CLAUDIO GROSSI Cardiac Surgery Ospedale Santa Croce

CUNEO (Italy)

Surgical left ventricular reshaping in postinfarctual cardiomyopathy: an unresolved issue

There are different possible ways to discuss this important topic: ü  Following the historical evolution of scientific events ü  Showing the rich literature of clinical I choosed the effects last one: ….I want to discuss with you ü  Looking at the physiopathological aspects Consequently ü  Talking I’m not about goingthe to consequences give you any solution of STICH trial ü  Speculating about the future possibilities of applying new approaches ü  Discussing the discrepancy among all those aspects

Post-infarctual ventricular remodeling

“It is now widely appreciated that remodeling is not just a manifestation of disease, but is an important mechanism of disease”

The surgical treatment of LV aneurysm was introduced in 1944: •  Claude S. Beck reinforced the wall of a left ventricular (LV) aneurysm with fascia lata aponeurosis in order to reduce excessive dilatation and avoid LV rupture

•  Further developments of LV aneurysm surgery lead to the use of numerous new LV reconstruction methods. •  The principal surgical techniques can be divided into two large groups:

Ø  the direct suture techniques Ø  the patch ventriculoplasty techniques.

•  The direct suture techniques

•  The patch ventriculoplasty techniques

SVR: Surgical Ventricular Reconstruction to d e gn erior i s e s d he ant e r u t ed g c n o i r l p nstruct a c i g r o u . c s e e r f p a o y h s up eling b d o r n g a a d e z o s i e s m b r re a ri l I c u s M c e i t R d ct pos ft ventr V S •  ra le e t e z n i u tim co p o to l l a w

“SVR: ..new term which includes operative methods that reduce LV volume and “restore” ventricular elliptical shape.”

RESTORE group: The Reconstructive Endoventricular Surgery, returning Torsion Original Radius Elliptical Shape to the LV

• 

The RESTORE group applied SVR to 1,198 post-infarction patients between 1998 and 2003.

Ø  Surgical ventricular restoration reduces volume and “restores” a more normal elliptical ventricular shape in dilated hearts after anterior infarction. Ø  Our data demonstrate a low operative mortality, improved systolic function, a gratifying five-year survival, and a low rate of rehospitalization for CHF..

Conclusions •  LVR surgery was accompanied by a favorable neurohormonal response. Decreased profiles of selected neurohormones were associated with improved LV function. •  These results support the hypothesis that direct improvement of cardiovascular function may reduce neuroendocrine activation by removing trigger mechanisms.

Cuneo, 2000-2009: 138 Pts Operative mortality 6/138: 4,4%

100

Survival

80

60

40

20

0 0

6

12

18

24

30

months

Short term follow-up: avarage 14,5 months (update to 2006)

36

42

•  …The SVR literature largely consists of retrospective single-center or multicenter database reviews •  To address this question, the STICH trial was designed to study the additive effect of SVR on revascularization in a prospective randomized fashion.

Death or Cardiac Hospitalization Kaplan-Meier Estimates of Primary Endpoint 0.7 HR 0.99 (95% CI: 0.84, 1.17), P=0.90

Event Rate

0.6 0.5 0.4 0.3 0.2

CABG

292 events

0.1

CABG+SVR

289 events

0

0

1

No. at Risk CABG 499 CABG+SVR 501

319 319

2 3 4 Years from Randomization 270 275

220 216

99 11

5 23 23

Conclusions

Ø  The STICH trial definitively shows adding SVR to CABG provides no clinical benefit beyond that of CABG alone in the study population. Ø  Both operative strategies provided similar short- and long-term relief of angina and HF and improvement in 6-minute walk test performance.

•  From 2002 to May 2008, 274 patients underwent left ventricular reconstruction for post–myocardial infarction scarring; •  117 of these patients would not have been eligible for the STICH trial.

