the kobe 19 patient with cytokine storm admitted with fever fever hypertension respiratory failure placed on mechanical ventilation then developing hemodynamic instability cytokine storm hypercoagulability it was placed on immo perfusion for three days leading to hemodynamic stabilization normalization of cytokine levels and decrease of inflammatory parameters with improved pulmonary exchanges until it was extubated not only that we found an improvement in miniature pressure diminished requirement of neural adrenaline and reduction of concentration of interleukin-6 but also improvement in function of the monocytes in terms of phagocytic capacity and production of mediators finally monocytes were demonstrated to improve their function by an improvement in antigen presentation as demonstrated by the improvement in hla dr expression and the number of monocytes expressed in dr this treatment has also been used in conjunction with ecmo in many patients and you see here the typical uh let's say a circuit in parallel with the ecmo circuit so in conclusion our recommendation which has been published in nature recently about these patients somehow recapitulates the possibility to use cytokine removal to use echoes to use specific membranes or to remove fluid in excess and leading to an improvement of the condition of the patient the recommendation however is to treat these patients quite early to avoid development of severe condition rather than cure them as mentioned by our chairman at the beginning you can follow many of our consideration on our youtube channel called cappuccino with claudio uncle and i really hope that you can also follow next year meeting our meeting was just held in november this year next year will be in october and if things will not be changing very likely this will also be held virtually from october 26 to 28th with this i thank you very much for your attention and i thank you for this very kind invitation thank you very much professor ronko and that as expected was quite enlightening and and i'm glad you also uh mentioned about the most contemporary topic as of today and that's the way we should be handling uh kovet but going back to uh the the subject and and something which is of common interest to us nephrologists and the cardiologists uh may i set the ball rolling and since we know that you you have uh another commitment and you have to leave a little early so we are having the question answer session uh soon after you're right after your talk and as i said to set the ball rolling may i go take you back to when you coined this term and then you had this typical cardio renal and renal cardiac in mind do you think it will help us if we stage it further the way we stage chronic kidney disease stage one two three four and five if we were to we were to sub classify cardiorenal syndrome as stage one two three trying to uh throw some light on the severity of a given syndrome because i'm sure you will agree we can't equate each and every cardioreal syndrome alike i mean there'll be uh cases where the severity is is quite minimal and you may not really want to use your strong weapons in that case so that's that's the first part of the question and the second is that if that is the case uh do you really believe in that your the way you tackle a given situation uh cardiorenal syndrome type one or two uh visa v3 and four your line of management is going to change so my question uh is will sub classification alter your line of management and does the existent classification uh indeed alter your line of management well thank you for for this uh complex question it will it may require actually a a meeting itself to be uh for discussion but in general i can tell you this it took approximately 10 years to familiarize with the classification of cardioreal syndromes by cardiologists and nephrologists that initially were reluctant to accept a classification we are aware that this classification is not perfect however it was not existing before and since we started this classification now cardiologists and nephrologists use a common language and when they say cardioreal syndrome type 2 they know what they mean now it would be certainly time probably to start considering within a specific type of cardioreal syndrome the level of severity but there is more on this there is evidence that one type may evolve into the other type for example a cardinal syndrome type some patients may not resolve acute kidney injury and because they do not resolve acute kidney injury they may end up with chronic kidney disease leading to cardioreal syndrome type 4 for example so i think it's extremely important to try to understand if there are interaction and evolution between the different classes furthermore once the group are familiarizing with the definition classification i think they may probably have the possibility to somehow stratify patients for risk and severity and this would be the next uh challenge probably but it should be done in conjunction cardiology and nephrologists together mr uncle a lot of a lot of questions as expected related to um uh angiotensin receptor and neptune hyzer inhibitor the typical psychobitril valsartan combination and its role uh in comparison to sglt2 inhibitors we've learned a lot about these two molecules over the last one decade or so or or even shorter than that so there's a few questions so one is uh can do do you foresee the role of arne in the mid ejection fraction range um uh of course we know that it's been so far advocated for usage in half ref so would you would you advocate its use in the mid range that's one and i'm sure the cardiologists are going to throw light subsequently so your take on that first i i think that this is an area that we need to study because of the renalism the nihilism in treating patients with chronic kidney disease in the past we have lost opportunity to learn a lot in the pharmacological approach to this patient i think today we cannot accept any more this type of nihilism and therefore we need to design specific studies on specific classes of patients now in order to receive the most let's say suitable information we need to be very strict in the enrollment of the patients and make sure that we are treating the same type of patient the same type of characteristics otherwise if the population is too heterogeneous we may have positive no results or even detrimental effects so we need to we cannot accept anymore to speak about therapy in patients with reduced renal function we need to speak about the therapy inpatient with the ckd stage one and two ckd stage three four and five i think that this is the challenge of our next studies well professor ronko there is always been an apprehension and we as nephrologists are always asked as to what is the cut off gfr value beyond which you would not want to use uh ras blockers and arnie would be an extension of the same question so would you would you really advocate a particular cutoff beyond which you would not want to use uh um well saturn as an army well you know not really you know people speak about 60 45 or 30 milliliters per million gfr and so on but first of all uh i think we need to apply the concept of precision medicine we need to consider that if the patient is accurately monitored probably can be treated with specific drugs even in presence of high risk for side effects but if the nephrologist and the cardiologist have a specific combined clinic these patients cannot probably be treated with these drugs even in condition of mild to severe reduction of kidney function nevertheless we need to monitor this patient to have a frequent monitoring if you consider uh for example the the use of insulin in diabetic patients you cannot recommend the optimal dose of insulin because you regulate this base on glycemia i think that we need to monitor this patient with the continuous akg with the continuous possibly or at least frequent potassium measurement and therefore we will find that a at least a fraction of patients may benefit from these drugs even in presence of severe reduction of kidney function again we need to to to develop a better way to monitor these patients the function of that question would be and as dr ahuja wants to know is there any evidence for rna in patients on hemodialysis would you be bold enough to continue use or or initiate treatment with the psychopath while certain combination even when your patient has already reached a stage of dialysis well if they actually are these are a group of patients that are optimally monitored because we see them every two days now i would not recommend this in an area where patients are seen by the doctor once a month or once every two months but