The Prognostic Value of Troponin Levels Adjusted for Renal Function in Heart Failure – A Systematic Review

Nonischemic CHF

LVEF 30 [25 – 35] %

CHF

LVEF < 45%

CHF

All LVEF

HF hospitalization

All-cause mortality

AHF

All LVEF

AHF

All LVEF

AHF

All LVEF

In-hospital mortality

All-cause mortality

Cardiovascular mortality

AHF

All LVEF

AHF

All LVEF

CHF

All LVEF

All-cause mortality

Composite endpoint of all-cause mortality or CHF-related rehospitalization

AHF

All LVEF

All-cause mortality

Readmission for worsening HF

Composite of mortality or readmission

AHF

LVEF 30 [24 – 38] %

Composite endpoint including worsening

HF despite treatment or worsening renal function

CHF

All LVEF

CHF

Reduced LVEF

All-cause mortality

HF mortality

Cardiovascular hospitalization

CHF

All LVEF

AHF

LVEF 26 ± 13 %

CHF

LVEF ≤45%

CHF

Reduced LVEF

Nonischemic CHF

LVEF <45%

AHF Median

LVEF 45%

AHF

All LVEF

CHF

LVEF 34 [26–43] %

AHF

Median LVEF 25%

All-cause mortality

Composite of 30-day mortality and rehospitalization

Dyspnea improvement at 6 and 24 h

Worsening HF or death to day 7

Length of stay

CHF

LVEF ≤40%

Composite endpoint (cardiovascular death or HF hospitalization)

Cardiovascular death

All-cause mortality

AHF

All LVEF

CHF

LVEF < 45%

AHF

LVEF 43.1 ± 13.8 %

All-cause mortality

HF hospitalization

WRF (defined as ≥0.3 mg/dL or 50% increase in creatinine within 5 days)

Step 1: randomized treatment, age, sex, hypertension, diabetes mellitus, coronary artery disease, history of stroke/(TIA), (BMI), heart rate, sinus rhythm and renal function ([CrCl])

Step 2: Step 1 + NT-proBNP

NT-proBNP, hs-TnT, hs-CRP were log2-transformed.

The prognostic model includes the three biomarkers.

Continuous variable

Log-transformed, natural logarithm

3 categories:

↓ hs-cTnT over time (changes < −15%)

Stable levels (changes between −15% and +15%), or

↑ levels (relative changes > +15%).

Median FU

ValHEFT 24 (1-3; 18-24) months

GISSI 47 (38 – 55) months

Val-HEFT 1.69 (1.49 – 1.92)

GISSI-HF 2.23 (1.86 – 2.69)

Val-HEFT 1.60 (1.41 – 1.82)

GISSI-HF 1.97 (1.58 – 2.46)

Val-HeFT: age, sex, BMI, LVEF (%), NYHA class (III or IV), ischemic etiology of HF, SBP, DBP, Hr, DM, AF, COPD, prescription of diuretics, beta-blockers or spironolactone, serum bilirubin, serum creatinine, log baseline hs-cTnT.

GISSI-HF: age, BMI, LVEF, NYHA class, ischemic etiology of HF, SBP, DBP, HR, DM, AF, COPD, prescription of diuretics or beta-blockers, serum bilirubin, serum creatinine, log baseline hs-cTnT.

Val-HEFT 1.59 (1.39 – 1.82)

GISSI-HF 1.88 (1.50 – 2.35)

Val-HeFT: previous parameters + baseline NT-proBNP and hs-CRP

GISSI-HF: previous parameters + baseline NT-proBNP and hs-CRP

Model 1: HR 1.45 (1.24 – 1.71)

Model 2: HR 1.36 (1.14 – 1.62)

Model 3: HR 1.27 (1.06 – 1.53)

Model 1 = Age, gender

Model 2 = Model 1 + renal function (eGFR), HF etiology, NT-proBNP

Model 3 = Model 2 + GDF-15, hs-CRP, galectin 3

Q2, HR 1.8 (1.1 – 2.9), p = 0.014;

Q3, HR 2.7 (1.7 – 4.2), p = 0.001;

Q4, HR 4.6 (3.0 – 7.0), p = 0.001;

Q1 reference

Q2, HR 1.4, 95% CI 0.9 to 2.4, p _ 0.15;

Q3, HR 1.9, 95% CI 1.3 to 3.1, p _ 0.008;

Q4, HR 3.1, 95% CI 1.9 to 5.1, p _0.001)

