Surgery for acute infective endocarditis: epidemiological data from a Spanish nationwide hospital-based registry

Surgery for acute infective endocarditis: epidemiological data from a Spanish nationwide... Abstract OBJECTIVES Infective endocarditis (IE) is a serious and eventually lethal disease with rising incidence in the past couple of decades. The aim of this study was to evaluate the contemporary epidemiological trends of surgical endocarditis patients, to analyse the clinical outcomes and to study their profile, associated prognostic factors and costs. METHODS This is a retrospective study of all patients admitted for IE in Spanish hospitals and discharged between 1 January 1997 and 31 December 2014. Data were extracted from the minimum basic data set of the National Surveillance System for Hospital Data in Spain provided by the Spanish Ministry of Health. Hospitalizations, comorbidities, outcomes and costs were analysed. RESULTS In total, 34 399 patients with IE were included; 15.7% of patients received surgical treatment and 84.3% received medical treatment only. Surgical patients were mostly men (71.9%) and had a lower mean age (59.2 ± 16.08 years) than the medical treatment group (P < 0.0001). Mortality among surgical patients showed a decreasing trend between 1997 (32.0%) and 2014 (22.7%) and increased with age (47.6% in ≥85 years of age). Length of hospital stay and the percentage of patients with organ dysfunction were also higher in this group. The cost of the surgical treatment group was higher and increased since 1997 (15 259.22 euros), remaining stable from 2010 (40 700 euros) (P < 0.0001). CONCLUSIONS Surgical treatment in IE has trended upwards in Spain during the last 2 decades. Patients are getting older and more frequently experience organ dysfunction. Mortality ratio steadily declined without changes in the length of hospital stay. Infective endocarditis, Epidemiology, Cardiac surgery, Mortality, Costs INTRODUCTION Infective endocarditis (IE) is an uncommon disease with a poor prognosis with rising incidence in the past couple of decades. The most recent epidemiological study reports an incidence of 3–10 cases per 100 000 persons/year [1–8]. The prognosis has not improved despite the improvements in the diagnosis and treatment, and nowadays, mortality rate remains high in spite of recent medical and surgical advances. Mortality is 15–50% depending on the series [7, 9–11], and this is probably due to an increase in microbiological resistance, comorbidities and association with healthcare [1, 2, 12]. The latest guidelines of the European Society of Cardiology (ESC) endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) on IE contemplate the management of IE by the endocarditis team. An appropriate team approach aims at reducing antimicrobials and surgery. In some cases, as peripheral aneurysms, percutaneous approaches are required [13–15]. Surgical treatment (ST) is performed in diverse proportions according to different studies. One possible explanation includes sample sizes, lack of homogeneity and different study designs. Surgical indications are well defined in the guidelines, and the main indication for surgery is heart failure [3, 5, 6, 16, 17]. Surgery is a part of an effective treatment in IE and provides good results in the short term, medium term and long term. Different studies analyse the impact of early surgery on outcomes. Case–control studies and a single randomized study aimed to elucidate this. However, heterogeneity is an issue and makes the interpretation of results difficult [18–20]. Epidemiological studies have some limitations but are useful for the understanding of the history of the disease. There is scarce information on the epidemiology of the ST of EI in Spain. The aim of this study was to define the current profile of IE, the need for ST and analyse the cost of surgery. METHODS Study design This is a retrospective study of all patients admitted for IE in hospitals in Spain and were discharged between 1 January 1997 and 31 December 2014. Data collection Data were extracted from the basic minimum data set (BMDS) of the National Surveillance System for Hospital Data in Spain provided by the Spanish Ministry of Health [in Spanish ‘Conjunto Minimo Basico de Datos’ (CMBD)]. The BMDS (also called national registry of hospital discharges) is the largest database of clinical data on hospitalized patients in the country and the most important source of treated morbidity data [21]. BMDS provides valuable although limited information on multiple healthcare-related topics. Informed consent was waived as this is a retrospective study based on public data. Data collected from the BMDS were encoded to avoid duplicity and were dissociated from any information that could uncover the identity of the patients. The minimum basic data set provides the encrypted patient identification number, gender, date of birth, dates of hospital admission and discharge, medical institutions providing the services, the diagnosis and procedure codes according to the International Classification of Diseases 9th edition, Clinical Modification (ICD-9-CM) and the outcome at discharge [22]. Case identification Cases were identified using the ICD-9CM code for IE (421, acute and subacute endocarditis) among the discharges between 1 January 1997 and 31 December 2014. All Spanish hospitals record the ICD-9CM codes for the main diagnosis and comorbidities of each patient on BMDS (see Supplementary Material, Appendix A1–A4). Demographic data (sex and age), presence of comorbidities, associated organ dysfunction, Charlson’s index and mortality data were extracted from the minimum basic data set. The study period was arbitrarily divided into calendar years and 4 calendar periods (1997–1999, 2000–2004, 2005–2009 and 2010–2014). The primary end point was ST. Secondary end points were length of hospital stay (LOHS), years of potential life lost and cost related to endocarditis. We divided the study sample into 2 groups: patients undergoing ST and non-surgical (NS). Mortality by years and periods was calculated to understand the trends. We analysed the correlation between age and type of treatment as well as the mortality between groups. LOHS was calculated as the number of days from admission (Day 0) to discharge or death at any time during the treatment. When patients were admitted and discharged the same day, 1 day of stay was assigned. Mean stay was estimated for the total group and separately by survival, year, type of treatment and age. Costs were calculated by diagnosis-related group, which classifies