David Cohen is one of the smartest docs on Twitter. I learned a bunch talking with him.

The procedure called transcatheter aortic valve implantation or TAVR is a damn miracle.

In days of old, a heart surgeon would have to saw open the chest and cut out the heavily calcified immobile aortic valve and sew in a new one. I watched a case as a young doctor and came away shocked that patients survive this surgery.

TAVR is even more stunning. Doctors place a valve up the aorta, across the diseased valve, and then place the new valve into the old valve. The verbs squishing or smooshing come to mind.

The other unbelievable thing about TAVR is that strokes are less common than you’d think. When I first heard about TAVR, I thought: how is it not limited by all that debris going into the brain?

Well, there is less debris than I would have thought. But not zero debris. In fact, there is one device on the market that forms a barrier between the aorta and the brain. We call it an embolic protection device (EPD) or cerebral embolic protection (CEP).

Early studies show that the device catches debris that would have occluded blood vessels in the brain—iow, caused stroke. The pictures almost sell the device—because, obviously, catching debris has to be beneficial.

But. But. There are always ‘but’s’ in Medicine.

The PROTECTED TAVR trial, which compared TAVR with and without an embolic protection device failed to show a statistically significant reduction in stroke. It was a good trial, but it did not close the door for the device. For two reasons: one was that the trial was underpowered. The lower bound of the 95% confidence interval allowed for a 1.7% lower rate of stroke in the treatment arm. Neurologists feel that a 1% risk reduction in stroke is clinically important. The other reason was that a secondary endpoint of “disabling” stroke was 60% lower with the device.

We needed more data. Another trial is not likely going to happen. Trials are expensive and take a long time. This is where Dr Cohen’s group comes in. They performed an observational study looking at more than 400k patients in a TAVR registry. About 13% got the device and 87% did not. This is where Sensible Medicine readers should start feeling a rash.

Why? Because you know how scary it is to try and compare outcomes in two groups of patients who were not randomized.

Cohen, however, tells me about a super-interesting way to approximate randomization in this comparison. It’s called an instrumental variable analysis. He explains this to me in clear terms during our conversation. I love methods so I was enthralled. But that isn’t all. The other thing is that his study, like the PROTECTED TAVR trial, came up with tantalizing close results. We discuss that as well.

I loved our talk. If you like evidence, methods, and great medical stories, I think you will also like this conversation. JMM

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A spirited discussion of craziness in medicine

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MM is 94 years old. Her only active medical issues are hypertension and vitamin D deficiency. She takes only 20 mg of lisinopril and 1000 units of vitamin D3 each day. She has no cognitive decline and gardens every day if the Chicago weather allows. Her Friday afternoon appointment is the doctor’s last of the week.

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I’ve already written a reflection on four things patients have taught me. After MM’s visit, I realized how much more there is to write on the topic. So here is a follow up with the unoriginal claim that the most valuable things I have learned from my patients are not about the practice of medicine. Though not profound, the lessons are universal. The longer I practice, and the older my patients get, the more frequently these truths are spoken.

Aging is Painful

Anybody who gets to middle age knows that things don’t work like they used to. Around my house we say that any day that nothing hurts is remarkable. My patients are full of pithy phrases to make the point that aging is physically difficult.

“Getting old is hard, but it beats the alternative.”

“Aging is not for wimps.”

“Every time I look in the mirror, I ask myself, how the hell did that happen?”

People respond to their progressive disability in all manners. Some fight at every turn. Every visit, irrespective of age, is spent discussing aches, pains, and things that can no longer be accomplished. There are demands for me to make things better. I find it challenging to address the concerns, rather than dismissing them with “it’s just age,” while also letting people know that some suffering is “part of the human condition.”

Other people accept frighteningly steep and acute declines. My challenge at these visits is to balance, “She’s not asking me to address the problem, so who am I to pry” with “This actually seems like something I should explore, even if she is willing to accept it.”

Where there is little diversity is our ability to adjust to disability. I was taught that people rate the quality of life with a disability higher when they are living with it than when they are watching other people live with it. Thirty years of clinical experience has made this real. We should add to the saying, “There but by the grace of God go I” the addendum “but, when I end up there, I’ll be OK.” 

Aging is Sad

When I was an intern, I admitted an elderly woman with pneumonia. Her biggest problem was not the pneumococcus but her depression. Her mood made her miserable and the associated psychomotor retardation was going to make her post-hospital rehabilitation impossible. She was already taking an SSRI and seeing a therapist. I called her primary care doctor, a geriatrician. Like a true intern, I expected he would have an answer to her misery. His response was, “Yup, it is a sad time of life.”

There is a lot to be said for the golden years: retirement, family, friends, greater financial security – but as the years go on, the psychological costs mount. Besides the physical decline, there is the constant loss. I repeatedly hear, “Everyone around me is dying.” Siblings, cousins, friends. It sometimes seems like those who are most connected suffer the most – that big family that has always provided support now provides an unending procession of funerals.

People mourn their losses as well as their own mortality. You cannot ignore what is to come when your peers are dying. Those who deal with this best seem to be the people who can be honest that their grief about the loss of a friend is partly the fear and sadness that they are next.