if you as in italy for example this patient can be actually accurately monitored and everything every drug can actually be used with attention with a prudent approach but may display some benefit in some patients so so uh in talking about the other form of therapy and of course the obvious comparison between rna and sdlt2 inhibitors so which do you think is the safer option now that you know that now that we know that sdlt2 inhibitors have been found to be efficacious and safe even at gfr's of uh up to 25 ml with double keyfrozen so so which one would you believe is the safer bet for your patients with heart failure well you know again i think we have to consider a single case patient to not generalize this because we have not done studies enough on this sense but we should consider uh different outcomes the outcome of uh worsening heart failure uh and therefore ejection fraction the second is presence of comorbidities the third is evolving of kidney failure so some drugs may present the benefit in one sense but not in the other and vice versa i think we have to define first what is the end point while we're using this drug and what is the final target you're trying to achieve the most fascinating for us of course today is the combination of an acceptable injection fraction in patients trying to reduce the evolution of worsening of kidney function so at this stage i want to bring in dr vino gopal and dr hari krishnan dr vino uh your your way i mean what you would want to know from dr ronko the way he would want to treat first of all let me express our thanks to dr bronco for an excellent review on the cardioreal syndrome there are a lot of questions that have come as far as the mid-range ejection fraction is concerned i think we would we'll be prescribing army in those patients provided there is no renal problems because there is no obvious data as to why it should not be used so basically i think all of us would agree that we'd be using army in these patients with mid-range ejection fraction that's my viewpoint yeah second thing is the second question was uh about sdlt2 and i think it's again debatable especially if the renal function is so bad probably the hdl2 inhibitors might not be useful in such a situation this is my take on that what would be i mean we are going lower and lower uh doctor venue i mean we thought 60 would be the cutoff line then came 45 then 30 with canada glyphosate and now 25 years time and we will address the issue of 20 ml yeah so i i think as professor said basically we have been keeping it level around 30 as the cutoff point for our practical use especially in the general population physicians so regardless it's good for us good drug for treatment of heart failure because i haven't i have been once scolded by a nephrologist himself that you should not use it in when the gfr is less than 30. so this is the point actually that's exactly what why i wanted that question um uh doctor to address because this is the calmness question we as nephrologists are asked and i'm glad dr clarified that i think if you if you know that you'll be able to monitor your patient well then i don't think you have any reason to deprive him of her of of the benefits of a potentially very useful class of faith be it rna or as young people dr christian your question is fraction our national heart failure registry of 10 000 patients also showed that middle injection production patients benefit almost the same like reduced injection fraction patients in indian situation also so that holds uh in fact even if you look at the heart failure pressure rejection fraction group people who you had a better outcome as those with a lesser rejection fraction in the hpf ef group yeah i i would like to i would like to to stress the importance of the uh control of volume in in these patients and uh i think that this should be a very multi-disciplinary approach and combining the uh let's say patient counseling and patient treatment and so on furthermore i think there is an area that we should consider that has not been well studied in the past and it is the use of ultrafilter extractor ultrafiltration not for rescue therapy not in conditions of uh let's say untractable uh fluid overload and pulmonary edema but in condition of elective therapy from time to time in order to establish a very nice fluid and electrolyte equilibrium and i can tell you that we are developing a system which we will call artificial diaries that is so easy to use so simple to apply even as a self-administered therapy for the patient that probably we can have a very important result and new horizons in the field and if you like in the future when we have the system uh completely developed i will be delighted to have a study conducted in india because i have seen a very nice collaboration between nephrologists and cardiologists like no other place actually so i hope that you can really uh be on on on my side in this concept approach for optimizing fluid management in cardioinopations i'm glad professor ronko that you brought it up and i i think that's the single most important determinant of patient uh doing well of cardiorenal syndrome so i think i will i will take it further and and need your strategies how to a certain and most appropriate drive it in your patient which all tools the the easy ones the subjective objective and finally the more sophisticated tools and i would also like to draw your comments on the role of bio impedance i mean something which we do very routinely nowadays for our patients on dialysis uh or even transplant patients to a certain they dry weight and obviously we all know in the in the setting of cardiorenal syndrome you can't afford to please hard at the expense of kidney or vice versa so your take on the best methods of asserting private well you know the the the truth is that we have to teach our students and young doctors about the message that guyton gave us many many many many years ago and it is heart circulation and kidney physiology i think that if they know well the cardioreal interactions and the importance of volume expansion i think that they will immediately understand that there are determinants that may play an important role in worsening or improving function of each organ as you can say you cannot improve one organ at the expense of the other so i think that the the window the therapeutic window for fluid balance is very very strict very narrow in this patient sometimes three four hundred cc more brings the patient into pulmonary edema three four under less brings the patient in tractable hypotension so this is extremely important i think that we should develop a better knowledge of by impedance because this is an instrument that is simple and it can be measured and repeated the measurement several hundred times like we can do for an online akg or other things the other thing is all instruments to remove fluid in the patient should be used with competence and very very much attention uh most of the studies done on extracorporeal ultrafiltration in cardiac patients were done with people that knew very little about the concept of blood volume relative blood volume changes uh intravascular feeling during extracorporeal therapies i think that this study should be done by people that know exactly how to do and once we have the results which apparently are good in terms of people that know how to do it we need to teach people on how to do it the same is very true for diuretics if you give diuretics in a very let's say uncontrolled way you may have detrimental effects and rising serum creatinine is typical in the second or third day of an admission of the patient for our failure so diuretics are important uh drugs but they should be used with attention as should be for extra corporate therapists yeah one question to process so when will you consider uh not treating the patient with angiotensin receptor blockers or acinibiters or army and when will you consider starting them on hydrolysis nitrate combination any any recommended well again again it's it's a kind of uh evaluation you do it you know my suggestion is and and i think we were successful in this go at the bedside together the cardiologists and the nephrologist and discuss case by case the advantages and the disadvantages of course as a nephrologist you can somehow um make uh uh save the use of arts uh and honest in patients uh in which initially it seems that side effects may uh advised not to to go for it or at the same time if these side effects continue you may actually say this is the case to discontinue and go for different solutions the same is true for diuretics i think that diuretics are important depending also on the target you want to