YOUR ROYAL HIGHNESS SULTAN OF SELANGOR : WE WISH YOU A SPEEDY RECOVERY

I read in the newspaper today that the Sultan of Selangor has decided to go to Stanford University Hospital, California, USA for his mitral valve surgery. I had heard from the grapevine that HRH was unwell one evening with acute heart failure and his physician rushed to the palace to attend to him. He was subsequently admitted to the Sime Darby Medical Center where he recovered well. He was diagnosed, I believe with acute heart failure from mitral valve incompetence. What is the cause. Well, at his age, ischemic heart disease will have to be excluded. Whether it be chronic ischemic heart disease or acute ischemic heart disease, I am sure that his attending physician will determine, with all the facilities at his disposal. I must say that I am concern that the mitral valve must have ruptured rather badly and suddenly ( making an acute process likely ). Usually, if there is a leaky mitral valve, the chamber before the mitral valve viz the left atrial chamber accomodates the regurgitant stream and heart failure sets in rather more gradually, as compared to the aortic valve, where a torn cusp will cause a severe leak and the left ventricle will decompensate very rapidly. Of course, the usual cause of mitral regurgitation, ie chronic rheumatic heart is unlikely here as we all know HRH to be a very fit man and he must have had many physical examination, by many prominent cardiologist, in the past. For the same reason, I think that congestive cardiomyopathy, though should be considered is also unlikely.
Going to Stanford, would be a good decision for two very good reasons. I would not wish to speculate as to why he chose to go to Stanford. I can only say that the Stanford Cardiothoracic Surgical Unit was established by Dr Norman Shumway, of heart transplant pioneering fame. The unit is very competent, and has a very good research arm, that researches all the newest and the best. By the way, Prof Alan Yeung, is a cardiologist and head of the department of Cardiology in Stanford University, and not a cardiac surgeon as reported in some newspaper. Dr Yeung is a very competent and pleasant cardiologist, a friend whom I know and also a frequent visitor to the East, especially China. He also likes to come by here whenever invited. The Stanford Unit is also good, because they do have a very good coronary artery by-pass team ( should that be necessary ) and also they have a cardiac surgeon, who can do mitral valve repair surgery, as oppose to mitral valve replacement surgery, that many of our surgeons here, prefer to do. If the cause of the acute mitral regurgitation is ischemia, and the coronary angiogram shows significant coronary artery disease, then he may nee coronary artery bypass surgery ( CABG ) in addition to mitral valve surgery. Many of us feel that whenever possible, the mitral valve should be repaired, as opposed to replacement, as mitral valve repair have been shown to preserve left ventricular function better, and it also avoids the need for long-term anticoagulation. Mitral valve replacement witha mechanical mitral valve has the problem of affecting left ventricular function and also requires long term anti-coagulation, something the very energetic Sultan may prefer to avoid if possible. By going to Stanford with their expertise, all the options are open.
I wish HRH a very speedy recovery, and a return to the best of health, quickly. I can safely say that the whole state, and also the country is praying for him.

ANOTHER NON-CARDIAC USE FOR STATINS

The HMG Co-A reductase or commonly called "statins " have never cease to amaze me. I was very impress with the early studies which showed that "statins " prevent coronary heart disease, primarily and secondarily. Then we learned that statins lower inflammation. By so doing ( besides LDL-C reduction ), it produces cardio and vascular protection. There is some data that it prevents hypertension, diabetes and atrial fibrillation. Cardiac wise, it would appear that statins lower LDL-cholesterol and also lowers hs-CRP. Those are all standard facts.
Well, at the recent American Urological Society scientific meeting, two groups, the workers from Mayo Clinic and the workers from Duke University presented their findings that those taking statins for cardiac protection, seem to have a lower incidence of prostatic cancer, and also prostatic inflammation. Patients taking statins also seem to have better erectile function. These finding are interesting, Does statins prevent Ca Prostate? Because some of us ( myself included ) think that too low an LDL-cholesterol may actually promote cancers. After all, we do need cholesterol for our cell wall function, and not to say, we need cholesterol for our sex hormone. It is interesting to postulate that statins in lowering cholesterol, will lessen testosterone and so lessens the risk of Ca Prostate. Interesting thought.
Be that as it may, the latest findings by Duke and Mayo may give us another good reason to start our patients on statins.
Statins indeed have pleotrophic effects.

