Cardiology Diagnostics Part 1 Diagnostic Medicine I - Fall 2023 Prepared by: John Bowers, MPAS, PA-C Objectives: By the end of this class, you should be able to: Understand the indications and/or contraindications (when applicable) for use of cardiac catheterization, cardiac stress testing, ESR/CRP, and cardiac “enzyme” testing. Apply acquired knowledge to clinical or case scenarios and appropriately order these diagnostic modalities. Understand limitations to these diagnostic tests (if any) and any available strategies to mitigate the effect of these limitations on diagnosis of disease states. Class Preview This class will cover: Cardiac Catheterization Cardiac Enzymes Stress Testing Basics ESR/CRP and the role of these diagnostics in cardiac/riskfactor testing Cardiac Enzyme Testing Troponin, CK-MB, etc. To Start, Let’s Define What We Are Looking for…. Identifying “ischemia” or “infarction” is the target of our testing. This occurs when any imbalance between the demand of oxygen (and/or nutrients) outweighs the supply of those things. This is the most common cause of cardiac injury. Possible causes = vessel stenosis or occlusion, extreme exercise when not conditioned, trauma, toxins, and/or certain infections Cardiac Injury Cardiac injury occurs when there is a disruption of the normal cardiac myocyte membrane. This results in a loss of intracellular contents into the into the extracellular space (think similar to RBC cell lysis) This leads to detectable levels of biologically active proteins/enzymes such as troponin, creatine kinase (CK), myoglobin in the blood stream. Measuring these enzymes helps to indicate cardiac injury or ischemia. When do we use enzyme testing? – Indications: When assessing for measureable evidence of cardiac injury (regardless of underlying reason). Examples include: MI/STEMI or NSTEMI, demand ischemia, myocarditis, etc. Clinical Example A 47 y/o male patient presents to the ER for c/o chest pain. He reports the pain began 2hrs PTA. The pain radiates across his chest from left side to R and is worse with prolonged ambulation. The pain is occurring at rest or with activity. The pain is described as dull, but occasionally sharp when at it’s worst, rated 7/10 at worst. No hx of similar. Vital signs only remarkable for elevated BP of 150/90. No recent injury to explain pain otherwise. No SOB, no leg swelling. No cough, dyspnea, orthopnea. History of tobacco use x 20 years (1 ppd) What do you want to do? About Cardiac Enzyme Testing Also referred to as cardiac biomarker testing These tests are indicative of myocardial injury Myoglobin (MB), Creatinine kinase (CK) Creatinine kinase MB isoenzyme (CK–MB), Cardiac troponins (troponin I or T) Which of these are most specific to the myocardium? CK-MB Note: small amount found in other tissues Cardiac troponins (more specific to myocardium than CK–MB) Note: *Troponin I is more cardiac specific than troponin T Cardiac Enzyme Timeline Which biomarker peaks first? First detected in bloodstream: Myoglobin (within 8 hours) Which biomarker persists longest? Last to clear bloodstream: Troponin(s) Note: Recent research results have allowed us to understand that troponins should begin to rise within 2- hours of acute-onset MI (previously thought 4 hours, at earliest). Conservative approach is now 4 hours. NSTEMI vs. STEMI: Classification (i.e. Chest pain) Following disruption of a plaque, patients experience ischemic discomfort resulting from reduced flow through an affected coronary artery. The flow reduction may be caused by a completely occlusive thrombus (right) or partial occlusion (left). Patients with ischemic discomfort may present w/ or w/o ST elevation. Of patients with STelevation, the majority (wide red arrow) ultimately develop a Q wave on the ECG (Qw MI), while a minority (thin red arrow) do not develop Q wave. (NQMI). These are old terms, not used today. Patients who present without ST elevation are suffering from either unstable angina or a nonST elevation MI (NSTEMI) (right green arrow), a distinction that is made based on the presence or absence of a serum cardiac biomarker In addition to plaque rupture or acute obstruction – what are other causes of cardiac troponin elevation? Cardiac tissue damage due to “demand ischemia” Tachyarrhythmias, profoundly anemic state with high cardiac demand, significant hypo/hyper-tension, HF, LVH, severe AS, PE, coronary vasculitis, coronary vasospasm, sepsis, acute respiratory failure Cardiac tissue damage not due to ischemia Cardiac contusion, recent cardiac surgery or ablation therapy, myocarditis, Takotsubo cardiomyopathy (apical ballooning), cardiotoxic agents, frequent or recent defibrillator shocks (appropriate or inappropriate) Extra-cardiac causes of elevated troponin? Cerebrovascular Stroke àThe most likely explanation in this setting is an imbalance of the autonomic nervous system, with resulting excess of sympathetic activity and increased