Vascular

In their article in this issue of the Cleveland Clinic Journal of Medicine, Kabach et al answer no to the question of whether stenting of severe renal artery stenosis improves outcomes compared with medical therapy alone.¹ They review the findings of four key studies^2–5 published between 2003 and 2014 and conclude that, in patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting with medical therapy can improve blood pressure control but has no significant impact on cardiovascular or mortality outcomes.¹

See related article

Furthermore, the authors state that in view of the risk of complications associated with stenting, medical management should continue to be the first-line therapy.¹ Indeed, the ASTRAL study (Angioplasty and Stenting for Renal Artery Lesions) investigators found substantial risks without evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.³

Nevertheless, I believe that this procedure may benefit certain patients.

MAYO CLINIC COHORT STUDY

In 2008, our group at Mayo Clinic Health system in Eau Claire, Wisconsin, published the results of a prospective cohort study in 26 patients with renal artery stenosis and chronic kidney disease who presented with rapidly worsening renal failure (defined as an increase in serum creatinine of ≥ 25%) while receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB).^6,7

These drugs—inhibitors of the renin-angiotensin-aldosterone system—slow the progression of chronic kidney disease but can acutely worsen renal function, especially in patients with renal artery stenosis, and withdrawing them in this situation was the focus of our study.

The patients (10 men and 16 women) ranged in age from 63 to 87 (mean age 75.3).

At enrollment, the ACE inhibitors and ARBs were discontinued, standard nephrologic care was applied, and the glomerular filtration rate (estimated by the Modification of Diet in Renal Disease Study equation) was monitored. After at least 2 weeks, percutaneous renal angioplasty with stent placement was considered if the patient met any of the following criteria:

• Persistence of renal failure
• Flash pulmonary edema
• Uncontrolled hypertension despite the use of at least three antihypertensive medications.

Nine patients underwent percutaneous angioplasty and stenting and 17 did not. The procedure was done on one renal artery in 8 patients and both renal arteries in 1. Indications for the procedure were recent worsening of renal failure in 8 patients and recent worsening renal failure together with symptomatic flash pulmonary edema in 1 patient. (Flash pulmonary edema is the only class I recommendation for percutaneous renal angioplasty in the 2006 joint guidelines of the American College of Cardiology and the American Heart Association.⁸) As noted above, all the patients were experiencing acute exacerbation of chronic kidney disease at the time.

We found clear evidence of additional improved and sustained renal function in the patients who underwent percutaneous renal angioplasty and stenting compared with the patients who did not (Figures 1 and 2).^6,7

In an editorial⁹ following publication of the ASTRAL study, our group reported a subsequent 82-month analysis of our 26-patient cohort completed in June 2009. In the 7 surviving patients who had undergone percutaneous renal angioplasty and stenting, the estimated glomerular filtration rate had increased from 27.4 mL/min/1.73 m² (± 12.7, range 11–47) at baseline to 50.3 (± 21.7, range 23–68) (P = .018) after 46.9 months.

PATIENT NUMBER 13

To illustrate how percutaneous renal angioplasty and stenting can reverse recently worsening renal failure in renal artery stenosis, I would like to discuss in greater detail a patient from our two previous reports.^6,7

Patient 13, a 67-year-old woman with hypertension, was referred to our nephrology service in September 2004 to consider starting hemodialysis for symptomatic renal failure. Her serum creatinine had increased to 3.4 mg/dL from a previous baseline level of 2.0 mg/dL, and she also had worsening anemia and hyperkalemia. She had been taking lisinopril 10 mg/day for the last 12 months. Magnetic resonance angiography revealed high-grade (> 95%) bilateral renal artery stenosis with an atrophic left kidney.

Lisinopril was promptly discontinued, and within 2 weeks her serum creatinine level had decreased by more than 0.5 mg/dL. In mid-November 2004, she underwent right renal artery angioplasty with stent placement. After that, her serum creatinine decreased further, and 3 months later it had dropped to 1.6 mg/dL. The value continued to improve, with the lowest measurement of 1.1 mg/dL, equivalent to an estimated glomerular filtration rate of 51 mL/min/1.73 m². This was in May 2006, 19 months after stopping lisinopril and 17 months after angioplasty and stenting. The last available serum creatinine level (August 2006) was 1.2 mg/dL, equivalent to an estimated glomerular filtration rate of 45 mL/min/1.73 m² (Figure 1). Unfortunately, the patient died of metastatic lung cancer in December of that year.

Also of note, the patient who underwent angioplasty because of recurrent flash pulmonary edema had no recurrences of it afterward.

We concluded that, in patients with hemodynamically significant renal artery stenosis presenting with acutely worsening renal failure, renal angioplasty with stenting has the potential to reverse renal failure, improve blood pressure control, and stop flash pulmonary edema.^6–8

In severe renal artery stenosis, no one treatment fits all

Notably, all patients in our study who underwent renal angioplasty with stenting had new-onset acute renal injury as defined by an increase in the baseline serum creatinine of more than 25% during the 3 months before stent placement.^6–8 Patients in the STAR,² HERCULES,⁴ and CORAL⁵ studies had renal artery stenosis but otherwise stable chronic kidney disease at the time of enrollment. In the ASTRAL study,³ 12% of the patients had acute kidney injury on study enrollment, defined as an increase in the serum creatinine level of more than 20% or of more than 1.13 mg/dL.³

While we strongly agree with aggressive yet monitored medical therapy for patients with hemodynamically significant renal artery stenosis, I posit that selected patients do indeed derive significant clinical benefits from renal angioplasty and stenting. Our group’s prospective individual-patient-level data support the paradigm that angioplasty with stenting is useful in patients with renal artery stenosis who experience “acute-on-chronic” kidney disease.

The pathophysiology of renal artery stenosis and the progression of chronic kidney disease are complex, and many factors affect patient outcomes and response to treatment. Thus, the message is that treatment of severe renal artery stenosis must be individualized.^9–11 No one treatment fits all.^10,11

In their article in this issue of the Cleveland Clinic Journal of Medicine, Kabach et al answer no to the question of whether stenting of severe renal artery stenosis improves outcomes compared with medical therapy alone.¹ They review the findings of four key studies^2–5 published between 2003 and 2014 and conclude that, in patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting with medical therapy can improve blood pressure control but has no significant impact on cardiovascular or mortality outcomes.¹

See related article

Furthermore, the authors state that in view of the risk of complications associated with stenting, medical management should continue to be the first-line therapy.¹ Indeed, the ASTRAL study (Angioplasty and Stenting for Renal Artery Lesions) investigators found substantial risks without evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.³

Nevertheless, I believe that this procedure may benefit certain patients.

