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ORIGINAL RESEARCH
Ahead of print publication  

Stress Echocardiography Audit: Experience of a Tertiary Care Center


 Department of Cardiology, Fortis Hospital Mulund, Mumbai, Maharashtra, India

Date of Submission23-Sep-2020
Date of Acceptance30-Apr-2021
Date of Web Publication06-Jul-2021

Correspondence Address:
Harin Kamleshbhai Vyas,
Fortis Hospital Mulund, Goregaon-Mulund Link Road, Mulund, Mumbai - 400 078, Maharashtra
India

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_63_20

  Abstract 

Background: Stress echocardiography is a very useful diagnostic and prognostic test in the evaluation of significant coronary artery disease (CAD) causing inducible myocardial ischemia. Stress echocardiography has higher sensitivity and specificity as compared to exercise stress electrocardiography, and therefore, the guidelines recommend opting for the former modality over the latter. There are data suggesting that the incidence of major cardiac events is <1% within 12 months of a negative stress echocardiogram showing no reversible ischemia. The present audit was performed to assess the predictive accuracy of stress echocardiography at our center for major cardiac events during the first year of the test. Methods: Data for all patients referred for stress echocardiography between March 10, 2015 and December 31, 2018 were captured. All patients were contacted after 1 year to evaluate for any cardiac event (cardiac death, nonfatal myocardial infarction, need for revascularization or hospital admission related to acute coronary syndrome, and/or heart failure). Analysis was performed using the standard statistical definitions. Results: Baseline information was available for 1205 patients (mean age 59 years, 60% males). Of these, 416 (34.4%) had documented CAD; 223 (18.4%) underwent stress echocardiography for chest pain evaluation, whereas 273 (22.6%) underwent the test for preoperative assessment before a noncardiac surgery. Dobutamine stress echocardiography was the modality in 1145 (95.0%) patients; ultrasound contrast was used in 1154 (95.8%) patients. One-year event rates were available for 1024 patients. Stress echocardiography was normal in 1009 (98.5%) of these patients, eight of whom had a cardiac event during the subsequent year, yielding a negative predictive value (NPV) of 99.2%. The test was abnormal in 15 (1.5%) patients, but two of them were later found to have normal coronary arteries, yielding a positive predictive value (PPV) of 86.7%. The NPV and PPV were thus both at par or even higher than most other centers. The incidence of complications during stress echocardiography was extremely low. Conclusions: This audit shows that stress echocardiography at our center has an excellent safety as well as accuracy for predicting major adverse cardiac events during the subsequent year. Stress echocardiography could thus obviate the need for coronary angiogram and even revascularization in many patients. Our findings also reinforce the value of stress echocardiography as a greatly useful preoperative test for cardiac fitness in patients undergoing a major noncardiac surgery.

Keywords: Diagnostic accuracy, dobutamine stress echocardiography, echocardiography contrast, exercise stress echocardiography, inducible reversible ischemia, stress echocardiography



How to cite this URL:
Vyas HK, Shah MA, More NV. Stress Echocardiography Audit: Experience of a Tertiary Care Center. J Indian Acad Echocardiogr Cardiovasc Imaging [Epub ahead of print] [cited 2021 Oct 24]. Available from: https://www.jiaecho.org/preprintarticle.asp?id=320782


  Introduction Top


Stress echocardiography is a noninvasive cardiac test to assess myocardial perfusion, viability, and in certain cases, assessment of valves. Myocardial ischemia occurs at cellular level first and then emerges as diastolic dysfunction, systolic dysfunction with reginal wall motion abnormality (RWMA) and finally reduction in left ventricular ejection fraction (LVEF). Electrocardiographic (ECG) changes occur much later in the ischemic cascade, followed by symptoms.[1] Exercise stress electrocardiogram, commonly called as treadmill stress test (TMT), is routinely used to assess significant coronary artery disease (CAD). However, routine TMT frequently gives positive results in the absence of symptoms. Nuclear myocardial perfusion scintigraphy (MPS), widely used for functional assessment, involves nuclear and radiation exposure. Stress echocardiography is superior test than TMT and equivalent to MPS or may be better in specificity. We believe stress echocardiography is underutilized in India due to the lack of understanding and expertise. We share our stress echocardiography experience to highlight its diagnostic and prognostic significance in the management of CAD. Continuous stress echocardiography audit is carried out to assess center's negative and positive predictive value (NPV and PPV, respectively) against global standards. Published literature mentions overall sensitivity of exercise echocardiography (ESE) for detecting CAD ranging from 71% to 97% and specificity ranging from 64% to 100%, with greater sensitivity in multivessel disease. Dobutamine stress echocardiography (DSE) has sensitivity of 67% to 97% (average 80%) and specificity of 65% to 100% (average 84%) for the detection of significant CAD causing inducible reversible ischemia.[2]


