Coarctation of the aorta (CoA) is associated with generalized arteriopathy that persists despite successful treatment/repair, and carries reduced survival [
The need for re-intervention of repaired CoA has been reported in approximately 30% [
Adults with native and repaired CoA undergoing exercise cardiac catheterization at a quaternary care center between January 2004 and November 2021 were retrospectively identified using an electronical search tool. The study was approved by the Mayo Clinic Institutional Review Board (Mayo Clinic Adult Congenital Heart Disease Registry, IRB#20-007695) and only patients providing research authorization were included in the study.
Cardiac catheterization was performed in a fasting state under light sedation. Exercise was performed via supine cycle ergometry or arm adduction with 4-pound weights, as previously described [
Pulmonary and systemic flows were calculated by the direct Fick method; alternatively, the indirect Fick or thermodilution methods were used. Cardiac output (CO) response to exercise was calculated as [ΔCO/(ΔVO2*0.006)] * 100; [
Continuous variables are presented as mean ± standard deviation or median (interquartile range) and nominal variables as counts (%). Comparisons between resting and exercise data were performed using paired Wilcoxon rank-sum test (non-parametric continuous variables). Statistical analysis was conducted with JMP for SAS V.14.1.0;
The final cohort consisted of 20 patients with only 1 individual having unrepaired CoA. Demographic and clinical data are presented in
Variables | n | |
---|---|---|
Sex, male (%) | 20 | 10 (50%) |
Age at diagnosis, years | 20 | 3.5 (0–12.3) |
Hypertension (%) | 20 | 17 (85%) |
Dyslipidemia (%) | 20 | 10 (50%) |
Diabetes mellitus (%) | 20 | 0 |
Body mass index, kg/m2 | 20 | 31.2 ± 6.5 |
Obstructive sleep apnea (%) | 20 | 6 (30%) |
Clinical diagnosis of heart failure (%) | 20 | 12 (60%) |
Coronary artery disease (stenosis >50%) (%) | 17 | 4 (24%) |
Prior atrial arrhythmias (%) | 20 | 10 (50%) |
Prior ventricular arrhythmias (%) | 20 | 2 (10%) |
CIED (%) * | 20 | 3 (15%) |
Chronic kidney disease (%) | 20 | 3 (15%) |
Loop diuretics (%) | 20 | 5 (25%) |
Thiazides (%) | 20 | 4 (20%) |
Pulmonary vasomodulator therapy (%) | 20 | 2 (10%) |
Beta blockers (%) | 20 | 12 (60%) |
ACEI/ARB (%) | 20 | 11 (55%) |
Aldosterone receptor antagonists (%) | 20 | 4 (20%) |
Calcium channel blockers (%) | 20 | 3 (15%) |
Hydralazine/nitrates (%) | 20 | 2 (10%) |
Notes: ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CIED = cardiac implantable electronic device.
*One patient had a pacemaker; two patients had an implantable cardioverter defibrillator.
Four patients (20%) were in New York Heart Association functional class III–IV, while 4 were asymptomatic. Nine patients had pre-procedural outpatient upper and lower limb blood pressure measured; median systolic pressure gradient was 25 (15–31) mmHg. Detailed information of pre-procedural imaging is depicted in
Variables | n | |
---|---|---|
Left ventricle ejection fraction, % | 20 | 60.8 ± 9.7 |
Left ventricular mass index, g/m2 | 17 | 97 (82–128) |
≥Moderate right ventricular enlargement, % | 20 | 3 (15%) |
≥Moderate right ventricular systolic dysfunction, % | 20 | 1 (5%) |
Right ventricular systolic pressure, mmHg | 18 | 38 (30–47) |
Mitral annulus medial e’ velocity, m/s | 15 | 0.07 ± 0.02 |
Medial E/e’ ratio | 12 | 12 (9–14) |
Mean mitral valve gradient, mmHg | 9 | 5 (3–7) |
≥Moderate mitral regurgitation, % | 20 | 2 (10%) |
Mitral valve prosthesis, % | 20 | 4 (20%) |
≥Moderate tricuspid regurgitation, % | 20 | 4 (20%) |
≥Moderate aortic valve stenosis, % | 20 | 5 (25%) |
Mean aortic valve gradient, mmHg | 15 | 7 (4–25) |
≥Moderate aortic valve regurgitation, % | 20 | 0 |
Aortic valve prosthesis, % | 20 | 4 (20%) |
Ascending to descending aorta mean gradient, mmHg | 17 | 13 (7–18) |
Time from catheterization, days | 16 | 26 (3–400) |
Distal aortic arch diameter, mm | 15 | 21 ± 3 |
Aortic isthmus/narrowest site diameter, mm | 16 | 16 ± 4 |
Distal descending aorta diameter (diaphragm), mm | 16 | 20 ± 4 |
Aortic isthmus ratio | 16 | 0.8 ± 0.2 |
Note: ┘Cardiac computed tomography or cardiac magnetic resonance.