•  Results:

ft year. e l , y ü Four in-hospital and 2 delayed deaths during the first t ali t r o m d a e t h t e a i l i b c w a •  In 101 patients with chronic heartafailure, revealed that r so MRI u s nts d e i l s t a e a p im uc n n d i i o n r m o preoperatively to p 26%nc±ti4% h t ü ejection fraction improved from n i o i W t u c f s: u r n r a t o l i s u s n 40% clu± 8%r ratec1omonthveand tric44% ± 11% at 1 year postop. n n o C t la •  f ll u e a l c i w r n t i r n nt volume ulaindex was reduced from 130 ± 43 ve end-diastolic e ü the c i m r t e v n e o r v p d im mL/m2 toca81 rre± 27 and 82 ± 25 mL/m2, respectively s large ü the end-systolic volume index was reduced from 96 ± 45 mL/ m2 to 50 ± 21 and 47 ± 20 mL/m2, respectively.

Discussion • 

Dr Robert H. Jones (Durham, NC): Has this neutral STICH result changed your equipoise for any of your health care diagnostic or treatment decisions for ‘‘STICH like’’ patients, irrespective of whether they were technically STICH protocol eligible?

• 

•  Dr Robert H. Jones (Durham, NC): • Dr Dor: Dr Dor: (..doesn’t (..doesn’t answer) answer) Has this neutral STICH result changed your equipoise for any of your health I cannot understand why the scarwhy was not Icare cannot understand theassessed. scar was not assessed. diagnostic or treatment decisions for ‘‘STICH like’’ patients, irrespective of In your trial there is not one indication about the size of the scar, its location, or its whether they were technically STICH protocol eligible? In yourand trial there notit one indication aboutthethe sizewas of the scar, its location, or its percentage, in the other is paper, was never precise whether ventricle scarred. percentage, and in the other paper, it was never precise whether the ventricle was Nobody discussed the situation of when a patient has no more ischemia, a totally scarred. destroyed ventricle, and a large scar involving more than 50% of the ventricle: How canNobody CABG alonediscussed improve this patient? .. the situation of when a patient has no

more ischemia, a totally •  Drdestroyed Dor: ventricle, and a large scar involving more than 50% of the ventricle: How CABGyou alone improvethe thisfact patient? .. can Dr Jones confirmed that you excluded severe patients to do not pollute your trial, .. and our presentation confirms the fact that the STICH trial is not reliable because patients with a scarred ventricle are not assessed or treated.

Discussion • 

•  Dr Jones.:

Dr Jones.:

The STICH trial was not designed to definitively answer the question of whether ventricular reconstruction should ever be done in patients with extensive scarring of the left ventricle. designed to definitively answer the question of whether

The STICH trial was not We documented best available baselinewith core laboratory measurement global ventricular reconstruction should ever bethedone in patients extensive scarringofof and regional dysfunction and ventricular size reported from the ECHO, SPECT, and the left ventricle. CMR core laboratories without knowledge of the treatment assignment of the patient.

We documented the best available baseline core laboratory measurement of global and regional dysfunction and ventricular size reported from the ECHO, SPECT, and •  Dr Dor.core laboratories without knowledge of the treatment assignment of the CMR patient.conclusion must add as a conclusion that all the cases that were not treated …Your by the STICH study team will be interesting for cardiologists. Second, regarding the volumes you mentioned, they are assessed by means of echocardiographic analysis, and again, in 2000’s magnetic resonance is more reliable to assess the volume of the heart before and after repair.

The credibility of the STICH trial is questioned by flaws listed below 1.  all patients needed to have akinesia, yet only 50% displayed this finding. 2.  akinesia developed from regional necrosis of 35% of muscle, yet the report fails to document this scar finding. 3.  CMR quantification of ventricular volume is needed in all patients before and after SVR. Instead, 19% underwent an invalid echocardiographic measurement, despite pretrial contact showing CMR measurement capacity in all initial 50 trial centers.