catecholamine effect on the myocardial cells Test Selection: Creatine kinase (CK) and it’s MB isoenzyme (CK-MB) were previously the most commonly used serologic tests for the diagnosis of MI prior to the widespread use of troponin(s). We can now diagnose “microinfarctions” by highly sensitive troponin assays. These highly sensitive assays may be positive even when CK-MB levels may be in the normal reference range. As such, cardiac troponins are the preferred biomarkers for diagnosis and prognosis of MI in many clinical settings. **It is often unnecessary to obtain both types of testing (i.e. troponin and CK-MB at the same time). Summary (cont’d) Myoglobin and lactate dehydrogenase should no longer be used for the evaluation of patients with ACS and/or acute MI. At one time, myoglobin’s early appearance in serum was postulated to be a useful adjunct to troponin or CK-MB for the early diagnosis of MI à But…clinical data suggests that cardiac troponin outperforms each of these tests in almost every way. Reference Ranges for Commonly Used Cardiac Enzymes Troponin I – Reference range = <0.35 ng/mL (may vary by institution and method tested) Troponin T – Reference range = <0.2 mcg/L (may vary by institution and method tested) CK-MB – Reference range = <9.0 ng/mL If you see any elevation of any of these above the reference range or upward trending you should consider myocardial ischemia *(Don’t forget to consider other diagnoses or reasons for elevated cardiac enzymes) Clinical Utility of Troponin – As used with the “HEART SCORE” *MACE = Major adverse cardiac event Clinical Utility of Troponin (cont’d) Using “serial” troponins (defined as measuring troponin in 2, 3, or 4 hour increments after an initial measure) helps reassure the provider and patient that a troponin is not trending upward. What if pt walks in now? Troponin likely will not show up in blood stream until 4 hrs after onset of infarction, thus why this is important. Troponin: clinical application Results from the “MIDAS” studyAn analysis was conducted of 1005 participants in the diagnosis of acute coronary syndromes MIDAS was a prospective observational cohort of Emergency Department patients enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome (ACS) The North American Chest Pain Rule (NACPR) = a patient is considered low-risk if they have no high risk criteria. Cardiac Stress Testing The “let’s see what happens” test Intro Cardiac stress testing: An important diagnostic and prognostic tool used to evaluate patients for suspected heart disease. Both exercise and pharmacologic types of stress testing assesses cardiac function by: Increasing the myocardial oxygen demand And thus, helps to reveal inadequate oxygen supply (hypo-perfusion) from diseased or narrowed coronary arteries Particularly helpful in any patient w/ symptoms that do not occur at rest (i.e. stable angina) Indications for Stress Testing Evaluation of: Exertional chest pain or symptoms suggestive of angina in a patient with moderate or high level of suspicion of CAD ***Pre-test history & risk assessment is key Assess significance or progression of known coronary artery disease Determine a patient’s general exercise capacity Valvular disease (to determine effect on exercise capacity) Select arrhythmias (to determine their effect on myocardial perfusion) To evaluate new-onset heart failure or cardiomyopathy (why?) Why = To evaluate for ischemic heart disease as a cause for that new heart failure (or a cardiomyopathy of uncertain etiology), assuming that coronary angiography has not already been planned or performed. Other Indications: Patients with chronic left ventricular dysfunction and coronary artery disease who are candidates for revascularization (via catheterization) (why?) Stress testing PLUS imaging can identify areas of myocardial ischemia and regions of viable myocardium This information is helpful in the planning of revascularization Acute chest pain of undetermined etiology Pain must resolve prior to stress testing Otherwise, you could incite a true MI (never send a patient with active chest pain to a stress test) Select high-risk patients undergoing non-cardiac surgery Why? Preoperative evaluation of patients prior to elective surgery, can help identify patients with active cardiac conditions that should undergo further evaluation and treatment prior to scheduled surgery Absolute Contraindications to Stress Testing Active chest pain concerning for ACS/MI, Unstable angina or known MI recently (<72 hrs) Uncontrolled arrhythmias with hemodynamic compromise Don’t make the mistake of sending a hypotensive patient to get a stress test! K, Thanks! Acute decompensated heart failure Known CHF, with acute worsening recently (of any etiology) Active or acute endocarditis, myocarditis, or pericarditis Acute aortic dissection Symptomatic severe valvular stenosis Acute pulmonary embolism, pulmonary infarction, or DVT Physical disability that