1. Structural Heart Live Cases
Supported by:
Medtronic Inc
Bard Inc
Acist Medical System
Terumo Medical Corp

2. Disclosures
Samin K. Sharma, MD, FACC None for today’s case Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, ABIOMED, CSI Annapoorna S. Kini, MD, FACC Nothing to disclose Partho Sengupta, MD, FACC Jagat Narula, MD, MACC Research funding and consulting for Medtronics

3. October 13th 2015 Structural Heart Live Case #7: KM 79 yr. M
Presentation: Pt with known HOCM presented on Sept 9th 2015 with progressive exertional dyspnea and fatigue – NYHA class III. Pt had mild inferior wall ischemia on stress MPI. Pt was placed on multiple medications for HOCM but could not tolerate due to near syncopal episodes and presently taking low dose Calcium channel blocker. Also has loop recorder implanted PMH: Hypertension, Hyperlipidemia, chronic diastolic HF Medications: Aspirin, Verapamil, Irbesartan, Atorvastatin, HCTZ TTE: Normal LV size and localized septal hypertrophy (21mm) with SAM of anterior mitral leaflet, high LVOT gradient (rest 22, valsalva 42 and peak stress 141 mmHg), hyperdynamic LV and mild-mod MR

4. Cardiac MRI

5. October 13th 2015 Structural Heart Live Case
Contd….
CMR: Moderate asymmetric septal hypertrophy with LV apical cavity obliteration, patchy areas of intra-myocardial enhancement (myocardial necrosis) and moderate to severe MR
Cardiac Cath: Non-obstructive CAD except 60% calcified mid LAD lesion, hyperdynamic LV and mild MR. FFR mLAD 0.86
Course: Patient was started on increasing doses of verapamil and HCTZ was discontinued. Remained symptomatic and could not tolerate verapamil
Plan Today: Patient is planned for echo guided alcohol septal ablation (ASA) for refractory symptomatic HOCM.
SLIDE TO BE EDITED BY JK

6. Issues Related To The Case
Alcohol septal ablation vs. Surgical my(om)ectomy in treatment of HOCM

7. Background Hypertrophic (obstructive) cardiomyopathy (HOCM/HCM) is
characterized by: - hypertrophy of IVS (>12 mm)
- narrowed LV outflow tract
- systolic anterior motion of MV resulting
in dynamic LV outflow obstruction (one third)
Is the most common genetic CV disease transmitted as
autosomal dominant trait
Occurs in 1 in 500 (0.2%) of general population
In the USA there are currently 300,000 people with HOCM
Most patients are identified in their 30’s and 40’s
<1% of patients are referred for echocardiography
Probably #1 cause of sudden cardiac death in young athlete
More common in men; women likely to be severely disabled

8. Background HOCM/HCM Asymmetric septal hypertrophic (ASH)
without obstruction ( 70%)
Asymmetric septal hypertrophic (ASH)
with obstruction ( 30%)

9. Myocardial Changes in HOCM Morphologic Features for Sudden Death
Disproportionate thickening of the ventricular septum (VS) with respect to left ventricular (LV) free wall; gross heart specimen from a 13-yr old.
Marked disarray of cardiac muscle cells in the disproportionately thickened VS forming typical disorganized architecture of HOCM
LV myocardium showing several abnormal intramural coronary arteries with markedly thickened walls and narrowed lumen, dispersed
Maron et al. JAMA 2002;287:1308

10. Clinical Manifestations
HOCM
Majority of patients are asymptomatic or only mildly symptomatic;
Shortness of breath occurs in 90% of symptomatic patients due to increased LVEDP
Fatigue, presyncope, syncope
Chest pain on exertion in 75% of patients, due to demand-supply imbalance, epicardial coronaries are usually normal
Rarely sudden death.

