonfatal cardiac arrest, pulmonary edema, stroke, or PAD symptoms increase. Results: We evaluated 124 patients (61.3% male; mean age 65.4 years). During the study, 57.9% of patients in the PAD group had an event versus 25.7% in the control group ( P = .011). The ITE was the most observed event (24.2%). After logistic regression, the odds ratio for ITE was 7.4 (95% confidence interval 2.2-25.0, P = .001). Conclusions: In patients submitted to noncardiac surgery, abnormal ABI is associated with a higher occurrence of a cardiovascular event. </jats:sec

Direct comparison of BNP and NT-proBNP for mortality prediction in patients with acute dyspnea

Abstract Background It is unclear whether BNP or NT-proBNP, their admission or discharge measurement or percentage change during hospitalization are preferable for mortality prediction in patients with acute dyspnea. Purpose To directly compare BNP and NT-proBNP regarding their potential in mortality prediction in patients with acute dyspnea and in patients with dyspnea due to AHF. Methods In a prospective multicenter diagnostic study the presence of AHF was centrally adjudicated by two independent cardiologists among patients presenting with acute dyspnea. The levels of BNP and NT-proBNP were measured at presentation and discharge. Patients were stratified according to their natriuretic peptide response (responders vs. non-responders: natriuretic peptide decrease ≥25% vs. &amp;lt;25% before discharge). Prognostic accuracy for 720-day mortality was quantified using the area under the receiver-operating-characteristic curve (AUC). Cox proportional hazard models were constructed to identify significant predictors for 720-day mortality. Results Among 1156 patients presenting with acute dyspnea, 353 (30.5%) died within 720 days of follow-up. Prognostic accuracy for death at 720 days was significantly higher for discharge compared to admission measurements for BNP (AUC 0.750 vs. 0.711, p&amp;lt;0.001) and NT-proBNP (AUC 0.769 vs. 0.720, p&amp;lt;0.001). When directly comparing discharge measurements, NT-proBNP levels exhibited a significantly higher accuracy (p=0.013). 632 (54.6%) and 600 (51.9%) patients were BNP and NT-proBNP non-responders, respectively. Among BNP and NT-proBNP non-responders 202 (32%) and 207 (34.5%) patients died within 720 days of follow-up. After adjusting for common covariates NTproBNP response was the strongest predictor for 720-day mortality in a Cox regression model (Hazard ratio for NT-proBNP non-responders: 2.096 (95% CI 1.550–2.835), p&amp;lt;0.001). Results were confirmed in a sensitivity analysis of 687 (59.4%) patients with adjudicated AHF. Conclusion Percentage change of NT-proBNP during hospitalization seems to be the strongest predictor for long-term mortality in patients with acute dyspnea in general and in those with dyspnea due to AHF in particular. ROC curve for direct comparison Funding Acknowledgement Type of funding source: None </jats:sec

Impact of the period of the day on mortality and major cardiovascular complications after vascular surgeries

Abstract Introduction Patients submitted to arterial vascular surgeries are at a high risk of postoperative cardiac and non-cardiac complications, therefore developing strategies to lower perioperative complications is essential to optimize outcomes for this subgroup. Recent studies have suggested that the period of the day in which surgeries are performed may influence postoperative major cardiovascular complications but there is still no evidence of this association in vascular surgeries. Purpose Our goal is to evaluate whether the period of the day in which surgeries are performed may influence mortality and cardiovascular outcomes in patients undergoing non-cardiac vascular procedures. Methods Patients who underwent non-cardiac vascular surgeries between 2012 and 2018 were prospectively included at our cohort. For this analysis, subjects were categorized into two groups: those who underwent surgery in the morning (7am - 12am) and those who underwent surgery in the afternoon/night (12:01pm - 6:59am). The primary endpoints were to compare the incidence of major adverse cardiac events (MACE - acute myocardial infarction, acute heart failure, arrhythmias, and cardiovascular death) and total mortality between morning and afternoon/night surgeries within 30 days and one year. The secondary endpoint was the incidence of perioperative myocardial injury (PMI) in both groups. PMI was defined as an absolute elevation of high-sensitivity cardiac troponin T (hs-cTnT) concentrations ≥14ng/L. Multivariable analysis using Cox proportional regression (with Hazard Ratio – HR and Confidence Interval – 95% CI) was performed to adjust for confounding variables, including emergency and urgent surgeries. Results Of 1267 patients included, 1002 (79.1%) underwent vascular surgery in the morning and 265 (20.9%) in the afternoon/night. After adjusting for confounding variables, the incidence of MACE at 30 days was higher among those who underwent surgery in the afternoon/night period (37.4% vs 20.4% – HR 1.43, 95% CI: 1.10–1.85; p=0.008). Mortality rates were also elevated in the afternoon/night group (21.5% vs 9.9%, HR 1.59, 95% CI: 1.10–2.29; p=0.013). After one-year of follow-up the worst outcomes persisted in patients operated in the afternoon/night: higher incidence of MACE (37.7% vs 21.2%, HR 1.37, 95% CI: 1.06–1.78; p=0.017) and mortality (35.8% vs 17.6%, HR 1.72, 95% CI 1.31–2.27; p&amp;lt;0.001). There was no significant difference in the incidence of PMI between groups (p=0.8). Conclusions In this group of patients, being operated in the afternoon/night period was independently associated with increased mortality rates and incidence of MACE. Mortality and MACE at one year Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): FAPESP - Fundação de Amparo a Pesquisa do Estado de São Paulo </jats:sec

