Table 2. Public Review Comments: Appendixes
The full comments from Dr. Miceli follow.
-60-year-old male with family history of coronary artery disease, hyperlipidemia and hypertension — Asymptomatic —Negative stress echocardiograms— MCG score of 2 — On his own went for cardiac catheterization with 20% LAD obstruction seen
This case emphasizes that the low score was indicative of only mild disease and this patient could have avoided cardiac catheterization.
-History of hypertension and hyperlipidemia -Elevated calcium score in 2007 -MCG score of 3.5 and asymptomatic -Stress echocardiogram: Difficult to perform. Exercise for 11 minutes and 30 seconds. Suggestion of septal hypokinesis in all views.
-Patient elected to go for cardiac catheterization
Catheterization: Showed normal coronary arteries with a mild diminished left ventricular function and mild diffuse left ventricular hypokinesis consistent with a mild cardiomyopathy.
This case emphasizes again the low score would indicate no significant obstruction. However patients with cardiomyopathy can have an elevated score. His true score was probably lower.
-80-year-old female with shortness of breath with exertion -Risk factor of hypertension and diabetes -MCG score of 8 -Cardiac catheterization: Significant critical right coronary artery lesion.
-Patient underwent stenting
-A few weeks postoperatively she presented with atypical chest pain -Repeat MCG score was now zero
-2 days later she complained of chest pain that sounded like GERD -Repeat MCG score still zero -Cardiac catheterization repeated and stent open
This case exemplifies how a severe score predicted significant disease and how after stenting, the MCG score could now predict whether or not the patient had a patent stent. Her chest pain was related to GERD not coronary artery disease.
-Patient weighed over 350 pounds
-Patient had prior coronary artery stenting many years ago -The patient developed shortness of breath, questionable secondary to weight -MCG score of 7.5 -Cardiac catheterization: Stent restenosis. Patient underwent angioplasty and stenting -Patient no longer short of breath
-8 months later patient developed shortness of breath just tying his shoes -Patient insisted the stented closed -Repeat MCG score of 2 -Repeat cardiac catheterization showed stents patent
This case shows how a high score predicted disease. Stenting caused a marked drop in his score. It predicted that the cardiac catheterization would be normal.
-Patient wheelchair-bound, heavyset with a history of right coronary artery occlusion -Patient admitted to the hospital with congestive heart failure -Troponin level was positive -ST segment elevations in the anterior precordium -Cardiac catheterization: Total right coronary artery obstruction but LAD was normal -The patient had repeated episodes of congestive heart failure -Repeat cardiac catheterization without change -Patient presented to me for evaluation -I suspect the coronary artery spasm -I did 5 MCG tests showing "consistently inconsistent numbers"
-This was consistent with coronary artery spasm -Patient was placed on Procardia and she's been asymptomatic since
This case shows how MCG can predict coronary artery spasm. Since this case I have had many others in which there is "consistently inconsistent numbers". This is where a score can vary between zero and an elevated number in multiple tests without consistency.
-60-year-old male with prior inferior wall myocardial infarction -MCG score 5.5, May 20, 2008 -MCG score 5.0 March 20, 2009 -CTA 2008-LAD greater than 65% obstruction, right coronary artery obstructed -Patient refused cardiac catheterization -Patient asymptomatic
This case exemplifies how MCG scores are very consistent even a year later. In my experience I found a patient can have a score of 2.0 and a year later be the same and another patient can have a score of 4.5 and be the same a year later. It also reflects a score of 5 being consistent with coronary artery disease.
-67-year-old male with multiple cardiac stents -Always asymptomatic -Stress echocardiogram periodically very abnormal -Each time he goes for an angiogram, it shows a significant lesion needing a stent -MCG score 4.0 on May 2008 -CTA showed patent stents -Patient developed a kidney stone and needed a ureteral stent -During his hospital stay he developed new right bundle branch block and atrial fibrillation -EKG showed new inferior- posterior wall myocardial infarction -After hospitalization MCG score repeated and was 7 -Tracings pre MI and Post MI difference was night and day -Graph of power in Watts versus frequency in Hertz, showed very little power produced from his heart after the myocardial infarction.
