Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure.
Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure.
复制标题
DOI：
10.1161/circulationaha.122.059486
复制
发表时间：
2022-05-24
期刊：
影响因子：
37.8
通讯作者：
Shah, Sanjiv J.
中科院分区：
文献类型：
--
作者：
Borlaug, Barry A.;Blair, John;Bergmann, Martin W.;Bugger, Heiko;Burkhoff, Dan;Bruch, Leonhard;Celermajer, David S.;Claggett, Brian;Cleland, John G. F.;Cutlip, Donald E.;Dauber, Ira;Eicher, Jean-Christophe;Gao, Qi;Gorter, Thomas M.;Gustafsson, Finn;Hayward, Chris;van der Heyden, Jan;Hasenfuss, Gerd;Hummel, Scott L.;Kaye, David M.;Komtebedde, Jan;Massaro, Joseph M.;Mazurek, Jeremy A.;McKenzie, Scott;Mehta, Shamir R.;Petrie, Mark C.;Post, Marco C.;Nair, Ajith;Rieth, Andreas;Silvestry, Frank E.;Solomon, Scott D.;Trochu, Jean-Noel;Van Veldhuisen, Dirk J.;Westenfeld, Ralf;Leon, Martin B.;Shah, Sanjiv J.
在REDUCE LAP-HF II试验中，心房分流装置的植入并没有为心力衰竭和保持或轻度降低射血分数（HFpEF/HFmrEF）的患者提供总体的临床益处。然而，预先指定的分析确定了亚最大运动时肺动脉收缩压、右心房（RA）容积和性别所定义的亚组的反应差异。分流术植入降低左心房（LA）压力，但增加肺血流量，这在肺血管疾病（PVD）患者中可能难以耐受。基于这些结果，我们假设有潜伏性PVD的患者（定义为运动时肺血管阻力升高）可能会受到分流器植入的伤害，相反，没有PVD的患者可能会受益。REDUCE LAP-HF II纳入626例HF、EF≥40%、运动肺毛细血管楔形压≥25 mmHg、静息PVR <3.5 WU的患者，按1:1随机分为心房分流器组或假对照组。主要结局是心血管死亡、非致死性缺血性卒中、复发性心衰事件和健康状况改变的分层复合，使用赢比进行分析。潜在PVD定义为随机化前测量的运动峰值时PVR≥1.74 WU（最高分位数）。与无PVD患者（n=382）相比，潜伏性PVD患者（n=188）年龄更大，房颤和右心功能障碍更多，静息时LA压升高的可能性更大。分流治疗与PVD患者预后较差相关（比为0.60,[95% CI 0.42, 0.86]; p=0.005），与无PVD患者临床获益相关（比为1.31 [95% CI 1.02, 1.68]; p=0.038）。RA容量较大的患者和男性使用该装置的结果较差，两组都更有可能使用起搏器、HFmrEF和LA容量增加。对于没有潜伏性PVD或起搏器的患者（n=313，占随机患者的50%），分流治疗产生了更强的临床获益信号（赢比1.51 [95% CI 1.14, 2.00]; p=0.004）。在HFpEF/HFmrEF患者中，有侵入性血流动力学运动试验发现潜伏性PVD的存在，可识别心房分流治疗可能恶化的患者，而没有潜伏性PVD的患者可能受益。运动性肺血管疾病使HFpEF患者对心房分流的反应恶化，而肺血管系统正常的患者可能受益。
In the REDUCE LAP-HF II trial, implantation of an atrial shunt device did not provide, overall, clinical benefit for patients with heart failure and preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, pre-specified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial (RA) volume, and sex. Shunt implantation reduces left atrial (LA) pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). Based upon these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance (PVR) during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. REDUCE LAP-HF II enrolled 626 patients with HF, EF ≥40%, exercise pulmonary capillary wedge pressure ≥25 mmHg, and resting PVR <3.5 WU who were randomized 1:1 to atrial shunt device or sham control. The primary outcome, a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status, was analyzed using the win ratio. Latent PVD was defined as PVR ≥1.74 WU (highest tertile) at peak exercise, measured prior to randomization. Compared to patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated LA pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio 0.60, [95% CI 0.42, 0.86]; p=0.005) and signal of clinical benefit in patients without PVD (win ratio 1.31 [95% CI 1.02, 1.68]; p=0.038). Patients with larger RA volumes and men had worse outcomes with the device, and both groups were more likely to have pacemakers, HFmrEF, and increased LA volume. For patients without latent PVD or pacemaker (n=313, 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio 1.51 [95% CI 1.14, 2.00]; p=0.004). In patients with HFpEF/HFmrEF, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit. Exercise pulmonary vascular disease worsens response to atrial shunt in HFpEF, while patients with normal lung vasculature may benefit.