I/C LIQUID PACLITAXEL FOR THE PREVENTION OF RESTENOSIS

Many of us may know that the NHAM is holding the MyLive ( live demo course ) in KL Hilton these few days ( 30th July-1st Aug 2009 ). Looks like there is not much new hard-ware, and it is mainly a meeting of friends with some discussion of techniques and how to avoid complications and how to deal with them should they happen. Of course, part of the reason that PCI has reached a plateau, is because there is not much more to innovate for PCI and the big American boys have become interested in percutaneous heart valve replacement, something we are waiting anxiously for proof of safety. I was MyLive briefly in the evening to chair a session and also to meet up with some old friends. Well, any time like minded interventionist meet together to exchange ideas is always good. The cost is another factor altogether. CME costs does impact on the consumer ultimately.
At night, I was invited to dinner to hear about the latest development in Drug-Eluting Balloon ( DEB ). Personally, I was hoping for some updates on the latest trial results, but I did not get to hear that. It was more a " my experience session ", and in that sense I was a bit disappointed. Of course the commadarie was good. I met many old friends and also make many new friends there. I was trying to see how to position the use of the DEB, in the whole armentarium available to me in the treatment of CAD. For the moment, I was trying out the use of the DEB in the management of select cases of " in-stent restenosis " . I was hoping that a wider review of PEP-CAD II would give me more support. Anyway, that did not come.
In the 22nd July on-line issue of Circulation : Cardiovascular Intervention, Dr C Herdeg and colleagues from Turbingen, published a small clinical trial called LOCAL TAX, on the use of I/C liquid Paclitaxel, in the treatment of CAD. They studied 204 patients with CAD who were divided into 3 groupd, group 1 were trated with bare metal stents + I/C liquid paclitaxel, Group 2 were treated with bare metal stents and Group 3, with the DES Taxus ( which is paclitaxel eluding ). Well, the 6 months late loss, was obviously worse with bare metal stents ( 0.99mm ) and the best with group 3 ( 0.44mm ). The late loss of Group 1 came in-between at 0.61mm ( not inferior to group 3 ). The difference in late loss of Gp1 and 3 did not translate to any significant clinical events. From this small pilot study, it would appear that we can just use I/C liquid paclitaxel. Of course, paclitaxel here is advangtages ( when compare to the limus group becoause paclitaxel is lipophilic and limus are hydrophilic.
Anyway, this trial raises a few issues in my mind. Firstly, look like Germans are very keen of not placing material in patients artery. They like DEB which will be removed and also liquid paclitaxel, which will be at the arterial wall and also washed away. The rest of Europe and the USA seem not so keen. Maybe that will why, it may be very difficult for DEB to get CE mark and US FDA approval. Secondly, looks like a bit of paclitaxel locally in the vessel wall can exert a significant activity and effect. We inflate the DEB for 20-30 secs and we retain the liquid by a perfusion like balloon for the same duration and get the effect. Will we see a day went we can just dip the balloon in a vial of Paclitaxel and then introduce it across the target site, and get positive results. Interesting thought. That will of course be cheaper then DES, DEB and IC liquid paclitaxel.
Well, I am back to chair another session this evening on " cutting edge PCI ". Lets see what they will teach me.

CARDIAC SURGERY, STANDARD OF CARE

It is always good to have outcome data, on treatment methods. I have just read in BBC news, the data published by the British Society of Cardiothoracic Surgery, of their 400,000 operations from 2001 - 2008.

