The STICH trial unravelled

The STICH trial was designed to compare coronary bypass (CABG) alone vs. CABG plus surgical ventricular reconstruction (SVR) in patients with left ventricular (LV) dysfunction and akinetic or dyskinetic LV segments from prior anterior wall myocardial infarction (MI). It reported that adding SVR to coronary bypass CABG was not associated with a greater improvement in symptoms, exercise tolerance, or reduced intermediate mortality. This trial was federally funded to provide evidence-based methodology for this comparison, but its implementation was faulty in many ways. Surgical ventricular reconstruction treats congestive heart failure (CHF) by reducing LV volume, perhaps the most powerful predictor of mortality in dilated cardiomyopathy and more predictive than ejection fraction (EF) –4 (Figures 1 and 2). The 490 patients who underwent SVR in STICH was predicated on favourable reports of recovery in over 5000 patients worldwide and registry data from approximately 1200 patients that decreased LV endsystolic volume index (LVESVI) 40% (ranging 30–58%, Table 1), –8 but had different results. Is SVR an improper concept or was the STICH trial improperly executed? Eligibility for STICH required that ‘all patients will be evaluated further for appropriateness of SVR indicated by evidence of absent viability in the anterior ventricle by nuclear scan determination, LVESVI ≥60 ml/m, and akinesia ≥35% of the anterior wall’ (http://clinicaltrials.gov/archine/NTC00023595/2005_06_23). Echocardiography was specifically excluded for measuring LV volume because of its inaccuracy when regional asynergy is present. Selection of STICH centres was based on capability to measure volume by cardiac magnetic resonance (CMR) imaging (Excerpt 1). However, STICH enrolled a quite different group of patients, namely those with NYHA Class II– IV CHF (within 3 months of entry), coronary artery disease that was amenable to CABG, an EF ≤35% [defined by echocardiogram, left ventriculogram, CMR, or gated single photon (SPECT) studies], and ‘dominant anterior left ventricular dysfunction’. Accurate viability and LV volume were not done in all patients as planned. STICH required that all patients have dyskinesia or akinesia with evidence of non-viability in 35% of the anterior ventricular wall (Excerpt 2). Dyskinesia is caused by no reperfusion of the LV after infarction. Akinesia accompanies early thrombolysis or angioplasty and results in a dilated but thick LV. STICH, however, reports that only half of patients had akinesia or dyskinesia and 13% had no prior history of infarction. Surgical ventricular reconstruction has never been reported or recommended in patients with regional dysfunction alone and absent scar. The STICH surgical therapy committee specifically defined SVR as ‘any ventricular reconstruction method that consistently results in a low operative mortality, an average EF increase of ≥10%, and an average LVESVI decrease of ≥30% as assessed on the four-month post-operative CMR measurement’ (Excerpt 3). STICH, however, measured LVESVI in only 212 of 490 patients (43%) in the CABG-only group and in 161 of 490 patients (33%) in the CABG plus SVR group by echocardiography. The number of CMR measurements is not given. STICH reported that SVR lowered LVESVI an average of only 19%. Patients should be excluded from the analysis if the originally defined goals were not met. Patients in the SVR trial underwent SVR based on qualitative rather than quantitative assessment. Perhaps they had hibernation of ischaemic areas or post-infarction stunning, both of which are clearly not indications for SVR. Surgeons cannot know when SVR should be performed without accurate viability and volume information. The STICH patients cannot be compared with previously reported patients with SVR. Dor’s 1000 patients and the 1198 patients in the RESTORE group had prior history of MI, akinesia, or dyskinesia involving ≥35% of the LV, reduced EF, and LVESVI ≥60 mL/m. Furthermore, only 49% of patients in STICH had NYHA class III or IV CHF vs. . 66% in the RESTORE registry. STICH trial original protocol deviations can be viewed in ‘history of changes’ on: http://clinicaltrials.gov/show/NCT00023595. Why was accurate LVESVI by CMR or nuclear study retracted? The principal investigator may change the protocol, but only with approval from the NIH grant administration officer. Though it does not require approval from other trial participants, the grant administrator must assume the responsibility for investigational review board (IRB) notification of changes for all trial participants. The STICH publication does not report changes during the trial.