Thursday, January 14, 2010

Readers are welcome to the NH Blog. We are in the process of learning something about the developmental history of cardiac drugs. This time, we shall see the history of Aspirin in regard to the heart.

Before we start, I have some news which made us proud. Our boss, Dr Sunita Maheshwari was featured on the Cover of the prestigious India Today Woman in the January 2010 issue. (Incidentally, the accompanying regular issue of India Today had Aamir Khan on the Cover!) It was a matter of pride for the entire institute.

The second news was the glory we basked in the Madras Medical Mission. The annual teaching programme of MMM for the DM equivalents was held a week back. Our senior fellow, Dr Vishal Changela got the award for best case presentation. Our fellows literally dominated the session and no answer got missed from them. It stands as the solid testimony for our training and the quality of our fellows.
With this, lets go back to our regular content of blog.

One of the finest accounts of the history of a drug was written by a scientist who was directly involved in the development of the drug. Written in German, its English translation is as fascinating and soul-touching. The author of this historical account is Arthur Eichengrun, whose original article was published in 1949 in a German journal called Pharmazie. It is a “must read” for any enthusiast of medical history and (in my personal opinion) for everyone. The drug is the ubiquitous ASPIRIN. What we shall see is the development of cardiac utility of aspirin, skipping the anti-inflammatory history. For those who would be interested in the entire legacy of Aspirin history, I would strongly recommend a fantastic article by Walter Sneader in BMJ in the year 2000.

Lawrence Craven was a busy surgeon in California. His busy schedule would allow him minimal time to interact with patients and any question of personal touch was usually ruled out. On one of his busy day, he performed a tonsillectomy for a boy. Unable to get in touch with the surgeon after the surgery, the parents of the boy offered him a chewable aspirin for analgesia. The young patient started bleeding, worrying his surgeon for possibility of re-exploration. However, good sense prevailed and the surgeon decided to wait. Under some stern questioning, the parents spilled the beans and the surgeon went into a thinking mode! He made enquiries with other patients asking just 2 questions: Have you taken aspirin as post-surgical analgesia? If yes, did you experience any bleed? To his surprise, the OTC was consumed by many without his knowledge and universally had experienced visible bleed! The scientist in the surgeon made an appearance and he decided to investigate this further. He learnt that one Gibson had tried the use of Aspirin in a small number of patients with vascular diseases with equivocal response. Craven decided to make it big, but ended up being crude.

He tried around 8000 patients who consumed aspirin and came out with a claim that would surprise a seasoned physician! He claimed that none of these 8000 suffered a heart attack!! He could not publish his studies in any major journal as the trail was not a controlled study. The anticlimax of the study was reached when Craven himself died of a heart attack even after taking aspirin. The sceptics would have ended the saga of aspirin with this irony. However, good sense prevailed again and Harvey Weiss in New York could re-establish the role of Aspirin in 1967. He categorically demonstrated the acquired impairment of platelet aggregation in the subjects consuming aspirin by demonstrating prolonged bleeding time. He was the first to suggest the anti-thrombotic nature of aspirin and its use in clinical medicine. He urged the scientists to take up a larger trail in this regard. When it happened, there was no looking back. Aspirin was proved to be an effective anti-thrombotic agent. However, it took many years to come to the right dose that was minimal enough not to cause side-effects, but sufficient enough to provide the desired anti-thrombotic effect. As of today, aspirin stands as one of the most precious drugs in cardiac pharmacology.

With this, I am concluding the “Developmental history of Cardiac drugs”. I have not received any suggestions from any of the readers (if such a population exists!!) on what aspects of history to write next. May be, for next few sessions, I shall write only interesting cases and take up the historical aspects after some thinking.

On a personal note, the year 2010 is seeing lesser number of OPDs in Pediatric side. Possibly the festive season in Tamilnadu might be the reason. We should have taken this opportunity to relax a bit, but some of the events happening never let us!

