The New Definition of Hypertension: Are You Closer to Having One?

On the New American guideline on HPT issued by the American College of Cardiology/American Heart Association

Many may be taken by surprise by the new Amerian Guideline on Blood Pressure Management. This new guideline was issued by a joint taskforce of American College of Cardiology (ACC) and American Heart Association (AHA) which coincided with the AHA Annual Scientific Meeting at Anaheim California. For yet another time, the American shocked the world with their all low, new definition of high blood pressure, bringing the definition of hypertension to 130/80mmHg compared to the existing level of 140/90mmHg. Now they have made this bold statement that blood pressure should be classified to one of four: normal (below 120/80mmHg), elevated (120-129/<80mmHg), Stage 1 hypertension (>130/80mmHg), Stage 2 hypertension (>140/90mmHg).

For those who have been reading Cardiology literature and guidelines, may recall how the Americans stirred the world in 2013 when they ‘removed’ the target level for treating hyperlipidaemia (LDL cholesterol) in their new guideline – which later was ‘repositioned’ and added a new target as well as new non-statin agent which initially was not mentioned.

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Then the Joint National Committee (JNC 8) released the new blood pressure guideline, to yet again stirred controversies on the opposite way when they suggested in older people above 60, the ‘normal’ blood pressure cut of was 150/90mmHg. As for younger people and target BP, it was all the same 140/90 mmHg. Of course, they are different and separate taskforce – but coming from the same continent, why there is so much difference of a 30mmHg in hypertension threshold, within a mere period of 3 years? Let’s not debate that since there had been numerous criticism on this JNC 8 (as much as the American new 2013 lipid guideline!) and a later publication suggesting an all new low BP target (refer to SPRINT – A Randomized Trial of Intensive versus Standard Blood-Pressure Control, NEJM Nov 2015).

So, was this new guideline on blood pressure driven by the surprise finding of SPRINT? Let’s examine briefly what this study was about. Prior to SPRINT, there had been a number of clinical trials such as HOT, ACCORD looking at lower BP target which did suggest lowering to a level of 130/80 may be beneficial. However the result of SPRINT seemed to be more impactful since it did also affect mortality, and the trial was stopped early due to the much lower event in the group assigned to lower BP target. The study recruited more than 9000 patients at high risk of cardiovascular events (note, they were not any ordinary person on the street with a slightly high blood pressure!) and randomised to two target BP groups: Standard – target BP <140/90 or Intensive arm – target BP <120/80 mmHg. Primary endpoint was myocardial infarction or other cardiac events and cardiovascular mortality.

What was the findings? In summary, the intensive BP group reached a level of systolic BP of 121.4mmHg while the standard group 136.2mmHg. The Intensive arm had a 25% lower primary endpoint (less overall incident of MI, other cardiac events and CV mortality 1.65 vs 2.19%) – individually it translated into reduction of CV death (by 43% – 0.25 vs 0.43%) as well as all cause death, and reduced Heart Failure by 38% (0.41 vs 0.67%). (All figures were annual incident by %) with median follow up of 3.2 years. Of note, incident of MI was reduced but not statistically significant. Therefore, what we can learn, in those patients with high risk of cardiovascular disease (or already having one), reducing their blood pressure to a target below 120mmHg will improve their overall outcome of death and heart failure, and overall cardiac events. This was a fairly short duration of study (median follow up 3.2 years), imagine the magnitude of benefit you are affording patients by treating their blood pressure to this low target over 10 or 20 years?

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What’s the catch, you may ask. What would happen if you lower blood pressure to that low level? As anyone might guess, there were more incident of hypotension (low blood pressure), syncope (fainting) and decreased glomerular filtration rate (GFR) which is a index of deterioration of your kidney. There is another thing which the main article in the journal did not cover. How was the blood pressure measured? In contrast to all other trials of BP lowering, which used standard “office”blood pressure measurement (BP measured by doctor or trained staff according to standard measurement protocol), SPRINT was the only trial that used ‘unattended’ blood pressure measurement. Patients in the trial were left in a quite room, BP measurement started after 5 minutes of rest and repeated automatically 3 times, an average reading was taken. So this is not a normal way of BP measurement, may be closer to a home BP (patients measure their own BP at home which usually gives lower reading than clinic BP).

 

OK, you are right, those clever Americans did not just rely on one isolated study to support their work, of course. It is to now one surprise that even earlier study like Framingham cohort and MRFIT population data suggested that a linear increase in future cardiovascular event started when your BP climbs to more than 120mmHg (systolic). Lewington et al in 2002 (Lancet) plotted a graph depicting a ‘normal’ BP level whereby there would be no increase in future CV event, was 115/75mmHg! This was the basis, and now further enhanced by a number of studies and meta analysis of observational data suggesting that BP level of 120-129mmHg systolic was associated with increased CVD event by 1.1 to 1.5 times, while BP above 130mmHg (130-130mmHg systolic) by 1.5-2.0 times.

Indeed, if we have a closer look at the ‘older’ guidelines, and consistently be it Americans, Europeans, Canadians or Australians, they have asserted that there is this so-called ‘pre-hypertension’ level of BP between 130-139mmHg, in fact some of them have made recommendation to treat this BP level in high risk populations. Therefore, re-classifying the hypertension BP cut off does make sense, perhaps to put more emphasis to the treating physicians to go all the way in optimising their patient’s care.

It is no secret  that any clinical trial that observed an increase in BP even as low as 2mmHg will be associated with a rise in CV events, in contrast those that showed BP reduction as little as 2 mmHg will be accompanied by lowering in CV events. To quote an example, there was an excellent HDL (high density lipoprotein) raising agent torcetrapib (CETP inhibitor) that showed impressive rise in HDL by 76%, however resulted in increase CV events, one of the reason which, was a rise in BP in the treatment arm (by 5mmHg)! (NEJM Nov 22, 2007). In the LIFE study comparing losartan (ARB) vs atenolol which proved an ARB to be superior in reducing CV outcomes among hypertensive, there was still a slight difference in BP of 1mmHg. Its miniscule, but remember what Lewington (Lancet 2002) et al had concluded in their meta analysis, of BP reduction as little as 2mmHg in clinical trials reduced CV events by up to 10%! Thefore any BP reduction does make a difference, implying the importance of lowering BP in patients at high risk or already having CV events.

So back to the new American guidelines, are you ready to accept being diagnosed as hypertensive by your doctor, if your BP is 130/80mmHg or more? Or even being told that your BP is on the high side, by having a measurement reading of 125/75mmHg? What is more important, perhaps is how do you treat the ‘new’ hypertension that matters. In this regard what being recommended is not a very new thing, since they are still dividing the hypertensive people to 2 categories (see the table). Which means, if you are a ‘normal’ person, not having diabetis or any cardiovascular risk factors, do not smoke, never being diagnosed with heart problem, having a blood pressure reading of 130/80mmHg, does make you a hypertensive person – though, you do not yet need any medication. However, if you already have a heart disease (angina/heart attack (MI)/stroke), or deemed at high risk by having one or more of those risk factors (and calculated ASCVD – atherosclerotic CV disease of 10% or more) then you should take blood pressure medication. This is no surprise, in fact, even before this guideline published, many doctors (cardiologists) would have recommended additional medications for similar situtation, despite you not being diagnosed hypertensive as yet. Basically, the guideline is recommending treating you as a whole person, rather than a blood pressure alone.

So what can you do if your blood pressure is 130/80 mmHg and you are now a new person with hypertension? Provided you have no other risk factors or heart disease, the recommendation is non-pharmacological intervention and regular check up of 6 monthly at least.

Non pharmacological intervention to prevent/delay HPT or reduce BP namely reduce weight, take the DASH (dietary approaches to stop hypertension) diet (high in fruit/vegetables), cut down sodium (salt), Potassium supplement – KCl, or fruit/veg & low fat dairy, regular exercise and cut down alcohol.

