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Archive for August, 2009

Conduction disturbance is a fairly common occurrence following  MI. Inferior STEMI is especially prone for AV blocks. This is because  the  blood supply to AV nodal  tissues and the inferoposterior surface of the heart  share the same arterial territory . AV node gets it supply  90% of time by right coronary artery(RCA )  and 10% by  LCX. Very rarely from both .

The common bradyarrhytmias that we encounter in inferior MI are

Sinus bradycardia

Sinus pauses ,SA blocks

AV blocks

Functional

Vagotonic

Organic

Ischemic

Necrotic

ECG types

1  degree AV block

2 degree  AV block – Type 1 Wenke bach

Complete heart blcok

Mechanisms

The inferior aspect of the heart has rich innervation of vagal nerve terminals (While the  sympathetic adrenergic system is concentrated in the anterior surface) . The moment infero posterior MI occur it stimualtes the vagus and a prompt bradycardic response occur .Many times the classical hypotension /bradycardia reaction is simply a reflection of heightened vagal tone.

Consequence of vagal tone on SA nodal and AV nodal conduction

As expected, vagal stimulation can result in a spectrum of arrhythmias from the  simple bradycardia to complete SA block  to  AV block. Extreme bradycardia , may release the junctional pace maker and result in junctional rhythm with a rate of around 40-50. There can be a functional AV dissociation between SA node and AV node. Careful ECG analysis is required here ,  as it can mimic organic AV block.The simple way to differentiate between organic AV block from simple AV dissociation is to look at the p waves.In AV dissociation both atrial rate and ventricular rate are nearly equal or VR  is slightly more than AR .In CHB atrial rate  exceeds ventricular  rate.

SA and AV block occur due to various mechanisms in inferior  MI

  • High vagal tone
  • Ischemia of SA/AV node
  • Necrosis of AV node
  • Drug effects -Like morphine
  • Reperfusion bradycardia*

Ischemic AV nodal arrhythmias are  some times very difficult to differentiate from vagotonia especially if occur within 24h.

Irreversible AV nodal block due to necrosis is rare.But if occur , usually  associated with extensive inferior mI/RVMI/ .AV block  that  persist beyond 48-72hours should raise the suspicion of damage to AV node.( As vagal tone is very unlikely;y to last beyond 48h)

* Some time a an episode of sudden severe  bradycardia  can be manifestation of RCA reperfusion.Flushing of SA nodal or AV nodal branch of RCA might trigger this. This has a potential  to  bring the heart to asystole.The resultant extreme bradycardia often triggers VT/VF .The reported high incidence of primary VF in infero posterior MI is attributed to this sudden RCA perfusion.

Medical management for CHB

Brady arrhythmia’s due to high vagal tone are generally benign .No specific intervention is required.Atropine will be suffice in most situations.Some times isoprenaline may be required. Aminophyline , now Ivabradine may have a role. Atropine not only corrects the HR it raises the BP also as  it counters  both cardioinhibitory and  vasodepressive  limbs of vagal stimulus mediated by  acetyl choline .

Pacing for Bradycardias in inferior MI.

  • Generally not necessary for sinus bradycardia.
  • Few with CHB require it
  • Persistent hypotension and RVMI  needs it often.(Dual chamber temporary pacing preferred as AV synchrony is vital here.)

Weaning of temporary pacing in inferior MI.

This could be a tricky issue. It can be weaned off in less than a week.A practical way is to use temporary pacing  only in back up mode at a heart rate of few beats less than the patients rhythm.Pacing for long hours  at high rates may delay the resumption of patients own rhythm and may result in false diagnosis of irreversible CHB and a subsequent PPM

How many will require permanent pacing following infero posterior MI ?

Only a fraction of patients with CHB require long term pacing . There are some centres tend to overuse PPM in this situation. Wait and watch policy may be the best.A unnecessary lead  within a  infarcted ventricle  has a potential to create problems .There have been  occasions a stable RV MI has been destabilised due to RV pacing lead triggered recurrent VF.

Tachycardias in inferior MI

It is relatively uncommon.Atrial involvement is more common with infero posterior MI and hence a greater incidence of atrial fibrillation .