MAYO CLINIC COHORT STUDY

In 2008, our group at Mayo Clinic Health system in Eau Claire, Wisconsin, published the results of a prospective cohort study in 26 patients with renal artery stenosis and chronic kidney disease who presented with rapidly worsening renal failure (defined as an increase in serum creatinine of ≥ 25%) while receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB).^6,7

These drugs—inhibitors of the renin-angiotensin-aldosterone system—slow the progression of chronic kidney disease but can acutely worsen renal function, especially in patients with renal artery stenosis, and withdrawing them in this situation was the focus of our study.

The patients (10 men and 16 women) ranged in age from 63 to 87 (mean age 75.3).

At enrollment, the ACE inhibitors and ARBs were discontinued, standard nephrologic care was applied, and the glomerular filtration rate (estimated by the Modification of Diet in Renal Disease Study equation) was monitored. After at least 2 weeks, percutaneous renal angioplasty with stent placement was considered if the patient met any of the following criteria:

• Persistence of renal failure
• Flash pulmonary edema
• Uncontrolled hypertension despite the use of at least three antihypertensive medications.

Nine patients underwent percutaneous angioplasty and stenting and 17 did not. The procedure was done on one renal artery in 8 patients and both renal arteries in 1. Indications for the procedure were recent worsening of renal failure in 8 patients and recent worsening renal failure together with symptomatic flash pulmonary edema in 1 patient. (Flash pulmonary edema is the only class I recommendation for percutaneous renal angioplasty in the 2006 joint guidelines of the American College of Cardiology and the American Heart Association.⁸) As noted above, all the patients were experiencing acute exacerbation of chronic kidney disease at the time.

We found clear evidence of additional improved and sustained renal function in the patients who underwent percutaneous renal angioplasty and stenting compared with the patients who did not (Figures 1 and 2).^6,7

In an editorial⁹ following publication of the ASTRAL study, our group reported a subsequent 82-month analysis of our 26-patient cohort completed in June 2009. In the 7 surviving patients who had undergone percutaneous renal angioplasty and stenting, the estimated glomerular filtration rate had increased from 27.4 mL/min/1.73 m² (± 12.7, range 11–47) at baseline to 50.3 (± 21.7, range 23–68) (P = .018) after 46.9 months.

PATIENT NUMBER 13

To illustrate how percutaneous renal angioplasty and stenting can reverse recently worsening renal failure in renal artery stenosis, I would like to discuss in greater detail a patient from our two previous reports.^6,7

Patient 13, a 67-year-old woman with hypertension, was referred to our nephrology service in September 2004 to consider starting hemodialysis for symptomatic renal failure. Her serum creatinine had increased to 3.4 mg/dL from a previous baseline level of 2.0 mg/dL, and she also had worsening anemia and hyperkalemia. She had been taking lisinopril 10 mg/day for the last 12 months. Magnetic resonance angiography revealed high-grade (> 95%) bilateral renal artery stenosis with an atrophic left kidney.

Lisinopril was promptly discontinued, and within 2 weeks her serum creatinine level had decreased by more than 0.5 mg/dL. In mid-November 2004, she underwent right renal artery angioplasty with stent placement. After that, her serum creatinine decreased further, and 3 months later it had dropped to 1.6 mg/dL. The value continued to improve, with the lowest measurement of 1.1 mg/dL, equivalent to an estimated glomerular filtration rate of 51 mL/min/1.73 m². This was in May 2006, 19 months after stopping lisinopril and 17 months after angioplasty and stenting. The last available serum creatinine level (August 2006) was 1.2 mg/dL, equivalent to an estimated glomerular filtration rate of 45 mL/min/1.73 m² (Figure 1). Unfortunately, the patient died of metastatic lung cancer in December of that year.

Also of note, the patient who underwent angioplasty because of recurrent flash pulmonary edema had no recurrences of it afterward.

We concluded that, in patients with hemodynamically significant renal artery stenosis presenting with acutely worsening renal failure, renal angioplasty with stenting has the potential to reverse renal failure, improve blood pressure control, and stop flash pulmonary edema.^6–8

In severe renal artery stenosis, no one treatment fits all

Notably, all patients in our study who underwent renal angioplasty with stenting had new-onset acute renal injury as defined by an increase in the baseline serum creatinine of more than 25% during the 3 months before stent placement.^6–8 Patients in the STAR,² HERCULES,⁴ and CORAL⁵ studies had renal artery stenosis but otherwise stable chronic kidney disease at the time of enrollment. In the ASTRAL study,³ 12% of the patients had acute kidney injury on study enrollment, defined as an increase in the serum creatinine level of more than 20% or of more than 1.13 mg/dL.³

While we strongly agree with aggressive yet monitored medical therapy for patients with hemodynamically significant renal artery stenosis, I posit that selected patients do indeed derive significant clinical benefits from renal angioplasty and stenting. Our group’s prospective individual-patient-level data support the paradigm that angioplasty with stenting is useful in patients with renal artery stenosis who experience “acute-on-chronic” kidney disease.

The pathophysiology of renal artery stenosis and the progression of chronic kidney disease are complex, and many factors affect patient outcomes and response to treatment. Thus, the message is that treatment of severe renal artery stenosis must be individualized.^9–11 No one treatment fits all.^10,11

In their article in this issue of the Cleveland Clinic Journal of Medicine, Kabach et al answer no to the question of whether stenting of severe renal artery stenosis improves outcomes compared with medical therapy alone.¹ They review the findings of four key studies^2–5 published between 2003 and 2014 and conclude that, in patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting with medical therapy can improve blood pressure control but has no significant impact on cardiovascular or mortality outcomes.¹

See related article

Furthermore, the authors state that in view of the risk of complications associated with stenting, medical management should continue to be the first-line therapy.¹ Indeed, the ASTRAL study (Angioplasty and Stenting for Renal Artery Lesions) investigators found substantial risks without evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.³

Nevertheless, I believe that this procedure may benefit certain patients.