  Methodology and Patient Demographics Top


We conduct continuous audit of stress echocardiography studies at our center and in this report, present data of 1210 patients who underwent the test between March 10, 2015, and December 31, 2018. All patients referred to us for stress echocardiography were included into the audit. Beta-blocker, ivabradine, and calcium channel blocker (diltiazem and verapamil) were withheld 48 hours before the test. All patients were kept nil by mouth, 3 hours prior to the test. Written consent was obtained from all patients after detailed explanation.

Basic transthoracic echocardiography was performed for all to rule out obvious contraindications, i.e., cardiac mass or clot, severe valvular stenosis or regurgitation, obvious nonviability, etc. Patients were selected for either ESE or DSE depending on the history of CAD and ease of obtaining echocardiography images. All patients had apical four-chamber, apical two-chamber, apical three-chamber, and parasternal long-axis and short-axis image acquisition for all stages.

Patients with no documented CAD with good exercise capacity and clear echocardiography images in spite of respiratory variation were selected for ESE; rest were selected for DSE. Echocardiography contrast, i.e., SonoVue (Sulfur hexafluoride; Bracco Imaging, Milan, Italy) or Definity (perflutren lipid microsphere; Lantheus Medical Imaging, Billerica, MA, USA) was used in patients if more than two left ventricular (LV) segments were not visible clearly. Contrast was also used for the assessment of myocardial perfusion and in patients with left bundle branch block (LBBB) or if the rhythm changed to atrial fibrillation.

In ESE, patients had baseline echocardiography screening followed by treadmill exercise using Bruce protocol. Patients were encouraged to go beyond target heart rate (THR) to ensure image acquisition at or above THR. Patients postexercise repositioned themselves onto echocardiography couch as soon as possible. Sixty seconds was considered as the cutoff for acquisition of peak exercise images from the time treadmill was stopped. Patients requiring echocardiography contrast had intravenous (IV) line inserted in upper limb and echocardiography contrast given for the rest and peak images.

In DSE, patients had IV line after initial echocardiography screening. Patients needing echocardiography contrast had one dose before every stage. Dobutamine dose ranging from 5 to 40 mcg/kg/min was given with 3 min increment till achievement of THR. Atropine was given in addition, if THR could not be reached with dobutamine alone. Images were obtained at baseline and during low dose, intermediate dose/stress, peak dose/stress, and recovery phases. Images of all stages were compared for any RWMA and myocardial thickening to determine reversible ischemia and/or viability. Majority reports were dispatched within half an hour along with the study images on a digital versatile disc.

All studies were performed on Philips Epiq7c (Andover, MA, USA) machine, under direct supervision of senior cardiologist with specific interest and training in cardiac imaging, especially in advance echocardiography.

All the data were recorded in a Microsoft Excel worksheet. Telephonic follow-up was done at the end of 1 year to enquire about any cardiac event that may have happened in the form of acute coronary syndrome (ACS), chest pain, heart failure, or cardiac-related hospital admission or further intervention. Positive reports for reversible ischemia were tracked for the outcome, wherever possible.

Various statistical parameters were analyzed as per standard definitions.

Definitions used for reporting

  • Negative for reversible ischemia: If LV contractility is normal (no RWMA) at baseline and contracts well with stress
  • Positive for reversible ischemia: If LV contractility is normal (no RWMA) at baseline and reduces (RWMA seen) with stress
  • Positive for reversible ischemia and viable: If LV contractility is reduced to start with (RWMA seen) RWMA seen but improves at low/intermediate stress and then reduces again at intermediate/peak stress
  • Negative for reversible ischemia and viable: If LV contractility is reduced to start with (RWMA seen), but continues to improve at low/intermediate/peak stress
  • Negative for reversible ischemia and nonviable: If LV contractility is reduced to start with (RWMA seen) and does not improve at low/intermediate/peak stress
  • Cardiac event within 1 year: Cardiac death, nonfatal myocardial infarction, need for revascularization, heart failure or cardiac event-related hospital admission within 1 year of stress echocardiography
  • True positive: If the patient had cardiac event within 1 year of a positive stress echocardiography
  • True negative: If the patient had no cardiac event within 1 year of a negative stress echocardiography
  • False positive: If the patient had no cardiac event within 1 year of a positive stress echocardiography and no intervention done
  • False negative: If the patient had cardiac event within 1 year of a negative stress echocardiography and/or intervention done.