RV MI can induce ventricular tachycardia arising  from the RV myocardium

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micro circulation shockHuman circulatory system consists  of  the heart , the arterial  and the venous  systems . Together they constitute the  three important limbs of circulatory system namely , the  pumping, delivering and retrieval systems .In physiological conditions approximately 6 liters of  blood  has to traverse  the entire   circuit every minute . The  purpose of the  circulatory system is not simply circulating the blood within the body,  but  it has to perfuse different vital organs like brain, kidney, liver . Of course ,   the heart has to self perfuse the coronaries  by it’s own contraction.The organ perfusion is determined by local and systemic  regulatory mechanism. A gamut of intrinsic and extrinsic neuro humoral modulators take up this job. A functionally intact autonomic nervous system is an absolute necessity to maintain tissue perfusion.  The perfusion pressure is highly variable in different organs and different cells. Similarly the ability to with stand ischemia and hypoxia also varies. Shock  is a general term used to imply ,  circulation is seriously compromised.Here we will confine our self  to the intricacies of peripheral circulatory shock

Traditionally shock is  classified as

  1. Cardiogenic shock
  2. Hypovolemic shock
  3. Vasodilatory /Redistributive/Septic /Warm shock (Can be called  as  arterial shock )

The hemodynamics of the first two are straight forward and easily understood. In  cardiogenic shock , the pumping action of heart is primarily affected .In hypovolemic shock  there is no  structural defect in any of the   circulatory limbs but there is  a loading defect due to low blood  volume as in hemorhagic shock .

The term vasodilatory shock or redistributive shock is most poorly understood and most difficult to treat.

The  concept is further confounded as  combinations of   above three mechanism in a same a pateint can occur . ( More commoner than we believe !) . An example could be a septic patient  with an  internal bleed and myocardial  depression either due to preexisting LV dysfunction or circulating toxins.

Since  we have always perceived heart as  the  sole  vital  component of circulatory   system , our understanding of the role of the vascular tree which is primarily responsible for delivering the blood is largely undermined and neglected. We are always happy if the EF %  is normal.

Classical features of  circulatory failure ?

The cardiac contraction is good.This is documented by normally contracting LV by echocardiography. The pulmonary capillary wedge pressure is normal (<12mmhg).Still the patient is in  hypotension with  evidence for vital organ under perfusion like oliguria and reduced mentation.

What is vascular tone ? What sustains  the flow of blood into the tissues  ?

The entire  vascular tree could form a   few 100 kilometer length.(Capillary /arterioles /venules included). While , it is easy to  percieve heart as  a dynamic pumping organ ,  it is a less recognised fact the entire vascular tree is also  pulsating  to every beat. That is the rhythm of life. What makes the vascular tree to pulsate ? Apart from  contraction of the heart  , there is an  intrinsic tone for the large , small arteries and the arterioles and veins  .This tone is vital for pushing the bllood into various organs and return into venous circulation and subsequently back into the heart.

microcirculation shock cardiogenic septic

The  millions of perivascular cuffings and the artreriolar smooth muscles  can be considered as  small micro pumping stations situated along side every cell.

It is very important to emphasize here,   if  tone in these microcirculation is less than optimal , the patient’s circulatory  system can never complete the desired circuit  even if the heart has 75% EF . This exactly is happening in circulatory shock . The vascular tree fails to accept and return the pumped blood  in timely fashion.

What controls this tone ?

It is chiefly under the control of autonomic nervous system.The endogenous vasoconstrictors , the adrenergic nervous system, the endothelins , the angoitensins constrict the vascular smmoth muscles while endothelial relaxing factors ,( EDRF -nitric oxide relaxes it ). There is a delicate balance between these forces.

A cardiovascular health of a person is not simply having a healthy heart , he has to have a healthy vascular system with intact biological activity.The fact that , not every one with sepsis react with poor vascular tone indicate inherent capacity to neutralise toxic vasodilatory neuro transmitters.

Is there a invisible parameter called vascular ejection fraction  in circulatory  system?

Yes. It must be . We rarely discuss it . The vascular tree has an important role for pumping the blood into the tissues.  It needs micro manometers to assess the systolic and diastolic dimensions of small arteries and arterioles . But  what  we know is ,  it is grossly impaired in circulatory failure.The vessels especially the arteriolar smooth muscles which determine the perfusion pressure of cells go into state of permanent relaxation. The vascular smooth muscles lose control from autonomic innervation and become flabby. It is the   DCM equivalent for blood vessels. The arterioles no longer regulate blood flow and fluids get sequestrated in various viscera,( often called thrid spaces) and organ dysfucntion sets in. The resultant hypoxia aggarvates the tissue stagnation by producing still unnamed vasodialtory mediators.

