Vasodilators in Acute Heart Failure: Who Needs Them and How Soon?


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  • Summary:

    Dr. W. Frank Peacock from the Baylor Medical College, Houston, TX, moderated the topic “Vasodilators in Acute Heart Failure: Who Needs Them and How Soon?” with Drs. Alexandre Mebazaa from Paris Diderot University, Paris, France; John Teerlink from University of California—San Francisco, San Francisco, CA; and James Udelson from Tufts Medical Center, Boston, MA. 

    The discussion focused primarily on:

    1. The role of vasodilation in heart failure (HF);
    2. the ideal patient population for vasodilators;
    3. chronic versus acute HF patients;
    4. hemodynamic models of acute HF;
    5. clinical studies using vasodilators;
    6. the role of blood pressure/hypertension;
    7. novel vasodilators;
    8. guidelines for using vasodilators; and
    9. the use of vasoconstrictors.

    (Med Roundtable Cardiovasc Ed. 2014;3(4):278–284)

    ©2014 FoxP2 Media, LLC

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DR. PEACOCK: I’m Frank Peacock, Emergency Physician at Baylor Medical College, and my interest is in heart failure (HF).

DR. TEERLINK: I’m John Teerlink, Professor of Medicine at the University of California, San Francisco, and Director of the Heart Failure Program as well as Director of the Clinical Echocardiography Laboratory at the San Francisco Veterans Affairs Medical Center.

DR. UDELSON: My name is James Udelson. I’m Chief of the Division of Cardiology at Tufts Medical Center in Boston, and I’m very involved in the care of patients with HF.

DR. MEBAZAA: I am Alexandre Mebazaa, Professor of Critical Care Medicine in Paris, and my area of interest is acute HF.

DR. PEACOCK: The first question today is “Should all HF patients get vasodilators and when should they be administered?” Dr. Teerlink, would you like to begin with your theories on vasodilation in HF?

DR. TEERLINK: I assume we are limiting our discussion to acute decompensated HF or acute HF today. I think the utility of vasodilators and the neurohormonal antagonists in chronic HF has been well established, but it’s in the field of acute HF where we’re still learning about these agents. Initially, our research in this field was a bit stymied as many of the early researchers were involved in transplant centers. The early picture of an acute HF patient was actually a pretransplant patient, and this is usually a patient with low systolic blood pressure (BP) who had chronic HF that had decompensated.

As we’ve looked forward towards people such as you, Dr. Peacock—professionals who are working in the emergency departments and are taking care of HF outside of the cardiology setting, per se—we realize that more than 50% of the patients actually present with a normal or elevated BP and that about half of these patients also have normal ejection fractions (EFs). These are appropriate targets for vasodilator therapy, which can decrease the abnormally elevated afterload as well as decrease the abnormally elevated preload through both arterial and venous vasodilation. So, I think this is a very promising area of research, which is why there have been a number of trials and new agents that have been developed to try to address this, as of yet, unmet need.

DR. PEACOCK: Yes, your epidemiology comments are quite accurate: we did start in the heart-transplant world, and as the Acute Decompensated Heart Failure National Registry (ADHERE) registry1 showed us, HF is slightly common in women—just over half of the HF population—and they certainly have more hypertension than we ever expected.

Dr. Udelson, you’ve been involved in many studies. What are your views on this?

DR. UDELSON: I agree that one of the important findings, upon careful examination of these registries, is that there is a completely different understanding of who these patients are from what we might have thought 10 years ago. An example is the finding that most people have high BP, not low BP, and preserved EF when they come in with decompensated HF and shortness of breath. So, it’s only by understanding that you can design therapeutic targets, and the fact that many people are hypertensive instead of hypotensive would suggest that there could be a further role for vasodilators beyond current practice. To this point, the trials that have been conducted in the last 8 to 10 years, in which Drs. Teerlink and Mebazaa and others have been involved, have not been beneficial with drugs such as tezosentan or nesiritide. So, the search continues. In addition, the pathophysiology rationale makes sense.