DO DES ( DRUG-ELUTING STENT ) LAST FOREVER?

Whenever I brief patients and relatives before obtaining consent for angioplasty and stenting, they often ask me how long do the DES last? Do DES last forever?. I will always reply that our experience and the worldwide experience with DES is 6 years and 8 years respectively. That is because there was no clinical trial longer then 5 years in a clinical practice type patient. The first clinical trial on DES, the RAVEL trial ( now 7 years ) is on the ideal patient. The everyday type patient trial which I was alluding to was the SIRIUS trial, which has just published their 5 year follow-up data. And everything continues to be good. SIRIUS of course compared CYPHER ( DES by Cordis ) with their bare metal stent. There was a slight increase rate of TLR in the Cypher arm annually, but this was much lower than the bare metal arm.
Well, the April 2009 issue of the Journal of the American College of Cardiology: Cardiovascular Interventions, carried a very interesting article by the German workers of the ISAR ( Individualized Drug-Eluting Stent System to Abrogate Restenosis ) group. Dr Robert Byrne et al, followed up 2030 patients who had three types of DES implanted. Gp1 received the Cypher stent, Gp2 the Taxus stent and Gp3 the ISAR stent. The ISAR stent is a proof of concept, experimental DES. This is a premounted, sand-blasted, stainless-steel, microporous stent that is coated on-site with rapamycin (sirolimus). Basically, you have the prepared stainless steel stent base and you coat on the rapamycin at the cath lab. ( interesting ). Therefore, the ISAR stent has no polymer. All patients had angiogram at 6 and 24 months. Slightly over 10% of patients had TLR before 2 years. This group was equally divided among the 3 groups ( shows that the on-site prepared ISAR was just as good as the branded DES ). The LL was 0.25 for Cypher and about 0,46 range for Taxus and ISAR. This was not statistically significant. What was interesting was that at 2 years, the additional LL was 0.17 for Cypher, 0.13 for Taxus and ),01 for the ISAR stent.
Now this is a very important finding. The cypher and Taxus stent both had polymers, while the ISAR stent is polymerless. It means that with time, some of the effectiveness of DES with polymers may be loss. The polymer seem to excite some reaction and may promote restenosis. If this study is correct then DES with polymer coating, does not last forever. Those without polymers, may. But at this moment, we do not have data on polymerless DES with two year followup on a clinical trial, comparable basis. The two polymer absorbable DES that I know of is the Excel stent and the Biomatrix stent. We have just seen the 2 year follow-up of the Excel stent published, and it looks very good. But the followup was 18 months and it is also essentailly an observational study. I have yet to see the Biomatrix data at two years.
When I read this paper, I was also very impress that you could make the DES in the cath. lab. Can you imagine, I could have abase prepared stent ? stainless steel ? cobalt chromium, or any other material, and in the cath. lab. coat which whichever drug that is good for that patient subset, then I can individualise the DES to my patient. Making a polymerless DES is not so difficult after all. It this true?
I am also aware that this is essentially an observational study. We will need a large multicenter trial to confirm this finding. But it is important to note that the two second generation DES, namely the Endeavor and XienceV, both show in their three years followup, that the MACCE rates from 2-3 years are both flat, meaning that there is no late catch-up.
So do DES last forever? Very like, the DES with polymers, does not, and maybe the polymerless ones do?? We need more data.

