Clinical bene t of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure

Clinical bene t of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure Bruce H Gray a, Jeffrey W Olin b, Mary Beth Childs c, Timothy M Sullivan d and J Michael Bacharach e Abstract: Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of ash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and ash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21). Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50 85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 6 32/23 mmhg to 148/72 6 24/14 mmhg (p < 0.001). Mean number of blood pressure medications decreased from 3 6 1 to 2.5 6 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 6 1.61 to 2.65 6 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 6 1.4 and poststenting was 0.3 6 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 6 0.9 prestenting to 1.6 6 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the rst year after renal artery stenting. Renal artery stenting decreased the frequency of congestive heart failure, ash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or ash pulmonary edema. Key words: angioplasty; congestive heart failure; renal artery stenosis; renovascular hypertension; stenting Introduction Atherosclerotic renal artery stenosis (RAS) is a frequent occurrence in patients who have peripheral arterial disease and coronary disease. 1 3 RAS may result in dif cult-to-control hypertension or unexplained azotemia. 4 8 In addition, there have been several case reports and small series describing patients with bilateral RAS or its equivalent, RAS to a solitary functioning kidney, who present with a Department of Vascular Medicine and Surgery, Greenville Hospital System Greenville, SC, USA; b Division of Cardiovascular Medicine, Mount Sinai School of Medicine, New York, NY, USA; c Frances Payne School of Nursing, Case Western Reserve University, Cleveland, OH, USA; d Divison of Vascular Surgery, Mayo Clinic Foundation, Rochester, MN, USA; e The North Central Heart Hospital, Sioux Falls, SD, USA Address for correspondence: Bruce H Gray, Department of Vascular Medicine, Greenville Hospital System, 890 West Faris Road, Greenville, SC 29605, USA. Tel: +1 864 455 7886; Fax: +1 864 455 7082: E-mail: bhgray@ghs.org Dr Christopher White served as guest editor for this paper. Ó Arnold 2002 recurrent congestive heart failure (CHF) or ash pulmonary edema. 9 1 6 Many of these patients have bene tted from percutaneous transluminal angioplasty, stent implantation 9,1 1 1 5 or surgical revascularization. 9,1 6 This report describes the consequences of renal artery angioplasty and stenting in a subgroup of patients with episodes of ash pulmonary edema or recurrent and refractory CHF. Methods and patients All patients undergoing renal artery angioplasty and stenting in the Cleveland Clinic Foundation s peripheral intervention laboratory were prospectively entered into a peripheral vascular registry. Between 1991 and 1997, 207 patients underwent stenting of the renal arteries for renovascular hypertension, azotemia, or CHF secondary to atherosclerotic RAS. Thirty-nine of these patients had recurrent episodes of CHF and/or ash pulmonary edema, and form the basis of this report. This represented 19% of all patients 10.1191/1358863x02vm456oa

276 BH Gray et al undergoing renal artery stenting in the peripheral interventional laboratory. Patient characteristics Patients were suspected of having RAS based upon the usual clinical clues. 1 7 Duplex ultrasound of the renal arteries was the initial method of noninvasive evaluation in the majority of cases. Details related to this technique have been previously published. 1 8 Demographic characteristics are shown in Table 1. Severe RAS was de ned as an angiographic luminal diameter reduction of >70% with a signi - cant pressure gradient (>20 mmhg). 