Extracardiac Abnormalities of Preload Reserve:

Diastolic Dysfunction Does Not Negate Health Status Benefits Of TAVR

Left ventricular diastolic dysfunction is associated with worse health status among patients with severe aortic stenosis, but TAVR leads to clinically meaningful symptomatic improvements regardless of the severity of that dysfunction, a single-center study shows.

Before the procedure, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores were lower in patients with the highest grades of diastolic dysfunction (P = 0.004). Within the first month after TAVR, however, there were substantial gains in health status across the board, with no significant differences between categories of diastolic dysfunction; those improvements were sustained out to 1 year.

Lead author Ali Malik, MD (Saint Luke's Mid America Heart Institute, Kansas City, MO), noted that poor LV diastolic function, which is found in most patients with symptomatic aortic stenosis, has been associated with increased mortality after TAVR. It's impact on functional status is less clear, however.

This new study, he told TCTMD, helps identify factors that can be used to better select patients likely to benefit from TAVR. "Diastolic dysfunction by itself should not be a contraindication for this procedure in patients who really need it," Malik said. "The symptomatic benefit of TAVR is consistent regardless of patients' underlying diastolic dysfunction."

Diastolic dysfunction is just one of many factors physicians take into consideration when evaluating a patient for suitability for TAVR, he pointed out. "Our analysis answers one piece of the puzzle, and there's room for further studies to extend our understanding about what are the factors that determine which patients would benefit the most from this procedure."

Numerically Higher Mortality With Worse Diastolic Dysfunction

For the study, published online November 27, 2019, ahead of print in JACC: Cardiovascular Interventions, Malik et al looked at data on 304 patients (mean age 81.1; 41.1% women) who underwent TAVR at Saint Luke's between January 2012 and October 2017 and had interpretable transthoracic echocardiograms. LV diastolic dysfunction was absent (grade 0) in 7.9%, mild (grade 1) in 17.8%, moderate (grade 2) in 61.2%, and severe (grade 3) in 13.2%.

As seen in prior studies, patients with worse diastolic dysfunction at baseline had higher rates of mortality at 1 year. There were no deaths among patients without dysfunction, with mortality rates of 5.9%, 7.7%, and 13.9% across the other categories. The differences did not reach statistical significance (P = 0.289), likely because of the small size of the cohort and the short duration of follow-up, Malik said.

Baseline KCCQ overall summary scores declined across categories of diastolic dysfunction, from 61.3 in patients without dysfunction to 44.4 in those with a grade 3 deficit.

Overall, health status improved after TAVR, from an average KCCQ overall summary score of 47.1 at baseline to 68.5 at 1 month and 68.4 at 1 year. A change of more than 5 points is considered clinically meaningful. The large gain in health status was seen across categories of diastolic dysfunction, with no difference in KCCQ scores between groups at either 1 month (P = 0.367) or 1 year (P = 0.354).

Moreover, among patients with echo data available during follow-up, there was no association between the change in diastolic dysfunction grade and change in health status seen at either time point.

"Once the aortic valve stenosis was resolved . . . Patients across the spectrum of diastolic dysfunction felt the same way in terms of their health status, their day-to-day life, their functional capabilities," Malik said.

Asked why diastolic dysfunction wouldn't have more of an influence on health status after TAVR, Malik said it's likely that before the procedure most of the symptoms patients were experiencing were due to the aortic stenosis—which was addressed by the new valve—and not the diastolic dysfunction. "That's why the patients felt similar across the spectrum of diastolic dysfunction after the procedure," he said.

Consider Earlier Intervention

Commenting for TCTMD, Y.S. Chandrashekhar, MD (University of Minnesota and Minneapolis VA Medical Center), said it's not particularly surprising that diastolic dysfunction wouldn't correlate strongly with symptomatic improvement after TAVR. A person's ability to participate in daily activities and have a good quality of life, he noted, is dependent on any number of factors besides diastolic function.

