Implications of hypertensive response to exercise in adults with repaired coarctation of the aorta

Abstract

Coarctation of the aorta has long been considered a benign condition ‘cured’ by surgery but this is no longer the case. Large studies have demonstrated a significant reduction in longterm survival of patients with repaired coarctation even after ‘successful’ surgical repair, mostly due to the accelerated effects of hypertension and cardiovascular disease. We recently demonstrated an accelerated decline in longterm survival after only the third decade of life compared with a matched normal population. Therefore, it is imperative to identify early those at highest risk of developing hypertension and is why the recently published study by Meijs et al investigating the clinical and prognostic implications of a hypertensive response to exercise after coarctation repair has significant implications for this population. While resting blood pressure has long been the most used method for the detection of hypertension given its ease, we now know that it may underestimate the true prevalence of hypertensive disease in the repaired coarctation population. Up to 60% of patients with repaired coarctation may be diagnosed with hypertension on 24hour ambulatory blood pressure monitoring (ABPM) with resting blood pressure measurements exhibiting a sensitivity of <50% in detecting an abnormal 24hour blood pressure in this population. Consequently, in the recent 2020 European Society of Cardiology (ESC) guidelines, correct blood pressure measurement in the followup of patients with coarctation was defined as 24hour ABPM on the right arm. However, 24hour ABPM can be cumbersome and poorly tolerated in some patients, particularly children. Exercise stress testing has been increasingly explored in patients with coarctation to determine the prevalence, risk factors, and importantly, the prognostic implications of a hypertensive response to exercise in this population. The multicentre, prospective registry study by Meijs et al is one of the largest studies of 675 adults with repaired coarctation and exercise stress testing at a median age of 24 years with a mean followup duration of 10.1 years. While baseline resting hypertension and hypertensive response to exercise was reported in 56% and 44% of patients, respectively, and peak exercise systolic blood pressure (SBP) was positively predictive of resting SBP and 24hour SBP at followup, it is in the stratification of patients based on their blood pressure status at baseline and at followup which is most enlightening (figure 1, Meijs et al). A similar though vast majority of patients with resting hypertension (>85%) continued to have resting hypertension at followup regardless of response to exercise at baseline suggesting little impact of exercise stress testing results on future hypertensive status when resting hypertension is already present. However, in patients with normal resting blood pressure, a greater proportion of patients who demonstrated a hypertensive response to exercise developed resting hypertension at followup compared with those with no hypertensive response to exercise (50% vs 35%). While the proportion of patients taking any antihypertensive medication and the number of antihypertensive agents taken increased overall during followup, these findings are despite an even greater increase in antihypertensive agent use in patients with a hypertensive response to exercise. These findings suggest that the addition of exercise stress testing to resting blood pressure measurements perhaps had the greatest practical and predictive impact on patients with normal resting blood pressure. While the study by Meijs et al was not designed to examine the impact or effectiveness of antihypertensive use in a repaired coarctation population, it was alarming to see 66% of their cohort of relatively young adults to have resting hypertension at followup despite an increased use of antihypertensive agents. It is well known that hypertension in patients with coarctation can be notoriously difficult to treat and the mechanism of which is often multifactorial and increasingly complex. While scrutiny for and prompt treatment of any arch reobstruction is paramount, many patients with repaired coarctation with hypertension have no evidence of any arch reobstruction. 3 The true impact of arch reobstruction in the current study by Meijs et al is unknown as only resting armleg gradient was examined rather than echocardiographic or computed tomography imaging parameters which have been demonstrated to be more sensitive in the detection of arch reobstruction. There is increasing evidence that endothelial dysfunction, dampened sympathetic baroreflex response, and increased arterial stiffness may contribute to the development of hypertension on 24hour ABPM and exercise stress testing even in patients with repaired coarctation without evidence of significant arch reobstruction. 6 Therefore, coarctation likely represents a complex generalised vasculopathy rather than an isolated anatomical narrowing ‘fixed’ by surgical repair, further emphasising the importance of lifelong stringent followup for this population. Despite being an overall young adult cohort with a median age of 24 years, Meijs et al reported 15% of patients had developed a major cardiovascular event (including aortic events) in just a mean of 10 years of followup. While there appeared to be no association between blood pressure and the risk of cardiovascular events based on peak exercise SBP and resting SBP, it is worth noting that baseline 24hour ABPM was not examined in this study. Similarly, Meijs et al reported no association between peak exercise SBP and left ventricular mass index at followup. The lack of association between peak exercise SBP and cardiovascular events in this cohort may be related to the high proportion of aortic complications and confounded by the high but not unexpected prevalence of bicuspid aortic valve in just over half of patients. We have previously demonstrated in a large cohort of 834 adult survivors of coarctation repair that patients with a bicuspid aortic valve were more than four times more likely to require an aortic valve or ascending aortic intervention compared with those with a normal tricuspid valve. In the current study, patients with bicuspid aortic valve demonstrated a lower blood pressure response to exercise which may be related to the degree of aortic stenosis Department of Medicine RMH, University of Melbourne, Melbourne, Victoria, Australia Department of Cardiology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia Heart Research, Clinical Sciences Murdoch Children’s Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia