Is Left Ventricular Diastolic Dysfunction a clinical predictor of Syncope?

Is Left Ventricular Diastolic Dysfunction a clinical predictor of Syncope? Abdul Jawwad Samdani, MBBS Mentor: Mrinalini Meesala, MD Yuji Saito, MD

What is Syncope? Why it is important? Common clinical problem Introduction 1 3.5 % of all emergency room visits 1 6 % of hospital admissions annually in the US Incidence increasing with age Maybe disabling Trivial to Life threatening causes. Challenging differential diagnoses Extensive testing with enormous financial burden.

Introduction Causes Of Syncope Reflex/ Neurally- Mediated Orthostatic Cardiac Arrhythmia Structural Cardio- Pulmonary 1 Vasovagal Syncope Carotid sinus syndrome Situational Cough Post- Micturition 2 Drug-Induced Dehydration/ Hypovolemia ANS Failure Primary Secondary 3 Brady SN Dysfunction AV Block Tachy VT SVT Long QT Syndrome 4 Acute MI AS or MS HCM PulmHTN/ PE Aortic Dissection Cardiac tumor/ thrombus Unexplained Causes = Approximately 1/3 DG Benditt, MD. U of M Cardiac Arrhythmia Center

Introduction What is the utility of echocardiogram in evaluation of syncope? An echocardiogram has been described as an important tool with variable utility in the workup of syncope. Traditionally mainly used for identifying and quantifying an underlying structural heart disease (LVOT obstruction, valvular heart disease and cardiomyopathy).

Introduction Echocardiography can provide additional information for diagnostic and risk stratification purposes. Certain recent studies suggest that a small left atrial volume and lower mitral A velocity (a measure of atrial kick in LV filling) can predict positive Head up Tilt Test seen in neurocardiogenic syncope. Other studies suggest that LVDD may have a PARTIAL role in pathogenesis of syncope in patients with HOCM and Severe AS

Introduction No direct studies to date to evaluate possible role of LVDD in pathophysiology of syncope There is an overlap in risk factor associated with syncope and LVDD (Age, obesity, HTN, DM) Pathophysiologically, we know that LVDD results in a smaller stroke volume and hence a lower cardiac output that may facilitate causation of syncope.

Objectives To elucidate If Left Ventricular Diastolic Dysfunction (LVDD) is a clinical predictor of Syncope If Echocardiography plays a role in risk stratifying patients presenting with syncope in the absence of underlying structural heart disease.

METHODOLOGY

Methodology Retrospective Chart Review Single center: SOCH Duration: January 2011 to Dec 2012 Adult patients 18 years 2 groups; Syncope and Comparison group (Control) IRB Approval obtained No conflicts of interest or financial disclosures

Methodology: Sample Selection Echocardiography database searched by Syncope Echocardiography database searched by Routine Pre op and Evaluate Cardiac/ LV function N = 421 N = 463 Exclusion Diagnoses of Seizure, TIA, Fall, Presyncope Exclusion EF < 50% Severe Aortic (AS) and Mitral Valve disease HOCM AFib/ Flutter Acute coronary syndrome CHF exacerbation Limited Echo Exclusion Diagnosis of Syncope. Incomplete data Syncope Cases: N = 197 Control Group: N = 170

Methodology: Data Collection Performa Demographics Co morbids and medications 2 D Echocardiographic parameters Cause of syncope per discharge summary

Methodology: Data Collection Echocardiographic measurements and grading of LVDD per American Society of Echocardiography guidelines.

