HEARTLUNG TRANSPLANTATION Adult Recipients 2018 JHLT 2018 Oct

HEART-LUNG TRANSPLANTATION Adult Recipients 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Table of Contents < Donor and recipient characteristics: slides 3 -13 < Post transplant survival and other outcomes: slides 1423 < Induction and maintenance immunosuppression: slides 24 -27 < Post-transplant morbidities: slides 28 -35 < Multivariable analyses: slides 36 -40 < Focus theme: slides 41 -48 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Donor and Recipient Characteristics 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Number of Transplants Reported by Year 250 200 150 100 50 0 19 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 2099 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 16 Number of Transplants 300 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 NOTE: This figure includes only the heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of heart-lung transplants worldwide has declined in recent years.

Adult Heart-Lung Transplants Average Center Volume by Location (Transplants: January 2009 – June 2017) Europe North America Other Percentage of Transplants 60 9 35 40 28 24 30 21 5 20 14 6 10 23 13 0 1 2 0 1 3 0 2 3 3 4 - 9 Average number of heart-lung transplants per year 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 7 0 % of Transplants Number of Centers 50 42

19 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 2099 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 16 Number of Retransplants Europe North America 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Other 6 18 5 16 14 4 12 3 10 8 2 6 1 4 2 0 0 % of Retransplants out of All Adult Heart-Lung Transplants Adult Heart-Lung Retransplants by Year and Location % of Retransplants

Adult Heart-Lung Transplants Diagnosis (Transplants: January 1982 – June 2017) Diagnosis N (%) PH-not IPAH 1, 227 (37. 7%) IPAH 962 (29. 5%) CF 464 (14. 2%) COPD 145 (4. 5%) IIP 124 (3. 8%) A 1 ATD 63 (1. 9%) Sarcoidosis 60 (1. 8%) ILD-not IIP 51 (1. 6%) Retransplant 41 (1. 3%) Non CF-bronchiectasis 33 (1. 0%) OB 23 (0. 7%) Other 64 (2. 0%) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Diagnosis by Era (Transplants: January 1982 – June 2017) 100% Other 90% Retransplant % of Transplants 80% Non CFbronchiectasis 70% IIP 60% COPD 50% 40% A 1 ATD 30% CF 20% IPAH 10% 0% PH-not IPAH 1982 -1993 (N=1, 243) 1994 -2003 (N=1, 251) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 2004 -6/2017 (N=763)

Adult Heart-Lung Transplants Major Diagnoses by Year (%) PH-not IPAH CF COPD IIP 100 80 70 60 50 40 30 20 10 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 1 20 0 1 20 1 1 20 2 1 20 3 1 20 4 1 20 5 16 0 19 % of Transplants 90 Transplant Year 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Since only major indications are shown, sum of percentages for each year is less than 100%.

Adult Heart-Lung Transplants Major Diagnoses by Year (Number) PH-not IPAH CF COPD IIP 160 140 120 100 80 60 40 20 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 1 20 0 1 20 1 1 20 2 1 20 3 1 20 4 1 20 5 16 0 19 Number of Transplants 180 Transplant Year 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Recipient Age Distribution (in Years) by Location (Transplants: January 2004 – June 2017) 18 -34 35 -49 50 -59 60+ 100% % of Transplants 80% 60% 40% 20% 0% Europe North America 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Other

Adult Heart-Lung Transplants Diagnosis Distribution by Location (Transplants: January 2004 – June 2017) 100% Other 90% Retransplant % of Transplants 80% Non CFbronchiectasis IIP 70% 60% 50% COPD 40% A 1 ATD 30% CF 20% IPAH 10% PH-not IPAH 0% Europe North America 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Other

Adult Heart-Lung Transplants Donor Age Distribution by Location (Transplants: January 2004 – June 2017) 6 -11 12 -17 18 -34 35 -49 50 -59 60+ 100% % of Donors 80% 60% 40% 20% 0% Europe North America 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Other

