FROM THE ESC, PARIS. 28th-31st 2011.

Well, many of our cardiologist are at present in Paris, attending the European Society of Cardiology, annual scientific meeting. I have not been attending this meeting for quite awhile now, as I feel that it was too time consuming ( ??sour grapes ), nothing big to announce, and that the internet has made the world flat.
Yesterday, the ESC started. From the internet I can see that there is nothing earth shuttering in the program. From my point of view, I think Sunday is dominated by two important papers.
1. The long term followup of ASCOT LLA.
You may remember ASCOT LLA was a study, presented and published in 2003, studying the effects of lowering blood pressure in a 19,000 strong cohort of hypertensives. There was also a 10,000 strong arm of hypertensives who had elevated lipids and was treated with Atorvastatin 10mg ( low dose statins ). In ASCOT LLA, their 3.3 years ( mean follow-up ) results were announced, showing a reduction in those on Lipitor 10 mg of CV events and CV deaths. Now after another 8 years of follow-up ( 11years follow-up in total ), we see that after the initial 3.3 years, there was reduction in all cause mortality, but no further reduction in CV mortality and morbidity. Interesting. What this would mean to me is that in the first 3.3 years of treatment, the CV deaths and suffering was reduced. After 3.3 years, these remain stable in both arms, and the further reduction in death rates in the study group was in non-CV deaths and suffering. A further analysis showed that there was a large reduction in death from Pulmonary infectuons. Interesting. This gives rise to many thoughts. Is it that low dose statins also in crase body resistance to fight infections? or does it act as an adjuvant to increase the potency of antibiotics? Whatever it is, taking 10 mg of lipitor ( at such a small dose, the side effect rates are very, very low ), is still beneficial from the cholesterol lowering point of view, the reduce inflammation point of view, and also in the longer term, in the lung infection point of view.
2. The Era of CETP ( Cholesteryl ester transfer protein ) inhibitors have arrived.
Last year, at the American Heart Association annual scientific meeting in Chicago, we saw the presentation of the DEFINE study, testing the safety and efficacy of Anacetrapid in the management of coronary artery disease. Anacetrapid is manufactured by Merck. The results were good. Anacetrapid was shown to be safe, increasing HDL-C by 138% without a concomitant increase in BP ( as was seen in Torcetrapid- and which cause the death of Torcetrapid ).
In Paris yesterday, Roche announced the result of dal-VESSEL, a study of their Dalcetrapid ( CETP inbitor by Roche ). The lead worker here is Dr Thomas Luscher of Zurich University. Yes, Dalcetrapid is also safe but not as powerful as Torcetrapid and Anacetrapid, in terms of HDL-C increase. Dalcetrapid only increase HDL-C by about 31%, but is was safe, with no increase in BP. However it did not meet its primary end point of improving brachial artery vaso-dilation and flow. The study was called dal-VESSEL because it was a study to show that Dalcetrapid, besides improving HDL-C, would also improve flow in the brachial artery. This is did not do.
Yesterday also saw the announcement of the follow-up study, dal-OUTCOMES, to enroll more patients and study the 18 months outcome ( study results should be know by 2013 ), on the use of Dalcetrapid in CV mortality and morbidity.
Yesterday, the boys from Mount Sinai hospital led by Dr Zahi Fayad, also presented their results on dal-PLAQUE, a study on the use of dalcetrapid on plaque inflammation and regression. This is a small study of 100 odd patients given dalcetrapid over 24 months, showed that there was no further plaque progression with MRI and also no pro-infammatory response in the plaque with the use of positron emission tomography.
All in all, there was plenty of CETP on the first day.
Well, lets see what day 2 brings.
To all my friends there, please learn much and come home and share with us , so that we can also learn from you.