What are the pharmocological approches to increase the vascular tone of a failing vascular tree ?

It is a very difficult problem even in this modern era of vascular medcine. Once set in ,  these patients invariably go downhill .The primary underlying problem  ,  often sepsis  need to be corrected. Usually these  patients need multi organ support.Vasoconstrictors like epinephrine,nor epinephrine , dopamine  can sustain vasoconstriction temporarily . As we know the vascualr smooth msucles can not be kept on this assited contrection mode for long.It is bound to fail .Patients native autonomic function has to recover fast to wean of this support.

What is normal circualtorty time .How is it altered in circualtory failure  ?

The normal circualtory time is 15-20 seconds.It is many times prolonged in circualtory failure inspite of the cardiac contraction being normal

What is effective circulatory volume ?

The body fluid compartment is divided into ICF,ECF & interstitial  spaces.At a given time , the fluid in the extracellular space  can only  take  part  in circulation. A good blood pressure does not always mean a good tissue perusion why ? This is very important to realise as blood pool has to dynamically exchange with intra cellullar compartment. At times of shock the blood can bye- pass the cells through the alternate circuits in the periphery of micro circulation. So what is circulating in the system may not be taking part in tissue perfusion .This is the concept of  effective circulatory volume.This is especially noted in hepatic shocks and in some terminally ill malignancy.

Is there a venous shock syndrome ?

Cardiologists  often show a  step motherly  attitude to venous disorders. In fact many  of the   cardiovascular  specialists   think their   job is  taking care of  heart ( Of course , a little bit of aorta and venacava !) .It is surprising  to know,  there is little  scientific data on determinants  venular and venous tone (Both small and large veins).

The power of venous system should not be under estimated  as it pumps  many litres of blood every minute  defying gravity ! For this to happen it needs a vigorous tone .Where do it get from ?  : The same  autonomic nervous system that controls the heart. Remember , in pathological states there is a  great chance for this to go out of control. So venous shock is a clinically distinct possibility. In fact inappropriate administration of nitrates which reduces the venous tone has resulted in many adverse events in RV shock.

In a patient with circulatory shock , we would  never know  how much is contributed by venous side and how much by arterial side .This is important as in circulatory shock we administer all vital drugs through veins.Now it is thought  systemic venous  dysfunction also contribute to shock state.

Clinical situations of circulatory failure or shock

Bacterial shocks

  • Gram negative sepsis
  • Staphylococcal shock

Viral shocks

Dengue/Swine flu etc

Others*

  • Dissiminated intravascular coagulation
  • ARDShypoxic shock
  • Elderly,Diabetic  autonomic neuropathy
  • Persistent post operative hypotension due to silent autonomic neuropathy.
  • Some cases of Spinal shock
  • Toxins – Scorpion etc(Intense vasoconstrictive shock )
  • Terminal shock in liver failure/Hepato pulmonary   syndrome

* Idiopathic unexplained persistent hypotension , with difficulty to wean off from vasoconstrictive agents is a commonly encountered problem in any intensive care unit.The exact mechanism is not known.When we are not clear about the mechanism  we  generally blame it on the  the autonomic nervous system !

How common is the mixed shock syndrome ?

This is more common than we realise .The classical description of multisystem failure is a direct consequence of this.

Can a cardiogenic shock transform into a peripheral circulatory shock ?

Such a scenario is  possible  .A  resuscitated cardiac arrest may end up with a recovered heart but a loss of vascular tone  possibly due to hypoxic vascular damage. .Many times cardiac patients are kept (Post PCI/CABG ) on large doses of  vasoconstrictors or IABP that can induce  tachyphylaxis. It may result in difficulty in weaning these drugs.

How can circulatory shock result compromised cardiac function ?

The common effect of any shock is  reduced organ perfusion.So even in peripheral shock , the coronary blood flow gets compromised especially if these patients have a silent coronary lesions which are otherwise not significant , becomes sites of hemodynamic hurdles during hypotension.This may result in global contractile dysfunction, or a coronary event.

What is vasoconstrictive shock ?

Epinephrine and nor epinephrine are  very potent  vasoconstrictors .If levels of these becomes excessively high , the blood vessels go in for sustained spastic state that can impair the micro circulation .Some times  this results  in a  good blood pressure in the major vessels but severely compromised tissue perfusion.This particular situation has been reported after scorpion envenomation , and in  rare cases of pheochromocytoma .

