- 1 hour high sensitivity troponin assay highly accurate in ruling out NSTEMI
- Among non-invasive imaging modalities, the best marker for LV remodelling appears to be an MRI-determined measure of LV end diastolic volume (EDV)
- ALBATROSS study shows no benefit from aldosterone blocking agents post-MI.
- Peri-infarct pacing in patients with acute MI and normal LV electrical conduction yields no benefit and should not be performed.
- CIRCUS study shows no benefit from cyclosporine administration to patients with acute MI in terms of LVEF and LV volumes post-MI.
D. Westermann reported the BACC trial on hsTn in the diagnosis of ACS.
This was a well conducted, large multicenter trial that sought to evaluate the accuracy of a one hour high sensitivity troponin value in ruling out a non-ST elevation MI (NSTEMI) in patients who came to an emergency ward complaining of chest discomfort. The results supported a number of earlier trials that have shown that a 1 or 2 hour hsTn test is very, very accurate in ruling out NSTEMI with negative predictive values in excess of 99%. Follow up revealed that the ruled out patients had very, very few subsequent ischemic events. The conclusion from this trial was that this rule-out protocol using hsTn in the first hour after presentation to an emergency ward enabled approximately half the patients to be discharged to home. The investigators also showed that the 1 hour protocol was more useful and more accurate than a 3 hour rule out protocol. In my opinion, this trial, alongside a number of similar earlier trials with similar negative predictive values, will speed the adoption of this protocol employing hsTn in emergency rooms throughout the world.
Rademakers et al, study on left ventricular remodelling
This multicenter, non-invasive imaging study evaluated a large number of ischemic heart disease patients with a number of non-invasive modalities to ascertain if there was an accurate marker for left ventricular (LV) remodelling. It has been known for a long time that LV remodelling carries with it a negative prognosis for the patient. Modalities tested included echo, CT, and MRI. The results demonstrated that the best test for LV remodelling was an MRI-determined measure of LV end diastolic volume (EDV), which increased by about 40 ml for all patient groups (post MI; no MI, etc). Essentially, all these coronary artery disease patients demonstrated LV remodelling (dilation) with time. Interestingly, the greatest relative increase in LV EDV occurred in the patients with the lowest initial LVEDV, although the absolute increases in EDV were similar in patients with low EDV initially and patients with high EDV initially.
Gilles Montalescot reported on the ALBATROSS trial on aldosterone therapy post MI in patients with normal LV function.
This randomized blinded trial performed in France with the support of the French Health System sought to follow up on earlier smaller positive trials that had shown benefit with aldosterone blocking agents in patients post MI. Earlier positive trials usually focussed on patients with reduced LV ejection fraction (LVEF) post MI. This trial enrolled patients with normal LVEF post MI and gave the patients an IV aldosterone blocker followed by spironolactone 25 mg once per day orally. The trial was negative; that is, no benefit from this therapy was demonstrated. My conclusion is that aldosterone blockers are beneficial when there is reduced LVEF regardless of etiology, but that no benefit accrues when the LVEF is normal in post MI patients.
Stone – Peri-infarct pacing to improve LV remodelling post MI
This multicenter trial sought to follow up on some positive signals in animal studies suggesting that pacing the LV next to a zone of acute infarction might change wall tension in the area and lead to less infarct expansion and hence, less overall LV remodelling in the direction of increased LV EDV. If this pacing protocol were positive, it might prove to be a beneficial therapy to decrease the incidence of post infarction heart failure. The trial was negative. Patients in the pacing group showed exactly the same LV sizes and LVEF compared with placebo. The investigators concluded that peri-infarct pacing in patients with acute MI and normal LV electrical conduction was a modality without benefit and should not be performed. The article is published today in the European Heart Journal.
Michel Ovize reported on the CIRCUS study of cyclosporine post MI
Earlier animal and one clinical trial had demonstrated a beneficial effect from the administration of the immunosuppressive drug cyclosporine to patients with acute MI. The beneficial effect was on post infarct reperfusion injury with improved LV function and decreased LV remodelling. This blinded trial failed to show any benefit with cyclosporine administration post MI. The values for LVEF and for LV volumes were the same in the cyclosporine and in the placebo groups. The discussant pointed out that this was yet another trial in a 40 year attempt with various agents to reduce post infarct reperfusion injury. All of these trials have failed to show benefit, including this one. My personal feeling after many discussions with my wife, Professor of pharmacology, Qin Mary Chen, PhD concerning why all of these attempts to limit reperfusion injury have failed is that the intervention might be administered too late to affect the ischemic myocardial injury. The animal models, which showed beneficial results from a variety of agents administered, employed all of these agents soon after myocardial infarction was induced and soon after reperfusion, and not late (often averaging 4 hours or more) after the onset of infarction as in the patient population. Further basic science investigations should be performed before more clinical trials are attempted given the negative results obtained with this trial and many, many others.