Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Kang D-H, Kim Y-J, Kim S-H, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 2012;366:2466-73.
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Contents Page I. Supplemental Study Procedures 2 II. Supplemental Surgical Procedures 3 III. Supplemental Tables A. Table S1. Case Fatalities after Randomization 4 B. Table S2. Embolic Events after Randomization 5 C. Table S3. Follow-up Results of Patients Treated Medically and Discharged Without Surgery 6 IV. Supplemental References 8 1
I. Supplemental Study Procedures Immunocompromised state was defined as patients with human immunodeficiency virus, acquired immunodeficiency syndrome, solid organ or bone marrow transplantation, receiving steroids, end-stage renal disease or recent chemotherapy (1). Operative risk was assessed using the European System for Cardiac Operative Risk Evaluation (EuroSCORE) (2). Transesophageal echocardiography was performed on all 134 patients diagnosed as definite infective endocarditis and vegetation length was measured in various planes and the maximal length was obtained (3). The degree of aortic and mitral valve disease was assessed semiquantitatively or using quantitative methods and classified as mild, moderate, or severe (4). Surgical procedures were performed with the use of a standard cardiopulmonary bypass. In patients with mitral valve (MV) IE, repair was preferred when possible, most often with excision of vegetation and reconstruction of involved leaflets. Aortic valve or MV replacements were performed using mechanical or bioprosthetic valves at the discretion of the surgeon. Operative mortality was defined as death within 30 days of the index procedure. In patients assigned to the conventional treatment group, the decision to perform surgery was made by close cooperation among specialists in infectious disease, cardiologists and cardiac surgeons. Patients were asked to call the study coordinators if they experienced any symptoms during follow-up. All serious adverse events were reported to the institutional review boards, and the boards recommended after each review that the study be continued without modification. 2
II. Supplemental Surgical Procedures Of 67 patients who underwent surgery, 66 patients had successful results of valve repair or replacement on echocardiographic assessment performed at 1 week after the surgery, but one patient in the conventional treatment group had moderate to severe mitral regurgitation due to paravalvular leakage after MV replacement, who underwent repeat MV replacement due to progression of mitral regurgitation at 28 months after the randomization. 3
III. Supplemental Tables Table S1. Case Fatalities after Randomization. Patient Age Sex Group Interval, d Randomization to Death Valvular Disease Surgery Detailed Information Related Death 1 50 M CONV 5 MR No Sudden cardiac death from electromechanical dissociation 2 66 M OP 451 MR MV replacement Pneumonia and quadriplegia related to delayed recognition of traumatic subdural hemorrhage due to slip on the stairs after heavy alcohol drinking 3 57 M OP 99 AR AVR and CABG MV surgery due to severe ischemic MR caused by papillary muscle infarction was performed on postoperative 33 days. Death occurred on postoperative 98 days due to renal failure, pneumonia and sepsis 4 75 M CONV 55 MR No Sudden death after completion of antibiotic treatment and discharge No 5 51 F CONV 1466 MR MV repair Colon cancer with liver metastasis No 6 67 F OP 734 MR MV replacement Gallbladder cancer with liver metastasis No AR, aortic regurgitation; AVR, aortic valve replacement; CABG, coronary artery bypass graft; CONV, conventional treatment; MR, mitral regurgitation; MV, mitral valve; OP, early surgery. 4