MAYO CLINIC COHORT STUDY

In 2008, our group at Mayo Clinic Health system in Eau Claire, Wisconsin, published the results of a prospective cohort study in 26 patients with renal artery stenosis and chronic kidney disease who presented with rapidly worsening renal failure (defined as an increase in serum creatinine of ≥ 25%) while receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB).^6,7

These drugs—inhibitors of the renin-angiotensin-aldosterone system—slow the progression of chronic kidney disease but can acutely worsen renal function, especially in patients with renal artery stenosis, and withdrawing them in this situation was the focus of our study.

The patients (10 men and 16 women) ranged in age from 63 to 87 (mean age 75.3).

At enrollment, the ACE inhibitors and ARBs were discontinued, standard nephrologic care was applied, and the glomerular filtration rate (estimated by the Modification of Diet in Renal Disease Study equation) was monitored. After at least 2 weeks, percutaneous renal angioplasty with stent placement was considered if the patient met any of the following criteria:

• Persistence of renal failure
• Flash pulmonary edema
• Uncontrolled hypertension despite the use of at least three antihypertensive medications.

Nine patients underwent percutaneous angioplasty and stenting and 17 did not. The procedure was done on one renal artery in 8 patients and both renal arteries in 1. Indications for the procedure were recent worsening of renal failure in 8 patients and recent worsening renal failure together with symptomatic flash pulmonary edema in 1 patient. (Flash pulmonary edema is the only class I recommendation for percutaneous renal angioplasty in the 2006 joint guidelines of the American College of Cardiology and the American Heart Association.⁸) As noted above, all the patients were experiencing acute exacerbation of chronic kidney disease at the time.

We found clear evidence of additional improved and sustained renal function in the patients who underwent percutaneous renal angioplasty and stenting compared with the patients who did not (Figures 1 and 2).^6,7

In an editorial⁹ following publication of the ASTRAL study, our group reported a subsequent 82-month analysis of our 26-patient cohort completed in June 2009. In the 7 surviving patients who had undergone percutaneous renal angioplasty and stenting, the estimated glomerular filtration rate had increased from 27.4 mL/min/1.73 m² (± 12.7, range 11–47) at baseline to 50.3 (± 21.7, range 23–68) (P = .018) after 46.9 months.

PATIENT NUMBER 13

To illustrate how percutaneous renal angioplasty and stenting can reverse recently worsening renal failure in renal artery stenosis, I would like to discuss in greater detail a patient from our two previous reports.^6,7

Patient 13, a 67-year-old woman with hypertension, was referred to our nephrology service in September 2004 to consider starting hemodialysis for symptomatic renal failure. Her serum creatinine had increased to 3.4 mg/dL from a previous baseline level of 2.0 mg/dL, and she also had worsening anemia and hyperkalemia. She had been taking lisinopril 10 mg/day for the last 12 months. Magnetic resonance angiography revealed high-grade (> 95%) bilateral renal artery stenosis with an atrophic left kidney.

Lisinopril was promptly discontinued, and within 2 weeks her serum creatinine level had decreased by more than 0.5 mg/dL. In mid-November 2004, she underwent right renal artery angioplasty with stent placement. After that, her serum creatinine decreased further, and 3 months later it had dropped to 1.6 mg/dL. The value continued to improve, with the lowest measurement of 1.1 mg/dL, equivalent to an estimated glomerular filtration rate of 51 mL/min/1.73 m². This was in May 2006, 19 months after stopping lisinopril and 17 months after angioplasty and stenting. The last available serum creatinine level (August 2006) was 1.2 mg/dL, equivalent to an estimated glomerular filtration rate of 45 mL/min/1.73 m² (Figure 1). Unfortunately, the patient died of metastatic lung cancer in December of that year.

Also of note, the patient who underwent angioplasty because of recurrent flash pulmonary edema had no recurrences of it afterward.

We concluded that, in patients with hemodynamically significant renal artery stenosis presenting with acutely worsening renal failure, renal angioplasty with stenting has the potential to reverse renal failure, improve blood pressure control, and stop flash pulmonary edema.^6–8

In severe renal artery stenosis, no one treatment fits all

Notably, all patients in our study who underwent renal angioplasty with stenting had new-onset acute renal injury as defined by an increase in the baseline serum creatinine of more than 25% during the 3 months before stent placement.^6–8 Patients in the STAR,² HERCULES,⁴ and CORAL⁵ studies had renal artery stenosis but otherwise stable chronic kidney disease at the time of enrollment. In the ASTRAL study,³ 12% of the patients had acute kidney injury on study enrollment, defined as an increase in the serum creatinine level of more than 20% or of more than 1.13 mg/dL.³

While we strongly agree with aggressive yet monitored medical therapy for patients with hemodynamically significant renal artery stenosis, I posit that selected patients do indeed derive significant clinical benefits from renal angioplasty and stenting. Our group’s prospective individual-patient-level data support the paradigm that angioplasty with stenting is useful in patients with renal artery stenosis who experience “acute-on-chronic” kidney disease.

The pathophysiology of renal artery stenosis and the progression of chronic kidney disease are complex, and many factors affect patient outcomes and response to treatment. Thus, the message is that treatment of severe renal artery stenosis must be individualized.^9–11 No one treatment fits all.^10,11

CHICAGO – Don’t automatically discontinue dual antiplatelet therapy for carotid endarterectomy because the neuroprotective effects may outweigh the bleeding risks, researchers concluded after a review of more than 28,000 patients who underwent the procedure during 2003-2014.

They found in the study that the 7,059 patients on perioperative dual antiplatelet therapy with clopidogrel (Plavix) and aspirin had about a 40% reduction in transient ischemic attacks (TIAs), strokes, and stroke-related deaths when compared with the 21,624 patients on aspirin alone.

The investigators found on multivariate analysis that bleeding bad enough for a return trip to the operating room was more common in their dual antiplatelet group (odds ratio, 1.73; P < .01), but they felt the neuroprotective effect was probably worth the “slightly increased bleeding risk.” Earlier research suggests that about half of vascular surgeons will discontinue clopidogrel a week or so before carotid endarterectomy (CEA) because of bleeding risks (Eur. J. Vasc. Endovasc. Surg. 2009;38:402-7).

“Although dual therapy increases perioperative bleeding, it confers an overall benefit by reducing stroke and death. Patients taking dual therapy at the time of CEA should continue treatment preoperatively. This study also suggests that initiating dual therapy is beneficial for asymptomatic patients,” lead investigator Dr. Douglas Jones of the New York Presbyterian Hospital in New York said at the meeting hosted by the Society for Vascular Surgery.

