1	"Aortic stenosis" Aortic stenosis Cardiology CME Update 2007 Dr. Yaron Shapira Rabin Medical Center
2
3	Etiology – effect of age (1986)
4	Etiology of AS Euro Heart Survey
5	# of leaflets in AS - modern era Isolated AVR, 1993-2004, n=932
6	# of leaflets in AS - modern era Isolated AVR, 1993-2004, n=932
7	Trends in AS
8	Evolution of Valve Disease in Industrialized Nations
9	AS - pathophysiology
10	AS – interrelations of AVA, flow rate and gradients
11	What is severe AS?
12	AS severity AVA >1.5 cm² (>0.9 cm²/m²) - mild 1-1.5 cm² (0.6-0.9 cm²/m²) - moderate <1 cm² - (<0.6 cm²/m²) - severe * Forward velocity across the valve moderate AS - 3.0-4.0 m/s Severe - >4 m/s Braunwald, 7^th Ed: <0.8 cm² for an average sized adult (<0.5 cm²/m²)
13
14	AS severity - ESC guidelines 2007
15	AS severity
16
17
18
19	Effect of valvulo-aortic impedence (“Z”)
20	Mechanism of low-flow, low-gradient severe AS with preserved LV function
21	"What are the reasons for..." What are the reasons for the discrepancies in AVA between cath and echo?
22	Aortic stenosis - physiology
23	Continuity equation AVA = CSA_LVOT × VT I_LVOT/VTI_Ao
24
25	Continuity equation AVA = CSA_LVOT × VT I_LVOT/VTI_Ao
26	Pressure recovery E_k® E_p (downstream) “Overestimation” of gradients (Vs. cath) Pressure recovery - increased pressure distal to vena contracta Values up to 10 mmHg in small St Jude valves May be confused with valve stenosis
27
28	EOA Correction
29	TEE in AS
30	CT in AS
31	MRI in AS
32	Agreement between MRI and other modalities regarding AVA
33
34	Heart catheterization in AS
35	"Retrograde heart catheterization" Retrograde heart catheterization A single German Hospital 152 AS pts: 101 – crossing AV 51 – not crossing AV
36	Findings Acute cerebral embolic events after the procedure: 22 (22%) patients Clinically apparent neurological deficits occurred in 3 (3%) patients None of the patients without passage of the valve, or any of the controls, had evidence of cerebral embolism as assessed by MRI.
37	Conclusion Retrograde catheterization of the aortic valve in AS imposes a substantial risk of clinically apparent cerebral embolism, and frequently causes silent ischaemic brain lesions. The procedure should be used only in patients with unclear echocardiographic findings when additional information is necessary for clinical management.
38
39
40	AS - natural history Yearly mortality in asymptomatic AS - <1% Crude adjusted operative mortality in AVR 4% for isolated AVR 7% for AVR + CABG No data to support prevention LVH & diastolic dysfunction by early AVR Symptoms ®2 year survival < 50%.
41	AS - natural history
42	AVR in symptomatic AS Rationale for AVR Reverse of dismal prognosis Acceptable operative mortality and morbidity Postoperative survival similar to that of age-matched normal adults.
43	Asymptomatic severe AS
44	Asymptomatic severe AS Landmark studies Otto et al. Circ 1997; 95: 2262-70 (Seattle) Rosenhek et al, N Engl J Med 2000;343:611-7 (Vienna) Pellika et al, Circulation 2005; 111: 3290-3295 (Mayo Clinic)
45	Asymptomatic AS
46
47
48
49
50	Influence of rate of progression of stenosis Moderately or severely calcified aortic valves + velocity increase by + 0.3 m/s/y - 79% underwent surgery or died within two years of the observed increase.