(… follows)

4. 100% required CMR volume measurement for trial entry,fuyet l only g n and CABG i n a 38% had any form of volume measurementm(CABG e e y v l e p i plus SVR) h s im a ac

s o m t n o o a r i t f s a e d is beyond lu60 mL/m2, 5. SVR is indicated only ifzESVI ryet volume c u e t n a o y l n candidates were not c a l y n f a i a e measurements for SVR or CABG without SVR e tr d r t n H a u C I c o T h s t S i n reported. a e W i h c t i t s s t i l t u a t s s e 6. 30% reduction ofaESVI at 4e.months by CMR study is required for r t h t s but ESVI was lowered only 19% in w a o b a h acceptable SVR procedure, t s a d d e the 33%flof to demonstrate an inadequate end point. awpatients 7. the original trial included 50 centers, averaging approximately 10 cases per center. Actually, 96 centers were used, averaging approximately 5 procedures per center

CASUALTIES OF STICH OUTCOMES 1.  The first casualty of this report may be the increasing CHF population with dilated hearts, which makes up approximately half of the CHF population, 2.  STICH may adversely affect cardiac surgery evolution and nontransplant heart failure surgery by limiting development of SVR 3.  The third casualty is scientific integrity 4.  The fourth casualty may be health care cost of CHF treatment, which may exceed $1 trillion per year in 2030 in USA

…. Anyway let’s go back to pathophiysiology:

Laplace - Young Law Radius x Intracavitary Pressure Wall Stress

= 2 x wall thickness

•  any reduction in diameter of ventricular chamber corrisponds to a reduction in wall stress necessary to squeeze the ventricle

What we look for…. A: CORRECT Hypothetical therapy that would induce a greater leftward shift of the ESPVR than EDPVR and cause an increase in net pumping capacity as shown by the pressurevolume loop (blue) B: WRONG Batista operation

Conclusions: •  The effect of volume reduction surgery on overall ventricular pumping characteristics is determined by the differential effects on end-systolic and enddiastolic properties, which in turn are determined by the material properties of the region being removed.

…few years ago we had, a clinical demonstration on humans:

Conclusions: •  Surgical ventricular restoration achieves normalization of left

Average steady-state pressure-volume loops before (PRE) and after (POST) ventricular volumes and improves systolic function and SVR, isolated RMA, and CABG.

mechanical efficiency by reducing left ventricular wall stress and mechanical dyssynchrony

…. But reanalysing the same data of the same patients other authors came to a different conclusion:

•  The isovolumic pressure–volume area (PVAISO) is a measure of the total possible mechanical energy the ventricle can generate at the specified preload pressure •  Thus provides an afterloadindependent measure of the pumping capability of the heart

•  the relationship between end-diastolic pressure and PVAISO is shifted downward after SVR, indicating that at any given filling pressure the heart is capable of less work than before the procedure.

•  In fact, the decreased afterload and marked elevation of enddiastolic pressure (increased preload) with no increase in SV observed after SVR could actually imply reduced pumping capability

about diastolic function…:

•  The changes in the pressure–volume loops and pressure– volume relationships resemble those observed in classic cases of diastolic heart failure.

…this was challenged by professor Dor:

•  … in our recent series the diastolic function improved concomitantly with systolic function, as shown by the

decrease in Left Atrial Volume Index, which is the best witness to the decrease in diastolic burden.

•  Conventional Doppler echocardiography can assess LV diastolic function by using transmitral flow velocity profiles (J Am Coll Cardiol. 1997;30:8-18).

Grade of diastolic dysfunction named diastolic pattern as evaluated by transmitral flow velocity curves

•  67 pts with LV systolic dysfunction underwent SVR (LV ejection fraction, 0.27 ± 0.10).

•  Patients were divided into three Conclusions: groups according to the Preoperative severe diastolic preoperative diastolic dysfunction may havefilling a patterns of transmitral significant impact onflow (impaired outcomesrelaxation, after SVRpseudowith normal, and restrictive filling heart failure. patterns).