inpatients into groups based on their diagnosis and attributes a specific hospital cost to each group. Diagnosis-related group data were extracted from the minimum basic data set. All costs shown were adjusted for the increment of the inflation in the same period in Spain. Statistical analysis Categorical variables are expressed as absolute and relative (%) frequencies, and continuous variables were expressed as the mean and standard deviation. Differences between groups were compared using the t-test with continuous variables and using the χ2 test or Fisher’s exact test with categorical variables. Statistical significance was established as P ≤ 0.05. Incidence and mortality rates were calculated for patients with a diagnosis of IE by year (1997–2014), which allowed assessing tendencies during the study period. The incidence and mortality associated with IE were calculated by year and by age group, for the total group, the ST and NS groups and by gender. Therefore, age- and gender-adjusted analysis of incidence and mortality were performed. The number of events within each calendar year was used as a numerator, and the number of persons at risk within each calendar year as the denominator [the number of persons registered in the census of Spain (National Statistics Institute; http://www.ine.es/)]. All statistical procedures were performed using the SPSS 21.0 software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY, USA: IBM Corp.). RESULTS Patient characteristics From 1997 to 2014, 34 399 IE patients were diagnosed in Spain. The incidence per 100 000 inhabitants was 3.17% in 1997 and 5.56% in 2014. It was more prevalent in men. ST was performed in 5414 (15.7%) patients and medical treatment in 28 985 (84.3%). Patients who underwent ST were younger (59.2 ± 16.08 years ST and 62.3 ± 18.8 years NS, P < 0.0001), had less comorbidities and a lower Charlson index (1.00 ± 1.13 ST and 1.14 ± 1.41 NS, P < 0.0001), with more organ dysfunction, mainly renal failure (27.6%). Mortality in the ST group was higher (26.0% ST vs 20.1% NS). ST patients had a 30-day readmission rate lower than the NS patients (10.4% ST vs 20.0% NS) (Table 1). Table 1: Clinical, epidemiological and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Values are expressed as absolute n (%) and mean ± standard deviation. DM: diabetes mellitus. Table 1: Clinical, epidemiological and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Values are expressed as absolute n (%) and mean ± standard deviation. DM: diabetes mellitus. The percentage of patients who underwent ST increased from 11.7% in 1997 to 17.8% in 2014; P < 0.05 (Fig. 1A). In all age groups, ST was less frequent. In 2 age groups, slightly above mean percentages were observed: in children younger than 5 years (17.3%) and in patients aged between 45 (20.7%) and 64 (21.3%) years (Fig. 1B). The NS patients were significantly older and had more comorbidities than ST patients. There was also a trend towards a higher incidence of New York Heart Association (NYHA) Class IV and congestive heart failure among ST patients (Table 2). The most common micro-organisms involved were Gram-negative bacilli (340; 6.3%), followed by Gram-positive cocci (313; 5.8%), fungi (44; 0.8%) and anaerobes (8; 0.1%). Table 2: Epidemiological, clinical and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment in Spain during 1997–2014 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) Values are expressed as absolute n (%) and mean ± standard deviation. a Percentage calculated based on the total cases of endocarditis in each period of time. DM: diabetes mellitus. Table 2: Epidemiological, clinical and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment in Spain during 1997–2014 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) Values are expressed as absolute n (%) and mean ± standard deviation. a Percentage calculated based on the total cases of endocarditis in each period of time. DM: diabetes mellitus. Figure 1: View largeDownload slide Percentage of patients with infective endocarditis, who were operated and not operated and mortality in Spain from 1997 to 2014. (A) Evolution over time, (B) evolution by age, (C) evolution of mortality and (D) mortality by age. Figure 1: View largeDownload slide Percentage of patients with infective endocarditis, who were operated and not operated and mortality in Spain from 1997 to 2014. (A) Evolution over time, (B) evolution by age, (C) evolution of mortality and (D) mortality by age. Overall mortality was higher in the surgical group (surgical 26.0% vs NS 20.1%). During the study, there was a decrease in mortality in the surgical group (32.7% in 1997 to 22.0% in 2014) (Fig. 1C). Although mortality in the NS group increased slightly (14.9% in 1997 to 21.1% in 2014). Another relevant issue was that the mortality of patients undergoing surgery increased with age, reaching 47.6% in those older than 85 years (Fig. 1D). Evolution of length of hospital stay and cost of patients with infective endocarditis The mean length of hospital stay during the study increased slightly in the surgical group (37.5 days in 1997 to 40.1 days in 2014) when compared with a decrease in the medical treatment group (27.2 days in 1997 to 23.1 days in 2014) (Fig. 2A). The mean length of stay was higher in the surgical group, with the highest being observed in the group of children younger than 5 years (57.6 days ST) (Fig. 2B). Figure 2: View largeDownload slide Evolution of length of hospital stay and cost of patients with infective endocarditis, who were operated on and not operated in Spain between 1997 and 2014. (A) Mean length of hospital stay per patient for surgical treatment and non-surgical treatment by study period, (B) mean length of hospital stay per patient for surgical treatment and non-surgical treatment by age group, (C) mean cost per patient for surgical treatment and non-surgical treatment by year and (D) mean cost per patient for surgical treatment and non-surgical treatment by age group. Figure 2: View largeDownload slide Evolution of length of hospital stay and cost of patients with infective endocarditis, who were operated on and not operated in Spain between 1997 and 2014. (A) Mean length of hospital stay per patient for surgical treatment and non-surgical treatment by study period, (B) mean length of hospital stay per patient for surgical treatment and non-surgical treatment by age group, (C) mean cost per patient for surgical treatment and non-surgical treatment by year and (D) mean cost per patient for surgical treatment and non-surgical treatment by