51
52
53	"Probability of remaining free of..." Probability of remaining free of cardiac symptoms while unoperated 1y - 82%, 2y- 67% 5y- 33%
54	Exercise testing in AS Goal: To elucidate symptoms / signs in sedentary / dissimulant patients Target population: Patients with moderate or severe AS, who claim to be asymptomatic, and are not excluded from surgery Contraindicated if Unequivocal heart failure Angina Presyncope/syncope
55	Exercise testing in AS Safety: Safe if conducted properly Endpoints: BP fall by >10 mmHg Symptoms Significant arrhythmia Significant ST depression NOT an indication to stop study if unaccompanied by symptoms / hemodynamic / arrhythmic complications
56	Event-free survival for patients with asymptomatic severe AS based on exercise testing results
57	Exercise Stress Echocardiography: a Useful and Safe Tool for the Evaluation of Asymptomatic Patients with Severe Aortic Stenosis. Weisenberg D, Shapira Y. Vaturi M, Monakier D. Battler A, Sagie A. The Dan Sheingarten Echocardiography Unit and Valvular Clinic, Department of Cardiology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
58	Methods - Patients 101 consecutive patients with asymptomatic severe AS AVA <1 cm²and/or mean transvalvular pressure gradient ≥ 50 mmHg)
59	Results ESE was abnormal in 67 pts. Symptoms developed in 48 pts: Dyspnea in 38 Angina in 9 Dizziness in 5 Significant fatigue in 4
60	Results Abnormal BP response : 44 pts (in 24 of them it was the only manifestation of test abnormality). ST segment depression >2 mm: 7 pts. There was no sustained ventricular arrhythmia. There were no cases of syncope or other major complications.
61	Results -Echo data Resting AVA averaged 0.74 ± 0.13 cm². Gradients(mmHg) rest post-exercise Peak 91±19 113±24 Mean 57±13 70±16 Abnormal contractile response: 12 pts.
62	Prognostic Importance of Quantitative Exercise Doppler Echocardiography in Asymptomatic Valvular AS Independent predictors of cardiac events were as follows: An increase in mean transaortic pressure gradient by > or =18 mm Hg during exercise An abnormal exercise test An aortic valve area <0.75 cm².
63	AS with low gradients AVR in AS + LV dysfunction: Higher operative mortality Worse if additional CABG Highest risk period: from induction to pump AVR is never late when associated with LV dysfunction if AVG is high
64	"Jean-Luc Monin et al" Jean-Luc Monin et al Circulation. 2003;108:319
65	Patients 136 patients with aortic stenosis – 6 centers Median age, 72 years(range, 65-77) Median aortic valve area, 0.7 cm² (≤1.0 cm²) Mean transaortic gradient 29 mm Hg F-Uwere obtained in all patients at a median interval of 14 mo(range, 7-29 mo)
66	DSE protocol Initial dose: 5 μg/kg/min Up-titration: 2.5 μg/kg/min every 5 min, up to 20 μg/kg/min or HR >10 above baseline Definition of contractile reserve: ≥20% increase in stroke volume
67	Dobotamine stress echo Presence of LV contractile reserve on the dobutamine stress Dopplerstudy was present in 92 patients (group I) Absent contractile reserve in 44patients (group II)
68	Results Operative mortality: 5% in group I with contractile reserve 32% (10 of 31 patients) in group II without contractile reserve ⁽^P^=0.0002⁾
69	Results
70	Conclusion In the setting of low-gradient AS, surgery seems beneficial for most of the patients with left ventricular contractile reserve. In contrast, the postoperative outcome of patients without reserve is compromised by a high operative mortality. DSE may be factored into the risk-benefit analysis for each patient.
71
72
73	DSE in AS
74	AVR for less than severe AS in patients scheduled for CABG
75	Results after 10 years in 100 patients with mild AS: CABG+AVR vs. CABG only
76	Results after 10 years in 100 patients with moderate AS: CABG+AVR vs. CABG only
77	AVR in mild to moderate AS scheduled for CABG operation No support for uniform policy of AVR for mild or moderate AS In aged (>60-65 years) patients with moderate AS (AVA<0.8 cm²/m²) - consider bioprosthesis All patients with severe AS (AVA<0.6 cm²/m²) and severe CAD should undergo combined surgery
78	Algorithm for AVR during CABG in non-severe AS
79	Should CABG surgery patients with mild or moderate AS undergo concomitant AVR?
80	Mortality and morbidity rates by age with various operations from the STS national database 1995-2000
81	Results
82	Conclusion Effect of age and gradients For average AS progression (5 mmHg/Y), AVR at the time of elective CABG should be based on patient age and severity of AS measured by echocardiography. For patients under age 70 years, an AVR for mild AS is preferred if the peak valve gradient is >25 to 30 mm Hg. For older patients, the threshold increases by 1 to 2 mmHg/Y, so that an 85-year-old patient undergoing CABG should have AVR only if the gradient exceeds 50 mm Hg.
