2. Evaluation of Patient with Shortness of Breath and Normal Ejection Fraction & How to Diagnose Diastolic Heart Failure Subodh K. Agrawal, MD,FACC

3. 56 year old Caucasian female who has history of hypertension, DM tupe 2 with 3 days of increasing sob, chest tightness pnd which develop to dysnoea at rest, cough with pink frothy cough Exam: dysnoe at rest, heart rate 110/min. BP 180/100, cold clamy skin, rales on both lung upto scapula, Jvd is not visible, S3 gallop and 2 pluse pedal edema Ekg : ST, LVH, x-ray pulmonary edema Patient with Shortness breath in the emergency room

4. HCT 45% creatinine 1.4mg/dl, BNP 800ng/dl, troponin RX in ER Lasix 40mg iv resulted in 1200ml of urine out put with resolution of sob and admitted for further management. After admission we found No evidence copd, no infection Meds enalpril 10mg/day, asa 81mg /day metformin 1000mg twice a day This 3 rd admission in last 2 years, she had, she non compliant of medication previos cath with nl lv and normal coronar yyarteries Previous 3 echo has shown NL LVEF and lvh Patient with Shortness breath in the emergency room

5. The Art of Physical Examination The history and physical exam remain the backbone of medical evaluation and assessment "Observe, record, tabulate, communicate. Use your five senses….Learn to see, learn to hear, learn to feel, learn to smell, and know that by practice alone you can become expert." – Sir William Osler Sir William Osler at a patient's bedside. Reprinted with permission. Photograph reprinted with permission of The Alan Mason Chesney Medical Archives of The Johns Hopkins Medical Institutions.

6. Patient with Shortness breath in the cath lab Once again Normal coronary arteries Normal LVEF 65% LVEDP is 25mm/Hg We proceed to do right heart cath: co 3.8L/min, CI 2.0L/Min/M square, Pcwp25, pa 60/40 mean 50. RV 60/15/ RA 10

7. Under these circumstances, a relatively small increase in central blood volume or an increase in venous tone, arterial stiffness, or both can cause a substantial increase in LA and pulmonary venous pressures and may result in acute pulmonary edema. NEJM 2004;351:1097-1105

10. N Engl J Med 2006; 355; 251 Increased prevalence of heart failure with normal EF A. A large study of patients (n=4596) hospitalized with HF at a single institution over a 15 year period demonstrated that the percentage of patients who have a normal EF has increased over time B. This was the result of an increased number of admissions for HF with a normal EF; the number of admissions for HF with reduced EF remained stable

11. N Engl J Med 2006; 355; 251 Survival curves for patients with heart failure with normal EF has not improved. Whereas survival for patients with HF with reduced EF was shown to be improving over time in this study from Olmsted County (A), no such improvement was observed for patients with HF normal EF (B).

14. Framingham Criteria for Dx of Heart Failure Major Criteria: – PND – JVD – Rales – Cardiomegaly – Acute Pulmonary Edema – S 3 Gallop – Positive hepatic Jugular reflex – ↑ venous pressure > 16 cm H 2 O

15. Dx of Heart Failure (cont.) Minor Criteria LL edema, Night cough Dyspnea on exertion Hepatomegaly Pleural effusion ↓ vital capacity by 1/3 of normal Tachycardia 120 bpm Weight loss 4.5 kg over 5 days management

16. JACC 1997;30:8-18 Diastolic Filling of the LV

17. Physiology Diastole encompasses the period during which the myocardium loses its ability to generate force and shorten and then returns to resting force and length. Normal diastolic function allows the ventricle to fill adequately during rest and exercise, without an abnormal increase in diastolic pressures.

18. Physiology Diastolic function is complex, but most important components are the processes of: – Active LV relaxation – Passive Stiffness LV relaxation is an active, energy dependent process that begins during the ejection phase of systole and continues through IVR and rapid filling phase Process during which the contractile elements are deactivated and the myofibrils return to their original (pre-contraction) length JACC 1997;30:8-18

19. EPICA Study Eur Journal Heart Failure 2002;4:531-539 Population based study showing increased prevalence of Diastolic HF with age and with female gender

20. Systolic vs Dialstolic Congestive heart failure Exertional Dyspnea Paroxysmal Nocturnal Dyspnea Jugular Venous Distinction Orthopnea Lung Crackles Displaced Aprical Impulse S3S3 S4S4 Systolic Heart Failure Diastolic Heart Failure Adapted from Echeverria et al, 1983

21. Patient has dyspnea with risk factors such as hypertension, diabetes, ischemia, elderly Clinical exam shows signs of HF, S 4. CXR confirms pulmonary congestion with a normal sized cardiac silhouette ECG may show LVH, AF. BNP elevated When to suspect Diastolic Heart Failure?