This case exemplifies the elevated score being consistent with a recent infarction and ischemia. It also shows how the recent myocardial infarction affected the power spectrum giving credence to the mathematical formulations produced by the MCG technology.
-63-year-old female with prior coronary artery disease -Cardiac catheterization 2007: 50-60% stenosis of the circumflex -LAD had a 50% lesion -Patient had stent to a large right posterior descending branch -Asymptomatic on medical treatment -MCG score 1.5, repeated last year at 3 and now 4.5 -Her stress test was normal until MCG 4.5 -Recent stress echo showed new septal hypokinesis with exertion -Repeat cardiac catheterization showed severe disease in the circumflex and LAD -Patient underwent cardiac stenting to these lesions
This exemplifies how MCG scores can be used in a serial fashion to monitor an individual who was coronary artery disease and predict when a stress test would become positive. Her initial low MCG score was probably secondary to collateral circulation.
-66-year-old female who needed an abdominal aneurysm resection -MCG score of 2.5 and 3 -History of emphysema -Stress echo: Poor exercise capacity of only 3 minutes with shortness of breath -Did shortness of breath represent emphysema or an anginal equivalent?
-Stress echo showed possibility of inferior and septal hypokinesis but heart rate very low and inadequate exercise -Cardiac catheterization preoperatively negative
This case shows how MCG scores can be used preoperatively for medical clearance. A low score would indicate the patient did not need further workup. A higher score would indicate the need for cardiological consultation and workup prior to surgery. This particular individual needed cardiac catheterization because of high risk surgery but in less high risk surgeries, a low MCG score would indicate low risk for cardiac disease and the patient could be cleared medically.
In my practice, the MCG test is invaluable.
How do I use it?
-score of 0----Reassuarance.
-score of 1or 2---Exercise, life style modification, asa and Statin. Retest in 1 year.
-score of 3---Most likely like scores of 1 and 2. Treat the same but add stress test.
If abnormal stres, treat as 4-7.
-score of 4-7---Treat as 1-3, but add stress testing. If positive send for cath. If negative (50% will have negative stress test), consider adding beta blocker or other agents as in the Courage Trial and retest in 3 months. Follow carefully. Cath if symptoms occur.
-scores greater than 7---Verify the accuracy with repeat testing, treat as 4-7 and consider cath or at least cta of coronary arteries.
-MCG provides a role for the detection of coronary artery disease, the continued followup and evaluation of coronary artery disease, as well as in the pre-operative evaluation. Coronary artery spasm can be detected, as well.
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The full comments from Dr. Strobeck follow.
Peer Review Report — John E. Strobeck, MD, PhD Introduction
I believe that the stated goals of the draft TA assume an existing US coronary diagnostic paradigm into which the MCG technology does not fit. The core assumption of the TA is that new ECG-based technologies will be better than the traditional ECG at “evaluating” symptomatic patients who are at low or intermediate risk of coronary events (according to the ACC/AHA 2002 Guideline Update for Exercise Testing ) or coronary artery disease. Thus, the diagnostic paradigm assumed in the TA document is that newer ECG technologies are “add-on” technologies that will merely improve the treating physician's ability to select patients for stress-ECG testing or stress-imaging with either echocardiography or scintigraphy. The MCG is not designed to fit this paradigm because it is designed to be a highly accurate predictor of who does not need stress testing or coronary angiography. That is why MCG was compared directly to coronary angiography in several prospective double blind clinical trials in which it predicted with over 87% accuracy whether patients have actual coronary stenosis requiring intervention or not. MCG does more than “evaluate” patients who are at low or intermediate risk of having coronary artery disease, as a first step in the traditional diagnostic algorithm -it can render other diagnostic tests unnecessary and may allow selected patients to proceed directly to angiography. In other words, the MCG clinical trials asked a different question than that being asked in the draft TA, namely, whether MCG could accurately predict which patients, from a group whose physicians believed needed coronary angiography, actually did need coronary angiography because they had relevant coronary stenosis. As a result of this consideration, it appears that the draft TA's underlying assumptions, and objectives, are not completely in synch with how MCG works and with the MCG clinical trial design and results. I am pleased that the authors evaluated the MCG technology and found the published trials to have been well-designed and conducted. The final TA should include MCG and contain a more detailed discussion of, the technology. To this end, I have three major concerns about the draft TA that will be discussed in my peer review: 1) the author's description of the MCG technology is inaccurate, 2) the assessment of the population selected for the clinical trials data is inaccurate, and 3) the conclusions with respect to the demonstrated clinical usefulness of MCG and its current status as a diagnostic tool are inaccurate.
