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Improve Hearts Pumping Power : Effect of Vymada on Cardiac Remodeling | DR. AFTAB KHAN

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Cardiac remodeling is a term that refers to changes in the heart’s size and shape that occur in response to cardiac disease or cardiac damage. When doctors talk about “remodeling,” they are usually talking about the left ventricle, though occasionally this term is applied to other cardiac chambers.

Uh good afternoon and i think we are already running pretty late we are almost an hour and a half late so i’ve just made the slides a bit lesser because i think we’ve already been sitting through this session a lot so my talk is to talk about a new molecule that is the rna also being branded as weimada and its role in cardiac remodeling i think we are all aware

That heart failure is a major problem for all our patients and heart failure is one of the commonest cause of hospitalizations and i think what happens is that most of these patients not only do they get admitted but the only other problem is that they tend to get readmitted so almost 44 of all our heart failure patients tend to keep coming back with heart failure

Within the first year itself after discharge and this is not just the data which is global uh this is the data which is also local so when we had the indian heart failure and we had the trivandrum heart failure registry this also had a similar data which was similar to the rest of the world where we saw that there is a similarity between all genders so whether

It’s the men on the women each of them is equally affected with heart failure and as i said the readmission rates are pretty high anywhere between 25 to 30 percent of patients get readmitted within a year of the first episode of heart failure and this again is something which is pretty distressing for many of our patients where economics also is an important

Factor and as i said it’s just not the economical factor it also means that patients who get readmitted also have a higher mortality so if your patient keeps coming back to the hospital for three admissions with heart failure we also have to understand that his overall mortality is also much greater and this was a problem that we had to always tackle despite

The medications that we are using and as dr depankar already talked about it the beta blockers the ace inhibitors the mras these still had a mortality benefit but over and over that we also had this new novel molecule known as the rna which had blocking effects on the ras inhibition as well as blocking the nepalison and this was the trial which showed the the

Paradigm heart failure trial which showed that as compared to another april uh rna had a much greater benefit and this was a great effect i mean we were talking about a 20 risk reduction of overall mortality not many trials have been powered to have such a great mortality benefit and this is one of such great trial which showed a superiority of rna over and in

All april itself in heart failure and based on this trial we had the recommendations on the accha guidelines which put it as a class one indication where in patients where you still had heart failure despite being on ac emitters you could switch them over from ac inhibitors to an rna to get an additional benefit and this was the strength of this data of the

Paradigm heart failure trial so we started looking at why exactly these patients did so well and the major reason was that we have to understand that why does this patients go into heart failure what what happens to a heart in these patients and the basic thing that happens is that i think we all understand is the inappropriate remodeling and this is something

That we learned way back in our physiology days also and there’s something known as remodeling that happens and this involves changes in the cardiac structure there is a myocyte death there is myocyte deformation and all of this leads to a dilatation of the heart there is an eccentric hypertrophy and an increase in the left ventricular end systolic and the end

Diastolic volumes most of the of the treatment protocols have gone towards what we call as reverse remodeling so whatever changes have happened in the heart muscles we want to get it back to a normal size we want to get it back to a normal shape and that is where these researchers have gone to try and reverse the models to get make sure that these patients have

Lesser heart failures so as i said earlier in patients who have a heart failure with a reduced ejection fraction again a sign of warning we are not talking about heart failure with a preserved ejection fraction we are talking about heart failure with a reduced ejection fraction and in these patients because of the volume overload there is a dilatation of the

Heart and over a period of time with chamber enlargement and eccentric hypertrophy there is a volume overload and this is condition of volume overload causes a thinning of the ventricular muscle it also causes a reduction in the systolic function and over a period of time a reduction in the lv uh increase in the lv volume also so the therapeutic strategies for

Heart failure reduce ejection fraction was basically to try and correct these pathophysiological changes so what we had to do is to kind of correct the hypertrophy we had to make sure that we could get rid of the apprentices and the necrosis and again as i said try and achieve a reverse remodeling to get back to a normal heart again we had again this is a busy

Slide and this talks about the different drugs that have been used earlier we had the renin-angiotensin strong mechanism we had beta blockers to block the sympathetic nervous system and this is the novel molecule the vimeta or the rna that we’re talking about which has additional benefits not only on the ras inhibition but also on nepalese in inhibition and

This is the relationship between what is the relationship between cardiac remodeling and prognosis and we had studies to say that one the one of the most important indicators of your survival benefits is your ejection fraction we have enough data over a period of time in many studies to show that the lower the ejection fraction greater is your mortality so if

You had an ejection fraction that was more than 45 percent the chances of your survival is much greater as compared to a patient who has an ejection fraction less than 35 both in terms of heart failure hospitalization as well as in terms of arrhythmic deaths relating to sudden cardiac death it also is based on the shape and this function of the valve the mitral

Valve we know is a dynamic structure whenever there is a dilatation of the chamber the mitral valve apparatus also gets stretched and there is vital regurgitation that sets in a vital regurgitation again causes a further aggravation of your left particular function by causing again a volume overload of the left ventricle and causing an infection contraction of

