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Exercise stress electrocardiography

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1 Exercise stress electrocardiography
Physiology and Protocol, Indications and Contraindications Frijo Jose A

2 Exercise physiology Sympathetic activation Parasympathetic withdrawal
Vasoconstriction, exept- Exercising muscles Cerebral circulation Coronary circulation ↑norepinephrine and renin

3 Exercise physiology ↑ventri contractility ↑O2 extraction(upto 3)
↓peripheral resistance ↑SBP,MBP,PP DBP –no significant change Pulm vasc bed can accommodate 6 fold CO CO - ↑ 4-6 times

4 Exercise physiology Isotonic exercise(cardiac output)
Early phase- SV+HR Late phase-HR

5 ↑ exercise work à ↑ O2 usage à Person’s max
↑ exercise work à ↑ O2 usage à Person’s max. O2 consumption (VO2max) reached V02 peak Oxygen consumption (liters/min) Work rate (watts)

6 The peak oxygen consumption is influenced by the age, sex, and training level of the person performing the exercise The plateau in peak oxygen consumption, reached during exercise involving a sufficiently large muscle mass, represents the maximal oxygen consumption Maximal oxygen consumption is limited by the ability to deliver O2 to skeletal muscles and muscle oxidative capacity (mucle mass and mitochondirial enzymes activity). V02 peak Oxygen consumption (liters/min) (VO2max) Work rate (watts)

7 The ability to deliver O2 to muscles and muscle’s oxidative capacity limit a person’s VO2max. Training à ↑ VO2max 70% V02 max (trained) V02 peak (trained) V02 peak (untrained) Oxygen consumption (liters/min) 100% V02 max (untrained) 175 Work rate (watts)

8 Respiration during exercise
during dynamic exercise of increasing intensity, ventilation increases linearly over the mild to moderate range, then more rapidly in intense exercise the workload at which rapid ventilation occures is called the ventilatory breakpoint (together with lactate threshold) Respiration during exercise Lactate acidifies the blood, driving off CO2 and increasing ventilatory rate

9 Blood Pressure (BP) also rises in exercise
systolic pressure (SBP) goes up to mm Hg during dynamic exercise; diastolic scarcely alters in isometric (heavy static) exercise, SBP may exceed 250 mmHg, and diastolic (DBP) can itself reach 180

10 Intense exercise à Glycolysis>aerobic metabolism à ↑ blood lactate (other organs use some)
lactic acid (mM) Lactate threshold; endurance estimation Relative work rate (% V02 max)

11 Maximum HR HR=220 - age in years

12 Post exercise phase Vagal reactivation Imp cardiac deceleration mech
↑in well trained athletes Blunted in CCF

13 MET Metabolic Equivalent Term
1 MET = "Basal" aerobic oxygen consumption to stay alive = 3.5 ml O2 /Kg/min Differs with thyroid status, post exercise, obesity, disease states

14 Key MET Values 1 MET = "Basal" = 3.5 ml O2 /Kg/min
2 METs = 2 mph on level 4 METs = 4 mph on level < 5METs = Poor prognosis if < 65; 10 METs = same progn with medical thpy as CABG 13 METs = Excell prognosis, regardless of othr exercise responses

15 Key MET Values 3-5 METs: raking leaves,light carpentry,golf,3-4 mph
exterior carpentry, singles tennis >9 METs: heavy labour, hand ball, squash, running 6-7 mph

16 Estimated Energy Requirements for Various Activities

17 Estimated Energy Requirements for Various Activities

18 Calculation of METs on the Treadmill
METs = Speed x [0.1 + (Grade x 1.8)] Calculated automatically by Device! Note: Speed in meters/minute conversion = MPH x 26.8 Grade expressed as a fraction

19 Treadmill protocol Bruce protocol Naughton protocol Weber protocol
ACIP(asymptomatic cardiac ischemia pilot) Modified ACIP

20 The Bruce protocol Developed in 1949 by Robert A. Bruce, considered the “father of exercise physiology”. Published as a standardized protocol in Remains the gold-standard for detection of myocardial ischemia when risk stratification is necessary.

