Table 1

Study designs and response outcome definitions

Study IDDesignParticipants recruitedHF/CRT participantsInclusion criteriaObservation periodAssessmentsECM biomarkersCRT responder definitionResponse rate
Dong et al26Prospective observational65 (20 healthy controls)45LVEF≤35%, NYHA III–IV, QRS>120 ms, SR and OMT6 monthsBaseline/3 months/6 months: NYHA, 6MWT, TTE, blood samplesPIIINP↓≥15% LVESVi and survived at 6 months22 (48.9%)
Tolosana et al24Prospective observational55 (13 excluded after recruitment)42LVEF≤35%, NYHA III–IV, QRS>120 ms and OMT or cardiac pacing indication (LVEF<35%)12 monthsBaseline/6 months/12 months: NYHA, QoL (MLHFQ), 6MWT, TTE, ECG, blood samplesMMP-2, TIMP-1↑>10% 6 MWT or if test not performed ↑>1 NYHA and survived/no heart transplant at 12 months25 (59.6%)
Truong et al25Prospective observational7373LVEF<35%, NYHA II–IV, QRS≥120 ms, OMT, HF decompensation <12 months24 months (IQR 20.4–24.0)Baseline: NYHA, ECG, TTE 1 month/3 months
6 months Clinical FU
Gal-3Improvement HF clinical composite score30 at 6 months40 (54.7%)
Umar et al10Prospective observational6464LVEF<35%, NYHA III–IV, QRS>120ms6 monthsBaseline/6 months: NYHA, TTE; QoL (MLHFQ), 6MWT, blood samplesPINP,
ICTP, proMMP-1,
↓≥10% LVESV at 6 months46 (71.8%)
Garcia-Bolao et al 9Prospective observational6159LVEF≤35%, NYHA III–IV, LBBB, QRS≥130 ms, OMT12 monthsBaseline/12 months: NYHA, QoL (MLWHFQ), 6MWT, TTE, ECG, blood samplesPICP,
MMP-1, MMP-2, MMP-9, TIMP-1
↑≥10% 6 MWT and survival from cardiac mortality at 12 months35 (59.3%)
Lopez-Andres et al8*Substudy randomised control trial: CARE-HF260 (CARE-HF cohort available)132 (CRT-P only)LVEF<35%, NYHA III–IV, QRS>150 ms or 120–149 ms with echocardiographic dyssynchrony, OMTSubstudy: 18 months; CARE-HF: 29.4 months (range, 18.0–44.7)Substudy Baseline/3 months/18 months: TTE, blood samplesPINP,
Survival and LVEF more than 35% at 18 monthsCRT-p (n=108): 72 (66.6%); OMT (n=117): 103 (88.0%), p=0.0001
  • *Median (IQR).

  • CITP, carboxy-terminal telopeptide of collagen type-I; CRT, cardiac resynchronisation therapy; CRT-p, CRT-pacemaker; ECM, extracellular cardiac matrix; Gal-3, galectin-3; HF, heart failure; ICTP, carboxy-terminal telopeptide of type I collagen; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVESVi, left ventricular end-systolic volume indexed; 6MWT, six min walk test; MLHFQ, Minnesota living with heart failure questionnaire; MMP, metalloproteinases; NYHA, New York Heart Association; OMT, optimal medical therapy; PINP, N-terminal propeptides of type I procollagens; PIIINP, N-terminal propeptides of type III procollagens; QoL=quality of life; SR, sinus rhythm; TIMP, tissue inhibitors of MMPs; TTE, transthoracic echocardiogram.