precludes safe or adequate testing Methods of Testing The two most common methods of exercise stress testing are: 1. ECG-based only = Exercise stress testing while connected to a live-recording ECG machine (to look for active changes with exertion) 2. Imaging based = Exercise stress (or by pharmacologic stress) with ECG, followed by imaging. Imaging is usually either ECHO or radionuclide testing Patient Monitoring During Testing Regardless of testing type, monitor the patient carefully by: Asking the patient to report subjective symptoms of chest pain, SOB or dyspnea, light-headedness/near-syncope, etc. These should be reason to stop the test Physical findings should also be assessed during testing such as peripheral cyanosis (i.e. signs of poor perfusion), hypotension, excessive increase or decrease in HR, pulmonary rales (signs of HF) Differences in Modalities? ECG-based exercise stress testing is the simplest measure to evaluate for exertion-induced myocardial ischemia as evidences by changes on the ECG during testing. Imaging-based stress testing (whether exercise-based or pharmacologic stress-induced can help to more specifically isolate where a flowlimiting lesion is within the coronary anatomy. Imaging-based modality is preferred in these patient groups: Those undergoing pharmacologic stress testing (due to lower sensitivity compared to exercise) Prior revascularization (due to abnormal coronary anatomy) Significantly abnormal resting ECG Patients using Digoxin Comparing types: ECG-Based Imaging-Based Commonly first-line in those who can exercise and have routine ECG findings at rest Better in select patients (mentioned on prior slide) (i.e. baseline ECG is not complex) Less expensive than imaging-based Less helpful to specifically locate a coronary artery lesion May be converted to imaging-based during test Particularly if elicited ECG abnormalities are non-specific Better to isolate area of a lesion/flow limitation May be the preliminary test if ECG portion was felt to be inaccurate, complex, or nonspecific in its findings Increasing in preferred prevalence SUMMARY: EXERCISE ECG ALONE OR AS A COMBO MODALITY? Exercise stress testing with electrocardiographic (ECG) monitoring should be the initial test of choice for the majority of patients who can exercise and who have an ECG which can be adequately interpreted. Exercise stress testing with imaging has certain advantages over the standard exercise testing, but there is insufficient evidence at this time to recommend exercise stress testing with imaging in all patients. Special Stress Imaging Stress Echocardiography Provides real-time cardiac functional assessment in several possible situations: At rest, During or after- dynamic exercise, Or during pharmacologic stress testing Helps to determine if there is need for a valvular repair /replacement. Particularly those pts with asymptomatic significant aortic stenosis (such as in congenital biscupid aortic valve) Why? To determine prognosis and/or severity of disease Other indications: Stress ECHO may also be performed to other valvular diseases such as: Severe mitral stenosis without symptoms, Moderate mitral stenosis with symptoms, Severe mitral or aortic regurgitation (when left ventricular size and function do not meet surgical criteria) Pharmacologic-based Stress Test Often indicated when a patient has a limitation which causes them to be unable to complete the normal treadmill exercise portion (either inadequately or cannot complete at all) -Examples: due to handicap, due to injury, poor exercise tolerance, neurologic deficit, severe arthritis, etc. Chemicals Used (2 Main Types) 1.) Ionotropes/Chronotropes: Dobutamine (a synthetic catecholamine) Stimulates beta1-adrenergic receptors à increasing the heart rate (chronotropic effect) & myocardial contractility (inotropic effect). 2.) Vasodilators: Including: Adenosine*; dipyridamole; and the selective A2A receptor agonists including: regadenoson, binodenoson, and apadenoson Theophylline and caffeine should be withheld 48 and 12 hrs before vasodilator stress resting, respectively, since these agents can decrease the effectiveness of vasodilators. Contraindications 1 For Inotrope/Chronotrope (Dobutamine) Stress Testing: Sustained or frequent ventricular arrhythmias and atrial fibrillation with rapid ventricular response (RVR) Why: (may precipitate a worse or life threatening, arrhythmia) Recent myocardial infarction (within one to three days) or unstable angina /complicated ACS Why: (contraindicated for all stress modalities) *Aortic dissection Why: (increased rate/pressure may increase risk of rupture) Moderate to severe systemic hypertension I.e. resting systolic blood pressure >180 mmHg Contraindications 2 For Vasodilator Stress Testing: Significant active bronchospastic airway disease Why: (these drugs may stimulate bronchospasm) Significant hypotension Why: (these drugs will further transiently lower