Loss is Never Easy

I never felt like I had enough time with MM. Not that she needed time for me to attend to her medical problems. She was blessed with enviable genes and an outlook that combined cheer and steel. I just wanted time to hear more about her life and her experiences. I wanted to learn from her.

On one unpressured Friday afternoon we chatted. I did not have another patient to see, another note to write, or another meeting to run to. Her daughter would not pick her up until 6:00 PM. I told her that I still thought about her husband, also a patient of mine, who had died about a decade earlier.

She paused and then remarked. “We lived together in the same old house for more than 60 years. Every time something stops working there, I curse the damn house and I curse Charles for leaving me alone in it. He was always puttering around, fixing things. Then, of course, I think of the wonderful years we had here. I cry because I still miss him, and then I thank the house for reminding me of him.”

I can’t write anything original about loss and grief and mourning. We’ve been writing about it for as long as we’ve had written language. What strikes me, though, watching so many people experiencing loss, is that it is always hard. Losing a loved one is hard. It does not matter if your father is 50 or 90. It does not matter if your mother’s death is sudden or expected. It does not matter if you have come to terms with the complexity of your relationship with your sister or have not.

Our losses become a part of us, they shape us. The tearing, searing grief might last days, or weeks, or months, or years, but it always ends. Nobody, however, ever “recovers.” Nobody “gets over it.” Having known, having loved, and having lost makes us who we are.

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A few short words about our conversation:

Two decades have passed and electrophysiologists have learned little about how to ablate atrial fibrillation. Now, and then, we simply ablate circles around the orifices of the pulmonary veins.

This works reasonably well. But we don’t—exactly—know why it works. For instance, some patients have total elimination of AF, but when they are restudied, they have reconnection of PV activity.

Observations like these suggest there is something else happening with our ablations—beyond building an electric fence around the veins.

One possibility is that we are affecting the neural input to the heart. Structures called ganglionic plexi sit next to the areas we ablate. We often see heart rate increases after AF ablation. Say, from 60 to 80 bpm. That’s because ablation has reduced parasympathetic input to the heart.

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Piotr and his team had to suspend typical AF ablation during the pandemic. Surgeons would not provide backup. This gave them the idea of a simple approach—only in the right atrium, with one catheter, and no anesthesia. It turns out that there is often a ganglionic plexus in the upper right atrium.

They found patients who had a history of vagally-mediated AF. They documented that these patients had high vagal tone. And… in these patients, simple ablation in the RA yielded a signal of benefit, a reduction of AF. Wow.

It’s a small single-center study. It’s just a signal. A first mile of a marathon. But for the curious regarding AF, it is super-interesting.

Many athletes and young people have vagally-mediated AF.

Here is the link to the paper: Cardioneuroablation of Right Anterior Ganglionated Plexus for Treatment of Vagally Mediated Paroxysmal Atrial Fibrillation

Here is Piotr. He works in Rzeszów, Poland. It’s a beautiful city to visit. I once ran a marathon there. JMM

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We discuss the state of medical education, Harvard music video, causal language at JAMA and more

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Gosh was this a great conversation about her recent paper on specification curve analysis of nutritional observational studies.

Here is Dr. Zeraatkar’s bio:

Dena Zeraatkar, PhD is an Assistant Professor in the Departments of Anesthesia and Health Research Methods, Evidence, and Impact (HEI) at McMaster University. She earned her doctoral degree at McMaster University in the Health Research Methodology graduate program. Following her doctoral training, she pursued postdoctoral training at Harvard Medical School, for which she was awarded a Banting scholarship.

Her research centers on evidence synthesis and evaluation—identifying and appraising research to optimally inform healthcare and public health decisions. She often works in areas in which the evidence is complex or conflicting, examples of which include nutrition and COVID-19 therapeutics. For her research, in 2023, she was awarded a Gairdner Early Career Investigator Award.

First, it would help to read my comments yesterday on the paper. Dr. Zeraatkar is well-spoken, clear and she explains a complicated topic in simple terms. Her work is exactly the type we love at Sensible Medicine. Stay for her final comment. It made me so happy.

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The Thomas Sowell quote, “On closer scrutiny, it turns out that many of today's problems are a result of yesterday's solutions” has been ringing in my head a lot lately.

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Gosh was I lucky to speak with Professor Erik Van Zwet from Leiden University in the Netherlands. He is the first author on a recent NEJM Evidence paper looking at more than 23,000 trials in the Cochrane Database. (I linked to an URL that should get by the paywall.)

There are technical aspects of this paper. We hit on some (not a lot) of them. The gist of it though is really important when we look at evidence. Erik did an excellent job of explaining P-values, trial power, and, at the end, we discuss how this work might inform the ability of trials to replicate.

This discussion also pairs well with one I had with computer scientist Ben Recht.

I hope you enjoy the conversation.

Please do consider subscribing or supporting our work as Sensible Medicine remains an ad-free user-supported place to learn about medical evidence. JMM

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Why have I been committed to medical education? Some of the reasons are admirable but not terribly novel. Others are a bit hard to admit, but just as true.

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