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In This Week’s Podcast
For the week ending April 14, 2023, John Mandrola, MD, comments on the following news and features stories.
First, some listener feedback. A listener pushed back on my coverage of large language models (LLMs).
“While I agree that LLMs have a lot of potential, please don't hype papers which basically have LLMs regurgitate text which is quite similar to stuff in Internet.
Also please talk about how the references that are provided are often fake and must be verified anyway. We have too many papers written where the references are wrong. And don't say what they claim or worse.
Finally, what happens when the AI scribe misses a point? How should society view this compared to a human scribe error? What are the implications for burnout of having to check for AI errors which may be in some ways more smoothly hidden that human transcription errors?”
I did some more testing this week, and the ChatGPT cranked out completely broken links. What’s weird is that when I pointed this out in a follow-up question, the computer simply said sorry, here are the correct links, and they were the same broken links.
Okay, like I said, this is the first inning of using artificial intelligence (AI). Stay tuned.
LAAC Expert Consensus Statement
The Journal of the Society of Cardiac Angiography and Interventions (SCAI) has published an expert consensus document on left atrial appendage closure (LAAC). SCAI and the Heart Rhythm Society (HRS) commissioned the document. The American College of Cardiology (ACC) and Society of Cardiovascular Computed Tomography have endorsed the document. Professor Jacqueline Saw is first author. SCAI also published an important editorial from two clear thinkers in Cardiology – Faisal Merchant and Mohamad Alkhouli.
First some summary points, then some comments, including a comparison to the European Consensus Document on LAAC published in 2020 with Professor Gliksen as first author. SCAI makes their first and strongest focus on patient selection.
Those with high stroke risk not suited for long-term oral anticoagulants (OAC) and “who have adequate life expectancy (minimum > 1 year) and quality of life to benefit from LAAC.” That is an important phrase, and I will come back to it.
SCAI also makes recommendations regarding experience, but as the editorialists write, these are empiric. Translation – they are guesses about how much experience an operator should have.
SCAI makes general recommendations on imaging but ultimately this will be left to the discretion of the operators.
There are also recommendations on post-procedure imaging at 45 to 90 days after LAAC.
Finally, they recommend against combination procedures wherein LAAC is done with pulmonary vein isolation (PVI) or other structural procedures, because of the lack of data.
Comments. I laud the emphasis on patient selection. As many of you know, my review of the seminal trials of this procedure lead me to believe that having a device is clearly worse than taking warfarin, unlikely to be better than direct OACs, and perhaps worse than no treatment in truly OAC ineligible patients.
But I am an outlier, and I accept that. As I have said, I lost the LAAC debate on five continents. For the rest of my comments, I will pretend the seminal trial data don’t exist.
The authors are right to focus on patient selection because what I have seen in the literature and witnessed in our neighboring hospitals leads me to believe we are choosing patients least likely to benefit.
In my very first debate, a crushing loss to Professor Horst Sievert in front of a huge crowd at the European Society of Cardiology (ESC) meeting, even he, one of the world’s most vocal and eminent proponents of percutaneous closure, said in the Q&A that older patients with multimorbidity are the least likely to benefit.
Why? Because of Andrew Foy’s four domains of treatment effect; that is, the flipside of treatment benefit is treatment harm. Older, frailer patients are at higher risk for procedural harm.
And the flipside of risk of an outcome (stroke or bleeding) is competing causes of bad outcomes. Here, older frailer patients may have higher stroke risk from emboli, but they also have higher risks of stroke from vascular causes. Competing risks is one of the most important concepts when deploying therapy in complex patients; it is one of the CORE problems with treating patients with heart failure with preserved ejection fraction (HFpEF).
Poor patient selection is not my opinion. There are registry papers showing that US implanters are choosing patients with much more co-morbidity than those in the seminal trials. I’ve co-authored one of those papers. Sadly, and I hope it isn’t our susceptibly to marketing, we are choosing to do this preventive procedure in patients least likely to benefit.
Here are the editorialists:
“Atrial fibrillation is increasingly prevalent in the elderly and those with multimorbidity. Many of these patients will reach an age or a level of morbidity or frailty where long-term anticoagulation is no longer a safe option. Should all of these patients undergo LAAC? Certainly not.”
The authors add the statement about expectation of 1-year lifespan, which is better than nothing but, in my opinion, it’s unlikely to improve decision making. I say that because the implantable cardioverter defibrillator (ICD) recommendations include a similar statement, and that did not stop the egregious use of ICDs in frail elderly patients who had no chance of benefiting from a preventive device during the period of irrational exuberance of ICD use.
