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How to Find BIockages without Angiography?

"REALISTIC GEOMETRIC CARTOGRAPHIC IMAGING”

 

Coronary artery blockages, till now, could not be measured by any tests except angiography, which is not only expensive but also exposes the patient to a number of risks and complications. Moreover, angiography needs an admission and now being use by most of the hospitals to compel patients to undertake next procedures like Bypass surgery or Angioplasty.

Good news for heart patients is that in the near future they will be able to find and measure the blockages without angiography, through a Hungarian developed investigation called Realistic Geometric Cartographic Imaging (RGCI).

RGCI can be done at the bedside of the patients, It takes roughly 20 minutes from start to finish. The procedure is done using few disposable electrodes. Complex parameters are obtained using high precision data accusation system. Pressure, volume, time of blood flow are collectively obtained by simultaneously recorded electrocardiography (ECG), phonocardiography (sound of the heart), non-Invasive continuous blood pressure and trans thoracic bio-impedance. The acquired parameters are then mapped against a mathematical model and cartogram is obtained, which is a collective behavioural pattern of the heart and its circulation status. Doctor gets a complete heomodynamic picture of the heart, as well as the location and severity of coronary artery disease and relative oxygen demand of the heart. This can help the doctor in taking appropriate decision regarding management of the patient.

RGC Imaging can detect coronary tube blockages as low as 20%, it is having a sensitivity and specificity of more than 92% which according to the experts is good enough for non-invasive test. This procedure can be used to substitute costly, dangerous and not so accurate procedures for accessing the coronary heart disease (i.e. Angiography). It is also used in the management of critically ill patients since its a bedside procedure.

Scientific papers were presented at the 8th European Congress of Intensive Care Medicines, Athens, Greece 1995; 12th International Congress "The New Frontiers of Arrythmia" Italy 1993; 3rd International Conference on Impedance Cardiography, Domdovan, Hungry 1997; 4th Asia Pacific symposium on Electro-physiology, New Delhi 1997. Recently papers was presented by Manipal Heart FoundaUon, Bangalore during the 50th Scientific Session of Cardiological Society of India, December 1998.

The authenticity of RGCI has been established in the last 10 years. The technique is being studied extensively in many part of Europe and India. The added advantage of RGCI is that people with minimum blockages can also detect their blockages by this procedure, allowing them to prevent heart disease in future.

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Angiograms and Ultrasound Are Not Accurate to Measure Profound Improvement Following Chelation

by Elmer M. Cranton, M.D.

 

It is hard to believe but scientifically proven less than 7 percent increase in the interior diameter of a diseased blood vessel will double the flow of blood. Angiograms and ultrasound imaging are only accurate to within approximately 20 percent and cannot measure such small changes.

 Blood is only about half liquid. The other half is composed of red and white blood cells. These cells rub along blood vessel walls and move much more slowly than more fluid blood in the center of an artery. This makes blood highly viscous and sticky close to the arterial wall. Because the distance relative to blood cells between the outer wall and the center of a vessel is much less in small blood vessels, a small increase in the internal opening will result in a very large increase in the flow of blood. Blood flow past plaques is turbulent, causing even more resistance to flow. In diseased arteries with plaque, an even smaller increase (less than 6 percent) can double the flow of blood and totally relieve symptoms.

 The liquid and cell-free portion of blood is more viscous than water because of its high protein content. Cell-free plasma is about 1-½ times as viscous as water. When blood cells are added, the viscosity increases to more than 3 times that of water.

 The cross sectional area in the opening in a blood vessel decreases exponentially with a decrease in diameter. An artery of half the diameter has only one fourth the cross sectional area.

 Combining all of these factors together, as proven by Poiseuille’ Law, doubling the diameter of the internal channel results in a 16-fold increase in the flow of blood (assuming no change in blood pressure or length). Put another way, a smooth healthy blood vessel will carry twice as much blood if the interior increases less than 7% in diameter. A blood vessel with plaque and has turbulent flow and a mere 5 percent or less increase in diameter of the internal opening will double the flow of blood.

 Angiograms and ultrasound imaging are only accurate to within approximately 20 percent. Even if repeated an hour later on the same patient using the same technique, the reading can vary by as much as 20 percent.  That explains why patients whose symptoms have improved dramatically following chelation therapy often do not show a significant change in reading on followup angiogram. For the same reason, calcium scores on followup ultra-fast, electron-beam, CT scan (EBCT) are also not a reliable way to measure benefit following chelation therapy.

It is a waste of time, a waste of money, and can involve unnecessary risk to do follow-up angiograms merely to document improvement from EDTA chelation therapy. The proof of the pudding is in the eating. If symptoms improve it is logical to assume that blood flow has increased. If that benefit can be retained by periodic maintenance chelation treatments with the most effective nutritional supplements, much can be achieved without surgery, stents or other potentially dangerous procedures. 

 

References

 http://www.answers.com/topic/poiseuille-s-law

 http://hyperphysics.phy-astr.gsu.edu/hbase/ppois.html

 http://www.cvphysiology.com/Hemodynamics/H003.htm

 

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Bangalore team's invention gets FDA approval

Our Bureau

Bangalore, July 21, A MEDICAL diagnostic device invented by a Bangalore research team has become the first such hi-tech Indian tool to win the US FDA approval for its clinical use in the US and certification from the EU.The device, called Haemotron, is non-invasive and uses 3D mapping technology or 3D cardiovascular cartography (3D-CCG) to measure the heart's functions and blood flow. The painless 3D-CCG technique takes barely 20 minutes and gives a comprehensive picture of the heart and any of its abnormalities in early stages, according to its inventors.

The Haemotron, developed over six years and in use for two years, has been invented by Dr Rajah Vijaykumar, Chief Scientific Officer, and his biomedical engineering team at the Centre for Advanced Research & Development (CARD) in Bangalore. Costing around Rs 35 lakh, it is manufactured by Scalene Cybernetics in India and Austin Systems, Inc, US, and ASKIT kft in Europe.

According to a panel of doctors at a press conference, the 3D CCG way costs Rs 3,500 each and can detect cardiovascular blocks very early at even 10 per cent of the blocks, compared to angiograms that are effective in cases with more than 40 per cent of blocks and are three to four times costlier. Prevention of heart attacks could begin five years earlier than with other tests.

