1. Percutaneous Septal Myocardial Ablation (PASMA) Cardiovascular Institute & Fu Wai Hospital Chinese Academy of Medical Science You Shi Jie MD 2010.7. 23 GuiYang 经皮间隔支化学消融治疗肥厚梗阻性心肌病

2. Introduction  Treatment of symptomatic patients with HOCM aims to reduce symptoms, improve function capacity and provide better quality life.  Aims directly to reduce the hypertrophied interventricular septum with consecutive expansion of the LV outflow tract and reduction of the LV outflow tract gradient and improve distolic function LV.  First choice druges treatment. At least 10% of patients with marked outflow tract obstruction have severe symptoms, which are unresponsive to medical therapy.  HOCM Myectomy  DDD-PM  ICD  PTSMA

3. Hypertrophic cardiomyopathy Epidemiological characteristics  Hypertrophic cardiomyopathy incidence of 0.2% (1:500), 0.16% in our country.  Hypertrophic cardiomyopathy incidence of 0.2% (1:500), 0.16% in our country.  The vast majority of patients with no symptoms,  25% of outflow tract obstruction occurred  only about 5-10% of patients with drug treatments fail or cause serious side effects of drugs effective dose.  Require treatment or surgical intervention in patients treated with only very few parts.

4. Pathophysiologic and clinical characteristics of HOCM Ventricular hypertrophy  Ventricular hypertrophy  Left ventricular outflow tract pressure gradient  Myocardial ischemia-angina pectoris.  Arrhythmia -.  Arrhythmia - ventricular tachycardia, fibrillation.  Clinical manifestations: dizziness, amaurosis, syncope, exertional shortness of breath, angina pectoris, heart disfunction and sudden death.  Generally considered: more severe hypertrophy, outflow tract obstruction near the LVOT sit, the more higher the obstructive pressure gradient were the more obvious clinical symptoms and the greater the potential threat.

5. The natural course of outflow tract obstruction  Level –any ages.  there is a big difference in Natural history  The natural course  The natural course not sure.  The more cardiac hypertrophy, the higher the pressure gradient, the greater the risk of sudden death.  The outflow tract pressure gradient of the clinical importance of the issue remains controversial, but it is generally considered an important clinical process indicators.  Nnual mortality rate of 2-4%, the incidence of sudden death ≤1%

6. The symptoms Whether the obstruction produced the clinical symptoms? not only with the degree of outflow tract obstruction and outflow tract pressure gradient, as well as the obstruction site. But also with ventricular diastolic function and the adequacy of venous return is also closely related. Increase the heart before and after load and myocardial contractility often cause noticeable clinical symptoms. Therefore, it will become more apparent after exercise. The patients should be treatment.

7. Diastolic dysfunction ♦ All patients had diastolic dysfunction – ♦ How the pressure gradient and symptoms ♦ And the extent and distribution of the hypertrophy has nothing to do. ♦ Whether normal or small ventricular cavity, due to increased heart weight, ventricular volume reduction, myocardial fibrosis, leaving ventricular stiffness increased, compliance decreased and caused the diastolic function damage. Pulmonary venous pressure and end-diastolic pressure were increased and heart disfunction.

8. systolic function  Systolic function is normal or supranormal in HCOM  Both obstruction and non-obstruction, Systolic dysfunction occurs in small subset (10-15%)  Result of progressive impairment of systolic function.  This transformation: wall thinning, cavity dilation, and fibrosis, increased mortality 11% (annual ) and risk of SCD.  Conventional UCG, M-mode, or EF, fractional shortening preserved despite impaiment long-axis function  Tissue Doppler image (TD)-derived systolic velocities: in the basal inferoseptal and anterolateral wall routinely in all patients on subsequent scans.

9. Myocardial ischemia Myocardial ischemia, the symptoms of angina pectoris are: High-power so that left ventricular myocardial oxygen consumption increased; Cardiac contraction strength of oppression the large myocardial coronary artery; Intramyocardial small coronary artery stenosis and intimal thickening abnormalities, leading to cardiac hypertrophy and coronary artery oxygen required due to an imbalance of oxygen supply.