Through highlighting and commenting on these issues, it is my hope that the information provided in my peer review will be helpful to the authors, and that they will seriously consider my comments, research analysis, and my real-life community clinical experience using MCG when they prepare the final version of the TA document. I have come to the conclusion, after a full review of the underlying biomathematics and basic science of the MCG technology, the prospective MCG clinical trial design and data analysis, and the first-hand clinical experience I and many other physicians in the US and world-wide have had with the device in our clinical practices, that the MCG is a well-validated diagnostic tool, and, that if used early in a symptomatic patient's evaluation, is able to very accurately predict which patients who are considered “at low or intermediate risk” of coronary artery disease by ACC/AHA 2002 criteria , actually do not have relevant coronary stenosis at the time of examination (i.e. stenosis >70% in one or more major epicardial coronary vessels or >50% left main stenosis which would require percutaneous or surgical coronary intervention) and, therefore, do not need further advanced stress testing, stress-imaging, angiography, or hospital admission for the detection of significant coronary disease.
Classification of the MCG, How it Works, and How it Differs from the SAECG
With regard to the description of the technology, there are fundamental differences between the MCG technology and conventional ECG measurements and analysis techniques. First and foremost MCG is simply not a signal averaging electrocardiogram (SAECG). In order to properly evaluate the MCG, it is critical that the authors fully appreciate the mathematical and “systems-analysis” approach relying on a digitized “reference clinico-pathologic database” against which the MCG analyzes the recorded electrocardiographic signals forming the basis of the test.
MCG is a computer-based, systems-analysis tool, using a computational mathematic model based on LaGrange-Eüler coordinates to measure the stress-strain relationships between the myocardium and intracardiac blood flow. MCG converts data obtained from two resting left ventricular leads (V5 and Lead II) into multiple mathematical functions useful in the detection of the presence or absence of obstructive coronary disease and local and/or global myocardial ischemia due to relevant coronary stenosis (defined as > 70% stenosis of the large epicardial coronary arteries and > 50% stenosis of the left main coronary artery).
The draft TA incorrectly defines MCG as being a type of Signal Averaging ECG (SAECG). On page 15 of the assessment, the TA contains the following definition of SAECG:
SAECG is a noninvasive technique for computing the average of numerous ECG complexes, which, in turn, increases the signal-to-noise ratio, allowing for the detection of small, microvolt signals. This technique is most often used in the detection of low amplitude signals at the terminal portion of the QRS complex (also known as ventricular late potentials). These late potentials may reflect inflammation, edema, fibrosis, or infarct, but not ischemia
Then under the title “SAECG-Based Device”, on page 27, implying ECG-based Signal Analysis device, the draft TA describes the general operations of MCG as the following:
The 3DMP device (also referred to as 3DMP/MCG/mfEMT) utilizes ECG data from two of the 12 standard leads (leads II and V5), to perform frequency and time domain analyses. Recordings for over 82 seconds are amplified, digitized, encrypted, and sent securely over the internet to Premier Heart Datacenter where signal analysis and six mathematical transformations are performed. The data are matched to a large empirical database to determine a "Final Diagnosis" and "Severity Score" and securely reported these data back over the internet within several minutes to the requesting provider.
