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Part of this data was presented as a poster abstract at the Annual Scientific Sessions of The Society for Cardiac Angiography and Interventions in 2002.

Abstract
Renal artery stenosis results in Renin-Angiotensin-Aldosterone mediated hypertension and volume overload. This is unfavorable in patients with angina or heart failure. To evaluate the effect of renal artery stenting in patients with renovascular hypertension presenting with angina or heart failure, 42 patients were followed for 20 ± 11 months. The mean CCS angina class decreased from 2.5 ± 0.6 to 1.3 ± 0.6 (p < 0.05), and the mean NYHA class decreased from 2.8 ± 0.8 to 1.6 ± 0.5 (p < 0.05). The mean number of anti-hypertensive drugs remained the same (baseline = 2.4 ± 0.9; follow-up = 2.5 ± 1.0, p = ns). The blood pressure decreased significantly at follow-up (systolic BP / diastolic BP at baseline, and follow-up was 175 ± 19 / 87 ± 16 and 142 ± 18 / 73 ± 9 mm Hg, respectively). Patients who underwent both coronary and renal artery revascularization, as well as those who had only renal artery stenting, demonstrated significant clinical improvement. In conclusion, renal artery stenting for renovascular hypertension significantly improves clinical outcome in patients presenting with angina or heart failure.

Background
Renal artery stenosis results in significant hemodynamic alterations, due to activation of Renin-Angiotensin-Aldosterone Axis. This causes peripheral vasoconstriction and salt and water retention (Figure 1). Clinically, this results in systemic hypertension and increased intravascular volume.^1,2 Systemic hypertension increases myocardial oxygen demand, while volume overload worsens pulmonary congestion.3 Therefore, hemodynamic alterations accompanying renal artery stenosis are likely to worsen clinical status of patients with angina or congestive heart failure.⁴

Renal artery stenting has been demonstrated to improve blood pressure in a majority of patients presenting with refractory hypertension.^5,6 Therefore, it is logical to hypothesize that revascularization of renal artery stenosis with resulting decrease in blood pressure and intravascular volume (especially in bilateral renal artery stenosis) will improve symptoms of angina and heart failure. The current study was undertaken to evaluate the clinical effects of percutaneous renal artery revascularization in patients with renal artery stenosis, presenting with predominant symptoms of angina or congestive heart failure.

Methods
Patients referred to cardiac catheterization laboratory for suspected ischemic heart disease, who were also hypertensive while treated with at least one anti-hypertensive, underwent renal arteriography as a part of a prospective registry over a 3-year period. This substudy represents a retrospective analysis of 45 patients who presented with predominant symptoms of angina or heart failure, and were subsequently treated using renal artery stenting. Drug refractory hypertension was defined as systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg, despite one or more anti-hypertensive drugs. While published literature has defined “refractory” or “resistant” hypertension as failure to control blood pressure despite 2 or 3 drugs in optimal doses, we prespecified a lower threshold since these patients were already scheduled to undergo arterial catheterization as a part of clinical evaluation. A breakdown of patients by clinical and angiogaphic characteristics is listed in Table 1. Patients underwent coronary revascularization if clinically indicated or feasible, based on treating clinicians' discretion. Patients were followed up in ambulatory clinic for a mean of 20 + 11 months.

Results
The results at 20 + 11-month follow-up following renal artery stenting are summarized in Table 2. Improvement in clinical status (defined as decrease in Canadian Cardiovascular Society or/and New York Heart Association class at follow-up compared to baseline) was seen in 37/42 (88%) %) of patients at follow-up. The number of antihypertensive medications at baseline was 2.4 ± 0.9, and at follow up was 2.5 ± 1.0 (p = ns).

Patients Presenting with CHF: Eighteen patients (18/42 = 43%) presented with predominant CHF symptoms. Of these, seven (7/18 = 40%) underwent coronary revascularization in addition to renal artery stenting while the remaining (11/18 = 60%) underwent only renal artery stenting. The clinical outcome of these 18 patients is summarized in Table 3.

Patients Presenting with CHF and Angina: Seven patients (7/42 = 17%) presented with symptoms of both angina and CHF. Of these, three (3/7 = 43%) underwent coronary revascularization in addition to renal artery stenting, while the remaining (4/7 = 57%) underwent only renal artery stenting. The clinical outcome of these 7 patients is summarized in Table 4.

Patients Presenting with Angina: Seventeen patients (17/42 = 40%) presented with a predominant symptom of angina. Of these, eight (8/17 = 47%) underwent coronary revascularization in addition to renal artery stenting while the remaining (9/17 = 53%) underwent only renal artery stenting. The clinical outcome of these 17 patients is summarized in Table 5.

Discussion
Presence of renovascular disease is clinically important in patients with angina or heart failure, since the increased afterload and intravascular volume that results from derangement of Renin-Angiotensin-Aldosterone axis may worsen the clinical symptoms.⁷ Renovascular disease frequently co-exists with coronary artery disease, so that a significant proportion of patients are likely to be affected by both ischemic heart disease and renovascular disease.^8-10

In our study, 88% of the patients who presented with predominant symptoms of angina or heart failure and underwent renal artery stenting due to drug refractory hypertension improved clinically (CCS class or NYHA class decreased) at a mean follow-up of 20±11 months, despite same number of anti-hypertensive medications. The benefit was evident, both in patients who underwent concomitant renal and coronary revascularization, as well as those who underwent only renal artery revascularization. This suggests that relief of renal artery stenosis may independently improve the symptoms of angina or heart failure. While this is an important hypothesis, larger prospective studies are required to evalualte this hypothesis. The obvious limitations of this study are a retrospective single-center design and a small number of patients. Clearly, larger prospective randomized trials are needed to define the benefit of renal artery stent revascularization in the context of angina or congestive heart failure.

The possible mechanisms that result in clinical improvement following relief of renal artery stenosis are:

1) Reduction in blood pressure and therefore afterload;

2) Reduced intravascular volume due to decreased aldosterone production and therefore less salt and water retention;
3) Increased perfusion pressure to the ischemic kidney, and therefore improved glomerular filtration and natriuresis.

In conclusion, based on this small retrospective study, patients presenting with symptoms of angina or heart failure and drug refractory hypertension should be screened for renal artery stenosis. Patients with significant renal artery stenosis should be considered for revascularization using renal artery stenting, in addition to clinically-indicated coronary revascularization and appropriate medical therapy.

Address for correspondence: Sandeep Khosla MD FACC, Chief, Section of Cardiology, Director, Endovascular Therapeutics, Mount Sinai Hospital, 1500 South California Avenue, Chicago IL 60608. E-mail: khos@sinai.org