Post-Transplant Survival and Other Outcomes 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Kaplan-Meier Survival (Transplants: January 1982 – June 2016) 100 Median survival = 3. 4 years Conditional median survival = 10. 3 years Survival (%) 75 N = 3, 998 50 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Kaplan-Meier Survival by Transplant Type (Transplants: January 1982 – June 2016) 100 Primary (N=3, 912) First Retransplant (N=46) Survival (%) 75 Median survival (years): Primary: 3. 4; Conditional=10. 3; Retransplant: 0. 2; Conditional=11. 2 50 p = 0. 0108 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Kaplan-Meier Survival by Era (Transplants: January 1982 – June 2016) 100 Median survival (years): 1982 -1993=2. 1; 1994 -2003=3. 7; 2004 -6/2016=5. 8; Conditional median survival (years): 1982 -1993=9. 0; 1994 -2003=11. 2; 2004 -6/2016=11. 5 Survival (%) 75 1982 -1993 (N=1, 600) 1994 -2003 (N=1, 426) 50 2004 -6/2016 (N=972) 25 1982 -1993 vs. 1994 -2003: p<0. 0001 1982 -1993 vs. 2004 -6/2016: p<0. 0001 1994 -2003 vs. 2004 -6/2016: p=0. 0789 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Kaplan-Meier Survival by Major Diagnosis (Transplants: January 1990 – June 2016) 100 PH-not IPAH (N=1, 036) CF (N=379) IIP (N=94) IPAH (N=732) COPD (N=106) Survival (%) 75 Median survival (years): PH-not IPAH=5. 0; IPAH=4. 5; CF=6. 2; COPD=2. 7; IIP=2. 1 50 25 No pair-wise comparisons were significant at p < 0. 05 except CF vs. COPD. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Kaplan-Meier Survival by Major Diagnosis Conditional on Survival to 1 Year (Transplants: January 1990 – June 2016) 100 PH-not IPAH (N=661) CF (N=266) IIP (N=56) IPAH (N=495) COPD (N=63) Survival (%) 75 50 No pair-wise comparisons were significant at p < 0. 05. 25 Median survival (years): PH-not IPAH=12. 7; IPAH=10. 1; CF=11. 8; COPD=7. 3; IIP=8. 0 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Functional Status of Surviving Recipients (Follow-ups: March 2005 – June 2017) 100% 10% - Moribund, fatal processes progressing rapidly 20% - Very sick, hospitalization necessary: active treatment necessary 80% 30% - Severely disabled: hospitalization is indicated, death not imminent 40% - Disabled: requires special care and assistance 60% 50% - Requires considerable assistance and frequent medical care 60% - Requires occasional assistance but is able to care for needs 40% 70% - Cares for self: unable to carry on normal activity or active work 80% - Normal activity with effort: some symptoms of disease 20% 90% - Able to carry on normal activity: minor symptoms of disease 0% 1 Year (N=247) 2 Year (N=208) 3 Year (N=186) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 100% - Normal, no complaints, no evidence of disease

Adult Heart-Lung Transplants Surviving Recipients Working Post-Transplant (Follow-ups: April 1994 – June 2017) 70% 60% 50% 40% 30% 20% 10% 0% 1 Year (N=471) 3 Years (N=369) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 5 Years (N=322)

Adult Heart-Lung Transplants Surviving Recipients Working Post-Transplant by Era (Follow-ups: April 1994 – June 2017) 70% 60% 50% 40% 30% 20% 10% 0% 1 Year (N=239) 3 Years (N=190) 5 Years (N=173) 4/1994 -2003 1 Year (N=232) 3 Years (N=179) 2004 -6/2017 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 5 Years (N=149)

Adult Heart-Lung Transplants Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April 1994 – June 2017) 100% 80% 60% 40% 20% No Hospitalization Hospitalized, Not Rejection/Not Infection Hospitalized, Rejection Only Hospitalized, Infection Only Hospitalized, Rejection and Infection 0% Up to 1 Year (N=594) Between 2 -3 Years (N=449) Between 4 -5 Years (N=386) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Induction and Maintenance Immunosuppression 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Induction Immunosuppression (Transplants: January 2004 – June 2017) 70 N = 306 % of Patients 60 50 40 30 20 10 0 Any Induction Polyclonal ALG/ATG 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 IL-2 R Antagonist Analysis is limited to patients who were alive at the time of the discharge.

