Lassen Ann-Kristin, Artemenko Yevheniia, Jerosch-Herold Michael, Kowalewski Ines, Olfe Jakob, Kheradvar Arash, Giertzsch Tobias, Sinning Christoph Robert, Mir Thomas S, Mueller Goetz Christoph, Rickers Carsten
Adult Congenital Heart Disease Section, Children's Heart Clinic, University Heart & Vascular Center Hamburg, Hamburg, Germany.
Department of Radiology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, USA.
Cardiovasc Diagn Ther. 2025 Apr 30;15(2):336-349. doi: 10.21037/cdt-24-452. Epub 2025 Apr 23.
The combination therapy of angiotensin-converting enzyme inhibitors (ACEi) or alternatively angiotensin receptor-neprilysin inhibitors (ARNis), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and recently sodium-glucose co-transporter 2 inhibitors (SGLT2is) has been hailed as a breakthrough in heart failure treatment for patients with structurally normal hearts, with international guidelines recommending these as first-line therapies ("fantastic four"). However, specific recommendations for adult with congenital heart disease (ACHD) and systemic right ventricle (sRV), who are at heightened risk for heart failure, are largely based on clinical experience or position statements, lacking robust clinical trial data. This study aims to evaluate the effectiveness and tolerability of these medications in ACHD patients with sRV.
This retrospective single-center cohort study included 21 adult patients with sRV and signs of heart failure [6 with d-transposition of the great arteries (d-TGA) post-atrial switch, 7 with congenitally corrected transposition of the great arteries (cc-TGA), and 8 with univentricular right heart in Fontan circulation]. Changes in functional New York Heart Association (NYHA) class, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, sRV function, and renal function were assessed before and after initiating or escalating heart failure pharmacotherapy with ARNi and/or SGLT2i. The median follow-up was 15 months (1.24 years).
The combination therapy was well tolerated among all patients, with no interruptions in therapy and no adverse effects such as hyperkalemia, renal dysfunction, or significant hypotension reported. Among the 21 patients with follow-up data, 12 were treated with the full combination of guideline-directed therapy, including ARNi and SGLT2i. NYHA class improved in 62.0% of patients (P=0.001), and the median NT-proBNP level decreased from 870 (range, 593-1,774) to 373 (range, 189-743) ng/L (P=0.001). However, no significant change in ventricular function was detected by echocardiography.
Our preliminary findings suggest that in ACHD patients with a sRV the new guideline-directed heart failure pharmacotherapy regimen is well tolerated and leads to improvements in NYHA class and reductions in NT-proBNP levels. Further randomized studies are needed to confirm these promising results and to explore the effects of SGLT2i, either alone or in combination, in this patient population.
血管紧张素转换酶抑制剂（ACEi）或血管紧张素受体脑啡肽酶抑制剂（ARNi）、β受体阻滞剂（BBs）、盐皮质激素受体拮抗剂（MRAs）以及最近的钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的联合治疗，被誉为结构正常心脏患者心力衰竭治疗的一项突破，国际指南推荐这些药物作为一线治疗方案（“神奇四联”）。然而，对于心力衰竭风险较高的先天性心脏病（ACHD）合并系统性右心室（sRV）的成人患者，具体建议很大程度上基于临床经验或立场声明，缺乏有力的临床试验数据。本研究旨在评估这些药物在ACHD合并sRV患者中的有效性和耐受性。
这项回顾性单中心队列研究纳入了21例患有sRV且有心力衰竭体征的成人患者[6例为心房调转术后的大动脉d型转位（d-TGA），7例为大动脉矫正型转位（cc-TGA），8例为Fontan循环中的单心室右心]。在开始或增加使用ARNi和/或SGLT2i进行心力衰竭药物治疗之前和之后，评估纽约心脏协会（NYHA）功能分级、N末端B型利钠肽原（NT-proBNP）水平、sRV功能和肾功能的变化。中位随访时间为15个月（1.24年）。
所有患者对联合治疗耐受性良好，未出现治疗中断，也未报告高钾血症、肾功能不全或显著低血压等不良反应。在21例有随访数据的患者中，12例接受了包括ARNi和SGLT2i在内的指南指导的全面联合治疗。62.0%的患者NYHA分级改善（P=0.001），NT-proBNP中位水平从870（范围593 - 1774）降至373（范围189 - 743）ng/L（P=0.001）。然而，超声心动图未检测到心室功能有显著变化。
我们的初步研究结果表明，在ACHD合并sRV的患者中，新的指南指导的心力衰竭药物治疗方案耐受性良好，可使NYHA分级改善，NT-proBNP水平降低。需要进一步的随机研究来证实这些有前景的结果，并探索SGLT2i单独或联合使用对该患者群体的影响。