Population characteristics

The clinical characteristics of the study population are presented in [Table 1].
Table 1: Population characteristics (n=1210)

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Out of 1210 patients, 1045 patients (86.4%) were referred from the outpatient department and 165 patients were referred from the inpatient department. Majority of them (808; 66.8%) were referred by cardiologists, whereas 19 patients (1.6%) were referred from cardiac surgical department and 383 patients (31.7%) were referred by other specialists. Data of five patients were missing due to technical issues with the Hospital Information System (HIS) and excluded from the statistical analysis. A total of 1161 patients (96%) were referred for the assessment of inducible ischemia, 42 patients (3.5%) for viability study, and two patients (0.2%) were referred for aortic stenosis (AS) assessment. A total of 1145 patients (94.6%) underwent DSE, while 60 patients (5%) underwent ESE [Figure 1]. Majority of the patients underwent DSE due to the strict criteria of being able to see all segments at peak and able to capture all images within 60 s of stopping the treadmill for ESE. Anyone with significant respiratory variation at rest, tested by asking them to take a few big breaths, was not subjected for ESE. Any person with existing RWMA was not subjected to ESE. Resting RWMA if shows improvement at low and intermediate dose, shows viability. If this improvement goes down at peak, indicates reversible ischemia which will be missed if only rest and peak images are obtained as in ESE. Anyone with existing CAD was not subjected to ESE to assess response at low and intermediate dose and to assess for perfusion by myocardial contrast enhancement if required.
Figure 1: Year-wise distribution of patients undergoing dobutamine stress echocardiography (DSE) and exercise stress echocardiography (ESE)

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Contrast was used in 1102 out of 1145 (96%) patients undergoing DSE and 52 out of 60 (87%) patients undergoing ESE. Most patients needed contrast due to departmental policy of using echocardiography contrast where endocardium of more than 2 out of 17 LV segments was not clearly visible. Atropine was used in 962 out of 1145 (84%) patients undergoing DSE. THR was achieved in 94.6% of the patients, as shown in [Table 2].
Table 2: Achievement of target heart rate during stress echocardiography

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The incidence of complications during stress echocardiography was very low, as shown in [Table 3]. The frequency distribution of various arrhythmias (sustained as well as nonsustained) during stress echocardiography is shown in [Table 4].
Table 3: Complications during stress echocardiography

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Table 4: Frequency distribution of arrhythmias (sustained and nonsustained)

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Statistical analysis

A total of 1210 patients underwent stress echocardiography from March 10, 2015, to December 31, 2018. Out of these, we were unable to get 1-year follow-up details for 148 patients (unable to contact, missing information or no further work-up done). In 2015, we had missing data of 20% of cases, mainly due to inability to contact them after 1 year. Initially, most of the phone numbers were collected from HIS, but later phone numbers were confirmed and recorded at the time of performing the test. This simple measure helped us reduce this number to 6% in subsequent years. This highlights the importance of meticulous data entry in HIS. Of the remaining 1062 patients, 1024 patients were tested for inducible ischemia, 36 patients for viability, and two patients were tested for aortic valve assessment [Figure 2]. Hence, 1024 patients were considered for the assessment of NPV and PPV of stress echocardiography in our department, in predicting cardiac events within 1 year of follow-up.
Figure 2: Distribution of primary subgroups referred for stress echocardiography. AV: Aortic valve

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  Results Top


Out of 1024 cases, there were 15 positive (1.5%) and 1009 negative (98.5%) stress echocardiograms. One-year follow-up revealed 13 true positive, 1001 true negative, two false positive, and eight false negative results.

Overall, the incidence of cardiac events and stress echocardiography outcome is summarized in [Figure 3]. The PPV was 86.7% and NPV was 99.2% [Figure 4].
Figure 3: Statistical analysis data for cardiac events at 1 year

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Figure 4: Statistical analysis data for positive predictive value and negative predictive value for cardiac events at 1 year.
NPV: Negative predictive value, PPV: Positive predictive value


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In preexisting CAD subset (n = 335), PPV and NPV were 100% and 99.1%, respectively.

