Maria Angela S. Cruz-Anacleto, MD

Maria Angela S. Cruz-Anacleto, MD
PHA INTERACTIVE CASE CONFERENCE Pains of the Heart Maria Angela S. Cruz-Anacleto, MD

Case 57/Female Menopausal Non-HTN, non-DM Hypothyroid (s/p RAI 1997)
Levothyroxine 100 ug OD

Case 5 Months PTA Stress Echocardiography Chest discomfort
Patient was apparently well until 5 months PTA, she began to experience increasing intensity of chest discomfort described as chest heaviness precipitated by exertion relieved by rest. Patient underwent a stress echo

Stress Echocardiogram

Case 5 Months PTA Positive Stress Echo Medications ASA 100 mg OD
Chest discomfort Positive Stress Echo Medications ASA 100 mg OD Metoprolol 50 mg OD Trimetazidine 35 mg BID

Case 5 Months PTA Thallium myocardial perfusion scan 3 Months PTA

Stress Echocardiography Dobutamine Stress Echocardiography
Which among the non-invasive test is least sensitive for detection of CAD among women? Exercise ECG Stress Echocardiography Dobutamine Stress Echocardiography Radionuclide Testing A B C D

Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Coronary Artery Disease Exercise ECG Sensitivity 61% Specificity 70% Stress Echo Sensitivity 81% Specificity 86% Dobutamine Stress Echo Sensitivity 80% Specificity 84% Radionuclide Testing (Tc) Sensitivity 91% Among the 4 screening test, Exercise ECG has the lowest sensitivity and specificity. The diminished accuracy is secondary to more frequent ST segment changes , lower ECG voltage and probably hormonal changes occurring in women. The addition of echocardiography to stress test improves the sensitivity and specificity comparable to DSE. MPI done using technetium has the highest sensitivity and specificity. Thallium another isotope yields higher false positive results due to attenuation of soft tissue such as the breast on the anterior and anterior lateral walls. For screening test a high sensitivity would be better. Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Coronary Artery Disease: Consensus Statement From the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention,American Heart Association Circulation 2005; 111:

Stress Echocardiography Dobutamine Stress Echocardiography
Which among the non-invasive test is least sensitive for detection of CAD among women? Exercise ECG Stress Echocardiography Dobutamine Stress Echocardiography Radionuclide Testing A B C D

Thallium Scan Her thallium scan revealed Mild Stress Induced Myocardial Ischemia in the apical to basal septal, anterior, anterolateral, and inferior walls

Case 5 Months PTA 3 Months PTA
Mild stress-induced ischemia on Thallium myocardial perfusion scan Advised coronary angiogram Medications Simvastatin 40 mg OD Losartan 50 mg OD Clopidogrel 75 mg OD ISMN 20 mg OD 3 Months PTA

Case 5 Months PTA 3 Months PTA Chest pain relieved with SL nitrates
CA possible PCI 1 Month PTA

Coronary Angiogram Here coronary angiogram revealed normal coronary arteries: Timi frame count: LAD 47 LCx 54 RCA 46

Coronary Angiogram Post NTG Pre NTG Cranial view pre and post NTG

IVUS Antegrade LM to LAD Antegrade LM to LCx
Intravascular ultrasound studies of the LAD and LCx showed no luminal irregularities nor atheroma Antegrade LM to LAD Antegrade LM to LCx

Salient Points Female Typical Angina Abnormal Stress Echocardiogram
Perfusion Defect on Thallium Normal Coronary Arteries on Angiogram We are presented with a female patient, menopausal with typical angina, evidence of stress induced ischemia and essentially normal coronary arteries,

The most likely diagnosis for this case is.....
Prinzmental Variant Angina Coronary Slow Flow Phenomenon Myocardial Bridging Cardiac Syndrome X A B The most likely diagnosis for this case is? C D

1Prinzmental Variant Angina 2Coronary Slow Flow Phenomenon
Pain at rest ST Elevation 1Prinzmental Variant Angina Young male smokers 2Coronary Slow Flow Phenomenon Variable presentation Systolic compression of epicardial a. 3Myocardial Bridging Prinzmental Variant Angina: coronary artery spasm occurring at rest and presents with ST elevation. it is not provoked by exercise, emotional upset, cold or a meal associated with smoking all of which are absent in our patient CSFP: essentially consists of a delay in the progression of the contrast injected in the coronary vasculature during angiography which is present in our patient. it is commonly found in young male smokers Myocardial bridging: is a congenital coronary anomaly with a segment of a major epicardial artery, running intramurally through the myocardium. This was not seen in her angiogram 1 Circulation. 2007;116: 2 J Am Coll Cardiol, 2010; 56: 3 European Heart Journal 2005; 26: 1159–1168