blood pressure) Sick sinus syndrome (SSS) and/or high-degree AV block without a functioning pacemaker Why: (these drugs may worsen preexisting conduction disease and/or incite 3rd degree block) Unstable or complicated acute coronary syndrome Why: (an increased risk for acute ischemic events is present with all stress modalities) BREAK TIME Cardiac Catheterization The gold standard test for true/thorough assessment of the coronary arteries. Spooky History of Catheterization: Fact or Fiction? In 1929 Werner Forssman, a resident surgeon at Eberswalde in Germany, inserted a urologic catheter into his right atrium from a left antecubital vein cutdown he had performed on himself using a mirror. After walking downstairs to the radiology suite, the position of the catheter tip was verified by a roentgenogram (now known as xray). This was the beginning of cardiac catheterization (i.e. the insertion and passage of small plastic catheters into arteries, veins, the heart, and other vascular structures for a variety of indications). Catheterization: How is it performed First – consent must be obtained. The procedure must be explained, including risks, if applicable (i.e. non-emergent situation) Emergent cath’s may not require consent (i.e. a life threatening condition) Second – a site of insertion of the catheter must be determined Femoral artery (most common currently) –vs.– . Radial artery (gaining popularity due to less complications) Then, a metal “guide wire” is passed into the artery and used to allow softer, more flexible plastic catheters to be introduced into appropriate areas of the heart. Once the catheter is in place (inside the heart or coronary artery of choice) pressures are measured and/or dye is injected (angiography) to allow the clinician to see filling defects, structural abnormalities, or atypical flow characteristics. How is it performed? (cont’d) If you click the link below you will see how the two methods of catheter insertion compare: https://youtu.be/vuHHjIRswDE?t=1m45s Videos: Click this link to see how cardiac catheterization can detect coronary artery abnormalities General animated instructional video (no sound) Click the link below to watch an actual case with live dye injection: https://youtu.be/JeH4zPzQgRc After clicking, forward to 1:16 once you have listened to the first 20 seconds (indication for procedure is announced). Right vs. Left Heart Cath Right heart catheterization is no longer a routine part of general diagnostic cardiac catheterization when evaluating the coronary arteries It is mainly used to evaluate the venous system / pulmonary arteries Indicated to evaluate: Unexplained dyspnea, valvular heart disease of the R side to determine extent of disease, pericardial disease, right and/or left ventricular dysfunction, congenital heart disease, and suspected intracardiac shunts. Right vs. Left Heart Cath Left heart catheterization is the gold standard method used to evaluate coronary vasculature As well as: left ventricular & left atrial filling pressures, and occasionally, the aortic valve When speaking of coronary artery disease and assessment as a whole, left heart catheterization is the gold standard. Right vs. Left Cath: Pathway Specific Indications for Left Heart Catheterization Cardiac catheterization is used to assess for and/or diagnose: *Atherosclerotic coronary artery disease Also: severe pericardial disease, cardiomyopathy, assess for causes of heart failure, and can be used in identifying valvular or congenital heart abnormalities. Please note: Ultrasound is increasingly being used to assess for and diagnose valvular heart disease. As such, in some cases that means catheterization may no longer be required Catheterization helps to determine extent and severity of cardiac dz & determine if medical, surgical, or other interventions are needed (i.e. medication management vs. bypass graft vs. stenting) General Info About Cath In general, cardiac catheterization is an elective diagnostic procedure (It has the potential for therapeutic intervention to address any issues discovered during the procedure) For emergent indications, particularly if the patient is unstable from a suspected cardiac cause such as acute MI, catheterization should be completed as soon as possible. Absolute Contraindications Generally speaking, there are no absolute contraindications for an emergently-indicated heart cath procedure Must simply do Risk vs. Benefit Note: You must have a well-prepared facility and trained provider to perform cardiac catheterization Not all hospitals have the tools or trained providers to perform catheterization Relative Contraindications Relative contraindications to cardiac catheterization include: Fever Significant/profound anemia Electrolyte imbalance (especially hypokalemia predisposing to arrhythmias) Renal failure (why?) Pregnancy (why?) Uncontrolled bleeding as in supratherapeutic anticoagulated state Acute GI bleed