HR 1.4 (95% confidence interval 0.9 to 2.4, p 0.16) for quartile 2, 1.7 (0.9 to 2.5, p 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4

Troponin T 99th percentile 1.7 (1.2–2.5) 0.003

Long-term all-cause mortality

Median follow-up 1.9 years

Continuous variable

Log-transformed, natural logarithm)

Continuous variable

Log-transformed, natural logarithm

Continuous variable

Log-transformed, natural logarithm

HFrEF OR 2.58 (95%CI 1.57 – 4.23)

HFmrEF OR 4.53 (95%CI 1.85 – 11.1)

HFpEF OR 1.48 (95%CI 0.89 – 2.46)

In-hospital mortality

Not statistically significant

6-month ACM HR 1.73 (95%CI 1.17 – 2.54)

12-month ACM HR 1.60 (95%CI 1.11 – 2.33)

24-month ACM HR 1.89 (95%CI 1.27 – 2.82)

Continuous variable

Log2-transformed

In-hospital mortality

HR 1.45 (95%CI 1.31 – 1.59)

In-hospital mortality

HR 1.30 (95%CI 1.07 – 1.60)

eGFR ≥ 45 ml/min: hs-cTnT > 40 ng/L

eGFR < 45 ml/min: hs-cTnT > 55 ng/L

eGFR ≥ 90ml/min AUC 0.75 (0.64 – 0.86)

eGFR 60 – 89 ml/min AUC 0.74 (0.62 – 0.85)

eGFR 45 – 59 ml/min AUC 0.77 (0.64 – 0.91)

eGFR 30 – 44 ml/min AUC 0.63 (0.50 – 0.75)

eGFR < 30 ml/min AUC 0.62 (0.49 – 0.74)

Tertile 1 HR 0.88 (0.37 – 2.11)

Tertile 2 HR 1.10 (0.55 – 2.18)

Tertile 3 HR 1.20 (0.69 – 2.07)

The median value of minimum cTnI was 0.03 ng/ml (IQR: 0.03 to 0.06 ng/ml

The median overall cTnI was 0.06 ng/ml (IQR: 0.04 to 0.1 ng/ml)

The median value of maximum cTnI was 0.15 ng/ml (IQR: 0.08 to 0.42 ng/ml)

delta cTnI equal to 0.01 ng/ml (IQR: – 0.05 to 0.09 ng/ml)

All-cause long-term mortality

(632 person-years)

Minimum cTnI: HR=5.8, 95% CI 1.7 to 19.7

Median cTnI: HR=2.3, 95% CI: 1.3 to 4.1

Delta cTnI: HR=1.1, 95% CI 1.04 to 1.23

Maximum cTnI was not associated with mortality

minimum TnI was the only TnI pattern significantly

associated with mortality, with a .2 value of 13.7, pb0.001 and HR of 13.7 (95% CI: 3.7 to 50.8)

minimum TnI > 0.04 ng/ml HR=1.6, 95% CI: 1.1 to 2.3,

Doubling of cTnI: OR 1.23 (1.01 – 1.50), p=0.035

20% increase of cTnI OR 3.39 (1.26 – 9.15), p=0.0158

Absolute change in troponin

OR 0.76 (0.57 – 1.02), p=0.063

Compared to patients with non-IHF and normal troponin, subgroup categories:

Non-IHF and ↑ troponin HR 1.77 (1.52 – 2.07), p<0.001

IHF and normal troponin HR 1.61 (1.26 – 2.06), p<0.001

IHF and ↑ troponin HR 2.29 (1.97 – 2.66), p<0.001

Compared to patients with non-IHF and normal troponin, subgroup categories:

Non-IHF and ↑ troponin HR 1.60 (1.36 – 1.88), p<0.001

IHF and normal troponin HR 1.44 (1.12 – 1.85), p=0.005

IHF and ↑ troponin HR 1.88 (1.60 – 1.55), p<0.001

Non-IHF

HR 3.08 (2.27 – 4.17), p<0.001

IHF HR 3.47 (2.02 – 5.93), p<0.001

Non-IHF

HR 2.47 (1.81 – 3.37), p<0.001

IHF

HR 2.91 (1.65-5.12), p<0.001

Non-IHF

HR 1.41 (1.18 – 1.68), p<0.001

IHF

HR 1.03 (0.81 – 1.32), p=0.79

Non-IHF

HR 1.36 (1.13 – 1.63), P<0.001

IHF

N/A

cTnT ≥ 50 ug/L

cTnI ≥0.5 ng/L