achieve because if the target is acute decongestion and improvement in symptoms this is one thing but if you want to have long-term reduced rate of re-hospitalization you need to achieve a much better and stable control rather than doing an acute uh dehydration of the patient so i think that every patient should be discussed at the bedside i mean i try to teach my fellows look less at the computer and go more at the bad side of the patient and go there together maybe i'm italian so it's a it's a kind of a different approach but um the de facto of our american friends is that they work with numbers they don't work with patients and i think that you know i've worked in america enough to to say that america is great but the the young american fellows just look at the computer they don't look at the patient dr you have any uh comments or questions for uh listening so before i hand it over back to dr vino kopal they've been um a few other questions probably a little unrelated but i think we will take advantage of this opportunity to ask you is it important to treat as dr bhattachara wants to know to treat asymptomatic hyperuricemia in chronic kidney disease i think so i think so because uric acid is a dangerous molecule it increases inflammatory response it has a direct damage into the cells and somehow it is a reflection of the hyper catabolic state so in my opinion it deserves to be treated even if i've been permanent so i thank you so much professor ronko i think this discussion can go on and on and i i think we are really uh very fortunate to have you over here today and and uh for the time constraints i'll hand it back uh to dr vino for the further proceedings thank you once again professor i will send you by email the titles of the books and uh suggest to your young fellows sure great that'll be great thank you so much thank you thank you so much thank you so much dr ronko for an excellent presentation and we enjoyed all the whole time all your wisdom the years of wisdom that you have with you now i think we'll go back to the next part of the program that is a case president this is a cardiologist's perspective on cardiovascular roman there'll be two case presentations first case will be present by dr jc mohan and then the second case from uh by dr bk shastri may now call upon dr casey jc mohan to present this case then we have the discussions we'll take one case and then the discussions and then we go to the next case dr mohan thank you at the outset i express my gratitude to heart failure association of india for having invited me to present this case in an important webinar where professor claudio rankov was the speaker i am going to present you our viewpoint on cardiorenal syndrome or you know cardiac syndrome by way of presenting a 66 year female patient with worsening heart failure and renal insufficiency dr ronko mentioned that there is a long-term bidirectional relationship between heart and kidneys and that is because they both have common risk factors and common shared pathophysiology and he also mentioned that at the moment there is endemic of heart failure and kidney disease currently anything between 20 to 65 of all patients with heart failure have significant ckd that is stage 3 or more and we also have learned over a period of time by studies legally in hypertension that kidney is the epicenter of synthetic overactivity and angiotensin too in heart failure with that preamble let me take you the case this is a 66 year female with diabetes hypertension she had rolled anterior marker infarction bypass surge in 2009 and she now in heart failure with ejection fraction of 28 some mitral registration scarred led territory and she has crossed three symptoms of heart failure and she is hemodynamically stable our therapy includes carbohydrates 6.25 milligram once a day sorry the i mean twice a day three point one two five milligram you are bred in digoxin uh furosemide cytoglyptin methamine glycolyzoid and rosuvastatin that is as it was on june 3 2018 our investigation really revealed him that the diabetes was not controlled hba1c was 8.4 serum creator 1.6 raised blood urea 54 electrolytes all right somewhat raised uric acid which we just discussed and of course the lipid profile which showed which was typical of uh ethrogenic diabetic dyslipidemia and some anemia with hemoglobin or 10.7 and one plus urinary protein she improved with increasing carbonyl all to finally 25 milligram uh a day which means 2.12.5 milligram twice a day addition of five milligram remember and 25 milligrams paranormal electron this is triple guideline directed medical therapy so right things have been done however despite the guideline directed medical therapy she was re-admitted three months back uh three months later on with the worsening heart failure and her creatine rose slightly her blood urea went up a little bit sodium and went down a little indicating some dilutional hyponatremia and of course at this time examination was exactly similar to what she was having earlier when she had ambulatory heart failure but patient did have evidence of old antioxidant function and mild right side plural fusion and a bnp of 685 kilogram per ml so these are the investigations which show actually old antiviral micro information sinus rhythm and the qrs duration is 106 millisecond and it is necessary for us cardiologists to mention that and of course cardiomegaly with permanent venous congestion echo showed of course an ejection fraction close to 30 percent while most abnormality in the in the territory of led and large left atrium and of course uh the doppler study did show a dilated inferior vena cava evidence of pulmonary artery hypertension and restrictive transmitter flow current pattern indicating significantly elevated left hand feeling pressures so she was treated with the intravenous torsimide tissue decongested one gram of ferric carboxylation was given because the iron levels were low and the ferritin level was low she was vaccinated for flu and pneumonia at the time of discharge and guideline directed medical therapy which was being given was continued so but she continues to need some iv furosemide once um once in a while and she visits the emergency department or or at home she needs furiously mild because she gets out of breath and she has restricted activity we know that people with worsening heart failure as the travendram heart failure register also showed have mortality which is nearly three times more than people who are relatively stable and don't have worsening heart failure let us come back to our point that she has an egfr of 39 ml and blood urine nitrogen is 36. now this is this is class 3 b the stage 3 b of c k and some of the data which we published actually last year um showed that stage 3 ckd in patients who have been discharged from the hospital after after adequate decongestion is there in about three or more is present in 29 of these patients so nearly one third of the patient has stage three or more ckd like our our patient however data from the western world shows a a greater prevalence because those patients are older and this is data from swedish heart failure registry showing that stage 3 ckd is present stage 3 or more secret is present nearly 45 of heart failure reduce ejection fraction and more in half f the data from the adhere registry also says that only nine percent of the people have normal egfr so our patient of course we need to classify adopt wrong percent what is it you might say that well it looks like a type 2 cardiorenal syndrome patient has heart failure and has a easier form of 39 you could also say it is a type 5 crs because the common pathogenesis diabetes diabetes there for 14 years so this could be causing both the things and this could be a type 5 cardio renal syndrome in patients with heart failure what causes actually reduced renal function reduce cardiac output reduce inner blood flow and of course reduce blood pressure the consequent of that is that there is an increased total blood body water total body sodium and of course increased extracellular volume and plasma volume renal dysfunction in heart failure even if there was no diabetes usually because of hypoperfusion venous congestion inflammation and oxidative stress and dr ronko went into great details in discussing the venous congestion finally that results in renal interstitial hypertension reduce renal salt and water excretion reduce inner blood flow increasing reduce egfr and of course over activation synthetic nervous system and raw system and he did mention that the hemodynamics whether it is because of diabetics or hyperperfusion because of the worsening heart failure leads to worsening renal function which