Detailed information about rest and exercise catheterization is shown in
Variables | n | n | ||
---|---|---|---|---|
LV systolic pressure, mmHg | 16 | 135 (123–162) | 7 | 168 (142–187) |
LV end-diastolic pressure, mmHg | 16 | 20 (14–28) | 7 | 25 (15–26) |
Systolic arterial pressure AAo, mmHg | 17 | 129 ± 19 | 16 | 159 (132–169) |
Diastolic arterial pressure AAo, mmHg | 17 | 70 ± 8 | 16 | 80 (73–93) |
Mean arterial pressure AAo, mmHg | 17 | 93 ± 12 | 16 | 111 (100–128) |
Systolic arterial pressure DAo, mmHg | 14 | 112 (104–134) | 9 | 121 (114–150) |
Diastolic arterial pressure DAo, mmHg | 14 | 69 (62–79) | 9 | 82 (69–96) |
Mean arterial pressure DAo, mmHg | 14 | 87 (81–102) | 9 | 103 (91–118) |
AAo to DAo peak-to-peak gradient, mmHg | 14 | 12 (3–16) | 9 | 16 (9–28) |
Right atrial pressure, mmHg | 20 | 7 (5–11) | 6 | 18 (10–23) |
Pulmonary artery mean pressure, mmHg | 20 | 27 (21–33) | 19 | 43 (32–68) |
PAWP/left atrial pressure, mmHg | 20 | 16 ± 5 | 18 | 29 ± 12 |
Cardiac index, l/min/m2 | 20 | 2.5 ± 0.6 | 9 | 4.1 (3.1–7.1) |
Systemic vascular resistance, dyn⋅s⋅cm−5 | 17 | 1425 (1065–1886) | 4 | 1059 (854–1324) |
Pulmonary vascular resistance, WU | 20 | 1.9 (1.4–3.9) | 9 | 1.5 (0.9–3.8) |
Cardiac output response, % | - | 9 | 82 (72–116) |
Notes: AAo = ascending aorta; DAo = descending aorta; dyn⋅s⋅cm−5 = dynes per second per centimeter−5; LV = left ventricular; PAWP = pulmonary arterial wedge pressure; WU = Wood units.
*Data correspond to peak exercise.
At rest, 10 patients (63%) had LVEDP >15 mmHg and 11 (55%) had PAWP >15 mmHg. Resting PH was present in 11 patients (55%): 7 (35%) combined and 4 (20%) isolated post-capillary. At peak exercise, 11 (61%) had PAWP ≥25 mmHg with 2 of them having normal resting PAWP. Thirteen individuals (68%) had an exercise mPAP ≥40 mmHg. Of 9 patients with CO measurement during exercise, normal cardiac output response was present in 6 (67%). ΔPAWP/ΔCO ≥2 and ΔmPAP/ΔCO ≥3 was found in 7 (78%) and 6 (67%), respectively. The composite variable of PAWP ≥25 mmHg or ΔPAWP/ΔCO >2 was present in 12 patients (86%) at peak exercise.
