A Comparative Study of Different Treadmill Scores to Diagnose Coronary Artery Disease
Condition: Stable Ischemic Heart Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases
Study type: Observational

Summary: 
      Exercise treadmill test (ETT) is frequently done, inexpensive, relatively safe investigation
      for diagnosis of ischemic heart disease and prediction of exercise capacity. Ischemic heart
      disease is increasing by leaps and bounds all over the world even in the developing countries
      like Bangladesh. The incidence rate of coronary artery disease (CAD) is not limited to male
      gender as previously seen. As a cause of industrialization and increased life expectancy,
      incidence of ischemic heart disease in females is escalating now in Bangladesh also. Though
      ETT is a well accepted investigation to diagnose CAD, it has a high false positive and false
      negative result if ST segment response alone is calculated for interpretation of the test.
      Duke Treadmill Test and Simple Treadmill Test are valid and well known scores which can
      predict coronary artery disease burden more efficiently than ST segment response alone.
      Computer generated Cleveland clinic score is another valid treadmill score which has a
      complex algorithm but effective way to predict 3 year and 5 year survivability. These three
      scores are well tested on western population but to our best knowledge there is little or no
      information regarding their predictability of CAD in Bangladesh. It's well known that ETT has
      a high false positive result in female population, so applying the scores may render ETT more
      efficient and abrogate unwanted risk of undergoing coronary angiography to diagnose CAD in
      females. In this study the investigator will try to find out the accuracy of commonly applied
      treadmill scores and ST segment response to diagnose CAD as well as accuracy of computer
      generated Cleveland Clinic Score will be tested. Total 110 people including male and female
      will be included according to inclusion and exclusion criteria and informed written consent
      will be taken. The patients who have undergone ETT and coronary angiogram with in six months
      for confirmation and identification of coronary artery disease in accordance with the
      recommendation of ACC guideline for CAG will be selected . All available data will be
      analyzed using SPSS. The accuracy of different scores will be calculated and compared with
      each other. According to currently available data from studies in western population the
      treadmill scores will have good predictability and will be efficient to abolish high false
      positive result in female population in Bangladesh.
    

Detailed description: 
      Introduction At present several treadmill scores have been proposed as means for improving
      the diagnostic accuracy of the exercise treadmill test (ETT) and to predict future risk of
      cardiac events (Berman et al., 1978 & Do et al., 1997). Although a large number of
      noninvasive stress testing modalities are currently available, the exercise ECG is still used
      as a standard for comparison with other clinical and testing risk markers. It is also the
      least costly of all provocative noninvasive tests. The Duke Treadmill Score (DTS),
      traditionally a prognostic score, was recently tested as a diagnostic score and shown to
      predict CAD better than the ST response alone(Shaw et al., 1998). But questions remain
      regarding the diagnostic accuracy of treadmill scores when applied to a different patient
      population; furthermore, many treadmill scores have not been compared with one another in the
      same population(Fearon et al., 2002).To date, no composite stress-test score or noninvasive
      risk index has been shown to provide both accurate diagnostic and prognostic risk estimates.
      Despite that exercise treadmill test remains a useful test for diagnosing coronary artery
      disease (CAD) in patients with chest pain and at intermediate risk for CAD (Do et al.,
      1997).The sensitivity and specificity of ETT varies considerably. According to a
      meta-analysis conducted by Gianrossi et al there was a wide variability in sensitivity and
      specificity of ETT [sensitivity 68± 16% (range 23-100%); specificity 77±17% (range: 17-100%).
      Another Meta analysis showed sensitivity of 81± 12% (range: 40-100%) and specificity of 66±
      16% (range: 17-100%) (Myers et al., 1994).Fearon WF et al showed sensitivity and specificity
      was higher when treadmill scores were applied in comparison to ST response alone. They used a
      consensus score consisting of the Morise, Dentrano and VA score and found predictive accuracy
      of the consensus score for stratifying patients to low and high likelihood for CAD was
      significantly higher than the predictive accuracy of DTS, 80(74-86)% versus 71(65-77)% (p<
      0.0001). But Fearon WF et al conducted the study only on male population in USA and the
      consensus score was calculated by average of computer generated treadmill scores. In 2012 Mao
      L et al have shown 73 out of 104 male patients were detected CAD both by ETT and CAG, the
      accuracy rate was 70.2% which was much higher than that (50.0%) of the female patients
      (p<0.05) and they only used ST changes alone to demonstrate ETT positivity In this study, we
      will compare the diagnostic accuracy of well known prognostic scores namely, Duke Treadmill
      Score, Simple Treadmill Score and Cleveland Clinic Score to identify significant coronary
      artery lesion in Bangladeshi male and female patients.