Coronary Slow Flow Phenomenon
Diffuse Intimal Thickening1 Widespread calcification along the vessel wall1 Atheroma not producing luminal irregularities on angiogram1 Although slow flow was appreciated in her angiogram she is unlikely to have coronary slow flow phenomenon, because in the IVUS study done there was no diffuse intimal thickening , widespread calcification, nor atheroma which is characteristic of patients with CSFP. Coronary flow reserve was not impaired 22 Int J Cardiol. 2008;12(3)358-61 . 1 Med Hypothesis 2010, doi: /j.mehy

The most likely diagnosis for this case is.....
Prinzmental Variant Angina Coronary Slow Flow Phenomenon Myocardial Bridging Cardiac Syndrome X A B Therefore the most likely diagnosis for this case is Cardiac Syndrome X. C D

Stress Induced/ Ischemia
Typical Angina Cardiac Syndrome X Stress Induced/ Ischemia Cardiovascular “syndrome X” refers to with a syndrome of angina or angina-like discomfort with exercise, ST-segment depression on exercise testing or other objective signs of ischemia , and normal or non obstructed coronary arteries on arteriography. This excludes patients with LVH, hypertension and DM From: ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction Normal Angiogram Circulation. 2007;116:

Abnormal Pain Perception Psychiatric Morbidity
Pathogenesis CSX Coronary Microvascular Dysfunction Abnormal Pain Perception Myocardial Ischemia Psychiatric Morbidity Inflammation Circulation. 2004;109: Chin Med J 2005; 118(21):

Pathogenesis ISCHEMIA Normal Epicardial Artery
Inappropriately Increased Vascular Tone Appropriate Stimulation of pain receptors ISCHEMIA Circulation. 2004;109: N Engl J Med.2002; 346:

Inappropriately Increased Vascular Tone
Pathogenesis Endothelial Dysfunction NO ET-1 Risk Factors Obesity Dyslipidemia Smoking Estrogen Deficiency Inappropriately Increased Vascular Tone ISCHEMIA Circulation. 2004;109: N Engl J Med.2002; 346:

Which among the following is an endothelium-independent vasodilator?
Endothelin Acetylcholine Nitroglycerin Prostacyclin A B C D

Coronary Vascular Tone
Contrictors Dilators Metabolic Endothelium Dependent Endothelium Independent Endothelin Nitrates Ach, Prostacyclin, ADP, EDHF, shear stress Adenosine & NO Endothelial Dysfunction in Vascular Disease 2007 Coronary Artery Disease 2001,12: Interventional Cardiology Secrets 2003

Microvascular Dysfunction
Coronary Flow Reserve1 Ratio of maximal hyperemia to basal flow Index of microcirculatory function Partly reversible1 Coronary Angiography + intracoronary doppler2 NEJM 2007;356: Circulation. 2010;121:

Transthoracic Echocardiographic Doppler Pulse Amplitude Tonometry
Which of the following non-invasive tests may be used to diagnose endothelial dysfunction? Transthoracic Echocardiographic Doppler Cardiac MR Pulse Amplitude Tonometry All of the above A B C D

TTE doppler Cardiac MR RH-PAT
CBF (peak/rest) < 2.0 Adenosine/Dipyridamole LAD TTE doppler Segmental & focal perfusion defects Regional and global CBF Cardiac MR Automatic Quantitative Practical RH-PAT Circulation. 2010;121: J Am Coll Cardiol 2010;55:

The PAT device comprises a pneumatic plethysmograph that applies uniform pressure to the surface of the distal finger, allowing measurement of pulse volume changes in the finger. It is applied to 1 finger of each hand with 1 serving as the control, A BP cuff is inflated in 1 arm to induce hyperemic flow. In response to hyperemic flow, digital pulse amplitude increases, a response that has been shown to depend in part on nitric oxide synthesis. RH PAT Criculation 2008; 117:

Transthoracic Echocardiographic Doppler Pulse Amplitude Tonometry
Which of the following non-invasive tests may be used to diagnose endothelial dysfunction? Transthoracic Echocardiographic Doppler Cardiac MR Pulse Amplitude Tonometry All of the above A B C D

Normal Epicardial Artery Enhanced sensitivity of pain receptors
Pathogenesis Normal Epicardial Artery Normal Vascular Tone Enhanced sensitivity of pain receptors Circulation. 2004;109: N Engl J Med.2002; 346:

