Medical Treatment for AS. Disclosures. Valvular Heart Disease. Aortic Stenosis. Severe Symptomatic AS Survival. Disease Progression in Aortic Stenosis

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1 Disclosures Valvular Heart Disease Akshay Desai, MD Brigham and Women s Hospital Harvard Medical School Consultant: Novartis Pharmaceuticals Boston Scientific Intel, Inc. Relypsa, Inc. Research Grants: AtCor Medical, Inc. Aortic Stenosis Disease Progression in Aortic Stenosis Otto C. N Engl J Med 8;359: Medical Treatment for AS Severe Symptomatic AS Survival Schwarz F et al. Circulation 1982;66:115 1

2 Severe Aortic Stenosis Surgical Treatment Indication ACC/AHA 1 ESC Symptoms I(B) I(B) Need for CABG/Ao Surgery I(C) I(C) LVEF <.5 I(C) I(C) Abnormal ETT IIb(C) IIa or b(c) Rapid Progression/Delay IIb(C) IIa(C) AVA <.6cm 2 IIb(C) Severe LVH (>15mm) IIb(C)* Case Study 84 year old man Active and asymptomatic Grade 3 late-peaking murmur ECG: LVH ECHO: Vmax 4.2 m/s, AVA.8 cm 2, EF.6 1. Bonow R et al. J Am Coll Cardiol 6;48; Vahanian A et al. European Heart Journal 7; 28: year old man Asymptomatic Case Study ECHO: Vmax 4.2 m/s, AVA.8 cm 2, EF.6 Watchful waiting Exercise testing TAVI? AVR Indications for Surgery Asymptomatic Severe AS Class IIb Abnormal response to exercise High likelihood of rapid progression Delay from symptom onset to surgery Extremely severe AS (AVA <.6 cm 2, V max > 5. m/s) with low (< 1%) operative mortality risk ACC/AHA Valve Guidelines 6 Transcatheter Aortic-Valve Replacement All Cause Mortality All-cause mortality (%) 6 4 Standard Rx TAVI HR [95% CI] =.54 [.38,.78] P (log rank) <.1 Months Smith CR et al. N Engl J Med 11;364: Numbers at Risk TAVI Standard Rx

3 Time-to-Event Curves for the Primary End Point and Other Selected End Points. PARTNER A 3 day 1 year TAVR AVR p TAVR AVR p Stroke/TIA All TIA Minor Major Major bleed < <.1 Smith CR et al. N Engl J Med 11;364: Data in % Smith C et al. ACC 11 Aortic Regurgitation Etiology VALVE BAV DISEASE RHEUMATIC IE MYXOMATOUS APLA FEN-PHEN? TRAUMA ROOT CT DISORDER DISSECTION IE AORTITIS HTN OTHER (Congenital) Acute Severe AR Urgent AVR 42 y/o woman MSSA AoV IE Normal valve Survival (percent) 6 4 Aortic Regurgitation Survival of Patients Treated Medically FC III-IV IV FC II FC I Survival (percent) 6 4 Aortic Regurgitation Survival After Aortic Valve Replacement p<.2 LVEF > 5% LVEF < 5% Time (years) from Dujardin et al. Circulation 1999;99: Time (years) Forman et al, Am J Cardiol 19;45:

4 Class I Symptoms Severe Aortic Regurgitation Indications for AVR Mild-moderate LV dysfunction (EF.25-.5) Need for other cardiac or aortic surgery Class II LVIDd > 75 mm; LVIDs > 55 mm or > 25mm/m 2 (IIa) LVIDd > 7 mm; LVIDs > 5mm; progressive (IIb) ACC/AHA Valve Guidelines 6 Asymptomatic with Normal LV Function (percent) Aortic Regurgitation Asymptomatic Patients with Normal LV Function 58% 6 n Annual Risk 3.8% 6.2% 4 Endpoints: 45% Symptoms Asymp LVD % of endpoints occur Death 2 4 before onset of symptoms Time (years) Bonow et al. Circulation 1991; 84: Borer et al. Circulation 1998; 97: Aortic Regurgitation Vasodilator Therapy BAV Disease Aortic Valve Replacement (%) 6 4 P=.29 Enalapril Nifedipine Control Years Mean SBP Evangelista A et al. NEJM 5; 353: Fazel SS et al. J Thorac Cardiovasc Surg 8; 135: Cardiac MRI BAV Disease BICUSPID AORTIC VALVE DISEASE CYSTIC MEDIAL DEGENERATION NORMAL VSMC APOPTOSIS? ROLE OF MMP-2 MARFAN BAV Nataatmadja M et al. Circulation 3; 18:II-329.

5 Bicuspid Aortic Valve Dilated Aortic Root Post-Natal Treatment with Propranolol vs Losartan Class I Indications for Surgery Maximal dimension > 5. cm or annual increase in size >.5 cm / year.* Maximal dimension > 4.5 cm and surgery indicated for severe AS or AR.* * Consider lower threshold values for patients of small stature of either gender ACC/AHA Valve Guidelines 6 Habashi J et al. Science 6; 312: Question 1 A 66 year old woman presents with mild dyspnea on exertion. HR 72 reg, BP 156/. Grade 3 late peaking murmur of aortic stenosis. ECG: NSR. LVH TTE: Calcified aortic valve, mean gradient 5 mm Hg, AVA=.8cm2. Wall thickness 1.5 cm. LVEF.75. Question 1 Which of the following treatments would you recommend? a. Diuretic and ACE-inhibitor with close follow-up b. Bioprosthetic aortic valve replacement c. Mechanical aortic valve replacement d. Percutaneous aortic balloon valvuloplasty Mitral Valve The Five Levels Mitral Regurgitation Etiology Leaflets Annulus LA endocardium Chordae tendineae Papillary muscles, LV Otto, CM. NEJM 1; 345:74 ACUTE MR Acute MI (Inf-Post) Endocarditis Trauma Acute on chronic CHRONIC MR Myxomatous Ischemic DCM Rheumatic MAC HOCM Other (APLS, etc.)

