Secondary Mitral Regurgitation in HFrEF: Optimizing Heart Failure Therapy Before TEER
COAPT and MITRA-FR reached different conclusions about this exact procedure, and one leading explanation is how thoroughly each trial's patients had their heart failure therapy optimized first.
R.P., a 66-year-old man, a retired postal supervisor, had a large anterior MI four years ago that left him with an ejection fraction of 30% and, more recently, a mitral valve that leaks more than it used to — not because the valve itself is diseased, but because his left ventricle has stretched and remodeled around it, pulling the leaflets apart just enough that they no longer coapt properly. This is secondary, or functional, mitral regurgitation: the valve is a bystander to ventricular disease, not the primary problem, and how a team treats it is inseparable from how well they've already treated the ventricle underneath it.
He has been short of breath climbing his porch steps for months, class III symptoms by any reasonable accounting, and his outside cardiologist referred him for evaluation of transcatheter edge-to-edge repair — the mitral clip procedure that COAPT found genuinely beneficial in patients like him. What his current team noticed on reviewing his medication list is that his heart failure therapy isn't actually optimized: he's on metoprolol and lisinopril, started after his MI, but has never been transitioned to sacubitril-valsartan, never started on an SGLT2 inhibitor, and his mineralocorticoid receptor antagonist dose has been at a low, unchanged level for over a year. COAPT and MITRA-FR reached different conclusions about TEER's benefit in secondary MR, and one of the most-discussed explanations for that divergence is that COAPT's patients were on more thoroughly optimized guideline-directed therapy before the procedure than MITRA-FR's were — which makes the sequencing question here not academic, but potentially decisive.
In the heart failure clinic, before the referral proceeds
I don't think TEER referral is wrong in principle — he's clearly symptomatic and his MR is significant — but COAPT's benefit was demonstrated in a population on genuinely optimized guideline-directed therapy, and he isn't there yet. Proceeding straight to a procedure without that optimization risks repeating what MITRA-FR found: a population whose heart failure, not their valve, was still the undertreated problem, and where TEER didn't move outcomes.
If he were already on full-dose quadruple therapy and still symptomatic with significant secondary MR, I'd be pushing hard for TEER myself — this isn't skepticism of the procedure, it's insistence on the sequencing that COAPT actually tested.
I'd add specifics to that: switching him from lisinopril to sacubitril-valsartan — stopping the lisinopril and leaving a 36-hour washout before the first ARNI dose, since overlapping neprilysin and ACE inhibition carries a real angioedema risk — starting an SGLT2 inhibitor, and uptitrating his MRA to target dose are each independently mortality-reducing in HFrEF, separate from anything they do to his MR. There's a real chance that optimizing all four pillars reduces his functional MR meaningfully on its own, since secondary MR often improves as the ventricle reverse-remodels on better therapy — which would change not just whether he needs TEER, but how severe his MR looks by the time that question gets asked properly.
I don't think optimization should be open-ended, though — GDMT titration in HFrEF has a real timeline, generally weeks, not months, before you can reasonably assess response. If we treat this as an indefinite delay rather than a defined titration period, we risk under-treating his symptoms while he waits.
That timeline question is exactly what I'd want us to commit to today rather than leave open. I'd set a defined 8-to-12-week window for GDMT optimization — lisinopril stopped today and sacubitril-valsartan started after the 36-hour washout, SGLT2 inhibitor added, MRA titrated to target with potassium and creatinine rechecked one to two weeks after each change — with a repeat echocardiogram at the end of that window to reassess his MR severity on optimized therapy. If his MR is still significant and he's still symptomatic at that point, the TEER referral proceeds on much stronger, COAPT-aligned footing than it would today.
Agreed: lisinopril stopped and sacubitril-valsartan started after a 36-hour washout, SGLT2 inhibitor added, MRA uptitrated to target dose with electrolytes and renal function monitored, and a repeat echocardiogram set for 8 to 12 weeks to reassess his MR severity on optimized therapy.
TEER referral is deferred or reconsidered entirely, since the valve findings may have resolved as a consequence of ventricular remodeling.
The TEER referral proceeds, now on evidence-aligned footing much closer to the population COAPT demonstrated benefit in.
His outside cardiologist will be updated on the optimization plan so the referral isn't lost, only appropriately sequenced.