feeds the heart failure by running and rendering activation and as well as of course the synthetic nervous system activity our patient is an easier for a 39 we have data actually that in diabetics chances of hospitalized or heart failure are high in those people who are easier for a lower egfr actually compared to more than 60 the patient our patient has a four times high chance of developing hospitalization for heart failure and of course this thing has been already discussed by dr ronko i wouldn't go in detail but what is important actually in our particular patient is uh the the and the hazard actually of mortality and how our heart failure keeps increasing as they have as the easier for keeps going down and with our patient having having actually a 39 egfr it is marginally increased compared to a person who is nearly normal so problem oriented medical record of this patient is preparation has we need to we need to actually aim at prevention or recurrence of heart failure management of ambulatory heart failure management type to diabetes management or ckd management anemia for which we already gave fairy carboxymaltese and what additional measure we can take for coronary artery disease and diet and dyslipidemia for the moment we will not be discussing coronary artery disease and this is lipidemia principles are optimizing care and heart failure this patient of course you achieve the target dose we are on 25 milligram carbohydrate law we can increase that look for iron deficiency we have done that optimize guideline directed medical therapy where comes the role of course rna modulate heart failure and of course we did discuss isd and hydrolyze in combination but we can shift to rna this patient is on ramipril and that's a reasonably good approach in a patient who is not so well controlled on ac inhibitors of course the the the we need to manage the comorbidities including sacred better so i was able to take our regular dose to 50 milligram twice daily actually that's a pretty stiff dose and final heart rate was 66 meters per minute that some help was also taken with the help of yoga braiding in this case the issue of beta blockers are actually much more useful in patients who have ckd than those people who in fact don't have ckd or have mild ckd data from the marital trial shows that number needed to treat with beta block and preventing mortality just four in case the egf are less than 45 so the most important thing in this particular patient with an egfr 39 is beta blockers and that is exactly what we have done what about mra we have continued spironolactone and the issue is the easier for 39 you are worried about hyperkalemia and we are also so you have you need uh close monitoring as dr ronko said but people with low ecfr or aj for about 60 draw similar kind of benefit from mra like spironolactone as shown in this trial although the chances of developing hyperkalemia are twice more and the reticence of not using spironolactone stems from miss fear of hyperkalemia at least 75 percent of patients are not going to develop hyperkalemia and 90 percent time you can continue spironolactone in such type of egfr without stopping the drug so the patient is on triple therapy still symptomatic hba1c is eight percent and of course hemodynamics are stable so let us try to fill the therapeutic hole in this heart failure with dkd i replace ramipril with army as i said after 36 hours gap 100 milligram twice a day and the guidelines also recommend the same that you should shift to rna in symptomatic patients with fref and of course the rna has big advantage because it is a dual modulator we wouldn't go in detail but the great advantage in patient egfr is when you compare actually the paradigm match of data and there is analogy compared to rna reduction in egfr annual reduction egfr actually is much more slowed in case you use rna compared to another print same kind of data actually is available uh in paramount study which essentially is a study of half path which shows that army compared to well saturn slows the reduction in egfr much more significantly this is nearly three times greater benefit with regard to slowing the kidney disease with arne compared to well saturn so this the same thing is true for paragon also in paragon natural study also whether you were using mra or without mra there was actually a similar kind of uh benefit so the predictors of successful initiation of sacral iron in this patient are already there the blood pressure above 120 there is a prior hypertension and there is no atrial fibrillation so out of six three in the things suggest that the patient would tolerate sacral and if possible take you to 200 milligram twice a day the next issue of course is that the hba1 is still eight percent so i decided to use the glyphosate because and that was started a year after actually somewhere in september 2019 when we had data coming from the departure study because the data strongly suggests that the drug reduces hospitalized for heart failure and of course cardiovascular mortality regardless of the egfr people with easier for less than 60 or more than 60 had equal kind of benefit and over a period of time starting beyond 12 months the decline in kidney dysfunction is slowed by dipole fluid is not an immediate effect in fact immediately there can be worsening and of course these patients require close monitoring because the substrate of vulnerable patient army and their reflection may develop acute kidney injury so drug regimen in this complicated patient was i stopped this oxygen because i once the the safety therapeutic range was narrow looked for iron deficiency corrected it kept the heart rate below 70 shifted to army did not worry much about dyslipidemia because i thought that that is not and i have to prevent progression of ckd i did not use uric acid lowering drugs or phosphate lowering drugs or vitamin d3 and i disagree with dr claudio that there is any big data to suggest that uric acid reduction really helps in these people i used hypoglyclusine for better control of diabetes and heart failure patient was vaccinated for flu and pneumonia and didn't look for reversible ischemia i thought that wasn't a a great thing there are of course unresolved issue in this patient you might think phosphate reduction might work uric acid reduction may work i'm not too sure the oxygen used which way whether i can use it as i said i am little reticent about using digoxin epo i think the red hs driver are negative i don't use epo despite a hemoglobin being low finranon may have a great role to play especially if the patient developed hyperkalemia and now with fidelio dkd study things look very positive role of icd can still be there but the data also suggests that people who actually have egfr which is less than 60 draw much less benefit from icd and this is really patient level largest meta-analysis available till date which says probably people with egfr which is low do not benefit from icd so i did not consider i said in this patient last seen december last month patient is class two hbmc now 7.3 heart rate is 64. serum creating 1.2 easier for 46. somewhat better echo is performed and now of course there is a reduction from hybrid pulmonary pressure and now it is actually more uh more delayed relaxation of grade one diastole dysfunction so ladies and gentlemen to summarize uh i presented to you a case of worsening heart failure with ckd stage 3b and i told you my approach and my i would like to say that not or i would rather you like say beginning 2021 whenever you see a patient with f ref and ckd ask yourself a question why is this patient not on rna and sdl to inhibitors i'm not sure about lowering uric acid giving soda bicarb phosphate reduction and acetylcysteine i don't think these work at least i don't have data and i would probably try to stay away from that thank you very much thank you dr mohan for an excellent case i think there is nothing more to add to the management yeah in an extremely very clear way of managing this patient order on the guidelines say whatever we know about heart failure management except for the icd and the rest of it you have brought in everything in clear perspective are you any comments no only thing is that uh a point which i uh to consider whether the reverse revascularization in this patient then that to look for ischemia that was only point of difference from dr mohan otherwise everything he has suggested so always ischemia should be a point of whether we can have some improvement unless the echo whether he has in data to show that the echo uh why is the uh my accounting is called and there is nothing to improve i thought the echo is more of unfair of a scar in