Thus, cardiac event-free survival rate at 1 year was 99.2% and 99.1% after a negative stress echocardiography in total study population as well as in the preexisting CAD subset, respectively.


  Discussion Top


In this audit of 1210 patients from a single center, we found very high NPV and PPV (99.2% and 86.7%, respectively; n = 1024) for stress echocardiography in predicting future cardiac events (cardiac death, nonfatal myocardial infarction, need for revascularization, heart failure, or cardiac event-related hospital admission) within 1 year of test.

True positive cases

There were 13 true positive cases where significant CAD was found on coronary angiogram (CAG). Out of these, two patients underwent coronary artery bypass grafting (CABG), six patients underwent percutaneous coronary intervention (PCI), and five patients were medically managed-two patients were post CABG, one patient had end-stage renal disease (ESRD) with diffuse CAD and two patients chose medical management. In two cases, impaired LVEF normalized within 3 months of revascularization (one had CABG and other had PCI to left anterior descending artery[LAD]).

True negative cases

There were 1001 true negative cases with no cardiac events within 1 year. Five cases were classified as false negative in spite of negative DSE as they had undergone revascularization. We were unsure for exact reason of revascularization in three cases, one patient had CABG along with aortic valve replacement (AVR) and one had reversible impairment in LVEF due to chemotherapy. We describe these cases in detail for better understanding.

A 78-year-old patient with right-sided chest pain and nonspecific ECG changes, despite negative DSE, underwent CAG which revealed multivessel CAD and CABG was performed. Second 68-year-old patient with previous PCI to LAD, left circumflex (LCx) and right coronary artery (RCA), but multivessel CAD on recent CAG, was referred for inducible reversible ischemia assessment. Despite negative DSE, the patient underwent CABG. Third patient with 60%–70% lesion in LAD was referred for inducible ischemia assessment, despite negative DSE, the patient underwent PCI to LAD. There is enough data and COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial clearly demonstrated no significant prognostic benefit between revascularization vs optimal medical therapy in stable CAD.[3]

One 66-year-old male with known AS underwent DSE for occasional left arm pain. The study revealed no inducible ischemia but the gradient across aortic valve increased from 51/28 to 91/48 mmHg at peak stress. Later, he underwent AVR with CABG.

Another 54-year-old female with Hodgkin's lymphoma, underwent DSE in view of chest pain. Baseline images revealed global hypokinesia with LVEF ~45%, but with incremental dobutamine stress, LV contractility improved. However, further three cycles of chemotherapy with doxorubicin led to global hypokinesia with markedly reduced LVEF (5-10%). LV function returned to baseline within 3 months of chemotherapy discontinuation.

False positive cases

Out of two false-positive cases, one patient, 46-year-old male, with no cardiac risk factors and normal echocardiography, underwent DSE for evaluation as a prospective kidney donor. Peak stress revealed global LV hypokinesia (LVEF <35%) with paradoxical motion of septum and anteroseptum, which persisted in recovery phase. The patient had chest pain and LBBB on ECG. Subsequent CAG revealed normal coronaries.

Second patient, 46-year-old female with hypertension and ESRD, underwent DSE for renal transplant cardiac fitness. Baseline echocardiography showed global hypokinesia (LVEF 44% by Simpson's biplane method). Low and intermediate dobutamine stress led to improvement in contractility which reduced severely at peak stress (LVEF 23% by Simpson's method). ECG showed T-wave inversion in inferior-lateral leads. LV systolic function returned to baseline during recovery. Subsequent CAG was normal. In hindsight, we feel both patients may have had stress-induced cardiomyopathy with takotsubo phenomenon. Both these patients did not have any cardiac event during the subsequent one year.

This observation is to emphasize the fact that dobutamine administration can lead to stress cardiomyopathy as a rare complication.[4]

False negative cases

Out of eight false-negative cases, one patient was a 50-year-old hypertensive male who underwent preoperative DSE for Whipple's surgery. DSE was negative for inducible ischemia and surgery was uneventful, but the patient had ACS after 10 months of the test requiring PCI to LCx. Second patient, 55-year-old female, with hypertension and diabetes underwent DSE for total knee replacement (TKR) fitness. Surgery was uneventful but she had an ACS after 6 months needing angioplasty (exact details are unavailable).