Enhanced sensitivity of pain receptors
Pathogenesis Increased Pain Perception Potassium release Adenosine release Mishandling of afferent stimuli by CNS Increased adrenergic activity Impaired parasympathetic activity Enhanced sensitivity of pain receptors Circulation. 2004;109: N Engl J Med.2002; 346:

Markers of Inflammation
Pathogenesis Markers of Inflammation CRPa IL-1a VCAM-1b ICAM-1b Chin Med J 2005; 118(21) : aAm J Cardiol 2004;94: 40-44 bAtherosclerosis 1995;68:

Management of CSX should include the following except:
Clopidogrel Beta-Blockers Calcium Channel Blockers Referral to Cardiac Rehab A B C D

Platelet Aggregation Heart 2004;90:457–463

Psychological Intervention
Therapeutic Options Anti-ischemics Analgesics HRT Psychological Intervention Anti Inflammatory Eur Heart J 2001;22: Chin Med J 2005; 118(21) :

Therapeutic Options Anti-ischemics Nitrates CCB Nicorandil Trimetazidine Beta-Blockers ACE-I Analgesics HRT Psychological Intervention Anti Inflammatory Eur Heart J 2001;22: Chin Med J 2005; 118(21) :

Therapeutic Options Anti-ischemics Analgesics Imipramine Electrostimulation TENS SCS Aminophylline HRT Psychological Intervention Anti Inflammatory Eur Heart J 2001;22:

Anti-ischemics Analgesics HRT Psychological Intervention Anti Inflammatory Therapeutic Options they have theorized that estrogen has a role in the pathogenesis of CSX because it predominantly affects post menopausal women. And estrogen deficiency has been linked to vasomotor instability. Transdermal estrogen has been shown to improve endothelial dependent coronary vasomotion and decrease anginal episodes, Eur Heart J 2001;22: Chin Med J 2005; 118(21) :

Anti-ischemics Analgesics HRT Psychological Intervention Anti Inflammatory Therapeutic Options Eur Heart J 2001;22: Chin Med J 2005; 118(21) :

Anti-ischemics Analgesics HRT Psychological Intervention Anti Inflammatory ASA Statins Therapeutic Options Eur Heart J 2001;22: Chin Med J 2005; 118(21) :

Cardiac Rehab Improves exercise tolerance Quality of Life
Psychological Morbidity Symptom severity JACC 2000;36: Menopause 15;3:

ACC/AHA 2007 Guidelines for the Management of Patients With UA/NSTEMI (Section on Cardiac Syndrome X) Beta blockers Calcium antagonists Nitrates Imipramine Estrogen Statin therapy Exercise training Cognitive behavioral therapy Circulation 2007;116;

What is the prognosis of patients with CSX?
Poor Excellent Uncertain A B C

Long-term prognosis of patients with cardiac syndrome X
155 patients with CSX Followed-up for months No patients died from cardiovascular causes or developed non-fatal MI Int J Cardiol 2010;140:

Which among the following non-invasive test would be best suited for follow-up of patients with CSX?
Thallium Scan Cardiac MRI Coronary CT Treadmill Stress Test A B C D

Treadmill Stress Test Coronary CT
Low sensitivity for detection of CAD1 CSX have stress induced ischemia3 Coronary CT Identifies the presence of CAC1 Anatomic definition of stenosis1 Accurate in the diagnosis of CAD for CAC < 6002 No Physiologic significance1 1Braunwald’s Heart Disease 8th Ed. 2 NEJM 2008;359: 3 Circulation 2005; 111: 4Circulation. 2007;116:

SPECT Cardiac MRI Physiologic significance of stenosis1
Improvement of perfusion with vasodilation 1 Multiple perfusion abnormalities with different levels of severity of CSX 2 Patchy vs clustered hypoperfusion2 Cardiac MRI Better than SPECT for detection of CAD1 Visualization of coronaries, assess perfusion, wall motion Accuracy of 87% 3 1Braunwald’s Heart Disease 8th Ed. 2 BMC Nuclear Medicine 2006;6:1 3 JACC Img 2008;1:436-45

A B C D Cardiac MRI Coronary CT
Which among the following non-invasive test would be best suited for follow-up of patients with CSX? SPECT Cardiac MRI Coronary CT Treadmill Stress Test A B C D

Cardiac Syndrome X Diagnosis Pathogenesis is multifactorial
Angina Stress Induced Ischemia Normal Coronary Angiogram Pathogenesis is multifactorial Management directed towards symptom control & quality of life Excellent Prognosis

PHA INTERACTIVE CASE CONFERENCE
Pains of the Heart

Maria Angela S. Cruz-Anacleto, MD

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