Showkat Hamid Mentor: Dr. Mrinalini Meesala MD, FACC. University at - - PowerPoint PPT 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

• utcomes 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-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

• f 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

• bstructive 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

Cases: Patients admitted to Catholic Health System from January 2009 onwards with a diagnosis of HFpEF 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

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>2 DT <160ms

• Av. E/e’>13

Grade II (42)

E/A 0.8-<1.5 DT 160-200ms

• Av. E/e’ 9-12

Grade I (25)

E/A<0.8 DT >200ms

• Av. 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

• n 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 !