the led territory yeah so so thank you uh very much jc moon and as always it's always a treat to listen to him and i think such a user presentation every time and you you tend to learn so uh dr knight would totally agree with the way you manage your patient and and basically this is in response to your last queries in relation to uric acid and bicarbonate well of course uric acid is debatable and there was a time about about five to ten years ago we were all very much optimistic about treating even asymptomatic hyperuricemia in chronic kidney disease because there were some initial data which subsequently as you rightly pointed out could not be substantiated so we're not very sure about managing uric acid hyperuricemia and especially there was controversy when it came to lowering it with the help of ebook substance and there's there's another controversy with the usage of books but about bicarbonate is the real controversy on one hand we as nephrologists would certainly be wanting to keep our patients bicarbonate value as close to 24 definitely over 22 million equivalents but the real problem is and and there is enough studies which have shown there is a reduction in the rate of deterioration of chronic kidney disease when you are treating them with alkali but the problem here is giving them sodium bicarbonate in a patient who is already volume overloaded on one hand you are wanting to discourage the use of sodium and you're restricting sodium obviously giving them bicarbonate at least when they have a significant cardiorenal element would not be judicious so so maybe once as you have already pointed out in your patient the gfr has improved it's already much better at one point two than it uh of creating than what it was at 1.7 if it improves further and heart failure is settled with the help of rne you have improved the patient's ejection fraction probably subsequently we can think of adding uh a cautious use of sodium bicarbonate but yes and and equally important is is i i think which cannot be over emphasized is to determine and the question which i had asked dr ronko as well you have to determine the right drive weight for your patient otherwise you are going to uh and i think that's the beauty of of of uh um learning with your own experiences it's just not uh the time tested uh looking at the skin interior and and uh getting edema or not i think we have to advance much more than that and with that in mind we are now taking the help of bioimpedance is a small machine it's it's uh handy you get the report within five minutes and of course uh the cardiologists always tell us the importance of the ivc filling i i think we need to have objective ways of of knowing our targets otherwise uh the same thing we will be pleasing the heart at the cost of the kidney and vice versa thank you once again currently we use actually lung ultrasound to monitor bulimia it is extremely cheap very easy to do any machine can do it and you get if you see b lines which are more than one two if they are zero it is absolutely fine but if you want to you are very happy but you will see five six seven lines certainly more needs to be done as far as this correction hyper bulimia is concerned and i strongly are through this platform that people should use lung ultrasound much more it can be used anywhere whether you are in icu you are in ward patients come to opd just just have a quick look it will take probably three four minutes actually like you said bio impedance is a much easier way of sorting out the issue quite cheap and effective and i think it's made is revolutionize the way we manage our dialysis patients because it's all about of taking appropriate care of their fluid management so i i think tools like these cert and you can't blindly follow them of course you ultimately will have to rely on your own clinical judgment but they certainly are good objective tools to help you yeah actually one of my one of the chap who is now actually the chief of medicine and cardiology in morgan university morgantown west virginia university and he was my fellow he just published some work showing that the the b lines actually are a much better way of following and prognosticating this individual heart failure not only these correlate with the feeling pressure the total body volume but they also correlate with prognosis quite totally uh can we go to the next case yes the time is [Music] three [Music] hey greetings everyone i thank uh heart failure session of india for giving me this opportunity unlike the previous case and unlike the previous speakers my presentation is going to be a little different i am basically presenting a case just like a third year resident and i want the opinion from the experts however it is to be managed what mistakes i get now this is going to be essentially a case presentation and very little theoretical discussion this is going to be a lengthy complicated case likely to be controversial please bear with it my patient is a 56 year old male patient he presented to us on 22nd march 2016. he has a known hypertension on while saturn he is a family history of coronary disease but no diabetes non smoke but no habits and he presented to us with class to disney abdominal discomfort and edema feet he had elevated jugular venous pressure pulse rate was uh 140 over 80 and he has fan systolic memory suggestion of trigonosphere regurgitation his ecg showed biatrial enlargement and left ventricular hypertrophy chest x-ray showed cardiac enlargement right enlargement svc was dilated pulmonary venous hypertension echocardiogram enlargement moderate mr severe pr good lb ru function for one tough time i am not showing i request you to take it at the face value these findings are real his routine labs are normal except for a diagnosis of hypothyroidism his new nuances newly detected hypothyroidism his ultrasound abdomen showed mild heptus minimally ascites and bilateral periodic fusion all suggesting to congestion heart failure he has specialty to rule out any inflammatory cardiomyopathy which was ruled out sarcados was not there or any inflammatory pathology was not there his cardiac mri was done which is suggestive of stick to cardiomyopathy but there is nothing like amyloidosis or other infiltrate or storage disorders he had hypertrophied intraventricular septum biatril dilatation patchy left frontal right atrial left title free wall and is carrying severe metal regurgitation moderate trichosphere regurgitation normal sized left frontal and right ventricle with good function so a diagnosis of idiopathic restrictive cardiovariety was made he is treated with diuretics lysix 40 mg well saturn and metabolism he was relatively stable for nearly two and a half years or from 300 years rather from march 2016 to october 2019 he was in function class 2 at the end towards the end of that his time period is slowly increasing breathlessness echocardiograms done or a period showed dragging increase in leptin directed to cells which i'll show you a table while lv size and function remain normal at the end of the period by october his rv was started dilating and there is mild rv dysfunction up there his biochemical parameters throughout the period were stable except blood area and serum creatine started increasing by occupants of the nitrogen so this is the chart you can see the urea creatinine but more or less okay by 16th october 2019 his uric reaction started increasing his bilirubin and sodium potassium immunoglobulin were failed so first time he admitted in 16th october 2019 with increasing shortness of breath orthopedic and abdominal fullness as i mentioned yuri okay elevated patient we thought we'll do a right hand catheterization in angiogram and see if anything more information we can get when we did right-hand calculations pulmonary hypertension and um showed non non-obstructive coronary disease heart transplant was considered inappropriate i'll show you the data so we just increase the dose of diuretics and continued certain so this is the first cardiac catheterization done on 16th october 2019 is capital vaccination is 29 p.a was severe pah with 53 main right ventricular pressures requests are elevated please note the cardiac output is quite low 1.7 liter example it has cardiac index was 0.92 his transformatory gradient was 24 pvr is 13.7 so this data is quite in a inappropriate currently for us to submit him for the such transplant surgery so he continued to be symptomatic and we discussed with transformed surgeons and of the endless legends in the country the family was not very clean but borderline they are willing to go if it is required so the cardiac surgeon the experienced surgeon suggested to look at hemodynamics and