Transcript Myocardial Ischemia Induced by Rapid Atrial Pacing Causes Troponin T Release Detectable by a Highly Sensitive Assay: Insights from a Coronary Sinus Sampling.

Myocardial Ischemia Induced by Rapid Atrial Pacing
Causes Troponin T Release Detectable by a Highly
Sensitive Assay: Insights from a Coronary Sinus
Sampling Study
Aslan T. Turer, MD, MHS,FACCa, Tayo A. Addo, MD,FACCa, Justin L. Martin, MD,FACC c,
Marc S. Sabatine, MD, MPH,FACCd , Gregory D. Lewis, MD, e Robert E. Gerszten, MD, e
Ellen C. Keeley, MD, MSf Joaquin E. Cigarroa, MD,FACCg, Richard A. Lange, MD,FACCh,
L. David Hillis, MD,FACCh, James A. de Lemos, MD,FACCa,b
a Department of Medicine, Division of Cardiology, and b the Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical
Center, Dallas, TX;
c Consultants in Cardiology, Forth Worth, TX;
d Department of Medicine, Division of Cardiovascular Medicine and the TIMI Study Group, Brigham and Women's Hospital and e Massachusetts General Hospital,
Harvard Medical School, Boston, MA;
f Department of Internal Medicine, Division of Cardiology, University of Virginia, Charlottesville, VA;
g Department of Internal Medicine, Division of Cardiology, Oregon Health and Science University, Portland, OR
h Department of Medicine, University of Texas Health Science Center, San Antonio, TX.
Background
• Cardiac troponins are the preferred biomakers
to detect myocardial infarction
• Recently, more sensitive troponin assays (hscTnT) have shown favorable test
characteristics compared to traditional assays
• It is unclear whether very low levels of
troponin detectable by these next generation
assays may reflect myocardial ischemia,
without myonecrosis
Study Questions
• Can low levels of troponin be detected
following periods of ischemia (or increased
cardiac work) without frank infarction?
• Will dynamic changes in troponin levels
detectable by highly sensitive assay be able to
distinguish ischemic from non-ischemic hearts
following pacing stress?
Methods
• 19 patients with stable angina referred for
coronary angiography were enrolled
• Patients were excluded for
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Valvular disease
Atrial fibrillation
Previous CABG
History of heart failure
Acute coronary syndrome
LBBB
Methods
• b-blockers and nitrates were held for ≥ 24hrs before
catheterization
• A 6Fr arterial cannula was placed in the brachial or femoral
artery
• A 7Fr Zucker catheter was placed into the coronary sinus
(CS)
• A baseline set of peripheral and CS blood samples were
obtained
• The atrium was paced at 20 beats/min above resting heart
rate and increased by 20 beats/min every 3 minutes
• Pacing continued until a goal HR=160 beats/min or angina developed
• Coronary angiography was performed after pacing procotol
was completed. No PCI was performed.
Methods
Study schema: Paired samples of peripheral and coronary sinus
blood were obtained at baseline, peak pacing and regular
intervals after cessation of pacing.
Methods
• Patients were classified into groups based on the
presence or absence of myocardial ischemia at
peak pacing.
• Ischemia groupings were determined by (1) the
presence or absence of CAD and (2) lactate
elution during pacing
(1) no significant CAD and no net lactate elution after pacing
[(CAD-/lactate-), n=5],
(2) significant CAD but no net lactate elution after pacing
[(CAD+/lactate-), n=7] and
(3) significant CAD with pacing-induced lactate release
[(CAD+/lactate+), n=7].
Methods
• Concentrations of troponin T were determined
using both a conventional fourth-generation
assay and a precommercial highly sensitive assay
• The lower limit of detection of the traditional
assay is 0.01 ng/mL, whereas that of the hs-cTnT
assay is 0.003 ng/mL (3pg/mL).
• Based on the manufacturer’s data from >1300 normal
subjects, the 99th percentile for the upper limit of normal
was reported to be 14 pg/mL for the hs-cTnT assay.
Results
Ischemic subgroup
Clinical characteristic
Age (years)
Gender (no., % female)
Race/ethnicity
White
Black
Hispanic
Hypertension (%)
Hyperlipidemia (%)
Diabetes mellitus (%)
Tobacco use (%)
Canadian Cardiovascular Society
Angina Score
I
II
III
LVEF [%, median (25th,75th)]
Creatinine [mg/dl, median
(25th,75th)]
Chronic medications
ACE-inhibitor/ARB
b-blocker*
Statin
Entire cohort
(n=19)
52±6
7 (37)
49±2
4 (80)
CAD+/
Lactate
elution(n=7)
52±8
0 (0)
6 (32)
8 (42)
5 (26)
14 (74)
13 (68)
8 (42)
11 (58)
2 (40)
3 (60)
0 (0)
5 (100)
2 (40)
0 (0)
3 (60)
3 (43)
2 (29)
2 (29)
5 (71)
6 (86)
4 (57)
4 (57)
1 (14)
3 (43)
3 (43)
4 (57)
5 (71)
4 (57)
4 (57)
2 (11)
9 (47)
8 (42)
53 (42,59)
1.0 (0.8,1.3)
1 (20)
1 (20)
3 (60)
55 (45,55)
0.9 (0.8,1.2)
0 (0)
6 (86)
1 (14)
50 (45,63)
0.9 (0.8,1.1)
1 (14)
2 (29)
4 (57)
51 (38,63)
1.3 (0.8,1.8)
12 (63)
16 (84)
11 (58)
2 (40)
4 (80)
1 (20)
4 (57)
6 (86)
5 (71)
6 (86)
6 (86)
5 (71)
CAD- /
Lactate
elution- (n=5)
CAD+/
Lactate
elution+
(n=7)
54±6
3 (43)
Baseline demographic and clinical characteristics of the study population.
Results
Ischemic subgroup
Clinical characteristic
Angiography
No. diseased vessels
0
1
2
3
Diseased vessel
LAD
LCx
RCA
Pacing-response
Peak heart rate (bpm)
Rate•pressure product
(bpm•mmHg)
Chest pain
ST-segment depression
Entire cohort
(n=19)
CAD- /
Lactate
elution- (n=5)
CAD+/
Lactate
elution(n=7)
CAD+/
Lactate
elution+ (n=7)
5 (26)
10(53)
3 (16)
1 (5)
5 (100)
NA
NA
NA
NA
4 (57)
3 (43)
0
NA
6 (86)
0
1 (14)
8 (57)
5 (36)
6 (43)
NA
NA
NA
2 (29)
4 (57)
4 (57)
6 (86)
1 (14)
2 (29)
146±16
21458±4216
150±18
22566±3028
144±11
20810±4662
145±22
21313±4892
13 (68)
9 (47)
2 (40)
3 (60)
5 (71)
2 (29)
6 (86)
4 (57)
Angiographic and pacing-stress characteristics of the study population.
Results
Results
Results
Conclusions