age group. Regarding the cost per patient and year, it was higher in those who received ST during the whole period analysed and experienced a considerable increase from 15 259.22 euros/patient in 1997 to 39 317.70 euros/patient in 2014. The maximum cost was observed in 2010 (40 000 euros/patient), remaining stable until 2014. In the NS group, costs also increased but in a lower proportion, from 5630.61 euros/patient in 1997 to 9851.46 euros/patient in 2014 (Fig. 2C). The greatest differences in costs were observed in patients aged between 70 and 85 years (ST 35 000 euros vs NS 12 000 euros) and in children younger than 5 years (ST 33 000 euros vs NS 12 000 euros) (Fig. 2D). The mean cost for surgical patients during the study was 30 073.10 ± 18 383.78 euros and 9257.73 ± 8541.72 euros in the medical group. DISCUSSION In our study—which included all cases of IE registered between 1997 and 2014—the incidence of IE in Spain increased (from 3.17% in 1997 to 5.56% in 2014), as well as the mean age of these patients, and similar results in Europe have been reported by other authors in smaller series [2, 6]. Data from the Danish registry, in the same period time, reported an incidence of 3.93 and 7.55 cases per 100 000/persons/year [1]. This increase in incidences and age may be related to an improvement in diagnostic techniques and a change in the profile of patients. They are older, present with more comorbidities and present with healthcare-related IE [1, 6, 23, 24]. These ranges, however, vary widely, reaching 12.7% [3]. When analysing the incidence of IE, it is important to take into consideration the characteristics of the healthcare centre where the study was conducted and the design of the study. The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) included data from 25 countries from different continents [25]. This means the epidemiological characteristics of the sample or differences in clinical practice may influence the incidence. One of the most relevant data of our study was the low percentage of patients who underwent ST. This percentage increased during the study period from 11.7% to 17.8% but is lower than reported by other series in which it reaches 48.2% in the ICE-PCS and 52% or 58.7% in the Euro Heart Survey [26]. Nevertheless, other authors reported lower rates 22.8% or 9.6% [6]. These differences may be due to the fact that some of the studies were carried out in reference centres where very ill patients were referred, and therefore, the percentage of patients who underwent ST was higher [2, 3, 25]. The results observed in terms of in-hospital mortality vary according to the type of centre and the experience of the teams in the treatment of endocarditis. In the Spanish dataset, we observed that mortality decreased throughout the study (32.7% in 1997 vs 22.0% in 2014); however, it was higher than those reported by other groups. This might be explained by variability in the characteristics of patients, such as age, comorbidities and Charlson index at diagnosis [2, 7, 10]. Data published by the Euro Heart Survey show lower mortality for both groups; mortality among the patients treated medically was 10.4% and 15.6% in the surgical group. Recently, Olmos et al. [26] reported a mortality rate of 28.6% in a study carried out in 3 reference centres for endocarditis patients in Spain. As reported in the results, the percentage of patients with full microbiology documentation was low. The most common micro-organisms were Gram-negative bacilli (6.3%). From the current database, it is unlikely that the impact of specific pathogens on surgical patients can be appropriately assessed. It is agreed that this is a major limitation with administrative databases. On the other hand, substantial information on other specific variables in IE has been collected. The mean hospital stay for both treatment groups varied a little during the study period, and the percentage of patients with dysfunction of any organ increased. The costs for both groups, and mainly in the surgical group, increased considerably. This was related to the profile of patients who were operated on in which the age increased discreetly (53.5–61.3%), and, as we have indicated, the percentage of dysfunction organs increased. The treatment of patients who present with organ dysfunction increases the cost associated with healthcare [9, 27]. These patients require intensive care more frequently and need combination therapies more often. On cost issues, the maximum expenditure recorded was in 2010 (40 000 euros/patient). From 2010 to 2014, the cost seems to stay stable, and it is possible that the economic crisis has some influence [21, 28]. With each passing decade, healthcare has consumed a larger share of gross domestic product (GDP). In the USA, the healthcare expenditure share of GDP more than tripled between 1960 and 2004, as it rose from 5.2% to 16.0% of GDP. In Spain, during the period of study, health spending consumption of GDP did not increase, and during the economic crisis, between 2009 and 2014, it dropped from 6.7% to 6.0% of GDP [21]. When we compare the results of our study with other published studies, it is important to take into account that data on clinical presentation, complications and outcomes are mainly obtained from series collected over prolonged periods, in single centres or over shorter periods in multicentre, multinational studies from selected centres. Consequently, they do not necessarily represent the current situation of a whole country. Most epidemiological studies on IE involve case series of referral centres encountering selection bias [29]. Population-based investigations are more accurate, but well-conducted prospective studies are few [25], study designs are often inaccurate, undersized or lack important clinical data, criteria for definite diagnosis are not always clear and follow-up data sometimes incomplete, as highlighted in recent meta-analysis [30]. Limitations This study has important limitations related with the type of the design. It is clear that administrative databases have a number of limitations due to the type of coding and amount of information stored and should only be used for pure descriptive analysis. No clinical extrapolations must be inferred from those administrative databases. Other important limitations of this study in terms of incidence calculation are potential errors in the transcription of the diagnosis of IE into the corresponding ICD code. Regarding the aetiology of the disease, the microbiological profile of patients could not be determined, as microbiological test