 

Source: The Hindu Business Line

(http://www.blonnet.com/2003/07/22/stories/2003072201051700.htm)

 

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Cardiovascular Cartography: The Message Is The Medium
Cardiovascular Cartography [CCG], a new non-invasive tool with a systemic approach for interpreting haemodynamics, is based on modelling and simulation techniques. Its clinical application is keyed to diagnoses, estimation of prognosis, and modification of therapeutic modalities — especially in coronary artery disease [CAD].

Dr G N Shirbur, Dr S S Sibia, Dr N T Murlimohan & Dr Rajasimha

Measure what is measurable, and make measurable what is not so. -- Galileo

The prevalence of CAD in India is of the highest magnitude. It has been confirmed by several studies.¹ It is also a construct that requires mass screening not only to detect anomalies, but also follow-up and strategy for cost-effective treatment.

The technique, which is simple, easy-to-perform, and painless, can be repeated as many times as may be required. Its sensitivity and specificity have no less been assessed and validated in a blind study with angiographic findings in confirmed CAD patients.² Our experience with about 1,900 patients screened contemplatively, so far, with angiograms, echocardiography, stress ECG and clinical assessment, has shown detection of CAD, with a mean accuracy of well over 90%.

There has been a great deal of misunderstanding or balderdash in the popular media about this technique. This explains why we need to set the record straight. We are the actual users. Inaddition, our [benefited] patients and we stand by its capabilities. More so, because the technique which was studied by a group of researchers with utmost scientific diligence and fidelity, not to speak of painstaking precision, has been acquiesced to with the stamp of authority, what with results presented in scientific forums in Europe and India.

We wish to briefly elaborate the functional theory behind cardiovascular cartography. In simple terms, the technique makes scientific sense and uses a very advanced method of modelling and simulation with a 24 parameter kinetic model.

Historically, kinetic models were built to assess continuously changing non-linear dynamics of large scale data in the field of electronic warfare, weather prediction, and nuclear physics. Its application in the cardiovascular domain was, in the first place, discovered by Kumar and co-workers.

Basic Theory — Get it Right
The cardiovascular system functions as a closed loop dynamic fluid mechanics system based on pressure, volume, time and flow principles which occur independently and simultaneously. In other words, it is non-linear. The efficacy, or any deviation, in its functions for assessment purposes requires measurement of various haemodynamic parameters responsible for a dynamic event of the heart. This is called the cardiac cycle — a product of non-linear physiological activity occurring in unit time.

The measurement of pressure, and volume, can be executed by methods like Doppler or radio nuclear studies, but flow measurement is possible only by way of Transthoracic Bio-Impedance [TBI]. The clinical use of TBI has been in vogue for more than 30 years. It was first formulated by Kubicek³ and only recently by Gomory.⁴

The usage of pulsatile changes that occur due to flow of blood is a function of TBI. TBI produces signals [curves] that are precisely time-related to other physiological curves like ECG, PCG etc., The signals produced are due to the electromechanical activity of the blood flow. The CCG integrates the measured and derived parameters from these curves, and the first derivative⁵, [dz/dt, which is similar to dp/dt curve] of the modulated curves. The numerical values of the individual beat, or cycle, of systolic time interval and diastolic filling phase are derived from this specific.

In like manner, the vertical lines plotted are used to compute the pre-ejection [PEP], ventricular ejection time [VET], and QS2 intervals [electromechanical systole/See Fig. 1]. With the amplitude modulations of TBI synchronous with pumping of blood in the heart and proportional to the amount of blood pumped out, the modulations are practically equivalent to stroke volume — an absolute value proportionate to the duration of systole, flow velocity and the resistance of blood, that depends on haematocrit^6,7

Thus, the value of stroke volume can be calculated from the measurable, modulated curve as well as its proportions related to the amount of fluid in the thorax and the volume of the connective tissues of the thoracic cavity with Kubicek formula², and corrected to body habitus. From the measurable data of these four recorded signals, the heart rate and the amount of blood pushed out by the heart per beat can be calculated, along with the cardiac output.^6,7,8 Furthermore, with the knowledge of the various systolic time intervals and the pressure values measured, the remaining/ derived haemodynamic parameters can be obtained for every beat.

 Principles of Cardiovascular Cartography
The 3-D mathematical modelling and simulation using high-speed computation enables non-linear haemodynamic parameters of a patient to be mapped against the mathematical model of the cardiovascular system. Using neural network computing, a predictive model of the patient is created. The measured haemodynamic behaviour is superimposed on the predictive model. The resultant dynamic deviation is represented in a form called cardiovascular cartogram. The resultant deviation difference is distributed as pressure zone, volume zone, time zone and flow zone, in a clockwise direction on the cartogram [Fig. 2]. The K-Scale on the cartogram is an independent scale. It has positivity and negativity elements and indicates the deviation difference, aside from reflecting a physiological, pathological or compensatory phenomenon to assessing the efficacy and function/s of the cardiovascular system.

The pattern of change that occurs in the flow zone of the cartogram [contractility, acceleration, after-load, ventricular depolarisation to peak ejection delays] is obviously related to the anterioseptal regions of the myocardium. The pattern of change in the volume zone [rate pressure product, stroke volume, cardiac output, and pre-load] is, thus, related to inferioseptal regions of the myocardium and the time zone; intracycle timings, and LV ejection rate are related to the lateral regions of the myocardium. In an ICU setting, it is these factors that we try to correct — especially in situations where there is myocardial infarction in the respective regions...

The Vertical Acceleration Detector [VAD] is a special device that picks up subsonic waves that are transmitted from the heart to the chest wall. It is similar to the seismic waves that get transmitted from deep inside the earth to the surface during a quake. The VAD picks up subsonic signals throughout the cardiac cycle. This includes every component of the first and second heart sounds, just as much as specialised spectrum analysis and digital signal processing enable us to detect and extract micro variations in the subsonic activity during early-, mid- and late-diastolic [passive] filling phase.

The second component of the second heart sound is of prime importance in cardiovascular cartography because it signifies the onset of diastole. The turbulence in flow is differentiated and extracted during a period when there is maximal coronary flow: a parameter that is used to detect primary presence of coronary obstruction. The power and frequency signifies the regions from which these signals originated. It is correlated with zonal [pressure, volume, time and flow] behaviour to obtain a three-dimensional array of information that is suitable for image reconstruction.

The first part of reconstruction is to identify the ischaemic zones and reconstruct the regions on the short axis slices of the LV muscle mass [Fig. 3]. This enables one to identify the major vessel supplying the region. The appropriate site of the lesions embedded on the realistic geometry coronary model also helps us to get the realistic geometric reconstruction of the most probable location of coronary occlusion.^9,10 [Fig. 4]. {Note: These are microsecond events that have been studied. There are no parallel methods available, at present, for detecting non-invasively CAD [positive/negative], with this aggregate}.