However, before you get diagnosed or confirmed hypertensive, ensure that at least two separate measurements (different times), first one preferrably on both arms have been carried out. There is a special condition called White Coat Hypertension – when your office blood pressure is high and home measurement is normal (below 120/80). If you are being diagnosed and medication being contemplated, it is worth to get a set of blood pressure machine (well validated one) to do your own measurement. Just make sure you do the measurement while at rest, not following a vigorous exercise or intake of any stimulant – preferably while seated after 5 minutes. If repeated measurement of home blood pressure is normal, while clinic reading always high, it is likely that you are having a WCH which do not require to be treated with medicines, though it’s still worth instituting all those healthy lifestyle measures.

Another important aspect is to have a thorough assessment of all cardiovascular risk factors which should include BMI, blood glucose and lipid, renal function, full blood count and ECG. A scoring system that predicts future risk of CVD such as the one recommended by the Americans (ASCVD calculator though may be at variance among Asians, may be helpful to gauge how intensive the treatment of blood pressure and other associated risk factors should be). One often forgotten risk factors but seen fairly common is family history of  heart disease at young age (below 55 for men, <65 for women), or family member who died sudden death – which the likely cause is more often cardiac. So now you understand it is not just about the number, it is one’s overall cardiovascular profile that matters. Existence of high blood pressure (the higher, the more risk) along with other risks such as diabetes, kidney disease, obesity, high cholesterol and family history will increase the risk of a person having future CVD.

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BATTLE OF NOACS – Real World Evidence and beyond…what’s left

There has never been any medical products which such a wealth of clinical evidence from randomised studies, supplemented by abundance of real world data, other than the New Oral Anticoagulants (NOAC).

As shown from registry data GARFIELD, usage of NOACs for stroke prevention in patients with Non-Valvular Atrial Fibrillation (NVAF) in 2015 came close to 40%, which is fast overtaking warfarin as the standard of care.

Is this an appropriate rise considering the high cost of these new medicine? Warfarin tablets (generic) cost a mere few cents while a month of NOAC treatment costs an average between RM240-300 depending on institution and subsidies. Is it worth the cost? Of course, in medicine there are things beyond cost, for example pharmacoeconomic etc which may not be a very straightforward thing in practice.

Comparing to warfarin, the landmark randomised clinical trials proved that NOACs are at least as effective as warfarin, with proven safety profile, while reduction of intracranial haemorrhage was consistently seen across all trials.

Aside from this, for clinicians treating patients with atrial fibrillation, they may be caught in the dilemma of which NOAC to prescribe, once they have decided warfarin is no longer the standard of care for these patients.

The researcher group led by Christian Ruff et al had conducted a meta analysis of all the four trials involving NOACs vs warfarin (RELY – dabigatran, ROCKET AF – rivaroxaban, ARISTOTLE – apixaban and ENGAGE AF – Edoxaban) published in Lancet Vol 383 March 15, 2014 which concluded that the NOAC as a group were superior to warfarin for stroke prevention (risk reduction by 19%) accompanied by a stastitically significant reduction in mortality (hazard ratio HR 0.9), as well as reduction in intracranial haemorrhage (HR 0.48). However there was a slight increase in gastro-intestinal bleed (HR 1.25). Low dose NOAC were found to have similar efficacy with warfarin. Therefore what the landmark clinical trials have done was established the efficacy and safety of NOAC, they were at least as good or even better than warfarin.

As to the question of which NOAC is best, one may never find the answer, or he/she would, depending on which set of data he or she believes in. Take it for fact, even in the issue of whether NOAC is better than warfarin, taking the randomised clinical data and real world evidence together, one would not reach a definite conclusion, if a fair and balance analysis were to be conducted. The simple reason because:

The randomised clinical trials of NOACs – all were conducted on a heteregenous group of patients. RELY was an open label trials conducted on patients with a lower CHA2DS2 score, while ROCKET AF recruited older patients, had higher risk patients (higher % of previous stroke for example) and CHA2DS2 score the highest. ENGAGE AF have somewhat closer profile patients with ROCKET AF, while Aristotle (and RELY) recruited more than 30% patients with CHA2DS2 score of 0-1! Therefore no direct comparison is possible.

How about real world data, all comers population? There are many publications on real world evidence of patients treated with NOACs, some sponsored while others independent. Some of the largest so-called real world evidence came from claims database of insurance like Medicare in US like that by Graham et al paper on comparison of dabigatran vs warfarin which showed warfarin to be superior to warfarin in mortality and stroke efficacy as well as safety (bleeding) except gastrointestinal bleed (increased). The same author also head another publication of real world data from Medicare, using propensity matched scoring, comparing dabigatran vs rivaroxaban (no warfarin comparator) – a much debated study which showed the superiority of dabigatran over rivaroxaban on bleeding and mortality but not stroke (indeed rivaroxaban came out superior to dabigatran for stroke reduction, though statistically not significant).

Graham’s controversial findings were apparently not the odd one, a number of other papers including that of European Danish registry had also highlighted the excessive bleeding risk in patients treated with rivaroxaban (compared to dabigatran or apixaban).

In short a number of these real world evidence publications have suggested the increased (or neutral effect) in mortality and bleeding with rivaroxaban when compared to dabigatran or apixaban. However when a warfarin comparator was available rivaroxaban seems to be comparable to warfarin in term of bleeding.

Let me be clear that I am not in the capacity of presenting a systematic analytical data of these real world evidence. What I am highlighting here is based on the individual publications as well as metaanalysis one of those by Lip et al since he is one of the well known authority in this field.

In short, looking at these real world data:

All the NOACs individually and as a group have similar or better efficacy than warfarin in stroke prevention. There are a number of publication showing rivaroxaban having a trend towards superiority in reducing stroke compared to the other NOACs, one study showing apixaban superiority, none showed dabigatran superiority (despite the randomised study RELY which suggested dabigatran 150mg the only NOAC superior to warfarin in reducing stroke).

All NOACs (individually and as a group) showed consistent reduction in intracranial bleeding comparing to warfarin.

Rivaroxaban appeared to have increased bleeding and (in some paper) mortality when compared to apixaban and dabigatran.

Rivaroxaban, and dabigatran (at least in a number of publications) have a risk of increased gastrointestinal bleeding.

Apixaban consistently showed low bleeding risk, including gastrointestinal bleed compated to the other two NOACs.

There are not many real world data accumulated on edoxaban to this date, in order to include for this cursory comparison.

With the above data, is it enough to make any meaningful conclusion regarding ‘superiority’ of one NOAC over another?

Perhaps the most conclusive statements that can be made are as follows:

NOACs as a group have consistently shown good efficacy and safety profile over warfarin, both in randomised landmark clinical trials and real world evidence.

NOACs have similar or somewhat better efficacy compared to warfarin in stroke prevention.

Reduced ICH with all NOACs comparing to warfarin.

Caution should be exercised in patients at risk of gastrointestinal bleed since NOAC may increase it (except apixaban).

NOACs as a group showing trend of superiority over warfarin in total mortality.

There are a number of studies suggesting increased major bleeding in patients treated with rivaroxaban. While there might be differences in the population of patients prescribed each individual NOAC, this may be a pointer for caution in prescribing rivaroxaban particularly in elderly or those with high bleeding risk. This statement in no way consign the drug to be any less than the other NOACs.

I have alluded all the above points, however there is a very recent publication (by Serebruany et al) on mortality among patients treated with NOACs compared to warfarin. The population was derived from the FDA Adverse Event Reporting System which contained more than 7 million records. After narrowing down to those adverse event reported on each NOAC, they have come up with over 120,000 records on NOACs and similar number on warfarin. This was a large database indeed, in which the number of mortality was somewhat 10 times the figure compared to other real world population. In short this study showed that NOACs as a group showed superiority over warfarin in term of reduced mortality, with the exception of dabigatran (showed increased mortality). Do bear in mind the AERS included all patients treated with NOACs, all indications taken together.