IN PRAISE OF COCOA, CARDIAC-WISE

In my readings this weekend, I came across a piece of work done by Dr Yamazaki et al, published in the American J of Physiology, vol 295, 2008. It was an elegant piece of work done in rodents, showing that epicatechins protect against ischemic myocardial injury. What is the relevance for us?
You see, catechins and epicatechins, are flavanols, found in cocoa beans. Flavanols, belong to a group of nutriceuticals ( I have alot of interest in this ), call flavanoids, of red wine popularity. Flavanoids, often associated in the skin of grapes used to make red wine, has been shown to be cardioprotective, the easiest evidence is that in the French paradox. French eat saturated fats and also drink alot of wine, which protects their heart so that the incidence of CAD in France ( for all the smoking and saturated fats that they consume ) have a low incidence of heart disease.
Flavonoids are said to have healthy effects including, anti-oxidant, anti-inflammatory, anti-adhesive, anti-thrombotic, vasodilatory and anti-tumor effects. I think that the anti-oxidant and anti-thrombotic effects are probably the most important for the heart.
Back to cocoa. Well cocoa contains plenty of flavanols, the darker, and the more bitter, the more flavanols. Once the chocolate manufacturer make the polish the cocoa and make it white and sweet, the flavanols are removed. Flavanols in cocoa, contains catechins and epicatechins. Yamazaki and colleagues show that rodents who were fed epicatechins before ligation of their LAD, showed smaller area of myocardial ischemia, after the LA ligature is removed, thereby
demonstrating that epicatechins may protect the rodent myocardium against ischemic injury.
It is a simple experiment, but may contain important information. There are many of us who take chocolates. Well, it is good to know that chocolates can help my heart, and pprotect me against a bad infarct. Only make sure that the chocolates that you consume, is dark and bitter. The sweet ones are only for the momentary pleasures and does nothing for the heart.

LDL-C REDUCTION AND STROKES

The May 2009 ( it is only April 2009 now ) issue of the Lancet, carries an article by French researchers, Drs P Amarenco and J Labreuche. They did a meta-analysis of 24 large RCT on LDL-C reduction with statins and the incidence of strokes. The meta-analysis involves 165,000 patients ( a very large number ). The trials included in this meta-analysis included many of the large ones like JUPITER, SEARCH, SPARCL, TNT, PROVE-IT, HPS, LIPID, IDEAL and CARE ( almost all the important ones ). They found that LDL-C reduction reduced ischemic strokes. For every 38mg/dl LDL-C reduction, there was a 21% stroke reduction, more so in the high risk population.
This study is fascinating because we are often taught that the cerebral circulation is quite different from the coronary circulation and hypertension was an important cause of strokes. The result of this large meta-analysis would suggest that strokes are due to plaque eruption or erosions from arterosclerotic plaques, and that we may also have to think of hard and soft plaques, as we do in coronary artery disease. I would rather think that this is a meta-analysis and so we must not read too much into it. We have a statistical observation which we have to explain, but may not suggest a causal relationship. It is also important to note that previous attempts to correlate cholesterol levels with incidence of strokes, were rather inconsistent.
Be that as it may, I suppose I do appreciate that reducing LDL-C for my heart may also help my head vessels. And if there is no important side effects, maybe a reasonable thing to do, especially in a high risk population like T2DM, hypertension, the elderly population, patients with previous strokes and patients with previous TIA.
As a small point, I also note that I can now buy books printed in 2009 from my favourate bookshop and also read medical journals of May 2009 in April 2009.

THE PROBLEM OF CABG IN THE YOUNG. CONTINUATION

Well, I did both the patients today. As expected, the patient who had three angioplasties over the last 10 years had some minor progression of CAD, but as it was not in a life-threatening location, I chose to advise continual medical therapy. The first patient, 60+ years with CABG when he was 40 years, well he had severe two vessel disease. The stents placed in the previous three angioplasties by me, in the LAD, were patent and functioning well. It perfused the prox LAD to the first septal perforator, and the large LADD1. The LIMA to LAD was large and patent, and it perfused the mid and distal LAD well. All the venous grafts are occluded. I spend 3 hours helping him. He was lucky. I was able to open the chronically occluded SVG to RCA, without complications. I used about 300 cc of dye ( remember he had diabetes and renal failure ) and in CCU after the procedure, he had PU twice already. I am sure that he will be ok for awhile.
Well that was the update.
I am convinced that CABG should not be done in the young ( 50 years or below ) unless the artery cannot be opened with angioplasty, and I mean by interventionist who are experienced, with high caseloads.