      Rationale

      Though exercise treadmill test has high false positive and negative rates(Zang et al., 2007)
      , it is cheap, easily available, less time consuming to the interpret results and its
      accuracy can be increased by calculating ST/HR index, treadmill score, QT dispersion and so
      on (Kronander 2010 &Dentrano 1989). On the contrary the gold standard test coronary angiogram
      for detecting CAD is expensive, time consuming, potentially hazardous with many complications
      and often the CAG shows normal coronary arteries in female population.ST-segment depression
      and chest pain as the classic criteria for CAD diagnosis are well known and accepted. Besides
      If treadmill score were used the diagnostic accuracy of ETT would had been higher. The
      accuracy of different treadmill scores in Bangladeshi population especially the female
      population is largely unknown. Duke Treadmill Score and Simple Treadmill Score are well
      validated score in western population and are used for diagnostic & prognostic interpretation
      of ETT. The predictive accuracy of DTS to diagnose CAD is 71% (Fearon 2002). In 2001 Raxwal V
      et al. showed simple treadmill score has sensitivity of 88% and specificity of 96%. If we
      calculate the accuracy of simple treadmill score using the formula "Accuracy = (Sensitivity)
      x Prevalence + (Specificity) x (1- Prevalence)" it sums up nearly 93% according to prevalence
      of CAD in urban population. Cleveland Clinic Score is a prognostic score of ETT. It gives
      value from which we can predict the probability of 3 year or 5 year survival. It was shown
      that it has a very high negative predictive value approaching 97%. Besides to the best of our
      knowledge Cleveland Clinic Score was not tested as a diagnostic predictor of CAD and there
      are few studies regarding treadmill scores predictability in Bangladesh. In our study we will
      use all of these three scores and compare their accuracy to predict significant CAD. DTS,
      Simplified Treadmill Score, and Cleveland clinic score can be implemented effectively to
      identify patients with low probability of CAD and excluded from undergoing expensive and
      potentially hazardous CAG if the real scenario of the treadmill scores is known in our
      population.

      Research question

      Howdo different treadmill scores (Duke Treadmill Score, Simple Treadmill Score, Cleveland
      Clinic Score) vary to predictability of Coronary Artery Disease in Bangladeshi population in
      a tertiary care hospital?

      General Objectives

      To identify difference of predictability of DTS, Simple Treadmill Score and Cleveland Clinic
      Score to diagnose significant CAD by Coronary Angiography.

      Specific Objectives

        1. To estimate accuracy of ST segment response, DTS, Simple Treadmill Score and Cleveland
           Clinic Score to predict CAD.

        2. To compare DTS, Simple treadmill score, Cleveland Clinic Score accuracy to predict
           coronary artery disease.

        3. To identify the relation of different level of treadmill scores with severity of CAD.

      Study Area

      University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU). BSMMU is a
      renowned institute in Bangladesh with good indoor and outdoor facility. It also has good
      inpatient and outpatient services for local and other patients coming from distant places.
      There is a good mix of male and female patients also which is needed to test the study
      hypothesis. Overall, the patients coming in outdoor facility to get treatment represent the
      Bangladeshi population very well and uniformly.