What does this new dataset contribute to our existing understanding on the performance of NOACs in the real world? Taken at face value, the study supports the notion that NOACs have shown consistent data in term of its superiority over warfarin (in reducing mortality), in general. Though, the data on dabigatran has to be treated with caution, and I would keep away from making direct conclusion or comparison as in the above case too. Furthermore we have no details as to how many percent of this mortality occurred among those AF patients or those in sinus rhythm, being treated with NOACs for other indications such as venous thromboembolism. Data from NOACs study among patients with acute coronary syndrome for example, have not shown favourable profile among all NOACs except rivaroxaban (ATLAS TIMI 52 trial), and the study on warfarin alternative among patients with valvular disease (including prosthetic valve) randomised to dabigatran or warfarin showed negative result with excess bleeding and CV events in the dabigatran arm. Could there actually be differences among NOACs when they are used for different indications other than stroke prevention in AF? Another possible conclusion from this mortality data is, that compared to warfarin, anti factor Xa based NOACs are showing favourable trend in mortality reduction (consistent data with patients on rivaroxaban, apixaban and edoxaban), while direct thrombin inhibitor showed the opposite trend. We await further data and key opinion leaders input on this issue.

(References on request)

ESC Congress 2017 – Further advances in cardiology with many positive clinical trials?

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The European Society of Cardiology (ESC) Congress this year took place in Barcelona, Spain from 26th to 30th August. The start of the event was just about a week before the alleged terrorist van attack at the street of Barcelona – La Rambla. No, it did not deter the hardcore cardiologists and scientists from attending, out of more than 32,000 attendees, there were only 40 who cancelled in the last minute. So, they were with the Spanish people, showing their sympathy and solidarity of the recent tragedy, chanting the magic words ‘No Tinc Por’ means I am not afraid. Aggrieved but not at all shaken by the threat, they move forward.

 

By far this could be the one ESC Congress that have presented with a significant number of groundbreaking clinical trials. Among the most notable ones are:

COMPASS – Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) trial

CANTOS – The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study

PURE – Prospective Urban-Rural Epidemiology (PUREstudy

CASTLE AF – Catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation

Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI)

 

New perspective in diet and CVD? Highlight from PURE study

This is a study which is set to challenge existing dietary guideline for CVD presented by the researches from Hamilton Canada. Prospective Urban-Rural Epidemiology (PUREstudy is a long term study involving more than 18 countries worldwide looking at the relationship between dietary behaviours and total and CVD mortality.

This was conducted in the form of Food frequency questionnaire in which the cohort is being followed up over time.

A total of 135,335 subjects were available for analysis.

It found that consumption of Fuit, vegetables and legumes was associated with moderately lower risk of mortality but not CVD mortality. The benefit was seen at 3-4 servings per day. Further they looked into dietary fat & carboydrate and found that, contrary to existing guidelines, dietary fats was protective against total mortality (but not CVD mortality) while increasing quartile intake of carbohydrate was harmful!

People might wonder, do all fats render the same benefit or some types of fats? How about saturated fat which the guidelines advise strict control? Surprisingly there was decreasing overall mortality with increasing concumption of saturated fat (SFA) and again, no effect on CVD mortality with the exception of a decrease in stroke risk.

Carbohydrate also did not increase CVD outcome, only overall mortality, so there were questions as to what mode of death associated with this increased total mortality, which the study did not address fully.

The results challenge current guideline recommendations on intake of saturated fat and carbohydrates.

So what can we learn form the result of this study? The cholesterol and statin skeptics may quickly jump to conclusion and claims the findings support their long term skepticism on the role of cholesterol in CVD…things may not be as simple, maybe we can adopt the advise from the principle investigator, Salim Yusuf – it is all about moderation. In dealing with food intake, we should strike a balance. In this case, clearly fruits and vegetable, including legume should be part of healthy diet, while controlling carbohydrate intake including sugar is important. Fats, you may ease off from the strict diet (provided your lipid profile is within ‘normal’), while decreasing your sugar and carbo, avoid trans fat (not covered in this study), do watch the total calorie intake though, since high calorie would be associated with the prevalence of obesity and metabolic syndrome which are still culprits in CVD.

 

Beyond LDL and conventional risk factors, time to focus on Inflammation –CANTOS trial

There had been debates on the role of inflammation in atherothrombosis. The earlier finding on role of hsCRP in development of CV events among people with low LDL had been highlighted by no one else but Paul Ridker, in 1999. Among patients diagnosed with ACS, despite advances in treatment, there are still residual risk remaining, it has been thought that this ‘residual risk’ areas could fall into either of Residual Cholesterol risk (highlighted by recent finding of further lowering of LDL resulting in better CV outcomes – FOURIER, IMPROVE-IT), Residual thrombotic risk (role of long term dual antiplatelets? Eg DAPT/PEGASUS study) or Residual inflammation risk – this was earlier demonstrated by Ridker when people, despite having low LDL still having excesse events, and JUPITER study that recruited people with ‘normal’ LDL level but high hsCRP treated with statin demonstrating reduction in risk of CV events in this primary prevention study).

 

In this study presented by Paul Ridker as the lead researcher, they recruited over 10,000 stable coronary artery disease patients post MI with high hsCRP (>2mg/dl) on statin and optimal medical therapy including statin (OMT). Patients were randomised to receive 50mg, 150mg or 300mg Canakinumab SC injection (3 monthly) vs placebo (4 equal arms).

Canakinumab is an interleukin 1B inhibitor which reduced IL6 and in turn causing reduction in the hsCRP. At a median follow up of 48 months, the groups treated with Canakinumab showed reduction in hsCRP between 26 to 41 % compared to placebo. It showed 15% reduction in endpoints of CV mortality, stroke and MI combined (150mg dose met the prespecified endpoints). There was no effect on cvd mortality or all cause mortality

The effect was observed to be consistent over large number of subgroups, with greater reduction of risk among those with greater hsCRP reduction (>median) 27% reduction in primary outcome.

There was additional non CV benefit including reduction in cancer mortality, 51% reduction in lung cancer. Groups treated with Canakinumab suffered less from arthritis incuding gouts and osteoarthritis

This was definitely a proof of concept that target inflamm (ILIB) resulting in further reduction of cardiovascular endpoints, independent of LDL. As to how it could be implemented in clinical practice still awaits further analysis and expert deliberation, bearing in mind the steep cost of the drug (price about USD 14000 per injection of 150mg dose!). There is also a concern on the increased incidence of fatal infection in Canakinumab recipients.

 

 

Afib Ablation early in Heart Failure to save life and improve symptoms

Castle AF is a study that helps to answer the question whether or not patients in heart failure who developed atrial fibrillation should benefit from conversion to sinus rhythm.

Out of 3000 patients screened (US sites), 397 (after further screening 165 vs 153 patients entered randomisation) patients with paroxysmal or persistent Afib and ejectioin fraction <35% were randomised to conventional treatment or AF ablation. They were special group of patients with optimal treatment, proven by the fact that all included patients have AICD or CRTD (resynchronization device with ICD) implanted – though it may not have any confounding issue in this trial. Pulmonary vein ablation was the standard procedure performed plus additional lesions/repeat ablation after blanking period, in the ablation arm.

Primary composite endpoint of 38% reduction favouring ablation. All cause mortality was also reduced, HR 0.53 p = 0.01. In addition, improved CV mortality and CV hospitalisation also seen among the active arm. The ablation group also saw increase in ejection fraction of 8%. High number of patients in the ablation arm remained in sinus rhythm at th end of study (AF burden of 28% vs 65%).

The caveat? The procedure was associated with increased incidence of acute pericardial effusion and severe bleeding (combined figure of 6%). Less Stroke, other notable adverse events were pneumonia, pulmonary vein stenosis, groin infection and acute heart failure.

