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  • Up-Titrating GDMT after M-TEER for Secondary MR in HFrEF Patients Associated with Better Outcomes – European Registry Analysis

    Among patients with heart failure with reduced ejection fraction (HFrEF) undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for treatment of secondary mitral regurgitation (SMR), increasing the dosage of guideline-directed medical therapy (GDMT) after M-TEER was associated with marked improvement in MR, survival and freedom from HF hospitalization (HFH), a new registry analysis shows.

    Marianna Adamo, MD, and Daniela Tomasoni, MD, of the University of Brescia, Italy, and colleagues reported these findings in a manuscript published Wednesday online in JACC: Cardiovascular Interventions.

    Before performing M-TEER, clinicians must optimize GDMT in patients with SMR and HFrEF. However, the effect of M-TEER on GDMT is not clear.

    Study details

    Therefore, Adamo, Tomasoni and colleagues evaluated the frequency, prognostic implications and predictors of increasing the level of GDMT after M-TEER in these patients. They retrospectively analyzed prospectively collected data from the EuroSMR Registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation).

    The analysis included 810 patients with HFrEF who underwent M-TEER to treat SMR at 11 high-volume European centers and who had GDMT data available both at baseline and 6-month follow-up. The patients were stratified according to whether their GDMT was up-titrated, which the authors defined as the initiation of a new HF drug class, increase in dose of at least one previously prescribed drug class without down-titration of any other drug class, or both.

    At baseline, the patients’ mean age was 71.6 ± 10.2 years, 72% were male, and 88% had New York Heart Association (NYHA) class III or IV heart failure. Characteristics were mostly similar between the no-up-titration and up-titration groups, but the no-up-titration group was more likely to be male (75% vs. 67%, p=0.022), had a lower mean arterial blood pressure (88 ± 16 mmHg vs. 93 ± 19 mmHg, p=0.001), was more likely to have had previous myocardial infarction (36% vs. 28%; p=0.018), had a higher median loop diuretic dose (30 mg [interquartile range (IQR): 15-60 vs. 20 mg [IQR: 10-40]; p=0.002), worse renal function, larger right ventricular dimensions and higher systolic pulmonary artery pressure.

    Before M-TEER, nearly all patients (98.5%) received GDMT, of whom 78% received angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor neprilysin inhibitors (ARNIs) or angiotensin receptor blocker (ARBs), 89% received beta-blockers, and 62% received mineralocorticoid receptor antagonists (MRAs).

    At 6-month follow-up, 38% (n=307) underwent GDMT up-titration, and 503 (62%) did not. More patients received ACE inhibitors, ARBs or ARNIs (84%), beta-blockers (91%) and MRAs (66%; p-value for all <0.001). Also, more patients received three HF drug classes at 6-month follow-up (51% vs. 47% at baseline, p<0.001). Rates of up-titration were 30.1% for ACE inhibitors, ARBs or ARNIs, 24.8% for beta-blockers and 20.7% for MRAs.


    At 6-month follow-up, 60% of the no-up-titration group was in NYHA class I or II, compared to 69% of the up-titration group (p=0.002), and the percentage of patients who improved by at least 1 NYHA class was also significantly lower in the no-up-titration group (80% vs. 95%; p=0.012). The no-up-titration patients continued to take higher loop diuretic doses (30 mg [IQR: 15-75] vs. 20 mg [IQR: 10-50]; p=0.001).

    The no-up-titration group also had higher median N-terminal pro–B-type natriuretic peptide (NT-proBNP; 2,493 ng/L [IQR: 1,090 to 6,025] vs. 1,793 ng/L [IQR: 717 to 4,599]; p=0.035), less change in NT-proBNP (-156 ng/L [IQR: -1,273 to 792] vs. -406 [IQR: -2,531 to 199]; p-0.043), and a lower percentage with grade 0 or 1 MR (44% vs. 54%; p=0.046).

    After multivariate analysis, the only variable independently associated with likelihood of GDMT up-titration after M-TEER was degree of MR reduction of three or four grades at 6-month follow-up (adjusted odds ratio: 1.71; 95% confidence interval [CI]: 1.08-2.71; p=0.022).

    At 3 years after M-TEER, the up-titration group showed significantly higher rates of both freedom from all-cause death (adjusted hazard ratio [HR]: 0.62; 95% CI: 0.41-0.93) and of the composite of freedom from all-cause death or HFH (adjusted HR: 0.54; 95% CI: 0.38-0.76).

    Study limitations included those common to retrospective analyses. The authors also pointed out the lack of a comparison group who did not undergo M-TEER during a similar time frame, but they added that because M-TEER occurred only after optimization of GDMT, it was not likely that patients who did not undergo M-TEER would have had further GDMT changes.

    ‘Our job … is not complete’

    In an accompanying editorial, David W.M. Muller, MBBS, MD, of St Vincent’s Hospital, Sydney, said the study “highlights the importance of maintaining maximally tolerated GDMT in patients with HFrEF including (and perhaps especially) in those who have had successful transcatheter therapy for severe secondary MR.”

    Muller added that SGLT2 inhibitors, which are now considered part of GDMT, were not included in the registry analysis. SGLT might be up-titrated when other parts of GDMT are not able to be, he said.

    Muller concluded that while the study does not “definitively answer the question” of whether GDMT up-titration improves outcomes or other factors might be involved, it does show that “our job as physicians is not complete with a successful mitral intervention for HFrEF.”

    “A successful intervention should provide a platform for further optimization of GDMT drug doses, with the aim of maximizing survival and minimizing the need for heart failure hospitalization in this highly vulnerable population,” he wrote.


    Adamo M, Tomasoni D, Stolz L, et al. Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Guideline-Directed Medical Therapy Up-Titration. JACC Cardiovasc Interv. 2023 Mar 22 (Article in press).

    Muller DWM. Optimizing Outcomes After Transcatheter Mitral Valve Repair: The Case for Maximizing Medical Therapy. JACC Cardiovasc Interv. 2023 Mar 22 (Article in press).

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