Quantifying the Potential Impact of SGLT-2 Inhibitors in Heart Failure - Episode 1

Pathophysiology of Different Types of Heart Failure

Nihar Desai, MD, MPH, and Steven Nissen, MD, review the pathophysiology of the different types of heart failure.

Transcript

Neil Minkoff, MD: Hello, and welcome to this American Journal of Managed Care® program titled “The Role of SGLT2 Inhibitors in Heart Failure.” I’m Dr Neil Minkoff, the chief medical officer of Coeus Consulting Group, coming from Sudbury, Massachusetts. Joining me today in our virtual discussion are some of my colleagues: Dr Nihar Desai, who is an assistant professor of medicine at Yale School of Medicine in the cardiovascular section, and an investigator at the Center for Outcomes Research and Evaluation in New Haven, Connecticut; Dr Jaime Murillo, who is a cardiologist and the national senior director of cardiology for UnitedHealthcare, joining us from Florida; and Dr Steven Nissan, who is the chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic in Cleveland, Ohio. Today our panel of experts will review current unmet needs in the management of heart failure, discuss how these needs may be addressed, and focus on the potential role of SGLT2 inhibitors. Let’s begin.

To make sure everyone is level set, I’m going to start off with the basics. Dr Desai, what is heart failure?

Nihar Desai, MD, MPH: Neil, it’s a good question, and thanks to the panelists for getting together for this discussion. It’s great to start with some basics. The question is actually a bit complex, and I use that word specifically. Heart failure is defined as a complex clinical syndrome that occurs because of a structural or functional impairment of the heart muscle, which impairs its ability to either pump blood to the other organs of the body or to do so without increased pressure in the different heart chambers.

We typically think about heart failure in a couple of different flavors. One is heart failure with reduced ejection fraction, where the primary issue is an inability of the heart muscle to pump blood forward and the squeezing function of the heart is impaired. Another is heart failure with preserved ejection fraction, where the squeezing function is relatively normal, but there is an impairment of relaxation that causes the pressure in the heart chambers to increase. The cardinal symptoms that we think about for heart failure are fatigue, shortness of breath, and swelling in the legs or in the lungs. This is a problem that is increasing quite dramatically in our population. Current estimates are that about 5.5 to 6 million Americans have heart failure of some kind. That’s projected to increase quite substantially over the next 5 to 10 years, probably to about 8 or 9 million Americans having this.

That’s a function of a couple of different things. One, the underlying comorbidities that contribute to heart failure are becoming more common. We also have emerging therapies, including those we’re going to talk about in this discussion, that have enabled us to manage patients with heart failure in a better way, relieve suffering, and improve outcomes. It’s quite an exciting time for treatment of heart failure, in general.

Steven Nissen, MD: Let me add a few comments if I may. First, that was a great summary. There are some demographic factors that are affecting this. We have an aging population. A lot of us are getting older, and the baby boomer generation is now getting into that age. Heart failure clearly goes up with age, as do the various comorbidities. The other thing that is a big driver is the obesity epidemic. Every year, we seem to get more obese, and there’s a very close linkage between obesity and heart failure. That includes both the systolic component and the diastolic component, with both the preserved ejection fraction and the reduced ejection fraction component.

One other comment I would make is that we should not leave out valvular heart disease as a pathophysiological abnormality. We see people with myxomatous degeneration of the mitral valve. They get mitral regurgitation, and if they are not treated promptly, they end up with a dilated left heart and left-sided heart failure. The other issues for right-sided heart failure are lung disease and people with COPD [chronic obstructive pulmonary disease]. We still have a significant fraction of the population that smokes. They develop COPD, their pulmonary artery pressures go up, they develop right-heart failure that can be very difficult to treat.

One of the things about heart failure that’s challenging is that it is a constellation of pathophysiological abnormalities that include everything from viral myocarditis leading to a nonischemic cardiomyopathy, to valvular heart disease. Unfortunately, we still see plenty of patients with myocardial infarctions [MIs] that develop abrupt left-heart failure that can be challenging to treat. We still see people after acute MI who are not treated appropriately and get this kind of late remodeling with dilation of the left ventricle. It is really not a single disorder, and that is a challenging factor in thinking through the best treatment.

The other thing is the interaction between kidney disease and the heart. A bit of left ventricular dysfunction in people who have difficulty with excreting salt and water due to kidney disease is also an exacerbating factor.