Methodology Statistical Analysis: SPSS version 20 Chi square 2 sample independent t test One way ANOVA p value of <0.05 considered significant

RESULTS

Results Demographics 70 60 50 40 30 20 66.5 65.5 p = 0.021 27.8 29.7 35.5 37.1 64.5 62.9 56.3 57.1 36.5 37.1 10 0 Cases Controls

Results Co morbids 5.1 4.1 4.6 6.5 19.3 17.6 18.8 22.9 26.4 32.9 46.2 49.4 75.1 75.3 12.7 12.9 21.3 22.9 80 70 60 50 40 30 20 10 0 Cases Controls Percentages

Results Medications Drugs Syncope (n=197) Control (n=170) p value Beta Blockers % 27.9 28.2 0.946 CCBs % 27.4 32.4 0.302 Diuretics % 29.9 29.4 0.911 ACEI/ARB % 38.6 38.8 0.962 Nitrates % 5.1 4.7 0.870 Hydralazine % 3.6 3.5 0.990 Clonidine % 5.6 5.3 0.903

Results LVDD Frequency Percentages 80 70 60 50 40 30 20 10 0 p< 0.001** p= 0.004** 73.6 58.9 57.1 45.9 13.7 10.6 1 0.6 LVDD Grade 1 Grade 2 Grade 3 Cases Controls **P-value adjusted for Age, BMI, Gender, Race, HTN and DM

Results Other Cardiac Parameters 8 7 6.8 6.6 6 5 Means 4 3 Syncope Control 2 p= 0.03 1 0.77 0.82 0.84 0.83 1 1.1 p = 0.003 0 0.12 0.13 E Velocity (m/s) A Velocity (m/s) E/A E' Velocity (m/s) E/E'

Results Other Cardiac Parameters Cardiac Parameters Syncope (n=197) Control (n=170) p value HR (Mean ± SD) 70.9 ± 14 71.9 ± 14 0.484 LVEF (Mean ± SD) 62.8 ± 7 61.5 ± 6 0.061 LVIDd (Mean ±SD) 4.5 ±0.7 4.5 ± 0.6 0.454 LVM index (Mean ± SD) 87.8 ± 27 90.9 ± 27 0.214 LVH % 33.5 40.0 0.197 LA size (Mean ±SD) 3.5 ±0.6 3.7 ±0.7 0.005** LA volume index (Mean ± SD) 24.3 ± 8 25.4 ± 9 0.228 E Velocity (Mean ± SD) 0.77 ± 0.2 0.82 ±0.2 0.030** A (Mean ± SD) 0.84 ± 0.3 0.83 ± 0.2 0.496 E/A (Mean ± SD) 1.0 ± 0.4 1.1± 0.4 0.115 DT (Mean ± SD) 245.5 ± 68 232.0 ± 65 0.054 IVRT (Mean ± SD) 88.7 ± 21 86.6 ± 22 0.349 E Velocity (Mean ± SD) 0.12 ± 0.04 0.13 ±0.04 0.003** E/E (Mean ±SD) 6.8 ±2.5 6.6 ± 2.4 0.279 LA pressure (Mean ± SD) 10.3 ± 3 10.0 ± 3 0.358

Results Sub group Analysis Orthostatic 17% Causes of Syncope Cardiac 14% Undiagnosed 46% Reflex/Neural 23%

Subgroup Analysis LVDD Frequency Percentage 100 90 80 70 60 50 40 30 20 10 0 p= 0.021 p= 0.001 LVDD Grade 1 Grade 2 Grade 3 Reflex/ Neural Cardiac Orthostatic

Comparison between Causes of Syncope 100 90 80 70 60 50 40 30 20 10 0 p< 0.003 p< 0.001 p= 0.006 p= 0.034 p < 0.001 Age (mean) HTN (%) DM (%) CAD (%) CHF (%) Reflex/ Neural Cardiac Orthostatic

Comparison between Causes of Syncope 120 100 p= 0.005 p= 0.019 80 60 p = 0.006 40 p< 0.001 20 p= 0.031 0 LVM index (gm/kg2) LVH (%) LA volume index cm3/ kg2 A (cm/s) E/E' Reflex/ Neural Cardiac Orthostatic