Another comment on the editorial: Merchant and Alkhouli tell us that there have been more than 100,000 LAAC procedures done at more than 650 implanting sites. Pause there. Stop and think. One of my greatest sources of regret about my field is that if a fraction of these patients were randomized, we would have answers. It’s a darn tragedy. If said trials showed benefit, I’d be a leading implanter and proponent, but if said trials found no benefit or harm, imagine the downsides — 100,000 procedures with no data. Gosh.
On the matter of training and expertise, SCAI is correct to set out some standards, though they should be loose. I have learned that some hospitals in the United States have multiple low-volume implanters. Small hospitals with four or five implanters is exactly not how to do procedures like this.
I have friends from super-high-volume centers who tell me that the learning curve involves hundreds of cases. If we wanted to do this right, it would be like lead extraction: you choose a small number of operators and let them do the bulk of cases.
Another important section is the matter of imaging to improve closure and assess for peri-device leaks. The editorialists rightly worry because the recommendation to do transesophageal echocardiography typically at 45 to 90 days happens at a time when most patients are still on a relatively intense antithrombotic/antiplatelet regimen.
“Thrombus may not form on a device until the regimen is tapered; therefore, the reported incidence of DRT (3%-5%) may be an underestimate....”
Finally, I would like to contrast this document with the ESC consensus document. The SCAI document includes no words on debate surrounding the existing data. SCAI makes the assumption that this procedure works.
ESC, however, asked John Camm and me to detail the controversies surrounding the data. Chapter 6 is titled: “Left atrial appendage occlusion (LAAO) vs oral anticoagulants: Doubts and unresolved issues regarding existing data.”
One of my assigned talks at the Portuguese Cardiac Society Meeting this week is on medical necessity vs therapeutic fashion. Or, what is the reason we voraciously believe every clinical trial?
The transformation of this procedure to an ensconced therapeutic fashion -- and surely it is a therapeutic fashion because there have been 100,000 procedures performed — is a great example of voraciously believing clinical trials.
Do you know how many patients were in PROTECT AF and PREVAIL? About 1100. And Watchman did not meet noninferiority in its first primary efficacy endpoint of stroke, systemic embolism, or cardiovascular (CV) death in PREVAIL. So, based on less than 1000 patients who had this device in trials vs warfarin, US doctors have done over 100,000 procedures. That is daunting.
There are two big trials ongoing of LAAC vs direct OAC in any patient with atrial fibrillation (AF) eligible for anticoagulation: CHAMPION AF and CATALYST. These are expected to be reported in 2027 and 2029. I hope I am alive to see the results. That is, if they aren’t terminated early for futility.
Semaglutide and Tirzepatide Disruption
Three journalists from the Wall Street Journal reported on disruptions in the weight loss market from semaglutide and tirzepatide injections. Since I talk to patients nearly every day about losing weight and since these drugs clearly cause weight loss, I will briefly mention a few more things I learned this week about this topic.
The first thing is that the reporters modified ‘diet industry’ with “76 billion dollars.” I knew it was a lot.
But these drugs are going to seriously disrupt the status quo. And there is tension here, right? On the one hand, obesity is bad, and the drugs work; 10% to 15% of body weight loss will lead to all sorts of better health parameters — lower blood pressure and better glucose control to name just a few. That’s good. No, that is great.
But opposing that benefit is nearly the entire diet industry, which has, essentially, been focused on diets of one sort or another. The question is, what will the diet industry do? Because if it embraces these drugs, there is much less need to sell diet plans, meal plans, exercise programs, etc.
For instance, WeightWatchers (WW) has spent the past 60 years telling members they can lose weight by tracking the food they eat, doing frequent weight checks and making other lifestyle changes.”
But membership to WW is declining. People seemed to be voting with their feet, which I understand because WW is sort of hard. The journalists tell us that WW is buying a telehealth company that connects WW members to doctors who can prescribe semaglutide and tirzepatide.
We are at the beginning of a new chapter, and I don’t know what will happen. One barrier for rapid adoption of these drugs now will be the high costs. So, if effective in the long-term, it will be another therapy that increases disparities in health access, because people with poor or no insurance will not be able to afford these drugs.
Another thing I learned this week – from Twitter — is that tirzepatide increases the rate of alopecia five times over placebo. I could not find it reported in the semaglutide trial. You think that’s nothing? You should think again. I’ve had many a struggle convincing patients who were losing their hair to stay on an effective drug.
I guess you can input this side effect, and it is clearly signal not noise, into the there-is-no-free-lunch when it comes to medications.