The vast amount of data acquired during a cardiovascular cartography study enables us in computing other vital information. Some of the important information that will have diagnostic, management and prognostic value are: regional myocardial blood flow, coronary flow reserve, global cardiac efficiency, arterial compliance [specially in diabetics], ANS predominance, besides pre-load, contractility, and after-load.

CCG Test Protocols and Procedure for CAD Detection
Following strict protocol, in our opinion, will ensure best results. Unlike many other test procedures for CAD detection, where linear changes in unilateral function like electrical conduction pattern in stress ECG or material uptake in stress thallium are ratified, CCG is based on non-linear dynamics of blood flow. Drugs, for example, alter cardiac haemodynamics and maintain a forced balance.

The Protocol We Use and Recommend

·      The patient should abstain from all drugs that alter cardiac haemodynamics for a period of 12 hours prior to the test. We have found that there is no significant change in the test results between a 12-hour avoidance or a longer period. [Note: CCG is based on relative beat to beat changes, and not on absolute values. If drugs do not interfere with the relative changes, this is sufficient]

·     Alcohol plays an important role, mainly as a diuretic. The patient should abstain from alcohol for a period of 24 hours prior to the test

·     Patients should abstain from all types of stimulants like coffee, tea and other soft drinks for a period of 12 hours prior to the test

·     The patient should generally be fasting [A light breakfast, or a glass of milk and some biscuits, two to three hours prior to the test do not alter test results]

·      It is important that the patient should empty his/her bladder and be relaxed during the entire test procedure. Test results will be inconclusive in non-co-operative patients

The patient is wired to the CCG system with meticulous care. Generating electrodes should not be interchanged with measuring [or, pick-up] electrodes. VAD should be placed at a site where the second heart sound is of maximum amplitude [this will need some practice]. The bed used should be at 180 degrees; any inclination will alter the pre-load and result in an error.

The test is performed in two phases: the first phase in supine position following the above protocol, and the second phase during the same sitting by creating a vasodilator response and altering the coronary flow reserve [CFR] that is severely decompensated at rest in case of certain types and severity of coronary occlusion [NYHA Class III-IV]. In certain cases, where there is a large by-lane flow [collateral flow], the CFR will be near-normal [4~5:1], but will start to get effected after induction of reactive hyperaemia, usually by the administration of a coronary vasodilator, where a steal phenomena is induced secondary to pre-stenotic vasodilatation.

To exactly understand the second phase of the cardiovascular cartography study, one has to have adequate knowledge of coronary circulation, factors governing coronary flow, dominion of auto-regulation, resistance, large and small vessel pathophysiology, type of stenosis [rigid, dynamic etc.,] and coronary artery steal. It is, however, beyond the scope of this article to discuss all these factors. For the purpose of understanding, we will only discuss a few of the important ones.

Dynamic Coronary Artery Stenosis

If coronary lesions were hard and geometrically fixed, physical activity would be proportional to the maximal luminal area reduction or coronary blood flow. It would also explain most of the signs and symptoms of coronary artery disease. Yet, anatomical studies indicate that most human coronary stenosis contain at least some normal wall segment.^11,12

A normal epicardial coronary artery vasoconstriction will decrease the luminal area, but this will have no significant effect on either flow or pressure across the vessel.¹³ On the other hand, for a truly circumferential stenosis, liable to change its size and shape, vasoconstriction will have no influence on its cross-sectional area or stenotic haemodynamic severity. For diffuse smooth muscle stenosis and eccentric stenosis, alteration in smooth muscle tone will have significant, physiologically important effects on the cross-sectional area, possibly causing rest or exertional angina.

Large vs Small Vessels
The large and the small coronary arteries respond differently to the same vasoactive substances. Table 1 shows the physiological and biochemical characteristics of small and large coronary arteries.¹⁴

For example, in whole_animal and isolated_heart preparations, the small vessel vasodilatation with nitroglycerine was found to last only 20 to 30 seconds, whereas the larger coronary arteries remained dilated for up to 10 minutes.¹⁵ The differences in response to vasoconstrictors between the large and the small coronary arteries have not been extensively studied.

Stenotic Modulation
Rigid stenosis is where there is a geometrically fixed stenosis, the arterial wall is rigid, and the luminal area cannot change. Regardless of the degree of stenosis, decreasing distal resistance always increases flow, while increasing distal resistance always decreases it. With mild underlying rigid stenosis, decreasing distal resistance leads to a large flow increase, while with a severe rigid stenosis decreasing distal resistance results in a greatly attenuated flow increase. Thus, a patient with mild rigid stenosis can perform substantial physical exercise such as running etc., whereas a patient with severe rigid stenosis can only perform light work such as climbing stairs.

In case of a dynamic stenosis, where vasoconstriction, perfusion pressure and distal resistance, can each alter luminal areas, interaction[s] among vasoconstriction, perfusion pressure and distal resistance can occur. Correspondingly, altering distal resistance changes the luminal area; decreasing distal resistance decreases the luminal area; and, increasing distal resistance increases the luminal area. Also, proximal coronary artery vasoconstriction can decrease the vessel size. For example, in mild underlying dynamic stenosis, proximal coronary artery vasoconstriction would decrease the luminal area, and the decreasing distal resistance would further decrease the luminal area. Additionally, due to such a definitive decrease in luminal area, the coronary blood flow increase would be less than the response observed for rigid stenosis. This patient will only achieve light to moderate work levels, such as jogging. For severe dynamic stenosis, proximal coronary artery vasoconstriction would decrease the luminal area, whereas decreasing distal resistance would further decrease the luminal area. This may cause a paradoxically small flow decrease as compared to rigid stenosis response. Thus, in a patient with severe dynamic stenosis maximal physical activity will be severely decreased and an imbalance in myocardial oxygen demand and coronary blood flow will occur at rest. These patients will also experience rest angina without any physical exertion.

 Table 1. Physiological and biochemical characteristics of large and small coronary arteries. 