He added that TAVR results in quick relief of the aortic stenosis, with slower resolution seen for the cardiac changes—including hypertrophy and fibrosis—that had developed over the years as the heart fought against the stenosed valve. So regardless of the severity of diastolic dysfunction, patients "felt well because the biggest limitation at that stage, the obstruction, was relieved," said Chandrashekhar, who wrote an accompanying editorial with Frank Flachskampf, MD, PhD (Uppsala University, Sweden).

These findings won't have much of an impact on clinical practice, Chandrashekhar said, because diastolic dysfunction, as Malik noted, is just one factor considered when evaluating a patient for TAVR. "For sure, nobody is going to say I'm going to do TAVR or not do TAVR based on the fact that [the patient] has severe diastolic dysfunction," Chandrashekhar said. "In that sense, this is more to understand the pathophysiology, and it's reassuring that no matter what happens to diastolic dysfunction, the patient feels well."

He added that one message that can be taken away here is that "if you are putting a TAVR valve in a patient who has severe diastolic dysfunction, you may have waited too long." If a physician is uncertain about whether to perform TAVR in a patient, but the diastolic dysfunction is increasing in severity over time, "that may make you think about pulling the trigger." Rather than wait until the patient has grade 3 dysfunction, which means more fibrosis than grade 1 and grade 2, they could try to intervene earlier, said Chandrashekhar.

In their editorial, Flachskampf and Chandrashekhar highlight the important role imaging can play in helping to improve patient care.

Malik agreed, saying that there remains a need for further research into factors that are associated with how well patients do after TAVR. "Imaging, including echocardiography, is a key toward achieving that, and this has been pointed out very nicely in the editorial. . . . There are so many other things that we can do by utilizing all the novel imaging modalities to identify fibrosis, to identify other factors that put patients at a high risk after this procedure. All of these insights taken together will really help us minimize the proportion of patients who do not benefit from TAVR or who actually have a bad outcome after TAVR, and I think that's the key as we expand the indications of TAVR to include low-risk patients."

Diastolic Dysfunction Appears To Worsen Over Time; Associated With ...

A follow-up of participants in a heart function study finds that the prevalence of left ventricular diastolic dysfunction (left ventricular filling [with blood] is abnormal and is accompanied by elevated filling pressures) had increased; that diastolic function had worsened in a nearly a quarter of patients; and that participants who had diastolic dysfunction were more likely to develop heart failure, according to a study in the August 24/31 issue of JAMA.

"There is an emerging emphasis on understanding the progression from heart failure risk factors to asymptomatic ventricular dysfunction and eventually to symptomatic heart failure and death. Therefore, it is important to have population-based information on changes in cardiac function over time," according to background information in the article. "… little is known about time-dependent changes in diastolic function or their relationship to clinical heart failure."

Garvan C. Kane, M.D., Ph.D., of the Mayo Clinic and Medical School, Rochester, Minn., and colleagues conducted a study to measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure. The study included participants enrolled in the Olmsted County Heart Function Study (OCHFS). Randomly selected participants 45 years or older (n = 2,042) underwent clinical evaluation, medical record abstraction, and echocardiography (examination 1 [1997-2000]). Diastolic left ventricular function was graded as normal, mild, moderate, or severe via testing. After 4 years, participants were invited to return for examination 2 (2001-2004). The group of participants returning for examination 2 (n = 1,402 of 1,960 surviving [72 percent]) then underwent follow-up testing for determination of new-onset heart failure (2004-2010).

The researchers found that from examination 1 to examination 2, the prevalence of diastolic dysfunction of any degree increased from 23.8 percent to 39.2 percent. Moderate or severe diastolic dysfunction increased from 6.4 percent to 16.0 percent. Over 4 years, 23.4 percent of participants experienced worsening of diastolic function, 67.8 percent remained unchanged, and 8.8 percent experienced improved diastolic function. Age was predictive of the development of diastolic dysfunction, especially ages 65 years or older.