1 9 Of 18 patients (46%) with bilateral RAS, 12 underwent bilateral stent placement. Six had unilateral renal artery stenting. In these six patients the nontreated kidneys were small (<7 cm) or had severe parenchymal renal artery disease. Twenty-one patients had a stent implanted in a renal artery supplying a solitary functioning kidney. Eleven patients (28%) had prior coronary artery bypass grafting (CABG) and six had prior myocardial infarction. Active myocardial ischemia, prior to renal intervention, was excluded using functional and hematologic testing. All had recurrent episodes of CHF and/or ash pulmonary edema despite maximal medical therapy. Twenty of 39 patients (51%) had normal or mildly impaired left ventricular (LV) function on echocardiogram prior to intervention. Twelve patients (31%) had moderate and seven patients (18%) had severe systolic LV dysfunction prior to stent implantation. Ten patients had repeat echocardiography after intervention with no interval change. Technical method of renal artery angioplasty and stenting Percutaneous access was obtained from the common femoral (8 French) or brachial (7 French) artery. A ush diagnostic arteriogram of the aorta and renal artery was done using appropriate oblique angles. A selective catheter (Sos Omni, Cobra, or multipurpose catheter; Angiodynamics, Queensbury, NY, USA) was used to cannulate the renal artery and assess the pressure gradient across the stenosis. A pressure gradient of at least 20 mmhg was deemed signi cant. 1 9 Aqueous heparin was given to establish an ACT of 250 seconds. The RAS was predilated with either a 5 or 6 mm noncompliant balloon. The optimum oblique arteriographic angle was determined, enabling precise placement of a balloon expandable Palmaz stent (Cordis Corporation, Miami, FL, USA) at the renal ostium. The shortest length of stent (P154 or P104) was selected to cover the lesion. The artery was then maximally dilated using a non-compliant balloon to a pressure of 6 12 atmospheres using the distal renal artery diameter for reference. Resolution of the Table 1 failure. Renal artery stenting for control of congestive heart Demographic characteristics (n = 39) Mean age (range) 69.9 (50 85) years Male 16 (41%) Female 23 (59%) Prior CABG 11 (28%) Prior myocardial infarction 6 (15%) Bilateral RAS 18 (46%) RAS to solitary kidney 21 (54%) pressure gradient across the lesion was veri ed prior to performing a completion arteriogram. De nitions Improvement in blood pressure was de ned as a decrease in one category according to the report of the Joint National Committee VI on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2 0 Blood pressures were recorded in the sitting position after 5 minutes of rest. The last blood pressure reading obtained in the outpatient clinic prior to renal artery stenting was used as the pre-blood pressure measurement. The blood pressure reading at the latest follow up was used as the post-blood pressure measurement. Any medication that could lower blood pressure was listed as an antihypertensive medication, even if used for cardiac indications. Improvement or worsening in renal function was de ned as a 20% decrease or increase, respectively, in serum creatinine. The values immediately preintervention and at the latest follow up were used for comparative purposes. Patients were followed with serial duplex ultrasound at six-month intervals for the rst year and yearly thereafter. If >60% stenosis was identi ed by duplex ultrasound examination, patients underwent angiographic and hemodynamic evaluation. Statistical analysis The pre and postprocedure comparisons of patients utilized the Wilcoxon rank sum test. Comparisons of ordered categories (i.e., creatinine improvement versus baseline renal function) utilized the Mantel Haenszel chi-squared test. Kaplan Meier estimates were computed to provide survival rates at various intervals. Results Blood pressure The mean 6 SD blood pressure prerenal artery stenting was 174/85 6 32/23 mmhg compared to 148/72 6 24/14 mmhg postrenal artery stenting (p < 0.001). There was a statistically signi cant decrease in the number of blood pressure medications (3.0 6 1 to 2.5 6 1) necessary after renal artery stenting (p = 0.006). Twenty-eight patients (72%) demonstrated an improvement in blood pressure control. Six patients who were normotensive (BP: mean 128/66 6 9/5 mmhg; range: 110 130/48 70 mmhg) preprocedure had an elevation in their systolic blood pressure posttreatment (BP: mean 156/74 6 14/8 mmhg; range: 130 172/46 84 mmhg). Renal function The mean 6 SD serum creatinine prior to renal artery stenting was 3.2 6 1.6 mg/dl compared to 2.7 6 1.9 mg/dl postprocedure (p = 0.06). Table 2 demonstrates the serum creatinine values in a group of patients who improved (20 of 39 patients, 51%), remained unchanged (10 of 39 patients, 26%) or worsened (nine of 39 patients, 23%). Seven of 12 patients (58%) with a serum creatinine of 2.0 2.9, ve of eight patients (63%) with a serum creatinine of 3.0 3.9 and six of 10 patients (60%) with a serum creatinine $4.0 demonstrated improvement in renal function after renal artery stenting.