Third patient, 69-year-old male, underwent DSE for breathlessness with a history of hypertension, ESRD on dialysis, and CAD (prior PCI to LCx). He had an ACS 8 months after the test and CAG revealed patent stent in LCx but 80% lesion distally requiring angioplasty.

All three cases had cardiac event after 6 months of the test, and all of them had significant cardiac risk factors. In general, a normal stress echocardiography carries a very low risk (<1% per year) of major cardiac events in the first year. Some studies show low risk for 4–5 years.[5],[6] In our study also, the event rate was <1% within one year after a negative stress echocardiography which is consistent with the published literature.

Remaining five cases who were classified as false negative based on the definition have been described in true negative cases.

Further analysis of data revealed some interesting outcomes as described below.

Chronotropic incompetence in liver cirrhosis and end-stage renal disease

Out of 63 patients where THR could not be achieved despite maximum pharmacological stimulation [Table 2], 31 patients (49.2%) had either chronic liver disease (22, 34.9%) or ESRD (9, 14.3%). This can be attributed to liver cirrhosis and ESRD leading to autonomic dysfunction and chronotropic incompetence in some patients.[7],[8]

Stress echocardiography in asymptomatic positive treadmill stress test: Should all patients with positive treadmill stress test undergo coronary angiography?

A total of 138 asymptomatic individuals with positive TMT during health checkup underwent stress echocardiography during the audit period. All of them had negative DSE with no cardiac events in the following year. Unnecessary CAG, leading to radiation and nephrotoxic contrast exposure, was avoided.

Exercise stress ECG test has a modest sensitivity and specificity for diagnosing CAD,[9] and the evidence suggests that it has a higher efficacy for excluding significant CAD rather than confirming.[10] There are several factors which limit the ability of ECG to detect transient ischemia.[11] The higher false positivity and false negativity makes it a nonideal test for the detection of CAD in various settings. As per the ischemic cascade [Figure 5],[1] ischemia at cellular level first leads to diastolic and then systolic dysfunction which is followed by ECG changes and lastly symptoms of angina. This means that DSE can pick up signs of inducible ischemia even before ECG changes develop. In addition, emergence of ECG changes but no RWMA during stress indicates false-positive ECG changes. Thus, stress echocardiography proves better than exercise stress ECG test in terms of diagnostic accuracy for detecting inducible ischemia.[6]
Figure 5: Ischaemic cascade. Sequence of pathophysiological events after a coronary artery occlusion. Different investigations can identify ischemic manifestations at different preclinical (yellow) and clinical (orange) stages

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Stress echocardiography with existing coronary artery disease on coronary angiogram: Do all patients with coronary artery disease need revascularization?

Out of 62 patients with >50% CAD, only four patients (6.45%) had positive DSE requiring revascularization; rest of the patients were medically managed without any cardiac events in the following year. This reinforces COURAGE trial findings and supports the early results of ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial which included patients with stable CAD with moderate-to-severe ischemia and followed-them up for a median duration of 3.2 years. Early invasive strategy did not reduce risk of the primary endpoint of cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest as compared to a conservative strategy.[3],[12]

Another study to evaluate prognostic value of stress echocardiography showed negative DSE in angiographically significant CAD, conferring benign prognosis with event rate <1% per year. Thus, stress echocardiography added incremental prognostic value to coronary angiography.[13]

Fractional flow reserve (FFR) is used by many centers to assess significant CAD, which can be easily achieved by noninvasive stress echocardiography with much lower cost. Assessment of myocardial wall thickening during stress echocardiography is a surrogate marker for coronary flow reserve (CFR) which cannot be assessed by FFR as it gives information about only epicardial coronary circulation.[14] CFR is the ratio of myocardial blood flow at maximal metabolic demand to the myocardial blood flow at rest. It is important to note that a patient with normal FFR but abnormal CFR, has a worse prognosis than a patient with an abnormal FFR and a normal CFR.[15] Stress echocardiography can be a good alternative to FFR in prognostication of future cardiac events in CAD.

Stress echocardiography in preoperative cardiac fitness

It is imperative to assess perioperative risk in patients with significant comorbidities who are undergoing noncardiac surgery. Lot of these patients have poor mobility due to various reasons, making it difficult to assess actual exercise tolerance.