Adult Heart-Lung Transplants Induction Immunosuppression (Transplants: January 2004 – December 2016) 100 90 Any induction Polyclonal ALG/ATG IL-2 R Antagonist 80 60 50 40 30 20 10 0 20 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 16 20 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 16 % of Patients 70 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Analysis is limited to patients who were alive at the time of the discharge.

Adult Heart-Lung Transplants Maintenance Immunosuppression Drug Combinations at Time of 1 Year Follow-up (Follow-ups: January 2004 – June 2017) 100% Other Sirolimus/Everolimus + Calcineurin Inhibitor + Cell Cycle Inhibitor 80% Sirolimus/Everolimus + Calcineurin Inhibitor 60% Tacrolimus + MMF/MPA 40% Tacrolimus + AZA Cyclosporine + MMF/MPA 20% Cyclosporine + AZA 0% Year 1 (N=252) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Analysis is limited to patients who were alive at the time of the follow-up.

Post-Transplant Morbidities 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Cumulative Post-Transplant Morbidity Rates in Survivors within 1 and 5 Years (Transplants: January 1994 – June 2016) Outcome Severe Renal Dysfunction* Within 1 Year Total number with known response Within 5 Years Total number with known response 7. 1% (N=494) 13. 7% (N=263) Creatinine > 2. 5 mg/dl (221 µmol/L) 3. 0% 9. 5% Chronic Dialysis 3. 8% 3. 4% Renal Transplant 0. 2% 0. 8% Diabetes 17. 1% (N=502) 26. 5% (N=264) Cardiac Allograft Vasculopathy 2. 5% (N=396) 6. 9% (N=131) Bronchiolitis Obliterans Syndrome 7. 1% (N=464) 31. 1% (N=219) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 * Severe renal dysfunction = Creatinine > 2. 5 mg/dl (221 μmol/L), dialysis or renal transplant

Adult Heart-Lung Transplants Freedom from Cardiac Allograft Vasculopathy and Bronchiolitis Obliterans Syndrome (Transplants: January 1994 – June 2016) Freedom from CAV and BOS (%) 100 75 50 25 Freedom from CAV (N=417) Freedom from BOS (N=489) 0 0 1 2 3 4 5 6 7 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 8 9 10 11 12 13 14

Adult Heart-Lung Transplants Freedom from Severe Renal Dysfunction (Transplants: January 1994 – June 2016) Freedom from Severe Renal Dysfunction (%) 100 N=518 75 50 25 *Severe renal dysfunction = Creatinine > 2. 5 mg/dl (221 μmol/L), dialysis or renal transplant 0 0 1 2 3 4 5 6 7 8 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 9 10 11 12 13 14 15

Adult Heart-Lung Transplants Cumulative Post Transplant Malignancy Rates in Survivors (Transplants: January 1994 – June 2016) 1 -Year Survivors Malignancy/Type No Malignancy (all types combined) Malignancy Type* 5 -Year Survivors 10 -Year Survivors 480 (94. 3%) 248 (89. 5%) 110 (82. 7%) 29 (5. 7%) 29 (10. 5%) 23 (17. 3%) Skin 3 14 15 Lymphoma 19 8 3 Other 5 6 6 Type Not Reported 2 1 0 * Recipients may have experienced more than one type of malignancy so the sum of individual malignancy types may be greater than the total number with malignancy. 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Freedom from Malignancy (Transplants: January 1994 - June 2016) Freedom from Malignancy (%) 100 90 80 70 All malignancy Lymphoma 60 Skin Other 50 0 1 2 3 4 5 6 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 7 8 9 10 11 12