10. Arrhythmia and Arrhythmia and sudden death  HOCM of patients with abnormal myocardial cells and the arrangement of disorder provides a basis for the arrhythmia.  However, abnormal myocardial arrangement and spontaneous arrhythmias and ventricular fibrillation threshold, the precise relationship is unclear.  About 25% of patients may have non-sustained ventricular tachycardia, the arrhythmia is sudden death of a good predictor, and negative predictive accuracy is 97%.

11. Risk factors for sudden death High-risk:High-risk: 1 Sudden death occurred in a successful rescue 2 continuous monomorphic ventricular tachycardia Clinical risk factors: 1 non-sustained ventricular tachycardia 2 movement abnormal blood pressure response ( ≥ 25mmHg) 3 unexplained syncope 4 early-onset family history of sudden death 5 severe left ventricular hypertrophy> 30mm 1 Sudden death occurred in a successful rescue 2 continuous monomorphic ventricular tachycardia Clinical risk factors: 1 non-sustained ventricular tachycardia 2 movement abnormal blood pressure response ( ≥ 25mmHg) 3 unexplained syncope 4 early-onset family history of sudden death 5 severe left ventricular hypertrophy> 30mm

12. The purpose of the treatment PTMSA  Treatment of symptomatic patients with HOCM  The PTMSA treatment of HOCM is a obstruction by blocking a the supply blood of parts of the septal hypertrophy of myocardial and myocardial injury in the region, leading to the area of myocardial necrosis, myocardial contractile function disappeared, Widened the left ventricular outflow tract, while lowering the outflow tract obstruction and the cardiac output increase. And improve clinical symptoms and hemodynamics.

13. PTSMA indication (1) Clinical indication Symptomatic patients  Drug refractory severe said effects medical treatment  Functional class III or IV  Functional class II with objective limitation or risk factors  Recurrent exercise-induced syncopes  Failure of prior myectomy or DDD-PM  Comorbitiy with increased surgical risk.

14. PTSMA indication (2) Hemodynamic indication in symptomatic patients  The pressure gradient at rest > 50mmHg or > 100mmHg with provocation. LV gradient ≧ 30 mmHg at rest or Provocable LV gradient ≧ 60 mmHg.  In 2008 ESC meeting, Seggewise that LV gradient ≧ 30 mmHg at rest or Provocable LV gradient ≧ 60 mmHg.  Valsalva  Post extrasystole.  No dobutamine gradients (Drugs) (There is no information that reduce the LVOT pressure to reduce sudden death, but the LVOT> 30mmHg and increased risk of death directly related to, New Eng l J Med 2003; 348:295-303) (There is no information that reduce the LVOT pressure to reduce sudden death, but the LVOT> 30mmHg and increased risk of death directly related to, New Eng l J Med 2003; 348:295-303)

15. Hypertrophic Cardiomyopathy Survival According to Outflow Tract Gradient BJ Maron et al; JAMA 281:650-655, 1999

16. PTSMA indication (3) Morophologic indication Echocariography Subaorrtic SAM-associated gradient Subaorrtic SAM-associated gradient Mid-cavitary gradient Mid-cavitary gradient Caution: papillary muscle involvement: Caution: papillary muscle involvement: MCE MCE No prolonged mitral leaflets No prolonged mitral leaflets Coronary angiography suitable septal branch. suitable septal branch.

17. Outflow tract obstruction sign in Echocardiograph M-mode echocardiogram in obstructive hypertrophic cardiomyopathy showing systolic anterior motion of the mitral valve (SAM) (arrows indicating septum and mitral valve leaflet contact)

18. Morphologic of HOCM Morphologic of HOCM New classfication of HOCM Methods: they were classified into 4 types according to the echocardiographic results: Type I :local subaortic obstruction of HOCM; Type II: predominant in midventicular obstruction; Type III: diffuse septal hypertrophic obstruction in outflow tract and midventicular obstruction; Type IV: multiposition hypertrophic obtruction. 1.asymmetrical septal hypertrophy (ASH), 2.Idiopathic hypertrophic subaortic stenosis (IHSS), 3.Apical or Japanese HCM. In this form of nonobstructive HCM, the thickest part of the left ventricle is at the tip or apex of the pump.4. the obstruction is not in the outflow tract but in the middle of the ventricle. A tunnel leads into a dilated apical portion, called an aneurysm, which has thin walls.

