Objectives

This study prospectively evaluated endomyocardial biopsies in patients with heart failure with preserved ejection fraction (HFpEF) to identify histopathologic phenotypes and their association with clinical characteristics.

Background

Myocardial tissue analysis from a prospectively defined HFpEF cohort reflecting contemporary comorbidities is lacking.

Methods

Patients with HFpEF (EF ≥50%) referred to the Johns Hopkins HFpEF Clinic between August 2014 and September 2018 were enrolled for right heart catheterization and endomyocardial biopsy. Clinical features, echocardiography, hemodynamics, and tissue histology were determined and compared with controls (unused donor hearts) and HF with reduced EF (HFrEF).

Results

Of the 108 patients enrolled, median age was 66 years (25th to 75th percentile: 57 to 74 years), 61% were women, 57% were African American, 62% had a previous HF hospitalization, median systolic blood pressure was 141 mm Hg (25th to 75th percentile: 125 to 162 mm Hg), body mass index (BMI) was 37 kg/m² (25th to 75th percentile: 32 to 45 kg/m²), and 97% were on a loop diuretic. Myocardial fibrosis and myocyte hypertrophy were often present (93% and 88%, respectively); however, mild in 71% with fibrosis and in 52% with hypertrophy. Monocyte infiltration (CD68+ cells/mm²) was greater in patients with HFpEF versus controls (60.4 cells/mm² [25th to 75th percentile: 36.8 to 97.8] vs. 32.1 cells/mm² [25th to 75th percentile: 22.3 to 59.2]; p = 0.02) and correlated with age and renal disease. Cardiac amyloidosis (CA) was diagnosed in 15 (14%) patients (HFpEF-CA: 7 patients with wild-type transthyretin amyloidosis [ATTR], 4 patients with hereditary ATTR, 3 patients with light-chain amyloidosis, and 1 patient with AA (secondary) amyloidosis), of which 7 cases were unsuspected. Patients with HFpEF-CA were older, with lower BMI, higher left ventricular mass index, and higher N-terminal pro−B-type natriuretic peptide and troponin I levels.

Conclusions

In this large, prospective myocardial tissue analysis of HFpEF, myocardial fibrosis and hypertrophy were common, CD68+ inflammation was increased, and CA prevalence was 14%. Tissue analysis in HFpEF might improve precision therapies by identifying relevant myocardial mechanisms.

中文翻译：

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保留射血分数的心力衰竭的心内膜心肌活检表征和心脏淀粉样变性的患病率。

目标

本研究前瞻性地评估了射血分数保留的心力衰竭 (HFpEF) 患者的心内膜心肌活检，以确定组织病理学表型及其与临床特征的关联。

背景

缺乏对反映当代合并症的前瞻性定义的 HFpEF 队列的心肌组织分析。

方法

2014 年 8 月至 2018 年 9 月期间转诊至约翰霍普金斯大学 HFpEF 诊所的 HFpEF（EF ≥50%）患者被纳入进行右心导管插入术和心内膜心肌活检。确定了临床特征、超声心动图、血流动力学和组织组织学，并与对照组（未使用的供体心脏）和 EF 降低的 HF (HFrEF) 进行比较。

结果

在纳入的 108 名患者中，中位年龄为 66 岁（第 25 至第 75 个百分位：57 至 74 岁），61% 为女性，57% 为非裔美国人，62% 曾因心衰住院，中位收缩压为 141 mmHg （第 25 至第 75 个百分位数：125 至 162 毫米汞柱），体重指数 (BMI) 为 37 kg/m ²（第 25 至第 75 个百分位数：32 至 45 kg/m ²），并且 97% 使用袢利尿剂。常存在心肌纤维化和心肌细胞肥大（分别为 93% 和 88%）；然而，71% 的轻度纤维化和 52% 的肥大。与对照组相比，HFpEF 患者的单核细胞浸润（CD68+ 细胞/mm ²）更大（60.4 个细胞/mm ² [第 25 至 75 个百分位：36.8 至 97.8] 与 32.1 个细胞/mm ²[第 25 至第 75 个百分位数：22.3 至 59.2]；p = 0.02) 并与年龄和肾脏疾病相关。15 名（14%）患者（HFpEF-CA：7 名患者患有野生型甲状腺素运载蛋白淀粉样变性 [ATTR]，4 名患者患有遗传性 ATTR，3 名轻链淀粉样变性患者和 1 名 AA 患者）被诊断为心脏淀粉样变性（CA） （继发性）淀粉样变性），其中 7 例是意外。HFpEF-CA 患者年龄较大，BMI 较低，左心室质量指数较高，N 端前 B 型利钠肽和肌钙蛋白 I 水平较高。

结论

在这项大型、前瞻性的 HFpEF 心肌组织分析中，心肌纤维化和肥大很常见，CD68+ 炎症增加，CA 患病率为 14%。HFpEF 中的组织分析可能会通过识别相关的心肌机制来改善精准治疗。