CCTA, THEY ARE GETTING THERE : CCTA + CT PERFUSION

Looks like the cardiac imaging boys are surely getting there. In the early part of this month, I wrote about the work of the East European work on CCTA FFR ( studying the vessel perfusion ) technique.
In the Aug 23rd issue of Circulation : Cardiac Imaging, there is a nice. small piece of work by the Austrians on CCTA / CT perfusion. Dr Gudrun Feuchtner and colleagues from the University of Innsbruck, Austria, studied 36 males and 3 females with intermediate coronary risk, with the standard CCTA using the 128 slice, dual source Siemens scanner, and then studied their myocardial perfusion at rest and after adenosine provocation. These patients were then subjected to invasive coronary angiogram as gold standard. There found a correlation of
Sensitivity : 98%
Specificity : 96%
Positive predictive value : 95%
Negative predictive value : 96% ( per vessel ).
All these numbers are very good. To top it all, the radiation exposure was only 1 mSv, and the scan time was said to be 0.3 sec., less than 1 heart beat.

Looks like the cardiac imaging boys are getting there. We have a much better scan now, that can look at anatomy and also myocardial perfusion. With the Latvia boys technique, we can also estimate vessel lesion FFR. If they are able to combine both the techiques ( myocardial perfusion with vessel FFR ), then ultimately the non invasive CCTA / CT perfusion / CTA FFR will probably replace the invasive coronary angiogram, and the coronary angiogram will then be use only as a guide to angioplasty. And if you are going for By-Pass surgery, then there little need for a coronary angiogram. Looks like the CCTA / CT perfusion / CCTA FFR will suffice.
Then the next question is cost. How much will a CCTA / CT perfusion / CCTA FFR cost?
Not to worry, the cardiologist will still do coronary angiogram as a prelude to angioplasty. At this point in time, I do not see any work on non-invasive angioplasty, so we are safe for awhile.
But watch this page. There is much work done and I am sure there will be more developments.

AMBULATORY BP MONITORING TO DIAGNOSE HYPERTENSION

For many years, we have thought that the diagnosis of hypertension is probably one of the easiest in medicine. Fix on a blood pressure cuff ( and we like the hardy mercury column syphynomanometer ), pump it up, lower the BP column slowly ( 1 millimeter per second ), and listen for thefirst pulsatile ( systolic) BP sound and then the loss of the pulsatile ( diastolic ) BP sound. There we have it, your BP is 120/80 mmHg. That seems simple enough.
The whole problem is that BP varies, and responds to the environment. It a stressful environment, the BP may rise, and in a calm and peaceful environment, the BP may fall. This is obviously because, the circulatory system, must increase its cardiac output for the human to have sufficient cardiac output to manage a stressful situation. Blood pressure is a function of cardiac output., so when cardiac output rises, BP rises, thereby increasing the circulation and so allowing more circulation ( more oxygen and nutirents being circulated ) to cope with the stress. So BP is also determined by circulation. Anxiety is the most common cause of a falsely elevated BP at a physician's clinic. We have a name for this - "white collar" hypertension.
Because of this fact, many hypertensives may be overdiagnosed, if the physician just takes a spot reading, and initiates treatment. That spot reading, in a stressful physician clinic, may be an "anxiety " reading. This fact, two devices have been brought into the market two near device.


The first is a professional device, called the 24 hrs ambulatory monitoring. This is usually uused by the professionals. The BP cuff is fixed on to the patient for 24 hours, and the BP cuff is pumped up automatically at regular intervals ( say every 2 hours ) and the BP is recorded digitally and stored in the optical hard disc which is attached to the cuff ( as shown in the image on the left ). With the BP cuff on, the patient can go about his normal activity ( a bit uncomfortable ), and all the BP for the whole day is stored. After 24 hours the recording is returned and analysed in a main computer, and a 24 hour tracing is printed out, showing us the patients BP for the last 24 hours. This is better obviously than a spot clinic check, but it is still not the best, as there is still an element of stress during that 24 hours, and it is not a pleasant device to carry around, as it does limit your activity, and also the regular pumping up of the cuff can be a nuisance, especially at night when you want to sleep. Imagine sleeping with something strap to your arm, which pumps up ( say 4 hourly ) through the night.

Then we have the home BP monitoring unit, which is very popular. Patients buy them ( they are quite affordable ), and keep at home. When they feel a headache or any usual symptom, they fix on the cuff and presses a button which pumps up the machine and records the BP digitally, with a monitor to display the number. See image on left. A popular brand in Malaysia is Omron. Nowadays, it is not unusual to have a patient come to the clinic with their daily BP recording for the last month.



