Chronic Primary Mitral Regurgitation The Case For Early Surgical Intervention William K. Freeman, MD, FACC, FASE
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Watchful Waiting...... Is Looking for Trouble
Quantitative Determinants of Outcome of Asymptomatic MR Initial Patient Characteristics 456 Asymptomatic patients with MR Mean age 63 ± 14 yrs MR regurgitant volume 66 ± 40 cm 3, ERO 40 ± 27 mm 2 ; (Gr IV/IV in 54%) LVEF: 70 ± 8%, LVESD: 34 ± 6 mm Systolic PAP: 38 ± 11 mmhg Sarano ME et al: NEJM 352:875, 2005
Quantitative Determinants of Outcome of Asymptomatic MR Patient Follow-up Follow-up: 5.1 ± 2.9 yrs 5 Yr freedom from surgery: 46 ± 3% 5 Yr freedom from surgery/death: 36 ± 3% Triggers for mitral valve surgery Cardiac symptoms: 41% LVESD 40 mm: 39% Other: 20% Sarano ME et al: NEJM 352:875, 2005
Quantitative Determinants of Outcome of Asymptomatic MR Events: Cardiac Death, CHF, New Atrial Fibrillation 70 60 ERO < 20 mm 2 ERO 20-39 mm 2 ERO 40 mm 2 62±8% 50 Rate of cardiac events (%) 40 30 P<0.01 40±7% 20 10 15±4% 0 0 1 2 3 4 5 Years Sarano ME et al: NEJM 352:875, 2005
Quantitative Determinants of Outcome of Asymptomatic MR Death From Cardiac Causes Cardiac Death (%) 50 40 30 20 ERO <20 mm 2 20-39 mm 2 40 mm 2 P<0.01 36±9% 20±6% 10 0 0 1 2 3 4 5 Years 3±2% Sarano ME et al: NEJM 352:875, 2005
Waiting for Symptoms...... Is Asking for Trouble
Adjusted survival from diagnosis (%) Early Surgery vs Conservative Therapy For Severe MR Impact of Preoperative Symptoms 100 NYHA I-II 84 NYHA III-IV 80 69 60 67 40 47 20 Early surgery Conservative Rx P < 0.02 0 0 2 4 6 8 10 Years Ling et al: Circulation 1997; 96: 1819 0 2 4 6 8 10 Years
Cardiopulmonary Exercise Testing in Asymptomatic MR: Is the Patient Truly Asymptomatic? 134 Asymptomatic patients; 63 ± 14 yrs MR regurgitant volume 68 ± 24 cm 3, ERO 35 ± 14 mm 2 ; LVEF 73±6% Reduced functional capacity (<84% predicted) related to MR in 19% Peak VO 2 22 ± 5 (74 ± 8% Predicted) Messika-Zeitoun D, et al. JACC 2006; 47: 2521
Patients with cardiac events or surgery (%) Cardiopulmonary Exercise Testing in Asymptomatic MR Events: Death, Heart Failure, Surgery, AFib 100 80 60 Functional capacity Reduced Normal 40 20 0 P=0.001 0 1 2 3 Years Messika-Zeitoun et al: JACC 47:2521, 2006
Asymptomatic MR: Exercise Induced Pulmonary Hypertension Is the Patient Truly Asymptomatic? 49 Asymptomatic patients with MR MR ERO 0.40 ± 0.14 cm 2, RVSP 30 ± 7 mmhg LVEF 67 ± 7 %, LVESD 31 ± 6 mm Symptom limited exercise echo VO 2 stress 24% with <80% functional aerobic capacity (FAC) Exercise induced pulmonary hypertension (RVSP 60 mmhg) the strongest multivariate predictor of poor FAC and onset of symptoms Suzuki K, et al. J Cardiol 2015; 66: 246
Sensitivity Asymptomatic MR: Exercise Induced Pulmonary Hypertension Is the Patient Truly Asymptomatic? 1.0 0.8 0.6 0.4 0.2 Systolic PAP Exercise* C = 0.88 Exercise Resting C = 0.52 *Adjusted for age and gender 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1-specificity Suzuki K, et al. J Cardiol 2015; 66: 246
Symptom-free survival Asymptomatic MR: Exercise Induced Pulmonary Hypertension Is the Patient Truly Asymptomatic? 1.0 0.8 0.6 Patients at Risk 0.4 0.2 0.0 No Exercise Induced Pulmonary HTN Exercise Induced Systolic PAP 60 mmhg 0 5 10 15 20 25 Months P=0.003 31 31 31 30 29 29 18 14 11 11 11 11 Suzuki K, et al. J Cardiol 2015; 66: 246
Asymptomatic MR: Exercise Induced Pulmonary Hypertension Post-Op Events: Heart Failure, Stroke, Death 104 Patients; mean age 64 ± 12 yrs MR ERO 0.40 ± 0.07 cm 2, RVSP 36 ± 7 mmhg LVEF 71 ± 5 %, LVESD 34 ± 6 mm Preoperative exercise echo: 58% of patients had exercise induced pulmonary HTN (RVSP 60 mmhg) Mitral surgery for isolated primary MR directed by ACC/AHA guideline triggers Magne J, et al. Heart 2015; 101: 391