DEATH RATES
Coronary artery bypass surgery alone:
2001: 2.3%
2008: 1.5%
All coronary artery bypass surgery:
2001: 2.6%
2008: 1.7%
Heart valve surgery alone:
2001: 5.2%
2008: 3.5%
Combined valve and coronary artery bypass surgery:
2001: 8.3%
2008: 6.1%

It is good to know. Now we have a benchmark to compare our own standards against that of a developed country. It is important to note that since 2001, in UK, the standard of care has improved significantly. Also, that when we compare surgery, we must always talk about the case mix and the compexity of the surgery. We should not just talk about bypass surgery. It can have so many forms, and with each complexity, the outcome may vary. In fact from 2001-2008, although they were being audited, the UK cardiac surgeons did not shy away from doing complex or more complex cases. ( There is a tendency when doctors outcome are being audited, they will tend to do " safe cases " so that their individual numbers will be good ). They were taking on older patients ( greater than 75yrs old ) regularly ( 20% of the patients were above 75 yrs old ), and still have good results. There were less re-operations too. However, the authors noted that the female gender seem to confer an additional risk. Female patients did not seem to do so well, as it is noted worldwide.
Overall the results from UK are very good and I can only hope that our Malaysian cardiac surgeons will be doing just as well.
I would also like to see similar figures out of UK, USA or Europe, on angioplasty, and see how we compare.

THE BEST US HOSPITALS

The US News and World Report 2009

The 'Best Hospitals' for 2009

Hospitals are listed below by total points. Here are the 21 hospitals that made the magazine's honor roll (two are tied for 10th place):

1. Johns Hopkins Hospital, Baltimore
2. Mayo Clinic, Rochester, Minn.
3. Ronald Reagan UCLA Medical Center, Los Angeles
4. Cleveland Clinic
5. Massachusetts General, Boston
6. New York-Presbyterian University Hospital of Columbia and Cornell
7. University of California-San Francisco Medical Center
8. Hospital of the University of Pennsylvania, Philadelphia
9. Barnes-Jewish Hospital/Washington University, St. Louis
10. Brigham and Women's Hospital, Boston
11. Duke University Medical Center, Durham, N.C.
12. University of Washington Medical Center, Seattle
13. UPMC-University of Pittsburgh Medical Center
14. University of Michigan Hospitals and Health Centers, Ann Arbor
15. Stanford Hospital and Clinics, Stanford, Calif.
16. Vanderbilt University Medical Center, Nashville, Tenn.
17. New York University Medical Center
18. Yale-New Haven Hospital, New Haven, Conn.
19. Mount Sinai Medical Center, New York
20. Methodist Hospital, Houston
21. Ohio State University Hospital, Columbus

Top Hospitals by Specialty

Here are the No. 1 hospitals in each specialty, according to U.S. News and World Report:

• Cancer: M.D. Anderson Center, University of Texas, Houston
• Diabetes and endocrine disorders: Mayo Clinic, Rochester, Minn.
• Digestive disorders: Mayo Clinic
• Ear, nose, throat: Johns Hopkins Hospital, Baltimore
• Geriatric care: Ronald Reagan UCLA Medical Center, Los Angeles
• Gynecology: Brigham and Women's Hospital, Boston
• Heart and heart surgery: Cleveland Clinic
• Kidney disorders: Brigham and Women's Hospital
• Neurology and neurosurgery: Mayo Clinic
• Ophthalmology: Bascon Palmer Eye Institute, University of Miami
• Orthopaedics: Mayo Clinic
• Psychiatry: Massachusetts General, Boston
• Rehabilitation: Rehabilitation Institute of Chicago
• Respiratory disorders: National Jewish Hospital, Denver
• Rheumatology: Johns Hopkins Hospital
• Urology: Johns Hopkins Hospital

John Hopkins is tops again for the 19th Year.

