Καρδιακή ανεπάρκεια : Ο ρόλος των κλασικών και νεότερων βιοδεικτών 39ο Πανελλήνιο Καρδιολογικό Συνέδριο Αθήνα 18-20 Οκτωβρίου 2018 Καρδιακή ανεπάρκεια : Ο ρόλος των κλασικών και νεότερων βιοδεικτών Αγάθη-Ρόζα Βρεττού Επιμελήτρια Α´ Καρδιολογίας Β´Πανεπιστημιακή Καρδιολογική Κλινική ΠΓΝ Αττικόν

Disclosures Nothing to disclose

Intern J of Cardiol 219 ;2016 :111–114

BNP Accuracy is 90% Negative predictive value=90% Optimal cut-off point determined @ 100 pg/mL 1.0 BNP=50 pg/mL 0.8 BNP=80 pg/mL BNP=100 pg/mL Positive predictive value=75% 0.6 BNP=125 pg/mL 0.4 BNP=150 pg/mL Sensitivity Final Diagnosis Heart Failure Final Diagnosis NOT Heart Failure BNP 100 pg/mL “Test positive” 673 227 BNP <100 pg/mL “Test negative” 71 Sensitivity =90% 615 Specificity =73% 0.2 Negative 0.0 predictive value=90% 0.0 0.2 0.4 0.6 0.8 1.0 1-Specificity N Engl J Med. 2002;347:161-167.

Identifying the right patients for echocardiography The use of NPs for rule-out heart failure in symptomatic patients in primary care Identifying the right patients for echocardiography < cut-off value Patient presenting with symptoms suggestive of heart failure Search for other explanation ? “Rule out” > cut-off value Maisel A. ESC 2018 Referral to specialist

Assesment of Heart Failure Probability Clinical History Physical examination ECG All absent ≥1 present Natriuretic peptides NT –pro BNP >125pg/ml BNP>35pg/ml HF unlikely Biomarkers not routinely done in clinical practice ESC Guidelines 2016 Echocardiography

STOP-HF trial Vs. Routine care (n=677) Routine primary care Cardiology care PRN BNP-directed care (n=697) Annual BNP check If BNP >50 pg/ml at any time: cardiology consult, echo, nurse-coaching 1° Endpoint: LV systolic or diastolic dysfunction, or heart failure 2° Endpoints: Emergency hospitalization for arrhythmia, TIA, stroke, MI, PE/DVT, HF JAMA. 2013;310(1):66-74.

JAMA 2013;310(1):66-74

Biomarkers for prevention

Biomarkers for Diagnosis

In high-risk patients with HFrEF, a strategy of NT-proBNP– GUIDE IT In high-risk patients with HFrEF, a strategy of NT-proBNP– guided therapy was not more effective than a usual care strategy in improving outcomes

Biomarkers for Prognosis

Confounders of NP interpretation Higher NP levels than expected Lower NP levels than expected Increasing age* Obesity ACS* Flash pulmonary edema Renal insufficiency Pericarditis/Tamponade RV dysfunction* Genetic polymorphisms Atrial fibrillation “Burned-out” Cardiomyopathy Pulmonary hypertension* Pulmonary embolism* Anemia/high output states* Sepsis Mitral Regurgiation* * Delineates likely elevation from Ventricular stretch

High Sensitivity Troponin in Heart Failure

Mechanism of Cardiac Troponin Release in Heart Failure J Am Coll Cardiol 2010;56:1071–8

Are they really false positives when the elevation gives you greater risk? Chronic HF Elevated in 50% Acute HF Elevated in >80%

Cardiac Troponin and outcome in Acute HF N Engl J Med. 2008 May 15;358(20):2117-2

Cardiac Troponin and outcome in Acute HF N Engl J Med. 2008 May 15;358(20):2117-2

Baseline hsTnT may identify patients with acute HF at very low risk No CV deaths through day 180 were observed in patients with hsTnT levels<0.014mg/l despite highNT-pro BNP Baseline hsTnT may identify patients with acute HF at very low risk for CV mortality

A combination of Natriuretic Peptide and PCT can A combination of Natriuretic Peptide and PCT can be used to better diagnose dyspneic patients Eur Journal of Heart Failure 2012;14: 278–286

ESC Heart Fail. 2017;4(3):203-208

IMPACT EU –BIC-18: Procalcitonin-guided antibiotic therapy does not improve mortality in patients with shortness of breath and suspected AHF NCT02392689 Terminated : At 75% patient completion overall mortality was much lower than expected and without significant difference at day 90. No chance to reach the primary endpoint.

sST2 soluble suppressor of Tumorigenicity 2 Arq Bras Cardiol. 2016; 106(2):145-152

sST2 –solid cutpoints >35ng/ml RISK

lBMI ST2 not effected by lAge lSex lEtiology of HF lAtrial Fibrillation lAnemia

The prognostic value of sST2 was not influenced by renal function In a cohort of 879 heart failure patients ST2 did not show any correlation with renal function whereas NT-proBNP concentrations increased significantly with decreasing renal function J Cardiac Fail 2013;19:768e775

independent of repeatedly measured Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF independent of repeatedly measured NT-pro BNP J Am Coll Cardiol 2017;70:2378–88

sST2 is a predictor of all-cause CV death JACC Heart Fail 2017;5:284

Why ST-2 levels might be better than NP levels to follow patients Natriuretic peptides Much day to day variability of BNP- diuretic use, salt load from meals, time of blood draw. “wet BNP” changes rapidly- which may justrepresent volume and not remodeling Difficult to use with CKD GUIDE IT negative sST2 Little variability Does not seem to be affected by volume as much Not effected by CKD ST-2 especially responsive to antifibrotic drugs like MRA and sacubitril–valsartan

sST2 unanswered issues Timing Frequency of testing Earlier evaluation after hospitalization Treatment escalation Initiation/uptitration of antifibrotic drugs Monitoring device ( Cardio-MEMS) Implantation?

Conclusions Several biomarkers have emerged as adjunct tools to clinical decision making and CV imaging Natriuretic peptides can be useful for prevention of LV dysfunction HF diagnosis in the ED setting Improved risk stratification of HF patients Cardiac Troponin may be considered for added risk stratification sST2 as a marker of myocardial fibrosis may also be considered for added risk stratification and relevant therapeutic decision making

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