Results Comparison between Causes Variables of Interest Reflex Cardiac Orthostatic p value n=45 n=27 n=34 Age (Mean) 58 76 69 <0.001 BMI (Mean) 28 27 27 0.453 HTN % 53 93 68 <0.003 DM % 9 33 24 0.034 CAD % 9 41 21 0.006 CHF % 0 22 3 <0.001 LVEF (Mean) 63 60 63 0.159 LVIDd (Mean) 4.5 4.5 4.4 0.860 LVM index (Mean) 81 102 85 0.005 LVH % 22 56 24 0.006 LA size (Mean) 3.2 3.9 3.5 <0.001 LA volume index (Mean) 20.3 29.4 22.5 <0.001 E Velocity (Mean) 0.74 0.84 0.73 0.062 A Velocity (Mean) 0.8 0.9 0.8 0.019 E/A (Mean) 1.1 0.9 1.0 0.148 DT (Mean) 253 256 231 0.237 IVRT (Mean) 84 96 86 0.047 E Velocity (Mean) 0.13 0.11 0.12 0.201 LA pressure (Mean) 9.5 11.4 10.0 0.031 RVSP (Mean) 32 40 32 0.004 LVDD % 56 93 73 0.021 Normal % 44 7 27 Grade 1 % 51 56 65 Grade 2 % 4 33 9 0.001 Grade 3 % 0 4 0

Conclusion Our results show that LVDD is more common in patients with syncope than the control group reaching statistical significance Hence LVDD is likely a predictor of syncope. Also, presence of LVH, larger LAV index, higher mitral A velocity, larger E/E and presence of LVDD are significant predictors of cardiac syncope in the absence of structural heart disease

Implications/ Future Considerations Hypothesis generation for future studies to explore the link between LVDD and Syncope Echocardiography may have additional role in the evaluation of syncope. Parameters like LVH, LAVI, A velocity and LVDD can likely be incorporated in the risk stratification tools/ score systems in evaluation of syncope and can be further studied.

Limitations Retrospective design Causal association can not be definitely established Hospital based data lacking generalizability

References 1. Manganelli F, Betocchi S, Ciampi Q, Storto G, Losi MA, Violante A, et al. Comparison of hemodynamic adaptation to orthostatic stress in patients with hypertrophic cardiomyopathy with or without syncope and in vasovagal syncope. Am J Cardiol 2002;89(12):1405 10. 2. Folino AF, Russo G, Buja G, Iliceto S. Contribution of decreased atrial function in the pathogenesis of neurally mediated syncope. Am J Cardiol 2006;97(7):1017 24. 3. Sarasin FP, Junod AF, Carballo D, Slama S, Unger PF, Louis Simonet M. Role of echocardiography in the evaluation of syncope: a prospective study. Heart 2002;88(4):363 7. 4. Moon J, Shim J, Park JH, Hwang HJ, Joung B, Ha JW, et al. Small left atrial volume is an independent predictor for fainting during head up tilt test: the impact of intracardiac volume reserve in vasovagal syncope. Int J Cardiol 2013;166(1):44 9. 5. Park SJ, Enriquez Sarano M, Chang SA, Choi JO, Lee SC, Park SW, et al. Hemodynamic patterns for symptomatic presentations of severe aortic stenosis. JACC Cardiovasc Imaging 2013;6(2):137 46. 6. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, 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. 7. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005 Dec;18(12):1440 63. 8. Puppala VK, Dickinson O, Benditt DG. Syncope: classification and risk stratification. J Cardiol. 2014 Mar;63(3):171 7. doi: 10.1016/j.jjcc.2013.03.019. Epub 2014 Jan 7. 9. Puppala VK, Dickinson O, Benditt DG. Syncope: classification and risk stratification. J Cardiol. 2014 Mar;63(3):171 7. doi: 10.1016/j.jjcc.2013.03.019. Epub 2014 Jan 7. 10. Thiruganasambandamoorthy V, Stiell IG, Sivilotti ML, Murray H, Rowe BH, Lang E, McRae A, Sheldon R, Wells GA. Risk stratification of adult emergency department syncope patients to predict short term serious outcomes after discharge (RiSEDS) study. BMC Emerg Med. 2014 Mar 14;14:8. doi: 10.1186/1471 227X 14 8.