The ventricle and we have enough data to say that not only the systolic but the lv diastolic function also gets compromised in a patient with lv dysfunction and these are the various remodeling patterns and each of them these studies over a period of time have shown that patients who have remodeled hearts so if you have a lv modeling that has already happened or

Your lv’s already got remodeled both in terms of hypertrophy or dilatation there is a greater chance of having both not only cardiovascular death but also strokes and heart failures and the studies are mostly targeted to show that if you could correct this for example if your ejection fraction improved you could see that your mortality suddenly drops down so for

An ejection fraction that was less than 35 percent as i said your mortality is much greater as the ejection fraction improves your sudden cardiac death mortality would also tend to come down as your heart pumping becomes better your size of your heart or the volume left end diastolic left hand endoster volume increases there also causes an increased risk of death

So as your lv function reduces the diastolic component of the heart or the filling of the ventricle would be much greater and all of this would contribute to a worsening of your outcomes and the same goes with your left ventricular and systolic volume also if your heart is not pumping adequately at the end of your systole there would be a great amount of volume

That is left behind in the ventricle and if your baseline ends systolic volume is high your chances of mortality also tend to go greater and this is a study where we looked at the impact of uh the or the prognosis of heart failure along with left particular end diastolic volume and end systolic volume and what was shown is that even if you could improve the if

There’s an increase in the left hand end diastolic volume or end systolic volume by even a small amount even a 10 ml increase in your systolic volumes could increase your risk of death or heart failure hospitalization from anywhere between 9 to 15 percent so in effect it may look a very small matter but all of this or cardiac remodeling also has a greater effect

On cardiac mortality and this is where the results of the the charm trial was also looked at and uh here this was basically with candisarton which is another arb and what was shown is that once your ejection fraction reduced there was a greater chance of heart failure hospitalization and cardiovascular death as compared to patients who had an ejection fraction

That was much better again the same thing which talks about the left hand color and systolic volume and we had devices such as the cardiac resynchronization therapy device and what it does is that we synchronize the heart so that we place both the left and the right side of the heart and we use the heart synchronously so that we can improve the effective cardiac

Output and in this group of patients where the crt group was looked at what was found is that as your left centricular and systolic volume was reduced by even 10 millimeter 10 it was translated as an improvement in mortality also so with the cardiac range synchronization therapy if you could remodel your heart so that you could reduce the end left ventricle

And systolic volume a small amount of reduction in end systolic volume translated into a greater benefit in terms of reduction of cardiac mortality also and the same thing which happens with left hand and diastolic volume also so like the systolic volume even a reduction in end diastolic volume will also translate into improvement in your ejection fraction and

Translate into greater cardiac benefits a reverse remodeling with rhymer has been shown in the heart failure reduced ejection fraction studies and the basic mechanism well this is a very busy slide but this this talks about the various uh proteins where the two drugs work on and this basically helps to reduce or to cause a reverse cardiac remodeling so why bender

Basically does what it does it acts by reducing the cell death and also prevents the eccentric hypertrophy and all of this basically translates into a better cardiac remodeling and we have data from clinical trials which are talked about the use of this drug with weimada and benefits have been seen as early as within the first year itself so within three to 12

Months of use of this drug we’ve seen that there has been a reduction in the vital regurgitation status there has been an improvement in the mitral valve flow patterns and an increase in the ejection fraction with a reduction in the end diastolic and the end systolic volumes again this is also important to see that the ejection fraction does not grow you don’t

Need a very dramatic increase in the drama injection fraction so it does not go up from say 20 to 60 but a small amount of improvement in the ejection fraction also will benefit these patients and this benefits both in terms of heart failure hospitalizations as well as in terms of a sudden cardiac death so if you had to use this drug in say 10 patients at least

Seven of these patients would improve in terms of an ejection fraction and this was seen in the paragon in the paradigm hf trial also again it is important to see that we are not talking only of idiopathic dilated cardiomyopathy we are also talking about ischemic dilated ischemic cardiomyopathies and in these trials as many as eighty percent of these patients

Were patients who had had a previous angioplasty or a previous bypass surgery and they were on this novel molecule so improvement in uh why meda is both for ischemic subsets as well as patients who have an elevated dysfunction relating from an idiopathic dilated cardiomyopathy and again as i said this improvement happens within a period anywhere between three

Months to 12 months of use of course the data is to continue this even beyond the 12 months also but amongst this trials when these patients were added on to wymada despite being on optimal medical therapy when i’m saying optimal medical therapy which means that these patients were already on beta blockers they were already on mras and they were on the other

Anti-arrhythmics also and as like i said again what it does is that it reduces the left ventricular end diastolic volume as well as reduces the end systolic volume significantly when you compare them over uh over the baseline without the use of of biometer as compared to another april uh so basically what to substitute to look at this what happens is that not