results were not appropriately documented on the CMBD. Microbiology findings have been documented in only 15% of the patients enrolled in the database, and therefore, it is not possible to know the eventual influence of microbiology in surgical patients. It should also be taken into account that we estimated mortality related to admissions for IE. As to the cost per patient, the limitation is that it was calculated only for the duration of hospital stay. CONCLUSION ST in IE has trended upwards in Spain during the last 2 decades. Patients are getting older and more frequently experience organ dysfunction. Mortality ratio steadily declined without changes in the LOHS. SUPPLEMENTARY MATERIAL Supplementary material is available at ICVTS online. ACKNOWLEDGEMENTS We would like to thank the ‘Subdirección General del Instituto de Información Sanitaria’, Ministerio de Sanidad, Servicios Sociales e Igualdad, Madrid, Spain, for providing the information on which this study was based. Funding This work was supported by the Carlos III Health Institute (PI15/01451); and the Regional Department of Health of the Autonomous Community of Castilla y León (‘Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon’) [GRS: GRS 1270/A/16 and GRS 1255/A/16]. Conflict of interest: none declared. REFERENCES 1 Erichsen P , Gislason GH , Bruun NE. The increasing incidence of infective endocarditis in Denmark, 1994-2011 . Eur J Intern Med 2016 ; 35 : 95 – 9 . Google Scholar CrossRef Search ADS PubMed 2 Muñoz P , Kestler M , De Alarcon A , Miro JM , Bermejo J , Rodríguez-Abella H et al. Current epidemiology and outcome of infective endocarditis: a multicenter, prospective, cohort study . Medicine (Baltimore) 2015 ; 94 : e1816. Google Scholar CrossRef Search ADS PubMed 3 Bor DH , Woolhandler S , Nardin R , Brusch J , Himmelstein DU. Infective endocarditis in the U.S., 1998-2009: a nationwide study . PLoS One 2013 ; 8 : e60033. Google Scholar CrossRef Search ADS PubMed 4 Slipczuk L , Codolosa JN , Davila CD , Romero-Corral A , Yun J , Pressman GS et al. Infective endocarditis epidemiology over five decades: a systematic review . PLoS One 2013 ; 8 : e82665. Google Scholar CrossRef Search ADS PubMed 5 Pant S , Patel NJ , Deshmukh A , Golwala H , Patel N , Badheka A et al. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011 . J Am Coll Cardiol 2015 ; 65 : 2070 – 6 . Google Scholar CrossRef Search ADS PubMed 6 Cresti A , Chiavarelli M , Scalese M , Nencioni C , Valentini S , Guerrini F et al. Epidemiological and mortality trends in infective endocarditis, a 17-year population-based prospective study . Cardiovasc Diagn Ther 2017 ; 7 : 27 – 35 . Google Scholar CrossRef Search ADS PubMed 7 Fedeli U , Schievano E , Buonfrate D , Pellizzer G , Spolaore P. Increasing incidence and mortality of infective endocarditis: a population-based study through a record-linkage system . BMC Infect Dis 2011 ; 11 : 48. Google Scholar CrossRef Search ADS PubMed 8 Federspiel JJ , Stearns SC , Peppercorn AF , Chu VH , Fowler VG. Increasing US rates of endocarditis with Staphylococcus aureus: 1999-2008 . Arch Intern Med 2012 ; 172 : 363 – 5 . Google Scholar CrossRef Search ADS PubMed 9 Leroy O , Georges H , Devos P , Bitton S , De Sa N , Dedrie C et al. Infective endocarditis requiring ICU admission: epidemiology and prognosis . Ann Intensive Care 2015 ; 5 : 45. Google Scholar CrossRef Search ADS PubMed 10 Sunder S , Grammatico-Guillon L , Baron S , Gaborit C , Bernard-Brunet A , Garot D et al. Clinical and economic outcomes of infective endocarditis . Infect Dis (Lond) 2015 ; 47 : 80 – 7 . Google Scholar CrossRef Search ADS PubMed 11 Bustamante J , Tamayo E , Flórez S , Telleria JJ , Bustamante E , López J et al. Toll-like receptor 2 R753Q polymorphisms are associated with an increased risk of infective endocarditis . Rev Esp Cardiol 2011 ; 64 : 1056 – 9 . Google Scholar CrossRef Search ADS PubMed 12 Khan O , Shafi AM , Timmis A. International guideline changes and the incidence of infective endocarditis: a systematic review . Open Heart 2016 ; 3 : e000498. Google Scholar CrossRef Search ADS PubMed 13 Figuerola-Tejerina A , Rodríguez-Caravaca G , Bustamante-Munguira J , SanRomán-Montero JM , Durán-Poveda M. Epidemiological surveillance and surgical site infection risk factors after cardiac surgery: prospective cohort study . Rev Esp Cardiol 2016 ; 69 : 842 – 8 . Google Scholar CrossRef Search ADS PubMed 14 O’Gara PT. Infective endocarditis 2006: indications for surgery . Trans Am Clin Climatol Assoc 2007 ; 118 : 187 – 98 . Google Scholar PubMed 15 Baddour LM , Wilson WR , Bayer AS , Fowler VG , Tleyjeh IM , Rybak MJ et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association . Circulation 2015 ; 132 : 1435 – 86 . Google Scholar CrossRef Search ADS PubMed 16 Head SJ , Mokhles MM , Osnabrugge RL , Bogers AJ , Kappetein AP. Surgery in current therapy for infective endocarditis . Vasc Health Risk Manag 2011 ; 7 : 255 – 63 . Google Scholar PubMed 17 Bin Abdulhak AA , Tleyjeh IM. Indications of surgery in infective endocarditis . Curr Infect Dis Rep 2017 ; 19 : 10. Google Scholar CrossRef Search ADS PubMed 18 Kim DH , Kang DH , Lee MZ , Yun SC , Kim YJ , Song JM et al. Impact of early surgery on embolic events in patients with infective endocarditis . Circulation 2010 ; 122 : S17 – 22 . 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Valve surgery for infective endocarditis is associated with high hospital charges . J Heart Valve Dis 2013 ; 22 : 110 – 17 . Google Scholar PubMed 28 Blázquez C , González N , Moreno P. Pharmaceutical expenditure as a determinant of health outcomes in EU countries . Estudios de Economía Aplicada 2013 ; 379 – 96 . 29 Kanafani ZA , Kanj SS , Cabell CH , Cecchi E , Oliveira Ramos A , Lejko-Zupanc T et al. Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults . Eur J Clin Microbiol Infect Dis 2010 ; 29 : 1203 – 10 . Google Scholar CrossRef Search ADS PubMed 30 Bin Abdulhak AA , Baddour LM , Erwin PJ , Hoen B , Chu VH , Mensah GA et al. Global and regional burden of infective endocarditis, 1990-2010: a systematic review of the literature . Glob Heart 2014 ; 9 : 131 – 43 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. 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Abstract