DES STENT ALLERGY

DES is a very good device to help in the management of CAD. I began implanting DES ( Cypher stents ) from May 2002. By now I would have implanted a thousand of DES, of various types. I find that DES has been a great help. With DES, So few restenosis occured that it has affected the sngio case loads in many cardiac cath labs.. But that is good, good for the patient. However, we do see the occasional case of DES mishap, be it restenosis or stent thrombosis. These are rare, but does still occur, just as they do occur even with bare metal stents. The cause of DES thrombosis, especially late or very late stent thrombosis, differs from the stent thrombosis with bare metal stents .
In the 20th July issue of Circulation, Dr Cook and colleagues from Switzerland, publish their findings of a research, in to the possible mechanisms for very late stent thrombosis. They studied 54 patients, 26 patients act as controls with DES and 28 had DES implanted and very late stent thrombosis. They found that those DES and very alte stent thrombosis, tend to have negative remodelling, malapposition and also a ppredominance of oesinophilic infiltrates and also areas of allergic vasculitis over some of the stent struts. These will make us suspect that the DES has induced a delayed allergic reaction. We are however uncertain as to which component of the DES device cause the allergy. Is it the stent platform, the polymer coating, or the drug? Most of us suspect that it is likely to be the polymer coating, thereby sprouting out a whole new generations of polymerless, or absorbable polymers. We are seeing more and more of these stents coming into clinical usage, although we are not sure of their long-term results, and whether or not it will abolish late and very late stent thrombosis.
Much work is also being done on a new generation of bioabsorbable DES. The old bioabsorbable stents were vertainly not good enough. The present types of bioabsorbable DES under study, looks promising.
Be that as it may, it is important even as I close, to emphasize that DES are good for treatment of CAD. There are still problems with DES, as there are with bare metal stents. DES has helped more than it has harmed. They should no longer be any concerns for using a DES if the clinical indications are there.

HEART DISEASE PREVENTION : THE BAD AND THE GOOD

Last week and early this week have seen the publication of three reports, two of which are very worrying and the third a piece of good news. It is all about lifestyle changes and prevention of coronary heart disease.
Dr M O'Flaherty of Liverpool reported in the July 14th issue of BMJ, that there is a growing trend in Scotland, that cardiac mortality and morbidity in the younger age group, 30-50 years, seem to be flattening, more so in the lower social economic groups, in the last 10 years or so. They seem not to eat healthily and exercise regularly. The poorer young people seem to have gone back to smoking and also eating the less healthy foods, including those with high trans-fat levels.
Dr Lee of Toronto, in the 20th July issue of the Canadian Medical Association Journal, also reported that in Canada, they have noticed that there seem a trend in their younger age group, for a flattening of the risk factor modification curve, especially in the pooere young, from 20-50 years range. There seem to be a rising incidence of risk factors again, including hypertension and obesity.
The good news is that the Dr Forman, of Peter Bringham and Women's ( Mass. USA ), published in the 22nd July issue of the Journal of the American Medical Association, that in a followup substudy of the Nurses' Health Study ( 83,882 nurses, mean age 27-44 years, followed up for the last 14 years, showed that those nurses ( mainly females ) who observed a heathy lifestyle ( Green veges, fruits and low salt diet-DASH diet, folic acid suplements ), together with moderate exercise, had a 80% lowewrr incidence of hypertension.
This paper was followed in the coming 29th issue of JAMA, by another paper by Dr Djousse also of Bringham and Women's, who followed up 20,900 males in the physician Health Study, over a mean of 22 years, and found that there was a significant reduction in the incidence of heart failure in those who followed a healthy cardiac lifestyle, namely ideal body weight, low salt, low cholesterol diet, greens veges and fruits, regular exercise, stop smoking.
It does appear that a healthy cardiac lifestyle is good, but can be difficult to observe and also to maintain. The young especially the pooere part of society, may find that basic day to day survival does not allow them to be so " Ideal ". They had to compromis significantly on their exercise and food, resulting in the increase in coronary risk factors, observed in the UK and Canadian study.
It may be iportant for the government, in their eternal quest to lower the healthcare budget, to offer incentives to the people, especially the less wealthy, to encourage them to kee to their healthy lifestyles and in so doing, lessen the incidence of heart disease, thereby reducing the healthcare budget. I see a small attempt at that in the new" US Healthcare reform " proposed by President Obama. I do hope that he succeeds, thereby giving us an example to follow.