Characteristics	Large	Small
Autoregulation Reactive hyperaemia Ischaemia Passive distension Total resistance [%] Adenosine Hypoxia KCN Mitochondria Succinic dehydrogenase	No Slight constriction Constriction Yes 5-20 Constriction No Dilation No Dilation 10/unit 1	Yes Dilation Dilation Yes 95-80 Dilation Dilation Dilation 23/unit 2.6

 Induction of reactive hyperaemia by administering vasodilators like nitrates is essential in performing the cardiovascular cartographic study because it is important to achieve arterial modulation of stenosis as some types of coronary artery disease may go undetected. Modulating and creating a coronary artery steal can unmask some of the disease regions not severely altered under basal conditions.

There are two potential types of coronary artery steals that can occur. Both require stenosis in the large coronary arteries. Type I steal involves only one coronary artery and is caused by a redistribution of flow between the endocardium and epicardium. As maybe known, subendocardium is subjected to greater stress and, thus, needs a higher blood flow. In the presence of a proximal stenosis, the epicardial vessels maybe maximally vasodilated even under resting flow conditions. Distal coronary arteriolar vasodilators result in a greater pressure decrease across the stenosis, resulting in a decrease in distal coronary pressure. This pressure decrease can cause a decrease in flow to the subendocardium. It also partially explains why ST-segment elevation is observed on stress ECG test.

The Type II steal involves a decrease in collateral blood flow, aside from an alteration of the coronary flow reserve [CFR]. With the gradual obstruction of a coronary vessel, collateral vessels develop from the other [donor] coronary vessels. Collaterals are thin-walled anastomotic connections that exist between coronary arteries without an intervening capillary bed. They are anatomically present from early life in the form of native collaterals, but mature only if a need for additional coronary flow exists in certain region/s of the heart.

These collateral vessels supply blood flow to the myocardium normally perfused by the diseased [recipient] vessel. The collateral blood flow maybe adequate to maintain the resting energy requirements of the myocardium. However, the collateral circulation is insufficient to meet the needs of the myocardium during periods of physiological stress. In such a vista, distal coronary arteriolar vasodilatation has been reported to shunt blood flow away from the diseased vessel [coronary artery steal]. Consequently, these vessels do not prevent the development of ischaemic changes in stress ECG or abnormalities of ventricular contraction and performance.

Coronary artery steal only occurs in the presence of proximal resistance in the donor circulation. Steal does not occur without stenosis in the proximal recipient artery. For a proximal rigid stenosis in the recipient circulation, coronary steal is due solely to the decrease in collateral blood flow. Likewise, the magnitude of flow reduction in a rigid stenosis is directly related to the decrease in collateral blood flow. In contrast, for a dynamic stenosis in the recipient circulation, coronary steal is due primarily to a decrease in flow through the diseased vessel. Thus, in dynamic stenosis the largest decrease in flow occurs through the native coronary vessel — a self-steal phenomenon.

During the second phase of cardiovascular cartographic studies, the patient is administered 10 mg sub-lingual nitroglycerine. It is advisable to wait till the patient's systolic blood pressure drops by about 10 to 15 mm Hg. The test is now repeated and another 1,024 beats are acquired and processed. Table 2 gives the outcome of a typical cardiovascular cartographic study during pre- and post-nitrate studies and their interpretation.

What You can Get out of CCG ?

Table 2. Cardiovascular Cartographic Study: Outcome and Interpretation 

Sudy Mode	Results
Basal study	+	-	+	-
Nitrate enhanced study	-	+	+	-
Interpretation	Type I coronary steal syndrom	Type II coronary steal syndrom	No steal syndrom	Normal No evidence of flow limiting lesions
	Mild endothelial dysfunction	Endothelial dysfunction	Severe endothelial dysfunction
	Small vessels compliant	Small vessels non-compliant	Small vessels non-compliant
	Ø CAD positive with dynamic stenosis	Ø CAD positive with rigid stenosis	Ø CAD positive with critical stenosis	Ø Normal Study

 The CCG indicates CAD lesions, LV functions, LV contractility, LV stroke work, cardiac reserve systemic vascular resistance, arterial compliance, global myocardial blood flow, regional myocardial blood flow, pulmonary capillary wedge presence and pulmonary pathology. The other clinical applications of CCG are post-MI rehabilitation, pacemaker programming, ICU monitoring and CCF follow-up,¹⁶ ventricular arrhythmias, and EPS. There are no `gold standards' to assess the global, or regional, blood flow but our assessment with expectations with coronary angiography, echocardiographic abnormalities and stress thallium, seems to be correlating well.

It will, therefore, be a good guide for clinicians for diagnoses, prognostication and modification of therapy depending on haemodynamic behaviours that are obtained non-invasively. CCG can also be of help in non-cardiac problems such as pre-operative evaluation of non-cardiac surgery, during haemodialysis, spinal anaesthesia during TURP [Transurethral Resection of Prostrate], and critical care monitoring of septicaemia: to name a few.

Conclusion
Cardiovascular cartography is a technique that is keyed to studying physiological [functional] effects that are secondary to an anatomical [structural] cause.

Its technology is complex, and difficult to understand, but with a little effort and open-minded approach, it should fall into place. Contrary to popular belief, CCG does not replace coronary angiography, but it gives a clear perspective of the underlying problems, haemodynamic behaviour and circulatory status, thus complementing coronary angiography by enabling the interventional cardiologist to be prepared to expect the unexpected.

Considering its simplicity, non-invasiveness, unambiguous interpretation and, of course, the cost, we should look at CCG as the future modality of mass screening of any population for cardiovascular disorders — especially coronary artery disease.

Acknowledgments
The authors wish to acknowledge the contributions of early researchers of TBI viz., Dr W Kubicek and Dr Gomory; Dr R V Kumar and his team for discovering the technique of mathematical modelling and simulation of the cardiovascular