I have posted this query in the past also, but it continues to haunt us on a regular basis. Hence, I am posting it again. This time, the patients are different, but the problem remains the same. We had one 16-year-old boy with Supramitral membrane with severe obstruction, Severe LVOT obstruction, large PDA and coarctation. The combination fits into Shone’s complex. The CoA was juxtaductal and the PDA was flowing right to left. The boy was desaturated in the lower limb with a significant drop in the LL saturation. His calculated baseline PVRI was 22 Wood units, which dropped to 9 Wood units with oxygen. Now the question remains the same. Is he operable? Isn’t the PVRI secondary to pulmonary venous hypertension reversible after correcting the cause? How much of PVRI is due to PDA and how much due to left heart obstruction? When put to vote, only a handful of people felt it was operable. The young guns of surgical team felt that the patient deserved to be operated as it might be his last chance for repair. However, the senior rung was not so much for it. They felt that the CoA was not much significant with PDA being the dominant lesion and it clearly shows inoperability. The decision was a bitter pill to swallow, but none of us have a concrete evidence for our stand. Such cases can be argued on either side. I questioned the need for cath study in such cases, as the pressure data and interpretations are dubious (may not be decision making in black and white) and the anatomical data might be much superior with a CT and a 3D reconstruction. However, the opinion favoured the cath study over CT. When I had to counsel the parents after the cath meet, I was choking for words. I personally felt that the boy should be given an opportunity to undergo surgery, accepting the high risk. However, the uneducated parents may not understand what we mean. I directed them to the surgical team. What bothers more is the fact that the next patient with similar problem would restart the enigma and we are no wiser by the experience of the present patient. Can anybody throw some light on this? I badly need some advice on management issues of such class of patients.

We came across an infant who had undergone artereial switch as a neonate. He is otherwise asymptomatic, except a murmur in the precordium. Echo showed bilateral branch PA stenosis. Cath showed a significant gradient in branch PAs. Is there a role of balloon dilatation in such cases? How far is it successful? The age may not permit us to stent. Is isolated balloon dilatation recommended? Should we go ahead with surgery directly or give a trail of ballooning? Put in your ideas.

This question has come up in the past, but is another case for lack of consensus. We have a 6-month-old boywith single ventricle physiology (DILV) with mild PS. His mean PA pressure in cath was 36mmHg. Now, should we be doing a PA band? How far can we offer a BDG for him in future? Is he better off as he is now? Our chief was in favour of a PA band so as to keep the future options open, but the surgical team vehemently argued against it. I thought of putting the issue with both possibilities to clear the concepts for myself! I questioned the surgical team if we can anticipate any progress in PS as a part of natural history in this subset. It was interesting to know that such incidents have happened when the level of obstruction was at restricting VSD to produce a PS in Holmes heart. My next question was on the naturally history of a scenario with present PA band, but not suitable for future BDG. Would the eventual pressure overload on single ventricle be worse than the otherwise natural history? The answer had 2 interesting facets to it. Not only such a scenario increases the pressure overload on the heart, it also increases the cyanosis, because the afterload of pulmonary circulation would be greater than that of systemic. The band enigma was another unresolved issue which made us not much wiser at the end of it.

Is it possible to have a TGA with normally related great arteries? We did see newborn with this picture. It had a clear VA discordance but the aorta came out of RV posteriorly, followed by the PA from LV, without the great arteries crossing each other. On the short axis, aorta was to the posterior and right with the PA anterior and left. Now, as per the segmental anatomy, they are {S,D,S}. Do they fit into NRGA? Is the component of crossing essential for defining normal relationship of great arteries? Can the term “Transposition” be applied if the vessels are normally related? Should we call it an isolated AV discordance or TGA? If anybody has seen such a picture before and had any thoughts gone into it, please enlighten us.

Does the definition of Shone’s complex involve the mitral valve, aortic valve and arch or does it involve left sided structures? We came across a case of corrected Transposition with sequential left heart obstruction. There was a tight supratricuspid membrane with subaortic membrane and a coarctation. Technically speaking, it does not fit the definition of Shone’s complex. This is the first time I have come across a cTGA with sequential left sided obstructive lesions. Our surgical team had a tough time operating this child. Tell me your experience if you have come across this combination anytime.

Send your comments. You can either use the comments section or use my email for posting your views and questions. Write about the issues you found perplexing and the way you have found the answer for them.



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