The team used the Society for Vascular Surgery’s (SVS) Vascular Quality Initiative database. Patients were about 70 years old on average and about 60% were men. Dual-therapy patients had more coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and diabetes.

On multivariate analysis to control for those differences, dual therapy was protective against TIA or stroke (OR, 0.60; P < .01); ipsilateral TIA or stroke (OR, 0.68; P = .05); stroke (OR, 0.62; P = .04); and stroke death (OR, 0.65; P = .03). It did not protect against myocardial infarction.

“More than 95% of patients received heparin for these cases,” said Dr. Jones, noting that protamine-reversal after the case “had the greatest protective effect” against major bleeding, which is consistent with previous reports. Protamine reversal reduced it by more than 50% (OR, 0.44; P < .01).

The results, for the most part, were similar on propensity matching of 4,548 patients on dual therapy to 4,548 on aspirin alone, all of whom had CEA after 2010. Dual-therapy patients were about twice as likely to return to the operating room for bleeding (1.3% vs. 0.7%), but also had fewer thrombotic complications (for instance, stroke 0.6% vs. 1.0% in the aspirin cohort).

Asymptomatic patients on dual therapy were again about twice as likely to return to surgery for major bleeding, but half as likely to have a stroke. Bleeding was more common in symptomatic dual therapy patients, as well, but for reasons that aren’t clear, a trend toward fewer thrombotic events in symptomatic patients on propensity matching did not reach statistical significance. “The protective effect was greatest among asymptomatic patients,” Dr. Jones said.

Patients on dual therapy were also more likely to have a drain placed, but drain placement did not protect against reoperation for bleeding (OR, 1.06; P = .75).

Dr. Jones has no disclosures. Other investigators disclosed consulting fees from Medtronic, Volcano, Bard, and AnGes.

[email protected]

CHICAGO – Don’t automatically discontinue dual antiplatelet therapy for carotid endarterectomy because the neuroprotective effects may outweigh the bleeding risks, researchers concluded after a review of more than 28,000 patients who underwent the procedure during 2003-2014.

They found in the study that the 7,059 patients on perioperative dual antiplatelet therapy with clopidogrel (Plavix) and aspirin had about a 40% reduction in transient ischemic attacks (TIAs), strokes, and stroke-related deaths when compared with the 21,624 patients on aspirin alone.

The investigators found on multivariate analysis that bleeding bad enough for a return trip to the operating room was more common in their dual antiplatelet group (odds ratio, 1.73; P < .01), but they felt the neuroprotective effect was probably worth the “slightly increased bleeding risk.” Earlier research suggests that about half of vascular surgeons will discontinue clopidogrel a week or so before carotid endarterectomy (CEA) because of bleeding risks (Eur. J. Vasc. Endovasc. Surg. 2009;38:402-7).

“Although dual therapy increases perioperative bleeding, it confers an overall benefit by reducing stroke and death. Patients taking dual therapy at the time of CEA should continue treatment preoperatively. This study also suggests that initiating dual therapy is beneficial for asymptomatic patients,” lead investigator Dr. Douglas Jones of the New York Presbyterian Hospital in New York said at the meeting hosted by the Society for Vascular Surgery.

The team used the Society for Vascular Surgery’s (SVS) Vascular Quality Initiative database. Patients were about 70 years old on average and about 60% were men. Dual-therapy patients had more coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and diabetes.

On multivariate analysis to control for those differences, dual therapy was protective against TIA or stroke (OR, 0.60; P < .01); ipsilateral TIA or stroke (OR, 0.68; P = .05); stroke (OR, 0.62; P = .04); and stroke death (OR, 0.65; P = .03). It did not protect against myocardial infarction.

“More than 95% of patients received heparin for these cases,” said Dr. Jones, noting that protamine-reversal after the case “had the greatest protective effect” against major bleeding, which is consistent with previous reports. Protamine reversal reduced it by more than 50% (OR, 0.44; P < .01).

The results, for the most part, were similar on propensity matching of 4,548 patients on dual therapy to 4,548 on aspirin alone, all of whom had CEA after 2010. Dual-therapy patients were about twice as likely to return to the operating room for bleeding (1.3% vs. 0.7%), but also had fewer thrombotic complications (for instance, stroke 0.6% vs. 1.0% in the aspirin cohort).

Asymptomatic patients on dual therapy were again about twice as likely to return to surgery for major bleeding, but half as likely to have a stroke. Bleeding was more common in symptomatic dual therapy patients, as well, but for reasons that aren’t clear, a trend toward fewer thrombotic events in symptomatic patients on propensity matching did not reach statistical significance. “The protective effect was greatest among asymptomatic patients,” Dr. Jones said.

Patients on dual therapy were also more likely to have a drain placed, but drain placement did not protect against reoperation for bleeding (OR, 1.06; P = .75).

Dr. Jones has no disclosures. Other investigators disclosed consulting fees from Medtronic, Volcano, Bard, and AnGes.

[email protected]

CHICAGO – Don’t automatically discontinue dual antiplatelet therapy for carotid endarterectomy because the neuroprotective effects may outweigh the bleeding risks, researchers concluded after a review of more than 28,000 patients who underwent the procedure during 2003-2014.

They found in the study that the 7,059 patients on perioperative dual antiplatelet therapy with clopidogrel (Plavix) and aspirin had about a 40% reduction in transient ischemic attacks (TIAs), strokes, and stroke-related deaths when compared with the 21,624 patients on aspirin alone.

The investigators found on multivariate analysis that bleeding bad enough for a return trip to the operating room was more common in their dual antiplatelet group (odds ratio, 1.73; P < .01), but they felt the neuroprotective effect was probably worth the “slightly increased bleeding risk.” Earlier research suggests that about half of vascular surgeons will discontinue clopidogrel a week or so before carotid endarterectomy (CEA) because of bleeding risks (Eur. J. Vasc. Endovasc. Surg. 2009;38:402-7).

“Although dual therapy increases perioperative bleeding, it confers an overall benefit by reducing stroke and death. Patients taking dual therapy at the time of CEA should continue treatment preoperatively. This study also suggests that initiating dual therapy is beneficial for asymptomatic patients,” lead investigator Dr. Douglas Jones of the New York Presbyterian Hospital in New York said at the meeting hosted by the Society for Vascular Surgery.