It appears to me that the authors did not realize that the MCG is not a Signal Average ECG technology, and that it does not detect low amplitude late potentials from the terminal portions of the QRS complexes to reflect inflammation, edema, fibrosis, or infarct [Page 15]. In fact, MCG technology completely ignores the familiar time-based ECG waveforms such as the traditional P, QRS (including the late potentials), ST, and T waves that are typically read from an analog ECG plot in favor of an entirely new diagnostic paradigm-shift toward direct detection and quantitative measurement of myocardial ischemia due to CAD. The 166 indices extracted by submitting the ECG signals to multiple mathematical transformation functions represents new information that conventional ECG methods have never been able to show or analyze in the past.
For further clarification, the MCG technology harvests multiple cycles of resting ECG analog signals from leads II and V5, then digitizes, encrypts and securely transmits the resting ECG data along with the patient's demographic information to Premier Heart's data center for processing. After receipt of the data by the server, the system performs a Fast-Fourier-Transformation of the signals from each lead, preparing them for further mathematical transformations, including determination of the auto-power spectrum, the transfer function, the phase-angle shift, the impulse response, the coherence function, and the cross-correlation function of each lead. The details of the six functions have been discussed elsewhere. [1, 2, 26]. These six transformation functions, along with the amplitude histogram of leads II and V5 comprise the backbone of the systems-analysis “engine,” which evaluates the dynamic interactions between heart muscle chambers and the intracardiac blood flow. Abnormal expressions of these functions can assist physicians in the detection of coronary ischemia from very early to very late stages. The functions are used to extract the non-linear functional relationships between the two leads, which are distilled to a set of indices, and then matched against existing patterns in a large empirical database to determine the presence or absence of local and/or global ischemia, and produce an overall disease severity score, 0-20, completely unlike the conventional ECG technologies cited in the draft Technology Report (See Fig. 1 below for an overview of the MCG process).
Fig. 1 — MCG Operational Flowchart
Reproduced with permission from Premier Heart, LLC
Table I. below is a useful comparison between the conventional ECG Analysis — a reductionistic approach, and MCG Analysis — a systems-analysis approach. Among
the significant differences to be noted are:
- A conventional ECG adopts the Einthoven Model — a plot of voltage over time which only considers the unidirectional electrical output of the heart — where MCG's approach is based on a LaGrange-Eüler mathematical model which reflects the multidimensional interaction between the myocardium (the solid) and intracardiac blood flow (the liquid) in a dynamic system (the beating heart).
- Where conventional ECGs (including SAECG) focus on portions of single cardiac cycles on individual leads, MCG instead uses an integrative “view over time”, operating on two leads simultaneously and evaluating multiple cardiac cycles. This allows MCG analysis to extract non-linear, multifunctional relationships which reveal latent information unavailable to conventional ECG techniques.
- Conventional ECG typically requires a subjective “over-read” by an experienced clinician to avoid misdiagnosis, which introduces both subjectivity and delay. In contrast, MCG's extensive, clinically validated, empirical, reference clinicopathological, patient database allows it to provide an entirely objective and quantitative diagnostic assessment quickly — often within minutes.
- MCG's diagnostic accuracy is unaffected by common resting ECG abnormalities such as arrhythmias, pacemaker rhythms, baseline ST-T abnormalities, or bundle branch blocks which can negatively impact conventional ECG technology accuracy. Where conventional ECG has ~50% sensitivity for diagnosis of CAD [Page 14] MCG has an overall sensitivity of 92.9% [Page 46, table 8] when compared directly to the reference standard — coronary angiography [2, 7, 24-26].
