Big Changes in Cardiology
Progress in cardiology has plateaued in recent years. A small single-center study involving pacemakers may have just sparked the next big advance in heart failure therapy
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There may be a big advance in cardiology coming soon. Really big.
No. It’s not a new drug. Or a new device. It’s even better.
Better because it involves thinking about the basics we learned in medical school. This newsletter loves thinking.
First some background: The most common problem a cardiologist sees is heart failure. While heart failure is a terrible term, it merely means that inadequate blood goes out to the body with each heart beat—and this results in congestion in the lungs and veins. People report breathlessness and swelling.
We used to call this CHF, or congestive heart failure, but now we have two new names. We separate heart failure into those who have reduced heart pump function and those who have normal pump function. The “ejection fraction,” or “EF,” is the term we use to denote squeezing function. So there is HFrEF and HFpEF.
You might wonder how someone with a normal squeeze (heart failure with preserved ejection fraction—HFpEF) could have problems with forward flow.
You have to remember that the heart does two things with its energy: contract and relax. The problem in HFpEF is relaxation. In HFpEF, the heart is too stiff. Doctors call the relaxation phase, diastole. So there is diastolic dysfunction.
Why the excitement? The great potential of this new revelation is that HFpEF is now the leading cause of heart failure. And it is increasing in incidence.
We do a great job for people when the problem is reduced pump function. We have four classes of drugs as well as defibrillators and special kinds of pacemakers that reduce death in these patients.
But nothing seems to work for patients with stiff hearts. There are many reasons for this, but not least is that patients with stiff hearts usually have multiple other problems—like obesity, high blood pressure, lung disease, or simply, aging.
Increasing longevity and the rise in obesity will only increase the problem of HFpEF.
Old thinking: For decades most (but not all) cardiologists felt that a stiff heart needed more time to fill. Slower rates were better. Think about it: if the heart has problems relaxing and letting blood in, you would want more time between beats to relax.
The most common way doctors reduce heart rate is with a drug class called beta-blockers. These are simple drugs that block the affects of adrenaline. They are used for many other things in medicine.
For instance, in the old days, before we opened arteries during a heart attack, beta-blockers improved outcomes after heart attack. Since we now open arteries and save heart muscle during heart attacks, many question the benefit of beta-blockers after MI.
Beta-blockers also reduce blood pressure—though studies show that there are better drugs. Beta-blockers also reduce death rates in patients with heart failure due to a reduced heart function.
I believed the rate-slowing drugs would help people with stiff hearts. So did most of my colleagues. The proof comes when you look at the HFpEF trials—more than 80% of patients in these trials took beta-blockers at baseline.
But beta-blockers weren’t the only non-evidenced-based fashion we used in HFpEF.
Many patients with stiff hearts are old. And older people often have disease in their natural electrical system which predisposes to slow heart rates. We never thought this was a problem so we let these patients hang out with low heart rates. We didn’t place pacemakers.
The New Study: A team at the University of Vermont had the idea to take patients who had (special) pacemakers and stiff hearts and randomize one group to higher rates and the other group to the normal out-of-the-box rate of 60 beats per minute. The active arm had an average heart rate of 75 bpm vs 60 bpm in the control arm.
The authors called this the myPACE study.
The results were strikingly better in the higher rate group. Patients felt better, they moved more, had less atrial fibrillation and lower levels of a blood test that measured pressure levels in the heart.
Small Study with Big Implications: You might be tempted to think, come on, Mandrola, this is a 100-patient study at one center involving a special kind of pacemakers.
I think this would be a mistake. These findings suggest that we may have had this massive blind spot about heart rate in patients with stiff hearts.
When you go back to basic physiology, it becomes clear that slower rates lead to higher pressures within the heart—which are more likely to lead to congestion in the lungs. It’s basic physics. See picture.
In a normal heart, you can fill, and fill, and the volume-pressure line has a gentle slope. But in stiff hearts, more volume can quickly lead to higher pressure. The slope of the volume-pressure curve is steeper.
A slightly higher rate decreases the time to fill and less volume means less pressure.
This is so basic! How could we have forgot this?
I wrote about these issues on TheHeart.org | Medscape Cardiology. I also discussed it on the This Week In Cardiology podcast. In these discussions, I cite more of the supporting basic and clinical studies. There is more detail in these discussions.
One really important supporting study comes from Valencia Spain. It didn’t garner much attention at the time but gosh it seems big now.
Researchers there took patients with HFpEF who were on beta-blockers and randomized one group to come off the drugs and the other to stay on. Patients who came off did better. See image.
I want to be realistic. This is all very early. And since there is no drug or device involved, big media attention is unlikely to amplify this new progress.
But if future studies reveal that we’ve been harming patients with beta-blockers and the allowance of slower heart rates, the reversal would be huge.
Millions of patients suffer with this condition. And nothing so far has made much of a difference.
Stay tuned. I will keep you updated. I am excited.
From my clinical observation as a young PCP, the largest (and often ignored) modifiable risk factor for people with HFpEF is sleep apnea leading to pulmonary hypertension and diastolic dysfunction.
I suspect we would probably get a lot farther if EVERYONE (patients with both HFrEF and HFpEF) had evaluations and optimization of their sleep.
Thanks for the article and insights. When I teach students about HF I ask them to think about the unifying issue in HFrEF and HFpEF, namely a reduced stroke volume and hence cardiac output. The mechanisms are different but the result is the same.
Cardiac output is a product of heart rate x stroke volume. It never made sense to me that reducing the heart rate would magically increase your cardiac output in HFpEF. Prolonging diastole in people with small poorly compliant ventricles will only prolong the duration of Diastasis. Most of the filling will be in early diastole, then you climb up your pressure volume loop and filling stops! Waiting a bit longer won’t achieve much.
There’s a reason that chronotropic incompetence leads to functional impairment. Augmenting cardiac output by increasing heart rate makes more sense to me.