6 Rheumatic MR Incidence (%) Incidence of Post-operative LV Dysfunction Stratified by Pre-operative LVESD Medical Therapy Chronic MR ABx prophylaxis when and if indicated No role for vasodilator therapy in asymptomatic, Management of AF normotensive patients with Management chronic of severe CAD MR and normal LV function ACE-I or ARB for HTN, reduced EF < 3 < 35 < 4 < 45 >/= 45 LVESD (mm) Matsumura T et al. J Am Coll Cardiol 3; 42: 458 Chronic Severe MR NYHA FC I Asymptomatic Severe MR Survival with Conservative Management Clinical Eval 6 mo Echo 12 mo EF >.6 ESD < 4 mm No AF? PHT? MV Repair Highly Likely? Yes Class IIa Yes Class IIa MV Repair* MVR MV Repair* EF <.6 ESD > 4 mm Class I No ACC/AHA Valve Guidelines 6 Survival (%) All Patients Flail Leaflet Expected Survival Years Rosenhek R et al. Circulation 6; 113:

7 Ischemic MR Ischemic MR Badiwala, M. V. et al. Circulation 9;1: Mitral Regurgitation in DCM Question 2 A previously asymptomatic 5 yr old woman with mitral valve prolapse and mild mitral regurgitation presents with NYHA Function Class II dyspnea of 6 months duration. She had dental work done 2 weeks before symptom onset without antibiotic prophylaxis. HR 84 reg, BP 12/76. T Grade 3 systolic murmur at the apex. Question 2 Echocardiography now shows moderate-severe MR with a partially flail posterior leaflet. LVEF is 65%. 6 blood cultures are negative. Question 2 Which of the following strategies would you pursue? Careful clinical follow-up with echo studies at 3-month intervals ACE inhibitor therapy Mitral valve replacement Mitral valve repair

8 MITRAL STENOSIS MITRAL STENOSIS ANTICOAGULATION AF: Paroxysmal, Persistent, Permanent Hx TIA/CVA, Systemic embolus Presence of LA thrombus LA > 5.5cm or Spontaneous Contrast PMBV CLASS 1 INDICATIONS Symptoms PA HTN (PA > 5 rest, > 6 ex) Predicated on: 1. Favorable morphology 2. Operator and Lab experience Absent: 1. Moderate to severe MR 2. LA thrombus 3. Inability to perform trans-septal puncture Infective Endocarditis Prophylaxis AHA Guidelines 7 Prophylaxis for dental procedures is recommended only for patients with the highest risk of adverse outcomes from IE. Prosthetic valve Previous IE Congenital heart disease* Cardiac transplant survivor with VHD Question 3 A 71 year old woman with a St. Jude MVR and AF is scheduled for laparoscopic cholecystectomy. She had a TIA 2 years ago. She takes warfarin, low dose aspirin, metoprolol succinate, and furosemide. Labs include INR 3.4, BUN 42, Scr 2.1. Prophylaxis is not recommended for GI or GU procedures. Circulation 7. Published online 4/19/7.

9 Question 3 Which of the following strategies for anticoagulation management would you advise? a. Taper warfarin and operate when INR 2. b. Hold warfarin for 5 days and operate c. Hold warfarin, admit for IV UFH when INR < 2.5 d. Hold warfarin, bridge with enoxaparin, 1 mg/kg bid SYNDROMES ASSOCIATED WITH CONGENITAL HEART DISEASE DOWN S: AV Canal, VSD, Primum ASD TURNER S: Coarctation, AS NOONAN S: PS WILLIAM S: SVAS, PS HOLT-ORAM: Secundum ASD MARFAN: Aortic aneurysm, MVP ATRIAL SEPTAL DEFECT ATRIAL SEPTAL DEFECT Types: secundum, primum, sinus venosus, coronary sinus Exam: Grade 2 MSM, fixed splitting S2 ECG: IRBB. LAD = primum. ECHO: RV volume overload, shunt flow, associated findings (MVP, cleft MV, APVD) SECUNDUM ASD PATENT FORAMEN OVALE Present in 25-3% of population Sometimes associated with interatrial septal aneurysm Implied role in Cryptogenic stroke Migraine Platypnea-orthodeoxia Decompression sickness

10 TETRALOGY OF FALLOT TETRALOGY OF FALLOT VSD (NON-RESTRICTIVE, LARGE) OVERRIDING AORTA RVOT OBSTRUCTION RVH COARCTATION AORTIC COARCTATION BAV DISEASE PRESENTATION: HTN, claudication ASSOCIATIONS: BAV, dissection, intracranial aneurysms, Turner s Syndrome (XO) EXAM: Murmur(s), BP Arm > Leg; pulse delay CXR: 3 Sign, Rib notching TREATMENT: Stenting, surgery OUTCOMES Lembeke A et al.circulation 3;17:e