<i>Burden of Sickle Cell Disease: A Brazilian Societal Perspective Analysis</i>

Introduction: Sickle cell disease (SCD) is a group of inherited disorders that shorten life expectancy. It is estimated that 300,000 children are born with the disease worldwide each year [1,2]. In Brazil is it estimated that 3,500 children are born with SCD each year [3]. The SCD is a multisystem disorder that leads to several complications (acute and chronic) including vaso-occlusive crisis [1,4]. SCD patients experience increase morbidity and mortality, the implications of which are known to impacts the whole society [2]. Although there is some knowledge about the clinical impacts of SCD, little is known about the societal costs. Due to the limited available, to the best of our knowledge there are no similar studies which have been conducted and published. The aim of this study is to estimate SCD societal costs based on a burden of disease model, utilizing the Brazilian societal perspective. Material and Methods: A burden of disease model (Figure 1) was built considering direct medical costs to adults and children and indirect costs, taking into account lost wages due to SCD related morbidity and death. Direct costs were estimated using a bottom-up strategy and micro-costing method, and indirect costs were estimated using a prevalence method. Disability-adjusted life years (DALYs) were calculated from the sum of years of life lost and disability. The rate and duration of SCD related complications (including death) was calculated using information from a Brazilian governmental healthcare public database (DATASUS). The prevalence of each complication was determined by literature data or medical experts. It is important to point that there is some uncertainty around the prevalence estimates. Direct costs for complications were captured from the Brazilian public healthcare system table of procedures and medications (SIGTAP). Indirect costs attributed to productivity loss were calculated using the human capital method. All values were reported in 2020 Brazilian real (BRL). Results: Considering a prevalence of 23.9 cases per 100,000 (50,000 patients in 2018) and a probability of death of 1.11% (560 deaths in 2018), the annual total SCD cost in Brazil was estimated at 1,519,473,501 BRL. Table 1 shows the contribution of the direct and indirect costs to the total cost for the SCD population in Brazil. Further, results were stratified by children and adults (56% and 44%, respectively). Indirect cost was the main driver of disease burden, estimated at 1,128,355,824 BRL. Approximately 40,829 DALYs were lost by SCD patients in 2018 (22,750 and 18,079 among adults and children, respectively). Direct medical costs represented 25.7% of total costs and were estimated at 391,117,677 BRL. Provision of standard of care was the main driver of direct costs in both populations (157,521,597 BRL for adults and 100,133,575 BRL for children). Chronic complication management was shown to be more expensive than acute complication management among adults, while the opposite was observed for children. Vaso-occlusive crisis was the acute complication most frequently observed in available literature and according to medical experts (75.0% among adults and 59.5% among children). Acute chest syndrome had the highest disability weight (0.33). Considering chronic complications, calculous chronic cholecystitis was considered the most frequent among adults (62.0%) and renal abnormalities (without failure) among children (20.0%). Conclusion: SCD patients generate a high economic burden for the Brazilian society greater than one point five billion BRL per year. Most of the cost is related to indirect burden due to increased mortality and morbidity. Investments in technologies and therapies that can decrease the impact of SCD on patients' lives by reducing morbidity and/or mortality are necessary. References: 1. Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, et al. Sickle cell disease. Nat Rev. 2018 Jun 15;4(1):18010. 2. Mburu J, Odame I. Sickle cell disease : Reducing the global disease burden. 2019;41(February):82-8. 3. Carneiro-Proietti ABF, Kelly S, Miranda Teixeira C, Sabino EC, Alencar CS, Capuani L, et al. Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil. Br J Haematol. 2018 Sep;182(6):895-908. 4. Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. Longo DL, editor. N Engl J Med. 2017 Apr 20;376(16):1561-73. Figure 1 Disclosures Pinto: Novartis: Consultancy. Costa:Novartis: Consultancy. Gualandro:Novartis: Consultancy. Fonseca:Novartis: Consultancy. Bueno:Novartis: Current Employment. Cançado:Novartis: Consultancy. </jats:sec