Or other systemic illnesses requiring emergent stabilization PCI vs. CABG Percutaneous coronary intervention (PCI) refers to: Non-stent procedures on one or more coronary arteries (such as balloon angioplasty) OR stent interventions There are a variety of types of intra-coronary stents. In general, stents are characterized according to: Type of material, thickness of struts, and as to whether or not they are capable of eluting medication(s) for local delivery in the artery Stenting is generally indicated when a vessel reaches >/=70% diameter* stenosis. *Under that value, it is at the discretion of the performing provider. PCI vs. CABG When a patient has significant multi-vessel disease, Coronary Artery Bypass Graft (CABG) is typically warranted. The percentages of each vessel may vary, so it is up to the performing provider to determine need for CABG There may be patient-specific and case-specific factors weighing in… CABG – Terminology Review Heart Catheterization Complications The incidence of major risks of stroke, death, and myocardial infarction is approximately 0.1% The minor risks of vascular injury, allergic reaction, bleeding, hematoma, and infection range from 0.04% to 5% and should be discussed. Pain post procedure in area of catheter insertion may be common, particularly within 48 hours of the procedure. High risk populations: Certain patient groups are at higher risk for complications (for a variety of reasons): Acute myocardial infarction (*), Advanced age (>75 y), Aortic aneurysm, Aortic stenosis, Congestive heart failure, Diabetes, Extensive three-vessel coronary artery disease, Left ventricular dysfunction (left ventricular ejection fraction <35%), Obesity, prior stroke, Renal insufficiency, left main coronary artery stenosis, Unstable angina (w/ plaque that may rupture) Other Considerations The following constitute groups who may need special consideration in testing: Patients with diabetes mellitus (Insulin use? Hypoglycemia risk?) For diabetic patients, long-acting or NPH insulin dosing should be adjusted overnight due to fasting state! Normal morning dose of insulin could cause hypoglycemia during procedure. Renal insufficiency (due to contrast dye use) Prior allergy to iodinated contrast media Prophylactic measures exist to reduce risks to these pts Allergic reactions to contrast agents occur in <5% of cases Use of ESR/CRP Labs The “not-so-specific” labs ESR = erythrocyte sedimentation rate CRP = serum C-reactive protein concentration. ESR/CRP Overview: ESR/CRP are both non-specific biomarkers of inflammation. Both cannot tell you WHERE the inflammation is – just that it “is” or “is not” present overall (Thus, the test is sensitive, not specific) ESR value changes slowly as patient's condition worsens or improves Whereas CRP changes more rapidly, and may better reflect acute disease/problems Timeframe comparison Reference Ranges: ESR= Normal for Males—1 to 17 mm/h; females—0 to 25 mm/h. CRP= Normal < 0.8 mg/dL Cardiac-Specific Implications? Since pericarditis is an inflammatory disease, laboratory signs of inflammation are commonly observed in pts with acute pericarditis. This may include elevations in the white blood cell count, ESR and/or CRP While elevation in these markers supports the diagnosis, they are neither sensitive nor specific for acute pericarditis. But, may be helpful in confirming a diagnosis in which you are suspecting… What other diagnostic abnormalities might you see to suggest pericarditis? Cautious Use ESR/CRP may also be elevated in autoimmune, rheumatologic diseases, diseases of chronic inflammation as well as postsurgical states. In these conditions, ESR/CRP may be of little use That said, be mindful that inflammatory processes are important contributors to vessel disease and vulnerability of an atherosclerotic lesion to rupture or erosion. Summary - CRP CRP is the most extensively studied biomarker of inflammation in cardiovascular disease (CVD). Increased serum CRP correlates with traditional cardiovascular risk factors. But, it should NEVER be used alone to determine cardiovascular risk It may reflect contributions of these risk factors toward vascular inflammation. Chronically elevated serum CRP has been associated with a higher risk of future cardiovascular events. *However, the value of this information for individual risk stratification and direction of therapy continues to be debated. Summary (cont’d) For the determination of cardiovascular risk, low-, average-, and high-risk values of CRP are defined as <1, 1 to 3, and >3 mg/L, respectively. These values can be used in certain risk-level populations to modify current therapies (may suggest need to add a statin, lifestyle modifications, etc.) *Values >10 mg/L should prompt concern of a specific source of infection or inflammation and likely necessitates repeat measurement of hs-CRP in 10-21 days. (highly-sensitive) = hs That’s all! Questions? ewald@musc.edu