CABG RE-DOs : THE PROBLEM OF CABG ON THE YOUNG

I was thinking very hard as to what to blog. There seem to be no new clinical trials or medical studies that are clinically useful, this last weekend. So I thought that I will share my work for tomorrow. Tomorrow, I have to do two difficult angioplasties. The first will be a 60+ yrs male with diabetes and who have CABG done when he was about 40yrs. I started to take care of him about ten years ago when his CABG began to fail and he began to develop positive stress ECG and now unstable angina. For the last 10 years, he already had at least 5 angioplasties. Of course, he refuse to undergo a re-CABG because of the risk. I am very concern that I may not be able to do much tomorrow. He also has renal failure probably from diabetes. The second male is also in the sixties and he had CAD treated by me over the last 10 years. He has had three angioplasties. If I have to do it again tomorrow, it will be the fourth in 10 years. Lets see what I will find tomorrow and see what I can do.
The point I am trying to discuss is whether, we should do CABG in young 40 year olds or shall we do angioplaties, until it is no longer feasible to do. Doing CABG in the young has the problem of CABG graft attrition. The LIMA graft may be good, but the SVG grafts invariably fail after about 10 years. We can plasty them, but with CABG, there is also a 30-40% risk of re-stenosis, especally in diabetics. With the new DES, that number drops to 15-20% ( still significant ). I remember abot 20 years ago, I send a rich male to UK for a repeat CABG by arguably the best cardiac surgeon in UK. He nearly died. Those were his exact words to me. The grafts blocked again, and he refused a third CABG, and I ghad to do repeat angioplasties to keep him going. He is still around, but the arteries and SVGs are all bad.
Early CABG with re-dos are both very expensive and also very risky. Early angioplasties with CABG only when angioplasties are no longer feasible, is an expensive strategy but much less risky.
If I should have significant, symptomatic CAD, I will opt for angioplasties, until they are no longer technically feasible. Then I may opt for CABG. Having seen many such patients. I think that is the best strategy, and I am aware of the guidelines.

NEURO-INTERVENTIONS-AHA,ASA RECOMMENDATIONS

I have always been very concerned at the development of neuro-intervention in this country and worldwide. I had the good fortune of being at the ringside seat to see neuro-intervention begin and her early development It began almost as a spin-off from coronary angioplasty, by almost the same guys, who felt that any stenosis or blockage was fair game to unblocking and angioplasty. Evidence was grossly lacking and they just went ahead. Overtime, we saw a discipline developed, now looking for evidence. How many patients have suffered along the way, only God knows.
Anyway, in my reading, I have just come across the American Heart Association (AHA) and American Stroke Association ( ASA ) recommendation on neuro-interventional procedures. I cut and paste completely, so that my biasness will not come in.

This came out in a document entitled, " Indications for the performance of intracranial endovascular neurointerventional procedures". A scientific statement from the American Heart Association Council.
The following are some of the main recommendations in the new document.