The team used the Society for Vascular Surgery’s (SVS) Vascular Quality Initiative database. Patients were about 70 years old on average and about 60% were men. Dual-therapy patients had more coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and diabetes.

On multivariate analysis to control for those differences, dual therapy was protective against TIA or stroke (OR, 0.60; P < .01); ipsilateral TIA or stroke (OR, 0.68; P = .05); stroke (OR, 0.62; P = .04); and stroke death (OR, 0.65; P = .03). It did not protect against myocardial infarction.

“More than 95% of patients received heparin for these cases,” said Dr. Jones, noting that protamine-reversal after the case “had the greatest protective effect” against major bleeding, which is consistent with previous reports. Protamine reversal reduced it by more than 50% (OR, 0.44; P < .01).

The results, for the most part, were similar on propensity matching of 4,548 patients on dual therapy to 4,548 on aspirin alone, all of whom had CEA after 2010. Dual-therapy patients were about twice as likely to return to the operating room for bleeding (1.3% vs. 0.7%), but also had fewer thrombotic complications (for instance, stroke 0.6% vs. 1.0% in the aspirin cohort).

Asymptomatic patients on dual therapy were again about twice as likely to return to surgery for major bleeding, but half as likely to have a stroke. Bleeding was more common in symptomatic dual therapy patients, as well, but for reasons that aren’t clear, a trend toward fewer thrombotic events in symptomatic patients on propensity matching did not reach statistical significance. “The protective effect was greatest among asymptomatic patients,” Dr. Jones said.

Patients on dual therapy were also more likely to have a drain placed, but drain placement did not protect against reoperation for bleeding (OR, 1.06; P = .75).

Dr. Jones has no disclosures. Other investigators disclosed consulting fees from Medtronic, Volcano, Bard, and AnGes.

[email protected]

CHICAGO – Pancreaticoduodenal and gastroduodenal artery aneurysms should be repaired at diagnosis, according to Dr. Michael Corey, a vascular surgeon at Massachusetts General Hospital in Boston.

The reason is “they rupture at small sizes. Most other small splanchnic artery aneurysms” – below 25 mm – “do not grow or rupture over time and can safely undergo surveillance imaging every 3 years,” he said at a meeting hosted by the Society for Vascular Surgery.

The insights come from Dr. Corey’s review of 264 splanchnic artery aneurysms (SAAs) treated at Massachusetts General Hospital from 1994 to 2014 .

Pancreaticoduodenal (PDA) and gastroduodenal (GDA) artery aneurysms were the most likely to cause trouble. Almost all of the 36 in the study were associated with high-grade celiac axis stenosis, and 12 (33%) were symptomatic at presentation, including 7 (19%) that had ruptured at a mean size of 27.4 mm, range 15-48 mm.

Those 7 accounted for more than half of the 13 ruptures in the study. There were also five ruptures among 95 splenic artery aneurysms – the most common aneurysm type in the study – at a mean of 42 mm, and one among 34 hepatic artery aneurysms at 40 mm. Thirty-day morbidity after rupture repair was 54% and mortality 8%.

Pancreaticoduodenal (odds ratio, 14.41; 95% confidence interval, 3.5-59.9; P = .0002) and gastroduodenal artery aneurysms (OR, 6.95; 95% CI, 1.1-45.1; P = .042) were far more predictive of rupture than aneurysm size (OR, 1.04; 95% CI, 1.01-1.08; P = .0042). The strongest predictor was type 4 Ehlers-Danlos syndrome (OR, 34.09; 95% CI, 2.4-479.8; P = .0089). Calcification, meanwhile, did not predict rupture, growth, or thrombus burden.

Dr. Corey and his colleagues reviewed Massachusetts General’s experience with SAAs because “no strong consensus exists in the literature concerning the indications for treatment; 2 cm is currently the indication for surgical treatment of asymptomatic lesions,” he said.

Two centimeters might be too aggressive in some cases. Among 176 aneurysms put under surveillance for a mean of 36.1 months, the mean aneurysm size was 16.3 mm but ranged up to 40 mm. Even so, none of them ruptured. Just 12 aneurysms grew during surveillance, and only 8 eventually needed intervention. Perhaps most “small asymptomatic lesions do not affect longevity,” Dr. Corey said. The mean aneurysm size was 31.1 mm in the 88 patients repaired within 6 months of diagnosis. Splenic, pancreaticoduodenal, gastroduodenal, and hepatic aneurysms were the most likely to be repaired early, the majority by coil embolization and other endovascular techniques. Thirty-day morbidity for intact repair was 13% and mortality 3%.

Most of the splenic artery aneurysms were asymptomatic at presentation. In the half that were watched, just six grew.

Similarly, 78 celiac artery aneurysms – the second most common in the study – all presented without symptoms. Just 3 of the 60 under surveillance grew over a mean of 43.6 months. “These aneurysms rarely change,” Dr. Corey said.

Most of the 34 hepatic artery aneurysms and 17 superior mesenteric artery (SMA) aneurysms were asymptomatic. Between both groups, 20 aneurysms were put under surveillance; growth was noted in 1, an SMA lesion.

Although there was a shift from open to endovascular repair during the study period, there were no statistically significant differences in morbidity or mortality between the two approaches.

Dr. Corey has no disclosures.

[email protected]

CHICAGO – Pancreaticoduodenal and gastroduodenal artery aneurysms should be repaired at diagnosis, according to Dr. Michael Corey, a vascular surgeon at Massachusetts General Hospital in Boston.

The reason is “they rupture at small sizes. Most other small splanchnic artery aneurysms” – below 25 mm – “do not grow or rupture over time and can safely undergo surveillance imaging every 3 years,” he said at a meeting hosted by the Society for Vascular Surgery.

The insights come from Dr. Corey’s review of 264 splanchnic artery aneurysms (SAAs) treated at Massachusetts General Hospital from 1994 to 2014 .

Pancreaticoduodenal (PDA) and gastroduodenal (GDA) artery aneurysms were the most likely to cause trouble. Almost all of the 36 in the study were associated with high-grade celiac axis stenosis, and 12 (33%) were symptomatic at presentation, including 7 (19%) that had ruptured at a mean size of 27.4 mm, range 15-48 mm.

Those 7 accounted for more than half of the 13 ruptures in the study. There were also five ruptures among 95 splenic artery aneurysms – the most common aneurysm type in the study – at a mean of 42 mm, and one among 34 hepatic artery aneurysms at 40 mm. Thirty-day morbidity after rupture repair was 54% and mortality 8%.