 

COMPASS – addressing the residual thrombotic risk in high risk CVD patients

Another groundbreaking study in high risk patients with coronary artery disease and/or peripheral arterial disease is called COMPASS – Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) trial

This landmark trial recruited over 20000 patients (602 sites, 33 countries)

with coronary or peripheral artery disease with additional risk factors to receive either rivaroxaban (2.5mg BD) plus aspirin, rivaroxaban 5mg BD or aspirin alone with median follow up of 23 months. There were 2200 primary outcome events with the event rate 4.1, 4.9, 5.4% in R+A, R and A groups respectively (primary components – cv death, stroke, MI). Individual components of All cause mortality, CV death and stroke also were significantly reduced in the R + A group. This came at a cost of increased major bleed 3.1, 2.8, 1.9% respectively, excess 1.7 HR (R + A), 1.51 (R alone) HR but not fatal bleeding or ICH

Further analysis combining the outcomes/efficacy and adverse events (fatal/critical organ bleed) showed net clinical benefit favouring Riva plus aspirin (2.5mg) for this high risk group with HR 0.80, (p=0.0005)

 

Further evidence in support of no Oxygen in acute MI? – DETO2X study

The subject of harmful effect of oxygen therapy in acute MI has been going around for a while. Earlier there was AVOID study which suggested that supplement of oxygen in patients with acute MI without hypoxia could be harmful, resulting in increase in early myocardial injury and infarct size at 6 months.

DETO2X AMI is a registry-based randomised clinical study conducted by the Swedeheart group involving all major cardiac centres in Sweden. In contrast to the usual prospective randomised study, a registry based randomised study recruits all subsequent patients in a non-restricted criteria, via randomisation process. All patients with suspected of AMI (O2 sats >90%) that were recruited, were randomised to receive 6L/min oxygen for 6-12 hours or room air. Primary endpoint was death from any cause at 365 days.

Over 6600 patients were recruited, making it the largest ever study on oxygen therapy in AMI so far.

Mean spO2 was 97% in both groups (Oxygen vs Ambient), More than 65% of subjects underwent PCI.

There was no difference in mortality at the end of the study. There was a trend towards increased cardiac arrest and death in the Oxygen group (non significant). Analysis of all subgroups showed similar pattern, except in compaing those with spO2 >95% or <95%, trend favouring oxygen for those with the lower saturation.

As a conclusion, Oxygen therapy was not associated with any benefit in mortality in Acute MI. The ESC have got this early and incorporated it in their guideline, therefore chaning the recommendation to only give oxygen in those with spO2 < 90% .

 

There are a number of other positive clinical trials that you may hear about in due course. Among notable one – in hypertension – promising result on blood pressure reduction (off medication) among patients treated with renal denervation (SPYRAL HTN OFF-MED study). Is this going to see renal denervation making a comeback in the treatment armamentarium of resistant hypertension? Too early, as Medtronic is yet planning a full scale randomised study with long term result.

The battle of New Oral Anticoagulation is till going – with the result of RE-DUAL PCI (Dabigatran in Afib patients undergoing percutaneous intervention), showing dual therapy regime of dabigatran and P2Y12 antiplatelet to be safer, causing less bleeding compared to warfarin.

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I would also like to share our abstract which we presented in poster form at the ESC Congress, entitled: Open-labeled randomised controlled study of double dose clopidogrel versus ticagrelor in stable coronary artery disease (CAD) patients with clopidogrel resistance – we found 29% of stable CAD patients resistant to clopidogrel (measured by multi-electrode aggregrometer, Multiplate). They were subsequently randomised to receive double dose clopidogrel for one month OR standard dose ticagrelor (90mg BD). The result showed both groups reached a mean value of AUC (this is how the platelet suppression measured) within therapeutic range. However, only the ticagrelor group showed uniform and consistent platelet suppression, with all of the patients treated reached target platelet suppression, compared to double dose clopidogrel (33% failure rate). This result is fairly convincing of the efficacy of the new P2Y12 antiplatelet ticagrelor, which we are using more often now particularly in patients with acute coronary syndrome or those with complex coronary disease undergoing PCI.

Besides the above late breaking clinical trials, there were also presentations on the new guidelines of practice, as well as number of sessions that focused on certain key issues in cardiology practice such as:

Acute coronary syndrome STEMI – new recommendations including multivessel PCI (but still a debate as to when to be done, perhaps as in patient rather than during the primary PCI), removal of the door to balloon or door to needle time, now changed to First ECG diagnosis, giving interventional cardiologist more control of their performance. A ‘comeback’ of fibrinolysis where it is still recommended when there is a possible delay of over 120 minutes from first diagnosis to primary PCI. This should be followed by ‘pharmacoinvasive’ strategy, means patients should undergo coronary angiogram within 3-24 hours post fibrinolysis.

There was also guidelines on dual antiplatelet therapy – this time focusing on patients rather than procedures, so the whole issue of duration of therapy has undergone extensive revision, which may make things more elaborate for treating physicians. Standard duration of therapy post PCI has been adjusted to 6 months DAPT for all, regardless of bare metal stents, any drug eluting stents (DES) or even drug eluting balloons (DEB)! However, there is some flexibility in which a patient who is deemed to need shorter duration of DAPT maybe given as little as one month therapy. On the other hand, there was also a concomitant recommendation for a more prolonged DAPT, extending up to 30 months (result of analysis of two studies – DAPT and PEGASUS), in those with high risk of events and low risk of bleeding, subject to physician’s discretion.

As regard blood pressure, a number of sessions on the new target blood pressure were highlighted. Basically as result of the much hyped SPRINT trial which advocated lower blood pressure target in those at risk population, now to below 130/80. But to avoid <120/80 and in elderly, the target maybe <140/90. However, this must not be confused as to the absolute threshold for treatment, in those without other associated risk factors or organ damage, in which the benefit is not seen till the level of >145mmHg SBP (as shown in HOPE 3 trial).

In the field of intervention, the congress coincides with the 40 year celebration of Angioplasty. 40 years of rapid advances in intervention now expanding to coronaries, peripherals, valves, structural and beyond. It only means more patients are able to be treated (nature of percutaneous intervention which may simply be carried out even at relatively higher risk patients, compared to surgery), the next phase may see intervention such as transcatheter aortic valve implantation (TAVI/TAVR) coming soon to be at equal footing to surgery (barring the high cost!).

Playing with statistics in medicine…

Finally the therapeutic dilemma came to an end…
There was this young ex-pat patient came to my clinic with new onset atrial fibrillation (irregular heart), as she has hypertension we recommended blood thinning medication (anticoagulation) called warfarin on her. Soon after, another doctor prescribed a new novel anticoagulant A, which costs >100 times more. When she came to my clinic she told me that she has not started the medication, as she was not sure whether it was good or not..
Apparently there was some lack of communication. So I went through a brief counselling till she asked, which one is better? I told her comparing the two, the new one, drug A is of course far better, as has been proven in clinical trials. However, taking warfarin strictly with good INR (a way to check your blood thinning index) is likely going to give you similar protection, with overall higher risk of bleeding – the cost however is the main obstacle.
Now the patient said: I trust your decision, doctor. And I am willing to spend the money….
Knowing she has a very young daughter diagnosed with SLE, I really pity her, and this put me in serious dilemma having to recommend a treatment costing over RM400 (or higher cost for her as foreigner) – and yet there is no sure way to tell her she will benefit more compare to her current treatment – its all about statistic – if the ‘number needed to treat’ is below 30 – then it is something very compelling – but in this case it is far more (167 for efficacy & 67 for serious bleeding)…of course there are other benefits like less interaction with food, drugs, and no need for blood test (INR clinic).
Sighed….in the end I advised her give it a try and see how she tolerates the new medication…today, she came back telling me that the new medication had caused her to have pain, cough and shortness of breath. She happened to suffer from flu as well. Well, not a direct adverse event from the medication, however, to remove the doubt, and due to her reluctance I advised her to revert to warfarin.
The lesson here, decision making in medicine may not be very straight forward especially when cost effectiveness is concerned. Patient counselling is an important part of management, do make the patient aware and understand the benefits and risk of the treatment, as well as potential cost effectiveness.