Abstract OBJECTIVES Infective endocarditis (IE) is a serious and eventually lethal disease with rising incidence in the past couple of decades. The aim of this study was to evaluate the contemporary epidemiological trends of surgical endocarditis patients, to analyse the clinical outcomes and to study their profile, associated prognostic factors and costs. METHODS This is a retrospective study of all patients admitted for IE in Spanish hospitals and discharged between 1 January 1997 and 31 December 2014. Data were extracted from the minimum basic data set of the National Surveillance System for Hospital Data in Spain provided by the Spanish Ministry of Health. Hospitalizations, comorbidities, outcomes and costs were analysed. RESULTS In total, 34 399 patients with IE were included; 15.7% of patients received surgical treatment and 84.3% received medical treatment only. Surgical patients were mostly men (71.9%) and had a lower mean age (59.2 ± 16.08 years) than the medical treatment group (P < 0.0001). Mortality among surgical patients showed a decreasing trend between 1997 (32.0%) and 2014 (22.7%) and increased with age (47.6% in ≥85 years of age). Length of hospital stay and the percentage of patients with organ dysfunction were also higher in this group. The cost of the surgical treatment group was higher and increased since 1997 (15 259.22 euros), remaining stable from 2010 (40 700 euros) (P < 0.0001). CONCLUSIONS Surgical treatment in IE has trended upwards in Spain during the last 2 decades. Patients are getting older and more frequently experience organ dysfunction. Mortality ratio steadily declined without changes in the length of hospital stay. Infective endocarditis, Epidemiology, Cardiac surgery, Mortality, Costs INTRODUCTION Infective endocarditis (IE) is an uncommon disease with a poor prognosis with rising incidence in the past couple of decades. The most recent epidemiological study reports an incidence of 3–10 cases per 100 000 persons/year [1–8]. The prognosis has not improved despite the improvements in the diagnosis and treatment, and nowadays, mortality rate remains high in spite of recent medical and surgical advances. Mortality is 15–50% depending on the series [7, 9–11], and this is probably due to an increase in microbiological resistance, comorbidities and association with healthcare [1, 2, 12]. The latest guidelines of the European Society of Cardiology (ESC) endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) on IE contemplate the management of IE by the endocarditis team. An appropriate team approach aims at reducing antimicrobials and surgery. In some cases, as peripheral aneurysms, percutaneous approaches are required [13–15]. Surgical treatment (ST) is performed in diverse proportions according to different studies. One possible explanation includes sample sizes, lack of homogeneity and different study designs. Surgical indications are well defined in the guidelines, and the main indication for surgery is heart failure [3, 5, 6, 16, 17]. Surgery is a part of an effective treatment in IE and provides good results in the short term, medium term and long term. Different studies analyse the impact of early surgery on outcomes. Case–control studies and a single randomized study aimed to elucidate this. However, heterogeneity is an issue and makes the interpretation of results difficult [18–20]. Epidemiological studies have some limitations but are useful for the understanding of the history of the disease. There is scarce information on the epidemiology of the ST of EI in Spain. The aim of this study was to define the current profile of IE, the need for ST and analyse the cost of surgery. METHODS Study design This is a retrospective study of all patients admitted for IE in hospitals in Spain and were discharged between 1 January 1997 and 31 December 2014. Data collection Data were extracted from the basic minimum data set (BMDS) of the National Surveillance System for Hospital Data in Spain provided by the Spanish Ministry of Health [in Spanish ‘Conjunto Minimo Basico de Datos’ (CMBD)]. The BMDS (also called national registry of hospital discharges) is the largest database of clinical data on hospitalized patients in the country and the most important source of treated morbidity data [21]. BMDS provides valuable although limited information on multiple healthcare-related topics. Informed consent was waived as this is a retrospective study based on public data. Data collected from the BMDS were encoded to avoid duplicity and were dissociated from any information that could uncover the identity of the patients. The minimum basic data set provides the encrypted patient identification number, gender, date of birth, dates of hospital admission and discharge, medical institutions providing the services, the diagnosis and procedure codes according to the International Classification of Diseases 9th edition, Clinical Modification (ICD-9-CM) and the outcome at discharge [22]. Case identification Cases were identified using the ICD-9CM code for IE (421, acute and subacute endocarditis) among the discharges between 1 January 1997 and 31 December 2014. All Spanish hospitals record the ICD-9CM codes for the main diagnosis and comorbidities of each patient on BMDS (see Supplementary Material, Appendix A1–A4). Demographic data (sex and age), presence of comorbidities, associated organ dysfunction, Charlson’s index and mortality data were extracted from the minimum basic data set. The study period was arbitrarily divided into calendar years and 4 calendar periods (1997–1999, 2000–2004, 2005–2009 and 2010–2014). The primary end point was ST. Secondary end points were length of hospital stay (LOHS), years of potential life lost and cost related to endocarditis. We divided the study sample into 2 groups: patients undergoing ST and non-surgical (NS). Mortality by years and periods was calculated to understand the trends. We analysed the correlation between age and type of treatment as well as the mortality between groups. LOHS was calculated as the number of days from admission (Day 0) to discharge or death at any time during the treatment. When patients were admitted and discharged the same day, 1 day of stay was assigned. Mean stay was estimated for the total group and separately by survival, year, type of treatment and age. Costs were calculated by diagnosis-related group, which classifies inpatients into groups based on their diagnosis and attributes a specific hospital cost to each group. Diagnosis-related group data were extracted from the minimum basic data set. All costs shown were adjusted for the increment of the inflation in the same period in Spain. Statistical analysis Categorical variables are expressed as absolute and relative (%) frequencies, and continuous variables were expressed as the mean and standard deviation. Differences between groups were compared using the t-test with continuous variables and using the