21 Protocol description Stage Time (min) M/hr Slope 1 1.7 10% 2 3 2.5 12%
1.7 10% 2 3 2.5 12% 6 3.4 14% 4 9 4.2 16% 5 12 5.0 18% 15 5.5 20%

22 Calculation of METs on the Treadmill
METs = Speed x [0.1 + (Grade x 1.8)] Calculated automatically by Device! Note: Speed in meters/minute conversion = MPH x 26.8 Grade expressed as a fraction

23 Procedure Standard 12 lead ECG- leads distally Torso ECG + BP
Supine and Sitting / standing HR ,BP ,ECG Before,after,stage end Onset of ischemic response Each minute recovery(5-10 mints)

24 Procedure- Lead systems
Mason-Liker modification RAD ↑inf lead voltage Loss of inf lead q New Q in AVL

25 Contraindications to Exercise Testing
Absolute Acute MI (< 2 d) High-risk unstable angina Uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise Symptomatic severe AS Uncontrolled symptomatic CCF Acute pulmonary embolus or pulmonary infarction Acute myocarditis or pericarditis Acute Ao dissection

26 Contraindications to Exercise Testing
Relative LMCA stenosis Moderate stenotic valvular heart disease Electrolyte abnormalities Severe HTN Tachyarrhythmias or bradyarrhythmias HOCM and other forms of outflow tract obstruction Mental or physical impairment leading to inability to exercise adequately High-degree AV block

27 Both MI and deaths have been reported and can be expected to occur at a rate of up to 1 per 2500 tests

28 Bayes' theorem A theory of probability
‘The post test probability is proportional to the pretest probability’

29 Classification of chest pain
Typical angina Atypical angina Noncardiac chest pain Substernal chest discomfort with characterstic quality and duration Provoked by exertion or emotional stress Relieved by rest or NTG Meets 2 of the above characteristics Meets one or none of the typical characteristics

30 Pretest Probability Based on the patient's history ( age, gender, chest pain ), physical examination and initial testing, and the clinician's experience. Typical or definite angina →pretest probability high - test result does not dramatically change the probability. Diagnostic testing is most valuable in intermediate pretest probability category

31 Pre Test Probability of Coronary Disease by Symptoms, Gender and Age

32 Pre-test Probability of CAD by Age, Gender, and Symptoms
Typical/Definite Angina Pectoris Age 30-39 Men Intermediate (10-90%) Women Intermediate Age 40-49 Men High (>90%) Women Intermediate Age 50-59 Men High Age 60-69 Women High

33 Pre-test Probability of CAD by Age, Gender, and Symptoms
Atypical/Possible Angina Pectoris: Age 30-39 Men Intermediate Women Very Low (<5%) Age 40-49 Women Low (<10%) Age 50-50 Women Intermediate Age 60-69 Men Intermediate

34 Pre-test Probability of CAD by Age, Gender, and Symptoms
Nonanginal Chest Pain: Age 30-39 Men Low Women Very Low Age 40-49 Men Intermediate Women Very Low Age 50-59 Women Low Age 60-69 Women Intermediate

35 Pre-test Probability of CAD by Age, Gender, and Symptoms
Asymptomatic: Age 30-39 Men Very Low Women Very Low Age 40-49 Men Low Women Very Low Age 50-59 Women Very Low Age 60-69 Women Low

Class I Adult patients (including RBBB or <1 mm of resting ST↓) with intermediate pretest probability of CAD Class IIa Patients with vasospastic angina.

Class IIb 1. Patients with a high pretest probability of CAD 2. Patients with a low pretest probability of CAD 3. Patients with <1 mm of baseline ST ↓and on digoxin. 4. Patients with LVH and <1 mm baseline ST ↓. Class III Patients with the following baseline ECG abnormalities: • Pre-excitation syndrome • Electronically paced ventricular rhythm • >1 mm of resting ST depression • Complete LBBB

38 Exercise Testing in Asymptomatic Persons Without Known CAD
Class I None. Class IIa Evaluation of asymptomatic T2 DM pts who plan to start vigorous exercise ( C) Class IIb 1. Evaluation of pts with multiple risk factors as a guide to risk- reduction therapy. 2. Evaluation of asymptomatic men > 45 yrs and women >55 yrs: • Plan to start vigorous exercise • Involved in occupations which impact public safety • High risk for CAD(e.g., PVOD and CRF) Class III Routine screening of asymptomatic