More on TIMI score

A lot of people have visited my posting on TIMI score, which had been posted quiet a good while ago. Let me update you a bit. There are TIMI score classification for both STEMI and UA/NSTEMI, they are separate of course.

The STEMI TIMI score takes into account many parameters that include ECG changes, presentation time and Killip’s score.

Killip score is a simple but useful risk stratification score of patient’s with MI based on their heart failure status (1 – no failure, 4 – cardiogenic shock).

Both scores are reproduced here (pic linked from cardiachealth.org). From Morrow et al, Antman et al Circ, JAMA 2000

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Is there an ‘easy’ way out to reduce blood pressure?

Anecdote of my personal experience managing my hypertensive patients this week.

At last I was relieved. What I have nearly lost last week, now is back under control!

Last week, I was quite frustated by two cases of severe hypertension patients that came to my clinic. One swas a very elderly lady whom I saw first time, previously treated at another centre. According to her daughter, home BP had been quite labile however lately better controlled around 140mmHg systolic. She was otherwise well with cocominant dyslipidaemia only, no diabetes. Her clinic BP at first measurement was 190/90mmHg. When I rechecked it was still at 180/90. Due to her age and the fact that she was due to undergo cataract surgery, I suggested a few days admission. The daughter declined. She was already on Losartan 100mg daily, so I added 5mg amlodipin to start with, urging the daughter to monitor the BP closely.

Early this week she turned up at the ward for preop admission. Her BP in the ward was still very high at 170-180mmHg. I increased her amlodipin to 5mg BD (sometimes I started this way just to allow patients to cope with the sudden increase in antihypertensive, usual dose of amlodipine is once daily). The next day, her BP was still around 170-190mmHg systolic! I allowed her anyway to undergo the surgery under LA. It went uneventful however the ophthalmologist now handed her case to me for postop BP control.

She is already on amlodipine max dose for at least 48 hours, BP still unchanged. Changing the meds to single pill ARB and CCB combination won’t do much I think, since she was already on both separately, therefore I decided to target a different system. Aldosterone, yes, some of these resistant hypertension may have secondary aldosteronism. I therefore started her on spironolactone 12.5mg once daily. After three doses of this drug, here is the BP monitoring chart…

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Even a minute dose has worked so well in dropping the BP by 20mmHg or more, awesome. This is an indirect evidence of her high sodium retention state (salt retention…secondary to secondary hyperaldosteronism). Well, we have also advised her to curtail salt intake.

Second case was another elderly lady whom I saw before, with severe hypertension. In the past the BP had been under control on atenolol and perindopril. This time she presented again because, according to her, BP check by clinic doctor has been persistently high. At my clinic her BP was 185/100mmHg. Heart rate 88, means not fully betablocked. There was no specific reason, she could be nervous, nothing showed on the ECG. Repeated check found no reduction in her systolic BP, looked dubious, however she also refused admission. I sent her TFT and renal function, and started her on diltiazem slow release (Herbesser R100mg). Last Friday she returned to my clinic, this time her BP had dropped to 140mmHg at home, around 156mmHg at clinic. Not yet at target, but she had moved away from danger zone. Now I changed her perindopril to Coversyl plus adding the diuretic component, to obtain an optimal BP reduction.

In both of these cases we have seen big drop in BP with addition of a single agent. I have maintained my practice of using the first three line of drugs A+C+D in most occasions (A=ACEI/ARB, C=CCB, D=Diuretics), however, there are times when I skip this rule especially in dealing with resistant cases. Whatever it is, the first aim in treating hypertension is to reduce BP to target. Next you have to think of the most appropriate agent, ie one that is likely to confer optimum benefit in term of prognosis. Then I will address comorbidity and risk factors, low threshold in initiating statin especially when there are two or more CVD risks present.

Help, how do I entertain this request to talk about a product I do not really favour…?

I am a doctor, I do not do marketing, I only present evidences…

If someone ask you to give talk to an audience about a product that you do not support, for the purpose of promoting it…what will you do? Hold on, there is some attractive honorarium for it, will you do it?

I was not in that kind of situation, but nearly. Now they had asked me to talk about this product H, that I do use, indeed, but not as my first choice. I have kindly obliged since they approached me in a very persuasive way and I know there is nothing wrong with this product anyway, just that I do not use it enough. Did I do it for money, no way, coz, I gave my agreement even before the rep told me that there is going to be honorarium – true, some company do not really give you anything substantial for speaking for them, I still do accept the invitation. For one, I treat this request as an academic exercise aka my own CME, furthermore it gives me opportunity to meet new people and broaden the horizon of my national appearance.

Here is what I did. First, yes, the product is genuine, endorsed by guidelines. I looked through the literature, some of which were old ie pre-2000, however, on browsing our own clinical practice guidelines, no doubt this product was mentioned as one of the approved treatments, listed at par with other, more established product that I frequently used. Therefore there is no conflict, it’s just that, I did not favour the product, due to my own exposure and previous experience.

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Second, as usual the company gave me the presentation materials. As a practice, I do not adopt the presentation material completely, instead, I will go through each slides and ensure that the content genuine and does not contradict with my own understanding and the established evidence. Then I only picked materials that are fairly neutral in contents, ie not too patronizing of the product, I keep on the generic rather than brand name in almost all the labelling if possible. Any of the material that is doubtful or overbearing of the product will be put aside.

Then I drew my own concept and perspective for the lecture. I outlined what I wanted to present, rather than what the ‘company want me to talk’. Obviously I have to supplement more than half of the content with additional materials obtained from my own research. This is where I like being given the task of giving a lecture, since it gives me the opportunity to explore and hence broaden my understanding of the subject, in a fair and unprejudiced way. Fortunately, this day it is  not very difficult to search relevant references through internet.

On the day when I arrived, the company rep had already set up a computer, and projected the slides of the presentation! I quietly went to the stage, and asked to use my own laptop, telling them that I had prepared my own material, combining with the material they have supplied. They had absolutely no problem with this, so I showed them the entire content of my presentation, to assure them that the presentation ‘does justice to their product’. They appeared to be pleased, in fact at the end of the presentation the company manager praised me for the wealth of contents that I have presented.

Therefore, by carrying out this exercise, I had given a lecture, which was fair, unbiased and highly academic. This was proven, when during the discussion, audience had thrown various questions that were quite general rather than too focused on the product. At the same time, the company were happy since enough justice was given to introduce their product to the intended audience.

You may be interested to know, if there had been occasions when I refused to talk about products? Yes, as far as I can recall twice. One about a product that now is being withdrawn from the market – I was sent for a special training workshop for it, but later declined to take further steps to promoting it. Another was a product, which is good and genuine, but I do not use it so much (very much like this case), but I declined coz the company rep was so pushy, then it was passed on to my junior colleague. There was another invitation for a special expert group of another product, which I had some doubt about its strength of evidence, however, I sat there merely as adviser or to give expert opinion, if it come to the stage of endorsement or promotion, I will have to take a stand depending on the nature of the proposal.

In principle, I found most if not all companies (at least their senior management personnel) will not allow promotion of their products beyond its approved label. Therefore, some of them will insist on going through the presentation material in advanced, not because they want to see how much you are promoting their products, its rather to rule out any off label marketing being presented.

Hearty Sharing about Heart Disease at Batu Enam Mosque Gombak

As a sequel to our successful forum at Alam Damai Cheras last month, where I was the moderator, this time I was invited to speak to the congregation of men and women of this Masjid Lama Batu Enam, Gombak.

The place was a little vague to me, despite the fact that I lived in Gombak about 7 years ago when I first settled in Malaysia. It took me 2 stops at two other mosques that were located nearby. Professor Mokhtar who represented the mosque committee – who happens to be my senior colleague at work had been in communication via FB prior to the event.

There were quite a sizeable crowd of men and women, altogether must be close to 80. The mosque is quite old, it was first opened in 1931. Apparently, when the community  built another newer and bigger mosque, Masjid AsSyakirin, which is located about 1km apart, they decided to leave this mosque intact to continue its function. The unique thing about its mosque, apart from its modest size, is its location which is along the main Gombak road, therefore leaving the attending congregation no space for parking. I was given special previlige to park opposite the mosque entrance, leaving half of the car resting over the heightened kerb.

