Division or Pediatric Cardiology, Department of Pediatrics (J.H.S., K.C., K.G.-D.), Vanderbilt University Medical Center, Nashville, TN.
Department of Biostatistics (M.X., J.C.S.), Vanderbilt University Medical Center, Nashville, TN.
Circ Heart Fail. 2023 Aug;16(8):e010040. doi: 10.1161/CIRCHEARTFAILURE.122.010040. Epub 2023 Jun 8.
Cardiopulmonary failure is the leading cause of death in Duchenne muscular dystrophy (DMD). Research into DMD-specific cardiovascular therapies is ongoing, but there are no Food and Drug Administration-approved cardiac end points. To adequately power a therapeutic trial, appropriate end points must be chosen and the rate of change for these end points reported. The objective of this study was to evaluate rate of change for cardiac magnetic resonance and blood biomarkers and to determine which measures associate with all-cause mortality in DMD.
Seventy-eight DMD subjects underwent 211 cardiac magnetic resonance studies analyzed for left ventricular (LV) ejection fraction, indexed LV end diastolic and systolic volumes, circumferential strain, late gadolinium enhancement presence and severity (global severity score, and full width half maximum), native T1 mapping, T2 mapping, and extracellular volume. Blood samples were analyzed for BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and troponin I. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome.
Fifteen subjects (19%) died. LV ejection fraction, indexed end systolic volumes, global severity score, and full width half maximum worsened at 1 and 2 years while circumferential strain and indexed LV end diastolic volumes worsened at 2 years. LV ejection fraction, indexed LV end diastolic and systolic volumes, late gadolinium enhancement full width half maximum, and circumferential strain associated with all-cause mortality (<0.05). NT-proBNP was the only blood biomarker that associated with all-cause mortality (<0.05).
LV ejection fraction, indexed LV volumes, circumferential strain, late gadolinium enhancement full width half maximum, and NT-proBNP are associated with all-cause mortality in DMD and may be the best end points for use in cardiovascular therapeutic trials. We also report change over time of cardiac magnetic resonance and blood biomarkers.
心肺衰竭是杜氏肌营养不良症（DMD）患者死亡的主要原因。目前正在研究针对 DMD 的心血管治疗方法，但尚未获得美国食品和药物管理局批准的心脏终点。为了充分进行治疗试验，必须选择适当的终点，并报告这些终点的变化率。本研究的目的是评估心脏磁共振和血液生物标志物的变化率，并确定哪些指标与 DMD 的全因死亡率相关。
78 例 DMD 患者接受了 211 次心脏磁共振检查，分析左心室（LV）射血分数、LV 舒张末期和收缩末期容积指数、周向应变、晚期钆增强的存在和严重程度（整体严重程度评分和半高全宽）、原生 T1 映射、T2 映射和细胞外容积。血液样本分析脑钠肽（BNP）、N 末端 pro-B 型利钠肽（NT-proBNP）和肌钙蛋白 I。使用全因死亡率作为结果进行 Cox 比例风险回归模型。
15 名受试者（19%）死亡。LV 射血分数、LV 收缩末期容积指数、整体严重程度评分和半高全宽在 1 年和 2 年时恶化，而周向应变和 LV 舒张末期容积指数在 2 年时恶化。LV 射血分数、LV 舒张末期和收缩末期容积指数、晚期钆增强半高全宽和周向应变与全因死亡率相关（<0.05）。NT-proBNP 是唯一与全因死亡率相关的血液生物标志物（<0.05）。
LV 射血分数、LV 容积指数、周向应变、晚期钆增强半高全宽和 NT-proBNP 与 DMD 的全因死亡率相关，可能是心血管治疗试验中使用的最佳终点。我们还报告了心脏磁共振和血液生物标志物随时间的变化。