Postop event-free survival (%) Asymptomatic MR: Exercise Induced Pulmonary Hypertension Post-Op Events: Heart Failure, Stroke, Death 100 90±4 90±4 90±4 90±4 80 60 85±5 79±5 67±7 Patients at Risk 40 20 0 No Exercise Pulmonary HTN Exercise Pulmonary HTN 37±14 0 12 24 36 48 60 72 84 96 Months Follow-up 43 37 26 6 2 59 48 37 15 4 P=0.003 Magne J, et al. Heart 2015; 101: 391
And we must be wary... of the ultimate end-point
Sudden Death in Severe MR Due to Flail Leaflet 348 Patients with flail MV leaflet Mean age: 67 ± 12 yrs; 48 ± 41 mo. F/U Under medical therapy: 99 deaths Sudden death: 25 patients (7.2%) Sudden death multivariate predictors : NYHA functional class LVEF (mean initial EF 63 ± 10%) Atrial fibrillation Grigioni F, et al. JACC 1999; 34:2078
Incidence (%) Sudden Death in Severe MR Due to Flail Leaflet 100 80 Total mortality Cardiac mortality Sudden death 60 40 20 0 53±5 43±5 19±4 0 1 2 3 4 5 6 7 8 9 10 Years after diagnosis Grigioni F, et al. JACC 1999; 34:2078
Sudden Death in Severe MR Due to Flail Leaflet: Relation to NYHA Functional Class 10 8 7.8 ± 3.2 Yearly rate of sudden death (%/year) 6 4 3.1 ± 1.0 2 0 1.0 ± 0.3 NYHA I NYHA II NYHA III-IV Grigioni F, et al. JACC 1999; 34:2078
Sudden Death in Severe MR Due to Flail Leaflet: Relation to LVEF 15 12.7 ± 5.2 10 5 1.5 ± 0.4 0.9 ± 0.6 0 60 50-59 < 50 LVEF (%) Grigioni F, et al. JACC 1999; 34:2078
Sudden Death in Severe MR Due to Flail Leaflet: Sinus Rhythm vs. Atrial Fibrillation 10 8 6 4.9 ± 1.6 4 2 0 1.3 ± 0.3 Sinus Rhythm Atrial Fibrillation Grigioni F, et al. JACC 1999; 34:2078
Sudden Death in Severe MR Due to Flail Mitral Leaflet In patients NYHA Class I-II, in sinus rhythm, LVEF 60%, and no history of CAD: Rate of sudden death = 0.8% / yr Grigioni F, et al. JACC 1999; 34:2078
If There Are No Randomized Controlled Trials...... Perform a Meta - Analysis
Early Surgical Intervention vs. Watchful Waiting for Asymptomatic MR A Meta-Analysis Observational studies; tertiary referral Asymptomatic patients without Class I Guideline triggers for surgery All primary (degenerative) MR etiology All included a watching waiting cohort Goldstone AB, et al. Ann Cardiothorac Surg 2015; 4: 220
Timing of Surgical Intervention for Asymptomatic MR (No Class I Trigger) All Cause Mortality (1,823 Patients) Study HR Lower limit Upper limit Z P HR (95% CI) Kang (2014) 0.509 0.241 1.076-1.769 0.077 Suri (2103) 0.520 0.346 0.781-3.149 0.002 Montant (2009) 0.190 0.093 0.388-4.566 0.000 0.38 0.206 0.708-3.057 0.002 0.1 0.2 0.5 1 2 5 10 Favors early surgery Favors Watchful waiting Goldstone AB, et al. Ann Cardiothorac Surg 2015; 4: 220
Timing of Surgical Intervention for Asymptomatic MR (No Class I Trigger) Mitral Repair Rate (1,631 Patients) Study HR Lower limit Upper limit Z P HR (95% CI) Kang (2014) 1.155 1.047 1.273 2.879 0.004 Suri (2013) 1.069 1.019 1.122 2.718 0.007 1.10 1.022 1.179 2.559 0.010 0.5 1 2 Favors Watchful waiting Favors early surgery Goldstone AB, et al. Ann Cardiothorac Surg 2015; 4: 220
A Stitch in Time...... Saves Nine
Surgery for MR: The Importance of Experience and Volume STS Database (13,614 MV operations) Hospital Mitral Procedures / Year 35 36-70 71-140 > 140 Operative Mortality MV Repair Rate 3.1% 2.3% 2.0% 1.1% 48% 55% 65% 78% Gammie JS, et al. Circulation 2007; 115: 881
Elective Mitral Repair For Severe MR vs. Risk of Sudden Death Risk of Sudden Death (0.8%/yr) Operative Mortality* (0-0.5%) * High volume, tertiary referral surgical centers Grigioni F, et al. JACC 1999; 34:2078 Kang DH et al. Circulation 2009; 119:797 DeBonis M, et al Eur Heart J 2013;34;13 Suri RM et al. JAMA 2013; 310:609 Yazdchi F, et al. Ann Thorac Surg 2015; 99:1992
Are we delaying surgery too long.... with the current guideline triggers to intervention?