19. Our classfication in PTSMA Maron Our typing in the I-type and Maron in the I- typing was the same as suitable for PTSMA treatment and Maron's II-type includes the type II and type III of our model, it is suitable PTSMA treatment. Therefore, our IV-type classification is the first made by ultrasound imaging features of HOCM, according to its characteristics in line with PTSMA treatment.

20. Target vessel  Select ablation of regional importance, particularly in the target vessel is not clear who the septal branch The first septal branch of the size and distribution are great variation  20% of patients first branch was supplied the free wall of right ventricle  40% of patients with of septal is not completely supported by the first septal branch  40% of patients with subaortic of septal is not completely supported by the first septal branch  5% of patients can not determine the target vessel of the region

21. Contrast echocardiography method in the target vessechoice Contrast echocardiography method in the target vesse choice 1.Injection of a small amount of dye (1-2ml) through the guidewire lumen of the inflated balloon catheter angiographically 2.Prior to alcohol injection 1-2ml of echo contrast medium is administered through the central lumen of the balloon catheter under UCG. determines the supply area of the target septal branch. Ensure that no areas involving non-obstructive, such as the papillary muscles and ventricular free wall and other parts.

22. Myocardial - Contrast - Echoin HOCM Myocardial - Contrast - Echo in HOCM Avoid LAD ballooningExclude LAD leakage

23. Septal Ablation in HOCM Myocardial - Contrast - Echo Levovist  In the interval of contrast agent injected into the branch to observe the distribution of vascular contr Alcohol  Shadow 

24. Levovist shadow

25. Echo sequence: Subaortic septum as targetbregion in typical SAM- associated, subaortic obstraction, ( D dotted line), E test injection of the echo contrast agent in balloon of the the first setal branch of a forward branch of position highlighting be basal half of septum plus a RV papillary muscle (white arrows). After super- selective balloon of other branch of first septal branch. Correct opacification.

26. MCE N=222 No MCE n=30 P Septal branches (n)1.0±0.11.3±0.2 <0.0001 Alcohol (ml)2.9±0.93.9±2.4 <0.0001 Balloon size (mm)1.9±0.42.4±0.2 <0.0001 CK max (U/l)534±248745±420 <0.001 CK-MB max (U/l)62±3096±62 <0.0001 H. Seggewiss et al, 49th Scientific Sessions ACC, 2000 Septal Ablation in HOCM Acute Results / Ablation Technique

27. H. Seggewiss et al, 49th Scientific Sessions ACC, 2000 Septal Ablation in HOCM Acute Results / Ablation Technique p<0.05 p<0.01

28. keys of TechnologyPTSMA keys of Technology of PTSMA The key technology: The key technology:  identification at subaortic and left ventricular  identification The pressure gradient at subaortic and left ventricular  identification suitable of target septal branches.  Must be inserted temporary pacemaker (to prevent the conduction block).  Simultaneous monitoring of aortic and left ventricular pressure.  Heparin ( to prevent catheter induced thrombosis).  Analgesic  Guiding catheter: supporting flexible and low injury  Suitable Over-the-wire balloon catheter

29. The keys of TechnologyPTSMA The keys of Technology PTSMA  Intraoperative ultrasound monitoring  Contrast echocardigraphy  Pay close attention to the pressure gauge  under fluoroscopy (observation balloon expansion of state).  Injection of alcohol dose and speed  determine whether should injury (catheter or alcohol) and the interval branch block (necrosis state) conditions  1 (with complications) or 2 septal branches ablation did not significantly reduce the pressure, and no increase alcohol dose  Remove balloon should be emptying alcohol of the balloon catheter and stagnation injection alcohol

