Clinical Biochemistry in Cardiac

Interventions

Dr Roy Sherwood
Clinical Biochemistry
KCH
Topics

• Natriuretic peptides in CABG

• Remote ischaemic preconditioning in

CABG

• TVAI (trans arterial valve insertion

The Natriuretic peptides
1981- de Bold et al showed infusion of atrial tissue
extracts caused a copious natriuresis. This
observation led to the isolation and cloning of atrial
natriuretic peptide (ANP).

ANP- member of family of peptides- which includes

brain natriuretic peptide (BNP) and C-type natriuretic
peptide (CNP) and Dendroaspis natriuretic peptide
(DNP).

Each produced as a prohormone, encoded by a

separate gene. In addition, there is tissue specific
distribution
Forms of Natriuretic Peptides

Atrial

Vascular
endothelium

Ventricular

• BNP has been shown to be the most stable and specific

of the natriuretic peptides.
Am Heart J 1998;135(5):914-23
Biochemistry of BNP

preproBNP (134 aa)

proBNP (108 aa)

NT-proBNP (1-76) BNP (77-108)

ProBNP is in the cardiac cell

It cleaves into BNP and NT-proBNP
as it is released into the blood
BNP concentrations correlate with
NYHA classification

Maisel A., Clinical Laboratory News (2001) 27, No. 3

Prognostic value of BNP in Acute
Coronary Syndromes

BNP range: 137.9 - 1456.6 pg/mL

BNP range: 81.3 - 137.8 pg/mL

BNP range: 43.7 - 82.1 pg/mL

BNP range: 5.0 - 43.6 pg/mL

Kaplan-Meier analysis showing the cumulative incidence of

death at 10 months according to the Quartile of BNP at enrollment
Patients in the 4th quartile had an 8 fold increase in mortality
DeLemos et al., New Engl J Med (2001) 345:1014-21
Pre-operative assessment for CABG

• Important aspect of the preoperative

evaluation of a cardiac surgical patient
involves estimating the extent of
underlying ventricular dysfunction.
• This can involve echocardiography,
MRI/PET imaging and/or natriuretic
peptides
BNP during CABG
• Avidan et al
• Aim: To investigate the release pattern of BNP
following cardioplegic arrest and the relationship
to troponin
• N=29. BNP measured before incision, before X-
clamp removal, 3 & 10 min after removal, 5 min
and 2 h post CPB termination
• In 3 cases samples were taken from the
coronary sinus
Results (1)
• Fall in BNP when X-clamp applied and
heart is isolated from circulation
• Slight but significant rise 3 min post clamp
removal
• Further increase following termination of
CPB
• No correlation between change in BNP
and X-clamp time
Results (2)
• BNP identical in arterial and venous
cannula
• BNP rapidly released and cleared from
circulation
• No spike in BNP following reperfusion of
the heart
• Lack of correlation between BNP and
troponin
BNP as predictive marker
• Attaran et al
• Aim: To determine if BNP could predict
outcome in cardiac surgery patients
• N=141. BNP measured pre-operatively
together with EuroSCORE and Parsonnet
score
• Clinical endpoints: atrial fibrillation,
inotrope use, renal impairment, early
deaths and hospital stay
Results
Variable BNP (ng/L) P-value

Urgent/elective 323/99 0.0017

Valve/CABG 273/125 0.0018

Inotrope use/no support 452/120 0.0015

Post-operative AF/no AF 237/145 0.109

Early death 1018/132 0.019

Conclusions
• Pre-operative BNP predicted requirement
for inotrope use, longer hospital stay and
early death
• Some pre-operative comorbidities
correlated with BNP including renal
impairment, PVD and low LVEF
• EuroSCORE and Parsonnet scores
correlated with BNP (p<0.001)
Remote ischaemic preconditioning

• Remote intermittent ischaemia (RI) has been shown

by some groups to have a protective action and
reduce troponin AUC following cardiac surgery
• RI is carried out using three 5-min cycles of upper
arm ischaemia by inflating a blood pressure cuff to
200 mmHg
• In between each cycle 5 min of deflation were
allowed for reperfusion
• The placebo group had a deflated cuff placed on the
upper arm for 30 min
Preconditioning study
Analyses
• cTnI and CK-MB measured pre-
operatively and 6,12,24 and 48h post
• BNP measured pre-operatively and 24 and
48h post
• Inflammatory markers (IL-2, IL-4, IL-6, IL-
8, IL-10, IL-1α, IL-1β, INF-γ, TNF-α and
MCP-1) were assayed by chip array
(Randox) pre-operatively, after each
ischaemia cycle and 24 and 48h post
Anaesthetic preconditioing
Results
• Although BNP, cTnI and CKMB all
increased post-CABG there was no
significant difference between RI and
placebo groups (p=0.9)
• There were the expected increases in IL-6
and IL-8 post-operatively
• There were no differences in the various
cytokines and chemokines between RI
and placebo groups
Conclusions
• RI does not provide myocardial protection
under a strict anaesthetic regime
• RI was not associated with changes in
cytokines or growth factors
TAVI
• Trans-arterial (femoral) or trans-apical
valve insertion
• Useful in patients for whom there is a
significant risk associated with open valve
surgery and cardiopulmonary bypass
Sapien TAVI valve
TAVI and AKI
• Dworakowski et al
• AKI is common after conventional cardiac
valve surgery
• The occurrence of AKI after TAVI is
unknown
• Biochemical markers of AKI, oxidative
stress and inflammation were studied
AKI and TAVI study
• 23 consecutive transfemoral (TF) and 22
transapical (TA) patients were included
• hsCRP, TNF-α and its receptors (TNF-
αR1 and R2), IL-6, myeloperoxidase
(MPO), oxidised LDL (oxLDL) and markers
for AKI, neutrophil gelatinase-associated
lipocalin (NGAL) and cysteine C, were
collected before TAVI, 24h and 48 h post-
procedure.
AKI definitions

• Stage 1 increase of creatinine >26.5 umol/l

or increase 1.5-2-fold from baseline
• Stage 2 creatinine increase >2-3-fold from
baseline
• Stage 3 creatine increase >3-fold from
baseline)
Incidence of AKI after TAVI
NGAL after TAVI
NGAL and TAVI
hsCRP after TAVI
TNFalphaR1 after TAVI
Myeloperoxidase after TAVI
Oxidised LDL
CKMB and cTnI
Haemodynamics
Conclusions
• In the first 6 hours after successful
transfemoral TAVI there is transient
systolic and diastolic dysfunction
• Rises in cardiac maarkers indicate some
myocyte damage occurs
• The haemodynamic changes are
accompanied by rises in ST2 and
aldosterone but not nt-ProBNP
Conclusions
• TAVI results in a significant activation of
inflammation and oxidative stress, which
correlates with AKI.
• The inflammatory response and the incidents of
AKI are significantly higher after TA TAVI
• Additional surgical trauma could explain higher
inflammatory response after TA TAVI
• NGAL is potentially useful marker of AKI after
TAVI
 Thank you Bernie
For teaching me all those years ago
For believing in me when at times I didn’t
For encouraging me to move onwards when
it was time to do so
Thank you
Have a happy retirement