Table S2. Embolic Events after Randomization. Patient Age Sex Group Interval, d Randomization to embolic event Involved Valve Microorganism Symptoms Diagnostic method Embolism Involved Severity Artery * Results of Imaging Studies Residual Deficit 1 71 F CONV 9 MV S. aureus Left hemiparesis Brain MRI Embolic infarction of right basal ganglia and periventricular white matter Aggravated to the bed-ridden state 2 68 F CONV 16 MV Other streptococci Dysarthria Brain MRI Left postcentral gyrus and subcortical infarct Dysarthria 3 62 M CONV 5 MV Culture negative Recent memory impairment Brain MRI, Multiple embolic infarcts in left frontal, right occipital lobe and right basal ganglia Cognitive impairment and gait disturbance 4 30 M CONV 3 AV Other streptococci Leg pain Angiography Popliteal Occlusion of distal popliteal and proximal anterior tibial artery Improved by emergent embolectomy 5 19 M CONV 3 MV S. aureus Headache Diplopia Brain MRI, both frontal lobe embolic infarct with mass effect Cognitive impairment 6 21 M CONV 4 MV Other streptococci Chest pain ECG, cardiac enzyme and echocardiography Coronary Apical and anterior wall akinesia Left ventricular dysfunction 7 49 M CONV 2 AV and MV Viridans streptococci Aphasia Brain MRI, new lesion Acute infarction in the left MCA territory Aphasia 8 49 F CONV 4 MV Culture negative Left flank pain Abdomen CT, Splenic Not severe Multiple splenic infarctions Absent AV, aortic valve; CONV, conventional treatment; CT, computerized tomography scan; MCA, middle cerebral artery; MRI, magnetic resonance imaging; MV, mitral valve. * An embolic event was considered severe if it caused death or irreversible organ damage or if it needed specific medical or surgical treatment (5). 5
Table S3. Follow-up Results of Patients Treated Medically and Discharged Without Surgery. Patient Age Sex Group Valvular Disease Symptoms Surgery Detailed Information Survival 1 71 F CONV MR Present Required Refusal of surgery due to severe disability related to embolic stroke 2 62 F CONV MR Present Required Refusal of surgery due to rectal cancer diagnosed during hospitalization 3 68 F CONV MR Present MV replacement Surgery was performed without events 4 16 M CONV MR Absent Not needed Asymptomatic during follow-up 5 * 70 M CONV AS Absent AV replacement Emergent AV replacement was performed due to recurrence of infective endocarditis and acute AR 6 54 M CONV MR Absent Not needed Asymptomatic during follow-up 7 72 F CONV AR Present Required Refusal of surgery due to old age 8 19 M CONV MR Present MV repair Successful MV repair was performed 9 51 M CONV AR Absent Not needed Asymptomatic during follow-up 10 21 M CONV MR Present Required Refusal of surgery due morbidity related to myocardial infarction 11 75 M CONV MR Absent Not done Sudden death at 1 month after completion of antibiotic treatment and discharge AR, aortic regurgitation; AV, aortic valve; CONV, conventional treatment; MR, mitral regurgitation; MV, mitral valve. * Case no. 5 received 6-week antibiotic therapy due to infective endocarditis caused by Streptococcus bovis and complicated with vertebral 6 No
osteomyelitis and psoas abscess. Five months later, he was presented to the emergency room with fever and dyspnea, and underwent emergent AV replacement because of acute aortic regurgitation and pulmonary edema. Mobile vegetations and perforation of noncoronary cusp were noted on operative findings and Streptococcus bovis with the same antibiogram of the first isolate was identified from blood cultures obtained at the emergency room. Case no. 1, 3, 8 and 10 are the same patients as Case no. 1, 2, 5 and 6, respectively, in the Table S2. Case no. 11 is the same patient as Case no. 4 in the Table S1. 7
IV. Supplemental References 1. Hasbun R, Vikram HR, Barakat LA, Buenconsejo J, Quagliarello VJ. Complicated leftsided native valve endocarditis in adults: risk classification for mortality. JAMA. 2003;289:1933-1940. 2. Nashef SAM, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16:9-13. 3. Kim DH, Kang DH, Lee MZ, et al. Impact of early surgery on embolic events in patients with infective endocarditis. Circulation. 2010;122:S17-S22. 4. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16:777-802. 5. Di Salvo G, Habib G, Pergola V, et al. Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol. 2001;37:1069-1076. 8