Hearing Loss and Heart Failure; Improved TAVR Outcomes

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include group A strep in the U.S., hearing loss and heart failure, a new medicine for multiple sclerosis, and making transcatheter aortic valve replacement outcomes better.

Program notes:

src:33 Transcatheter aortic valve replacement outcomes improved

1:33 Dapagliflozin (Farxiga)

2:33 Looked at comorbidities

3:srcsrc Tolebrutinib for relapsing multiple sclerosis

4:srcsrc Annualized relapse rate

5:srcsrc Works in the central nervous system

6:srcsrc First endpoint wasn’t proven

6:2src Invasive group A strep

7:2src Become more resistant to antibiotics

8:src1 Not a single type of group A strep

8:25 Hearing loss and heart failure

9:25 Psychological distress mediates

1src:25 With hearing aids you would think it would go down

11:2src Everything looks associated

12:src3 End

Transcript:

Elizabeth: Does hearing loss have anything to do with heart failure?

Rick: What’s going on with invasive group A strep in the United States?

Elizabeth: Taking a look at another medication for [multiple sclerosis].

Rick: And making transcatheter valve replacement safer.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, how about if we turn right to NEJM, a soft toss to you? How can we make this valve replacement safer?

Rick: All right. So first of all, I need to correct myself because we’re not really making it safer, but we’re making the outcome better after it’s been performed. One of the newer treatments for people that have a blockage of their aortic valve is to put in a new valve, but do it through a catheter rather than through surgery. That’s proved beneficial, especially in older individuals and those that have risk factors for having poor outcomes with traditional surgery. About 2src% of individuals still experience a poor outcome in the subsequent year. They either have death or worsening heart failure that results in hospitalization.

So what can we do to decrease that rate? We know that the administration of a new diabetes medication, what’s called a sodium-glucose cotransporter-2 or SGLT2 inhibitor, dapagliflozin, is beneficial in people that have heart failure. If we take individuals that are undergoing transcatheter aortic valve replacement and give them this SGLT2 inhibitor, can we prevent some of the adverse outcomes?

So that was tested in over 1,2srcsrc patients. These are patients that had previously had heart failure. They had their valve replaced through this transcatheter procedure, and they also either had renal insufficiency, diabetes, or their heart function was poor. So they were at high risk, and half got standard care and half got standard care plus dapagliflozin, and they followed them over the course of the next year.

Those that received dapagliflozin in addition to standard care had about a 3src% reduction in the risk of death or worsening heart failure resulting in hospitalization. Were there any side effects? There was a slightly increased risk of genital infection and hypotension in about 6% of individuals, but overall it was fairly well tolerated.

Elizabeth: One of my questions is, did they stratify these folks based on their comorbidities to see whether the dapagliflozin had a more beneficial impact in, for example, those who had pre-existing diabetes versus kidney disease?

Rick: Yeah. You’re right. They did a lot of pre-specified analysis looking at age and gender, and the presence of diabetes and hypertension, and whether heart function was poor or not. Overall, it didn’t matter which group you looked at. In all of them, dapagliflozin was better than just standard care.

Elizabeth: This sounds like yet one more of these medicines that we’re going to consider this global approach to people utilizing it.

Rick: Yeah. Because it’s been shown that in people that have heart failure, regardless of the cause, it’s been beneficial.

Elizabeth: Staying in NEJM then, let’s turn to this examination of a new medicine for relapsing multiple sclerosis — it’s called tolebrutinib — and an existing medicine it’s compared against, teriflunomide [Aubagio].

This tolebrutinib is an oral medication that actually gets into the brain and this is, I think, one of the reasons they thought it was attractive in this particular application. It’s also a bioactive Bruton’s tyrosine kinase inhibitor, and that modulates peripheral inflammation and persistent immune activation within the central nervous system, including these disease-associated microglia and the B cells that are attendant in that process.

This is a report on two phase III, double-blind, double-dummy, event-driven trials called GEMINI 1 and GEMINI 2, in which people who had relapsing multiple sclerosis either got the tolebrutinib or the teriflunomide, each with a matching placebo. And their primary endpoint was their annualized relapse rate, but they also had secondary endpoints, worsening of disability that was sustained for at least 6 months. They had 974 participants in GEMINI 1, 899 in GEMINI 2, and their median follow-up 139 weeks.

Unfortunately, their annualized relapse rate was virtually the same in both of these groups, so the tolebrutinib was not superior. I would say that they did note that the confirmed disability worsening was 8.3% with the tolebrutinib and 11.3% with the teriflunomide, so it sounds like it could be slightly better for that. But in toto, they really were not able to show that there was a superiority overall for this agent.

Rick: You’re right. They chose this particular agent because most of the agents they use that are anti-inflammatory work primarily in the periphery. They don’t cross the blood-brain barrier and don’t work specifically in the brain, and this new agent does.

And there are several different aspects you can look at. One is does it prevent relapse and this agent was no better than existing agents. You can look at MRI plaques and say does it reduce the number or size of MRI plaques, and this agent wasn’t particularly better. This particular agent at least gives a signal that it does prevent worsening of disability. That could be an important endpoint, so it’s going to require some additional studies.