χ2 test or Fisher’s exact test with categorical variables. Statistical significance was established as P ≤ 0.05. Incidence and mortality rates were calculated for patients with a diagnosis of IE by year (1997–2014), which allowed assessing tendencies during the study period. The incidence and mortality associated with IE were calculated by year and by age group, for the total group, the ST and NS groups and by gender. Therefore, age- and gender-adjusted analysis of incidence and mortality were performed. The number of events within each calendar year was used as a numerator, and the number of persons at risk within each calendar year as the denominator [the number of persons registered in the census of Spain (National Statistics Institute; http://www.ine.es/)]. All statistical procedures were performed using the SPSS 21.0 software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY, USA: IBM Corp.). RESULTS Patient characteristics From 1997 to 2014, 34 399 IE patients were diagnosed in Spain. The incidence per 100 000 inhabitants was 3.17% in 1997 and 5.56% in 2014. It was more prevalent in men. ST was performed in 5414 (15.7%) patients and medical treatment in 28 985 (84.3%). Patients who underwent ST were younger (59.2 ± 16.08 years ST and 62.3 ± 18.8 years NS, P < 0.0001), had less comorbidities and a lower Charlson index (1.00 ± 1.13 ST and 1.14 ± 1.41 NS, P < 0.0001), with more organ dysfunction, mainly renal failure (27.6%). Mortality in the ST group was higher (26.0% ST vs 20.1% NS). ST patients had a 30-day readmission rate lower than the NS patients (10.4% ST vs 20.0% NS) (Table 1). Table 1: Clinical, epidemiological and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Values are expressed as absolute n (%) and mean ± standard deviation. DM: diabetes mellitus. Table 1: Clinical, epidemiological and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Medical treatment Surgical treatment Number of patients  All period 28 985 (84.3) 5414 (15.7)  1997–1999 3724 (12.8) 515 (9.5)  2000–2004 6785 (23.4) 1190 (22.0)  2005–2009 8416 (29.0) 1658 (30.6)  2010–2014 10 060 (34.7) 2051 (37.9) Age (years) 62.31 ± 18.80 59.25 ± 16.08 Gender  Male 19 150 (66.07) 3895 (71.94)  Female 9835 (33.93) 1518 (28.04)  Unknown 0 (0.00) 1 (0.02) Underlying condition  Ischaemic heart disease 1368 (4.7) 257 (4.7)  Heart failure 6833 (23.6) 1738 (32.1)  Peripheral vascular disease 1362 (4.7) 332 (6.1)  Stroke 1243 (4.3) 169 (3.1)  Dementia 452 (1.6) 11 (0.2)  Chronic lung disease 4052 (14.0) 746 (13.8)  Rheumatic disease 484 (1.7) 70 (1.3)  Mild liver disease 1386 (4.8) 136 (2.5)  Mild-to-moderate DM 4110 (14.2) 605 (11.2)  DM with chronic complications 1105 (3.8) 122 (2.3)  Hemiplegia 514 (1.8) 94 (1.7)  Chronic renal disease 1641 (5.7) 260 (4.8)  Moderate-to-severe liver disease 772 (2.7) 72 (1.3) Charlson index  Valor medio 1.14 ± 1.41 1.00 ± 1.13  0 11 851 (40.9) 2162 (39.9)  1 8651 (29.8) 1889 (34.9)  2 4756 (16.4) 869 (16.1)  >2 3727 (12.9) 494 (9.1) Acute organ dysfunction  Cardiovascular 436 (1.5) 141 (2.6)  Haematological 1202 (4.1) 310 (5.7)  Hepatic 511 (1.8) 126 (2.3)  Neurological 391 (1.3) 62 (1.1)  Renal 4629 (16.0) 1494 (27.6)  Respiratory 227 (0.8) 357 (6.6)  Metabolic 371 (1.3) 116 (2.1) Micro-organisms  Gram-positive cocci 2338 (8.1) 313 (5.8)  Gram-negative bacilli 1426 (4.9) 340 (6.3)  Anaerobes 19 (0.1) 8 (0.1)  Fungi 151 (0.5) 44 (0.8) Readmission 5793 (20.0) 562 (10.4) Emergency admission 24 659 (85.07) 3647 (67.36) Exitus 5737 (20.1) 1396 (26.0) Values are expressed as absolute n (%) and mean ± standard deviation. DM: diabetes mellitus. The percentage of patients who underwent ST increased from 11.7% in 1997 to 17.8% in 2014; P < 0.05 (Fig. 1A). In all age groups, ST was less frequent. In 2 age groups, slightly above mean percentages were observed: in children younger than 5 years (17.3%) and in patients aged between 45 (20.7%) and 64 (21.3%) years (Fig. 1B). The NS patients were significantly older and had more comorbidities than ST patients. There was also a trend towards a higher incidence of New York Heart Association (NYHA) Class IV and congestive heart failure among ST patients (Table 2). The most common micro-organisms involved were Gram-negative bacilli (340; 6.3%), followed by Gram-positive cocci (313; 5.8%), fungi (44; 0.8%) and anaerobes (8; 0.1%). Table 2: Epidemiological, clinical and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment in Spain during 1997–2014 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) Values are expressed as absolute n (%) and mean ± standard deviation. a Percentage calculated based on the total cases of endocarditis in each period of time. DM: diabetes mellitus. Table 2: Epidemiological, clinical and microbiological characteristics of patients with infective endocarditis who received surgical treatment versus medical treatment in Spain during 1997–2014 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) 1997–1999 2000–2004 2005–2009 2010–2014 Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Non-surgery Surgery Number of patients 3724 (87.85)a 515 (12.15)a 6785 (85.08)a 1190 (14.92)a 8416 (83.54)a 1658 (16.46)a 10 060 (83.06)a 2051 (16.93)a Gender  Male 2573 (69.1) 370 (71.8) 4484 (66.1) 861 (72.4) 5464 (64.9) 1192 (71.9) 6629 (65.9) 1472 (71.8)  Female 1151 (30.90) 145 (28.15) 2301 (33.91) 328 (27.56) 2952 (35.07) 466 (28.10) 3431 (34.10) 579 (28.23)  Unkown 0 (0.00) 0 (0.00) 0 (0.00) 1 (0.08) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Age (years) 53.04 ± 20.37 53.53 ± 16.71 59.46 ± 18.81 58.03 (16.03) 62.96 ± 18.26 59.36 ± 15.66 67.12 ± 16.94 61.31 ± 15.87 Comorbid condition  Ischaemic heart disease 102 (2.7) 15 (2.9) 323 (4.8) 67 (5.6) 466 (5.5) 83 (5.0) 477 (4.7) 92 (4.5)  Heart failure 588 (15.8) 105 (20.4) 1364 (20.1) 373 (31.3) 1988 (23.6) 532 (32.1) 2893 (28.8) 728 (35.5)  Peripheral vascular disease 76 (2.0) 15 (2.9) 288 (4.2) 55 (4.6) 417 (5.0) 96 (5.8) 581 (5.8) 166 (8.1)  Stroke 126 (3.4) 19 (3.7) 324 (4.8) 24 (2.0) 317 (3.8) 49 (3.0) 476 (4.7) 77 (3.8)  Dementia 32 (0.9) 1 (0.2) 107 (1.6) 3 (0.3) 120 (1.4) 4 (0.2) 193 (1.9) 3 (0.1)  Chronic lung disease 278 (7.5) 40 (7.8) 749 (11.0) 157 (13.2) 1255 (14.9) 241 (14.5) 1770 (17.6) 308 (15.0)  Rheumatic disease 31 (0.8) 4 (0.8) 93 (1.4) 12 (1.0) 172 (2.0) 23 (1.4) 188 (1.9) 31 (1.5)  Mild liver disease 118 (3.2) 13 (2.5) 283 (4.2) 18 (1.5) 441 (5.2) 47 (2.8) 544 (5.4) 58 (2.8)  Mild-to-moderate DM 271 (7.3) 31 (6.0) 811 (12.0) 113 (9.5) 1290 (15.3) 203 (12.2) 1738 (17.3) 258 (12.6)  DM with chronic complications 50 (1.3) 9 (1.7) 200 (2.9) 12 (1.0) 338 (4.0) 40 (2.4) 517 (5.1) 61 (3.0)  Hemiplegia 48 (1.3) 7 (1.4) 105 (1.5) 19 (1.6) 123 (1.5) 15 (0.9) 238 (2.4) 53 (2.6)  Chronic renal disease 255 (6.8) 31 (6.0) 547 (8.1) 95 (8.0) 609 (7.2) 93 (5.6) 230 (2.3) 41 (2.0)  Moderate-to-severe liver disease 67 (1.8) 4 (0.8) 152 (2.2) 14 (1.2) 238 (2.8) 18 (1.1) 315 (3.1) 36 (1.8) Charlson index  Valor medio 0.72 ± 1.10 0.69 ± 1.02 1.05 ± 1.37 0.97 ± 1.12 1.21 ± 1.44 1.00 ± 1.09 1.30 ± 1.46 1.10 ± 1.16  0 2171 (58.3) 286 (55.5) 3089 (45.5) 499 (41.9) 3245 (38.6) 665 (40.1) 3346 (33.3) 712 (34.7)  1 883 (23.7) 155 (30.1) 1886 (27.8) 397 (33.4) 2562 (30.4) 558 (33.7) 3320 (33.0) 779 (38.0)  2 396 (10.6) 43 (8.3) 961 (14.2) 188 (15.8) 1406 (16.7) 288 (17.4) 1993 (19.8) 350 (17.1)  >2 274 (7.4) 31 (6.0) 849 (12.5) 106 (8.9) 1203 (14.3) 147 (8.9) 1401 (13.9) 210 (10.2) Acute organ dysfunction  Cardiovascular 41 (1.1) 13 (2.5) 82 (1.2) 32 (2.7) 132 (1.6) 37 (2.2) 181 (1.8) 59 (2.9)  Haematological 106 (2.8) 19 (3.7) 246 (3.6) 60 (5.0) 351 (4.2) 101 (6.1) 499 (5.0) 130 (6.3)  Hepatic 33 (0.9) 7 (1.4) 89 (1.3) 16 (1.3) 163 (1.9) 25 (1.5) 226 (2.2) 78 (3.8)  Neurological 33 (0.9) 10 (1.9) 96 (1.4) 17 (1.4) 112 (1.3) 11 (0.7) 150 (1.5) 24 (1.2)  Renal 300 (8.1) 78 (15.1) 820 (12.1) 261 (21.9) 1402 (16.7) 449 (27.1) 2107 (20.9) 706 (34.4)  Respiratory 25 (0.7) 22 (4.3) 52 (0.8) 70 (5.9) 82 (1.0) 131 (7.9) 68 (0.7) 134 (6.5)  Metabolic 13 (0.3) 5 (1.0) 44 (0.6) 19 (1.6) 107 (1.3) 27 (1.6) 207 (2.1) 65 (3.2) Micro-organisms  Gram-positive cocci 192 (5.2) 14 (2.7) 569 (8.4) 58 (4.9) 768 (9.1) 113 (6.8) 809 (8.0) 128 (6.2)  Gram-negative bacilli 110 (3.0) 13 (2.5) 253 (3.7) 44 (3.7) 427 (5.1) 101 (6.1) 636 (6.3) 182 (8.9)  Fungi 17 (0.5) 2 (0.4) 31 (0.5) 16 (1.3) 43 (0.5) 11 (0.7) 60 (0.6) 15 (0.7) Emergency admission 3205 (86.1) 344 (66.8) 5777 (85.1) 794 (66.7) 7181 (85.3) 1093 (65.9) 8496 (84.5) 1416 (69.0) Readmission 614 (16.5) 57 (11.1) 1234 (18.2) 108 (9.1) 1684 (20.0) 170 (10.3) 2261 (22.5) 227 (11.1) Exitus 610 (16.7) 151 (29.3) 1273 (18.9) 341 (28.8) 1749 (21.0) 392 (23.7) 2105 (21.4) 512 (25.3) Values are expressed as absolute n (%) and mean ± standard deviation. a Percentage calculated based on the total cases of endocarditis in each period of time. DM: diabetes mellitus. Figure 1: View largeDownload slide Percentage of patients with infective endocarditis, who were operated and not operated and mortality in Spain from 1997 to 2014. (A) Evolution over time, (B) evolution by age, (C) evolution of mortality and (D) mortality by age. Figure 1: View largeDownload slide Percentage of patients with infective endocarditis, who were operated and not operated and mortality in Spain from 1997 to 2014. (A) Evolution over time, (B) evolution by age, (C) evolution of mortality and (D) mortality by age. Overall mortality was higher in the surgical group (surgical 26.0% vs NS 20.1%). During the study, there was a decrease in mortality in the surgical group (32.7% in 1997 to 22.0% in 2014) (Fig. 1C). Although mortality in the NS group increased slightly (14.9% in 1997 to 21.1% in 2014). Another relevant issue was that the mortality of patients undergoing surgery increased with age, reaching 47.6% in those older than 85 years (Fig. 1D). Evolution of length of hospital stay and cost of patients with infective endocarditis The mean length of hospital stay during the study increased slightly in the surgical group (37.5 days in 1997 to 40.1 days in 2014) when compared with a decrease in the medical treatment group (27.2 days in 1997 to 23.1 days in 2014) (Fig. 2A). The mean length of stay was higher in the surgical group, with the highest being observed in the group of children younger than 5 years (57.6 days ST) (Fig. 2B). Figure 2: View largeDownload slide Evolution of length of hospital stay and cost of patients with infective endocarditis, who were operated on and not operated in Spain between 1997 and 2014. (A) Mean length of hospital stay per patient for surgical treatment and non-surgical treatment by study period, (B) mean length of hospital stay per patient for surgical treatment and non-surgical treatment by age group, (C) mean cost per patient for surgical treatment and non-surgical treatment by year and (D) mean cost per patient for surgical treatment and non-surgical treatment by age group. Figure 2: View largeDownload slide Evolution of length of hospital stay and cost of patients with infective endocarditis, who were operated on and not operated in Spain between 1997 and 2014. (A) Mean length of hospital stay per patient for surgical treatment and non-surgical treatment by study period, (B) mean length of hospital stay per patient for surgical treatment and non-surgical treatment by age group, (C) mean cost per patient for surgical treatment and non-surgical treatment by year and (D) mean cost per patient for surgical treatment and non-surgical treatment by age group. Regarding the cost per patient and year, it was higher in those who received ST during the whole period analysed and experienced a considerable increase from 15 259.22 euros/patient in 1997 to 39 317.70 euros/patient in 2014. The maximum cost was observed in 2010 (40 000 euros/patient), remaining stable until 2014. In the NS group, costs also increased but in a lower proportion, from 5630.61 euros/patient in 1997 to 9851.46 euros/patient in 2014 (Fig. 2C). The greatest differences in costs were observed in patients aged between 70 and 85 years (ST 35 000 euros vs NS 12 000 euros) and in children younger than 5 years (ST 33 000 euros vs NS 12 000 euros) (Fig. 2D). The mean cost for surgical patients during the study was 30 073.10 ± 18 383.78 euros and 9257.73 ± 8541.72 euros in the medical group. DISCUSSION In our study—which included all cases of IE registered between 1997 and 2014—the incidence of IE in Spain increased (from 3.17% in 1997 to 5.56% in 2014), as well as the mean age of these patients, and similar results in Europe have been reported by other authors in smaller series [2, 6]. Data from the Danish registry, in the same period time, reported an incidence of 3.93 and 7.55 cases per 100 000/persons/year [1]. This increase in incidences and age may be related to an improvement in diagnostic techniques and a change in the profile of patients. They are older, present with more comorbidities and present with healthcare-related IE [1, 6, 23, 24]. These ranges, however, vary widely, reaching 12.7% [3]. When analysing the incidence of IE, it is important to take into consideration the characteristics of the healthcare centre where the study was conducted and the design of the study. The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) included