Final message

Primary circulatory failure or shock (With largely intact cardiac function without hypovolemia) is a common problem in critically ill.  The entire  macro and micro vascular tree goes for a  stunning reaction and  goes for  a sleep in a  semi dilated  state  . It can  be termed as  Arterial  or Arteriolar   shock. Contrary to  all those hi-tech   mechanical stuff for supporting a failing heart (LV assist, Impalla, Abiomed , ) the available options are very little here  . The response to vasoconstrictive agents are  also unpredictable. Correcting the multi organ failure  and targeting the primary cause  is the only hope.

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Logic would suggest  any two structures  in close proximity can have  some sort of anatomical , physiological or sometimes pathological relationship .Esophagus and heart  share a strategic  anatomical  space within the mediastinum  . The left atrial wall  is abetting the esophagus with only few millimeters separating the two. Trans esophageal  echocardiography has utilised this proximity for it’s  advantage . With the probe in esophagus we can get a  100%  interior view of left atrium . Both these structures can mutually compress one another at times of pathology . ( LA compression on esophagus in mitral stenosis , Esophageal compression of LA in hiatus hernia or esophageal growths) . Now ,  we also  realise , esophagus  a   functionally unrelated structure  to  cardiovascular system  can have a impact on cardiac functioning.

Hiatus hernia of gastroesophageal junction can mechanically compress the posterior aspect of heart and result in atrial  arrhythmias and pericarditis  ?

Reference

1 Duygu H, Ozerkan F, Saygi S, et al. Persistent atrial fibrillation associated with
gastroesophageal refl ux accompanied by hiatal hernia. Anadolu Kardiyol Derg
2008; 8(2):164-165.

A case report from South africa

http://www.saheart.org/journal/index.php?journal=SAHJ&page=article&op=view&path[]=115&path[]=109

Read further for esophagus- heart  stories.

  • Esophageal ulcers , spasm can trigger electrical activity that can mimic cardiac event  or rarely precipitate a real angina  , what is often referred to as  linked angina .
  • A rare case of pneumopericardium due to rupture of esophagus into pericardial space
  • ST elevation in ECG due to esophageal spasm

http://www.drsvenkatesan.com

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cardiologist Is he a person who puts  a   metal coil  coated with a synthetic fungus   in  a   incidentally  detected  block  inside a  small coronary artery and sends the bill to the Insurance company ?

Is he a person in a  cosmopolitan  hospital  who opens up a    chronically   closed  coronary artery , in an asymptomatic patient  and  live telecasts  his achievement trans continentally ?

Is he a person who   checks in by  the early morning flight and  puts multiple wires in  an  aged   patient   with  class 3 heart failure and  make  him walk  20 meters extra at a cost of  1000$ / Meter ?

Is he a person living in   Wall   street  ,   who   looks  for variety of holes In  the heart and trying to occlude  it  with   exotic   devicespci ptca stent

Is he the unknown   physician   who Intervenes in the natural history of Rheumatic heart disease   and arrests   immune mediated   valve damage by giving the  monthly injections  penicillin in remote parts of our country ?

Is he the person   who   Intervenes to prevent young   persons   from  smoking and help maintain  their  coronary endothelium  enriched with nitric oxide  & arrest  the coronary epidemic ?

cardiologist 2

Is he the small town doctor  who  Intervenes  to treat a breathless cardiac failure patient  with  digoxin and frusemide  and  dramatically alleviate the  symptoms and  prolong the  life of our poor country men?

Is she the village health nurse from an inaccessible health  centre  located in a  hilly terrain ,  Intervening  successfully, by   pulling out  live babies  from  severely anemic pregnant  mothers with failing hearts ?

pci ptca cardiologist coronary angiograms

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Early repolarisation syndrome, (Also called ERS) is a common ECG observation among general population.It is diagnosed when  ST elevation occurs   with concavity upwards in anterior chest leads and inferior leads or both. The exact  incidence is variable (Up to 2%). It forms an important variant in young males .Females form a minority  with this finding.

The ST segment instead of  staying at baseline drift superiorly .The descending limb of qrs ,  ie the S wave is  prematurely interrupted as it travels downhill before reaching the baseline , the ST segment is inscribed resulting in a elevated ST segment.

ers early repolarisation syndrome

What is the mechanism ?