Table I — Comparison of Conventional ECG and MCG
Reproduced with permission from Premier Heart, LLC
Traditional ECG vs. MCG
||[I] Conventional ECG Reduction Approach
||[II] MCG, A Multifunction Cardiogram Systems Analysis Approach
||Simplifies the ECG data by mapping it to a single dipole, plotted on the Einthoven ECG 2-D Scale Model (time vs. voltage).
||Processes the ECG data to process a LaGrange-Eüler multifunctional model which accurately represents the solid/liquid interaction of a beating heart.
||Segmental single-cycle approach focusing on a single lead at a time, and evaluating sections of the waveform (e.g. ST Segment, T-Wave, late QRS, waveform potential such as SAECG...)
||Operates on two leads simultaneously (II & V5), and across multiple cardiac cycles to extract non-linear functional relationships between the two LV leads.
||Requires an on-site experienced clinician to interpret (or over-read) tracings to avoid misdiagnosis.
||Compares transmitted ECG data to a large clinically validated, digital, multi-patient database to produce a real-time diagnosis of cardiac ischemia/coronary artery disease from two decades of research.
||Accuracy impaired by common resting ECG abnormalities (e.g. arrhythmias, bundle branch blocks).
||Accuracy unaffected by common ECG abnormalities.
||Provides a subjective and qualitative assessment.
||Provides an objective, quantitative measure of disease severity.
January 16, 2010
©Premier Heart, 2008
In summary, MCG is a non-traditional systems-analysis tool that builds a mathematic model to detect myocardial ischemia due to underlying obstructive coronary artery disease. It is not a Signal Average ECG (SAECG) or any other modified ECG waveform analysis technology, but rather an entirely new methodology based on a multifunction mathematical model of the electro-mechanical function of the heart and an analysis of the integrity of that system over multiple cardiac cycles, not a portion of one cycle.
Clinical Trial Design, Comparison to Angiography, and Pre-test Risk of Trial Population
Table II contains the aggregate data from the four published prospective double-blind clinical trials referenced in the draft assessment [2, 7, 24-26]. The goal of these trials was to validate MCG's accuracy in detecting hemodynamically relevant coronary artery disease, defined as 50% or greater stenosis of the Left Main and 70% or greater stenosis of the epicardial coronary arteries, as determined by comparison to the coronary diagnostic “Gold Standard” — coronary angiography.
Table II - MCG Meta-Analysis Trial Results
Reproduced with permission from Premier Heart, LLC
Meta Analysis Data Table [Ref #1]
||Positive Predictive Value
||Negative Predictive Value
||% With Critical Stenosis via coronary angiogram
|< 65 years
|≥ 65 years
|Female, < 65 years
|Female ≥ 65 years
|Male, < 65 years
|Male ≥ 65 years
|Revasc Of Any Type
Summary of Overall MCG Data For the Detection of Relevant Coronary Stenosis. Revasc = coronary revascularization in medical history; PCI = Percutaneous coronary intervention in medical history; % Correct = % of patients correctly identified as having relevant coronary stenosis or not by MCG compared to coronary angiogram.
January 16, 2010
©Premier Heart, 2008
Clinical trials directly comparing a resting ECG-based diagnostic method with coronary angiography are rare — in fact I am unaware of any such trials. MCG accuracy was compared directly to coronary angiography for the following reasons:
- MCG's fundamental purpose is the detection of coronary ischemia due to obstructive coronary disease. Coronary Angiography has been the definitive and most accurate tool used to diagnose relevant, “interventionable” coronary artery disease. The authors of the draft TA also agree with this conclusion regarding coronary angiography as the preferred standard for diagnosing coronary disease [Page 6, Table].
- Resting ECG analysis, including the 12-lead ECG, typically has significantly less sensitivity in detecting ischemia. Clinical studies have reported a wide range of sensitivity from 20% to 70%, and the accuracy is subject to the reader's knowledge of a patients' history of or lack thereof, previous myocardial infarction [9-10].