Reference 

1.      Enas A Enas et al. Prevalence of Coronary Artery Disease in Asian Indians, Am J Cardiol 1992;70:945-949. 2.      Ravi Kishore et al. Cardiovascular Cartography Œ A New Tool to Detect and Assess Coronary Artery Disease, Ind Heart J 1999, Vol.50.pp 719. 3.      Kubicek W, Patterson R P et al. Impedance Cardiography as a Non- Invasive Method of Monitoring Cardiac Functions and other Parameters of the Cardiovascular System. Annals New York Academy of Sciences, 1970, 724-732. 4.      Gomory A, Horvaty S. et al. Possibility of Impedance Cardiography in Clinical Practice. Hungerica 1990, 19, 21-34. 5.      Lababidi et al. The First Derivative Thoracic Impedance Cardiogram. Circulation, 1970, 41:651. 6.      Fuller H D, The Validity of Cardiac Output Measurements by Thoracic Impedance: A Meta-analysis. Clin Invst Med, 1992, 15-103-112. 7.      Pikette B, Beul J C. Validity of Cardiac Output by Compute Averaged Impedance Cardiography and Comparison with Thermodilution Determination. Am J Cardiol, 1992, 69-1354-1358. 8.      Paul Pianosi et al. Comparison of Impedance Cardiography with Indirect Factor [CO2] Method of Measuring Cardiac Output in Healthy Children During Exercise. Am J Cardiology, 1996, 77:745-749. 9.      Chandra S. et al. Realistic Geometry Cartographic Imaging in Evaluating Patients with Coronary Artery Disease during Pre- and Post-intervention Phase. Euro Heart J. 1999, 20:309. 10.  Coleman T G, Mathematical Analysis of Cardiovascular Function. IEEE Transaction on Biomedical Engineering Vol.32, No.4.1985. 11.  Freudenberg H, Lichtlen P R. The Normal Wall Segment in Coronary Stenosis. A Postmortem study. Z Kardiol 1981; 70:863-9. 12.  Vladover Z, Edwards J E. Pathology Coronary Atherosclerosis. Prog. Cardiovasc. Dis, 1971; 114:256-74. 13.  Brown B G. Coronary Vasospasm: Observation Linking the Clinical Spectrum of Ischaemic Heart Disease to the Dynamic Pathology of Coronary Atherosclerosis. Arch Inter Med, 1981; 41:716-22. 14.  Winburg M M. Proximal and Distal Coronary Arteries. In: Samtamore W P, Bove A A [Eds]. Coronary Artery Disease: Aetiology; Haemodynamic Consequences; Drug Therapy; Clinical Implications, Baltimore Urban and Schwarzenberg, 1982;63-77. 15.  Cohen M V, Kisk E S. Differential Response of Large and Small Coronary Arteries to Nitroglycerin and Angiotensin: Autoregulation and Tachyphylasis Œ Circ Res 1973; 33:445-533. 16.  Hubbard, W W et al. The Use of Impedance Cardiography in Heart Failure. Int J Cardiology 1986,12:71.   Top

[First Published: BioMed, August 2000 ]

Dr G N Shirbur - Simha Heart Foundation/Mysore
Dr S S Sibia - Sibia Medical Centre/Ludhiana
Dr N T Murlimohan
Dr. Ambedkar Medical College & Hospital/Bangalore

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RGCI DETECTS BLOCKS YEARS BEFORE HEART ATTACK

Ludhiana: 19 Feb, 2000: India’s seventh Cardiovascular Cardiographic Imaging System (CVC) was installed today at Sibia Medical Centre, Ludhiana. This new non-invasive technique to detect Coronary Heart Disease in the form of Realistic Geometric Cartographic Imaging (RGCI) brings a new diagnostic advantage for chest pain patients for complete evaluation. It will help doctors monitor and diagnose heart problems even in early stage making timely protective treatment possible. RGCI is an advanced technique based on 3D mathematical modeling and simulation, that accurately informs of the probable location and severity of flow limiting lesions in heart’s blood vessels and its oxygen demand / supply with the help of measurement of heart muscle blood flow.

This equipment works on the principals of Integration of time related physiological curves derived out of transthoracic Bioimpedance, Electrocardiography and subsonic thoracis transverse waves to detect various cardiac parameters relating to pressure, volume, time and flow. A team of experts from Delhi, Bangalore and Mysore visited the city and addressed the leading cardiologists and physicians on this occasion where Dr.L.S.Chawla founder Vice Chancellor of Baba Farid University of Health Sciences was the chief Guest. Dr Rajah Vijay Kumar, Chairman Centre for Artificial Intelligence and Non Linear Studies, Bangalore and co-inventor of RGCI explained that doctors prefer to gain maximum accurate information about the cardiovascular system non-invasively. In invasive techniques catheters have to be inserted to know the status of coronary vessels and risks of injury, rupture, infection and radiation always exist. If the doctors get accurate data about heart functions without inserting any equipment, it would minimise the risk and simplify the process. This new technique does exactly that and could be repeated any number of times without any harm.

            The new noninvasive system uses skin electrodes and sensors that acquire and monitor the data in just 30 minutes. RGCI is providing continuous accurate data about any changes in haemodynamics such as the heart rate, stroke volume, cardiac output and other 24 parameters. Dr.G.N.Shirbur a leading cardiologist from Simha Heart Foundation, Mysore added that RGCI is the only technique that takes into consideration upto twenty four parameters and can be applied on a patient at rest with total safety and no pain or difficulty. This highly sensitive and accurate test detects flow limiting lesions even as little as 20 percentage with over ninety percent accuracy while other existing tests like angiography detect only above 40 percent and TMT becomes positive only above 60 percentage blocks in heart’s blood vessels. This sensitivity helps early detection, prevention and treatment of Coronary Artery Disease which kills almost eight lacs Indians every year that is about 90 Indians every hour and more than three million worldwide. For the undiagnosed victims delay can be costly or even fatal. RGCI is the only non invasive system that can give an accurate diagnosis even in acute heart problems in more than ninety percent patients.

Dr.Shirbur mentioned that this low cost screening test should be part of every master health check up for all persons above 30 years of age and is specially useful for persons at high risk having diabetes, high blood pressure, overweight, smokers, alcoholics, high cholesterol and persons with family history of heart disease, sedentary and stressful lifestyle, etc. Other uses of RGCI include follow up after angioplasty (ballooning, stents etc) and bypass surgery. It is also ideal for mass screening of clients and staff of institutions, corporates, insurance companies etc. Special tests like Nitrate enhanced, stress cartography etc can also be done with RGCI.

Dr.O.P.Aggarwal a senior cardiologist from Bareilly who is using RGCI for a long time told that RGCI is the only investigational tool in the field of cardiology which does not have any difference of opinion. Contrary to that all investigations including angiography have differences of opinion if placed before different cardiologists. Furthur he added all preoperative patients must undergo RGCI which in this case takes only 60 seconds to evaluate the safety of anaesthesia and surgery in the patient.Another doctor from Bareilly, Dr.Ram Babu Aggarwal ex-vice president Indian Medical Association of Uttar Pradesh said RGCI is also useful in young children and chest diseases and he stressed that RGCI does not require any admission for doing the test.

Dr.Sibia has a vision that such equipment would be part of every physician’s setup for early diagnosis, follow up and the selection of modalities of treatment - medical or surgical together with appropriate life style modification.