ST segment represents the major part of  ventricular  repolarisation. The ionic channel responsible forthis current is K+ efflux from the cells. The potassium channel opening determines the speed with which replorisation happens. The kinetics  K+ channels are  greatly dependent on genetic inheritance (As do long qt syndromes) .The high degree of variance of ST morphology in normal population is attributed to potassium channel heterogeneity.

Is ERS a benign entity ?

For long . . .we believed so !  now evidence indicates it may not be . . .

early repolarisation syndrome ers ecg  primary vf

The importance of ERS  not lies in it’s ECG appearance , the fact that ,  it occurs in a critical time of cardiac cycle makes it a potential threat. We know ST segment encloses the   electrically  unstable  QT interval .Any alteration in it’s morphology can trigger a electrical heterogeneity. In fact there is some truth in the observation ERS prolongs the QT interval when compared to controls.

Haissagure has elegantly studied this issue in NEJM and provided evidence ERS may have a strong propensity for ventriculaarrhytmias (Read below)

But , there is no need to panic , ERS  is still considered benign, but  waht is posible is persons with  this abnormality could be prone for primary VF when confronted with a episode of ischemia.

What is exercise response in ERS patients?

One of the following can occur.

  1. ST segment normalises
  2. Stays  elevated
  3. Junctional depression

ST segment normalisation is the expected response. Some believed the resting ST elevation tend to prevent the true ST depression in times of ischemia  . Often , classical ischemic ST depression can occur in  patients with CAD.

Dynamic ERS

The most tricky finding is fluctuation in ST segment magnitude with reference to vagal tone, heart rate can occur.This can mimic a coronary syndrome , and enzyme levels are necessary to rule out .

Reference

1.Haïssaguerre M, Derval N, Sacher F et al. Sudden cardiac arrest
associated with early repolarization. N Engl J Med, 2008; 358:
2063–2065.

2. Early repolarization syndrome: Is it always benign?
International Journal of Cardiology, Volume 114, Issue 3, Pages 390-392
K. Letsas, M. Efremidis, L. Pappas, G. Gavrielatos, V. Markou, A. Sideris, F. Kardaras

Link to the best  review article on ERS

http://www.viamedica.pl/gazety/gazeta1/darmowy_pdf.phtml?indeks=97&indeks_art=1264

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Fundamental principle  of  human biological system is to live in harmony with nature and environment.Each cell  has a unique reaction  when it comes into contact with  external  material. This reaction can be acute or chronic  ,   local or systemic. The most severe form of allergy is called anaphylaxis  that can result in instantaneous loss of life. There  is a whole gamut of disorders  that  resulted  in a  separate  speciality called allergic medicine .

Further ,the transplantation  science have   taught us  an  organ or cell can be rejected at any point of time after implantation (Hyperacute -chronic) .With advancement of science we have started implanting a variety of devices  with complex metallurgy ,inside human body, metal clips, prosthesis, valves, wires, etc .How the body handles them .The consequences can be a mild reaction to major ones occasionally.

Consider ,a local allergy due to a orthopedic prosthesis  in one of the leg bones  is far less serious than a metal within a coronary artery  irritating the intima .

Remember hypersensitivity reactions can be severe . This lady reacted  like this to a sandal slipper -A  fiery red  infiltration

contact dermatits stent allergy pci coronary

Imagine  if a stented coronary artery react like this what would be the possible consequence ?

In susceptible  individuals  , can a metal cause

  • Intimal hyperemia
  • Intimal induration
  • Intimo-medial edema  following stent deployment

pci stent coronary angiogram thrombosis des

Why drug eluting stents are more prone for hypersensitivity ?

The answer is simple , while metal allergy is a comparatively rare phenomenon, the drugs we  coat and the polymers used are  many fold likely to result in hypersensitivity reaction.

While  the world is worried  more  about penicillin , sulpha allergy which occurs in 1 in 100000 ,  we tend to ignore the metal and drug  reactions within  the tender coronary arteries.

stent des rejection virmani  pci

What is  the clinical expression of  stent hypersensitivity ?

It is  often a coronary event in the acute phase and restenosis in chronic phase.

How much of acute stent thrombosis is related to stent allergy mediated reaction ?

The exact incidence  will  never be known. It could be high. Whenever a sudden unexpected early stent occlusion can be a suspect .

Is stent allergy a local reaction or systemic reaction ?

It is most often local .The drugs the stent elute can elicit a systemic reaction occasionally.