NSAIDs and Heart Failure
The authors used a nationwide registry and found:
Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased risk of HF hospitalization (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.27-1.63), most notably in subgroups with age ≥ 80 years (OR: 1.78; 95% CI: 1.39-2.28), or patients with elevated HbA1c levels treated with antidiabetic drugs (OR: 1.68; 95% CI: 1.00-2.88).
This story is sort of an outlier, in that you’ve heard me say how fast medicine can change; how old trials ought to have expiration dates; how three of the procedures I do most often today were not even thought of when I did my electrophysiology fellowship.
Well, not NSAID-association studies. When I trained at Indiana University Medical Center, the chair of medicine was Craig Brater, a pharmacologist. You could barely go a week without hearing how bad NSAIDs were for older patients. How much these drugs increased the risk of HF, kidney failure, and gastrointestinal bleeding.
That was three decades ago. Nothing has changed on this topic in 30 years. Except my point of view. I used to be an anti-NSAID evangelist. No discussion. These were bad drugs. Stop them. Period. Now I think differently.
Association studies will always suffer from selection bias. A doctor had to choose to use an NSAID in an older patient. It’s extremely unlikely that the risk of these drugs is unknown. That means that sicker patients, those with pain and arthritis, get prescribed these drugs.
Of course, the renal effects of NSAIDs surely may cause HF in some patients but also, I am certain, and you should be too, that sicker patients are prescribed these drugs. And even though the Danish authors are smart as heck, no number of statistical adjustments can negate the non-random comparisons.
But there’s a more important reason I’ve dropped my anti-NSAID evangelism.
Patients have to move. Chronic pain stinks. And I know, you’ll say there is physical therapy, and joint replacements, and acetaminophen, etc. And I am not saying these options are useless, but some patients just feel better on a daily NSAID. To me, their choice to take an NSAID is preference-sensitive, and our job is to educate.
Finally, I was one of the dumb doctors who once believed the lie that low dose opioids were safe to use as a chronic pain drug. This might be one of the biggest errors of our generation.
NSAIDs are like coffee and blueberries: we don’t need any more studies showing their hazard. Their hazard is a known tradeoff. Mobility and pain relief is their benefit. Some patients can get those benefits from less hazardous means. Some cannot. For those who cannot, we are left with tradeoffs.
This podcast loves thinking about tradeoffs and counterfactuals.
The American Society of Echocardiography has issued rules and regulations for becoming an interventional echocardiographer. No, wait, I misspoke, they write in their disclaimer that “this report contains recommendations only and should not be used as the sole basis to make medical practice decisions or for disciplinary action against any employee.”
And they go on to write... “The statements and recommendations contained in this report are primarily based on the opinions of experts, rather than on scientifically-verified data.”
I have a number of comments:
We could do with a lot less expert opinion. Here’s the thing that many academic leaders may not realize: Cardiology is being practiced in the private world. If you aim to tell practicing doctors who are life-long learners how many procedures they have to do, how many test questions they have to answer, bring more than expert opinion. Bring empirical data.
As I said, I had to learn AF ablation, conduction system pacing, and cardiac resynchronization therapy on my own. There was no set number of procedures, no experts telling us exactly what to do. Everyone my age went through a similar learning process.
Well, the same is happening in structural heart disease. I don’t think my colleagues need experts in academic center giving guidance on how many procedures or test modules they need to do. There is a thing called judgement. And professionalism.
Another point I noted in the document is that two huge sections involve learning how to be an interventional echocardiographer for tricuspid interventions and percutaneous LAAC.
Imagine spending that much time learning techniques for procedures that have no definitive evidence of benefit. I’ve already spoken about LAAC, but I covered the TRILUMINATE trial in the March 10 episode. The short recap is that TRILUMINATE was positive but only because of quality of life measures, and it was an unblinded trial comparing tricuspid clipping vs medicine.
A friend of mine in academics tells me that cardiology fellows spend oodles of time in the echo lab, learning the ins and outs of measuring the left atrial appendage. This seems crazy to me, because fellowship seems an apt time to learn how to be a doctor, to learn from master clinicians.
What’s more, isn’t it possible that AI will soon be better able to do the robotic task of measuring structures such as the LAA? Note to self: tasks that are repetitive and require little human-to-human interaction will surely be replaced by machines.
Finally, I worry about these kinds of expert statements, because, as much as they say they are not rules, consensus documents become standard of care. So, I close this week by reiterating my call to experts to create fewer expert opinions.
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Cite this: Apr 14, 2023 This Week in Cardiology Podcast - Medscape - Apr 14, 2023.