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Most of the audience were of the older age, there were a few young people including the chairman. They provided a decent Powerpoint projector and a good public address system. I began by flashing a slide denoting someone’s status ‘how to have a good heart’. I assuredly said that people who attend the mosque are on the right way of getting a good heart, since everytime they are leaving their house to the mosque, they would recite the du’a among which so that Allah will give send light to their hearts…

Heart disease as number one killer, is no longer a strange statement, though by producing various data derived from the European and international studies, I boldly stated that the true prevalence of cardiovascular disease (that means all heart diseases plus stroke and peripheral arterial diseases) approaches 40-50% globally. However, most worrying is the increasing incidence among young people, which I spent a while demonstrating with examples, including angiogram picture of a 26 year old patient of mine who presented with MI and severe two vessel disease. Women, albeit young are no exclusion, again I mentioned how a 38 year old woman could present with acute MI and severe three vessels disease requiring coronary artery bypass graft. In addition, I brought another striking example of how I had to perform coronary angiogram on a very young patient of 23 year old, though it was almost normal, the guy has a very strong family history of MI, has diabetes and metabolic syndrome. My point was, coronary heart disease in Malaysia is very aggressive and affect people from a very young age group. The special thing about coronary disease in this young group, they tend to be severe and involve multiple vessels.

Further I went on showing alarming statistics of cardiovascular risk factors, based on the old NHMS figure that more than 60% of Malaysians have at least one cardiac risk factor. Accummulation of risk factors increases one’s risk of getting heart disease. Furthermore certain comorbidity especially diabetes doubles the risk. There are systematic risk predictors that can be used to guide therapy such as Framingham risk calculator and European ‘SCORE’.

Lastly, on prevention. Healthy eating, healthy lifestyle – exercise and weight reduction, plus smoking cessation were emphasised repeatedly throughout the lecture. I also gave brief outline of treatment for coronary disease including risk factors modification, medication and revascularisation. Videos of heart anatomy and function, atherosclerosis and MI, and revascularisations with CABG and PCI were shown.

The question and answer session was lively with audience throwing various questions covering medications, how to deal with symptoms of heart diseases, popular issue such as supplement and types of diets etc.

I would like to thank Prof Mokhtar, the committee of the mosque and all the audience present. I hope I have shared some useful highlight and motivate the people to adopt healthy heart living. Afterall, I feel more satisfied now with the changes in approach of the lecture this time. I do hope to improve this further and would not mind accepting future invitation to speak on the same topic. Well, it’s my small deed, at least I can contribute to the society and educate them on this subject that I posses some expertise on.

When all you see is blood….ugh not another complication!

I am starting the day free and easy. Good start of the weekend when I managed to join the Subuh prayer at the surau, and as usual excused myself as soon as prayer ended, went home and awoke the rest of the household between reciting daily portions of the Quran. Kids have school commitment and football but I didn’t need to send them coz they got their motors. Oh, but my mind is fully occupied and I got so many paperworks to do that I don’t think I am talking about going out – though we have at least 2 functions to attend today, and tomorrow evening is my public lecture at a mosque in Gombak (which I am yet to prepare). Therefore I have a good personal reason not to be at the Perhimpunan Rakyat today – furthermore as I stated in my FB status 2 months ago, I have minor disagreement with the nature of the organisation of this gathering, by any means, I do stand with the people and certainly support the spirit of this gathering. Between the time I am reading my PhD student’s thesis – need to be done by Monday, and I have yet to finalise the slides for my lecture to GPs this Wednesday. Now I must concentrate on all these jobs as my priority and not anything else, ooopss why I am writing my blog now??

Yesterday, at the conclusion of Friday prayers at our mosque at PPUKM, the Imam made an announcement inviting the congregations to join a congregational ‘Solat Hajat’ or ‘Supplication prayer’. Though I rarely join such activity, this time I decided for it, well why not, this would be a form of charity for the day, and there is one special reason, I wanted to make a special prayer for an elderly lady patient of ours (DH) who had sustained a complication from pericardiocentesis (a procedure to evacuate fluid accumulation in the pericardial space of the heart).

Here the (sad) story goes…DH is an 70 plus year old patient who had been diagnosed with left atrial myxoma (a kind of tumour in the heart) and chronic pericardial effusion, previous TB but not sure if the effusion was due to TB. Anyway, she was readmitted two days previously with dyspnoea. I reviewed the echocardiogram which showed features of cardiac tamponade, namely a huge accumulation of fluid giving that ‘swimming heart’ appearance with classic diastolic collapse of right ventricle. Since I was only alerted of the echo finding the day after, I immediately rushed to the ward to find out. A decision was made to transfer her to the coronary care for urgent pericardiocentesis. Patient and family, who initially were opposed to any form of cardiac interventions, had on this occasion agreed to undergo the procedure on the basis that it was urgent. Clinically she was quite stable, no tachycardia but had some features like Kussmaul’s sign and pulsus paradoxus.

Najma our previous Cardiac Medical Officer who is now incharged of the patient had requested my kind permission to perform the procedure, of course fully supervised by me. The first puncture was successful yielding straw colour fluid which clearly meant that the needle was in pericardial space. I helped her to thread the wire, next dilator followed by the pigtail catheter. However subsequent aspiration drew blood stained liquid which colour grew more intense and later evidence of clot. This was suspicious, and I performed bubble test which failed to show bubble appearance neither in the pericardial space nor heart chambers. We have drawn out almost a litre and the pericardial space now diminished. I was a bit wary, anyway concluded that there could have been small blood vessel torn by the wire or introducer, or injury to the pericardial surface in some sort.

The nightmare started when I was called half an hour later, DH collapsed with systolic BP of 50mmHg. Echo was repeated and showed re-accumulation of fluid. Not that fast so something must be wrong. The guys were fast in alerting the cardiac surgeons team. I was baffled, clearly the pigtail was in the pericardium, now still aspirating. In order to clear the confusion I decided to attempt a fresh puncture followed by a new pigtail, however this resulted in the same nature of aspirate, this time, of course more dense haemorrhagic fluid. Long discussion took place with the surgeon who were initially reluctant to proceed due to fear of TB pericarditis. In the end they took the patient to the OT. What was found, was phenomenal. Patient collapsed and went asystole on the table, on opening the pericardium huge amount of clot was found lining up the whole space. Once the clot cleared, the bleeder was found, a distal end of right ventricular branch of Right coronary artery perforation! Thankfully the operation went well and the patient is now recovering.

In this unique scenario of event, I must admit that we had taken all the necessary precautions with no shortcut. Diagnosis was made, supported by clinical assessment, explanation and consent obtained from the patient, family informed, they were made aware of the potential complications, the procedure was performed in the presence of a full compliment of cardiac team, the place was right. Each step of the procedure was taken in a systematic and appropriate manner. How human we are, to give a guarantee that a procedure will not cause complications? In fact, if you believe in Murphy’s law, well God’s law is above all, many times, complications happen when you least expect it. I mean at least in this case, I never expected that the procedure is of a high risk – what is pericardiocentesis if it is not one of routine cardiac procedure that required skill. The fact that the puncture was done by an MO (she was seriously traumatised by this event!) under a full supervision of a consultant – did not in any way make the procedure any riskier or of lesser quality assurance. Every step was done in the best way that we knew, of course it is a ‘blind’ procedure with known risk. I have not seen this kind of complication in my entire life.

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We had once, a junior specialist performed a tap in which the pigtail ended in the right ventricle (I promptly diagnosed this with the bubble injection) – patient survived following successful surgery – this sort of thing is  different in the sense that, something wrong was already detected at the start ie at puncture, in contrast to our situation when the puncture was clearly precise with clear fluid and no blood.