Elizabeth: I agree, and the authors explain this outcome and why they didn’t really emphasize it. They say that when they saw this disability — this confirmed disability — worsening that it appeared to be lower with tolebrutinib. “This finding could not be confirmed owing to the termination of the hierarchical testing procedure on the basis of nonsignificance of the results for the primary endpoint.” That’s why they backed away from making any strong case on that, but I agree that the distinct advantage of crossing the blood-brain barrier is really a big thing.

Rick: You look at one endpoint, and if that looks like it’s beneficial, then you go to the next endpoint, and if the first one doesn’t show it’s significant, then the rest of them you can’t really remark on, and that’s what happened here. Their very first endpoint was did it prevent relapse? And if the answer was no, then you really can’t test the others methodically.

Elizabeth: Let’s move on to your next one. That’s in JAMA.

Rick: Invasive group A strep — this is a bacterial infection and it’s an infection that can involve the skin and soft tissues. Well, it can cause just a sore throat or pharyngitis or it can be quite invasive. It can cause frank necrosis and sepsis resulting in death, pneumonia, bone and joint infections, and we know from about 1995 till about 2src12 that the incidence of this stayed relatively flat. There became a signal about 2src12 that the incidence could be rising. The authors noticed that and they decided to look at 1src states using a population-based surveillance tool called the Active Bacterial Core surveillance network. It looks at 35 million people across 1src different states to ascertain what the incidence was of invasive group A strep — we’ll call it GAS.

Over the last 1src years, the incidence of invasive group A strep has pretty much doubled — a higher incidence or growth rate in American Indians or Alaska Native persons, in people that are homeless, people that inject drugs, and residents of long-term care facilities. Unfortunately, it’s become a little bit more resistant to some of the normal antibiotics that we might give, so this ends up being a serious problem that needs to be addressed.

Elizabeth: Sure sounds like it, and it sounds like it’s going to, of course, start with surveillance. And comment if you would on the infectivity of this organism one person to another.

Rick: Right. When they examined it, it wasn’t large outbreaks. It ended up being small clusters. Individuals that are in long-term care facilities, they’re congregated in facilities, they have underlying medical conditions, they oftentimes have skin breakdown as well, and they’re elderly. So, most of the outbreaks occurred in groups that were smaller than 15, so it wasn’t something like the measles. Furthermore, it wasn’t a single type of group A strep.

Elizabeth: OK. Then among residents of long-term care facilities, for example, what factor has changed that accounts for this doubling?

Rick: Probably an increase in the number of underlying medical conditions, like obesity and diabetes, more skin breakdown, less care available to many of these individuals. All of those things contribute to that risk.

Elizabeth: Finally, let’s turn to the BMJ and this is a study that purports to take a look at the relationship between hearing impairment, psychological distress, and incident heart failure.

Their data comes from the U.K. Biobank study of 164,srcsrcsrc+ participants. These were people in whom they had a hearing test that is called the Digit Triplet Test and it’s quantified by speech reception threshold (SRT). They also had data on their incident heart failure through hospital admission and death records, and in their follow-up of just shy of 12 years they had 2.7% of their participants develop incident heart failure.

They found that the risk of heart failure increased if you also had hearing loss. There was kind of a dose response — the more hearing loss you had, the greater your risk of developing heart failure. And when they broke that out to look at, well, what might be coincident with that, they found that psychological distress mediated what they say is 17% of this association between hearing loss and heart failure, and social isolation and neuroticism also were factors that were a part of this.

They’re saying that, hmm, maybe hearing health and psychological well-being should be considered in cardiovascular risk assessment going forward with an eye toward prevention. Although what contradicts that is their observation in the paper that even among those people who had hearing loss and used hearing aids, they still were at risk for heart failure, so I’m struggling a bit to figure out this relationship.

Rick: Yeah. Elizabeth, this is a very difficult study to interpret. There’s not a large amount of biologic plausibility, number one. Number two is if hearing loss is associated with heart failure and you correct it with hearing aids, you’d expect that the heart failure incidence would go down.

When you compare the individuals that have normal hearing with those that have poor hearing — and they looked at 19 different characteristics — 18 of them were significantly different. Things like age and gender, and BMI, and what their race was, and their college or university degree, their smoking status, alcohol consumption, yada yada yada. So when 18 of 19 characteristics are different among groups, they try to adjust those things statistically and you’re not likely to do that very accurately when there are more things that are dissimilar than there are similar. So as a cardiologist, I’m having a hard time saying, gosh, I’m going to put a hearing test as a part of my risk management in individuals that have heart failure or may have heart failure.

Elizabeth: Well, in particular, because this notion that even if you correct the hearing it’s not going to impact on the risk of heart failure just suggests that they are two independently assorted variables.

Rick: Exactly. You know, and if you look hard enough, everything looks like there’s an association. For example, gray hair appears to have an association with heart failure. Well, not surprisingly, because most gray-haired people are older and age itself, and you may not be able to entirely correct with that statistically. So, I’m going to put this in the interesting-but-hard-to-believe studies that we’ve covered over the last two decades.

Elizabeth: OK. On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up, don’t have heart