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THE HINDU
Date:27/07/2003 URL: http://www.thehindu.com/2003/07/27/stories/2003072701460500.htm

Southern States - Karnataka-Bangalore
Machine for 3D mapping of heart developed

By Our Special Correspondent

The Haemotron developed by the Bangalore-based Heart and Vascular Research Centre

Bangalore July 26. What cardiologists are increasingly depending on to diagnose heart ailments is a "3D map" of that vital organ.

Making this possible is the Bangalore-based Heart and Vascular Research Centre which has designed a fourth-generation Haemotron to do the mapping. Cardiovascular 3D cartography has become a new technique for early detection of coronary artery disease (CAD). A cardiologist can also evaluate the functional status of the heart and the circulatory system. Both are needed to plan further treatment.

It is a non-invasive procedure, and the patient is "wired" to Haemotron using 12 sterile electrodes and a highly sensitive transducer. The recordings are made for 1,024 heartbeats while the patient is lying down and repeated after a drug that causes mild stress is given. A high-speed computer makes all calculation and prints out the results. The entire procedure takes six to 10 minutes.

The cardiologist gets data that was earlier not possible, through non-invasive methods. The records obtainable include details such as the amount of blood pumped for every beat of the heart, pressure, volume and time relationship, relative oxygen demand, and the state of the heart as a pump. These parameters give the patient's complete cardiac and circulatory status.

The 3D maps of the heart have a positive predictive accuracy of 98.28 per cent and a negative accuracy of 82.16 per cent in detecting heart disease. Angiography measures the quantity of blockages in the heart but does not give other causes for the reduced blood flow. Blockages in the arteries contribute to only 70 to 80 per cent of the reasons for the reduced blood flow.

Y. Parameshwara, cardiologist and winner of the B.C. Roy National Award, who was present at the launch-demonstration of Haemotron, said the machine helped in non-invasive and painless mapping of the heart, and was an important tool to detect coronary heart disease early.

 

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CARDIOVASCULAR CARTOGRAPHY

Mass mapping of Cardiac Blood Flow Non-invasively

Poster Presentation at - 7^th Punjab Science Congress,

Department of Human Genetics, Guru Nanak Dev University, Amritsar

 

Dr.Parneet Baring, PhD, Dr.S.S.Sibia, MBBS, MD, Dr.Harpreet Kaur Sibia, MBBS

Sibia, Medical Centre, B/XIX-573, Civil Lines, Ludhiana - 141001

 

Five hundred suspected patients of Coronary Artery Disease underwent Cardiovascular Cartography test done to assess the haemodynamic parameters including myocardial blood flow prior to nutritional guidelines, lifestyle modification and where required other treatments. The device is a new technique for early detection of Coronary Artery Disease and also for the evaluation of functional status of the heart and the circulatory system (haemodynamics). The information is safely obtained in about 30 minutes without any catheterization or radiation. Some of the information obtained was never possible, non-invasively, earlier. CAD is a progressive, often silent killer and if left undetected at its earlier stage, can lead to Angina pectoris, Myocardial infarction and sudden death. Persons with high cholesterol, blood pressure, diabetes, obesity, smokers, sedentary persons and those with a strong family history of heart disease can know about their disease status in time and hence take timely measures. Dietary management and lifestyle modifications are more effective the earlier they are initiated. Hence Cardiovascular Cartography can play a major role in controlling the rapidly increasing incidence of Coronary Artery Disease in Indians by providing a cost effective mass mapping test. The poster provides details of the over thirty parameters obtained by Cardiovascular Cartography.

 Keywords: coronary artery disease, Cardiovascular Cartography, haemodynamic, myocardial blood flow, nutritional guidelines, lifestyle modification, circulatory system, catheterization, radiation, non-invasive, CAD.

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PRESS RELEASE

RGCI DETECTS BLOCKS YEARS BEFORE HEART ATTACK

Ludhiana: 19 Feb, 2000: India’s seventh Cardiovascular Cardiographic Imaging System (CVC) was installed today at Sibia Medical Centre, Ludhiana. This new non-invasive technique to detect Coronary Heart Disease in the form of Realistic Geometric Cartographic Imaging (RGCI) brings a new diagnostic advantage for chest pain patients for complete evaluation. It will help doctors monitor and diagnose heart problems even in early stage making timely protective treatment possible. RGCI is an advanced technique based on 3D mathematical modeling and simulation, that accurately informs of the probable location and severity of flow limiting lesions in heart’s blood vessels and its oxygen demand / supply with the help of measurement of heart muscle blood flow.

This equipment works on the principals of Integration of time related physiological curves derived out of transthoracic Bioimpedance, Electrocardiography and subsonic thoracis transverse waves to detect various cardiac parameters relating to pressure, volume, time and flow. A team of experts from Delhi, Bangalore and Mysore visited the city and addressed the leading cardiologists and physicians on this occasion where Dr.L.S.Chawla founder Vice Chancellor of Baba Farid University of Health Sciences was the chief Guest. Dr Rajah Vijay Kumar, Chairman Centre for Artificial Intelligence and Non Linear Studies, Bangalore and co-inventor of RGCI explained that doctors prefer to gain maximum accurate information about the cardiovascular system non-invasively. In invasive techniques catheters have to be inserted to know the status of coronary vessels and risks of injury, rupture, infection and radiation always exist. If the doctors get accurate data about heart functions without inserting any equipment, it would minimise the risk and simplify the process. This new technique does exactly that and could be repeated any number of times without any harm.

            The new noninvasive system uses skin electrodes and sensors that acquire and monitor the data in just 30 minutes. RGCI is providing continuous accurate data about any changes in haemodynamics such as the heart rate, stroke volume, cardiac output and other 24 parameters. Dr.G.N.Shirbur a leading cardiologist from Simha Heart Foundation, Mysore added that RGCI is the only technique that takes into consideration upto twenty four parameters and can be applied on a patient at rest with total safety and no pain or difficulty. This highly sensitive and accurate test detects flow limiting lesions even as little as 20 percentage with over ninety percent accuracy while other existing tests like angiography detect only above 40 percent and TMT becomes positive only above 60 percentage blocks in heart’s blood vessels. This sensitivity helps early detection, prevention and treatment of Coronary Artery Disease which kills almost eight lacs Indians every year that is about 90 Indians every hour and more than three million worldwide. For the undiagnosed victims delay can be costly or even fatal. RGCI is the only non invasive system that can give an accurate diagnosis even in acute heart problems in more than ninety percent patients.