- Stress-ECG testing also has limited sensitivity and specificity, particularly in the detection of single-vessel CAD, as well as detection in women, and patients with underlying arrhythmia, baseline ST-T abnormalities, and conduction disturbances. In addition, exercise ECG has a reported specificity of 80%, under ideal clinical trial conditions, however, in routine clinical use its sensitivity is typically not better than 50-60%, and shows significant gender bias [11, 13-15].
- Stress-imaging techniques such as stress-nuclear or stress-Echo testing have a wide range of reported sensitivities and specificities in detecting severe myocardial ischemia, are frequently limited by attenuation defects, heart rates achieved during testing, spatial resolution of the perfusion or wall motion images, ECG gating problems, conduction disturbances such as bundle branch block, and the extent of disease (often obstructive disease needs to be present in two or more epicardial coronary arteries before there is accurate detection).
Therefore, it was elected not to compare MCG to the above less accurate modalities and instead compare MCG directly to the coronary angiogram [2, 7, 24-26]. When the comparison was made, as evidenced by the data in the meta-analysis Table II, there was considerable accuracy and a high negative predictive value (NPV) shown for MCG in the whole study population as well as important sub-groups such as women vs men, age <65 vs age >65, male age < 65 vs male age >65, female age <65 vs female age >65, patients with no previous revascularization vs patients with previous revascularization of any type, patients with previous PCI vs patients with no previous revascularization, and patients with CABG vs patients with no previous revascularization.
It is also important to note that MCG had already been retrospectively validated during the pain-staking development of the large, multi-patient, clinical-pathologic database used by the technology in the above referenced clinical trials that prospectively evaluated each patient's MCG data. The purpose of the blinded, MCG clinical trials referenced in the TA was to prospectively validate the accuracy of MCG technology in detecting relevant coronary stenosis. The authors of the TA themselves expressed a desire to see such a comparison to coronary angiography with regard to the other technologies discussed as that type of trial design provides a valuable degree of insight into the true accuracy and usefulness of any coronary diagnostic technology under study.
In summary, the decision to evaluate MCG by direct comparison to coronary angiography was reached based upon the revolutionary nature of the MCG technology, limitations of the other existing diagnostic modalities available, and the desire to validate MCG against the best available reference standard, coronary angiography.
With regard to the selection and enrollment of patients in the prospective clinical trials, Page 37 of the draft TA includes the following statement: “(MCG) Study quality was good with two exceptions” The first exception was… “it was unclear if subjects were selected at random or consecutively”. With reference to the selection methodology, it is clearly stated in all four trial publications that the study populations represented convenience samples of patients scheduled for coronary angiography. Since patients with acute coronary syndrome or acute coronary ischemia scheduled for emergency cardiac catheterization were not included in the study populations. The final sample did represent a “consecutive” sample of patients scheduled for elective coronary angiography.
The second exception was that “The (trial) selection criteria likely selected for a sample population with greater disease severity than would be seen in the population of interest”. [Page 37] I believe this is an incorrect conclusion. Table III shows the risk age and gender-adjusted criteria to which the draft TA referred.
Table III. Pre-Test Probability of CAD by Age, Gender, and Symptoms
|Age Typical/Definite Atypical/
Probable Nonanginal (yrs)
High: Greater than 90% pre-test probability; Intermediate: Between 10% and 90% pre-test probability; Low: Between 5% and 10% pre-test probability; Very Low: Less than 5% pre-test probability. Note no data exists on Pre-Test Probability of CAD in patients below age 30 of above age 69. Reproduced with permission from ACC/AHA 2002 Guideline Update for Exercise Testing (8).
Based on the published meta-analysis of the MCG clinical trials, the patients who participated in the published trials had an overall pre-test probability of coronary disease ranging from 32% to 54% in the different study center populations, and from 28% to 58% in study subpopulations, using the criteria in the 2002 ACC/AHA Guideline Update for Exercise Testing. This range is clearly an intermediate risk range, not a high-risk range as suggested in the draft TA.