• Ruptured aneurysms: Endovascular coil occlusion of the aneurysm is appropriate if the aneurysm is deemed treatable by either endovascular coiling or surgical clipping (class I, level of evidence B).
• Unruptured aneurysms: The authors deem it "reasonable" to consider endovascular occlusion for unruptured aneurysms if the aneurysm is thought to require intervention over conservative management and is amenable to endovascular treatment according to an endovascular specialist (class IIa, level of evidence B).
• Intracranial stenosis: For symptomatic atherosclerotic stenosis greater than 70% and failing medical therapy, endovascular revascularization with angioplasty or stenting might be reasonable (class IIb, level of evidence B).
• Acute ischemic stroke: For patients with a major stroke syndrome lasting six hours or less, and who are either ineligible for or who have failed intravenous thrombolysis, it is "reasonable to consider intra-arterial thrombolysis in selected patients" (class I, level of evidence B). For patients with a major stroke syndrome lasting eight or more hours, it "may be reasonable" to use mechanical disruption to restore blood flow in selected patients (class IIb, level of evidence B).
• Cerebral arteriovenous malformation (AVM): For patients with hemorrhage referable to a pial AVM, endovascular treatment in combination with other therapies, such as surgery or radiosurgery, should be considered as a preoperative adjunct or palliative treatment to prevent recurrent hemorrhage (class IIb, level of evidence C). For those with neurologic symptoms or hemorrhage referable to a dural arteriovenous fistula, endovascular treatment alone might be curative or might be used in combination with other therapies, such as surgery or radiosurgery, as palliative treatment to prevent stroke or hemorrhage (class IIb, level of evidence C).

I do hope that practitioners doing neuro-intervention will based their therapy on good robust clinical evidence. The " oculo-stenotic " reflex should be curb as much as possible. " I can see, I think that I can do, so I will do" kind of logic should be avoided. It must havce evidence to show that it will help the patient. Each practitioner must draw their own line.

HELPING AND NOT HELPING WITH MORE DATA -DES /BMS

Very often, clinical studies are done so that we can have more data to help medical practice. Lately, we have had some clinical trials where more data seemed to have confused us. I remember September 2006 when the Berne and Rotterdam researchers gave us data that seemed to show that DES are bad. That shook the lay media and clinical interventionist worldwide, alleging that DES was a death trap. Many patients were alarmed and were asking us to explain.
Since then, much more information has come out and have shown to us ( in my opinion conclusively ) that DES are a help and not a harm. Well, at the just concluded ACC 2009 at Orlando, Dr Pamela Douglas, and colleagues from Duke Research Clinic, presented a paper on the use of DES Vs BMS in the elderly population. It was a very impressive study because they studied 260,000 medicare patients, comparing 217,000 patients with DES and 45,000patients with BMS. Their intention was to show that DES was save when compared to BMS, and that DES was better. That they showed. They showed that patients with DES had obviously less AMI and death when compared to BMS, but DES was only slightly better than BMS in terms of repeat -revascularisation. This is where the confusion is. The conventional wisdom is that DES reduced re-stenosis and so should show an obvious reduction in repeat revascularisation. In fact DES may not be much better than BMS in terms of AMI and death reduction. We must try and understand the data from Dr Douglas.
So Dr Douglas and colleagues has given us more data that may increase our confusion. Looks like more data may mean more confusion.
Be that as it may, it is true, from all the data so far, that DES is here to stay. It is a multi-million dollar industry, and that DES is safer than BMS and lessens the need for repeat revascularisation.

MORE EVIDENCE FOR THE FITNESS FREAKS

I have always taught my patients that one of the best ways to lower mild to moderate blood pressure is a healthy lifestyle, including alot of greens, fruits, exercise and lose weight. We all know that not all mild to moderate hypertensives need drug therapy to start, especially if they are obese and have a low risk profile with no target organ damage.
Just just concluded ACC 2009 at Orlando had a small paper out by investigators from University of North Carolina, Chapelhill, showing that subjects with mild to moderate hypertension had BP reduction on the DASH diet when compared to usual therapy. Those who were also on a regime of exercise and weight reduction ( in addition to the DASH diet ), had even better BP control. The DASH diet is basically a diet rich in greens veges and fruits. This is a small study with about 49 subjects in each of the arms ( the usual therapy arm, the DASH diet arm and the DASH + exercise + weight reduction arm. The subjects all had mild to moderate hypertension and were with BMI 33 or more. Small study ( size apart ), this is a well conducted trial. Healthy lifestyle is what we should all promote.
I suppose the message that I would like to convey would be that if you are overweight and have just been told that you have mild hypertension, go on a weight reducing diet, including alot of green veges and fruits and also exercise regularly. It is very healthy, cheap, and effective without side effects. Of course, it requires sacrifice and also discipline. In a way, that is the way life is.