…on the other hand:

(J Thorac Cardiovasc Surg 2010;140:285-91)

•  Baseline diastolic dysfunction occurs in most patients affected by ischemic dilated cardiomyopathy referred for SVR. •  In the present study, we found that the worsening in diastolic function induced by SVR did not affect clinical status and survival

(J Thorac Cardiovasc Surg 2010;140:285-91)

•  Patients in whom diastolic restriction develops late postoperatively had preoperatively larger, more spherical ventricles with a lower ejection fraction and more conical apex. LV shape was of nonaneurysmal type •  A possible explanation is that the significant improvement in systolic function and the optimal medical treatment, which is not discontinued after surgery, counteracts diastolic dysfunction

SYSTOLIC FUNCTION AFTER SURGICAL VENTRICULAR RESHAPING :

.. the improvement in the ejection fraction after the operation is more algebrical than physiological: EF= SV/EDV

EF= EDV-ESV/EDV

EDV= a preop. ESV= b preop. EDV= a-x postop. if x is the volume removed with SVR ESV= b-x postop. EF preop.= (a)-(b) / (a)

EF postop.= (a-x)-(b-x) / (a-x)

EF preop.= a-b / a

EF postop.= a-b+2x / a-x

if x is positive a-b+2x > a-b if x is positive a-x < a

EF postop > EF preop.

Ø …it is intuitively obvious that reduction of EDV without an increase in EF would result in inadequate SV. •  With “usual” inotropic interventions (adrenergic agents, resolution of ischemia), an increase of EF results from an increase in SV with little change in EDV. •  In contrast, the increase in EF observed with SVR results from a decrease in EDV with little change in SV

stroke volume: how does it change with surgical reshaping?

•  Surgical ventricular restoration improves contractility of myocardium in border-zone and remote regions, resulting in increased stroke volume index from the posterior left ventricle. •  An endoventricular patch on the anterior LV would seem to exert a restrictive effect on the previously dilated border-zone myocardium, improving the contractility of myocardium in the border zone and also in remote regions.

…BUT:

(J Thorac Cardiovasc Surg 2010;140:1325-31)

•  …several investigators noted a reduction in SV and others reported an increase in SV •  …However in our study the response was heterogeneous in that SVI decreased in 165 (71%) of the patients and increased in 69 (29%) of the patients after SVR. q This could fit with the theory showing that with regard to the impact on pump function, SVR could be ü  detrimental in patients whose wall to be excluded is hypokinesia, ü  would be neutral in patients whose wall to be excluded is akinetic, ü  and would be beneficial in patients whose wall to be excluded is dyskinetic.

(J Thorac Cardiovasc Surg 2010;140:1325-31)

Our data indicate that ‘‘early’’ stroke volume reduction is transitory and is linked, at least partially, to preoperative ventricular properties (patients with a SVI decrease had a preoperative larger EDV) Postoperative changes in EDVI, ESVI, SVI, and EF in the overall study population (248 pts). All changes are significant at P 60 mL/m2). •  These findings suggest that SVR might be considered as a therapeutic option for patients with HF in less-advanced stages of the disease.

•  In these high-risk patients, SVR successfully increased ejection fraction and decreased symptoms.

Ø  A preoperative left ventricular end-systolic volume index of 80 to 120 may be the ideal range for SVR procedures..

…many problems ü  we need to prove the efficacy of surgical therapy ! ü  we need to define the proper indications ! ü  we need to establish the technique and the achievable targets !

fluid dynamic evaluation :

•  After the surgical procedure, washout was slightly lower (not significantly different) compared with before SVR despite the significant alterations in shape and fluid dynamics. •  Our findings of similar fluid washout in the ball-shaped ventricle of the patient after surgery despite changes in ejection fraction, shape, and fluid dynamics may explain the fact that patients after SVR are not at greater risk for thrombus formation than before. •  The presented analysis describes an attractive tool to assess the fluid patterns in the heart in patients with ischemic heart disease.

And looking the things from another side, it’s noteworthy…:

•  Little is known about the changes in material properties that occur as the infarct heals •  We believe that increases in material compliance (reduction in stiffness) that occur during infarct healing and maturation contribute to the immediate and progressive loss of cardiac function experienced by many patients after MI.

•  LV remodeling after MI is manifest by progressive LV dilatation, reduction in EF, and increased filling pressures: one explanation for this phenomenon based on our results would be that infarcts become more compliant as they heal and mature. •  Our results also support the potential therapeutic value of stiffening the infarct as a means of preventing, limiting, or reversing LV remodeling after MI.