      Sampling Procedures

      Patient presented with stable chest pain, who have undergone ETT according to Bruce protocol
      and admitted for CAG, will be selected as case considering inclusion and exclusion criteria.
      Detailed and thorough clinical assessment will be done and recorded. All available previous
      medical documents will be checked meticulously. Patients with previous revascularization,
      left bundle-branch block, paced rhythms or Wolff-Parkinson-White syndrome (WPW) on resting
      electrocardiogram (ECG), or valvular heart disease, congenital heart disease will be excluded
      from the study. To avoid falsely increasing the accuracy of the exercise treadmill test,
      patients with a previous myocardial infarction by history or by diagnostic Q wave will be
      excluded.

      With history, clinical findings and investigations cases other than stable chest pain will be
      excluded. Informed written consent will be taken from the patient. CAG report will be
      collected from the Cath lab after the procedure.

      Data collection:

      Data will be recorded in pre-designed questionnaires by history, clinical examination and
      investigation with the patient of University Cardiac Center, BSMMU.

      Quality assurance strategy:

      A set of questionnaire will be formulated & checked. To make the study credible, reliable &
      dependable data will be collected by principal investigator by using those questions over a
      month of period. Again the questions will be edited accordingly & necessarily after
      discussion with the guide and co-guide of this study.

      Ethical Issues At first ethical clearance will be taken from the ethical review committee of
      Bangabandhu Sheikh Mujib Medical University (BSMMU). The study will be carried out according
      to 1964 Helsinki Declaration for Medical Research involving Human subjects and amended by the
      64th World Medical Association General Assembly, October 2013. No drugs or placebo will be
      used for this study. Each participant will enjoy every right to participate or refuse
      participation. They will be free to withdraw their participation at any stage of the study.
      Data taken from the participants will be regarded as confidential. Data will be used only for
      this scientific study. Participants will be informed in detail about the nature and purpose
      of the study, and informed written consent will be taken from each participant.

      Sample size calculation

      Sample size is calculated by using the following equation (One sample comparison of
      proportion):

      n=⌈Zβ√(p(1-p) )+Zα√p1(1-P1)⌉^2/((p-p1)²) n = required sample size p = Proportion under
      alternative hypothesis that is proposed to be detected or worst possible outcome p1=
      Proportion under null hypothesis or proportion in the population Zα = 1.96 (5% level of
      significance) Zβ = 1.28 when power is 0.9 According to Fearon WF et al (2002) the predictive
      accuracy of DTS is 71% (0.71).

      If we assume: p1= 0.71 P = 0.55, Power = 0.8, α = 0.05 Sample size n =

      ⌈1.28√(.55(1-.55) )+1.96√(.71(1-.71))⌉^2/((.55-.71)²) = 91

      Correction for non-response:

      Nf=100/100- Nr If Nr= Percentage of expected non-response is 10% Nf=100/100- 10 = 1.11 Final
      sample size will be estimated sample size (n) x Nf = 91 x 1.11 = 102. So our required sample
      size is at least 102.

      StatisticalMethods Using angiographic evidence of CAD as the reference, area under the curve
      (AUC) of receive operator characteristic (ROC) plots will be determined for the ST response
      alone and for each treadmill score. The AUC for each treadmill score will be compared with
      the AUC of the ST response alone and the AUCs of the other treadmill scores. The predictive
      accuracies of the DTS, the Simple Treadmill Score and Cleveland Clinic Score to stratify
      patients into high or low likelihood for CAD will be calculated and compared. Statistical
      analysis will be performed with the SPSS.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        All stable patients visited University Cardiac Center, Bangabandhu Sheikh Mujib Medical
        University (BSMMU) for evaluation of stable chest pain.
      
Keywords: Treadmill Scores; Coronary Angiogram; Coronary Artery Disease