We understand that the 2002 ACC/AHA criteria above refer to the determination of risk of individuals, not groups of patients, however the bottom-line from the practicing physician's perspective is whether patients actually have critical coronary stenosis at the time of exam and whether they will be managed medically or by surgical or percutaneous intervention. While it is possible the MCG trials enrolled some patients who might be classified at high risk according to the ACC/AHA guidelines, the results of actual angiography on all enrolled patients showed that, as a group, the pre-test risk of relevant coronary stenosis was intermediate with a low “a priori” risk (defined by a knowledge of the actual population rates).
Bayes' theorem allows calculation of the positive (PPV) and negative predictive values (NPV) for any “a priori” risk (prevalence of the disease in the population in question) based on the sensitivity and specificity determined in clinical studies in populations that may have different disease prevalence . Table IV shows the calculated PPV and NPV for different a priori risks based on the sensitivity and specificity determined from the meta-analysis across all four blinded, prospective MCG trials [2, 7, 24-26].
Table IV - Calculated Positive & Negative Predictive Values based on MCG meta-analysis
|Overall Study Population
|Very Low Risk
These calculations show that MCG has a very high ability to rule out hemodynamically relevant stenosis in subjects with very low to intermediate risk (NPV > 90% for risk < 50%; NPV > 97% for risk < 20%). Therefore, MCG is, from a statistical perspective, especially suited to prevent unnecessary coronary angiography in patients with low to intermediate “a priori” risk of CAD. One practical consequence of this is that when MCG is employed early in the patient's evaluation, a significant number of patients will not need to undergo any form of “add-on” stress-imaging testing, angiography, or even hospital admission if their MCG severity scores are low (i.e. < 4.0). Because MCG testing can be performed at the point of care, the management of these patients can be dramatically improved and the overall cost of care reduced. No ECG-based Signal Analysis technology has been able to make this type of determination with the accuracy of the MCG. In the typical community setting, most patients experiencing symptoms of chest pain will be seen first by their internist or family physician. If MCG testing is performed by them and confirms a very low likelihood of relevant coronary stenosis treatment can continue without the need for cardiology consultation and/or additional “add-on” stress testing or stress imaging. The MCG score could also easily be incorporated as a pre-certification screen for any subsequent “add-on” testing by Medicare or Commercial carriers.
The Draft TA's Conclusions Regarding the MCG Technology
MCG is a technology that has been prospectively shown to accurately predict the presence of relevant coronary stenosis in patients at intermediate risk of CAD in well-designed clinical trials. [2, 7, 24-26] While I appreciate that the draft TA described the MCG trials as well-designed, I disagree with the conclusion that MCG is merely a “promising” diagnostic tool. I believe that the foregoing discussion of MCG technology, and of the design, and statistical evaluation of the MCG clinical trials in this peer review demonstrates that the accuracy and validity of MCG in detecting relevant coronary stenosis is well validated and supported by the trial results. It is my hope that the final TA will incorporate these concepts and conclude that MCG is a validated, clinically useful early diagnostic test for patients at low to intermediate risk for coronary disease.