Pancreaticoduodenal (odds ratio, 14.41; 95% confidence interval, 3.5-59.9; P = .0002) and gastroduodenal artery aneurysms (OR, 6.95; 95% CI, 1.1-45.1; P = .042) were far more predictive of rupture than aneurysm size (OR, 1.04; 95% CI, 1.01-1.08; P = .0042). The strongest predictor was type 4 Ehlers-Danlos syndrome (OR, 34.09; 95% CI, 2.4-479.8; P = .0089). Calcification, meanwhile, did not predict rupture, growth, or thrombus burden.

Dr. Corey and his colleagues reviewed Massachusetts General’s experience with SAAs because “no strong consensus exists in the literature concerning the indications for treatment; 2 cm is currently the indication for surgical treatment of asymptomatic lesions,” he said.

Two centimeters might be too aggressive in some cases. Among 176 aneurysms put under surveillance for a mean of 36.1 months, the mean aneurysm size was 16.3 mm but ranged up to 40 mm. Even so, none of them ruptured. Just 12 aneurysms grew during surveillance, and only 8 eventually needed intervention. Perhaps most “small asymptomatic lesions do not affect longevity,” Dr. Corey said. The mean aneurysm size was 31.1 mm in the 88 patients repaired within 6 months of diagnosis. Splenic, pancreaticoduodenal, gastroduodenal, and hepatic aneurysms were the most likely to be repaired early, the majority by coil embolization and other endovascular techniques. Thirty-day morbidity for intact repair was 13% and mortality 3%.

Most of the splenic artery aneurysms were asymptomatic at presentation. In the half that were watched, just six grew.

Similarly, 78 celiac artery aneurysms – the second most common in the study – all presented without symptoms. Just 3 of the 60 under surveillance grew over a mean of 43.6 months. “These aneurysms rarely change,” Dr. Corey said.

Most of the 34 hepatic artery aneurysms and 17 superior mesenteric artery (SMA) aneurysms were asymptomatic. Between both groups, 20 aneurysms were put under surveillance; growth was noted in 1, an SMA lesion.

Although there was a shift from open to endovascular repair during the study period, there were no statistically significant differences in morbidity or mortality between the two approaches.

Dr. Corey has no disclosures.

[email protected]

CHICAGO – Pancreaticoduodenal and gastroduodenal artery aneurysms should be repaired at diagnosis, according to Dr. Michael Corey, a vascular surgeon at Massachusetts General Hospital in Boston.

The reason is “they rupture at small sizes. Most other small splanchnic artery aneurysms” – below 25 mm – “do not grow or rupture over time and can safely undergo surveillance imaging every 3 years,” he said at a meeting hosted by the Society for Vascular Surgery.

The insights come from Dr. Corey’s review of 264 splanchnic artery aneurysms (SAAs) treated at Massachusetts General Hospital from 1994 to 2014 .

Pancreaticoduodenal (PDA) and gastroduodenal (GDA) artery aneurysms were the most likely to cause trouble. Almost all of the 36 in the study were associated with high-grade celiac axis stenosis, and 12 (33%) were symptomatic at presentation, including 7 (19%) that had ruptured at a mean size of 27.4 mm, range 15-48 mm.

Those 7 accounted for more than half of the 13 ruptures in the study. There were also five ruptures among 95 splenic artery aneurysms – the most common aneurysm type in the study – at a mean of 42 mm, and one among 34 hepatic artery aneurysms at 40 mm. Thirty-day morbidity after rupture repair was 54% and mortality 8%.

Pancreaticoduodenal (odds ratio, 14.41; 95% confidence interval, 3.5-59.9; P = .0002) and gastroduodenal artery aneurysms (OR, 6.95; 95% CI, 1.1-45.1; P = .042) were far more predictive of rupture than aneurysm size (OR, 1.04; 95% CI, 1.01-1.08; P = .0042). The strongest predictor was type 4 Ehlers-Danlos syndrome (OR, 34.09; 95% CI, 2.4-479.8; P = .0089). Calcification, meanwhile, did not predict rupture, growth, or thrombus burden.

Dr. Corey and his colleagues reviewed Massachusetts General’s experience with SAAs because “no strong consensus exists in the literature concerning the indications for treatment; 2 cm is currently the indication for surgical treatment of asymptomatic lesions,” he said.

Two centimeters might be too aggressive in some cases. Among 176 aneurysms put under surveillance for a mean of 36.1 months, the mean aneurysm size was 16.3 mm but ranged up to 40 mm. Even so, none of them ruptured. Just 12 aneurysms grew during surveillance, and only 8 eventually needed intervention. Perhaps most “small asymptomatic lesions do not affect longevity,” Dr. Corey said. The mean aneurysm size was 31.1 mm in the 88 patients repaired within 6 months of diagnosis. Splenic, pancreaticoduodenal, gastroduodenal, and hepatic aneurysms were the most likely to be repaired early, the majority by coil embolization and other endovascular techniques. Thirty-day morbidity for intact repair was 13% and mortality 3%.

Most of the splenic artery aneurysms were asymptomatic at presentation. In the half that were watched, just six grew.

Similarly, 78 celiac artery aneurysms – the second most common in the study – all presented without symptoms. Just 3 of the 60 under surveillance grew over a mean of 43.6 months. “These aneurysms rarely change,” Dr. Corey said.

Most of the 34 hepatic artery aneurysms and 17 superior mesenteric artery (SMA) aneurysms were asymptomatic. Between both groups, 20 aneurysms were put under surveillance; growth was noted in 1, an SMA lesion.

Although there was a shift from open to endovascular repair during the study period, there were no statistically significant differences in morbidity or mortality between the two approaches.

Dr. Corey has no disclosures.

[email protected]

A 45-year-old woman presents with shortness of breath that has been progressively worsening for 3 weeks. She has no history of medical conditions and is taking no medications. Her blood pressure is 132/68 mm Hg, pulse 90 beats per minute, respirations 14 per minute, and oxygen saturation 95% on room air by pulse oximetry.

Physical examination reveals clear lung fields and no jugular venous distention or peripheral edema. However, she has a grade 3 of 6 continuous murmur audible over the entire precordium that does not change in intensity with respiration.

1. Which of the following is the likely cause of this patient’s cardiac murmur?

• Ventricular septal defect
• Atrial septal defect
• Ruptured sinus of Valsalva aneurysm
• Aortic regurgitation
• Patent ductus arteriosus
• Pulmonic stenosis

Table 1 summarizes the characteristics of the murmurs caused by these various cardiac defects.