This article is in some ways prompted by a clinical study by the National Institute of Health Research, UK, studying the cost effectiveness of ambulatory BP monitoring in the diagnosis of hypertension. The researches found that 24 hrs ambulatory BP monitoring was the the most cost effective way of diagnsosing hypertension and have been able to save cost. They found that the traditional two clinic visits, to confirm hypertension, still tend to over-diagnose hypertension by almost 25% resulting in 25% of patients being treated. 24hr BP monitoring tend to cost more upfront due to the cost of the device and also the cost of generating the report. This initial cost is off set by the cost savings from treating 25% less patients.
While this may be true for UK, I must say that my own preference will be for properly coached and properly supervise home BP monitoring using one of those home monitoring device. For those hypertensives without target organ damage, I would spend time explaining to them how to take their BP at home. I usually like a 3 times a day regime, where they take their BP using one of those digital devices, after 5-10 mins rest ( exhaling and inhaling deeply ), This should be repeated at 7.30am, 6pm and 10.30pm. The BP should be recorded and the average calculated, and recorded. They are all advise that should they take it during a crisis or stress, it is bound to be elevated. I find this a good means of managing hypertension. It also gets the patient to care for himself/herself, and increases compliance. Of course, the digital BP machines need calibration and adjustments yearly or two yearly.
The NICE recommendation may be good for UK, where patient understanding and compliance may be good. I find the BP cuff inflation and deflation a nuisance. Of course 24 hr Ambulatory BP monitoring requires a medical center referral, and the additional cost, and it is also not infallible.
It is true that in our local population, there is a high percentage of "white collar" hypoertension as we are subjected to more and more stress from the 21st century demands. In my practice, I seem to see matbe a 40-50% incidence of "white collar" hypertension. Once proven, these patients can be help with just regular assurances, relaxation techniques, green veges and fruits and no added salt diet. Simple and cheap.
Of course all these patients have no target organ damage.

EATING PROCESSED MEATS INCREASE STROKE RISK

It is obvious that in Western countries, eating process meat is common and perhaps the norm in winter. Low fat turkey, ham, bacon, bologna, etc are continental favourates.
There is a clinical, epidermiological study done in Sweden, using the Cohort of Swedish Men registry, to see the associations between the eating of processed meats and the risk of strokes. The Cohort of Swedish Men is something like the Swedish equivalent of the Framingham Study. In the Cohort of Swedish Men, this started in 1997, the population of Swedish men over the age of 47-79yrs were followed up, and given questionaires about their health and in this case, their eating habits. They were followed for 10 years, and the incidence of stroke determined. This study was led by Dr Susanna Larsson. This study was published in the August issue of the American Journal of Clinical Nutrition. They found that the eating of precessed meat carries with it a 23% increased incidence of strokes. The stroke rates were 23% higher between those who consume minimal amounts of processed meat compared to the high consumers. The strokes were mainly ischemic strokes. Of the 40,291 men in the cohort, there were 2409 strokes over 10 years.
The eating of fresh red meat as a whole, did show a slight increase risk of strokes, but the numbers were not significant.
Of course, the thoughts are on the why? Is it the salt in the process meat, being associated with hypertension? Is it the nitrites in the processed meat? Or are there other agents in the processed meats. Looks like the why has not been well worked out.
For Malaysians, the need to eat processed meats should be minimal, with so many fresh meats around us. Whether it be chicken, beef, fish or pork, we have them in abundance. Please take fresh meat, and for that matter, fesh veges and fruits, to try and reduce the blood pressure and so also strokes.

THE GENOUS STENT. IS THIS THE END?

