Multi‐Drug–Resistant Hypertension Caused by Severe Aortic Coarctation Presenting in Late Adulthood

Abstract

Aortic coarctation, a congenital narrowing in the region of the ligamentum arteriosium, is a rare etiology for multi‐drug–resistant hypertension in adulthood; however, advances in stenting modalities may offer long‐term improvements in morbidity and possibly even cure. We report on a female patient in her late 50s presenting with refractory hypertension and severely elevated renin levels, ultimately diagnosed with aortic coarctation and treated with percutaneous stent implantation, which resulted in successful blood pressure control with verapamil monotherapy. This case highlights the efficacy of endovascular stent implantation for the treatment of coarctation and the need for clinicians to consider this disease entity in the differential diagnosis of refractory hypertension even in late adulthood

The prevalence of multi‐drug–resistant hypertension in the United States is estimated to range between 9% and 12%1, 2, 3 and is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including a diuretic. The most frequent causes include poor medication compliance, excessive salt intake, physician inertia, and secondary hypertension,4 with the latter most commonly caused by chronic kidney disease, sleep apnea, renal artery stenosis, hyperaldosteronism, and rarely aortic coarctation.5, 6 While newer techniques such as renal artery denervation have been developed in an effort to help treat multi‐drug–resistant hypertension, it is important in this modern era of medicine that physicians continue to evaluate for all possible causes of this increasingly common problem.

We report on a woman in late adulthood, presenting with multi‐drug–resistant hypertension and extremely high renin levels, who was eventually diagnosed with aortic coarctation and successfully treated with percutaneous stent implantation.

Case

A 57‐year‐old Caucasian woman was referred for evaluation of resistant hypertension and the onset of renal insufficiency. The patient had been medically treated for hypertension since her early 20s but was otherwise healthy with no family history of cardiovascular disease. The patient's medical regimen at this time included moexipril 15 mg, amlodipine 10 mg, verapamil 180 mg extended‐release, hydrochlorothiazide 50 mg, minoxidil 10 mg, and candesartan 16 mg.

On initial evaluation, the patient was asymptomatic. Review of systems was positive only for mild depression. The patient's blood pressure was 165/85 mm Hg in bilateral upper extremities, and heart rate was 80 beats per minute. Physical examination was notable for a grade II/VI systolic murmur auscultated over the precordium. Direct fundoscopic examination was normal, lungs were clear, and there was no lower extremity edema.

Results from serum laboratory tests demonstrated a creatinine level of 1.6 mg/dL, estimated glomerular filtration rate of 32 mL/min, and estimated creatinine clearance of 53 mL/min, consistent with stage III chronic kidney disease. The patient's renin level was markedly elevated at 267 μU/mL (nL <5 μU/mL), urine aldosterone was 14.1 μg/24 h (nL <20 μg/h), and catecholamine levels were within the normal range.

Given that the patient had multi‐drug–resistant hypertension with extremely high serum renin level and renal insufficiency, the initial differential diagnosis focused on renal artery stenosis, adverse drug effect, and reninoma. The patient underwent renal magnetic resonance imaging and magnetic resonance angiography (MRA), which demonstrated normal renal arteries bilaterally and symmetrically sized kidneys with no evidence of infarction. Given the high suspicion for renal artery stenosis, invasive aortography with renal angiography was performed and findings were normal from the level of the diaphragm to the iliac bifurcation, showing no evidence of atherosclerotic disease.

Candesartan was suspended, yet this resulted in a rise of serum creatinine, renin, and plasma renin activity (PRA) to 2.9 mg/dL, 3259 μU/mL, and 34,800 ng/dL/h (nL <10), respectively. This PRA level represented the highest recorded value at our hospital laboratory. The patient was thereafter referred for cardiac echocardiography in the setting of her murmur. The results demonstrated mild concentric left ventricular hypertrophy with normal left ventricular function and no significant valvular disease. On evaluation of the aorta, however, an aortic coarctation distal to the left subclavian artery with a peak velocity through the coarctation of 4.7 m/s and a corresponding peak gradient of 85 mm Hg was found.

The patient was subsequently referred for cardiac MRA to better evaluate the coarctation. MRA demonstrated that the coarctation was in the region of the ductus arteriosus, distal to the origin of the left subclavian artery (Figure 1). There were several prominent collateral intercostal arteries visible on the left with a large left subclavian (measuring 1.5 cm in diameter) and a prominent left internal mammary artery.

Figure 1.