39 3. Low-risk UA pts >8 to 12 hrs & free of active ischemia/CCF
RISK ASSESSMENT AND PROGNOSIS IN PATIENTS WITH SYMPTOMS OR A PRIOR HISTORY OF CAD Class I 1. Initial evaluation with susp/known CAD, includingRBBB or <1 mm of resting ST Depression 2.Susp/ known CAD, previously evaluated, now significant change in clinical status. 3. Low-risk UA pts >8 to 12 hrs & free of active ischemia/CCF 4. Intermed-risk UApts > 2 to 3 days & no active ischemia/ CCF Class IIa Intermed-risk UA pts – initial markers (N),rpt ECG –no signi change, and markers >6-12 hrs (N) & no other evidence of ischemia during observation.

Class I 1. Before discharge (submaximal --4 to 6 days). 2. Early after discharge if the predischarge exercise test was not done (symptom limited to 21 days). 3. Late after discharge if the early exercise test was submaximal (symptom limited --3 to 6 weeks). Class IIa After discharge as part of cardiac rehabilitation in patients who have undergone coronary revascularization.

41 Submaximal protocols predetermined end point, often a peak HR 120 bpm, or 70% predicted max HR or peak MET - 5 Symptom-limited tests to continue till signs or symptoms necessitating termination (i.e., angina, fatigue, ≥ 2 mm of ST↓,ventricular arrhythmias, or ≥10-mm Hg drop in SBP from the resting blood pressure)

42 The incidence of fatal cardiac events(inclu fatal MI & cardiac rupture)-- 0.03%
Nonfatal MI and successfully resuscitated cardiac arrest % Complex arrhythmias, including VT --1.4%. Symptom-limited protocols have an event rate that is 1.9 times that of submaximal tests

Class IIb 1. Patients with the following ECG abnormalities: • Complete LBBB • Pre-excitation syndrome • LVH • Digoxin therapy • >1 mm of resting ST-segment depression • Electronically paced ventricular rhythm 2. Periodic monitoring in patients who continue to participate in exercise training or cardiac rehabilitation. Class III 1. Severe comorbidity likely to limit life expectancy and/or candidacy for revascularization. 2. At any time to evaluate pts with AMI with uncompensated CCF, arrhythmia, or noncardiac exercise limiting conditions. 3. Before discharge to evaluate pts who have already been selected for, or have undergone, cardiac cath. Although a stress test may be useful before or after cath to evaluate or identify ischemia in the distribution of a coronary lesion of borderline severity, stress imaging tests are recommended.

44 Clinical indications of high risk at pre-discharge
Strategy 3

45 Clinical indications of high risk at pre-discharge
Cardiac cath

46 Exercise Testing Before and After Revascularization
Class I 1. Demonstration of ischemia before revascularization. 2. Evaluating recurrent symps suggesting ischemia aft revascularization. Class IIa Aft discharge for activity counseling and/or exercise training as part of rehabilitation in pts aft revascularization. Class IIb 1. Detection of restenosis in selected, high-risk asymptomatic pts < first 12 months aft PCI. 2. Periodic monitoring of selected, high-risk asymptomatic ps for restenosis, graft occlusion, incomplete coronary revascularization, or disease progression. Class III 1. Localization of ischemia for determining the site of intervention. 2. Routine, periodic monitoring of asymptomatic pts after PCI or CABG without specific indications.



49 Stress Testing Modality Sensitivity Specificity Exercise test 68% 77%
Nuclear Imaging 87-92% 80-85% Stress Echo 88-95%

50 Investigation of Heart Rhythm Disorders
Class I 1. Identification of appropriate settings in pts with rate-adaptive pacemakers. 2. Evaluation of cong CHB in pts considering ↑activity/competitive sports. (C) Class IIa 1. Evaluating known or suspected exercise- induced arrhythmias. 2. Evaluation of medical, surgical, or ablative therapy in exercise-induced arrhythmias

51 Investigation of Heart Rhythm Disorders
Class IIb 1. Isolated VPC in middle-aged pts without other evidence of CAD. 2. Prolonged 1˚AV block or type I-2˚AV block , LBBB, RBBB, or VPC in young pts considering competitive sports. (C) Class III Routine investigation of isolated VPC in young pts.