11. Implications of LV Outflow Tract Obstruction
1,101 consecutive patients with HCM (outflow gradient ≥30 mmHg
Maron et al., N Engl J Med 2003;348:298

12. Effect of LV Outflow Tract Obstruction on Clinical Outcome in HOCM
100 80 60 40 20
No obstruction, <40 yr age
No obstruction, 40 yr age
Freedom from
CHF III-IV
& death (%)
Obstruction, <40 yr age
Obstruction, 40 yr age
Years after gradient measurement
No. at Risk
No obstruction, <40 yr of age
No obstruction, 40 yr of age
Obstruction, <40 yr of age
Obstruction, 40 yr of age
Maron et al., NEJM 2003;348:295

13. Evaluation of LVOT Obstruction
Brockenbrough-Braunwald phenomenon – reliable sign of dynamic obstruction
Mechanism: increased ventricular filling overwhelming by increase in contractility; arterial pulse pressure fails to increase as expected (or decreases)
Dynamic obstruction during the strain phase of a Valsalva maneuver

14. LVOT Obstruction and Symptoms
Mitral Regurgitation
Atrial Fibrillation
Pulmonary Hypertension
Low Cardiac Output
Intermittent Hypotension (Syncope)
Sudden Cardiac Death
ASH
SAM
HOCM
Genetic
disorder
HCM

15. HOCM Management
Goals of Treatment
Improve symptoms
Heart failure, Angina, Syncope
Reduce incidence of SCD
Protect the remainder of the family

16. Primary Treatment Strategies for Subgroups within the HCM Clinical Spectrum
Overall Population with Hypertrophic Cardiomyopathy Clinical Spectrum
Genotype-Positive
Phenotype-Negative
Longitudinal FU
None or
Mild Symptoms
No treatment or
drugs for HOCM
Progressive Heart
Failure Symptoms
Drug therapy
High Risk of
Sudden Death
Implantable Cardioverter-
Defibrillator
Atrial Fibrillation
Pharmacological
rate Control
Cardioversion
Anticoagulation
Drug-refractory Heart Failure Symptoms
Maron B. JAMA 2002;287:1308

17. Primary Treatment Strategies for Subgroups within the HCM Clinical Spectrum
Progressive Heart Failure Symptoms
Drug therapy
Drug-refractory Heart Failure Symptoms
Alternatives to Surgery
- Alcohol Septal Ablation (ASA)
- Chronic Dual-
Chamber Pacing
Obstructive HOCM
(Rest or Provocation)
Ventricular Septal
Myomectomy-Myotomy
Nonobstructive HCM
(Rest or Provocation)
Heart Transplantation
(for end-stage systolic dysfunction)

18. When to Consider Surgery for HOCM
Factors Favoring Myectomy
Young age (including pediatric patients and adolescents)
Massive myocardial thickening >3.0 cm
Intrinsic significant valvular disease or membrane
Significant coronary stenoses, unsuitable for PCI
Baseline LBBB
Midcavity obstruction
Large institutional experience with excellent surgical outcomes

19. Mechanism of Action of ASA in HOCM-
HOCM
Genetic
disorder
HCM +
Obstruction
ASH
SAM
Feedback
Symptoms
LVH

20. Alcohol Septal Ablation in HOCM
Results at Follow-up 3.01.3 Years
Stress-induced LVOT
(mm Hg)
Resting LVOT
(mm Hg)
Peak Oxygen Consumption
(ml/kg/min)
LVEF %
Shamim et al. N Engl J Med 2002;347:1326

21. Alcohol Septal Ablation in HOCM Reduction in Septal Thickness (N=63)
2.5 2
1.5 1
0.5
2.1
1.6
1.3
1.2
1.2
1.1 1
Baseline 3 mo year 2 years 3 years 4 years years
Spencer, Clin Cardiol 2005;28:124

22. When to Consider ASA for HOCM
Factors Favoring ASA
Advanced age
Significant comorbidities that would elevate surgical risk
(i.e., severe lung disease)
Previously implanted pacemaker or ICD
Previous open-heart surgery (including prior failed myectomy)
Prior stroke
Ideal anatomy for alcohol septal ablation: small, focal septal bulge and appropriate sized and placed septal perforator to the target myocardium
Baseline RBBB
Large institutional experience with excellent ASA outcomes

