Atrial Shunt Therapy for Heart Failure: An Update

Figures

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  Figure 1. Proposed heart failure with preserved ejection fraction (HFpEF) subtypes defined by invasive hemodynamic testing. CO, cardiac output; CpcPH, combined postcapillary and precapillary pulmonary hypertension; EILAH, exercise-induced left atrial hypertension; Ex, exercise; FAC, fractional area change; FWS, free wall strain; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RAP, right atrial pressure; RELAH, resting left atrial hypertension; RV, right ventricular; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.

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  Central Illustration. Interatrial shunt therapies currently under investigation in humans. CS, coronary sinus; LA, left atrium; PTFE, polytetrafluoroethylene; RA, right atrium; RCT, randomized clinical trial.

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  Figure 2. Effect of placebo/sham on health status (Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) in completed heart failure (HF) randomized clinical trial (RCT) compared with open-label interventional HF trials. For the pharmacological HF trials, baseline KCCQ scores correlated inversely with delta KCCQ scores in the placebo group (R2 = 0.76, P = .002), suggesting that the change in KCCQ scores over time is dependent on the starting (baseline) KCCQ score. This is particularly relevant to open-label interventional HF trials because baseline KCCQ scores tend to be lower than most pharmacological HF trials except those such as PARALLAX, which have an upper threshold for KCCQ values. In the RCT, patients in the placebo group are blinded, whereas patients in the open-label interventional HF trials are unblinded, which may enhance placebo effects, as suggested by the higher delta KCCQ in the unblinded (open-label) vs blinded (sham control) patients in the Corvia REDUCE LAP-HF vs REDUCE LAP-HF II trials, respectively. FIH, first-in-human.

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  Figure 3. Net wins for the composite hierarchical efficacy end point in the atrial shunt device vs sham-control groups across values of peak exercise pulmonary vascular resistance (PVR) in the REDUCE LAP-HF II trial. In patients enrolled in the Corvia REDUCE LAP-HF II trial, there were divergent treatment effects in the atrial shunt group vs sham-control group depending on whether patients had a baseline peak exercise PVR < 1.74 Wood units (WU) (no latent pulmonary vascular disease [PVD]) vs PVR ≥ 1.74 WU (latent PVD). In the win ratio analysis of the composite efficacy end point (hierarchy cardiovascular death, nonfatal ischemic stroke, total (first and recurrent) heart failure (HF) events, and Kansas City Cardiomyopathy Questionnaire [KCCQ]), each patient in the atrial shunt group was compared with each patient in the sham group. There were more wins in the atrial shunt group in patients with no latent PVD (suggesting a beneficial effect with shunting) whereas there were more wins in the sham group in patients with latent PVD (suggesting a detrimental effect with shunting); P = .0006. Note: patients with pacemakers and defibrillators were excluded from this analysis. RCT, randomized…