52 Interpreting TMT

53 Normal ECG changes during exercise
↓ PR, QRS, QT ↑ P amplitude Progressive downsloping PR in inf leads j point depression

54 The Exercise ECG 1 = Iso-electric 2 = J point 3 = J + 80 msec
FIGURE 10-8 Magnified ischemic exercise– induced electrocardiographic pattern. Three consecutive complexes with a relatively stable baseline are selected. The PQ junction (1) and J point (2) are determined; the ST 80 (3) is determined at 80 msec after the J point. In this example, average J point displacement is 0.2mV (2mm) and ST 80 is 0.24mV (24mm). The average slope measurement from the J point to ST 80 is −1.1 mV/sec. 1 = Iso-electric 2 = J point 3 = J + 80 msec

55 Criteria for Reading ST-Segment Changes on the Exercise ECG
ST DEPRESSION: Measurements made on 3 consecutive ECG complexes ST level is measured relative to the P-Q junction When J-point is depressed relative to P-Q junction at baseline: Net difference from the J junction determines the amount of deviation When the J-point is elevated relative to P-Q junction at baseline and becomes depressed with exercise: Magnitude of ST depression is determined from the P-Q junction and not the resting J point

56 J point depression of 2 to 3 mm in leads V4 to V6 with rapid upsloping ST segments depressed approximately 1 mm 80 msec after the J point. The ST segment slope in leads V4 and V5 is 3.0 mV/sec. This response should not be considered abnormal. Upsloping

57 ST HR > 130/min ST HR ≤ 130/min

58 Criteria for Abnormal and Borderline ST-Segment Depression on the Exercise ECG
1.0 mm or greater horizontal or downsloping ST depression at 80 msec after J point on 3 consecutive ECG complexes BORDERLINE: 0.5 to 1.0 mm horizontal or downsloping ST depression at 80 msec after J point on 3 consecutive ECG complexes 2.0 mm or greater upsloping ST depression at 80 msec after J point on 3 consecutive ECG complexes

59 Normal Rapid Upsloping Minor ST Depression Slow Upsloping

60 Horizontal Downsloping Elevation (non Q lead) Elevation (Q wave lead)

61 In lead V4 , the exercise ECG result is abnormal early in the test, reaching 0.3 mV (3 mm) of horizontal ST segment depression at the end of exercise. Consistent with a severe ischemic response.

62 The J point at peak exertion is depressed 2
The J point at peak exertion is depressed 2.5 mm, the ST segment slope is 1.5 mV/sec, and the ST segment level at 80 msec after the J point is depressed 1.6 mm. This “slow upsloping” ST segment at peak exercise indicates an ischemic pattern in patients with a high coronary disease prevalence pretest. A typical ischemic pattern is seen at 3 minutes of the recovery phase when the ST segment is horizontal and 5 minutes after exertion when the ST segment is downsloping.

63 Becomes abnormal at 9:30 minutes (horizontal arrow right) of a 12-minute exercise test and resolves in the immediate recovery phase. This ECG pattern in which the ST segment becomes abnormal only at high exercise workloads and returns to baseline in the immediate recovery phase may indicate a false-positive result in an asymptomatic individual without atherosclerotic risk factors.

64 ST Elevation(localising)
Abnormal response J ↑ ≥0.10mV(1 mm) ST 60 ≥0.10mV(1 mm) Three consecutive beats Q wave lead (Past MI) Severe RWMA, ↓EF, ↓Prognosis Non Q wave lead (Past MI) Severe ischemic response Non Q wave lead (No past MI)-1% Transmural reversible myocardial ischemia vasospasm, ↑coronary narrowing

65 A 48-year-old man with several atherosclerotic risk factors and a normal rest ECG result developed marked ST segment elevation (4 mm [arrows]) in leads V2 and V3 with lesser degrees of ST segment elevation in leads V1 and V4 and J point depression with upsloping ST segments in lead II, associated with angina. This type of ECG pattern is usually associated with a full-thickness, reversible myocardial perfusion defect in the corresponding left ventricular myocardial segments and high-grade intraluminal narrowing at coronary angiography. Rarely, coronary vasospasm produces this result in the absence of significant intraluminal atherosclerotic narrowing.(

66 ECG Patterns Indicative of Myocardial Ischaemia
ECG Patterns Not Indicative of Myocardial Ischaemia

67 ECG changes during stress test

68 ST Heart Rate Slope Maximal change in ST with heart rate calculated at the end of each stage Heart rate adjustment of ST segment depression - improve the sensitivity Calculation of the maximal ST/heart rate slope in mV/beats/min - linear regression An ST/heart rate slope >2.4 mV/beats/min - abnormal >6 mV/beats/min - three-vessel CAD.