Renal artery stenting for CHF 277 Table 2 Effects of renal artery stenting on renal function. Serum creatinine Serum creatinine Serum creatinine improved unchanged worse [20/39 (51.4%)] [10/39 (25.6%)] [9/39 (23%)] pre post pre post pre post 1.4 1.1 1.1 1.1 1.6 3.7 1.7 1.3 1.4 1.7 1.6 2.3 2.0 1.4 1.5 1.3 2.0 2.4 2.1 1.2 1.6 1.4 2.2 3.2 2.2 1.5 1.8 1.5 3.7 5.4 2.2 1.5 2.5 2.6 4.1 6.7 2.7 1.3 2.6 2.5 4.3 ESRD 2.7 1.7 2.6 2.4 5.5 ESRD 3.0 2.0 3.4 2.8 7.9 ESRD 3.1 1.4 3.6 4.0 3.2 2.5 3.5 2.8 3.7 1.6 3.7 2.9 4.0 2.7 4.2 2.8 4.4 2.2 5.3 2.2 5.3 3.1 7.8 1.3 ERSD, end-stage renal disease. Prior to renal artery stenting, only six of 39 patients (15%) were receiving angiotensin converting enzyme (ACE) inhibitors whereas 19 of 39 patients (49%) received ACE inhibitors after renal artery stenting (p = 0.004). Table 3 shows the distribution of ACE inhibitor use based upon LV function by echocardiography prior to renal artery stenting. While none of the patients with severe LV dysfunction prior to renal artery stenting were able to tolerate ACE inhibitors, four patients tolerated ACE inhibitors well postrenal artery stent placement. Congestive heart failure Despite recurrent episodes of ash pulmonary edema and CHF, 51% of patients had normal or mildly impaired LV function. Thirteen of 39 patients (33%) had a systolic blood pressure <160 mmhg at the time of CHF presentation. The mean 6 SD number of hospital admissions in the preceding year due to congestive heart failure prior to renal artery stent placement was 2.4 6 1.4 (range of 1 6). The mean number of hospitalizations postprocedure was 0.3 6 0.7 (range 0 3) throughout the entire followup period (mean Table 3 Left ventricular function and ACE inhibitor use. LV by n AGE inhibitor use echocardiography Prestent Normal 15 5 5 Mild 5 0 3 Moderate 12 1 4 Severe 7 0 7 Poststent Total 39 6 (15%) 19 (49%) p = 0.004 21.3 months), p < 0.001. Table 4 shows the number of hospitalizations before and after renal artery stenting. Thirty of 39 patients (77%) had no hospitalizations for CHF after renal artery stent implantation during the period of follow up. The New York Heart Association Functional Class decreased from 2.9 6 0.9 before renal artery stent placement to 1.5 6 0.9 after-renal artery stent placement (p < 0.001). The American Heart Association Functional Class improved in 23 of 30 patients (77%) and remained stable in seven patients. Restenosis Four patients (four of 51 arteries, 8%) had >60% stenosis on duplex ultrasound during follow up. This was con rmed with selective arteriography and shown to be in-stent hyperplasia. All patients underwent repeat angioplasty and stenting with excellent results and no evidence of recurrent restenosis at the latest follow up. Follow up The mean period of follow up for the entire cohort was 21.3 months (range 1 61 months). Nine patients died during the follow up from cardiovascular causes. Eight of the nine patients died within one year. Seven of these nine patients (78%) had moderate to severe LV dysfunction on echocardiography at baseline. This compares to 12 of the 30 living patients (40%) who had moderate to severe LV dysfunction. Using Kaplan Meier estimates the mean 6 SE demonstrated that 95 6 4% were alive at one month, 87 6 5% at six months, 77 6 7% at 12 months, 77 6 7% at 24 months, and 72 6 8% at 36 months. Discussion RAS is known to cause hypertension and azotemia that can lead to end-stage renal disease. 5 Patients with hypertension who present with clinical symptoms of CHF and normal LV function by echocardiography are often thought to have diastolic dysfunction. 2 1 However, serial echocardiography merely excludes systolic dysfunction, regional wall motion abnormalities, or mitral regurgitation as contributory rather than proving hypertension-induced diastolic dysfunction as the etiologic mechanism. 2 2 We have shown that a group of patients with RAS experience episodes of ash pulmonary edema and recurrent CHF. Furthermore, endovascular treatment of the RAS led to marked cardiovascular bene t. This bene t was evidenced by improved blood pressure control, Table 4 Effects of renal artery stenting on control of congestive heart failure. Hospitalizations Before stenting After stenting for CHF n (%) N (%) 0 31 (79.5) 1 13 (33.3) 6 (15.4) 2 13 (33.9) 1 (2.6) 3 6 (15.4) 1 (2.6) 4 3 (7.7) 5 2 (5.1) 6 2 (5.1)

278 BH Gray et al stable or improved azotemia, and less frequent hospitalization for CHF. The mechanism for RAS inducing ash pulmonary edema is unclear. Pickering et al 9 described 11 patients with RAS who presented with pulmonary edema that resolved after revascularization (PTA-8, bypass-3). The overall incidence of pulmonary edema in their patients with renal artery disease was 23%, not dissimilar to our 19%. Most (nine of 11) of their patients had bilateral disease or stenosis of the artery to a solitary kidney as was seen in our series (39 of 39). This suggests that the entire renal parenchyma must be ischemic. This may predispose the patient to CHF by signi cant volume expansion. This pathologic process is induced by an initial elevation in renin, angiotension II and aldosterone causing substantial salt and water retention. These patients cannot adequately excrete this salt and water load because of reduced pressure naturesis. 4,5 There are many studies demonstrating that intervention (percutaneous transluminal angioplasty, stent implantation and surgical revascularization) is effective in improving blood pressure control and in preserving renal function. 