Transcript Postgraduate Research Presentation

Showkat Hamid
Mentor: Dr. Mrinalini Meesala MD, FACC.
University at Buffalo; State University of New York;
Sisters Hospital IMTP
June 12th 2013
Disclosures:
 None
Topic:
 Evaluation of electrogenic properties of
myocardium in patients with HFpEF
with Tp-e/QT ratio as marker of
ventricular repolarization.
Introduction:
 Nearly one-half of patients presenting with heart failure
have preserved left ventricular ejection fraction 1.
 Patients with low ejection fraction are known to be
susceptible to arrhythmias and device therapy (ICD/CRT)
is a basic tenet to decrease sudden death 2.
Ref:
1.
Yancy CW, Lopatin M, Stevenson LW, et al. Clinical presentation, management,and in-hospital outcomes of
patients admitted with acute decompensated heart failure with preserved systolic function: a report from
ADHERE) Database. J Am Coll Cardiol 2006; 47:76–84.
2.
Smith GL, Masoudi FA, Vaccarino V, et al. Outcomes in heart failure patients with preserved ejection fraction:
mortality, readmission, and functional decline. J Am Coll Cardiol 2003; 41:1510–1518.
 Mortality of patients with HFpEF is not markedly
different from patients with decreased ejection
fraction.
Ref:
1.
Yancy CW, Lopatin M, Stevenson LW, et al. Clinical presentation, management,and in-hospital
outcomes of patients admitted with acute decompensated heart failure with preserved systolic
function: a report from ADHERE) Database. J Am Coll Cardiol 2006; 47:76–84.
Background:
 T-wave: a manifestation of ventricular repolarazation.
 Tp-e interval corresponds to the dispersion of ventricular
repolarization.
 Amplification of dispersion of ventricular repolarization is a substrate
for ventricular arrhythmias
Ref:
Antzelevitch C. T peak-Tend interval as an index of transmural dispersion of repolarization. Eur
J Clin Invest 2001;31:555.
 Antzelevitch C. The role of spatial dispersion of repolarization in inherited and acquired sudden
cardiac death syndromes. Am J Physiol Heart Circ Physiol 2007.
 Antzelevitch C. Heterogeneity and cardiac arrhythmias: an overview. Heart Rhythm 2007;4:964.

Cellular basis of T wave and Tp-e Interval:
Ventricular
myocardium is
comprised of 3
distinct myocardial
cell types—
•Epicardial,
•Endocardial, and
•Masonic
Midmyocardial
Moe cells - M cells.
Ref:
Antzelevitch C, Sicouri S, Litovsky SH, et al. Heterogeneity within the ventricular wall:
electrophysiology and pharmacology of epicardial, endocardial and M cells. Circ Res 1991;69:1427.
M-cells
 Histologically similar; Electrophysiologically different.
 Located in sub-endocardial layer
 Longest action potential (APD) than epicardial or
endocardial cell at lower rate or in response to action
potential prolonging agents.
Ref:
 Antzelevitch C, Sicouri S, Litovsky SH, et al. Heterogeneity within the ventricular wall:
electrophysiology and pharmacology of epicardial, endocardial and M cells. Circ Res
1991;69:1427
 Heterogeneity persists but is less pronounced in
intact ventricular wall due to well coupled adjacent
myocytes.
Ref:
 Antzelevitch C, Sicouri S, Litovsky SH, et al. Heterogeneity within the ventricular wall:
electrophysiology and pharmacology of epicardial, endocardial and M cells. Circ Res
1991;69:1427
Ref :
Circulation 1998;98:1928, PACE 2006;29:1130, and Heart Rhythm 2008;5:585.
 QT interval is specific to species, so-called normal QT
interval for that species.
 QT interval and Tp-e interval increase linearly with
increase in body weight.
Ref:
 Guo D, Zhou J, Zhao X, et al. Calcium channel recovery kinetics versusventricular repolarization:
preserved membrane-stabilizing mechanism across species. Heart Rhythm 2008;5:271
Adapted from Heart Rhythm 2008;5:271.
Adapted from Heart Rhythm 2008;5:271.
 Tp-e/QT ratio is an index of ventricular repolarization
that remains constant within a very narrow range of
value despite dynamic physiological changes in HR
and also evolutionary changes across species.
Ref:
 Guo D, Zhou J, Zhao X, et al. Calcium channel recovery kinetics versusventricular repolarization:
preserved membrane-stabilizing mechanism across species. Heart Rhythm 2008;5:271
 Tp-e interval serves as an index of total dispersion of
repolarization (transmural, apicobasal, or global)in
vivo.
 Changes in this parameter from the baseline value may
forecast the risk of arrhythmia.
Ref :
 Prasad Gupta,Gan-Xin Yan, MD, PhDa, Tp-e/QT ratio as an index of arrhythmogenesis Journal
of Electrocardiology 41 (2008) 567–574
Rationale of the study:
 Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are
prolonged in patients with moderate and severe
obstructive sleep apnea.