30. A 51-year-old woman’s LVOT gradient was monitored continuously just before the balloon occlusion. (PG=80mmHg) LV AO

31. Her LVOT gradient 10 minutes after septal ablation （ PG=12mmHg ） LV AO

32. A 36-year-old man’s LVOT gradient tested by Doppler echocardiography before PTSMA (PG=219mmHg)

33. His LVOT gradient 6 months after PTSMA ( PG=15mmHg)

37. PG120mmHg before procedure

38. PG=40mmHg after injection of 4.8 ml alchohol

39. Great attention Echocardiography showed ventricular septal hypertrophy over 30 mm in HOCM, necessary to performeing PTSMA should be very cautious and careful. May be there were a thick septal branch, and control wide, and collateral-rich septal branch of support, treatment had a higher risk and improve the clinical symptoms and hemodynamics have difficulties, so surgery mytomce may be a better choice.

40. It is very big septal branch > 2.5mm and too long. There is quite danger to PTMSA

41. PTSMA contraindications  No significant pressure gradient in hypertrophic cardiomyopathy or very diffuse obstructive.  Merge other needs surgery heart disease Mitral valve abnormalities and their own form of papillary muscles involved in the formation of pressure gradient, or mitral valve prolapse and regurgitation.  can not determine target vessel or the obstruction of regional no suitable target vessel.  Contrast echocardiography can not determine target vessel or the obstruction of regional no suitable target vessel.  Target vessel supply to non-obstruction other regions such as: papillary muscle, free wall, etc.  Not suitable  Not suitable Over-the-wire balloon.

42. PTSMA complications (1)  Hospital mortality rate :1-2%  DDD-pacemaker :2-10%  Myocardial infarction Reason: alcohol leakage into the parts of inappropriate, collateral branch opening, alcohol into the inappropriate parts cause no-reflow, LAD / LM / RCA injury  Emergency surgery Reason: coronary artery injury, acute mitral regurgitation (papillary muscle rupture )  Bundle branch block: about 50% and RBBB- based

43. PTSMA complications (2)  Height or III °-AVB Factors: whether the method of application of myocardial contrast echocardiography. Dose of alcohol and speed. Dose of alcohol and speed.  Left anterior descending artery dissection, coronary thrombosis, ventricular fibrillation and ventricular tachycardia, acute mitral regurgitation, right ventricular infarction, left ventricular free wall infarction.

44. PTSMA shortcomings  Injury of the left coronary artery required emergency bypass or stent  Can not enter the target septal branch  Can not enter the target septal branch  Can not determine the target branch of support  For mitral and papillary muscle anomalies and abnormal septal hypertrophy the best choice the surgery  Mitral valve injury required emergency surgery.  Permanent conduction block occurs treatment should be PM

45. PTSMA limitations  Some young patients to reduce the pressure gradient effect is not satisfactory, the possible reasons: The septal branch with good collateral circulation. The septal branch with good collateral circulation.  The vessel can not thoroughor incomplete ablation (remaining smaller branches), self- revascularization.  The vessel can not thorough or incomplete ablation (remaining smaller branches), self- revascularization.  A higher degree of septal hypertrophy, a higher degree of fibrosis, Parts of the septal ablation scar formation poor.

46. PTSMA in Fuwai Hospital From Dec 2000 to May 2009, 171 patients underwent PTSMA in Fuwai Hospital.From Dec 2000 to May 2009, 171 patients underwent PTSMA in Fuwai Hospital. Procedure success was achieved in 141 patients ， success rate was 82.6%.Procedure success was achieved in 141 patients ， success rate was 82.6%.