IS LESSER BETTER : MINIMALLY INVASIVE CORONARY BYPASS

Medicine is becoming more and more costly, especially in USA where a nights stay in a medical center could cost a few thousand USD. This has spun a near branch of medicine called minimally invasive surgery. Many of these surgery make use of the fact that videoscopes can be inserted through keyholes, thereby causing less trauma and so faster recovery and faster discharge. So we hear of laparoscopic cholecystectomy ( removal of gallbladder ), arthroscopic knee surgery ( operating on the knee joint through a videoscope ). Some even attempt laparoscopic worm removal, etc., etc. We also have a procedure called minimally invasive coronary bypass ( keyhole heart bypass ), which requires the leg veins ( the conduits used for the bypass ) to be harvested through a keyhole so that there is no need for a long leg incision. Cosmetically it looks better and recovery is faster. As we all know, the veins ( conduits for bypass ) is a very important part of the bypass. Yes, it is important to graft ( stitch ) the veins to the heart and the aorta. But if the conduit ( veins ) are not properly harvested, they can be damaged at the time of the harvesting ( through the videoscope ), and cause early blockage of the veins, thereby resulting in early reblockage of the bypass. For many years, many of us have suspected the minimally invasive coronary bypass does not work as well as the standard CABG ( coronary bypass surgery ), because of the higher bypass re-blockage rate following surgery. The initial studies done with follow-up over 6 months showed no difference between standard bypass using the heart lung machine and minimally invasive coronary bypass.
However, a sub-group analysis of the recent clinical trial, The PREVENT IV trial with longer followup shows this not to be so. The investigators from Duke University Durham ( a very wellknown cardiac hospital ) shows this not to be so. The investigators led by Dr Renato Lopes ( published in the July 15th issue of the New England J of Medicine ) found that veins after 18 months, 30% of the vein bypass have re-blocked.
It is not difficult to explain why. When I was in training, the very famous cardiac surgeon, the late Victor Chiang, use to tell us that probably the most important part of the coronary bypass procedure is harvesting the veins. He use to teach his fellows to harvest all the veins very gingerly and not damage any part of it. Veins do have many tributaries, and in harvesting, each of these tributaries must be meticulously tied off and handled with care so that no part is damaged. Otherwise, the damage part will result in blood clots forming on them once they are grafted, and this will result in blockage of the graft. Dr Chiang's coronary bypass use to be world re-known to last as long as the arterial grafts that some other surgeons use.
I once saw a video tape of the videoscopic harvesting of the veins. It was so rough with tugging and pulling to mobilise the veins. I knew that these kind of techniques goes against the basic understanding of medical science, and will surely fail.
The evidence is now provided by Dr Renato and colleagues. However, I am confident that with more training ( and minimally invasive surgery have a very long and steep learning curve ) the technique will evolve and get better.
So remember, less trauma does not necessarily mean better outcome. There is a rather steep learning curve and choosing the right surgeon is important.

DEATH OF TEOH BENG HOCK

I apologize to all those who read this blog for cardiac information. I am very, very saddened by the totally unnecessary death of Mr Teoh. I wrote this letter to the editor of Star. Just in case they refuse to publish, I would like to publish it here. I would also like to ask all who love Malaysia, to show their protest, in whatever way they feel appropriate. Enough is enough. We cannot have innocent people die while in the custody of government institutions. Please forgive me for my outburst.

