Diastolic BP, Heart Rate Strongly Linked to Death in Chronic Aortic Regurgitation

Diastolic blood pressure and resting heart rate provide important prognostic information for patients with hemodynamically significant chronic aortic regurgitation (AR), new data show.

Diastolic readings below 70 mm Hg and resting heart rates above 60 beats per minute (bpm) were strongly associated with all-cause mortality in medically managed patients, even after accounting for potential confounders like hypertension, use of various medications, and guideline indications for valve surgery, lead author Li-Tan Yang, MD (Mayo Clinic, Rochester, MN), and colleagues report.

“I think the importance of this is that it’s the first time that diastolic blood pressure and heart rate have been formally evaluated for their association with mortality in aortic regurgitation, and this has in my mind changed some of the clinical paradigms that were believed in our community regarding these two parameters and aortic regurgitation,” senior author Hector Michelena, MD (Mayo Clinic), told TCTMD.

The robust link between these measures and mortality is particularly important because “it is not a high-tech new technology that’s telling us something, it is basic blood pressure taking and heart rate measurement, which is done every day all over the world and has minimal cost or no cost,” he added.

The bottom line, Michelena said, is that “there is no doubt that diastolic blood pressure and resting heart rate are independently associated with death in patients with significant aortic regurgitation. In fact, they increase, albeit not in an enormous manner, . . . the risk discrimination of death above baseline clinical characteristics and current surgical triggers.

This has in my mind changed some of the clinical paradigms that were believed in our community regarding these two parameters and aortic regurgitation. Hector Michelena

“So it appears as though this thing is for real,” he continued, “and it should in some way or form be included in the armamentarium that we have to evaluate these patients, perhaps as a red flag of increased or heightened death risk that should prompt physicians to do a deeper evaluation or to have a closer monitoring of these patients.”

The study was published in the January 7/14, 2020, issue of the Journal of the American College of Cardiology.

Robust Relationships

The investigators note that current guidelines “hypothetically caution against the use of medications that could worsen volume overload by causing bradycardia and also hypothetically caution about marked diastolic BP reduction that could impair coronary perfusion. However, these concerns are only conjectural because the clinical significance of diastolic BP and resting heart rate in patients with AR is unknown.”

To explore the issue, they retrospectively looked at data spanning from January 2006 to October 2017 on 820 patients with moderate-to-severe AR (mean age 59 years; 92% men). During an average follow-up of 5.5 years, nearly half of patients (49%) underwent valve surgery and 153 (19%) died, including 104 on medical therapy and 49 after valve surgery.

After adjustment for demographics, comorbidities, and guideline-based surgical triggers (including symptoms, LVEF, and LV end-systolic diameter index), the risk of all-cause mortality under medical management was elevated with decreases in baseline diastolic BP (adjusted HR per 10 mm-Hg increase 0.79; 95% CI 0.66-0.94) and increases in baseline resting heart rate (adjusted HR per 10-bpm increase 1.23; 95% CI 1.03-1.45).

Those relationships remained significant in a variety of additional analyses that accounted for the severity of AR, the presence of hypertension, medication use, time-dependent aortic valve surgery, and average diastolic BP and resting heart rate during follow-up (as opposed to a one-time measurement at baseline).

Mortality risk was greater in patients with AR than in their age- and sex-matched counterparts from the general population, and that risk increased as diastolic BP fell (starting at below readings of 70 mm Hg then peaking at 55 mm Hg) and as resting heart rate increased (starting at readings of 60 bpm).

After aortic valve surgery, the relationship between heart rate and mortality remained, but there was no longer an association with diastolic BP, “presumably because the pathophysiology underlying the low diastolic BP was corrected by aortic valve surgery,” the authors say.

Guiding Patient Evaluation

Yang et al note that the link between increasing heart rate and mortality conflicts with the idea that bradycardia should be avoided in patients with chronic AR.

“In our study cohort, 45% of patients presented with resting heart rate ≤ 60 bpm, supporting the clinical observation of relative bradycardia in patients with hemodynamically significant AR,” they write.

“We hypothesize that increased total stroke volume in AR could activate parasympathetic tone, which slows resting heart rate in patients with well-compensated AR. We further suggest that as the severity of AR overwhelms the LV, sympathetic tone activation occurs, resulting in higher resting heart rate, increased myocardial oxygen consumption, and further LV burden, resulting in worse outcomes,” they continue. “Likewise, we hypothesize that very low diastolic BP could result in coronary hypoperfusion of an already hypertrophied myocardium, leading to worse outcomes.”

They add that these hypotheses need to be evaluated in future studies, but, Michelena indicated, clinicians can act on the findings of this new analysis now.

Although no conclusions about causality can be drawn from these data, the associations of diastolic BP and heart rate with mortality are robust and can help guide evaluation of these patients, he said. Because risk is a continuum, strict cutoffs should not be used, Michelena suggested; rather, lower diastolic readings and higher heart rates—especially when changes in these parameters are seen over time—should serve as signs that a patient carries a heightened risk of poor outcomes.

“These are clearly risk factors and markers of death, which means that something is happening and this disease is progressing,” Michelena said. “If I am already a specialist, I need to look deep into what’s going on to see if this patient needs surgery now, or if I’m not a specialist, I need to refer this person to somebody who knows about valves to see if we need to act upon this patient or not regardless of whether the patient [has] symptoms.”

In an accompanying editorial, John Chambers, MD (Guy’s and St Thomas’ Hospitals, London, England), agrees that low diastolic BP and high resting heart rate “can already provide a red flag to alert the clinician to the need for greater vigilance.

“This includes taking note of even nonspecific symptoms, considering an exercise test, and rechecking serial echocardiograms for adverse changes,” he explains. “The authors suggest that they can also be triggers for referring to a heart valve team, but we believe that all patients with severe and even moderate AR should already be seen by cardiologists with specialist valve competencies ideally in a specialist valve clinic.”

He concludes by stating that the study “is useful in our time of ever-increasing diagnostic sophistication for highlighting the importance of simple physiological markers on the routine clinical examination, which can readily be obtained by all clinicians.”