Ventricular septal defect causes murmurs that are characteristically holosystolic and heard best at the lower left sternal border with radiation to the right lower sternal border, which overlies the defect.

The murmur of restrictive ventricular septal defect is most often holosystolic because the pressure difference between the ventricles is generated almost instantly at the onset of systole with a left-to-right shunt continuing throughout ventricular contraction. In contrast, nonrestrictive ventricular septal defects generally do not generate a murmur, since pressure is equalized across the defect. This left-to-right shunting may lead to right ventricular volume overload, resulting in delayed closure of the pulmonary valve and a widely split S2. Irreversible pulmonary hypertension with shunt reversal may occur if the defect remains untreated.¹

Atrial septal defect. The most characteristic feature of atrial septal defect is a fixed split S2 resulting from right ventricular volume overload due to left-to-right atrial shunting of blood flow. As flow is shunted from the left to the right atrium and subsequently into the right ventricle, ejection of excess blood through the pulmonary valve produces a midsystolic flow murmur, heard best over the left upper sternal border, that may radiate to the back.

Ruptured sinus of Valsalva aneurysm. The pressure is higher in the aorta than in the right atrium throughout the cardiac cycle, and if a shunt is created between the two structures by a ruptured sinus of Valsalva aneurysm, the blood flow across this shunt throughout the cardiac cycle produces a continuous murmur. In contrast, if a sinus of Valsalva aneurysm ruptures into the right ventricle, the murmur is accentuated in diastole and attenuated in systole, and is often associated with pounding pulses and a thrill along either the left or right sternal border.¹

Aortic regurgitation causes a diastolic murmur as blood flows retrograde into the left ventricle through the incompetent aortic valve. This murmur is usually described as a blowing, decrescendo murmur heard best at the third left intercostal space.

Patent ductus arteriosus is a communication between the descending thoracic aorta and the pulmonary artery that fails to close at birth. The hallmark murmur associated with this defect is a continuous “machine-like” murmur located at the upper left sternal border, often radiating down the left side of the sternum into the back. Of note, increasing the systemic pressure by the Valsalva maneuver or handgrip exercise will increase the diastolic component of the continuous murmur associated with ruptured sinus of Valsalva aneurysm, helping to differentiate it from patent ductus arteriosus.²

Pulmonic stenosis causes a systolic murmur heard best at the second intercostal space along the left sternal border and having a crescendo-decrescendo intensity and harsh quality. As the right ventricle takes longer to eject its blood volume through the stenotic pulmonary valve, the delay in closure between the aortic and pulmonary valve is widened, resulting in a significant splitting of the S2. In addition, any maneuver that increases preload will also increase the intensity of the murmur.³

Our patient has a murmur that is continuous, is heard across the entire precordium, and has no respiratory variation. These features are most consistent with a sinus of Valsalva aneurysm that has ruptured into the right atrium.

The 2008 update of the joint American College of Cardiology and American Heart Association guidelines⁴ recommends further evaluation of diastolic or continuous murmurs with echocardiography, as these murmurs are most often signs of a pathologic condition. In addition, echocardiography is warranted to evaluate grade 3 or higher systolic murmurs and those that are holosystolic.⁴

SINUS OF VALSALVA ANEURYSM

Sinus of Valsalva aneurysm is rare, with an incidence of 0.09% to 0.15%. From 65% to 85% are in the right coronary cusp, 10% to 30% are in the noncoronary cusp, and fewer than 5% are in the left coronary cusp.⁵

This condition is most often congenital, accounting for up to 3.5% of congenital cardiac anomalies, though it can be acquired. Formation of the aneurysm is generally related to weakening of elastic fibers and muscular tissues that progresses over time.

Many cases of sinus of Valsalva aneurysm are associated with additional cardiac defects.¹ Ventricular septal defect is the most common coexisting congenital anomaly, occurring in up to 53% of patients and frequently associated with aneurysms involving the right coronary cusp and with sinus of Valsalva aneurysm.⁶ Other congenital anomalies often accompanying sinus of Valsalva aneurysm include pulmonary stenosis, atrial septal defect, bicuspid aortic valve, tetralogy of Fallot, patent ductus arteriosus, coarctation of the aorta, and subaortic stenosis. Another associated condition is aortic regurgitation, for which more than half of affected patients eventually require aortic valve replacement.²

Acquired sinus of Valsalva aneurysm can be the result of endocarditis, trauma, surgery, cardiac catheterization, or inflammatory or degenerative processes including, rarely, tertiary syphilis.³

Sinus of Valsalva aneurysm often remains asymptomatic, but symptoms may arise if the aneurysm ruptures, resulting in intracardiac shunting or aneurysm-associated compression of adjacent cardiac structures such as coronary arteries. Rupture may be spontaneous, secondary to chest trauma or excess exertion, or iatrogenic.

Imaging studies such as echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging are essential in diagnosing and managing sinus of Valsalva aneurysm and identifying coexisting cardiac anomalies.

Rupture occurs most commonly into the right ventricle, followed in frequency by the right atrium or left atrium. Once rupture occurs, median survival is 1 to 2 years if left untreated, with death often secondary to congestive heart failure or infective endocarditis.⁷

Surgery remains the preferred approach to the treatment of ruptured sinus of Valsalva aneurysm. Operative risk is reasonably low and long-term outcomes are good. The appropriate therapy for unruptured and asymptomatic sinus of Valsalva aneurysm remains less clear.

Successful transcatheter closure of ruptured sinus of Valsalva aneurysm has been described using Amplatzer devices, a procedure that avoids sternotomy and cardiopulmonary bypass. Despite advances in percutaneous techniques, open surgery with or without aortic valve replacement remains the current standard of care.⁸

BACK TO OUR PATIENT

In the case described above, the initial diagnostic study done to evaluate the patient’s dyspnea and murmur was transthoracic echocardiography, which demonstrated a relatively preserved ejection fraction with mild aortic regurgitation and an aneurysmal structure extending from the aortic root toward the right atrium.

Transesophageal echocardiography confirmed this finding (Figure 1). Cross-sectional imaging of the aortic valve (Figure 2) showed the aneurysm arising from the noncoronary cusp and communicating with the right atrium. Color flow Doppler (Figure 3) confirmed continuous flow between the aneurysmal sinus and right atrium throughout the cardiac cycle, consistent with the continuous murmur noted on physical examination.

