But we should always question composite end-points, especially when they are the primary endpoint of a study. In this case, the primary endpoint was defined as "By intention to treat, a composite of all-cause mortality, HF-related urgent care (any unplanned hospital visit requiring intravenous heart-failure therapy), or greater than 15% increase in left ventricular end-systolic volume index by echocardiography, over a mean 36-month follow-up."
Note the word "or" between each of these measures.
What I found interesting in this trial was that most of the composite endpoint benefit was driven primarily by the echocardiographic measure of left ventricular volume index. (A portion of Table 2 from the New England Journal of Medicine is duplicated below):
|biV Pacing||RV Pacing||biV ICD||RV ICD|
|Event Related to LV Volume Index||56||79||31||36|
|Urgent Care Visit for Heart Failure||40||38||16||23|
It is not surprising that biventricular pacing improves the LV volume index (biventricular pacing improves the coordination of contraction of the medial and lateral LV walls by its very physiology). But the as far as heart failure and death as subsets of the therapy, there really wasn't much of a difference.
To me, this is not that surprising. In the MIRACLE trial (the sentinel Medtronic trial of biV pacing in heart failure that I participated in years ago), patients were required to have left ventricular ejection fractions (LVEF) less than 35% and a QRS complex greater than 130 msec. Subsequent analysis of that trial showed that LVEF improved on average about 5-6% with biventricular pacing (a small but significant improvement). Patients with severely reduced LV functions at the outset of the MIRACLE trial, then, had the most to gain clinically from the 5-6% LV function improvement compared to patients whose LV functions were less compromised. Therefore, it is not surprising to me that biV pacing had less effect on the clinical indices of heart failure visits or death in the BLOCK-HF's cohort of patients whose LV functions were more robust.
It will be interesting to see if CMS sides with Medtronic's conclusions and agrees to pay for the extra lead placement in complete heart block patients with only mildy reduced LVEF less than 50%.
Since I implant these devices, I certainly hope so.