melanoma inclusion and at the first sight it looked very hard for me because his relu function was good is not bad looking back it is probably mind rv dysfunction so anyhow because of his wisdom we thought we'll try so he was admitted on 8th january 2020 he received builder on inclusion from 8th january to 13th january and we did a repeat right-hand characterization even then the right-hand pressures are pretty high so he was contradicted for orthotropic or transplantation and because of restrictive automobility could only function neither a candidate for health options are heartland transplantation or heterotopic heart transplantation for either of us the patient decreased the question is how can we reduce the pulmonary emotion and medication can we ever make him a candidate for our transaction now these are the parameters before the melanoma inclusion i want you to pay attention uh this is the basically we are discussing about cardiod cardiovascular if you look at it on 7th january he had 70 urea created two point zero seven some two point four on three and ninth january we started welding on nutrition over six days the union creation have remarkably decreased and our motion became normal please note now second product catheterization showed a still the primary category of depression and righteous main pressures are invaded however there is significant fall with melanoma and lysing situation in the capillary pressure from 29 to 20 rna mean pressure decrease from 30 to 18 chronic output and cardiac index have increased but ultraviolet resistance remained high so there is a fixed component of the pulmonary artery hypertension there is a long-standing distributor guarded with the increased backward pressure remodeling of the pulpit articulatory and fixed content of the permanent habitation obviously with a pvr of 16.8 uh nobody will start waiting for any hard transportation so we we decided to manage and preservatively in the next month he again came with questioning heart failure with class four symptoms and orthopedia his creatine was initially two point one seven again we gave increments metronome and license he became symptomatically better and again i keep talking about this all the time that bring the group to pulmonary evaporation generally we don't give pulmonary vessels we are taking addition to use my friend my standard with these patients now the renal pyramid is on ultra infusion in february you can see on third february united are elevated but as they started building information and one previous returns and last six efficient the union creation gradually increased by 10th but when we stopped it for a period of time again gradually started increasing so anyhow we can't continuously be giving background inclusion we sent him home on increased laws of priorities after observing for two days in the hospital [Music] then from march to he was seeking television consultations and gradually though he said he was all right probably is not accepting much his creatine and urea which he got from the local labs started gradually increasing because of the increasing edema and breathlessness we started metal down also increased diuretics so and again we prayed with it to increase and decrease like that however by 8th december he came with significant worsening of symptoms he had alluded for worsening heart failure increasing visneya and morphine abdominal fullness his activities of the daily living were impaired his clarity at the time was 2.5 milligrams uh because of this grossly fluid outward condition i sent him to a nephrologist for regular dialysis or ultra preparation patient refused and wanted to try built on inflation once again as he felt better earlier on two occasions so we thought okay we'll try the same unfortunately nitrogenic he'd had a primary bloodstream infection with gravity bacteria in the hospital for thought were dropped and cleared and increased for a couple of days however if sepsis respond to iv antibiotics she became more referral and you know improved so on 10th 11th or 12th got him admitted after admission you know i told you because of the criminal reception documented it is clearly not good route but once with antibiotics with containing welding on inclusion and nastics nutrition his creation improved and the union sorry he further lost weight he complained of weakness historic preparation was 90. the however high diuretics were normal to not urea increased to 149 from 92 and created also increased so both cardiac output and this is highlights the importance of the forward trigger as well as backward failure body output should be optimal and condition should be minimum so in this in if you don't treat them properly we don't create and keep increasing so he continued on the diuretics we didn't continue building up as i mentioned forever they initially gave her four days again during milner inclusion creatine drop once we stop it which is increasing so as on today his systolic blood pressure is hundred milligram millimeters urea was 114 and created 1.9 milligrams so these are the serial echocardiographic findings i'm sorry i'm not showing the pictures because of the amount of time as you see the right hand side gradually increased our period of three enough yields and reflection size also gradually increased showing the progressive nature of the restricted cardiovascular health function remained the same ejection fraction was good all through right to the shortest person this indicates the fixed increase in the public hybridization fixed component and as an early dysfunction person symptoms were said and his pressure was always high he always had severe mitral and triggers so points for discussion are this case typically illustrates changing linear function with methanol infusion diuretics as a function of changes in the cardiac output and filling pressures whenever the particle output increased with milder on the urea creating decreased along with dietetics and are giving the decrease in the filling pressures and decreased so what is the ideology of this heart failure is always a restrictive body memory most likely neuropathy this patient has to start with some concentric hypertrophy there is a genetic genetic variant of bipolar cardiomyopathy progressing to restrictive cardiomyopathy there is no way of knowing it i am not sure for all practical purposes without any specific treatment now program this case we will discuss further i should have considered heart transplant in this patient much earlier this is one of the western sidelines in this patient and this patient belongs to type 2 cardiac syndrome there is and you know all these factors this has been uh emphasized low cardiac output all these things are chronic hyperbolic increased venous pressure increased venous resistance genetically researched anemia all these things contributed in chronic heart failure to initiation of the kidney damage and professionals [Music] now traditional medication in this patient when we are giving the high diuretics because they decrease the central venous pressure and clean up the adrenal venous pressure is decreased this patient felt better why not ultra filtration we will discuss this in the next slide patient got midnight and he felt better it's individual that in the presence of good rba function vietnam should not be helpful but as i mentioned his first thing started when the army started dilating and dysfunction arbitration is generally a sign of failure in the brains of pressure and volume or load and this patient has both pressure overload with a high pvr as well as the secret drivers regurgitation and there is likely to be rv output mismatch sometimes with the boundary hypertension in the presence of severe country venous hypertension can go through three phases where passive backward transmission passive constriction architecture changes probably because of the long standing super country venous hypertension this patient has severe remodeling and physical fixed pulmonary habitation which may not regress with pulmonary vasodilators but there are some case reports i will show you the coming to the ultra filtration why this patient was not a candidate for atrocities this is a controversial area even 2017 acchd guidelines recommend ultra filtration in some patients occasional patient may really get benefit but four clinical trials which of course involved mostly the particular type one they did not show much benefit there is increase in plasma and activity with interpretation and stepwise pharmacological care you know increased price or inactivity is not good there is larger rate of fluid loss but no change in the serum i showed in the unknown and rapid heart failure trials there