Dear Editor,

As a citizen of Malaysia, I am very, very sadden that Mr Teoh could die in the custody of the MACC. Firstly, my condolences to Mr Teoh's family and loved ones. Have no fear, Mr Teoh, your death will not be in vain. Mr Teoh will find justice, if not on this earth, surely in the hereafter. Secondly, why is there a need to interrogate someone who is not a criminal, who is only assisting in an investigation, till 3.30am in the morning?. Thirdly, why was he refused counsel? With only he and the MACC officers in the room, anything could happen and be covered up? We doctors need a chaperone whenever we examine a female patient, both to protect the patient and also to protect us. Why was Mr Teoh not allowed a counsel to be present, both to protect him and his rights and also to protect the " good" MACC, unless MACC intends foul play. How do you account for a political secretary, hale and healthy, probably very happy, about to be married, to die such a horrible death. We Malaysians would liike answers to all these questions. I support the call to have an independent investigation to into this untimely and cruel death of Mr Teoh. Who is next? How can this happen in Malaysia. Mr Prime Minister, Mr Government, enough is enough.

Deeply Disturbed

Dr Ng Swee Choon

29-31, Jalan SS 15/5A Subang Jaya

47500 Subang Jaya, Selangor

03-5634 6035

Update: For any who are interested, there will be a vigil for Mr Teoh at the Kelana Jaya Stadium from 4.30 PM to 8.00 PM this Sunday.

For those who are able, his funeral will be held in Alor Gajah on Monday. More details can be found in this link http://justiceforbenghock.blogspot.com/2009/07/maps-to-tbhocks-residence-in-alor-gajah.html

FDA APPROVES PRASUGREL ; AMIDST SOME CONTROVERSY

There are some of you who believe that the FDA is fair, transparent and right, in the many decisions that she makes. In some ways, what happens in FDA should not affect us/ But the truth is that FDA decision goes a long way to to affecting clinical practice patterns wourlwide.
Well, last friday, FDA approved the use of prasugrel, in the management of acute coronary syndrome, primarily on the basis of the TRITON-TIMI 38 study. That is surprising, as the TRITON-TIMI 38 study showed that there was an excess of clinical bleed in the patients given prasugrel. Also, to base a drug approval base on one clinical trial result alone is unusual. What is even more controversial was that the Dr Sanjay Kaul, a cardiologist member of the FDA Drug Advisory Panel meeting on the 3rd Feb 2009, was disinvited from the Panel meeting after protest from Ely LiLy. That is most strange. Ely Lily has known that Dr Kaul had done an independent analysis on the TRITION-TIMI 38 data can came out with different conclusions, suggesting that majoy bleeding was a major concern. It is obvious that Ely Lily was unhappy to have Dr Kaul at the Panel hearing and requested the Panel chairman to dis-invite Dr Kaul. This was carried out. That meeting approved the use of prasugrel. This got to the ear of the House subcommittee overseeing the FDA budget, and the FDA chairman agreed that it was a mistake to have excluded Dr Kaul, but the approval decision was allowed to stand, and that the FDA ppromise to look into the shortcomings of the approval process and correct the mistake, for the future. Funny that the panel did not choose to re-convene with Dr Kaul there to submit his imput?
This is adds more fuel to the many of us who feel that the FDA needs are-vamp and that in its present state, they are not impartial and have found to be acting on behalf of the big pharmas in many of their approval decisions. Not to forget that the pharma industry is a multi-billion dollar industry and many FDA officers, upon retiring, end up in pharma boards. How convenient. Yes, there is corruption in Malaysia, but it certainly looks like it is not much different in USA. Perhaps it differs only in the quantum of pay offs or golden handshakes.
Coming back to my first point, yes, prasugrel has been approved for us in management of acute coronary syndrome, with a black-bok labelling of the need to observe for major bleeding. Prasugrel, a cousin of clopidogrel, and more powerful, belongs to a group of anti-platelet agent acting on the ADP receptor, thereby blocking plaltelet adhesiveness and aggregation. The fact that it is effective is not in doubt. Perhaps the problem may be that it is too effective, thereby causing bleeds. So far, we have not notice any report of prasugrel resistance, a problem now well recognised with clopidogrel.
Maybe the FDA felt that they needed to end the dominance of clopidogrel, but I must say that they way they did it make it lose her impartial and up-right status. One wonder, how many of the their decisions make previously, those on statins, ACE-I, ARBs, stents, anti-diabetic drugs, etc., too many to name, were also tainted by controversies such as this.
We are indeed waiting for a post-American world, whereby we no longer have to see American as the only big brother, whom we follow, sometimes blindly.