So what can be done to prevent this complication ?

Drug companies in it’s  package regularly  include the warning  message ! What does it imply to have a caution  on the covers ? .This warning simply represent about our ignorance in this issue. We presume it is a minor problem.

pci stent thrombosis stent allergy metal

Questions unanswered

  1. How does a cardiac patient knows whether he is hypersensitive to stainless steel or nickel ?
  2. Is it practical to have a stent allergic test in every patient before PCI ?
  3. Is routine administration of corticosteroids for few days after PCI an answer ?

Reference

R.Virmani , circulation 2004

http://circ.ahajournals.org/cgi/content/full/109/6/701?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=stent+%27allergy%22+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

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Atrial  septal defects  are one of the commonest forms of congenital heart disease.

  • The commonest being the ositum secundum ASD     ( Which is in fact is a defect in the development of septum primum)
  • The next common is ostium primum defect which is a part of AV canal or atrio ventricular septal defect.

Other forms of ASD include

  • SVC type /Also  called sinus venosus type of ASD .
  • IVC type
  • Coronary sinus defect -Also called partial or complete forms of unroofed coronary sinus

asd svc asd sinus venosus

SVC type ASDs

They are in the strict sense can not be called as ASD. This is because there is no defect in  any of the  embryological  inter atrial septal component.

There is no direct communication between RA and LA, instead   a window  or passage of communication   between pulmonary vein and SVC. Right upper lobe pulmonary vein  is usually the culprit .Some times more than one PV  communicates with SVC.

The exact area of this PV-SVC window occur between anterior surface of right upper lobe PV with postero lateral surface of SVC.

PAPVC partial anomalous pulmonary venous drainage can be considered an integral part of this defect as RUPV is linked with SVC.

Can we have a combination of SVC ASD and OS ASD ?

This is possible .But two embryological errors need to occur. This is often seen as a large OS ASD with deficient or absent superior rim. So whenever superior rim of IAS is deficient a PAPVC and a SVC ASD should be looked for.

Clinical features

  • SVC type ASDs  generally shunt lesser blood than OS ASDs. (Often<2:1) .This is because it is not the LA that is communicating with RA instead only a
  • It is usually a single PV (some times 2) that shunts from left to right.

There is a distinct possibility of missing this lesion in routine echo.Minimal RA,RV enlargement may give us a clue.The classical subcostal or  4 chamber  view in echocardiography may not visualise  these defects.

So, whenever one encounters mild dilatation  of RA and RV and the IAS appears  intact, a meticulous search and a focused echo in the superior aspect of IAS is warranted. Angled  superior views may pick up this defect.A transesophageal echocardiogram (TEE) is often required to  confirm it.

Therapeutic issues

  • Device closure is not possible
  • Surgery involves little more technicality than ASD OS.
  • Small defects can be patch closed.
  • Some times the SVC has to be disconnected from the PV and anastamosed separately on right atrial appendage. SVC resection  will  aid the surgeon in proper patch closure.
  • Post operative follow up is necessary as SVC obstruction or PV obstruction may be a delayed consequence

References

svc asd sinus venosus

http://ats.ctsnetjournals.org/cgi/content/full/59/6/1588?ijkey=4f42649bc5805f3cf7d60f5728ec7f871356277b

http://asianannals.ctsnetjournals.org/cgi/content/full/10/3/231

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Research is the  guiding force for advancement in medical science.New drug and devices are developed every year that result in major break throughs.There need to be  a strong purpose and meaning for every research concepts in Medicine.The fundamental  principle in medical research  should be . . .

In basic science

It need to  generate a  new concept  that should help solve a existing  problem  or find an  eluding  answer ( Eg mechanism of an organ or cell function,  Genetic research  etc)

In clinical science

  1. An applied scientific concept  that can generate new treatment  modalities.
  2. Development of new diagnostic tools that can add new information to the existing imaging modalities.It should have either a cost or effectiveness advantages .
  3. Development of new drugs  or devices or surgical methods with  less side effects.
  4. Development of new drugs, which has a new additional benefit with less side effects.

A .What is Junk research or duplication of research

Most of the research methods testing  “non inferiority”  hypothesis can be considered junk  research (Note – Exceptions will be there. )

The most exploited concept in drug research  is  the concept of testing   non inferiority as it  allows comparing  new drugs with a proven old  drugs .Why should some one produce a drug which is likely to have a same effect  with  no additional benefit. Huge amount of time  , money  efforts  are wasted in  such  research

What is the need for 20 different ACE inhibitors  and 10 different ARBs when the basic structure  and function is almost similar ? Similarly Statins, analgesics, H2 receptor blockers, various forms of heparin  the list is end less . . .