is no significant difference in weight loss at the end of the study in all the studies there is increased serum to add now 0.23 milligrams was a decrease of 0.04 with diuretics in the carriage heart failure trial higher rate of adverse events with ultra filters in both calories heart failure and avoid heart failure trials and there is no significant correlation but increase heart failure infection at 90 days in avoid heartburn so taken everything together ultra ultra filtration is not particularly beneficial or the gradual incremental discrete use of the dietics uh however the occasional patient may basically benefit now coming [Laughter] became a transplant candidate similarly similar reports are reported case studies are reported from other authors with this i close my session thank you very much thank you dr shastri for that excellent case presentation i have one question to ask you see all throughout the mro cvr do you think that tackling the mr in any way would have changed anything in this patient because although the mrs severe so so is there any looking at that is there anything yeah or something or something yeah that is mine see every time with this severe mark so doing something like a mitral clip would it have made any difference i am not sure if you have got a very good energy starting function and even perpendicular hypotension long-standing [Laughter] [Laughter] so that has probably tilted the balance of this patient going to army dysfunction and renal failure probably that was the point of discussion whether they are tackling non non uh surgically whether that there is an option in the presence of regulation without a dilated left ventricle without being acute lvdp 30 means intrinsic myocardial disease of the electrode in such situations if you tackle the mr also they will continue of course mr would have added to the uh when we were special but the lvdp itself is like a high level if there is severe mr lv has to dilate there is no way lv would not dilate and that is why the echo data which you are shown the lv is dilated all throughout even 55 millimeter is dilated lv in this country where average actually the lv size about 47 millimeter and either the silver mr has to be wrong or the lu dimensions have to be wrong in case lu is not dilated but your point that whether mitra clip will help these people or not we have no idea certainly nobody has used this stuff in restricted cardiomyopathy with severe mbr that is true but your use of pulmonary vasodilators is interesting and now that i recall we have used as a desperate measure in some patients with reasonable results never had the courage to show these cases to anybody why your case at least we are now feeling that some in some patients as a desperate measure endothelial endothelin receptor antagonist probably could be a choice of treatment we have the your point is not like a common card in rheumatic miter regurgitation or mvp of mass there is obviously some prediction of the electron but not the usual common uh metal resistance you know earlier we used to think of left ventricular endomycol fibrous not a dilated lv then you have severe mr and severe pulmonary hypertension in fact we even used to diagnose pre-capillary pulmonary average patients with lvmf now we are not seeing those cases at present but when you suspected a restrictive cardiomyopathy this is one of the thoughts that went through my mind especially because of very severe pulmonary hypertension but your mr cardiogama did not show any evidence of emf yeah there is definitely data in heart failure rejection fraction you have two types of patients where people have severely elevated pulmonary hypertension documented as a result of both pre-capillary as well as post-capillary hypertension and those with the pre-capillary tends to do very badly when compared to those with only mildly elevated post-capillary parliament ribbon the exact etiology why they're going for a primary vascular disease pulmonary vascular disease is not clear but then that that is probably what prompted you to use the pulmonary vasodilators uh regarding the use of pulmonary vasodilators the kerala prokaryotic history of 2000 patients of permanent hypertension 60 of the patients were having a type 2 class 2 that is left heart disease 5 of the patients were prescribed pulmonary vasodilators because people consider that there is no other option like dr j simon has said so people are uh prescribing as a last resort uh in such patients when there is no other option we can use but you should know that uh so without giving adequate diuretics eq only one divisor there can be a problem you have to give very high dose of uh diuretics and make sure that uh positive when operate is maintained with good iron is there any chance of an autoimmune disease in this patient because four years we have seen and there is no other constitutional symptoms what about any genetic genomic study and any done i because we have families of idiopathic restricted cardiomyopathy even now on follow-up where the grandmother had mother had and the daughter has and and and and so is interesting and some of these people have mild light left ventricle hypertrophy i am sure that there must be some you know genetic mutation which can explain this thing and we need to look at this familial or maybe genetic restricted cardiomyopathy little more carefully i i'm not too sure in this particular patient whether any kind of uh strain imaging would have helped us this or that way but um you do have mr mri which shows lg positivity in lv ra and la which actually tells us that this and that is patchy so this tells us that we are really dealing with the case of uh idiopathic restricted cardiomyopathy there could be a genetic origin so initially strained and imagined about minus -19 sir then later on towards the end last month it is about minus 17 so there is something the last actually heart failure association of india meeting our group actually had presented a series of patients who presented with restricted cardiomyopathy but had only involvement of the left atrium the left ventricle had normal left ventricle size or normal the e to e prime was now e prime was normal and luv strain was normal only l strain was markedly reduced we strongly believe that one of the subtypes of restricted cardiomyopathy is a disease predominantly confined to left atrium any comments oh i i think the nephrologists approach has already been highlighted and i i think we often have to resort to uh extra corporeal therapies so so the the data suggests that yes they may not be making a huge difference mortality wise but as a short-term measure to relieve the patience of their symptoms so many times if the diuretics fail we are in a fix i mean what more can we offer these patients and i think at times like this probably i personally believe that we have not really explored the the potential role which peritoneal dialysis can play in these roles the gentler form of um i would say methodology to take care of the ultra of the fluid overload and and without um causing too much of pressure either on the heart and and being rather gentle onto the kidneys as well so it's unfortunate that even though we realize the importance of peritoneal dialysis in such a scenario we have not been uh energetic enough to really capitalize on this so so but having having said that i would certainly want to learn from my cardiology colleagues today that if you look back and and reflect on the improved scenario as far as the heart failure prognosis is concerned uh what would be your take on because you see we all these years been in uh uh using all the other drugs the only new weapons in our armamentarian have been either either rna or sdlt2 inhibitors i mean that's short of the devices that you use so so can i ask this is an open question to anyone what is the single most uh thing which you believe is has revolutionized the management of heart failure with or without kidney disease yes um your point about patient is well taken actually in fact we had someone else enthusiastic and we had quite a few patients who we managed on cpd ultra filtration basically uh but the the outcomes are not greatly satisfactory there is some quality of life improvement definitely but for a period of time and for many people it's a new sense to maintain the predominantly the moment you say dance is patient but of course there are patients and if there is a therapeutic failure you have to use it personally i think the dramatic results are same with army hdlp to inhibitors still we have to have time and say and if you see this like dr jc mohan and i can say that over a period of time right from consensus style ac inhibitors