Combined Cardiopulmonary Failure in COPD: SPIROMICS HF

年，慢性阻塞性肺疾病(COPD)的死亡率和住院率翻了一番 过去的50年里。三分之一的慢性阻塞性肺疾病住院患者与心力衰竭重叠，大多数患者射血功能受损。 心功能(HFpEF)，但尚未有大型COPD研究确定心功能。《红楼梦》的多民族研究 动脉粥样硬化(MESA)COPD研究被资助以检验肺气肿的内皮假说和 检查COPD患者右室内径缩小(“微小肺源性心脏病”)。在梅萨慢性阻塞性肺病研究II中，我们发现 肺微血管血流量减少与肺气肿的相关性似乎不是 低氧性肺血管收缩和CT肺气肿预示RV消退 五年了。我们还开发了进一步分型肺气肿和慢性阻塞性肺病的方法，并将其扩大到 慢性阻塞性肺疾病研究中的亚群和中间结果测量(SPIROMICS)。我们使用的是无人监督的 机器学习来发现新的肺气肿亚型，这些亚型是常见的，有分子起源。 另外，我们发现26%的成年人有节段性呼吸道变异，这与COPD和 发育基因FGF10和RARA。这两种基因都会影响右心发育。在试点工作中，我们 发现一株RV株发生了显著变化，另一株与肺心病有关。最后，我们 研究发现，有支气管炎症状的吸烟者，即因气体滞留而过度充气的人，可能会增加 左室舒张功能不全。因此，COPD的心脏改变是复杂的，但COPD的最新进展 分型可能允许他们进行个性化的诊断和治疗。SPIROMICS是NHLBI资助的前景 这项研究招募了患有COPD和对照组的吸烟者，并正在重新检查2000名参与者的金牌- 标准肺表型，包括全肺CT。我们建议增加综合超声心动图(ECHO) 对1,000名SPIROMICS参与者进行心脏力学斑点跟踪，并在700和 600人的心肺MRI，以检验以下假设：1)机器学习的肺气肿亚型 CT与心脏结构和功能的特殊改变有关，这些改变从肺心病到 2)有节段性气道变异的受试者右室结构异常， 3)有症状的吸烟者有左室后负荷增加和左室舒张功能障碍的体征。 该应用的创新方面包括使用新的回波和磁共振测量在一个大的，井- 具有特征的COPD患者队列。假说的确认将定义 HFpEF在慢性阻塞性肺疾病中的作用，并确定心肺功能障碍的靶向治疗的患者亚群。

The death rate and hospitalizations from chronic obstructive pulmonary disease (COPD) have doubled in the last 50 years. A third of COPD hospitalizations overlap with heart failure, mostly with preserved ejection fraction (HFpEF), yet no large COPD study has ascertained cardiac function. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study was funded to test the endothelial hypothesis of emphysema and examine reduced RV dimensions (“cor pulmonale parvus”) in COPD. In the MESA COPD Study II, we found that associations of reduced pulmonary microvascular blood flow with emphysema do not appear to be confounded by hypoxic pulmonary vasoconstriction and that emphysema on CT predicted RV regression over 5 years. We also developed methods to further subtype emphysema and COPD and scaled them up to the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). We used unsupervised machine learning to discover new emphysema subtypes that are common and have molecular origins. Separately, we found that 26% of adults have segmental airway variants, which are associated with COPD and the developmental genes FGF10 and RARA. Both genes affect right heart development. In pilot work, we found one dramatically altered RV strain and the other associated with cor pulmonale parvus. Finally, we found that bronchitic ‘symptomatic smokers,’ who have hyperinflation from gas trapping, may have increased LV diastolic dysfunction. Hence, cardiac alterations in COPD are complex but recent advances in COPD subtyping may allow their personalized diagnosis and treatment. SPIROMICS is an NHLBI-funded prospective study that recruited smokers with COPD and controls and is re-examining 2,000 participants with gold- standard lung phenotyping including full-lung CT. We propose to add comprehensive echocardiography (echo) with speckle-tracking for cardiac mechanics for 1,000 SPIROMICS participants, with exercise in 700 and cardiopulmonary MRI in 600, to test the following hypotheses: 1) machine-learned subtypes of emphysema on CT are associated with specific alterations in cardiac structure and function, which vary from cor pulmonale to LV diastolic dysfunction; 2) participants with segmental airway variants have abnormal RV structure and function; 3) symptomatic smokers have signs of increased LV afterload and LV diastolic dysfunction. Innovative aspects of the application include the use of novel echo and MRI measures in a large, well- characterized cohort of COPD patients. Confirmation of the hypotheses would define the mechanisms of HFpEF in COPD and identify subsets of patients for targeted treatment of cardiopulmonary dysfunction.