Myocardial Ischemia Induced by Rapid Atrial Pacing Causes Troponin T Release Detectable by a Highly...

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, ORh 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 (hs-cTnT) 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 • Valvular disease• Atrial fibrillation• Previous CABG• History of heart failure• Acute coronary syndrome• LBBB

Methods• -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.

ResultsIschemic subgroup

Clinical characteristic

Entire cohort (n=19)

CAD- / Lactate

elution- (n=5)

CAD+/ Lactate elution- (n=7)

CAD+/ Lactate elution+

(n=7)Age (years) 52±6 49±2 52±8 54±6Gender (no., % female) 7 (37) 4 (80) 0 (0) 3 (43)Race/ethnicity

White 6 (32) 2 (40) 3 (43) 1 (14)Black 8 (42) 3 (60) 2 (29) 3 (43)Hispanic 5 (26) 0 (0) 2 (29) 3 (43)

Hypertension (%) 14 (74) 5 (100) 5 (71) 4 (57)Hyperlipidemia (%) 13 (68) 2 (40) 6 (86) 5 (71)Diabetes mellitus (%) 8 (42) 0 (0) 4 (57) 4 (57)Tobacco use (%) 11 (58) 3 (60) 4 (57) 4 (57)Canadian Cardiovascular Society Angina Score

I 2 (11) 1 (20) 0 (0) 1 (14)II 9 (47) 1 (20) 6 (86) 2 (29)III 8 (42) 3 (60) 1 (14) 4 (57)

LVEF [%, median (25th,75th)] 53 (42,59) 55 (45,55) 50 (45,63) 51 (38,63)Creatinine [mg/dl, median (25th,75th)] 1.0 (0.8,1.3) 0.9 (0.8,1.2) 0.9 (0.8,1.1) 1.3 (0.8,1.8)

Chronic medicationsACE-inhibitor/ARB 12 (63) 2 (40) 4 (57) 6 (86)-blocker* 16 (84) 4 (80) 6 (86) 6 (86)Statin 11 (58) 1 (20) 5 (71) 5 (71)

Baseline demographic and clinical characteristics of the study population.

ResultsIschemic subgroup

Clinical characteristic

Entire cohort (n=19)

CAD- / Lactate

elution- (n=5)

CAD+/ Lactate elution- (n=7)

CAD+/ Lactate elution+

(n=7)Angiography

No. diseased vessels 0 5 (26) 5 (100) NA NA1 10(53) NA 4 (57) 6 (86)2 3 (16) NA 3 (43) 03 1 (5) NA 0 1 (14)

Diseased vessel LAD 8 (57) NA 2 (29) 6 (86)LCx 5 (36) NA 4 (57) 1 (14)RCA 6 (43) NA 4 (57) 2 (29)

Pacing-responsePeak heart rate (bpm) 146±16 150±18 144±11 145±22Rate•pressure product (bpm•mmHg)

21458±4216 22566±3028 20810±4662 21313±4892

Chest pain 13 (68) 2 (40) 5 (71) 6 (86)ST-segment depression 9 (47) 3 (60) 2 (29) 4 (57)

Angiographic and pacing-stress characteristics of the study population.

Results

Results

Results

Conclusions