then we develop escape at every step we were thinking that we are far ahead so latest after paradigm study and uh rna apparently there's many patients who we can manage better and probably hdlt to inhibitors even i was only wanting to relieve the patient of the symptoms whatever leaves of life they get is probably a much much better quality of life for those six months one year maximum two years uh i mean we've had some some rewarding results i'm not saying that we could prolong their lives whatever lease of life they had it was it was reasonably comfortable you know i i was trying to answer you the first part what is the single most important thing which has happened in the field of frap beta blockers yes they cut down mortality as much as 43 if you put all randomized control trials together that is the single most important thing when we keep adding everything to that actually you do get in real in in relative terms greater benefit but in absolute terms what beta blockers do are phenomenal and that is why the most guidelines say that make sure that you are for heart failure reduce ejection fraction my own feeling is that certain subcategories like we talked about ckd patient they draw far more benefit from beta blockers but they are grossly underused quite true sir and i'm glad you you brought it up because and and you see interestingly most of the data as far as the ckd patients are concerned relates to athenalog so even though we may be criticizing the the molecule on other forums but i think the majority of the data in ckd has has been related to adrenology even then it's been found to be quite useful because we all know there is a lot of sympathetic over activity in our patients of uh ckd so so certainly beta blockers uh would be our choice and and as dr ronko had shown in one of his slides the the even though it's moderate evidence and it's very familiar slide to all of us the evidence is only with beta blockers till the time we have it with the sent to inhibitor there are two questions from the chat box one is how to decide fluid intake for different ejection fractional gfr combination i think it's a question to cardiologists and approaches together i think we are both agreed that the fluid intake has to be restricted whether it is reduced ejection fraction or increased decreased gfr the volume has to be maintained that's the reason why i was wanting to ask that question uh to everyone including dr ronko because you see ultimately we know we have the weapons in on our side but how to best use them ultimately we have to have a particular value you see your patient is going to be discharged you have to give him a particular value of the weight that okay you are going back at the weight of 65 i want you to be uh approaching 63 but not any lesser than 63 at the same time don't cross 66. so i think ultimately uh to ascertain that weight and that's the point i'm repeatedly wanting to make today and i think is very relevant in today's discussion that ultimately boils down to give that particular value of the weight to your patient who is not a doctor and until the time he or she sees you again maybe after two weeks or one month or whatever they must try to achieve that weight till the time you you decide the the next time that the dry weight has gone up maybe the appetite was better and patient has gained some dry weight and that that you have to revise the way so i think i will probably want to manage uh based on what we have discussed today the clinical judgment as well as the objective tools and and that's how you use your diuretics one point i want to make is that the if you follow up a patient after a week after discharge the outcomes have been found to be much better than reviewing them at a later time yes so always make sure that your patient is reviewed at least within seven days of discharge that makes a lot of difference that improves the mortality so very very important in both the point of view and the cardiology point so doctor is interesting the aha recently actually um i think uh a few months back came out with a with a with a scientific statement saying that the first visit has to be within seven days yes sir very interesting actually this this is actually usually not talked about what they say should be within seven days very very important if the patient cannot come at least ask your nurse to call and find after one week although earlier the western literature said otherwise but i'm glad acc has also agreed to our viewpoint yes that is what is the opinion regarding feasibility of subcutaneous classics in refractory heart failure i have not used anybody has any experience of subcutaneous classics in heart failure may not be a good idea because the absorption may not be good might not be good yeah issue perfusion being bad right now but one of the things i think we need to discuss now that dr kuhler is here and the japanese have been very fond of it i myself have been reviewer to many articles published in european heart journal and japanese circulation journal about use of ester zolamide and use of tulvaptin in refractory heart failure of people with net uretic resistance and i think it is a high time we we have some kind of discussion on that aspect because and people who have written these small studies 140 case 150 cases swear by the fact that that in some patients especially those with hypochloremic situation estrozolamide works very well now dr mohan i agree with you you know i've talked to some of the japanese cardiologists and they are pretty liberal in using toll repton much more than what we people do so i i think you will have to consider that on a case-by-case basis i mean you see if the patient already has a significant cardiorenal syndrome and that's why i wanted dr ranco's opinion as to who do you want to braid because barely saying that's a type 2 cardioreal syndrome may not mean much because you see you classify further how bad is the severity of individual component cardiac as well as renal is important now my my concern with the use of acetazolamide would be in the context of significant chronic kidney disease or renal failure i mean you are going to have a significant acidosis and and that probably will offset the advantages which you which you uh get out of acetone might use is not to be used alone loop directives cause metabolic alkalosis okay and estrogen causes metabolic acidosis so the combination has to be used as a sequential nephron blockade and they will neutralize the the the ph effects of each other so i think this is like uh having the various components of the kidney in front of you when you're prescribing your therapy and you're starting with the citazilla mine you are looking at the loop of henle you are also looking at distal convoluted tubules with the thiazides if they they work do not work like the usual ones then probably metallus own and then finally what dr oprah has said exit point but interesting is to add the role of sj lt2 inhibitors ultimately it's all about sodium so so it's just not of any use if you if you target all others and forget about sodium and i think sdlt inhibitors from that point of view will be a game changer certainly actually i use quite a bit of tall weapon in people who are diuretic resistance people who actually are not responding to diuretics and i get a reasonably good response but this is one area where more work needs to be done so it's basically a combination sorry judicious use because you have at least seven eight different uh molecules to attack at different levels and it's just the right combination and now that we have phenomenon probably that inherent fear of causing hyperkalemia will not be as much as it was earlier so maybe i think the next five or ten years will will be certainly a lot different uh in terms of the management of heart failure than what we were doing all these years i think exactly a lot of them last comments by hari yeah i think it was a very nice session and we had uh 940 people attending uh the session that is a very good attendance i think both nepal crowd and our cardiology crowd were there so it is a nice i think [Music] so that is the thing so thank you everyone thank you dr kular for joining us and we will be collaborating with you and the technology team for further there are many programs which we want to do together because now this is the platform to take it forward thanks so much really honored to uh thank you for your invitation thanks so much thank you all right bye right right so thank you all from here and ending the meeting so there was a time when um i was doing mbbs if you mentioned beta blockers and heart failures you were sure to fail now you're also playing offline you