Background:Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process.Methods:We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer.Results:Paralleling the stepwise decline in diastolic function across the groups (E/e′ ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=–0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=–0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (–0.1% [–1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [–1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=–0.43; P=0.004).Conclusions:A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

中文翻译：

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射血分数保留的心力衰竭运动引起的肺充血的能量基础

背景：运动期间短暂的肺充血正在成为射血分数保留的心力衰竭（HFpEF）运动能力降低的重要决定因素。我们试图确定异常的心脏能量状态是否是这一过程的基础。方法：我们招募了各种舒张功能障碍和 HFpEF 的患者（对照组，n=11；2 型糖尿病，n=9；HFpEF，n=14；重度心力衰竭患者）。心脏淀粉样变性导致的舒张功能障碍，n=9)。使用磷光谱测量心脏能量学以确定心肌磷酸肌酸与 ATP 的比率。通过心血管磁共振电影成像和超声心动图评估心脏功能，并使用磁共振质子密度图评估肺水。研究是在休息时和次最大运动期间使用磁共振成像测力计进行的。结果：与各组舒张功能逐步下降（E/e'比；P <0.001）平行的是 NT-proBNP（N端）的增加脑钠肽前体；P <0.001）和磷酸肌酸/ATP 比率降低（对照，2.15 [2.09，2.29]；2 型糖尿病，1.71 [1.61，1.91]；HFpEF，1.66 [1.44，1.89]；心脏淀粉样变性，1.30 [1.16，1.53]；P <0.001）。在 20 周运动期间，左心室舒张期充盈率较低（r=0.58；P <0.001），左心室舒张期储备较低（r=0.55；P <0.001），左心房扩张（r=–0.52；P <0.001） 、右心室收缩储备降低（右心室射血分数变化，r=0.57；P <0.001）和右心房扩张（r=–0.71；P <0.001）均与较低的磷酸肌酸/ATP 比率相关。除了这些变化之外，肺质子密度图显示 HFpEF（+4.4% [0.5, 6.4]；P =0.002）和心脏淀粉样变性（+6.4% [3.3, 10.0]；P =0.004）患者出现短暂性肺充血，这在健康对照 (–0.1% [–1.9, 2.1]; P =0.89) 或无 HFpEF 的 2 型糖尿病 (+0.8% [–1.7, 1.9]; P =0.82)中未观察到这一现象。运动引起的肺充血的发展与较低的磷酸肌酸/ATP 比值相关（r=–0.43；P =0.004）。结论：整个 HFpEF 谱系中存在心肌能量缺陷的梯度。即使在低工作负荷下，这种能量不足也与所有 4 个心室的明显异常运动反应有关，这与可检测到的肺充血有关。这些发现为 HFpEF 中短暂性肺充血提供了能量基础。