83	Conclusions Effect of progression rate In slow progressors (<3 mm Hg/year), CABG is favored for all patients with AS gradients <50 mm Hg In rapid progressors (>10 mmHg/year), CABG/AVR is favored except for patients >80 years old with a valve gradient <25 mm Hg. Individual comorbidities should also be taken into account
84
85
86	AS – comparison of guidelines
87	AS – comparison of guidelines (cont’d)
88	AS – comparison of guidelines (cont’d)
89	Summary of current approach to AS LV dysfunction – strong argument for AVR (new in AHA/ACC) Importance of exercise test (upgrade in European, downgrade in AHA/ACC Rapid progressors with severe AS – stronger in European Rapid progressors with non-severe AS scheduled for CABG (AHA/ACC) Importance of contractile reserve
90
91	AS – European guidelines
92	AVR - adjusted operative mortality (STS database)
93	Systematic review of the outcome of aortic valve replacement in patients with aortic stenosis Meta- analyzes of the change in LVM and EF after AVR in adult patients 27 articles published between 1980 and 2003 in 1546 AS patients
94	EF change following AVR Increase in EF after surgery was more pronounced in pts who had low preoperative EF (28% vs 40%)
95	LV mass regression following AVR LV mass regression was predominant within the first 6 P/O months - 181 vs. 124 g/ms².) uniformly achieved regardless of age, sex, time of operation, or types of valve substitute.
96	Aortic stenosis Balloon valvotomy 1st experience - Cribier, 1985 Post-procedural AVA 0.7-1.1 cm² Hospital mortality 3.5-13.5% 20-25% - ³1 complication within 24h If not operated - few months of alleviation of symptoms. Benefit disappears within 2 years Later AVR - improves survival
97	PBAV
98
99	Complications of PBAV
100	Survival of octogenarians with AS
101	Balloon valvuloplasty in critical AS with shock
102	Balloon valvuloplasty in critical AS with shock The only independent predictor of mortality is duration of shock 0/10 (0%) survival if shock >48h 4/4 (100%) survival if shock <48h
103	Aortic stenosis Indications for balloon valvotomy Class IIB Hemodynamically unstable patients, as a bridge to AVR (Class IIA in 1998) Palliation in serious comorbidities Class III Alternative to AVR Certain younger adults without valve calcification may be an exception Withdrawn from 1998 Palliation when urgent non-cardiac surgery indicated
104	Limitations of PBAV Final AVA 1 cm² (usually 0.8-0.9 cm²) High procedural mortality High restenosis rate
105	AVR in the Elderly Euro Heart Survey
106	AVR in the Elderly Euro Heart Survey
107	AVR in the Elderly Euro Heart Survey
108	Percutaneous AVR
109	Percutaneous AVR ~ 1/3 of elderly patients with severe AS are declined by cardiac surgeons for AVR and therefore, there is a real need for non surgical AVR. This concept might become a feasible option for treating patients with relevant aortic valve disease but a high operative risk
110	Percutaneous AVR the 1^st case (April 2002) 57-year-old man Severe AS and in cardiogenic shock. Comorbidities Subacute ischemia of the right leg (aorto-bifemoral bypass in 1996, recent occlusion of right limb) Silicosis Lung cancer (lobectomy in 1999) Chronic pancreatitis LVEF of 10%.
111	Percutaneous aortic valve replacement: Myth or reality?
112	Transseptal AVR Antegrade vs retrograde approach
113
114	Percutaneous AVR – acute effects
115	Extended experience Cribier Mean gradient (mm Hg) 43 → 8.5 (p=0.0076). The AVA was 0.56 → 1.69 cm² (P=0.0076)
116	Cribier-Edwards valve Technical failures in USA with antegrade approach Catastrophe in live TCT demonstration (acute MR) 15/6/05 – USA study withheld (3 months after its start) Successful implantation using retrograde approach (St. Paul hospital, British Columbia)
117	Treatment of Calcific Aortic Stenosis With the Percutaneous Heart Valve Mid-Term Follow-Up From the Initial Feasibility Studies: The French Experience
118	Methods N=36 AVA ≤0.7 cm2 NYHA functional class IV Severe comorbidities Formally declined for surgery, were recruited on a compassionate basis.