Peak-to-peak CoA gradient was measured at rest in 14 patients and during maximal exercise in 9. Comparison between rest and exercise peak-to-peak CoA gradients did not show statistically significant differences (12 [3–16]
Following catheterization, 7 patients (35%) underwent subsequent intervention due to re-coarctation. Their hemodynamic profile is presented in
To the best of our knowledge, this is the first study to assess rest and exercise invasive hemodynamics in adults with CoA. The main findings of the study are: (1) most patients demonstrated evidence of LV diastolic dysfunction/elevation in left filling pressures, particularly during exercise; (2) similarly, in this cohort, the prevalence of PH was high, with exercise unmasking underlying abnormal pulmonary vascular reserve; (3) most patients failed to show significant increases in CoA peak-to-peak gradients with arm exercise, and despite CoA re-intervention, multidrug antihypertensive treatment was still required.
Lifelong follow-up of patients with repaired CoA is mandatory due to long-term comorbidities and common need for re-intervention [
We present herein invasive hemodynamic evaluation in CoA, which is gold standard for diagnosis of diastolic dysfunction and PH. Our findings confirm previous non-invasive observations, demonstrating abnormal pulmonary vascular reserve and hemodynamic response to exercise in this population. In our cohort, LV diastolic dysfunction was highly prevalent and >50% had elevated PAWP at rest. Furthermore, exercise data showed high prevalence of impaired diastolic reserve and abnormal left heart compliance as shown by the composite of PAWP ≥25 mmHg or ΔPAWP/ΔCO >2 in 86%. These findings are of clinical importance, particularly in the evaluation of symptomatic patients late after CoA repair or those with noninvasive evidence of elevated pulmonary pressures. In addition, they provide further pathophysiologic basis for non-invasive observation of abnormal left atrial function [
Noteworthy, all patients with resting PH had concomitant elevated PAWP. These findings provide hemodynamic support to classifying patients with CoA and elevated pulmonary pressures as group II PH based on their anatomic substrate and expected pathophysiology [
Despite still being the ultimate diagnostic test, the invasive assessment of hemodynamics of native CoA and especially re-coarctation remains a clinical challenge. Gradients can be highly variable according to structural (presence of collateral vessels, for example) or physiologic (degree of sedation or need for general anesthesia) substrates. To mitigate this, some authors have studied the hemodynamic response to inotropes during cardiac catheterization. A recently published study in a younger CoA population (mean age at catheterization 27.3 ± 13.2 years) analyzed the use of epinephrine for gradient provocation prior to CoA intervention. In patients with low baseline CoA gradient but high gradients (>20 mmHg) after epinephrine administration, percutaneous intervention resulted in significant decrease in hypertension prevalence at mid-term follow-up [
Invasive exercise evaluation might therefore represent a more physiologic test, better compared to noninvasive stress tests currently recommended by the guidelines. Most of our patients failed to show significant increases in blood pressure and CoA peak-to-peak gradients with exercise. Pressure gradient across an anatomic stenosis is determined by cross-sectional area and flow across the stenosis. One could argue that arm exercise could have been suboptimal for gradient provocation as flow augmentation in the descending aorta could have been insufficient with this form of exercise [
The optimal method for the hemodynamic evaluation of re-coarctation remains to be elucidated and further studies are warranted to establish whether exercise and pharmacologic stress protocols at the time of catheterization could be used to unmask CoA severity. It is possible that using these provocative maneuvers, patients with unrepaired CoA and particularly re-coarctation could be categorized into 2 groups: those with true severe CoA who may benefit from invasive intervention [
Lastly, it should be noted that the only 2 patients with significant increase in CoA peak-to-peak gradients underwent exercise via supine cycle ergometer instead of arm adduction, highlighting the need to further investigate whether the diagnostic accuracy of these 2 types of exercise for CoA severity assessment is comparable. In addition, the “expected” gradients during exercise in those with and without anatomical obstruction need to be defined, as the cut-off of 20 mmHg used for resting gradients might not be applicable.