In the analysis of the diastolic function of healthy participants (without hypertension, diabetes, coronary artery disease, heart failure, or use of cardiovascular medications), incidence of diastolic dysfunction of any degree increased from 11.3 percent at examination 1 to 29.8 percent at examination 2. Among 423 healthy participants, 19.9 percent showed worsening diastolic function, 75.2 percent remained the same, and 5.0 percent improved.

During 6.3 years of additional follow-up, 81 participants developed heart failure. Age 65 years or older was the strongest predictor of heart failure. The authors found that persistent or worsening diastolic dysfunction was associated with heart failure. "Cumulative heart failure incidence was 2.6 percent in participants whose diastolic function remained normal or normalized between examinations; 7.8 percent in those with persistent, or progression to mild diastolic dysfunction; and 12.2 percent in those with persistent, or progression to moderate or severe diastolic dysfunction."

"Longitudinal evaluation of participants in the population-based OCHFS cohort reveals that left ventricular diastolic dysfunction is highly prevalent, tends to worsen over time, and is associated with advancing age. Worsening diastolic function can be detected even in apparently healthy persons. Although confirmation in other studies would be helpful, our data suggest that persistence or progression of diastolic dysfunction is a risk factor for heart failure in elderly persons," the researchers conclude.

Diastolic Dysfunction Linked To Heart Failure Risk

Left ventricular diastolic dysfunction increases risk of heart failure, finds study published in JAMA. "There is an emerging emphasis on understanding the progression from heart failure risk factors to asymptomatic ventricular dysfunction and eventually to symptomatic heart failure and death. Therefore, it is important to have population-based information on changes in cardiac function over time," according to background information in the article. "… little is known about time-dependent changes in diastolic function or their relationship to clinical heart failure." Garvan C. Kane, M.D., Ph.D., of the Mayo Clinic and Medical School, Rochester, Minn., and colleagues conducted a study to measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure. The study included participants enrolled in the Olmsted County Heart Function Study (OCHFS). Randomly selected participants 45 years or older (n = 2,042) underwent clinical evaluation, medical record abstraction, and echocardiography (examination 1 [1997-2000]). Diastolic left ventricular function was graded as normal, mild, moderate, or severe via testing. After 4 years, participants were invited to return for examination 2 (2001-2004). The group of participants returning for examination 2 (n = 1,402 of 1,960 surviving [72 percent]) then underwent follow-up testing for determination of new-onset heart failure (2004-2010).

The researchers found that from examination 1 to examination 2, the prevalence of diastolic dysfunction of any degree increased from 23.8 percent to 39.2 percent. Moderate or severe diastolic dysfunction increased from 6.4 percent to 16.0 percent. Over 4 years, 23.4 percent of participants experienced worsening of diastolic function, 67.8 percent remained unchanged, and 8.8 percent experienced improved diastolic function. Age was predictive of the development of diastolic dysfunction, especially ages 65 years or older.

In the analysis of the diastolic function of healthy participants (without hypertension, diabetes, coronary artery disease, heart failure, or use of cardiovascular medications), incidence of diastolic dysfunction of any degree increased from 11.3 percent at examination 1 to 29.8 percent at examination 2. Among 423 healthy participants, 19.9 percent showed worsening diastolic function, 75.2 percent remained the same, and 5.0 percent improved.

During 6.3 years of additional follow-up, 81 participants developed heart failure. Age 65 years or older was the strongest predictor of heart failure. The authors found that persistent or worsening diastolic dysfunction was associated with heart failure. "Cumulative heart failure incidence was 2.6 percent in participants whose diastolic function remained normal or normalized between examinations; 7.8 percent in those with persistent, or progression to mild diastolic dysfunction; and 12.2 percent in those with persistent, or progression to moderate or severe diastolic dysfunction."

"Longitudinal evaluation of participants in the population-based OCHFS cohort reveals that left ventricular diastolic dysfunction is highly prevalent, tends to worsen over time, and is associated with advancing age. Worsening diastolic function can be detected even in apparently healthy persons. Although confirmation in other studies would be helpful, our data suggest that persistence or progression of diastolic dysfunction is a risk factor for heart failure in elderly persons," the researchers conclude.

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Source-Eurekalert

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