Postgraduate Research Presentation

Showkat HamidMentor: 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.

Ventricular myocardium is comprised of 3 distinct myocardial cell types—

•Epicardial,

•Endocardial, and

•Masonic Midmyocardial Moe cells - M cells.

Cellular basis of T wave and Tp-e Interval:

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-cellsHistologically 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 QuestionWhat 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

Cases:Patients admitted to Catholic Health System from January 2009 onwards

with a diagnosis of HFpEFControls:

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

Inclusion Criteria:

• Discharge

diagnositic code for HFpEF

• EF ≥50% • Clinical and

Biochemical evidence of HFpEF within 1 year .

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

Randomization and Blinding: None

Total (967)

Excluded(828)

Unclassified (999 group)

(16)

Controls (49)

Patients(90)

Included(139)

Grade III(7)

E/A>2DT

<160msAv.

E/e’>13

Grade II(42)

E/A 0.8-<1.5DT 160-200msAv. E/e’ 9-12

Grade I(25)

E/A<0.8DT

>200msAv.

E/e’≤8

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

attemptedPatients 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, MBBSDr. Sachitanand MD (Chair IRB)Ms Danielle Casucci (IRB)Staff of Echo Lab Sisters Hospital

Thank you !