 Tp-e interval and Tp-e/QT ratio is increased in patiests
with ankylosing spondylitis
Ref :
 Kilicaslan F, Cebeci BS. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in
patients with moderate and severe OSA patients. (PACE 2012; 35:966–972)
 Acar G, Bozoglan O. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing
spondylitis. Mod Rheumatol. 2013 Apr 12. [Epub ahead of print]
 Left ventricular hypertrophy amplifies the QT, and
Tp-e intervals and the Tp-e/QT ratio of left chest ECG
 Tp-e/QT ratio may serve as a prognostic predictor of
adverse outcomes after successful pPCI treatment in
STEMI patients.
Ref :
 Zhao Z, Yuan Z, Ji Y, Wu Y, Qi Y. Left ventricular hypertrophy amplifies the QT, and Tp-e
intervals and the Tp-e/ QT ratio of left chest ECG J Biomed Res. 2010 Jan;24(1):69-72. doi:
10.1016/S1674-8301(10)60011-5.
Big Question
What happens to Tp-e/QT
ratio in HFpEF
???
Research Hypothesis:
“In patients with HFpEF cellular and metabolic
changes in myocytes are associated with changes
in electrogenic properties of the ventricular
myocardium reflected as prolongation of Tp-e/QT
intervals suggesting increased risk of ventricular
arrhythmias ”.
Research Design and Methods:
 Retrospective Study
Patient Population
Randomization and Blinding: None
Cases:
Patients admitted to Catholic Health System
from January 2009 onwards with a diagnosis of
HFpEF
Exclusion Criteria:
•Primary/secondary
diagnosis of A.Fib.
•IVCD.
•Anti-arrhythmic
drugs
•Intracardiac device.
•Poor quality echo
images .
•Recent CABG/or
structural heart
disease.
•Acute MI
•Severe MR
•Severe COPD
•Flat T waves or T
wave obscured by U
wave
Inclusion Criteria:
•Discharge
diagnositic code for
HFpEF
•EF ≥50%
•Clinical and
Biochemical
evidence of HFpEF
within 1 year .
Controls:
Patients who had echo done for different
reasons and found to have normal systolic
and diastolic functon, and have none of
the following(exclusion criterias):
•Primary/secondary diagnosis of A.Fib.
•IVCD.
•Anti-arrhythmic drugs
•Intracardiac device.
•Poor quality echo images .
•Recent CABG/or structural heart disease.
•Acute MI
•Severe MR
•Severe COPD
•Flat T waves or T wave obscured by U
wave
Total
(967)
Included
(139)
Excluded
(828)
Controls
(49)
Grade I
(25)
E/A<0.8
DT >200ms
Av. E/e’≤8
Patients
(90)
Grade II
(42)
Grade III
(7)
E/A 0.8-<1.5
DT 160-200ms
Av. E/e’ 9-12
E/A>2
DT <160ms
Av. E/e’>13
Unclassified
(999 group)
(16)
Methodology:
Naugeh SF, Appleton CP, Evangelista A. Recommendations for the evaluation of left ventricular diastolic
function by echocardiography. J. Am Soc Echocardiogr. 2009 Feb;22(2):107-33. doi: 10.1016/j.echo.2008.11.023
Methodology cont:
 EKGs were analyzed for T wave morphology.
 T peak and T end interval (Tp-e) were measured by
(Standard Tangential Method) identifying two points
on isoelectric line:
1) Perpendicular to the isoelectric line from crest of T
wave
2) The point at which the tangent to the down curve of T
wave intersects the isoelectric line.
Results:
Tp-e/QT
Conclusion:
 There is no significant prolongation of Tp-e/QT to
demonstrate increased risk of ventricular
arrhythmias hence sudden death in patients with
HFpEF in this study.
 A decreasing trend in Tp-e/QT ratio with increasing
grade of diastolic dysfunction was observed which
did not achieve statistical significant due to small
cohort of subjects.
Strengths Of the Study:
 Echo and EKG parameters collected in different times
to avoid observer bias.
 Internal as well as external comparison were
attempted
 Patients with EF>/= 50% strictly were taken for study.
 Patients with clinical syndrome of HF along with
biochemical evidence of HF taken.
Limitations of Study:
 Retrospective Study
 Small population size
 Extrapolation of results of Wedge Electro-gram to
chest ECGs.
 Tp-e/QT ratio is a relatively new parameter and not
much is known about its significance in HFpEF.
Questions?
Acknowledgements:
 Dr. K.J.Qazi , MD (Program Director)
 Dr. Mrinalini Meesala, MD (Research Mentor)
 Dr. Micheal Banas, MD (Advisor)
 Dr. Salim Memon, MBBS
 Dr. Sachitanand MD (Chair IRB)
 Ms Danielle Casucci (IRB)
 Staff of Echo Lab Sisters Hospital
Thank you !