119
120	Results Successful implantation – 27 (23 antegrade, 4 retrograde) Increase in AVA - 0.60 ± 0.11 cm2 to 1.70 ± 0.10 cm2, p < 0.0001) Decrease in AV gradient - 37 ± 13 mm Hg to 9 ± 2 mm Hg, p < 0.0001). Paravalvular AR 0 to 1 (n = 10) grade 2 (n = 12) grade 3 (n = 5).
121	Improvement in AVA
122
123	LV function 1W post-procedure, improvement in left ventricular function (45 ± 18% to 53 ± 14%, p = 0.02) was most pronounced in patients with ejection fraction <50% (35 ± 10% to 50 ± 16%, p < 0.0001).
124
125	Improvement in LVEF (1W) Patients with LVEF<50% (n=15)
126	Complications 30d major adverse events after successful implantation were 26% pericardial tamponade Stroke Arrhythmia Urosepsis One death unexplained at autopsy.
127	Follow-up 11 patients are currently alive F-U 9 months (n = 2) 10 months (n = 3) 11 months (n = 1) 12 months (n = 2) 23 months (n = 1) 26 months (n = 2). All patients experienced amelioration of symptoms (>90% NYHA functional class I to II). Percutaneous heart valve function remained unchanged during follow-up, and no deaths were device-related.
128
129
130
131
132
133	Percutaneous AVR open questions Duarbility Perivalvular leak Migration Resection of native valve Implantability
134	Revive study REVIVE Trial: Registry of EndoVascular Implantation of Valves in Europe
135
136
137
138
139
140	AS and pulmonary HTN N=388, symptomatic AS, direct PAP measurement PAP<30 - 35% PAP 31-50 - 50% PAP >50 - 15% Poor correlation between PAP and AVA or LV function Good correlation between PAP and LVEDP, PCW pressure and trans-pulmonary gradients
141	AS and pulmonary HTN PHT more prevalent in associated systemic HTN PHT mainly reflects diastolic dysfunction Conflicting data on surgical outcome PAP regression - better in larger prostheses
142	Can we delay AS progression?
143
144
145	AS progression Yearly rate of AS progression 0.1 cm² 0.3 m/s 6-8 mmHg Considerable individual variability Methodological flaws Selected population Many with short F-U period Technical difficulties, esp. in critical stenosis
146	Potential determinants of AS progression Echo factors Leaflet calcifications Leaflet thickening Baseline AVA Clinical factors Men Older age Smoking Cholesterol CRF/dialysis Ca/Phos product Hypertension Etiology
147	Pathophysiology and Concepts in AS Progression Lipid process - (“cholesterol hypothesis“) Inflammatory process Renin angiotensin system Calcification and ossification Genetic factors All these processes are involved in atherosclerosis
148
149	Effect of lipid lowering on AS progression
150	Effect of lipid lowering on AS progression
151	Moura et al, Rosuvastatin Affecting Aortic Valve Endothelium (RAAVE) to Slow the Progression of Aortic Stenosis. J Am Coll Cardiol, 2007; 49:554-561
152
153
154	Conclusions Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process.
155	Future studies (ongoing) 2 prospective, randomized, placebo-controlled multicenter studies of lipid-lowering therapy to prevent AS progression: ASTRONOMER (the Aortic Stenosis Progression Observation: Measuring Effect of Rosuvastatin) (Canada) SEAS (the Simvastatin and Ezetimide in Aortic Stenosis) (Europe)
156
157	Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis Khot et al, N Engl J Med 2003; 348; 1756-63
158	Background Vasodilators are considered to be contraindicatedin patients with severe aortic stenosis because of concern thatthey may precipitate life-threatening hypotension. However,vasodilators such as nitroprusside may improve myocardial performanceif peripheral vasoconstriction is contributing to afterload.
159	Aim To determined the response to intravenous nitroprussidein 25 patients with severe aortic stenosis and left ventricularsystolic dysfunction
160	Results After 6h of therapy with nitroprusside the cardiac index had increased to 2.22 After 24h of nitroprusside infusion the cardiac index had increased further, to 2.52
161	Results
162	Results
163	Conclusions Nitroprusside rapidly and markedly improves cardiacfunction in patients with decompensated heart failure due tosevere left ventricular systolic dysfunction and severe AS. It provides a safe and effective bridge to AVR or oral vasodilator therapy in these criticallyill patients.