DEATH OF AN ICON : THE CARDIOLOGIST PERSPECTIVE

Undoubtedly, the most important headlines this week is the death of Michael Jackson. It was headlines news over all the newspapers, all over the world. On the 25th June 2009, Michael Jackson was pronounced dead at the University of California, Los Angeles Medical Center. He was said to have died from a cardiac arrest. That on its own, is not a proper cause of death. We are all anxiously waiting for the autopsy report. Well, what do the cardiac boys' say. It is common knowledge that MJ was under tremendous stress, with a 50 concerts due to start in about two weeks, he was to start an international tour to kick start his career again. He is USD400million in debt, he is 50years and have not performed for many years. He is high on drugs,including painkillers and occasional opiates. It is known that he was regularly on IV demerol, and also oxycontin. He was underweight when they did the autopsy, and allegedly quite emarciated.
What are the possible causes of a cardiac arrest? Or is it a cardiac arrest? His doctor, Dr Murray, was with in the house when he had the cardiac arrest. Dr Murray noted that he had a faint femoral pulse, when he arrived at the bedside. That would suggest that he may have been in respiratory failure, before the cardiac arrest. That raised the possibility of drug induced respiratory suppression as one would get with the opiates or other sedative group of drugs. IV Demerol could also cause hypotension, in someone dehydrated enough, to cause a hypotensive cardiac arrest. It is also interesting to note that MJ was under the care of a non-board certified cardiologist. Dr Murray is not board certified. Of course, Dr Murray tried to do CPR, but without opiate antagonist to reverse the opiate respiratory suppression ( if at all that is the cause ), and without endotracheal intubation, his CPR efforts would have been futile, as we now know it was. It was also alleged that Dr Murray performed the CPR without putting MJ on the hard floor. External cardiac massage would have been very ineffective, on the soft MJ bed.
Of course, he could have a cardiac arrest from other forms of drugs that he was taking. That is why we are awaiting the toxicology reports. With poor diet, and emarciated conditions, he may have been somewhat dehydrated, so that electrolyte imbalance and a cardiac arrest may have occurred.
It is also well know that MJ suffers from SLE. Lupus can also affect the heart, sometimes causing heart blocks, sometimes causing myocarditis and cardiac inflammation, thereby causing a cardiac arrest.
There is a distant possibility that at 50yrs, MJ could have had a heart attack, with that causing the cardiac arrest. MJ, though 50yrs old, never had a stress ECG? His cardiologist, Dr Murray felt that he looked well and so there was no need for a stress ECG, although all his concerts are heavily insured. Anyway it is important to note that a cardiac arrest is when the heart stops, either from ventricular fibrillation ( the heart fibrillating ) or complete heart block. A heart attack is when the patient has coronary artery disease ( maybe silent arteriosclerosis ) with atherosclerotic plaques on his coronary arteries. Should those plaque rupture, as it can do under severe stress, the resulting coronary thrombosis ( blood clot in the artery, blocking the artery ) causes the heart muscle cell death, we call a heart attack.
There is even a report that MJ may have committed suicide as his rehearsals were not going well. After not performing for so many years, and not being in perfect physical condition, he can hardly be expected to do the "moon walk ". Rather then face a flop on his comeback, he wanted to be remember for what he achieved earlier, not to mention the financial loss should the concerts flop. So he took his own life.
Whatever had happened, we would all have to await the whole autopsy report, including the toxicology report, before we can arrive at a definitive conclusion.
25th June has seen the death of an icon. May MJ rest in peace. His work on earth is done.