There need to be a  strict vigil  on which research question the industry is trying to raise  and answer ?

Drug are released periodically  like movies with same old  screen play ( With a new  name  of course !) but with   a huge  cost.If any novel or music or art work or done in similar fashion there is  vibrant media to expose it, or  some times even legal action follows.  Alas . . . In medicine  it is free for all as  any one can legally plagiarise with  loopholes in plenty. Some times these drugs are hurriedly marketed as it has to generate the funds  before risk of it getting banned due to unforeseen side effects. In this sense some drugs exactly mimic a movie with good box office run for the initial few weeks.

A autonomous  world body ( Say WHO ) should supervise which research can be pursued in this world that can help betterment of human health . Currently tighter  regulations come into force only  during human testing .We need act  earlier   to prevent junk research in lab itself ! This can save huge resources .Some  may argue ,scientific work should not be curtailed  however futile they are !  I leave it your judgement .

B.Placebo compared superiority : This is another controversial concept  .This was a prerequisite  for a drug research in the earlier era .Now a drug need to be compared with the best current treatment! not with placebo.

Why superiority studies  are rarely designed by drug companies ?

Realise , how rare it would be to find  a study   where  a patented drug  is  compared  for superiority over another patented drug . Can you  guess the reason . . .  because they can do  superiority studies  easily over the placebos  !

Do we need to restrict drug development with similar structure and function?

The only argument can be in a global economy no body has a right to prevent any company  from  producing whatever they want  to  ! Survival of such  drugs  in this world is left to  market forces .The consequence  such approach could be disastrous ,  as  the  cheap  generic drugs with a  maximal  proven beneficial effect (Eg Hydrocholrthiazide in Hypertension ,  ) may not be manufactured at all in the near future . (Link to msf)

Is  the need for choices ,  an excuse ?

Like any commodity , people need choices so what is wrong  if a same drug is produced by 100 companies.Let the best survive !

Remember drugs can not be compared with other commodities. Even in other sectors , there are restrictions .( You can not allow 100 flights in a same sector or 10 mobile phone companies in a single city ,  however free the economy is ! )Every drug and device company should have a moral and legal obligation not to reduplicate the already proven concepts. Many tend to masquerade as new concept with a very subtle difference.

What is the favorite game  played by the drug companies ?

It is a too competitive market out there in world pharma industry. Drugs and device are developed at huge cost.They have to spend billions of dollors for R &D. They need money. The  manpower , time and cost involved are enormous. A drug or device has to pass on many acid tests and hurdles before releasing into market.Even after releasing there is a very good chances of it being  recalled  in the first few years as real human data start pouring.Apart from these many drugs and devices fail to take off at various levels. There can be a huge financial loss.(Eg Torcirapid HDL reducing agent).

So what is the solution ?

Drug companies involve in futile research that is imitating already proven concepts .And a drug which was approved for one indication by FDA is tested for many other indications as it becomes easier for increasing the market  share.This is can be  called as  the  “Phenomenon of  drugs  looking for a  new indication” .This  against  spirit of clinical research .

The classical example is  the attempt to  widen the  indication  for statins , amiodarone ,  ( Aortic stenosis   etc )Instead our energy  should be focused   into  developing  drug  for incurable  diseases

When can duplication of research  be beneficial ?

Scientists are working hard for a total artificial heart for years.Many teams are pursuing different methodology and concepts. Here the  competition is welcome. Like this there are so many labs  trying to create a solution for a genuine medical issue.

Disclaimer

This article has nothing against any pharma industry. It aims to reason out the futility in medical research which is to be addressed for the betterment of human health.

Read related topic in my blog.

Can a Aim of a study be wrong ?

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Annual workshops for interventional cardiologists has been  hugely popular events.They have  become the forum for all technological breakthroughs. Some of the popular ones are

Japanese have gained a unique place in  complex cardiovascular  therapeutics interventions especially in chronic occlusions.

Landmark article for CTO crossing

cto chronic total occlusion  Katoh coronary angiogram

www.cct.gr.jp/2003/wirehand/index.html

www.cct.gr.jp  cto japan

How to reach Japan ?

Click below

CCT2010

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