About 1 year ago, I wrote that the TRIAS 1 results on the Genous ( EPC capture stent ), was poor when compared to the first generation drug eluting stent.
Well Dr Margo Klomp, from the University of Amsterdam, Netherlands, has just published their 1 year followup of their study, comparing the Genous stent with the commercially available DES ( a mixture ), and showed that the Genous stent had double the rate of re-stenosis when compared with commercially available DES, not even comparable with the second generation DES. The 304 patients that were in Dr Margo's study was part of the enrollees for the TRIAS HR study, which was still enrolling patients.
Probably as a result of Dr Margo's publication, the TRIAS HR study was discontinued prematurely.
When I were introduced to the Genous stent almost 10 years ago now, I was quite impressed with the concept that you could use monoclonal antibodies to turn on Epithelial Progenitor cells and have them coat your stent. What a smart idea, and wow, the video pictorials were captivating. Cells were floating all over, and selected ones were sticking to the stents. The impression then were " We are not a Drug Eluting Stent " we are a new concept, cellular stent. I have always argued at international meetings that when you turn on a cellular reaction, you often do not get one straight answer, as the body cells are complicated structures. More so the vascular endothelium. It is not exactly a simple computer bit/byte response. If the EPC concept is straight forward, we should at least see less stent thrombosis. This is also not so. I remember the earlier days when the University of Singapore doctors were doing a trail to show that this EPC capture stent, when placed in patients following an acute heart attacks ( these are the patients with high risk of stent thrombosis ), had less stent thrombosis. That did not work out, so Singapore Uni had given up on that. We tried to sound the alarm bells, but of course being an Asian Chinese, nobody listens to you. ( The white man knows best, right ). This was despite the fact that the company that first discovered this stent ( Orbus Niche ) was a Chinaman own company based in Hong Kong with factory in Shenzhen.
Anyway, when eHealing registry came out almost 1-2 years ago ( my memory is slipping ), their big marketing guy came out to convince me that the eHealing registry data of over 5,000 patients was great. I took a look at the data, and was trying to convince him, on his own data, that it was not. Of course, at the end of that meeting, we agreed to disagree.
Well, we have just seen the publication of the select 1640 patients from the eHealing refistry with 1 year follow-up ( that previous 5,000 patients was with 5 year follow-up ), showed that at best the Genous stent, was no worse or no better then the first generation Taxus stent in terms of MACCE events and TLR. This latest publication on the select eHealing registry, was authored by Dr Robbert de Winter from the University of Amsterdam, Netherlands.

	Genous (n = 304)	DES (n = 318)
TLFa	17.4%	7.0%
Cardiac Death	2.0%	1.0%
MI	4.3%	1.3%
TLR	15.2%	5.7%
Stent Thrombosis	2.7%	1.0%

What I also failed to understand is that there is one private medical center that uses almost exclusively the Genous stent, knowing the poor performance. That really stumps me. In the light of all the data now available, how can you justify using a Genous stent when you have, easily available, at reasonable cost, a second generation DES? How can you justify to your patients? maybe there are some non-medical reasons for doing so, and I do not wish to speculate.

Is this the end of Genous, now that TRIAS HR has been called off? Perhaps not, I am also aware, and have seen the preliminary data on a combo Genous + sirolimus eluting stent. Now JnJ Cordis had teamed up with Orbus Niche, to produce a stent that is coated one side with the EPC capture monoclonal antibody, and the abluminal surface with sirolimus, hoping to reduce intimal hyperplasia with sirolimus and reduce stent thrombosis with EPC capture. The early data looks promising, like many else. Lets wait and see. The problem is JnJ Cordis, the prime mover of this stent, is now no longer in the stent business. By December 2011, they would have closed the division. I had written about this earlier. So is this the end of Genous? I really do not know.

Well, I would not be surprise, if the company is not looking for a buyer. The sad thing is that, I do have some friends ( I hope they still consider me one, after all that I have written ), in Orbus Niche. No, I think that when you try to fine tune God's handiwork in the vascular endothelium, I suppose also any of the other body cells, you have to think as smart as God, and few of us can.

A PROPOSAL ; THE RE-CYCLING OF DRUGS IN MALAYSIA.