Adult-Heart Lung Transplants Cause of Death (Deaths: January 1992 – June 2017) CAUSE OF DEATH OB/BOS 0 -30 Days (N=480) 31 Days - 1 Year >1 Year - 3 Years >3 Years - 5 Years >5 Years (N=366) (N=297) (N=177) (N=561) 0 14 (3. 8%) 70 (23. 6%) 38 (21. 5%) 117 (20. 9%) 7 (1. 5%) 8 (2. 2%) 6 (2. 0%) 1 (0. 6%) 3 (0. 5%) 0 7 (1. 9%) 12 (4. 0%) 8 (4. 5%) 12 (2. 1%) 1 (0. 2%) 8 (2. 2%) 14 (4. 7%) 7 (4. 0%) 44 (7. 8%) 0 2 (0. 5%) 2 (0. 7%) 1 (0. 6%) 1 (0. 2%) Infection, non-CMV 81 (16. 9%) 130 (35. 5%) 84 (28. 3%) 45 (25. 4%) 117 (20. 9%) Graft failure 129 (26. 9%) 76 (20. 8%) 44 (14. 8%) 32 (18. 1%) 82 (14. 6%) 39 (8. 1%) 15 (4. 1%) 22 (7. 4%) 19 (10. 7%) 55 (9. 8%) Technical 113 (23. 5%) 12 (3. 3%) 3 (1. 0%) 3 (1. 7%) 7 (1. 2%) Multiple organ failure 52 (10. 8%) 54 (14. 8%) 15 (5. 1%) 7 (4. 0%) 38 (6. 8%) Other 58 (12. 1%) 40 (10. 9%) 25 (8. 4%) 16 (9. 0%) 85 (15. 2%) Acute rejection Lymphoma Malignancy, other CMV Cardiovascular 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants Relative Incidence of Leading Causes of Death (Deaths: January 1992 – June 2017) OB/BOS Graft Failure Infection (non-CMV) Cardiovascular Technical % of Deaths 40 30 20 10 0 0 -30 Days (N=480) 31 Days - 1 Year (N=366) >1 -3 Years (N=297) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 >3 -5 Years (N=177) >5 Years (N=561)

Multivariable Analysis 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants (1999 -6/2016) Statistically Significant Risk Factors For 1 Year Mortality with 95% Confidence Limits 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 (N = 1, 515)

Adult Heart-Lung Transplants (1999 -6/2016) Statistically Significant Risk Factors For 1 Year Mortality Continuous Factors (see figures) Recipient age Donor age 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants (1999 -6/2016) Risk Factors For 1 Year Mortality with 95% Confidence Limits Recipient age Hazard Ratio of 1 Year Mortality 2. 5 p = 0. 0304 2. 0 1. 5 1. 0 0. 5 0. 0 20 30 40 50 Recipient age (years) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 (N = 1, 515) 60

Adult Heart-Lung Transplants (1999 -6/2016) Risk Factors For 1 Year Mortality with 95% Confidence Limits Donor age Hazard Ratio of 1 Year Mortality 2. 5 p = 0. 0101 2. 0 1. 5 1. 0 0. 5 0. 0 15 20 25 30 35 40 45 50 Donor age (years) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 (N = 1, 515) 55

Focus Theme 2018 JHLT. 2018 Oct; 37(10): 1155 -1206

Adult Heart-Lung Transplants % of Multiorgan Transplants by Location (Transplants: January 1995 – June 2017) 5. 0% % of Transplants 4. 0% N = 6 3. 0% N = 14 2. 0% N = 19 1. 0% 0. 0% Europe (N=1, 334) North America (N=743) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 Other (N=168)

Adult Heart-Lung Transplants Donor and Recipient Characteristics (Transplants: January 1995 – June 2017) Multiorgan transplant (N = 39) Heart-lung alone transplant (N = 2, 206) p-value Recipient age (years) 35. 0 (19. 0 - 55. 0) 39. 0 (20. 0 - 57. 0) 0. 0426 Donor age (years) 34. 0 (10. 0 - 53. 0) 32. 0 (14. 0 - 54. 0) 0. 7829 Recipient gender (% male) 51. 3% 45. 3% 0. 4559 Donor gender (% male) 46. 2% 45. 7% 0. 9553 A 1 ATD 6. 5% 0. 6% CF 48. 4% 11. 7% COPD 0% 3. 2% IIP 0% 3. 2% 19. 4% 29. 4% 0% 1. 2% PH-not IPAH 19. 4% 41. 7% Retransplant 0% 0. 8% Other 6. 5% 8. 2% Diagnosis IPAH Non CF-bronchiectasis 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 <0. 0001 Continuous factors are expressed as median (5 th – 95 th percentiles)