Dr.Shirbur mentioned that this low cost screening test should be part of every master health check up for all persons above 30 years of age and is specially useful for persons at high risk having diabetes, high blood pressure, overweight, smokers, alcoholics, high cholesterol and persons with family history of heart disease, sedentary and stressful lifestyle, etc. Other uses of RGCI include follow up after angioplasty (ballooning, stents etc) and bypass surgery. It is also ideal for mass screening of clients and staff of institutions, corporates, insurance companies etc. Special tests like Nitrate enhanced, stress cartography etc can also be done with RGCI.

Dr.O.P.Aggarwal a senior cardiologist from Bareilly who is using RGCI for a long time told that RGCI is the only investigational tool in the field of cardiology which does not have any difference of opinion. Contrary to that all investigations including angiography have differences of opinion if placed before different cardiologists. Furthur he added all preoperative patients must undergo RGCI which in this case takes only 60 seconds to evaluate the safety of anaesthesia and surgery in the patient.Another doctor from Bareilly, Dr.Ram Babu Aggarwal ex-vice president Indian Medical Association of Uttar Pradesh said RGCI is also useful in young children and chest diseases and he stressed that RGCI does not require any admission for doing the test.

Dr.Sibia has a vision that such equipment would be part of every physician’s setup for early diagnosis, follow up and the selection of modalities of treatment - medical or surgical together with appropriate life style modification.

 

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3D-Cardiovascular Cartography: A Novel Non-invasive
Technique for Coronary Screening in Aircrew
by Gp Capt GS Nayar (Retd) Former Senior Advisor (Aviation Medicine), IAF
Dr GN Shirbur Cardiologist, Heart Care Foundation, Bangalore

Abstract
Cardiovascular screening to exclude coronary artery disease (CAD) forms a very important part of any aircrew evaluation. A routine ECG forms part of initial evaluation for aircrew duties. As the incidence of CAD is age-related, repeat ECG examination and even periodic Bruce protocol stress test are mandatory requirements by certain Regulatory Agencies including India. Routine use of cardiac stress testing has been controversial because of inadequate specificity when applied to an asymptomatic population. At times further invasive tests for delineation of the coronary arteries become necessary with avoidable stress and even risk to life to the apparently normal aircrew. Availability of population health data and increasing use of computer applications in medical database management have made risk analysis and risk stratification easier and more reliable.

This paper discusses the use of a truly non-invasive protocol for routine coronary screening, especially of aircrew. The first part of the protocol involves the use of a simple computer-based algorithm developed using the Framingham study with various risk factors including age, gender, family history, smoking habit, body mass index, blood pressure, cholesterol and HDL levels. The software predicts the coronary risk of the individual based on population data. The second part of the protocol involves the use of a novel new technique of 3-D Cardiovascular Cartography (CCG). This is based on 3-D mathematical modeling and simulation using high speed computation enabling non-linear haemodynamics to be evaluated from beat-to-beat recording of the cardiac cycle. The regional coronary circulation is displayed and a number of physiological data of cardiac functions are calculated. It is recommended that the scope of using these non-invasive methods in routine cardiovascular evaluation of the aircrew be considered. The data obtained by these techniques will also be useful in aircrew maintenance programmes based on preventive cardiology.

Keywords: Aircrew evaluation, coronary risk stratification, coronary cartography, aircrew maintenance

Flying an aero plane is an occupation that demands repeated successful demonstration of a minimum standard of physical and mental fitness by its operator. The objective of the regulatory authority will always be to rule out even the remotest possibility of a sudden incapacitation of the pilot while at the controls. The medical regulations thus insist on clauses to preclude such events as epilepsy, incapacitating angina, altered consciousness or sudden death.

Cardiovascular Screening
Cardiovascular screening to exclude coronary artery disease (CAD) thus forms a very important part of any aircrew evaluation. A routine ECG forms part of initial evaluation for aircrew duties. As the incidence of CAD is age-related, repeat ECG examination and even periodic Bruce protocol stress test are mandatory requirements by certain Regulatory Agencies including India1. The following are some of the important considerations in this respect:

• The resting ECG is an insensitive tool for the detection of pre-symptomatic CAD although it identifies a small number who have suffered a silent myocardial infarction (MI)2.

• The risk of sudden death from an unheralded heart attack increases with age. Thus, when compared to a man of 30 years, the risk of sudden death from acute MI increases 8 times at 40 years, 36 times at 50 years and 100 times at 60 years. Further, 50% of those dying suddenly do so without premonitory symptoms 3.

• Sudden death is the initial presentation in more than one third of MI with up to 60% of patients dying in the first hour. Other initial symptoms may include incapacitating angina or altered consciousness, both equally dangerous when occurring inside the cockpit environment.

• Aeromedical stresses such as heat, hypoxia, hyperventilation, and high Gz manoeuvres may provoke dysrhythmia or infarction in individuals with pre-existing coronary artery lesions⁴.

Exercise ECG is not a routine mandatory requirement for aircrew evaluation in the ICAO ISARPs5 nor in the JAR6. The positive predictive value of an abnormal treadmill test for significant CAD in men average about 21%, with values ranging from 5% to 46%, but in most studies were less than 25%7. The poor yield of exercise testing due to the relatively low prevalence of CAD in the healthy aviator population must be recognized.

While there is general agreement that CAD is a disqualification in the context of military aviation, careful consideration supported by detailed evaluation is made mandatory in the case of civil aircrew. Regulatory authorities may often take the easy option of denying licenses to civil aircrew detected to have CAD on routine testing. The Federal Aviation Authority (FAA) has an exceptional record of granting medical waivers to pilots with evidence of CAD following painstaking evaluation as can be seen from the figures in Table 1.

Table 1. Medical certification of pilots with CAD - FAA (January 2001)

Event	Type of  License
	Class I	Class II	Class III
Myocardial infarction	299	323	2,819
Percutaneous transluminal angioplasty	354	278	2,233
One or more coronary stents in the same time frame	213	173	1,289
Coronary artery bypass grafting	256	295	3,197
Atherectomy	51	10	227

 Some of the newer tests for coronary evaluation, though not yet widely available, include the following: 

• Imaging for coronary artery calcification

• Stress radionucleide imaging

• Stress echocardiography

• Non-invasive coronary angiography, such as electron beam computed tomography (EBCT), magnetic resonance angiography (MRA)

Coronary angiography is the 'gold test' which forms the basis for evaluating whether a lesion is Non-significant or Significant depending on the degree of occlusion of any coronary artery as indicated in Table 2.