Thank you Questions?

Supplementary Slides

Results Demographics Syncope (n=197) Control (n=170) p value Age (Mean ±SD) 66.5 ± 17.9 65.5 ± 15.7 0.541 Gender Male % 35.5 37.1 Female % 64.5 62.9 0.762 Race Caucasians % 56.3 57.1 African Americans % 36.5 37.1 Other % 7.1 5.9 0.894 BMI (Mean ±SD) 27.8 ± 7.3 29.7 ±8.3 0.021**

Results Comorbids Syncope (n=197) Control (n=170) p value HTN % 75.1 75.3 0.970 DM % 26.4 32.9 0.170 CAD % 19.3 17.6 0.686 CHF % 5.1 4.1 0.663 CVA % 4.6 6.5 0.423 Paroxysmal Afib % 3.6 3.5 0.990 COPD/ Asthma % 18.8 22.9 0.327 DL % 46.2 49.4 0.538 Active Tobacco % 21.3 22.9 0.709 CKD % 12.7 12.9 0.943 Previous Syncope % 10.2 0

RESULTS SUBGROUP ANALYSIS CAUSE of SYNCOPE Unknown n (%) 91 (46.2) Reflex/ Neural n (%) 45 (22.8) Cardiac n (%) 27 (13.7) Orhtstatic n (%) 34 (17.3)

RESULTS LVDD Frequency Syncope (n=197) Control (n=170) p value LVDD % 73.6 57.1 0.001** Adjusted*** <0.001** Grade 1 % 58.9 45.9 Grade 2 % 13.7 10.6 0.011** Grade 3 % 1.0 0.6 Adjusted*** 0.004** *** Adjusted for Age, Gender, Race, HTN, DM and BMI

Results Comparison between Causes Unknown Reflex Cardiac Orthostatic p value Age (Mean) 67 58 76 69 <0.001** HTN % 84 53 93 69 <0.001** DM % 34 9 33 24 0.014** CAD % 17 9 41 24 0.008** CHF % 3 0 22 3 <0.001** LVEF (Mean) 64 63 60 63 0.138 LVIDd (Mean) 4.5 4.4 4.5 4.4 0.887 LVM index (Mean) 88 81 102 85 0.009** LVH % 36 22 56 24 0.016** LA size (Mean) 3.6 3.3 3.9 3.5 <0.001** LA volume index (Mean) 25.4 20.3 29.4 22.5 <0.001** E Velocity (Mean) 0.79 0.74 0.84 0.73 0.098 A (Mean) 0.87 0.75 0.93 0.83 0.029** E/A (Mean) 1.0 1.1 0.9 1.0 0.399 DT (Mean) 244 253 256 231 0.437 IVRT (Mean) 90 84 96 86 0.091 E Velocity (Mean) 0.12 0.13 0.11 0.12 0.291 E/E (Mean) 6.9 6.2 7.7 6.6 0.064 LA pressure (Mean) 10.5 9.5 11.5 10.0 0.064 LVDD % 77 56 92 74 0.004** Grade 1 % 62 51 56 65 Grade 2 % 14 4 33 9 0.004** Grade 3 % 1 0 4 0

Methodology: Sample Selection Echocardiography database searched by Syncope N = 421 Echocardiography database searched by Routine Pre op and Evaluate Cardiac/ LV function N = 463 Exclusion Diagnoses of Seizure, TIA, Fall, Presyncope Exclusion EF < 50% Severe Aortic (AS) and Mitral Valve disease HOCM AFib/ Flutter Acute coronary syndrome CHF exacerbation Limited Echo Incomplete data Exclusion EF < 50% Severe Aortic (AS) and Mitral Valve disease HOCM AFib/ Flutter Acute coronary syndrome CHF exacerbation Limited Echo Incomplete data Exclusion Diagnosis of Syncope. Syncope Cases: N = 197 Control Group: N = 170