Adult Heart-Lung Transplants Donor and Recipient Characteristics (Transplants: January 1995 – June 2017) Multiorgan transplant (N = 39) Heart-lung alone transplant (N = 2, 206) p-value 0% 0. 9999 Europe 48. 7% 59. 6% North America 35. 9% 33. 0% Others 15. 4% 7. 3% Recipient hypertension 5. 9% 18. 5% 0. 3361 Donor hypertension 23. 1% 11. 3% 0. 1810 Recipient diabetes mellitus 35. 0% 10. 2% 0. 0032 0% 3. 1% 0. 9999 Retransplant Location Donor diabetes mellitus 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 0. 1243

Adult Heart-Lung Transplants Donor and Recipient Characteristics (Transplants: January 1995 – June 2017) Multiorgan transplant (N = 39) Heart-lung alone transplant (N = 2, 206) p-value 8. 3% 3. 0% 0. 3143 Recipient creatinine (mg/dl) 0. 9 (0. 6 - 8. 9) 1. 0 (0. 5 - 1. 8) 0. 2370 Recipient total bilirubin (mg/dl) 1. 2 (0. 2 - 5. 0) 0. 8 (0. 3 - 3. 7) 0. 1052 Ischemic time (hours) 3. 0 (1. 2 - 6. 8) 3. 8 (1. 9 - 6. 3) 0. 0058 76. 9% 58. 5% 0. 1812 Recipient history of prior dialysis Induction* Multiorgan transplants with liver (N=32) Creatinine (mg/dl) 0. 9 (0. 5 - 1. 9) Bilirubin (mg/dl) 1. 2 (0. 2 - 5. 0) Continuous factors are expressed as median (5 th – 95 th percentiles) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 * Analysis is limited to patients who were alive at the time of the discharge.

Adult Heart-Lung Transplants Diagnosis of Multiorgan Transplants by Era 100% 90% Other % of Transplants 80% Sarcoidosis 70% 60% PH-not IPAH 50% IPAH 40% 30% CF 20% 10% A 1 ATD 0% 1991 -1999 (N=17) 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 2000 -6/2017 (N=21)

Adult Heart-Lung Transplants Kaplan-Meier Survival by Transplant Type (Transplants: January 1991 – June 2016) 100 Multiorgan transplant (N=45) Heart-lung alone transplant (N=2, 949) Survival (%) 75 50 p = 0. 7365 25 0 0 1 2 3 4 5 Years 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 6 7 8 9 10

Adult Heart-Lung Transplants Cause of Death Stratified by Transplant Type (Deaths: January 1992 – June 2017) Transplant Type Cause of Death OB/BOS Acute Rejection Malignancy Infection Multiorgan transplant Graft Failure Cardiovascular Technical Multiple Organ Failure All known causes OB/BOS Acute Rejection Malignancy Infection Heart-lung alone Graft Failure transplant Cardiovascular Technical Multiple Organ Failure All known causes 2018 JHLT. 2018 Oct; 37(10): 1155 -1206 ≤ 1 Year > 1 Year 0 0 0 7 (46. 7%) 1 (6. 7%) 0 2 (13. 3%) 15 14 (1. 7%) 15 (1. 8%) 16 (1. 9%) 206 (24. 8%) 204 (24. 5%) 54 (6. 5%) 123 (14. 8%) 104 (12. 5%) 831 1 (9. 1%) 0 1 (9. 1%) 4 (36. 4%) 1 (9. 1%) 0 0 0 11 224 (21. 9%) 10 (1. 0%) 96 (9. 4%) 246 (24. 0%) 157 (15. 3%) 96 (9. 4%) 13 (1. 3%) 60 (5. 9%) 1, 024 Only the most frequent causes of death are shown on the slide.