23. Alcohol Septal Ablation in HOCM
Method
One or more septal perforators
1-5cc absolute (desiccated) alcohol
Temporary pacemaker via RIJ
Co-axial guide catheter to avoid trauma to LMCA
Small short balloons (Maverick /9mm)
Runthrough or BMW or any hydrophilic floppy wires
Contrast echocardiography
Liberal use of Versed and Morphine
1cc/min slow continuous alcohol infusion, guided by echo
Measure gradient – catheter and echo
In CCU for 2 days with TPM and then d/c once CKMB <60U

24. ASA: Safety and Complications
In-hospital Mortality
0.7% in North American Registry (n=874)
0.7% in European Multi-center Registry (n=421)
0.3% in Scandinavian Registry (n=313)
Data are similar to Surgical Myectomy mortality as
shown in Mayo Clinic, Cleveland Clinic and Toronto
General Hospital (i.e. <1%)

25. Complete Heart Block after ASA
Multivariate Predictors of PPM Placement after ASA
261 consecutive pts
37 had PPM/AICD before ASA
14% (31/224) developed CHB and required PPM post-ASA
30 pts developed CHB in-hospital, 1 pt came back with CHB in 1 week
Clinical and Echocardiographic Outcome of Pts
Who Require vs Who did Not Require PPM
Chang et al., J Am Coll Cardiol 2003;42:296

26. Alcohol Septal Ablation Vs. Myectomy in HOCM
Average Pressure Gradients at Follow-up
Alcohol Septal Ablation (n = 25)
Myectomy (n = 26)
P=NS
Resting PG (mmHg)
P<0.001
P<0.01
Before Immediately after Follow-up at 3 month
Qin et al., JACC 2001;38:1994

27. Alcohol Septal Ablation Vs. Surgery in HOCM
One-Year Results
Alcohol septal ablation
(n=41)
Surgery P
LVOT gradient (mmHg)
8  15
4  7
<0.01
NYHA class (%): I 88 78 NS II 12 20
III - 2
CCS angina class I (%)
100 93
Presyncope (%) 5 17
Permanent pacemaker (%) 44 41
Due to heart block (%) 9 1
<0.05
Cardiac medications (%)
Beta-blockers 59
Ca antagonists
Disopyramide 7
Amiodarone
none
Sotalol 4
CV death, other events were not different
Nagueh et al., JACC 2001;38:1701

28. Alcohol Septal Ablation vs Myectomy

29. Sudden Death After Invasive Therapy

30. Alcohol Septal Ablation vs Myectomy

32. Survival After Alcohol Septal Ablation
Sorajja et al., Circulation 2012;126:2374

33. Alcohol Septal Ablation vs Myectomy or MT for HCM

34. Mortality and SCD in 1,047 Patients with HCM
Med Treatment (n=124)
ASA (n=321)
Myectomy (n=253)
Control (Non-onbstructive HCM (n=349) %

36. Alcohol Septal Ablation Recommendations
Class I Recommendations:
Septal reduction therapy should only be performed by experienced operators* in the context of a comprehensive HCM clinical program and only for the treatment of eligible patients with severe drug-refractory symptoms and LVOT obstruction.
*Experienced = 20 procedures, then, 5-10 per year afterwards

37. Alcohol Septal Ablation Recommendations
Class IIa Recommendations (select):
Consultation with centers experienced with performing both surgical septal myectomy and alcohol septal ablation is reasonable
Surgical septal myectomy, when performed in experienced centers, can be beneficial and is the first consideration for the majority…

38. Alcohol Septal Ablation Recommendations
Class IIa Recommendation (select):
When surgery is contraindicated or the risk is considered unacceptable because of serious comorbidities or advanced age, alcohol septal ablation, when performed in experienced centers, can be beneficial…

39. Alcohol Septal Ablation Recommendations
Class IIb Recommendations:
Alcohol septal ablation, when performed in experienced centers, may be considered … when, after a balanced and thorough discussion, the patient expresses a preference for septal ablation.
The effectiveness of alcohol septal ablation is uncertain in patients with HCM with marked (i.e. >30 mm) septal hypertrophy, and therefore the procedure is generally discouraged in such patients.

40. Alcohol Septal Ablation Recommendations
Class III Recommendations (select):
Alcohol septal ablation should not be done in patients with HCM with concomitant disease that independently warrants surgical correction.
Alcohol septal ablation should not be done in patients with HCM who are less than 21 years of age and is discourage in adults less than 40.