data from 25 countries from different continents [25]. This means the epidemiological characteristics of the sample or differences in clinical practice may influence the incidence. One of the most relevant data of our study was the low percentage of patients who underwent ST. This percentage increased during the study period from 11.7% to 17.8% but is lower than reported by other series in which it reaches 48.2% in the ICE-PCS and 52% or 58.7% in the Euro Heart Survey [26]. Nevertheless, other authors reported lower rates 22.8% or 9.6% [6]. These differences may be due to the fact that some of the studies were carried out in reference centres where very ill patients were referred, and therefore, the percentage of patients who underwent ST was higher [2, 3, 25]. The results observed in terms of in-hospital mortality vary according to the type of centre and the experience of the teams in the treatment of endocarditis. In the Spanish dataset, we observed that mortality decreased throughout the study (32.7% in 1997 vs 22.0% in 2014); however, it was higher than those reported by other groups. This might be explained by variability in the characteristics of patients, such as age, comorbidities and Charlson index at diagnosis [2, 7, 10]. Data published by the Euro Heart Survey show lower mortality for both groups; mortality among the patients treated medically was 10.4% and 15.6% in the surgical group. Recently, Olmos et al. [26] reported a mortality rate of 28.6% in a study carried out in 3 reference centres for endocarditis patients in Spain. As reported in the results, the percentage of patients with full microbiology documentation was low. The most common micro-organisms were Gram-negative bacilli (6.3%). From the current database, it is unlikely that the impact of specific pathogens on surgical patients can be appropriately assessed. It is agreed that this is a major limitation with administrative databases. On the other hand, substantial information on other specific variables in IE has been collected. The mean hospital stay for both treatment groups varied a little during the study period, and the percentage of patients with dysfunction of any organ increased. The costs for both groups, and mainly in the surgical group, increased considerably. This was related to the profile of patients who were operated on in which the age increased discreetly (53.5–61.3%), and, as we have indicated, the percentage of dysfunction organs increased. The treatment of patients who present with organ dysfunction increases the cost associated with healthcare [9, 27]. These patients require intensive care more frequently and need combination therapies more often. On cost issues, the maximum expenditure recorded was in 2010 (40 000 euros/patient). From 2010 to 2014, the cost seems to stay stable, and it is possible that the economic crisis has some influence [21, 28]. With each passing decade, healthcare has consumed a larger share of gross domestic product (GDP). In the USA, the healthcare expenditure share of GDP more than tripled between 1960 and 2004, as it rose from 5.2% to 16.0% of GDP. In Spain, during the period of study, health spending consumption of GDP did not increase, and during the economic crisis, between 2009 and 2014, it dropped from 6.7% to 6.0% of GDP [21]. When we compare the results of our study with other published studies, it is important to take into account that data on clinical presentation, complications and outcomes are mainly obtained from series collected over prolonged periods, in single centres or over shorter periods in multicentre, multinational studies from selected centres. Consequently, they do not necessarily represent the current situation of a whole country. Most epidemiological studies on IE involve case series of referral centres encountering selection bias [29]. Population-based investigations are more accurate, but well-conducted prospective studies are few [25], study designs are often inaccurate, undersized or lack important clinical data, criteria for definite diagnosis are not always clear and follow-up data sometimes incomplete, as highlighted in recent meta-analysis [30]. Limitations This study has important limitations related with the type of the design. It is clear that administrative databases have a number of limitations due to the type of coding and amount of information stored and should only be used for pure descriptive analysis. No clinical extrapolations must be inferred from those administrative databases. Other important limitations of this study in terms of incidence calculation are potential errors in the transcription of the diagnosis of IE into the corresponding ICD code. Regarding the aetiology of the disease, the microbiological profile of patients could not be determined, as microbiological test results were not appropriately documented on the CMBD. Microbiology findings have been documented in only 15% of the patients enrolled in the database, and therefore, it is not possible to know the eventual influence of microbiology in surgical patients. It should also be taken into account that we estimated mortality related to admissions for IE. As to the cost per patient, the limitation is that it was calculated only for the duration of hospital stay. CONCLUSION ST in IE has trended upwards in Spain during the last 2 decades. Patients are getting older and more frequently experience organ dysfunction. Mortality ratio steadily declined without changes in the LOHS. SUPPLEMENTARY MATERIAL Supplementary material is available at ICVTS online. ACKNOWLEDGEMENTS We would like to thank the ‘Subdirección General del Instituto de Información Sanitaria’, Ministerio de Sanidad, Servicios Sociales e Igualdad, Madrid, Spain, for providing the information on which this study was based. Funding This work was supported by the Carlos III Health Institute (PI15/01451); and the Regional Department of Health of the Autonomous Community of Castilla y León (‘Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon’) [GRS: GRS 1270/A/16 and GRS 1255/A/16]. Conflict of interest: none declared. REFERENCES 1 Erichsen P , Gislason GH , Bruun NE. The increasing incidence of infective endocarditis in Denmark, 1994-2011 . Eur J Intern Med 2016 ; 35 : 95 – 9 . Google Scholar CrossRef Search ADS PubMed 2 Muñoz P , Kestler M , De Alarcon A , Miro JM , Bermejo J , Rodríguez-Abella H et al. 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All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: Apr 12, 2018

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