Exercise-Induced Left Atrial Hypertension in HFpEF
- Exercise-induced LA hypertension (EILAH) with normal resting LA pressures in HFmrEF and HFpEF is common, though can be difficult to diagnose without exercise hemodynamic assessment.
- Creation of an atrial shunt compared to a sham procedure did not improve a composite outcome of cardiovascular death or nonfatal stroke, HF events, and change in health status in patients with EILAH.
- Although characteristics of atrial shunt responders were more common in the EILAH group, further studies are needed.
Based on the REDUCE LAP-HF II trial, in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF or HFpEF), what is the difference between those with normal resting left atrial (LA) pressures but exercise-induced LA hypertension (EILAH) compared to those with resting LA hypertension (RELAH)? How do outcomes differ in these groups with creating an atrial shunt?
This is an analysis of the REDUCE LAP-HF II trial, which was a multicenter study of 626 patients with left ventricular ejection fraction (LVEF) ≥40% with an exercise pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg. Patients were randomized to atrial shunt or sham procedure. No difference in the primary outcome was noted. In this study, patients with EILAH (resting PCWP <15 mm Hg, exercise PCWP ≥25 mm Hg) were compared to patients with RELAH (resting PCWP ≥15 mm Hg, exercise PCWP ≥25 mm Hg) for the hierarchical composite primary outcome of cardiovascular death or nonfatal stroke, HF hospitalization or intensification of diuretics, and change in health status.
Of the 626 patients in the study, 29% had EILAH. Symptom severity was similar between the EILAH and RELAH groups. Compared to the RELAH group, EILAH was independently associated with less atrial fibrillation, less loop diuretic use, lower systolic blood pressure, higher 6-minute walk distance, lower natriuretic peptide level, and lower LV end-diastolic dimension. There was no difference between atrial shunt treatment and sham for the primary outcome in either the EILAH (win ratio: 1.08; p = 0.69) or RELAH (win ratio: 0.98; p = 0.85) groups. Characteristics that were previously associated with a positive response to atrial shunt therapy compared to sham (peak exercise pulmonary vascular resistance <1.74 WU, no cardiac rhythm device) were more likely in patients with EILAH. Safety events were comparable between the groups.
Compared to patients with RELAH, patients with EILAH had similar baseline symptoms but less evidence of cardiac comorbidities, congestion, and cardiac remodeling. Patients with EILAH did not have improvement in the hierarchical composite primary outcome of cardiovascular death or nonfatal stroke, HF hospitalization or intensification of diuretics, and change in health status. However, these patients were more likely to have characteristics previously associated with atrial shunt responsiveness.
In this study of patients with HFmrEF and HFpEF, normal LA filling pressures at rest were quite common, seen in just under 30% of participants. This highlights the difficulty of diagnosing patients with symptomatic HF in this population when overt volume overload is not present at rest but symptoms with exertion are present. Careful hemodynamic assessment with exercise may be needed. For this population of patients with EILAH, the next challenge is identifying the best treatment strategies, which may be limited if standard therapies like loop diuretics are unhelpful. This study highlights the importance and need of novel therapeutics in HF and better phenotyping. While the results of this study did not demonstrate that atrial shunting was associated with significant benefit in patients with EILAH, these patients had characteristics of possible responders. This should be an area for future study with dedicated randomized trials powered to detect meaningful outcomes.
Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Exercise, Hypertension
Keywords: Blood Pressure, Diuretics, Exercise, Heart Failure, Hemodynamics, Hypertension, Natriuretic Peptides, Physical Exertion, Pulmonary Wedge Pressure, Stroke, Stroke Volume
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