69 The ST/heart rate index
Average change of ST segment depression with heart rate throughout the course of the exercise test. > abnormal

70 Confounders of Exercise Treadmill Test Interpretation
Digoxin Produces an abnormal ST-segment response to exercise. This abnormal ST depression occurs in 25% to 40% of healthy subjects studied and is directly related to age. Left Ventricular Hypertrophy Decreased specificity of exercise testing, but sensitivity is unaffected. Therefore, a standard exercise test may still be the first test, with referrals for additional tests only indicated in patients with an abnormal test result. Resting ST Depression Resting ST-segment depression has been identified as a marker for adverse cardiac events in patients with and without known CAD. Left Bundle-Branch Block Exercise-induced ST depression usually occurs with left bundle-branch block and has no association with ischemia. Even up to 1 cm of ST depression can occur in healthy normal subjects. There is no level of ST-segment depression that confers diagnostic significance in left bundle-branch block. Right Bundle-Branch Block The presence of right bundle-branch block does not appear to reduce the sensitivity, specificity, or predictive value of the stress ECG for the diagnosis of ischemia. Beta Blocker Therapy For routine exercise testing, it appears unnecessary for physicians to accept the risk of stopping beta-blockers before testing when a patient exhibits possible symptoms of ischemia or has hypertension. However, exercise testing in patients taking beta- blockers may have reduced diagnostic or prognostic value because of inadequate heart rate response.

71 Early repolarization and resting ST↑
Return to the PQ junction is normal Hence ST↓ determined from PQ junction Not from the elevated J point before exercise

72 Duke Treadmill Score Treadmill Score=Exercise time
-5X (amount of ST-seg. deviation in mm) - 4X exercise angina index (0-no angina, 1 angina, 2 if angina stops test). High Risk= -11, mortality >5% annually. Low Risk= +5, mortality 0.5% annually. Ann Intern Med 1987;106:793.

73 ACC/AHA Guidelines: “Patients with a high-risk exercise test result (mortality ≥ 4%/yr), should be referred for cardiac catheterization.”

74 ACC/AHA Guidelines: “Pts. with an intermediate-risk result (mortality of 2% to 3%/yr), should be referred for additional testing, either cardiac catheterization, or an exercise imaging study.”

75 Pseudo normalization pattern
No prior MI Nondiagnostic finding Prior MI Suggests Reversible myocardial ischemia Needs substantiation by rev myo perfusion defect

76 R Wave amplitude LVH Voltage criteria
ST seg – less reliable to ∆ CAD even in the absence of LV strain pattern Loss of R wave (MI) ↓Sensitivity of ST response in that lead

77 U inversion Occasionally in precordial leads at HR<120
Relatively nonsensitive Relatively specific

78 Abnormal BP Response Failure to ↑SBP >120 mmHg
Sustained ↓(15 secs) >10mmHg ↓SBP below resting BP during progressive exe Inadequate ↑ of CO 3VD,LMCA-d,cardiomyopathy,arrhythmias, vasovagal,LVOTobs,hypovolemia, prolonged vigorous exe Normal responses: Increase in SBP (> mmHg) No change or fall in DBP

79 Maximum work capacity Important prognostic measurement
Work performed in METs Not the no: of minutes of exercise

80 Exercise Capacity Stage 2 = 6 - 8 METS Stage 3 = 8 -10 METS
VO max = (mph x 26.8) x (0.1 + [% grade X 1.8] + 3.5 1 MET (metabolic equivalent) = 3.5 ml 0 /kg/min Stage 1 = METS Stage 2 = METS Stage 3 = METS 2 2 Aerobic cost or oxygen consumption.MET=oxygen comsuption at rest.The strongest predictor of death in normal&CAD,1MET=17% reduction in all cause mortality.Data from large study from Mayo (3K pts)& St. James Women Take Heart project.