I read with great interest, the government's proposal to ask patients not to throw medications that they do not wish to take, away into the dusk bin, but to throw it into a re-cycling bin, so that the drugs can be re-cycled. This "joke" appeared in the front page of the STAR on Sunday. While it is true that some medication is wasted by patients who throw them away, I do not think that re-cycling medication is the way to go to save money.
Firstly, if the government agrees that medication is good for the patient then they should find out why patient throw away medication? Is it because of poor medical care?, is it due to poly-pharmacy, is it poor communication between healthcare provider and patient? is it that you do not treasure things that are given free?, is it because of side effects? As always, in science, we need to know the reason why, if we believe that medication can help and save lives. Just accepting that people throw away medications, without finding out why, will not solve the problem. Whatever you do thereafter, there will still be wastage, as the problem have not been corrected. This morning, I read in the STAR again, that the government is saying that their doctors are prescribing too many medications, thereby causing wastage. This also may be true, as the standard of medical graduates from our 30+ medical schools is poor and getting poorer. We have written about this before. There is now a moratorium on the building of medical schools, but as always, we are shutting the gates after the horse has bolted, or after the cronies have "stolen the cake".
If the government is serious about saving money and not spending so much on drugs and medicines, the easiest way ( by the stroke of the pen ), is too stop the " Pharmaniaga Scam". This Pharmaniaga scam has been going on for years.
What is the Pharmaniaga scam? This is bolehland's way of procuring medication for government hospitals. Let me illustrate. The government hospital needs drug A for hypertension treatment. He identifies the medication and orders it. Now, the importing company for drug A cannot sell it directly to the ministry of health. That will be too clean and too simple. He must sell it to Company X ( I am sure we know who owns company X ). Company X who does not know anything about drugs, who does not even need to see the drug A, buys the drug and sells it to Pharmaniaga, who then sells it to the ministry of health. Lets say that the drug for hypertension cost RM 10 to the importer, who would normally have sold it for RM 15 to the government ( the mark-up to cover cost or storage, transport, administration etc ). Now he does not and cannot do that. The importer sells it to Company X at RM 15. Company X sells it to Pharmaniaga at RM 30 ( remember company X does not even take delivery or sees the drug, he just paper passes it on ), and Pharmaniaga then sells it to the government for RM 45.
We call this layering and leakages. I am sure we all know who company X and Pharmaniaga belongs to. If the government wish to save taxpayer's money, stop the layering, that will save almost half the healthcare pharmacy budget, plain and simple. But then their UMNO middlemen will have no money to spend.
Coming back to the Sunday STAR, are the poor who seek care in Public Hospital so neglected as to be given re-cycled medications? with the risk of poor storage, uncertain efficacy, uncertain expiry, poor handling, mixed up in pills? Are we that bad off that we have to used pills picked up from the garbage box? Do our poor patients deserve that?
As we say in private practice, the biggest gain to the private practice in Malaysia is to have a fumbling government with poor policies and execution. Poor government healthcare service is the cause of a thriving private healthcare service. In other words, the way to limit private healthcare profits, is to have a good public service. For some reason, the government does not wish to improve public healthcare service. These hair brain schemes of re-cycling medications and bringing out poorly qualified doctors into public service is the cause of the rise in healthcare cost. If public hospitals are good, private hospitals will be affected. But there again, in Malaysia, is the same as asking if pigs can fly.

IATROGENIC BLOOD LOSS FOR HEART ATTACK PATIENTS

As I was reading, I find this paper very interesting. After 31years of cardiology, I did not realise that a patient admitted for heart attack, could loss so much blood from medical tests.
Dr Adam Salisbury and colleagues from the Mid America heart and vascular institute, published an interesting paper in the Aug 8th online issue of the Archives of Internal Medicine entitled " Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction" They review the records of 17,676 patients from 57 medical centers across the USA, retrospectively. These patients were admitted with an acute myocardial infraction. They found that on the average, the patients loss about 53-109.6 cc of blood from blood taking for diagnostic tests. About 20% of patients had a Hb of less than 11gm% on discharge. 12% of patients had loss >300 cc of blood ( that is more than half pint ). I never realise that it could be that much, or so bad.
We all know that a low Hb count is associated with higher inpatient and 30 day mortality following an acute myocardial infarction.
I was just thinking, maybe if they take 10 cc of blood each time and run 3 serial samples of cardiac enzymes, like we are all taught, and if we do some renal profiles, that may come to 50-100 cc. If you add blood loss from primary angioplasty, with anticoagulants on board, may mean another 50-100cc blood loss.
I suppose it is something that we cardiologist have to be aware of. Also, the lab people must give us smaller tubes and more efficient diagnostic analytical machines, so that a small amount of blood, maybe 2 cc, can do the whole spectrum of standard clinical chemistry and hematology.
Certainly, we do not wish to take so much blood out of a patient, and then have to replace them with blood transfusion.
I suppose the message is clear. Blood loss from plebotomies can be an issue with acute heart attacks. We must order test that are helpful in decision making. Having smaller blood tbes, and more efficient analytical techniques and machines, may help limit the amount of blood necessary for any given test.
After all, we are healers, not vampires.

