Gaps in Device Therapy
Cardiac resynchronisation therapy (CRT) has played an important role in the past decade in decreasing hospitalisations and increasing survival of patients with HFrEF. Though benefits are clear for symptomatic patients in sinus rhythm with typical left bundle branch block (LBBB) (particularly with QRS width >150 ms), there are some populations where data are equivocal.20 Post-hoc analysis of the major CRT trials showed no significant benefit in subgroups with non-LBBB morphology or subgroups with QRS duration <150 msec.21,22 Results are pending of the recently completed Pacing Affects Cardiovascular Endpoints in Patients with Right Bundle-Branch Block (PACE-RBBB) trial, which is evaluating whether univentricular right ventricular (RV) pacing can restore synchronisation in patients with right bundle branch block (RBBB) (NCT01169493). The benefits of CRT are also unclear in patients with AF where efficient CRT delivery is compromised by underlying conduction. Thus these patients have been excluded from most major CRT trials.23 In the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) that evaluated CRT in patients with mild-to-moderate HF, subsets of patients with permanent AF had no clinical benefit with CRT.24 An ongoing RCT is evaluating the strategy of atrioventricular junction ablation to increase CRT response in patients with permanent AF (NCT01522898). Finally, although up to 30–45 % of CRT-implanted patients receive little benefit, the management of these CRT non-responders remains controversial.25 A meta-analysis suggests small improvement in left ventricular ejection fraction (LVEF) with CRT optimisation procedures, but it is unclear whether this would translate into hard outcomes, and the ideal optimisation protocol remains undefined.26
Device-based clinical management interventions for HF have shown mixed results. Previous trials of thoracic impedance monitoring and remote monitoring systems have failed to show improvement in outcomes.27,28 More recently, however, the Influence of Home Monitoring on Mortality and Morbidity in Heart Failure Patients with Impaired Left Ventricular Function (IN-TIME) trial showed that an implantable cardioverter defibrillator (ICD)-based telemonitoring system dramatically reduced mortality when compared with standard care (HR 0.37, 95 % CI 0.16–0.83).29 Another device, an implantable pulmonary artery pressure monitor, was shown in the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Functional Class III Heart Failure Patients (CHAMPION) trial to decrease HF hospitalisation (HR 0.72, 95 % CI 0.60–0.85).30 However, in both these positive trials the contribution of additional patient–physician interaction on outcomes cannot be underestimated. Notably there was a delay in FDA approval of the pulmonary artery pressure monitoring device over question of potential bias in preferential support of treatment group.31 Neither the ACCF/AHA nor the ESC Guideline endorses a remote monitoring strategy.
From a structural standpoint, new data about transcatheter mitral valve repair is encouraging. Secondary mitral regurgitation (MR) is a common consequence of left ventricular (LV) enlargement and dysfunction, but surgical repair has not been proven to be superior to medical therapy for functional MR.32 Two recent non-randomised trials reported results of transcatheter mitral valve repair MitraClip in patients with severe MR who were deemed too high-risk for surgery.33,34 In both studies more than 70 % of patients had functional MR. After mitral valve repair using MitraClip device, patients experienced improved clinical symptoms, decreased LV dimensions, and in one of the trials decreased mortality compared with a propensity matched cohort. Further prospective controlled trials are ongoing to define transcatheter mitral valve repair’s role in patients with symptomatic functional MR (NCT01626079 and NCT01772108). Pending results from these RCTs, the ACCF/AHA Guideline gives transcatheter mitral valve repair for functional MR an ambivalent Class IIb/LOE B recommendation, and the ESC Guideline does not give a specific class of recommendation about this topic.