81 Exercise Capacity “The strongest predictor of the risk of death among both normal subjects, and those with cardiovascular disease”. “Each 1-MET increase in exercise capacity conferred a 12% improvement in survival”. A study from Frolicher, 6200 men followed for 6 yrs. After adjustment for age. NEJM 2002;346:

82 FIGURE Age-adjusted relative risks of all-cause mortality by quintile of exercise capacity in 2534 subjects with a normal exercise test result and no history of cardiovascular disease and 3679 subjects with an abnormal exercise test result or history of cardiovascular disease. The mean duration of follow-up was 6.2 ± 3.7 years. Quintile 5 was used as the reference category. For each 1-MET increase in exercise capacity, the survival improved by 12 percent (From Myers J, Prakash M, Froelicher V, et al: Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 346:793, 2002 N Engl J Med 346:793, 2002.) For each 1-MET increase in exercise capacity, the survival improved by 12 percent N Engl J Med 2002

83 Exercise Capacity In pts. with CAD > 13 METS (Stage IV) prognosis excellent regardless of whether medical or surgical therapy is selected.* Documented CAD, ≥ 2 mm ST-segment depression. Stage IV had a 100% 5-year survival rate.** *Circ 1984;70:226. **Circ 1982;65:482.

84 Exercise Capacity In the Coronary Artery Surgery Study (CASS), patients with 3-vessel disease, and high exercise capacity (≥ 10 METS), showed no benefit from surgery. JACC 1986;8:

85 Heart rate response Inappropriate ↑ at low work load
Anxiety (<1minute-transient) Persisting several minutes AF,physically deconditioned,hypovolemic, anemic,marginal LV function

86 Heart rate response Chronotropic incompetence
Inability to attain THR OR Abnormal HR Reserve(<80%) {%HR Reserve=(HRpeak-HRrest)/(220-age- HRrest)} Autonomic dysfunction,SN dysfuntion, drugs,myocardial ischemia ↑long term mortality (not on β blockers)

87 Chronotropic Incompetence
Framingham Heart Study Circ 1996;93:1520.

88 Heart Rate Recovery During exercise, HR increases due to withdrawal of vagal tone, and increase of sympathetic tone. During recovery, there is a rapid reactivation of vagal tone leading to a decrease in heart rate.

89 Heart Rate Recovery Abnormal: 1 minute TMT (upright) < 12 bpm
TMT (supine) < 18 bpm An upright value <22 bpm at 2 minutes is abnormal Poor prognosis independent of other factors AT 2 MINUTES < 22 BPM IRRESPECTIVE OF BETA-BLOCKER USE.

90 Heart Rate Recovery After Exercise Testing Predicts Outcome in CAD

91 Exercise induced Chest discomfort
Usually after ischemic ST changes May be associated with DBP In some, only chest discomfort In CSA, CP less freq than ST↓ Angina with no ST ↓- MPI useful to assess ischemic severity.

92 Angina during Stress Test
Mortality (+) Stress Test with angina %/yr. (+) Stress Test, no angina %/yr. Circ 1984;70:

93 Markedly Positive Stress Test
ECG changes in the first three minutes. ECG changes that last through recovery. Hypotensive response.

94 Adverse prognosis & multivessel CAD
Symptom limiting exercise < 5METs Abnormal BP response ST↓≥2mm or downsloping ST↓ <5METs, ≥5 leads, persisting ≥5 mins into reco ST↑ Angina at low exercise work loads Reproducible sustained/symptomatic VT

95 Indications for Terminating Exercise Testing
Absolute indications Drop in systolic BP >10 mm Hg from baseline when accompanied by other evidence of ischemia Moderate to severe angina ↑ CNS sympts (ataxia, dizziness, or near-syncope) Signs of poor perfusion (cyanosis or pallor) Technical difficulties in monitoring ECG or systolic BP Subject’s desire to stop Sustained VT ST ↑ (≥1.0 mm) in leads without Q-waves (other than V1 or aVR)

96 Indications for Terminating Exercise Testing
Relative indications ↓ in systolic BP (≥10 mm Hg) in the absence of other evidence of ischemia ST or QRS changes such as excessive ST↓ (>2 mm of horizontal or downsloping ST↓ ) or marked axis shift Arrhythmias other than sustained VT, including multifocal PVCs, triplets of PVCs, SVT, heart block, or bradyarrhythmias Fatigue, shortness of breath, wheezing, leg cramps, or claudication Development of BBB or IVCD that cannot be distinguished from VT Increasing chest pain Hypertensive response


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