FROM ACC 2009 : JUPITER PLUS DVT

Well, the ACC 2009 at Orlando has ended. We have all learn the lessons that we had learn. I wanted earlier to write something about the Jupiter trial, and forgot. I thought that there were more interesting things to comment on, and so left this one and forgot about it.
Anyway, I wanted to write that the Jupiter trial had a secondary end-point of incidence of Deep Vein thrombosis. The investigators wanted to find out, since this was a large population under study, about 18,000 in all, whether taking Rosuvastatin reduces the incidence of DVT. And the answer is yes, taking rosuvastatin, does reduce DVT, but not acute pulmonary embolism. Looking through the figures, I did not see the breakdown of the numbers that correlated DVT and hs-CRP? I wonder whether the investigators looked into that.
These results made me think. Why did rosuvastatin reduce DVT. The deep veins are venous structures, subjected to low pressure systems, and LDL-cholesterol hardly play a role here. If you then minus hypertension and dyslipidemia from the equation, and still have less thrombosis, then we must come to a conclusion ( mechanistic wise ) that it rosuvastatin plays a role in vasculopathy or vessel wall reaction to trauma or inflammation. Interesting, that must also mean that people who travel frequently in airplanes, maybe those in " coach class " should take rosuvastatin before they fly.
Of course, the other question that will come to mind is whether this benefit is confined to rosuvastatin, or is it a statin class effect? That is left to be determined.
Well, ACC 2009 is over. We have all learned alot. Nothing revolutionary, but plenty of clinical material to help our patients.

FROM ACC 2009 : THE ZEST TRIAL

Even as the ACC 2009, Orlando draw to a close, we have indeed learn much. No, I do not think that there were any great revolutionary therapy come out, this time. But we did see more clinically relevant data, that should help clinicians practice. One of the last late breaking trial to be presented yesterday was the ZEST trial. This is essentially an interventional cardiology trial, carried out in Korea under Dr SJ Park of Asan Medical Center. The results were presented yesterday. It was a 2,600 patient trial, non-inferiority trial comparing the use of the first generation DES ( Cypher and Taxus ) and the second generation DES ( Endeavor ), over a 1 year follow-up. These stents were implanted in almost real-world patients with few exclusion criteria. The investigators were willing to use the DES in many cases which may have been considered " off-label " use in USA, bifurcations, calcified lesions, long lesions, small vessels,etc.
Well, the results ( in a nutshell ) showed that Endeavor was better than Taxus, in terms of repeat TLR and TVR, with a trend towards lesser death and MI. But Cypher was marginally better than Endeavor. In otherwords, in head-to-head comparison of the 3 DES, Cypher came out best, second was Endeavor and third was Taxus. This was in an Asian population with almost all-comers included in the trial. I have always felt that the -limus drug is a more suprior drug when compared to the paclitexal drug.
Well, congratulations to SJ for pulling off such a well executed trial.
In the meantime, even as the data was being presented in Orlando, we have also learned that the Endeavor DES has received Japan FDA approval. When I was at the Beijing meeting in mid-March, I also saw the 2 year data of the Endeavor Resolute DES and the results were good. Looks like Medtronic International is not staying still. They are continuing to innovate and improved upon an already good stent.
As you can see, the field of interventinal cardiology is never staying still. It is continually being improved upon, so that the patient continue to get better and better care. Albeit, the only downside is cost. I am please to note that Medtronic Malaysia tells me that the new Endeavor Resolute, will cost the same as the Endeavor stent. Good for my patients.