Experience Using MCG in My Clinical Cardiology Practice for the Past 2.5 Years
I have been in the practice of clinical cardiology in northern New Jersey for the past 25 years. I currently perform coronary angiography and own and use nuclear and ultrasound diagnostic equipment in my office. The Nuclear Cardiology Board personally certifies me and my nuclear laboratory is certified by the Inter-societal Commission on Nuclear Laboratories. I care for a generally elderly population that is composed of Medicare beneficiaries (65%) and non-Medicare beneficiaries (35%) many of whom have known or suspected coronary disease. The introduction of MCG into my office 2l years ago has created a profound change in the way I manage my patients with symptoms suspicious of underlying coronary disease. I also have concluded that in the case of the MCG clinical trials that the trial design comes very close to the way I feel it is appropriate to use the MCG in clinical practice. Thus, I believe the trial design and published trial results are very applicable to the real life situations I encounter in the community practice of cardiology, which increases my comfort level using the device. I have found through testing a large number of symptomatic patients, that patients with no evidence of ischemia determined by MCG and an overall MCG severity score of <4 can safely be managed medically with attention to coronary risk factor reduction and adoption of a healthy lifestyle. These patients, in my practice, are not referred for stress testing or stress-imaging, or angiography unless a significant change (worsening) occurs in MCG results when performed as necessary in follow up (e.g., if symptoms worsen significantly). In my view, this clinical use and application of the MCG technology is readily supported by all four of the MCG clinical trials. In the overall MCG trial population, approximately 40% of the patients who were scheduled for and underwent coronary angiography had overall MCG severity scores less than 4.0 and thus, could safely have been managed medically, and avoid all additional testing including angiography.
The patient with an MCG score 2 4.0 does not have as clear a path to follow. There are currently no prospective clinical trials showing that these patients can be managed in any specific manner or by any specific treatment algorithm. While it is my understanding that further trials and a comprehensive patient registry are being planned and need to be done to clarify how best to manage a patient with an MCG severity score 24.0, in my clinical experience, and based on data from the Courage Trial , patients with scores 2 4.0 and: 7.5, have been managed safely through adherence to evidence-based optimum medical management of suspected coronary disease with the use of further advanced stress-imaging or coronary angiography only when there is symptomatic failure of optimum medical management. The decision to perform additional stress-imaging tests in this situation, however, must remain with the treating physician, based on the clinical circumstances and his judgment in each case. A patient with an MCG result showing significant local or global ischemia and a severity score > 7.5, should, in my view, be strongly considered for coronary angiography, independent of the result of any other stress-imaging tests or lack of progression of symptoms. This clinical pathway will also require further controlled clinical trial data to fully support its adoption in routine clinical practice.
It is my understanding that a number of avenues of further research are being pursued at this time by Premier Heart, Inc. to help address the clinical management questions that arise when the MCG severity score is 24.0, including measurement of the MCG score before and after a pharmacologic stress is applied. Information such as this could further enhance our understanding of ischemic syndromes in general as well as the device's function and limitations.
Conclusion and Summary of Peer Review Findings
MCG is a computer-based, computational electrophysiology systems analysis tool that physicians can use to make accurate and timely diagnosis of relevant CAD at the point of care. It is not comparable to SAECG or other direct ECG-based waveform analysis techniques, and has many distinct differences and advantages over those older technologies.
The MCG clinical trials conducted thus far have clearly included patients with “intermediate pre-test risk” of CAD, not “high pre-test risk” patients as the draft TA concluded. I agree with the authors desire to have all new non-invasive, ECG-based technologies designed to detect coronary disease, compared to coronary angiography. To my knowledge, MCG is the only technology where such a comparison has been done. Furthermore, in my opinion, it is not appropriate to compare a technology like MCG to an “add-on” ECG-based technology, the intended use of which is entirely different from the intended use of MCG.
I believe that the accuracy of MCG for the diagnosis of relevant coronary disease has been definitively validated through well-designed prospective double-blind clinical trials comparing MCG to coronary angiography, and that it has performed very well over a 2l year time frame as a clinically useful early diagnostic tool for physicians at the point of care treating symptomatic patients with known or suspected coronary disease. It has definitely reduced the number and complexity of “add-on” stress or stress-imaging tests I have ordered since beginning to use the device.
I would appreciate the opportunity to meet with or have a conference call with the authors of the draft TA to discuss the fine points of discussions contained in this peer review, and to explain them in more detail, if necessary.
My contact information is as follows: John E. Strobeck, MD, PhD, 297 Lafayette Avenue, Hawthorne, NJ 07506. 973-423-9388 Tel; 973-423-2502 Fax; firstname.lastname@example.org email.
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