Current (2014) Guideline Indications Triggering Surgery for Severe MR Is There an Outcome Penalty? 1,512 Patients: Surgery for Primary MR Class I Triggers: Class II Triggers: Class II Triggers: Cardiac Symptoms, LVEF < 60%, or LVESD > 40 mm (n = 794) Clinical complications: New AFib, or pulmonary HTN (n = 195) Early Asymptomatic: Gr 4/4 MR, High probability of MV Repair only (n = 523) Sarano ME, et al. J Thorac Cardiovasc Surg 2015; 150: 50 Nishimura RA, CM Otto, et al. JACC 2014; 63: e57
Guideline Indication Triggers for Surgery in Severe MR: Impact on Post-Op Survival Post-op survival (%) Patients at Risk 100 80 60 40 20 0 Triggers 94±1 87±2 84±1 86±2 73±3 64±2 Class II - High Prob Repair Class II - New AFib, PHTN Class I Sxs, LVEF, LVESD 70±3 53±4 42±2 P<0.0001 61±5 40±7 27±3 0 5 10 15 20 Years 523 488 403 68 6 195 168 127 38 3 794 664 461 135 13 Sarano ME, et al. J Thorac Cardiovasc Surg 2015; 150: 50
Guideline Indication Triggers for Surgery in Severe MR: Impact on Outcome 80 60 40 20 0 Patients at Risk Heart Failure Triggers Class II - High Prob Repair Class II - New AFib, PHTN Class I Sxs, LVEF, LVESD P<0.0001 14±1 10±2 3±1 Death or Heart Failure P<0.0001 0 5 10 15 0 5 10 15 Years 24±2 21±3 6±1 35±2 27±4 15±3 24±2 20±3 Years 46±2 39±4 65±2 55±4 478 383 61 478 382 61 155 110 33 155 110 33 592 383 107 592 383 107 7±1 19±2 37±3 Sarano ME, et al. J Thorac Cardiovasc Surg 2015; 150: 50
Overall survival (%) Left Ventricular End-Systolic Dimension (LVESD) in Severe MR MIDA Database: 739 Patients with Flail Lealflet 1.0 Watchful Waiting Surgical Intervention 0.8 0.6 0.4 0.2 0.0 LVESD (mm) <40 40 0 2 4 6 8 10 Years 64±5 48±10 P<0.001 72±3 64±5 P=0.04 0 2 4 6 8 10 Years Tribouilloy et al: JACC 2009; 54:1961
Left Ventricular End-Systolic Dimension (LVESD) in Severe MR Risk of Mortality With Watchful Waiting Risk Ratio of Death 10 3.2 1.0 Indexed cut-point for increased mortality: LVESD 22 mm/m 2 0.3 20 25 30 35 40 45 50 LVESD (mm) Tribouilloy et al: JACC 2009; 54:1961
Severe MR: The Fallacy of Normal Preoperative LV Function LVEF (%) Post-Op LV Ejection Fraction 50% (n = 1,391) < 50% (n = 314) Pre-Op Post-Op LVESD (mm) Pre-Op Post-Op 66.8 ± 4.8 65.3 ± 4.0 59.2 ± 5.8 41.8 ± 6.2 34.2 ± 4.6 37.7 ± 4.4 33.4 ± 5.1 41.9 ± 5.4 p<0.001 p<0.001 p<0.001 Quintana E, et al. J Thorac Cardiovasc Surg 2014; 148; 2752
Severe MR: Predictors of Early Postoperative LVEF < 40% * OR (± 95% CI) RVSP > 49 mmhg 4.40 (2.35-8.23) LVESD > 36 mm 6.46 (3.31-13.61) 1 2 3 4 5 6 7 8 9 10 11 12 13 * Post-Operative Death HR = 1.74 (1.03-2.92) Quintana E, et al. J Thorac Cardiovasc Surg 2014; 148; 2752
Severe Primary Mitral Regurgitation: The Case for Early Surgical Intervention Conclusions Unoperated severe MR has serious clinical consequences, even if asymptomatic Clinical symptom status is often unreliable Stress testing discriminates elusive functional status and prognosticates Early surgical intervention improves outcome Selection of surgical center and surgeon is critical Current ACC/AHA guideline triggers to surgery may delay intervention, resulting in suboptimal outcome Why wait for the inevitable, and increase patient risk?