The synergy of myopathic valvular disease

Abstract

With recent advancements in the treatment of heart failure with reduced ejection fraction (HFrEF) including the addition of angiotensin receptor–neprilysin inhibitor, sodium–glucose cotransporter 2 inhibitors (SGLT2i) and transcatheter edgetoedge mitral valve repair (TEER), the treatment of patients with cardiomyopathy and secondary mitral regurgitation (SMR) has become increasingly complex and can lead to suboptimal utilisation of indicated therapies. Tanaka and colleagues have provided a realworld analysis of guidelinedirected medical therapy (GDMT) among HFREF patients with SMR and managed with TEER. Their findings reinforce the importance of engaging focused heart failure (HF) cardiologists and allied teams to optimise medical therapy before and after TEER. Consistent with the 2021 European Society of Cardiology guideline on HF management, the authors define GDMT as modulation of the renin–angiotensin–aldosterone and sympathetic nervous systems with triple therapy including renin–angiotensin system (RAS) inhibitors, betablockers (BBs) and mineralocorticoid receptor antagonists (MRAs) noting that SGLT2is were approved after study completion. Their results demonstrated the clinical benefits of maintaining triple therapy neuromodulation following TEER. They have thus provided a pragmatic and simple threshold of GDMT that will undoubtedly improve the care of patients with SMR undergoing TEER. Tanaka et al retrospectively divided patients with SMR and left ventricular ejection fraction (LVEF) <50% who underwent TEER into GDMT and nonGDMT cohorts. Local heart teams optimised medical therapy and decided when to perform TEER. As such, this is a realworld population of patients with SMR managed with TEER. GDMT was defined as patients who received triple therapy at the time of discharge with RAS inhibitors, BBs and MRAs of any doses. Nevertheless, among the GDMT cohort, only 21% of patients received target doses of BBs, and only 12% received target doses of RAS inhibitors. NonGDMT patients were prescribed optimal medical therapy per the local heart team consensus including BBs in 84% (16% with target doses), and RAS inhibitors in 60% (12% at target doses). While all GDMT patients were prescribed MRAs, only 22% of nonGDMT patients were prescribed MRAs. Among patients without GDMT, 42% had factors related to ineligibility (ie, systolic blood pressure <100 mm Hg, heart rate <60 bpm or estimated glomerular filtration rate <30 mL/min/m). This underscores the difference between relative ineligibility to a medication and the intolerance to this medication with the inherent complexity of providing detailed reasons for intolerance of GDMT, which were not recorded in this study. We are not sure if the lack of triple therapy in the nonGDMT cohort and the less than target doses of medications in both cohorts represents the absolute maximally tolerated medical therapy. Twoyear mortality was compared between groups after calculating propensity scores and performing an inverse probability of treatment weighting (IPTW) analysis. Patients discharged with tripletherapy GDMT (BBs, RAS inhibitors and MRAs) had markedly lower incidence of mortality compared with those discharged without GDMT (19.8% vs 31.1%, p=0.011). Patients with GDMT similarly had a higher rate of left ventricular reverse remodelling 1 year after TEER compared with those without GDMT. As pointed out by the authors, this study must be interpreted within the limitations of a retrospective, observational study. While the authors attempted to correct for selection bias by using an IPTWadjusted approach, confounders may have impacted the outcomes. The ability to tolerate tripletherapy GDMT may convey a favourable prognosis. Patients discharged with tripletherapy GDMT were younger and had better renal function with less haemodialysis. Nevertheless, the obvious conclusion as suggested by the authors is that optimisation of medical therapy with a combination of RAS inhibitors, BBs and MRAs is crucial to improve clinical outcomes in patients undergoing TEER for SMR. The working definition of GDMT of triple neurohormonal inhibition with BBs, RAS inhibitors and MRAs serves as a minimal threshold when TEER may be considered and as a priority for discharge following TEER. The relatively low rate of target doses in both groups emphasises the difficulty in achieving targeted doses and the importance of involving a HF expert in the management of patients with HFrEF. Among patients in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial, 8.65% of those randomised to TEER and GDMT started a new BB or increased their current BB dose by 100% compared with 3.8% randomised to GDMT alone (p=0.01) consistent with the frequent clinical observation that TEER increases SBP and facilitates enhanced medical therapy. Importantly, given no significant change of GDMT doses on followup after TEER, the Tanaka study redemonstrates the need for longitudinal care with continued, ongoing attempts to find the maximally tolerated dose of GDMT. These TEER findings mirror the results from several other accounts of underutilization of GDMT in patients with HFrEF. In 2018, the Change the Management of Patients with Heart Failure, CHAMPSHF registry collected rates of GDMT across community cardiology and primary care practices revealing a shocking underutilization of appropriate therapies in patients with HFrEF (less than 25% were on triple therapy as previously mentioned and only 1% were on target doses). Continued gaps in GDMT optimisation were again confirmed in the 2021 Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure, CONNECTHF study revealing suboptimal GDMT rates, despite hospital and postdischarge quality improvement efforts. The implantable cardioverter defibrillator (ICD) and cardiac resynchronization device study that found HF medical therapy to be under prescribed before and after ICD/cardiac resynchronisation device implantation, and patients with optimal medical therapy after rhythm device therapy to have increased survival and fewer HF hospitalisations. The recent HFrEF guideline codifies the term Improved LVEF referring to patients with previous HFrEF who now Cardiology, Intermountain Medical Center, Murray, Utah, USA