Only does the vymeta reduce the mod remodeling there’s also a reduction in the miter flow in flow patterns so this is also important because when you’re many of the echocardiographic follow-ups that we do we look at the microflow inflow patterns to look at how your your rebottling is happening and there is a significant deduction when the use of imoda is used in

This group of patients and again this those this benefit is dose dependent so the guidelines talk about using 200 milligrams twice a day and that’s the optimal doses that we want to reach of course we do start with the smaller dose in this group of patients we do start with 50 milligrams twice a day and then build up based on their hemodynamic response and their

Creatine response to reach try and reach 200 milligram twice a day and as i said earlier the increase in the ejection fraction happens pretty early in the course of the disease and within a period of three months in this trial we could see that there is a significant improvement in the dosage of in the ejection fraction uh so i think what we need to understand is

That there are larger triads going on which are looking at the use of y murder in ventricular remodeling or on large vessels also and two such trials what i’d like to mention is one is the evaluate hf trial whereas compared to ace inhibitors or anaerobic y meta has been compared in a one is to one fashion in a double blended trial to look at the aortic stiffness

So this is one of the indirect methods to look at the ventricular remodeling to see how much is the resistance and this trial is going to look at a randomization over a period of almost two years and uh as i said this is a double blinded trial where the first run-off within the first 12 weeks is double-blinded with wi-meda and another pearl and after the 12

Weeks period it’s going to be an open label trial where these patients are going to be on the energy alone and the other trial that we are talking about is the proof hf trial and this trial is also going to look at the nt pro bnp which is one of the markers of heart failure and it’s also going to look at cardiac remodeling modeling assessed by echocardiography

And all these parameters that we talked about end systolic and diastolic volume left atrial volume index mitral inflow patterns to see how much is the baseline as compared to a one-year follow-up and these two trials are basically we are still awaiting the results of these trials and these will give us an idea about how the uh the remodeling happens with waimada

As compared to the other optimal medical group that we have so to summarize we know that heart failure is a major disease for us patients have a problem of coming back with rehospitalizations and we know that these hospitalizations have a mortality effect also we now have a new novel molecule which is the rna or the angiotensin receptor nebulizing inhibitor why

Mudder which can improve remodeling these patients with heart failure and not only on those patients who are not been on be on these medications earlier but also a switch can be made from ac inhibitors or arbs to those to rna for those patients who have been on optimal medical therapy previously thank you for your patient hearing thank you dr khan now this session

Is open for question is there any question i have one question please a long-standing diabetic patient having ckd a teatrine clearance about 45 to 50 had dilated cardiovascular it has been detected now now what should be the ideal treatment for this patient right so i think what we there’s a very good question the first thing is that we need to identify and

Try and identify correctable causes for the lb dysfunction and we know that as the bunker also talked about there are many causes which can produce lb dysfunction and ischemia being one of the the commonest cause so in this patients we need to evaluate and find out whether the patient has an estimated component whether there’s an episode of reversible coronary

Artery disease whether there is angina or reversible ischemia that we can tactile and this could be by means of a treadmill or for patients or not very active by means of other imaging modalities or dopamine stress echo or stress thalium or any other methods to find out whether there’s reversible ischemia now as you said the patient already has a kidney disease

So therefore the decision in terms of making a decision in terms of further invasive management say an angiography or a further bypass surgery or an angioplasty will be based on the area of risk so if the patient has a large area of myocardium at risk where not treating the ischemia is going to produce lb dysfunction then i think it may be worthwhile taking a

Risk and going ahead with an angiography but if there’s a small amount of area at risk then probably optimal medical management with anti-anginals may be good enough for this patient the second thing also is correction of correctable factors as i said like of hypertension or many other correctable factors diabetes per se itself we need to correct diabetes well

To get a good amount of lv function improvement and as the punk are also presented we have data with the sgl2 inhibitors the doppler hf which also has shown benefits and amongst the molecules that we’re talking about rna that we talked about just now the guidelines are to not use it beyond less than 30 ml creatine clearance so one has to be careful once using

Rna in this group of patients and one must repeat a creatine clearance even in the borderline group to say that we are not ending up with hyperkalemia or reversing of the creatine factors so beta blockers can probably be used safely we can use the other medical pump that we used to talk about uh aprisol with uh nitrate with the nitrate inhibit with the nitrogen

Without oral nitrate so preload and post load both can be reduced with nitrates and and with apres also these are good drugs with hydrolysis so that these are good drugs to use in this group of patients and of course judicious use of diuretics also so one has to be again balancing risk of causing symptom benefit with increasing the creatine and worsening the

Creatine clearance by increasing too much of aggressive diuresis in this group of patients also so again i think there are a lot of correctable factors that we need to first identify and again as i said try the best optimal medical therapy both in terms of the beta blockers ace inhibitors preload and after load reduction and if at all the bottom line more than

30 we could try rna still in this group of patients you

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Improve Hearts Pumping Power : Effect of Vymada on Cardiac Remodeling | DR. AFTAB KHAN By Medvideo Qubix