Nevertheless, this incident highlight a few important points. First, diagnosis is important, as much as prompt action. Correct diagnosis will justify the relevant treatment or management. This brings up the point on the necessity of performing the procedure, especially in a reluctant patient such as this case. Second, thorough consultation with patients and family must not be overlooked, explanation of the nature of the procedure and each potential major complications should be clearly expressed. Thirdly invasive procedures with potential for serious complications, must be done with appropriate preparations and techniques. Fourthly teamwork and the presence of adequate personnel helped. When complication happen, most of the time it is, more than likely, better to act in a most comprehensive manner, such as done in this case, when the surgeon was called early and treatment carried out immediately.

God knows what is best, we are only His deputies on this earth who should follow His rules and laws. Let’s pray for the wellbeing of this patient, and not to forget all the caregivers involved, may God keep them in the straight path and give them strength in their hearts and minds to face all these challenges without ever losing hopes.

Finding solace in the midst of complexity and crisis….

From hypotensive crisis to LM stenting…keeping life in balance

I don’t mind leading life full of challenges and crisis. I don’t pray for it, but take it for fact, life is already complicated as it is. It really depends on how you look at it. It is my choice, sometimes there is good in looking at something as crisis, so you can act on it, the positive result may boost your confidence and bring you closer to your goal.

Anyway, life as interventionist is never an easy one. I always try to keep the balance between aggressiveness and safety, between extravagance and moderation, more importantly balancing between harm and benefit in the long term. Unfortunately many of those aspiring interventionists are driven by passion to acquire certain skills or status who go on performing procedures of questionable indications or of debatable benefit. Most often scenario is revascularisations by means of PCI for patients with stable coronary disease.

Nevertheless even when you try to keep a most balanced attitude there would be many occassions when you would be required to act or else be seen as  a loser. Or face a demanding patient who dictates you what to do with his or her coronary lesions…to the extent of telling you which devices and which stents to use (ouch…).

Ok enough of moaning. Lets have a little flashback of the this past 7 days or so in my little intervention world.

When hypotension pays you a visit…

First is how do you face a hypotensive patient on a cathlab table. I had this wonder last week and had to get my mind working fast or else face an embarassing case of a perfectly well patient collapsing during a simple, routine angiogram. The patient is a middle aged man who had a coronary bypass 3 years ago now back with recurrent angina. The operation report indicated that he had a left internal mammary on his LAD and two SVGs, one to RCA-PDA and the other a jump graft to Diagonal and obtuse marginal. I had completed the SVG injection when suddenly noted that patient’s aortic pressure dipping rapidly from 140 to 60mmHg. Patient appeared quite ok though. No significant ECG changes, and I did not think that I had caused any damage to the graft. Since this was an elective case then there isn’t any reason of patient decompensating from an acute closure or the like despite severe native coronary disease.

The access was femoral since it was a graft study. Arterial puncture was straight forward, no haematoma on the site and advancement of catheter did not meet any resistance or anything funny, therefore I would not suspect any peripheral complication like retroperitoneal haematoma or iliac or aortic dissection. What I was left with was the little possibility of anaphylaxis or idiosyncratic reaction from contrast media. I quickly administered hydrocortisone and chlorpheniramine, followed by subcutaneous adrenaline injection. Intravenous plasma fluid was administered and the patient now complained of some funny feeling on his throat and chest. The tongue appeared large and thick. However his breathing not affected and I did not have the previlige of auscultating his lung to detect any ronchi. There were diffuse reddish skin discolouration on his upper trunk.

The BP returned swiftly and the symptoms improved. Now I still had to complete the angiogram by shooting the LIMA. So I changed the contrast media from Iopramide to Omnipaque. However the patient complained of extreme chill and started to shiver, I therefore had to accept suboptimal result by several subselective injection of LIMA to dilineate the distal anastomosis. IV fluid was continued and another injection of steroid repeated later, the patient returned to the ward uneventfully.

I still think its a bid odd to accept anaphylaxis when the patient was ok till that point, rather than having immediate reaction following the first injection of contrast. However the rest of clinical picture very much consistent with anaphylaxis.

Another hypotensive patient…

The above was not an infrequent event and we have a sort of rehearsed protocol to deal with it, dictated by what we think the most likely underlying cause is. However this nightmare of hypotensive patients don’t just happen in the cath lab. More frightening is when it happen in the ward, in the middle of night, managed by your poorly informed MOs (err…most of our MOs are well informed ones).

However, that very same day, while I was doing my daily round in the private ward, Hamat my specialist called me about another patient who was post PCI, having a sudden drop in BP. Reportedly the BP was recorded at 50mmHg SBP on arrival to the ward, from the cath lab! Knowing the patient was post PCI, done by me I was feeling utmost responsibility to salvage him whatever the cost. They told me that there was some ECG changes suspected of acute stent thrombosis, therefore a return to cath lab is being arranged so the freshly implanted stents can be relooked at. Hmm not very convincing I thought. Unless the ECG showed a barn door changes of ST elevation MI, I am not going to buy the idea of stent thrombosis this time. For a patient who just returned from cath lab to develop hypotension, there are lists of things that must be immediately ruled out. Stent thrombosis/reinfarction is just one, another is bleeding of course, especially if femoral route had been employed like in this case. But I am concerned with the third possibility of a tamponade. Well, I was told an echo was done, and the result was negative for pericardial effusion.

However, on arrival the patient was obviously distressed, complaining of central mediastinal chest pain. His peripheries were ice cold. The systolic BP was around 70mmHg, an inotropic support had been started. First I told them to transduce and connect the femoral line to the monitor, what a relieve when the arterial pressure waveform showed systolic reading above 100mmHg. I looked at the ECG – there were some peaked T waves anteriorly, mild diffuse ST changes at the inferior leads. The story, the patient underwent elective PCI of an occluded RCA. The RCA was previously patent proximally with occluded distal/PDA, however on reangio that day, the proximal vessel was already occluded. Therefore I decided to intervene on the proximal-mid section. Wire was successfully threaded distally, presumably to the PDA, I was able to pass small balloon distally with no resistance, however elected not to dilate the distal tree. Proximal to mid RCA was ballooned and subsequently stented uneventfully. Final angiography was fine.

Looking at the ECG there was a distant possibility of a stent thrombosis or in another word unlikely. However I was wary of the chest pain in case a dissection had taken place, not a very likely thing though since there was no ostial stenting performed and angiography did not suggest such harrowing phenomena. Bleeding, retroperitoneal haematoma…hmm I need to work on this fast. Another is bleeding from other source such as sudden GI bleed (with high dose antiplatelets loaded it is a certain possibility) – they had sent the Hb though it was ok I would not take it as final, as the changes in Hb may be seen a little later. Physical examination did not suggest any bleeding cause. Heart sounds quite ok. No pulsus paradoxus etc. Despite the initial echo failed to show any effusion, I decided another echo would do no harm. Surprisingly this time a large effusion was detected with evidence of RV partial collapse.

We arranged an immediate evacuation via pericardiocentesis. Pure blood was extracted, about 200ml or so. Since it was still under 4 hours post procedure, I ordered half dose protamine sulfate. Following the pericardiocentesis, pigtail was left in situ to drain. Echo repeated at two hours did not show any reaccumulation and the Hb remain stable with SBP remaining around 120mmHg, while patient was symptomatically better.

Diagnosis: wire perforation – it typically produces delayed pericardial effusion, since the fluid (blood) accumulation takes place slowly. In fact effusion could develop as late as 4 to 6 hours.

This reminded me of another similar event years ago. Sorry, sometimes you must not trust MO to do everything (my hardworking, trustworthy MOs excluded…). There was this elderly lady who was post PCI with successful implantation of stents to LAD. She was fine on return to ward but about 4 hours later developed hypotension. The MO who called me was quite casual in his presentation, giving impression that ‘its the usual hypotension, I just put up fluid and inotrop it should settle…’. I quickly ordered him to do Echo, he said yes. Alas, I later forgot about the case completely, only to return the next morning noting that patient’s BP was hovering around 80mmHg. Thankfully she was otherwise ok! I was deeply annoyed on finding out that Echo was never done, despite my order…I quickly did one and a large effusion was present. Again, the BP returned spontaneously following pericardiocentesis. Another case of wire perforation.