Baseline angiogram demonstrating aortic coarctation.

Based on the findings of MRA, the patient was referred for stenting of her coarctation. She underwent this procedure with balloon sizing (Figure 2) and placement of a Palmaz 3110 stent (Johnson & Johnson, New Brunswick, NJ; Figures 3 and 4) resulting in a decrease in the gradient across the coarctation from 40 mm Hg to 5 mm Hg (Figure 5). She tolerated the procedure well and was discharged home the following day on verapamil and amlodipine.

Figure 2.

Angiogram demonstrating balloon sizing of coarctation.

Figure 3.

Angiogram demonstrating stent placement.

Figure 4.

Angiogram demonstrating stent deployment.

Figure 5.

Angiogram demonstrating coarctation after stent deployment.

The patient's condition and renal function continued to improve. By 3 months post‐procedure, the patient's creatinine and PRA decreased to 1.5 mg/dL and 2.1 ng/dL/h, respectively. At this time, the patient's blood pressure was 120/80 mm Hg on verapamil monotherapy. On follow‐up examination 1.5 years after the stenting procedure, the patient's blood pressure remained 120/65 mm Hg on 180 mg of controlled‐release verapamil and 25 mg of hydrochlorothiazide, daily. Further, there was no murmur auscultated on examination, indicating relief of the aortic narrowing with retirement of collateral flow following the endovascular procedure.

Discussion

This case report demonstrates an extremely rare presentation of adult coarctation in an untreated woman surviving into late adulthood. Coarctation of the aorta is a discrete narrowing in the region of the ligamentum arteriosum and accounts for approximately 6% to 8% of congenital heart disease in infants and children.7 The majority of coarctation cases are congenital and are thought to originate from either underdevelopment of the fetal aortic arch secondary to reduced antegrade intrauterine blood flow or ductal tissue migration into the thoracic aorta wall.8, 9 Up to 75% of patients with this structural abnormality are men.10 Presentation in adulthood is rare, as the average survival age in patients with unoperated coarctation is only 35 years with a 75% mortality rate by age 46 and 92% by age 6011, 12; however, it may account for up to 0.2% of adult hypertension.13

The patient described in this report survived, with medical treatment alone, for more than 20 years beyond the expected age of death for untreated coarctation. She also failed to present with other consequences of persistent hypertension including congestive heart failure, atherosclerosis, and endocarditis, but she did demonstrate renal insufficiency indicative of inadequate forward output distal to the coarctation. A systolic murmur on physical examination was the only potential indicator of a diagnosis of coarctation, although in retrospect one would also have expected her lower extremity blood pressures to be discrepant from those obtained in her upper extremities. This report encourages inclusion of coarctation in a differential diagnosis for resistant hypertension, even in late adulthood.

Until recently, surgical repair was the gold standard for native coarctation and balloon valvuloplasty was the treatment of choice for recurrent or residual coarctation but both procedures result in similar rates of restenosis and aneurysm formation.14, 15 Transcatheter‐based stent implantation has emerged as a viable therapeutic option for native and recurrent coarctation as it is less invasive and demonstrates lower complication rates.16

The successful treatment in this patient highlights the efficacy of endovascular stenting as a therapy for adult native coarctation. Single‐center studies demonstrate similar excellent initial and mid‐term results.17, 18, 19 Stent implantation yields lower rates of restenosis and aneurysm formation compared with balloon angioplasty,20, 21 and the majority of complications appear to occur acutely, including stent migration.19, 22

Recently published data from the Congenital Cardiovascular Interventional Study Consortium registry demonstrated a long‐term cumulative success rate (>18–60 months post‐procedure) of 77% after successful initial stenting; however, only 21% of the patient population (n=302) completed long‐term follow up.22 Future clinical studies with larger sample sizes would shed further light on how long‐term outcomes of stenting compare with those of surgery and balloon angioplasty alone. Late results from the ongoing prospective, randomized, controlled Coarctation of the Aorta Stent Trial (COAST) will further evaluate the safety and efficacy of stents, which are currently utilized in an off‐label fashion.

Conclusion

Coarctation should be considered in the differential diagnosis of multi‐drug–resistant hypertension even in late adulthood. Endovascular stent implantation is a safe and effective treatment modality for native and recurrent coarctation in this population; however, current data are insufficient to ascertain long‐term outcomes.

J Clin Hypertens (Greenwich). 2015;17:313–316. DOI: 10.1111/jch.12495. © 2015 Wiley Periodicals, Inc.