Table 2. Criteria of severity of CAD 

Degree of severity	Occlusion in any coronary artery	Aggregate of occlusion
Minimal Coronary Artery Disease (MCAD)	< 40%	< 120%
Significant Coronary Artery Disease (SCAD)	> 40%	> 120%

 The prevalence of CAD in asymptomatic military pilots is reported to be extremely low even though published figures are not available for India. Among the commercial aircrew and private pilots, this prevalence may be closer to that of the general population. With the treadmill stress test being made mandatory among Indian civil aircrew above the age of 35 years since over 5 years now, a huge database must be available for detailed analysis with a view to review the practice and give very valuable inputs to other international regulatory authorities. An abnormal treadmill test continues to generate a lot of anxiety among the aircrew and many physicians are unhappy to subject them to further invasive procedures knowing that the predictive significance of the positive treadmill test in an unselected aviator population may be less than 10% for angiographic significant CAD8. Further, as the treadmill tests are being done outside the direct supervision of the physicians of the medical evaluation centres, this policy needs to be reviewed to ensure standardization of the aircrew evaluation procedures.

Coronary Risk Stratification

A suggestion gaining increasing acceptance internationally is the need for risk stratifying the aviator population prior to performing screening tests in order to improve their predictive value.

The authors propose that this suggestion be accepted at the earliest and recommend the following procedures: 

• History, physical examination, laboratory investigations, etc be utilized to assess the classical CAD risk factors.

• Use of simple computer-based risk calculators can be used to assess the risk factors quickly and effectively.

• An example of such an approach will be the use of a Framingham risk index.

• If the risk index is above the specified threshold, a graded exercise test may be conducted which will show a better predictive value.

• If the stress test is positive, other tests including coronary angiography can be conducted to establish the diagnosis.

Cardiovascular Cartography (CCG)

A novel technique of 3-D Cardiovascular Cartography (CCG) has recently been developed by Indian scientists. This is based on 3-D mathematical modeling and simulation using high speed computation enabling non-linear haemodynamics to be evaluated from beat-to-beat recording of the cardiac cycle⁹.

As far as the patient and the doctor are concerned the technique is as simple as recording an ECG but with a little more elaborate and precise preparation of the patient. The equipment (Fig 1) uses a vertical acceleration detector that picks up subsonic waves that are transmitted from the heart to the chest wall throughout the cardiac cycle. The recordings of 1024 heart beats include beat-to-beat stroke volume, systolic time intervals, flow turbulence and arterial blood pressure. Using specialised digital signal processing and neural network computing, a predictive model of the individual is created and the measured haemodynamic behaviour is superimposed on the predictive model. The resultant deviation difference is distributed as pressure zone, volume zone, time zone and flow zone in a clockwise direction on the cardiovascular cartogram (Fig 2). The regional coronary circulation is also displayed (Fig 3). CCG is scale independent but has positivity and negativity indicating the deviation difference, reflecting physiological, pathological or compensatory phenomena and thus assesses the efficacy and function of the cardiovascular system. A more detailed description of the technique is out of the scope of this presentation.

CCG is a novel non-invasive tool with a systemic approach for interpreting haemodynamics based on modeling and simulation techniques. Its clinical application is oriented especially to diagnosis, estimation of prognosis and modification of therapeutic modalities in coronary artery disease (CAD). Carefully conducted studies have indicated that CCG has a sensitivity of 91%, specificity of 92%, positive predictive accuracy of 98% and negative predictive accuracy of 75% (Table 3).

Table 3. Sensitivity and specificity of CCG 

	Primary presence of  CAD	Anterioseptal region  (LAD)	Inferioseptal region      (RCA)	Lateral region (LCX)
Sensitivity	91%	83%	80%	72%
Specificity	92%	76%	74%	80%
PPA	98	85%	80%	81%
NPA	75%	74%	74%	70%
Mean Accuracy	91%	81%	78%	75%

 The CCG technique is adequately sensitive and specific in the detection of CAD even at a very early stage of the disease. CCG results compare favourably with other available invasive and non-invasive tests to detect CAD and can be a low cost solution for mass screening of a population for early detection of CAD.

Risk Modification

One of the significant advantages of this combined system of CAD risk stratification followed by non-invasive CCG will be in the field of primary prevention of CAD. As the entire process involves transparent and easy-to-understand presentations, the subject, viz., aircrew in our context, has total involvement in the evaluation and gets full grasp of the salient features of the underlying mechanisms in the development of CAD. This will help in motivating the aircrew on the preventive measures to improve the clinical risk profile through life style management and other measures.

Conclusion

A novel method of using computer-aided risk analysis and stratification followed by a non-invasive process of CCG is recommended to carry out coronary screening among aircrew. Prompt acceptance of the findings and recommendations on the part of the aircrew will bring about a favourable shift in their attitude towards primary prevention of CAD. Early identification of the risk factors will help in improving their health status with a positive impact on air safety.

REFERENCES 

1. AIC 4/1995, DGCA, Ministry of Civil Aviation, Government of India

2. Taggart P, Carruthers M, Joseph S, et al. Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteries. British Heart J. 1979; 41:14-225.

3. Doyle JT, Kannel WB, McNamarra PM, et al. Factors relating to suddenness of death from coronary artery disease: Combined Albany-Framingham studies. Am J Cardiol. 1976; 37:1073-1078.

4. Clinical Practice Guideline for Coronary Artery Disease, Aerospace Medical Association (Internet)

5. ICAO. Interntional Civil Aviation Organization: Interntionals Standards and Recommended Practices (ISARPSs) - Personnel Licensing, Annex 1 to the Convention on International Civil Aviation. Montreal: ICAO. 1988

6. JAA. JAR-FCL 3: Flight Crew Licensing Medical. Joint Aviation Authorities, Hooddorp. 1998.

7. Schlant RC. Guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association task force on assessment of cardiovascular procedures. J Am Coll Cardiol. 1986; 8(3): 75-738.

8. Rayman, RB, Clinical Aviation Medicine, 3rd edition, Castle Connolly Graduate Medical Publishing, LLC, 2000, pp. 162.

9. Kumar RV, Shirbur GN, Augustus RJ, et al. Cardiovacular cartography - a new non-invasive technique to detect coronary artery disease. Fourteenth IEEE Symposium on Computer-Based Medical Systems, 26-27 July 2000, Bethesda, Maryland.  

 

 

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