41. Alcohol Septal Ablation Vs. Myectomy in HOCM
Procedural Data and Choice
Alcohol Septal
Ablation (ASA)
Surgical Myectomy
(SM)
Length of stay (days)
4  2
8  3
PPM
Higher (20%)
Lower (<5%)
Procedure mortality
<1%
Available F/U (yrs)
>5
>30
Septal thickness (mm)
15-25
>25 mm
Treatment of choice
Elderly
with co-morbidities and no significant MR
Young with
no comorbidities and other valve disease/CAD

42. Alcohol Septal Ablation in HOCM
Mount Sinai Hospital Experience (9/ /2014)
N = 168
Mean age (years)
53  12
Female gender (%) 70
Baseline resting gradient mean (mm Hg)
46  18
Baseline post-PVC gradient (mm Hg)
110  32
Post ASA resting gradient (mm Hg)
12  6
Post ASA post-PVC gradient (mm Hg)
32  20
Alcohol dose (cc)
2.5 (1-5)
Peak CPK/ peak MB (U/L)
1800  550 /212 32
Need for permanent pacemaker 12
In-hospital death
1 pt (ref VT)
Average LOS (days)
3  2

44. Evolving Modalities of Treatment for HOCM
Nonalcoholic Percutaneous Transluminal Septal
Ablation Using JOMED Stent Graft
Pre
Post LAD stenting
Vanderheyden et al. AJC 2002;89:361

45. Take Home Message: Alcohol Septal Ablation vs. Myectomy for HOCM
Septal reduction therapy of surgical myectomy &/or ASA are viable options in symptomatic HOCM pts and should be tried only in drug refractory or drug intolerant pts
Alcohol septal ablation is a reasonable treatment option in older HOCM pts (>40yrs) especially with comorbidities which makes them high surgical risk. Need for PPM is >10-20% and may play important role in decision making for alcohol septal ablation

46. Question # 1
Following statements are true regarding surgical myectomy vs. alcohol septal ablation (ASA) for HOCM except:
Improved survival with myectomy vs ASA on long-term
Improved survival after ASA vs myectomy on long-term
Higher residual gradient after ASA vs myectomy
Similar need for PPM with ASA and myectomy

47. Question # 2
Based on the available data, ASA for HOCM will be preferred in the following subset of HOCM pt:
70 year old male with 50mm LVOT gradient and 60% LAD lesion
40 year old male with 50mm LVOT gradient and 80% LM lesion
70 year old male with 50mm LVOT gradient and 4+MR
40 year old male with 50mm LVOT gradient and LBBB

48. Question # 3
Following technique of alcohol injection during ASA for HOCM is associated with higher incidence of need for PPM:
A. Slow injection of 2cc of alcohol
B. Rapid bolus of 2cc of alcohol
C. Intermittent infusion of 4cc of alcohol
D. Alcohol infusion technique has not shown to correlate with PPM need

49. Correct answer: C Answer to Question # 1
Following statements are false regarding surgical myectomy vs. alcohol septal ablation (ASA) for HOCM except:
Improved survival with myectomy vs ASA on long-term
Improved survival after ASA vs myectomy on long-term
Higher residual gradient after ASA vs myectomy
Similar need for PPM with ASA and myectomy
Correct answer: C

50. Correct answer: A Answer to Question # 2
Based on the available data, ASA for HOCM will be preferred in the following subset of HOCM pt:
70 year old male with 50mm LVOT gradient and 60% LAD lesion
40 year old male with 50mm LVOT gradient and 80% LM lesion
70 year old male with 50mm LVOT gradient and 4+MR
40 year old male with 50mm LVOT gradient and LBBB
Correct answer: A

51. Correct answer: B Answer to Question # 3
Following technique of alcohol injection during ASA for HOCM is associated with higher incidence of need for PPM:
A. Slow injection of 2cc of alcohol
B. Rapid bolus of 2cc of alcohol
C. Intermittent infusion of 4cc of alcohol
D. Alcohol infusion technique has not shown to correlate with PPM need
Correct answer: B