DR. PEACOCK: Dr. Mebazaa, you’ve had some experience with different agents and patient selection. Who do you think should be receiving vasodilators? What patient population is ideal?

DR. MEBAZAA: Your question on the population is very interesting because the more we are learning through investigations in acute HF, the more we are discovering that it includes a wide range of patients with a comorbidity of age. The population goes from frequent flyers and patients with chronic HF who come in regularly with low BP who are often very well treated with many medications, to patients who come in with high BP who are not well treated. It’s true that it seems difficult to have one drug that will save all those patients, but maybe vasodilators will help many of those acute HF patients.

One point I would like to mention is that we should rethink the term “vasodilation.” Maybe it does not necessarily mean a decrease in BP and maybe we do not necessarily need the decrease in BP to see an improvement in a patient’s condition. In one of our last trials, we showed that although dyspnea improved in patients with high BP and low BP, there was a trend toward improved mortality in patients with low BP when they were administered vasodilators.2 But, maybe we are focusing too much on the role of vasodilators on the arterial side for reducing BP and forgetting about what Dr. Teerlink was mentioning, which is the action of the venous beds: they cause a reduction in central venous pressure and improvement in organ dysfunction. Perhaps, if we improve organ dysfunction, we may save lives more than we would by just reducing blood pressure, per se.

DR. PEACOCK: So, it sounds like you’re very supportive of some kind of hemodynamically active drug that builds space within the vasculature, regardless of BP. As long as patients have functional BP, you would add it. Is that your position?

DR. MEBAZAA: Yes, BP is very easy to measure. I mean, everyone knows how to measure BP, and when the BP is decreasing, we feel that the drug is working. But maybe, within the organs, there are some special effects of vasodilators and sometimes, we forget that some, or maybe most, of the vasodilators have some local effects. Drugs such as nitrates and ularitide have some biochemical local effects, and we maybe forgetting those effects, which could either potentiate the decrease in BP or have their own positive effect on outcome.

DR. PEACOCK: Dr. Teerlink, you and I have talked about the hemodynamic models of acute HF and the variations of how that could work. Can you expand on that a little bit?

DR. TEERLINK: Yes, I think Dr. Mebazaa has mentioned a very important point as well, that BP is not necessarily a reliable reflection of what the mechanism of action is for many of these vasodilators. We’ve had to walk a very careful line here because the early trials with tezosentan and other vasodilators such as nesiritide, cenderitide and cinaciguat were largely hampered by episodes of hypotension during the early development and later development program. So, I happen to agree that vasodilators can be very useful in the setting of patients who have increased afterload but still don’t have low BP. In that pathophysiologic state, one can be given an arterial vasodilator that will decrease the afterload, allowing for an increased stroke volume that actually preserves or may even improve systolic BP.

There was a very informative study by Gary Francis and his colleagues,3 wherein they administered nitroprusside to patients with aortic stenosis and severe HF, which is supposedly one of the exact examples of the pathophysiologic state where you should not, by traditional teachings, administer vasodilators. Yet, these patients showed significant improvements and achieved multiple beneficial outcome variables. So, I think there is definitely a very important target on the arterial side in patients who have severely reduced cardiac output and markedly elevated afterload, where afterload reduction can be very beneficial.

On the other hand, you have patients with hypertensive crisis. Patients who have this marked and rather sudden ventricular arterial impedance mismatch will also, I believe, benefit substantially from targeted afterload reduction. In between, you have the other pathophysiologic state of pulmonary venous congestion. Such patients clearly benefit from venodilators, and we are reminded of the article from 1931 by Dr. Winton4 that suggested that much of the renal dysfunction that is associated with acute HF is due to elevation in central venous pressure. So, in terms of end-organ damage, vasodilators that work on the venous side may help improve renal function as well.

DR. PEACOCK: Let me direct this question to Dr. Udelson. If we look at the ADHERE data,1 only about 15% of all HF patients receive any kind of vasodilator in the first 24 hours of their hospitalization. Suppose I am the physician in the emergency department, how do I decide on who receives the vasodilator, and should the number of patients receiving vasodilators be higher?