1 1,2 3 3 0 Messina et al, 1 6 detailed the surgical treatment for 17 patients with recurrent pulmonary edema caused by bilateral renal artery disease or disease to a solitary functioning kidney. Prior to revascularization the mean blood pressure was 207/110 mmhg and serum creatinine was 3.8 mg/dl. Echocardiography showed normal LV function in 65% of these patients. After revascularization, which included bypass (94%), angioplasty (6%), and contralateral nephrectomy (41%), the blood pressure improved in all patients and the serum creatinine improved to a mean of 1.7 mg/dl at a mean follow up of 2.4 years. Our data showed that when treating patients for recurrent and resistant CHF, the blood pressure was improved in 82% of patients. Paradoxically, six patients postintervention actually had an increase in blood pressure following percutaneous revascularization. Similar blood pressure changes were seen in each of these patients with a 20 42 mmhg increase in systolic pressure irrespective of LV function (three had severe and three had mild LV dysfunction). The mechanism of this is not known. It is unlikely that progressive renal parenchymal disease led to this blood pressure change (i.e., contrast nephropathy, atheroemboli) considering renal function remained stable or improved throughout follow up in these six patients. A large number of patients in the current series demonstrated an improvement in renal function (Table 2). Improvement occurred in some patients with advanced azotemia. Six of 10 patients with a serum creatinine greater than 4.0 mg/dl signi cantly improved. The concept promulgated by some investigators 3 1 that renal revascularization is ineffective in those with advanced renal dysfunction is not supported by these ndings. In these patients who progressed to end-stage renal disease, their serum creatinine prior to intervention ranged from 4.1 to 7.9 mg/dl. On the other hand, there were six patients with a serum creatinine prior to intervention ranging from 4.0 to 7.8 mg/dl who demonstrated substantial improvement after renal artery stenting (1.3 3.1 mg/dl) (Table 2). No patient characteristic was identi ed as predictive of outcome. Four of the 10 patients had moderate to severe LV dysfunction. There are several possible pathogenetic mechanisms for CHF in patients with bilateral RAS or stenosis to a solitary functioning kidney. Some patients have poorly controlled hypertension or surges in blood pressure that may explain their cardiac decompensation. However, in one third of the patients, there was no documentation of poor blood pressure control prior to or at the time of presentation of CHF. Therefore, good blood pressure control should not dissuade against the possible diagnosis of RAS. While unilateral RAS is a renin-mediated form of hypertension, bilateral disease or disease to a solitary functioning kidney is volume mediated in the chronic state. 4,5 These patients are often volume expanded, thus explaining CHF at least in some patients. As noted, however, half of the patients had normal systolic LV function on echocardiography. Those patients with preserved systolic function may have diastolic dysfunction leading to a noncompliant LV mediated through the complex interaction between the renin-angiotensin system and the neurohormonal system. 3 2 Another potential mechanism of improvement was our ability to use ACE inhibitors after renal artery stenting. Many of these patients had moderate to severe systolic dysfunction; the use of ACE inhibitors in these patients with bilateral RAS or stenosis to a solitary functioning kidney induced worsening of renal function. After stenting we were able to utilize safely ACE inhibitors in many patients with moderate to severe LV dysfunction. ACE inhibitors and the newer class of angiotension II receptor antagonists have been shown to prevent cardiovascular morbidity and death. The bene ts seem to extend beyond a reduction in blood pressure. 3 3,3 4 Evaluation for the presence of RAS may be particularly bene cial in patients intolerant (worsening azotemia) to ACE inhibitors. Most patients who died within one year of intervention had moderate or severe CHF. Renal artery intervention did not seem to change the echocardiogram for those undergoing repeat study. This seems to be a consistent nding for CHF patients in general. 1 5,1 6 Limitations This is a nonrandomized, nonblinded trial and there may have been selection and treatment bias in that we only stented those patients who were referred to us for suspected renal artery disease. However, all of these patients failed an aggressive medical regimen for CHF. The medical care was provided by multiple physicians, which introduces variability in medical treatment. Only a minority of our patients had a follow-up echocardiogram. Ideally we would have liked to have had repeat echocardiograms in all patients. While there was a statistically signi cant decrease in hospitalizations, the numbers are too small to draw any conclusions on mortality bene ts. Conclusion In patients with recurrent heart failure and bilateral RAS or its equivalent, episodes of CHF and the number of hospitalizations are decreased with renal artery stenting. Patients with ash pulmonary edema or unexplained recurrent bouts of CHF (irrespective of LV function) who do not have active cardiac ischemia should be evaluated for the presence of RAS. These data support the use of endovascular stenting to treat RAS with the expectation of improved

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