Out of 337 patients, who underwent DSE for preoperative cardiac fitness, 91 patients (27%) had preexisting CAD. There were 332 true negative cases with uneventful peri-operative course. Two cases were labelled as false negative, as they did have cardiac event within the year, but none had perioperative cardiac complications. These cases have been discussed in detail in earlier section.

Two patients had positive DSE with reduction in LVEF during stress but had normal CAG. As mentioned earlier, these could be due to takotsubo phenomenon. This, although false positive, can help in predicting cardiac response to surgical stress and guiding treating physician to optimize medical therapy.[16] One case for elective TKR had true positive DSE and angiography showed significant CAD, requiring revascularization. Elective surgery was postponed, and possible perioperative complication avoided.

Epidemiologically, CAD is considered as the leading cause of peri-operative morbidity and mortality following general and vascular surgeries. As there are limitations to the exercise stress testing, owing to limited exercise capacity, either due to arthritis or other debilities, pharmacological stress echocardiography appears to be the first choice in this subgroup of patients.[17]

Limitations

All patients did not undergo CAG, so sensivity and specifity of stress echocardiography in identifying CAD could not be determined.

Majority of our population seems low risk as judged by the very low rate of abnormal stress echocardiograms. Therefore, it may have inflated our NPV.

We did not collect cardiac risk factors data to calculate atherosclerotic cardiovascular disease risk to risk stratify patients further.


  Conclusions Top


Stress echocardiography with contrast performed in our laboratory had very high NPV (99.2%) and PPV (86.7%) in predicting future cardiac events (cardiac death, nonfatal myocardial infarction, and need for revascularization) within 1 year. Majority of patients had DSE with contrast with very low incidence of complications. Stress echocardiography seems suitable for majority of the patients with very few exclusion criteria. All asymptomatic positive TMT cases may not need to undergo CAG. Patients having CAD on angiography do not always need revascularization. Stress echocardiography is a useful tool in the assessment of cardiac fitness for general and vascular surgeries. Stress echocardiography has incremental value in the prognostication of CAD. Stress-induced cardiomyopathy, although rare, can occur during stress echocardiography. Chronic liver and kidney disease patients are more likely to show chronotropic incompetence due to autonomic dysfunction.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
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2.
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Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-16.  Back to cited text no. 3
    
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McCully RB, Roger VL, Mahoney DW, Karon BL, Oh JK, Miller FA Jr, et al. Outcome after normal exercise echocardiography and predictors of subsequent cardiac events: Follow-up of 1,325 patients. J Am Coll Cardiol 1998;31:144-9.  Back to cited text no. 5
    
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Klein DA, Katz DH, Beussink-Nelson L, Sanchez CL, Strzelczyk TA, Shah SJ. Association of chronic kidney disease with chronotropic incompetence in heart failure with preserved ejection fraction. Am J Cardiol 2015;116:1093-100.  Back to cited text no. 8
    
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Pais P. Treadmill stress tests should not be part of “routine health check package”. Indian Heart J 2018;70:934-6.  Back to cited text no. 9
    
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Herring N, Paterson DJ. ECG diagnosis of acute ischaemia and infarction: Past, present and future. QJM 2006;99:219-30.  Back to cited text no. 11
    
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Al-Lamee R, Jacobs AK. ISCHEMIA trial: Was it worth the wait? Circulation 2020;142:517-9.  Back to cited text no. 12
    
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Yao SS, Wever-Pinzon O, Zhang X, Bangalore S, Chaudhry FA. Prognostic value of stress echocardiogram in patients with angiographically significant coronary artery disease. Am J Cardiol 2012;109:153-8.  Back to cited text no. 13
    
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Bioh G, Senior R. Stress echocardiography in the era of fractional flow reserve. Curr Cardiovasc Imaging Rep 2020;13:2.  Back to cited text no. 14
    
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van de Hoef TP, van Lavieren MA, Damman P, Delewi R, Piek MA, Chamuleau SA, et al. Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity. Circ Cardiovasc Interv 2014;7:301-11.  Back to cited text no. 15
    
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Medina de Chazal H, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D, et al. Stress cardiomyopathy diagnosis and treatment: JACC state-of-the-art review. J Am Coll Cardiol 2018;72:1955-71.  Back to cited text no. 16
    
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Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2008;9:415-37.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

 
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