25. Tissue Doppler Mitral Annulus Velocity Sohn et al: JACC, 1997 Mitral flow Mitral annulus velocity Normal Ab Relax Pseudo Restrictive Normal Ab Relax Pseudo Restrictive Grade 1 Grade 2Grade 3 Grade 1 Grade 2Grade 3

26. Diastolic Dysfunction LV pressure Grade 1 Grade 2 Grade 3 Grade 4 Mitral flow Tissue Doppler Pulmonary vein CP1008785-63 E/e’ E e’ < 10 10 -15 >15>15

27. Nagueh et al: JACC, 1997 Ommen et al: Circ, 2000 45 40 35 30 25 20 15 10 5 01051520253035 E/e’ PCWP (mm Hg) r = 0.87 n = 60 Annulus e Mitral E E/e As LV filling pressure 

28. Ln BNP PCWP (mm Hg) Correlations of PCWP to BNP versus PCWP to Mitral E/e’ CP1156944-1 Dokainish et al: Circ, May 25, 2004 Ln BNP vs PCWP Mitral E/e’ vs PCWP Mitral E/e’ PCWP (mm Hg) r=0.32 p=0.02 r=0.32 p=0.02 r=0.69 p<0.001 r=0.69 p<0.001 EF <50% EF  50% EF  50% EF  50%

29. Prognosis of Patients with E/e’ Ratio of 15 Survival Follow-up (months) EF <40% Hillis et al: JACC 43(3):360, 2004 E/e’<15 E/e’ >15 72 52 29 11 4 4 No. at risk EF >40% E/e’ <15 E/e’ >15 178 143 84 38 11 CP1141593-3 Follow-up (months)

30. e’ = 18 cm/s ConstrictionMyocardial e’ = 5 cm/s Tissue Doppler Early diastolic mitral annulus velocity (e’)

31. Left Atrial Volume During diastole, when the mitral valve is open, the left atrium is exposed to the loading pressure within the left ventricle Over time, exposure of LA to increased filling pressure will result in its remodeling and increased volume Left atrial size is a useful marker for chronicity of diastolic dysfunction (“HgbA1c of heart disease”) JACC 2003;41:1036-1043

32. Left Atrial Volume LA volume measurement has been shown to be predictive of an individual’s risk of stroke, MI, A fib and heart failure In clinical practice, volumes are more useful because they allow accurate assessment of asymmetric remodeling of the chamber LA volumes are best calculated using ellipsoid model or Simpson’s rule JACC 2003;41:1036-1043

33. JASE 2004;17;3:290 Because E/A ratio, DT and IVRT are altered by filling pressures, they follow a parabolic curve pattern. Further measurements which are less load dependent may be necessary to accurately assess degree of diastolic abnormality.

34. JASE 2004;17:290-297

35. Patient with Shortness of breath in out patient clinic Seventy year old male with shortness of breath for last six months. He was recently admitted to hospital for acute pulmonary adema and cardiac workup was negative. Shortness of breath has worsened and has persistent severe hypertension. He has been treated with severe hypertension, on four anti hypertensive medication and office blood pressure is 180/110 mm/Hg. How to evaluate this patient in office setting?

36.  Overnight Pulse Oximeter:

37. Overnight Pulse Oxymetery

38. Prevalence of Sleep Apnea Co-morbidities Sjostrom et al. Thorax 2002 Logan et al. J. Hypertension 2001 Javaheri et al. Circulation 1999 O’Keefe, Patterson. Obes Sugery 2004 Einhorn et al. Amer Diab 2005 Somers et al. ATS Pres. 2004

40. Mottram, P. M et al. Heart 2005;91:681-695 Suggested schema for echo Doppler categorisation of diastolic function in patients with normal LV systolic function.

41. Mottram, P. M et al. Heart 2005;91:681-695 Stepwise approach to clinical evaluation of the dyspnoeic patient with normal LV systolic function for the presence of diastolic heart failure.

42. ACC/AHA 2005 Guideline Update for the Management of Patients with Chronic Heart Failure, JACC 2005

44. Conclusions Diastolic Dysfunction is responsible for about one-half of cases of CHF. Morbidity and mortality associated is high and similar to LV systolic dysfunction. Older age, hypertension and female sex are commonly associated. Non invasive imaging techniques can be used for diagnosis. At this time, further studies are needed to determine optimal treatment strategies.