47. Patient Characteristics CharacteristicsPatients (n=171) Age (yrs)45.37±17.71 Men/women122/49 (71.35%/28.65%) Symptoms Dyspnea93 (54.39%) Angina73 (42.69%) Syncope76 (44.44%) NYHA functional class （ II/III/IV ） 136(79.53%) /32(18.72%)/ 3(1.75%) Family history42 (24.6%) Medication Beta-blockers106 (62%) Verapamil52 (30.4%) Diltiazem38 (22.2%) Amiodanone13 (7.6%)

48. Results of PTSMA PTSMA (n=171)p Septal thickness (pre-PTSMA) 22.67±5.35mm Septal thickness (post-PTSMA 3days) 20.68±4.61mmNS Septal thickness (post-PTSMA 6months) 16.77±4.39mm<0.05 LVOTPG (pre-PTSMA) 97.58±38.23mmHg LVOTPG (post-PTSMA 3days) 52.36±35.7mmHg<0.001 LVOTPG (post-PTSMA 6months) 47.26±38.62mmHg<0.001 LA Diameter (pre-PTSMA) 43.78±7.33mm LA Diameter (post-PTSMA 3days) 42.41±7.52mmNS LA Diameter (post-PTSMA 6months) 32.76±15.58mm<0.05

49. Complications in our patients In-hospital death Up to May 2009, two patients died in those 171 patients （ 1.17% ） who underwent PTSMA in Fuwai Hospital. One was because of alcohol leakage to the Left anterior decending artery, another occurred drug-induced liver injury.Up to May 2009, two patients died in those 171 patients （ 1.17% ） who underwent PTSMA in Fuwai Hospital. One was because of alcohol leakage to the Left anterior decending artery, another occurred drug-induced liver injury. Complete heart block Transitory trifascicular blocks occurred at a rate of 52.05% （ 89 patients).Transitory trifascicular blocks occurred at a rate of 52.05% （ 89 patients). Only one patient (0.59%) underwent permanent pacemaker implantation due to permanent complete AV block.Only one patient (0.59%) underwent permanent pacemaker implantation due to permanent complete AV block.

50. Complications in our patients One patient (0.59%) occurred ventricular fibrillation, but he recovered well after the procedure.One patient (0.59%) occurred ventricular fibrillation, but he recovered well after the procedure. Right bundle branch block occurred at a rate of 48.54% （ 83 in 171 patients).Right bundle branch block occurred at a rate of 48.54% （ 83 in 171 patients). No dissections of the LM and LAD. No dissections of the LM and LAD. No emergency CABGNo emergency CABG Acute mitral regurgitation also did not occur.Acute mitral regurgitation also did not occur.

51. Follow-up in our patients by echo  Left ventricular outflow tract pressure gradient was continued to a significant decrease is an important feature: Compared with the acute phase, 56% of patients 3 months resting and stimulate the pressure gradient will continue to decline further; Compared with 3-month period, 43 % of patients one year the pressure gradient is still further reduced. Compared with the acute phase, 56% of patients 3 months resting and stimulate the pressure gradient will continue to decline further; Compared with 3-month period, 43 % of patients one year the pressure gradient is still further reduced.  After 3 months 40% of patients with pressure gradient completely reduced, a year later this value was promoted to 62%.  43 months later, 90% of the patients of the pressure gradient completely eliminated by echocardiographic

52. CONCLUSIONS ♦PTSMA is an effective non-surgical procedure for symptomatic patients and associated with LVOTO in HOCM because of its low risk and its significant hemodynamic and symptomatic improvement. ♦Ablation area should be appropriate, as small as possible, to avoid a large scar formation. ♦Echocardiographic observations plays an important role in that will help to finalize define the choice of septal ablation and the ablation efficacy and reduce risks and Long-term follow- up of treatment efficacy. ♦Echocardiographic observations plays an important role in that will help to finalize define the choice of septal ablation and the ablation efficacy and reduce risks and Long-term follow- up of treatment efficacy.

53. Advice Who have no symptoms or mild symptoms of the patient, determined not to consider the line to reduce outflow tract obstruction of any therapeutic intervention measures (including surgical and interventional treatment)!!! Who have no symptoms or mild symptoms of the patient, determined not to consider the line to reduce outflow tract obstruction of any therapeutic intervention measures (including surgical and interventional treatment)!!!