Quantifying inflammation using interleukin-6 for improved phenotyping and risk stratification in acute heart failure

Abstract Background Acute heart failure (AHF) is the most common cause of hospital admission and continues to have unacceptable high rates of mortality and morbidity. In contrast to acute myocardial infarction, the pathophysiology of AHF is incompletely understood and risk-prediction is poorly defined. Aim We aimed to quantify systemic inflammation to assess its possible role in the pathophysiology and risk stratification of patients with AHF. Methods Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/l) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. Plasma concentrations of NT-proBNP (open label) and Interleukin-6 (blinded) were measured at presentation and at discharge. The final diagnosis of AHF and the AHF phenotype were adjudicated by two independent cardiologists. 1-year mortality was the prognostic endpoint. Results Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF. Interleukin-6 concentrations were significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1–26.5] ng/l vs 9.0 [3.2–32.3] ng/l, p&amp;lt;0.0005). Among patients with AHF Interleukin-6 concentrations were elevated (&amp;gt;4.45ng/l) in 83.7% of them. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0–164.2] ng/l) and lowest in patients with hypertensive HF (9.3 [4.8–21.6] ng/l, p=0.001). Inflammation as quantified by Interleukin-6 was a strong predictor of 1-year mortality both in AHF as well as in other causes of acute dyspnea (Figure). During in-hospital treatment Interleukin-6 concentrations significantly decreased in AHF patients. However, changes in the extend of systemic inflammation (delta Interleukin-6) were poorly correlated with changes in hemodynamic stress as quantified by NT-proBNP (delta NT-proBNP, Φc=0.11, p=0.004). Conclusions An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation that can be quantified by Interleukin-6, which seems to contribute to the AHF phenotype and to the risk of death. Kaplan Meier curves for mortality Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation, European Union, Stiftung für kardiovaskuläre Forschung Basel, University of Basel, University Hospital Basel </jats:sec

Direct comparison of the accuracy of preoperative high-sensitivity cardiac troponin T to predict mortality, acute heart failure and perioperative myocardial infarction/injury after non-cardiac surgery

Abstract Background Death, acute heart failure (AHF) and perioperative myocardial infarction/injury (PMI) are the most relevant cardiovascular complications following non-cardiac surgery. Unfortunately, the incidence of these complications are higher than expected. Currently available tools to predict these complications have only modest accuracy. Purpose To determine the accuracy of preoperative high-sensitivity cardiac troponin T (hs-cTnT) concentrations for prediction of mortality, AHF and PMI after non-cardiac surgery. Methods We prospectively included 4,709 patients at high cardiovascular risk undergoing non-cardiac surgery. Hs-cTnT concentrations were measured before surgery and, daily after surgery, for two days. PMI was defined as an absolute increase of 14ng/L (the 99th percentile of the assay used) from hs-cTnT baseline values. The primary endpoint was the diagnostic accuracy of preoperative hs-cTnT concentration to predict death, AHF and PMI within 30 days, as quantified by the area under the receiving-operating curve (AUC). Multivariate logistic regression analysis was performed to test the association between preoperative hs-cTnT and each endpoint. Results All-cause mortality occurred in 133 (3%), AHF in 84 (2%) and PMI in 742 (16%) patients. Preoperative hs-cTnT concentrations had good accuracy for prediction of death, AHF and PMI (AUC = 0.75 [95% CI, 0.71–0.79], 0.72 [95% CI, 0.67–0.77] and 0.73 [95% CI, 0.71–0.75], respectively). After adjusting for confounders, hs-cTnT remained an independent predictor for death with an adjusted odds ratio (aOR) of 2.1 (95% CI, 1.7–2.7, P&amp;lt;0.001) and for PMI (aOR 2.2, 95% CI, 1.9–2.4, P&amp;lt;0.001), but not for AHF (aOR 1.0, 95% CI, 0.7–1.4, P=0.99). An hs-cTnT concentration below 5ng/L was found in 526 (11%) patients, and this cut-off yielded a negative predictive value of 99.6% for the occurrence of death, 99.2% for AHF and 95.6% for PMI. Conclusion The preoperative hs-cTnT concentration has a good accuracy to predict mortality, AHF and PMI after non-cardiac surgery, but is an independent predictor only for mortality and PMI. A cut-off value of 5ng/L identifies a subgroup of patients at low risk for these complications. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Foundation, Swiss Herat Foundation </jats:sec