Good Questions that I was Asked at the Cardiology Society of Australia and New Zealand Meeting

I’m in Sydney at the CSANZ meeting. Here are questions I was asked yesterday during a session for cardiology fellows:

What has cardiology gotten spectacularly right, and spectacularly wrong, over the past 30 years?

Spectacular: The treatment of acute coronary syndrome and MI. Young clinicians may not be able to remember how MI care was transformed with emergency PCI and stents but it is amazing. People with MIs often leave the hospital the next day with only a band-aid on their wrist. The heart and person saved.

This has led to fewer cases of heart failure and arrhythmia. I live in a city of million people and rarely do primary prevention defibrillators for ischemic-related cardiomyopathy—because of all these fixes.

The corollary to acute care has also been disease-modifying therapy for CAD. When I started my career, an MI was often followed by another and another. Now, with optimal medical therapy, recurrent events are much lower. Patients with MI usually live long enough to die of something else.

Heart failure care has also been transformed with the four classes of HF medicines. What was once a miserable death sentence has been transformed into a livable chronic condition. Of course, the challenge in HF care is using it wisely, because most cases of HF are not in ambulatory males with solid blood pressure, but in older patients with many co-morbidities.

Catheter ablation technology has been a spectacular success for every arrhythmia except AF. Ablation renders patients with arrhythmias from focal areas like surgical patients: cured. We still have a huge knowledge deficit in AF pathophysiology. More on that below.

In structural interventions, TAVI is nothing short of spectacular. We can extend the quality and quantity of life for many older adults who faced certain death from aortic stenosis—without open heart surgery.

What we have been most wrong about:

I am still shocked that percutaneous left atrial appendage closure is so popular. The seminal trials found higher ischemic stroke rates, and no decrease in major bleeding. This is exactly what the most recent CHAMPION AF and CLOSURE AF trials found. Yet 600,000 people have had this device. Our acceptance of this procedure baffles me. And I worry that it has to do with the influence of industry. Patients not able to take oral AC were excluded from the trials, so we are flying blind in these patients.

Other than LAAC, I don’t think we are doing too badly. Out biggest challenge now is not having something to do for a person but whether we should do it. Patients in trials represent best-case scenarios. Most of the patients I see are older and sicker and the question is whether we should intervene at all.

I also worry that the high cost of new interventions create a situation seen in oncology where low value high-cost interventions strain both the patient’s and society’s financial resources. Another challenge of modern cardiology: how to provide the bast care to the greatest number of people.

One area that I am extremely hopeful in is the GLP1a. Given the high prevalence of cardiometabolic disease in Australia and North America, these drugs could be transformative. Everyone talks about the weight loss, and this is remarkable, but I’ve seen middle-aged people completely transform their ASCVD risk. I suspect this class of drug may make statins look weak. But I would not put this in the spectacularly correct category yet, because we need more data.

How do you recognize genuine innovation instead of hype?

This is easy; go look at the KM curves of the old cardiology trials. ACE-I, MRA, and ICD trials show clinically significant and statistically robust signals of mortality benefit. Not benefits in composites of nonfatal outcomes, but mortality.

We haven’t had one of these in a while. But that is ok. Iterative progress in bioengineering has been great. PFA for instance in EP. Valve technology in structural cardiology and GLP1a's in prevention.

As for hype, I would encourage everyone to have their eyes open to papers that distract attention from the primary endpoint. RITA-2 is the classic paper for this. When the primary endpoint of an experiment is null, you need to be careful about saying much about other endpoints. Don’t look for bias in the analysis of trials, look for it before the first patient is enrolled. Trial design is where the bodies are.

When you read a new trial, what convinces you, or makes you immediately sceptical?

Again, convincing are clinically important and statistically robust findings in an important endpoint. You have to have both.

Take DANGER Shock, the micro-axial flow pump (Impella) in cardiogenic shock trial. You get a 26% reduction in mortality. ARR is a massive 13%. But the p-value is 0.04 and just 1 or 2 endpoints in the different group would render the trial non-significant. So… I think the trial, which took 10 years to find 360 pts, shows that the micro-axial flow pump probably works in super select group of patients.

When I read a paper, I like to start with the purpose of the study. Are the authors trying to answer an important question about a therapy? Or are they simply been hired to sell more product for a company.

That said, I don’t think we can label all industry trials as biased. The TAVI trials are exemplary, for instance. Medtronic ran a 7000-patient trial called WRAP IT to test whether their ABX pouch reduced infection. It did. And it was a clean trial.

You’ve changed your mind publicly over the years. This can be a difficult thing to do. How should emerging cardiologists learn to change theirs?

If you haven’t changed your thinking a number of times, you aren’t thinking enough. Change in Medicine is normal. The thing about training is that you don’t know what you don’t know, not because you are not smart, but because change is such a constant.

For instance, when I trained at Indiana University in the 1990s, the three procedures that I do most often today had not even been thought of yet. BiV and conduction system pacing as well as AF ablation had yet to be discovered.

I actually love changing my mind. It’s one of the joys of this job.

Imagine you’re back at CSANZ in 2046 speaking to today’s fellows, now consultants. What do you think they’ll look back on and say “What were we thinking?

Whenever I finish an AF ablation and go talk to the patient, they want to know if their AF is gone. Yet all we do is isolate PVs. A robot could do it. It’s mindless. Sometimes it works, but we don’t know when it will. Future doctors will surely think we were idiots when it came to AF ablative therapy.

I also hope the thinking on LAAC changes. It’s sort of changing now, but surely future doctors will be shocked that we did this in the face of all the contrary evidence.

Interventional therapy for acute MI and stroke will hold up, but I think preventive therapy will further erode the need for revascularization in chronic CAD. I would not be surprised if left main disease is treated medically in 20 years.

I give it at least a 25% chance that the combination of imaging and AI will improve targeted revascularization and future doctors will think it silly that we decide on placing a stent by how ugly a lesion looks on an angiogram.

Is there one landmark trial that has most shaped the way you think about evidence, and what did it teach you?

CAST – should be taught in all medical schools. It’s the most important trial not just in cardiology but all of medicine.