Other cases of extravasation as result of subintimal passage of wire/devices, or extension of subinitimal haematoma leading to perforation, usually happen more acutely and dramatically, on a small number of cases we fail to revive these patients despite aggressive measures. So do not take things lightly, timing of hypotensive episodes mean a lot.

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And yet…another hypotensive patient!

This was another episode that happened quite a while ago, though simple but let me have it mentioned for the sake of sharing and learning. This was a middle aged man, who had a successful implant of a dual chamber pacing. Returned to ward in a stable form and monitored under routine monitoring. A few hours later I overheard one of the registrars were talking over the phone to an MO in the ward who reported the man has ‘collapsed’ and had low BP. The registrar immediately ordered the ‘routine’ treatment of fluid and inotrope. I shouted, asking what’s the case and was informed that this was the man who we just implanted PPM. Well, I said, get an immediate CXR.

Again, somehow it was a very hectic day that I completely forgotten the case. Apparently CXR was only done sometimes after midnight, a large pneumothorax was diagnosed and a chest drain was performed at 6am in the morning! On knowing the case I was utterly dismayed at the mediocre management of this case. Some people never learned the difference between a routine and urgent or even emergency…

In a patient who is post-PPM implant, becoming SOB or hypotensive, think of pneumothorax. Other cause such as bleeding from the puncture or subclavian/SVC perforation from wire or lead; or RV wall perforation is a rare thing.

Work better when under pressure? Then, take the challenge…

Today is a Thursday. I am yet facing another busy Thursday. By default Thursday is a long cath lab day. However today I had to finish by around 1pm, go home and get ready to drive to the North – Kuala Kangsar where my wife is having a school meeting. Suddenly I recalled that there is a private coronary angiography case coming. And yet, another last minute addition, of a complex left main stenting. I checked the list, there were already 6 cases (including one PCI), not including the two additional cases. How I am going to finish them by midday? No way. As the only in-house Interventional Consultant, I need to be there till the end of the cath lab day. At this 11th. hour I texted David, apologetically begging him to come to my rescue…furthermore, David, I need an experienced colleague presence for that complext LMS case…thankfully David responded favourably, stating that he should turn up in the lab by around midday, which was perfect for me.

As I arrived at cath lab in the morning, the staf informed me that the PCI case did not turn up, another cancellation so we were left with 4, plus the two additional cases of mine. Hmm not a bad start for the day. We started with two angiogram with provisional PCI – both did not proceed. Then I started the private angiogram cases, which turned out to be much longer than expected – well, its a 73 year old man with hypertension and query recent MI. The radial artery was tortuous first of all, which took a while to negotiate, then the brachial/innominate vessels were supertortuous, even to get the catheter down was a challenge, manipulating was out of question. This set me back for almost 40 minutes. Now it’s 1130 time to start the LMS PCI.

This was a man in his 70’s who previously attended a highly reputed centre for his IHD, diagnosed with severe 3 vessels disease and a tight distal LMS, refused surgery. Knowing the centre, I would have expected they offer him PCI option, there was no mention of same, which could mean that the anatomy was complex enough. Yes, it must, with (on report) CTO of the RCA and LCX, and tight proximal LAD in addition of the distal LMS. If this was not bad enough, the man had an impaired LV with EF of 35%, and a stage 2 CKD. He was admitted to the private ward for an urgent cranial surgery for a rapidly enlarging cerebral tumour. Of course the Surgeon and anaesthetic would not proceed with the tight LMS.

I was thinking of options, well there arent much options are there? I could do a dobutamine stress test…if he passed then just keep him on a betablocker and proceed. But knowing the tight LM and LAD, he’s basically left with nothing, DSE itself could be dangerous, apart from the likelihood of yielding result that you already know. Or, let him go as a high risk case, full betablockade, no way, patient would be ultraworried, and the surgeon and anaesthetist would never take the risk, further they would think that I am such a loser for not doing anything….

A last minute decision to perform a LM stenting…? And I just got under 1 hour to do it…

So, I am left with a high risk LM stenting…I thought I will first delineate the anatomy, then possibly intervene with the highest risk lesions alone ie the LM and LAD, thats it. Do I need an AIBP, this has to be kept in mind. So, I fasted the man early morning, ordered an echo – which confirmed the impaired LV function though on new estimate not as bad, EF estimated at 46%, therefore this has taken him away from the higher risk category. Access via femoral, I started with a 6Fr. Coronary angiography showed a tight LMS and proximal LAD which was rather large, occluded proximal LCX and severe ostial RCA lesion with proximal stenosis as well, followed by CTO from mid segment.

Took a deep breath…we loaded the patient with Ticagrelor 180mg, I kept the 6Fr sheath since the LM stenting is not likely going to involve kissing balloon inflation. First I targeted the RCA in order to allow some decent circulation as a backup during the LM stenting. I managed to cross a Pilot 50 wire distally to PDA. However repeated attempt to cross balloons, including a 1mm balloon failed. Finally I settled with POBA of the ostial/prox RCA which now appeared better up to the point of occlusion.

The patient remained stable so I proceeded with the LM stenting. Standard JL catheter, wired with a BMW. IVUS was performed which confirmed tight proximal LAD and distal LM has a circumference of 4.7mm2. No concentric calcium. Means things are favourable for simple balloon followed by stenting now. Since there are sizeable gaps of more than 5mm between the LAD and distal LM lesion, which IVUS proved the area to have less than 50% plaque burden, I have the option of spot stenting the prox LAD and distal left main with two stents with or without overlap. I looked around, David was not around yet, I should keep going in view of time. Next I predilated with 2.5mm balloon, everything went smooth. David just arrived, I felt more relaxed to have a senior and experienced colleague like David around, not that I could not do this alone, its more of getting assurance that I am doing right! David agreed with my strategy.

I choose a 3.5mm x 13 Genous stent for prox LAD lesion, dilated up to 16atm. Then I took a 4.0 x 13mm Genous stent for the distal LM lesion, cross over to LAD but not overlapped with the first stent. Brief inflation over nominal (12atm) performed, there was a momentary chest pain complained though patient remained stable. Angiography and IVUS showed slightly underexpanded stent at the distal LM tight lesion. I therefore went on with a non-compliant balloon postdilation with a 4.0x10mm balloon. Repeat IVUS looked good with areas >9mm2. Final angiography was excellent.

We planned to keep patient on the ticagrelor for at least 15 days, following this he may undergo the surgery. Should an emergency arise, ticagrelor may be witheld and surgery can be undertaken within 3 days.

Praise be to God everything went well. This is a second case of LM stenting pre-op non-cardiac surgey that I had performed successfully with Genous, to allow patient to undergo surgery in a timely manner. According to OCT study, 15 days post implant is enough to give a 70% coverage, which according to renown pathologist Renu Vermani, regarded as minimum coverage required to safely avoid stent thrombosis.

I looked at the time, it was just 15minutes past one. I chatted with David regarding stenting strategy in patients undergoing non-cardiac surgery, and brief update of current DES. Then we spoke about FREEDOM, a latest head to head comparison of PCI with DES vs CABG in Diabetic patients with multivessel diseases. The result, as expected favoured CABG for all cause mortality and reinfarction. There was a trend toward less cardiac death in CABG group though statistically non-significant. The PCI group patients tend to have less stroke, as expected. Another ‘defeat’ for interventionalist? What now after OAT, COURAGE and hence FREEDOM, PCI is getting nowhere better than CABG, or even optimal medical therapy in stable CAD? Interventionalists may still have FAME and FAME 2 to defend themselves, but whichever arguments being put forward, in the overall sense, it is still true that PCI in stable CAD does not confer any prognostic advantage. As for angina relief, it may not be as great, as suggested by COURAGE itself where angina relief were only relevant in the first 3 years.