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Page 8 of 10 Toy et al. Vessel Plus 2024;8:22 https://dx.doi.org/10.20517/2574-1209.2023.149

DISCUSSION
Anxiety and uncertainty about exercise may negatively impact the cardiovascular and mental health of TAD
survivors by leading them to restrict their activities. In contrast to case reports that inform current guideline
recommendations, this pilot study is the first randomized controlled trial of exercise in TAD survivors. The
unique objectives of this study are to assess the effects of an at-home exercise program on hemodynamic
and mental health outcomes. The primary outcome is a clinically significant change in the PROMIS-29
summary T-score or mental health summary score. Secondary outcomes include the change in the burden
of ambulatory hypertension and nocturnal dipping as assessed by ambulatory blood pressure monitoring.
The guided exercise program was proved to be safe for trial participants, and we found that grip strength, a
significant predictor of cardiovascular death, increased by 30% in the first three months of
participation [20,21] . We also observed adverse ABPM characteristics in many participants that are associated
with increased cardiovascular mortality, such as nocturnal hypertension, blunted nocturnal dipping, or
elevated pulse pressure. Ambulatory peak blood pressure and blood pressure variability predicted
significant exertional hypertension. These observations highlight the high cardiovascular risk of the trial
cohort. While self-reported anxiety was increased in trial participants, there was no correlation between
initial PROMIS anxiety T-scores and ambulatory or exertional hypertension.

As the study progressed, we made several adjustments to home exercise instructions and the virtual visit
protocol to account for the frailty and decreased physical strength of many TAD participants. The exercise
instructions were altered so that participants were able to maintain moderate intensity effort without
physical strain. Participants were instructed to scale up individual exercises incrementally, by increasing
repetitions in 15-s increments or by two repetitions per week. When starting home exercises, we allowed
participants to decrease the initial speed and incline settings of the treadmill, the angle of the wall sit, and
the target rate on the stationary bicycle. The virtual visit protocol was amended to collect additional
information about contacts with healthcare providers. We also provided personalized counseling to
individuals who developed exertional hypertension during the in-person exercise training sessions to
modify the intensity of specific exercises and to minimize Valsalva maneuvers during isometric exercises.
New participants in the guided exercise study arm received the updated exercise instructions at the initial
enrollment visit. Previously enrolled participants received updated instructions and teaching at virtual
follow-up visits.

Limitations
The principal limitations to study recruitment were the requirements for participants to have access to
exercise equipment at home and for travel to in-person study visits. Technological barriers did limit timely
virtual follow-up visits with some participants. The follow-up period of this trial is not long enough to
determine if exercise can reduce aortic events. We plan to address these obstacles in a larger and longer trial
that will be adequately powered to determine if guided exercise can reduce aortic events and prevent deaths
due to TAD. In such a trial, we will collect longitudinal data on aortic enlargement, arterial stiffness, cardiac
function, and serial changes in blood pressure responses to exercise over time. To promote accessibility, we
plan to mail portable exercise equipment directly to participants. In the short term, we plan to adapt this
protocol to create personalized exercise prescriptions for patients, and in the long term, we hope that these
studies may eventually be used to develop evidence-based exercise guidelines.

Conclusions
Guided exercise is safe for aortic dissection survivors. Ambulatory blood pressure can predict exertional
blood pressure responses and may improve risk stratification and medical optimization of TAD patients
who plan to begin an exercise program. Short-term exposure to guided exercise increased confidence and
decreased the anxiety of study participants.