Background: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest.

Methods and Results: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of “PCWP/CO slope” in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo₂ (P<0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P=0.03) at a median 5.3-year follow-up.

Conclusions: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis.

背景：静息时左心室充盈压的单次测量缺乏敏感性，无法确定劳累性呼吸困难患者的心律失常并伴有射血分数保留（HFpEF）。我们假设运动血液动力学测量（即，以心输出量[CO]为指标的肺毛细血管楔压[PCWP]的变化）可能更敏感地区分HFpEF和非HFpEF疾病状态，反映有氧能力并预测患有以下疾病的个体的心力衰竭结果正常PCWP处于静止状态。

方法和结果：我们研究了175位接受血液动力学监测的心肺运动测试患者：对照（n = 33），静息PCWP≥15mm Hg的HFpEF（n = 32）和劳累性呼吸困难且静息PCWP正常且左心室射血分数（ DOE-nlrW； n = 110）。在整个运动过程中的1835次配对PCWP-CO测量中，我们使用了回归技术来定义对照组中“ PCWP / CO斜率”的标准范围，并测试了PCWP / CO斜率与运动能力和复合心脏结果（定义为心源性死亡，突发事件）之间的关联在DOE-nlrW组中静息PCWP升高或心力衰竭住院。相对于对照组（PCWP / CO斜度为1.2±0.4 mm Hg / L / min），HFpEF患者的PCWP / CO斜度为3.4±1.9 mm Hg / L / min。我们使用2 mm Hg / L / min的阈值（比对照组平均值高2 SD）来定义异常。校正年龄，性别和体重指数（危险比，3.47；P = 0.03）后，中位数为5.3年，随访后o ₂（P <0.001）和不良心脏预后。

结论： DOE-nlrW中运动过程中PCWP / CO斜率升高（> 2 mm Hg / L / min）是常见现象，可预测运动能力和心力衰竭结局。这些发现表明，目前在休息期间仅基于单一测量方法对HFpEF的定义是不够的，并且对运动PCWP / CO斜率的评估可能会改善HFpEF的早期诊断。