We acknowledge the small sample size and retrospective nature of the study. Patients referred for cardiac catheterization in current practice are typically more complex and this is reflected in the demographics of our cohort; thus, our results may not be fully applicable to all asymptomatic patients post-coarctation repair. For PH definition, we intentionally chose a mPAP cut-off value of ≥25 mmHg since our aim was to be more specific than sensitive. Peak-to-peak CoA gradient was not available in all cases; however, it was assessed in every case where there was concern of significant coarctation/re-coarctation. The type of exercise was chosen at the operator’s discretion, resulting in inherently heterogeneous results. Nevertheless, to the best of our knowledge, this is the first report of rest and exercise invasive hemodynamics in adults with CoA.
CoA is associated with significant vascular and myocardial disease at young ages. Prevalence of diastolic dysfunction and PH in our cohort was high, and exercise unmasked underlying abnormal diastolic and pulmonary vascular reserve. Most patients failed to show significant increases in CoA peak-to-peak gradients with exercise; further studies are warranted to establish the best diagnostic method to assess severity of CoA and select those patients who might benefit from CoA intervention.
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline catheterization | Rest | Exercise | Rest | Exercise | Rest | Exercise | Rest | Exercise | Rest | Exercise | Rest | Exercise | Rest | Exercise |
Arm | Arm | Arm | Cycle | Cycle | Cycle | Arm | ||||||||
LV systolic pressure, mmHg | 114 | - | 145 | 149 | 124 | - | 166 | - | 125 | - | - | - | 108 | 132 |
LV end-diastolic pressure, mmHg | 19 | - | 60 | 15 | 13 | - | 31 | - | 20 | - | - | - | 10 | 12 |
Systolic arterial pressure AAo, mmHg | 112 | 169 | 123 | 123 | 121 | 133 | 154 | 183 | 130 | 167 | 117 | 126 | 105 | 136 |
Diastolic arterial pressure AAo, mmHg | 66 | 107 | 67 | 72 | 69 | 74 | 82 | 91 | 65 | 70 | 71 | 75 | 54 | 72 |
Mean arterial pressure AAo, mmHg | 86 | 134 | 91 | 95 | 92 | 104 | 111 | 130 | 85 | 109 | 90 | 97 | 73 | 98 |
Systolic arterial pressure DAo, mmHg | 97 | 152 | 112 | - | 105 | 121 | 141 | 147 | 110 | 103 | 100 | 110 | 89 | 117 |
Diastolic arterial pressure DAo, mmHg | 65 | 105 | 62 | - | 60 | 66 | 94 | 100 | 60 | 59 | 72 | 77 | 53 | 71 |
Mean arterial pressure DAo, mmHg | 81 | 128 | 86 | - | 81 | 90 | 115 | 121 | 80 | 79 | 86 | 94 | 69 | 92 |
AAo to DAo peak-to-peak gradient, mmHg | 15 | 17 | 11 | - | 16 | 12 | 13 | 36 | 20 | 64 | 17 | 16 | 16 | 19 |
Pulmonary artery mean pressure, mmHg | 26 | 41 | 25 | 32 | 22 | - | 22 | 49 | 17 | 26 | 31 | 75 | 12 | 20 |
Mean PAWP, mmHg | 16 | 31 | 14 | 19 | 14 | - | 12 | 39 | 11 | 20 | 22 | 55 | 5 | 8 |
Cardiac index, l/min/m2 | 2.7 | - | 3.8 | - | 3.4 | - | 1.7 | 3.6 | 2.8 | 7.9 | 2.1 | 4.2 | 2.3 | - |
Pulmonary vascular resistance, WU | 1.7 | - | 1.7 | - | 1.2 | - | 3.1 | 1.5 | 0.9 | 0.3 | 2.0 | 2.2 | 1.3 | - |
Note: AAo = ascending aorta; DAo = descending aorta; LV = left ventricular; PAWP = pulmonary arterial wedge pressure; WU = Wood units.