AMI PRIMARY PCI. TREATING THE CULPRIT LESION ONLY.

Balloon angioplasty remains the best way to revascularise the myocardium following an acute heart attack. It is an established fact that should your heart artery occlude suddenly, the best thing is to reach a tertiary care medical center, with facilities to do acute angiogram and angioplasty. It would be best if these can be done within 90 mins of chest pain. That gives the best result.
Often, when we do an acute angiogram following an acute heart attack, we see two or three vessels with severe blockages, and we are tempted to try and open up all the arteries, maybe because of our wanting to be perfect, on the mistaken belief that should I bring more blood to the heart, the patient will do better. Sometimes, on pressure from patients relatives, hoping to save money. Otherwise, if you just do the culprit artery, the patient will have to return later for a second angioplasty. And sometimes, because you cannot decide which is the culprit artery, for example an inferior infarct and you have ragged 90-95% stenosis in the Right coronary artery and the Left circumflex coronary artery.
Well, in the 9th August issue of the Journal of the American College of Cardiology, there are two review articles, clarifying this issue, and their conclusion is in line with the clinical practice guidelines for management of acute STEMI. That when we do primary PCI for acute myocardial infarction, we should only do the culprit vessel only and defer the angioplasty for the other vessels ( if it is multi-vessel disease ) till a second seating. If you try and do it at the same seating, the 30 day mortality can be 3-5x higher and so also the 1 year mortality. This fact is well established and these two clinical studies, one by Dr Ron Kornowski ( HORIZON AMI ) and the other by Dr Pieter Vlaar, serves only to reinforce this point. Of course, there are certain exception to these rules, namely, if the patient is hemodynamically compromised, or if the culprit lesion is uncertain. Interventionist must explain to the patient and relatives, that trying to do all together, to save the money, would mean taking a bigger risk, which is not acceptable.
In own practice, I usually defer them, do a stress ECG to see significant ischemia, and then go in if the stress ECG is positive and tidy up. This philosophy has served me well, and also make more sense.
However, what these latest papers did not tell us, is when will be the best time to go in and complete the job? Shall we go in before the same hospital discharge or shall we go in 2 weeks later or 1 month later, or even later. This question of timing the second deferred PCI is not addressed by the present trial data.
At the end of the day, the deferred angioplasty timing may have to depend on the insurance reimbursement policy that the patient holds, especially in USA. Like many things else in the practice of medicine nowadays, the final clinical decision, may be made by the non-clinician who holds the purse.

NON - INVASIVE FFR, THEORY

There is much work on non-invasive FFR with CCTA. It obviously have a useful role for the detection of significant CAD with CCTA, as current anatomical CCTA scans, only tells what you see based on computerise volumetric reconstruction. The average CCTA has a positive predictive value of 60-80% and a negative predictive value of 95%.
With the use non-invasive FFR, these numbers all become better. From what I can understand, the computer engineers and also the bio-engineers have become very good. They can estimate flow and pressures with the CCTA scans and colour code them. By so doing, they can induce hyperemia in the same way that we do in the angio room, using IV adenosine. They then measure the pressure induce in the central aorta, and also in the pressure and flow across any given stenosis seen on the CCTA. This can be made obvious using their colour coding techniques. I will try and illustrate this.







How smart of them. What we need now is clinical correlation and more data, so that we know that it can be easily reproducible. How I wish that our local boys with the CCTA, will embark on such a correlation program, to document our own numbers, regarding accuracy and predictive value.