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Postgraduate Research Presentation

Postgraduate Research Presentation. Showkat Hamid Mentor: Dr. Mrinalini Meesala MD, FACC. University at Buffalo; State University of New York; Sisters Hospital IMTP June 12 th 2013. Disclosures:. None. Topic:.

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Postgraduate Research Presentation

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  1. 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

  2. Disclosures: • None

  3. Topic: • Evaluation of electrogenic properties of myocardium in patients with HFpEF with Tp-e/QT ratio as marker of ventricular repolarization.

  4. 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: • 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 CollCardiol 2006; 47:76–84. • Smith GL, Masoudi FA, Vaccarino V, et al. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J Am CollCardiol 2003; 41:1510–1518.

  5. Mortality of patients with HFpEF is not markedly different from patients with decreased ejection fraction. Ref: • 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 CollCardiol 2006; 47:76–84.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Ref : Circulation 1998;98:1928, PACE 2006;29:1130, and Heart Rhythm 2008;5:585.

  11. 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

  12. Adapted from Heart Rhythm 2008;5:271.

  13. Adapted from Heart Rhythm 2008;5:271.

  14. 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

  15. 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

  16. 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 ankylosingspondylitis 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 ankylosingspondylitis. Mod Rheumatol. 2013 Apr 12. [Epub ahead of print]

  17. 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.

  18. Big Question What happens to Tp-e/QT ratio in HFpEF ???

  19. 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 ”.

  20. Research Design and Methods: • Retrospective Study

  21. Patient Population Randomization and Blinding: None 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 • 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 .

  22. Total (967) Included (139) Excluded (828) Controls (49) Patients (90) Grade I (25) E/A<0.8 DT >200ms Av. E/e’≤8 Grade II (42) E/A 0.8-<1.5 DT 160-200ms Av. E/e’ 9-12 Grade III (7) E/A>2 DT <160ms Av. E/e’>13 Unclassified (999 group) (16)

  23. 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

  24. 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.

  25. Results:

  26. Tp-e/QT

  27. 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.

  28. 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.

  29. 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.

  30. Questions?

  31. 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

  32. Thank you !

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