The aneurysm was also noted on aortography (Figure 4) obtained before the patient underwent surgery to correct it. The surgery was successful, no complications occurred, and the murmur and associated dyspnea had completely resolved at subsequent follow-up.

This case highlights the importance of imaging studies such as echocardiography in diagnosing and managing sinus of Valsalva aneurysm, and also the importance of physical examination in guiding the diagnostic evaluation and differentiating this condition from other cardiac disorders.

A 45-year-old woman presents with shortness of breath that has been progressively worsening for 3 weeks. She has no history of medical conditions and is taking no medications. Her blood pressure is 132/68 mm Hg, pulse 90 beats per minute, respirations 14 per minute, and oxygen saturation 95% on room air by pulse oximetry.

Physical examination reveals clear lung fields and no jugular venous distention or peripheral edema. However, she has a grade 3 of 6 continuous murmur audible over the entire precordium that does not change in intensity with respiration.

1. Which of the following is the likely cause of this patient’s cardiac murmur?

• Ventricular septal defect
• Atrial septal defect
• Ruptured sinus of Valsalva aneurysm
• Aortic regurgitation
• Patent ductus arteriosus
• Pulmonic stenosis

Table 1 summarizes the characteristics of the murmurs caused by these various cardiac defects.

Ventricular septal defect causes murmurs that are characteristically holosystolic and heard best at the lower left sternal border with radiation to the right lower sternal border, which overlies the defect.

The murmur of restrictive ventricular septal defect is most often holosystolic because the pressure difference between the ventricles is generated almost instantly at the onset of systole with a left-to-right shunt continuing throughout ventricular contraction. In contrast, nonrestrictive ventricular septal defects generally do not generate a murmur, since pressure is equalized across the defect. This left-to-right shunting may lead to right ventricular volume overload, resulting in delayed closure of the pulmonary valve and a widely split S2. Irreversible pulmonary hypertension with shunt reversal may occur if the defect remains untreated.¹

Atrial septal defect. The most characteristic feature of atrial septal defect is a fixed split S2 resulting from right ventricular volume overload due to left-to-right atrial shunting of blood flow. As flow is shunted from the left to the right atrium and subsequently into the right ventricle, ejection of excess blood through the pulmonary valve produces a midsystolic flow murmur, heard best over the left upper sternal border, that may radiate to the back.

Ruptured sinus of Valsalva aneurysm. The pressure is higher in the aorta than in the right atrium throughout the cardiac cycle, and if a shunt is created between the two structures by a ruptured sinus of Valsalva aneurysm, the blood flow across this shunt throughout the cardiac cycle produces a continuous murmur. In contrast, if a sinus of Valsalva aneurysm ruptures into the right ventricle, the murmur is accentuated in diastole and attenuated in systole, and is often associated with pounding pulses and a thrill along either the left or right sternal border.¹

Aortic regurgitation causes a diastolic murmur as blood flows retrograde into the left ventricle through the incompetent aortic valve. This murmur is usually described as a blowing, decrescendo murmur heard best at the third left intercostal space.

Patent ductus arteriosus is a communication between the descending thoracic aorta and the pulmonary artery that fails to close at birth. The hallmark murmur associated with this defect is a continuous “machine-like” murmur located at the upper left sternal border, often radiating down the left side of the sternum into the back. Of note, increasing the systemic pressure by the Valsalva maneuver or handgrip exercise will increase the diastolic component of the continuous murmur associated with ruptured sinus of Valsalva aneurysm, helping to differentiate it from patent ductus arteriosus.²

Pulmonic stenosis causes a systolic murmur heard best at the second intercostal space along the left sternal border and having a crescendo-decrescendo intensity and harsh quality. As the right ventricle takes longer to eject its blood volume through the stenotic pulmonary valve, the delay in closure between the aortic and pulmonary valve is widened, resulting in a significant splitting of the S2. In addition, any maneuver that increases preload will also increase the intensity of the murmur.³

Our patient has a murmur that is continuous, is heard across the entire precordium, and has no respiratory variation. These features are most consistent with a sinus of Valsalva aneurysm that has ruptured into the right atrium.

The 2008 update of the joint American College of Cardiology and American Heart Association guidelines⁴ recommends further evaluation of diastolic or continuous murmurs with echocardiography, as these murmurs are most often signs of a pathologic condition. In addition, echocardiography is warranted to evaluate grade 3 or higher systolic murmurs and those that are holosystolic.⁴

SINUS OF VALSALVA ANEURYSM

Sinus of Valsalva aneurysm is rare, with an incidence of 0.09% to 0.15%. From 65% to 85% are in the right coronary cusp, 10% to 30% are in the noncoronary cusp, and fewer than 5% are in the left coronary cusp.⁵

This condition is most often congenital, accounting for up to 3.5% of congenital cardiac anomalies, though it can be acquired. Formation of the aneurysm is generally related to weakening of elastic fibers and muscular tissues that progresses over time.

Many cases of sinus of Valsalva aneurysm are associated with additional cardiac defects.¹ Ventricular septal defect is the most common coexisting congenital anomaly, occurring in up to 53% of patients and frequently associated with aneurysms involving the right coronary cusp and with sinus of Valsalva aneurysm.⁶ Other congenital anomalies often accompanying sinus of Valsalva aneurysm include pulmonary stenosis, atrial septal defect, bicuspid aortic valve, tetralogy of Fallot, patent ductus arteriosus, coarctation of the aorta, and subaortic stenosis. Another associated condition is aortic regurgitation, for which more than half of affected patients eventually require aortic valve replacement.²

Acquired sinus of Valsalva aneurysm can be the result of endocarditis, trauma, surgery, cardiac catheterization, or inflammatory or degenerative processes including, rarely, tertiary syphilis.³

Sinus of Valsalva aneurysm often remains asymptomatic, but symptoms may arise if the aneurysm ruptures, resulting in intracardiac shunting or aneurysm-associated compression of adjacent cardiac structures such as coronary arteries. Rupture may be spontaneous, secondary to chest trauma or excess exertion, or iatrogenic.

Imaging studies such as echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging are essential in diagnosing and managing sinus of Valsalva aneurysm and identifying coexisting cardiac anomalies.

Rupture occurs most commonly into the right ventricle, followed in frequency by the right atrium or left atrium. Once rupture occurs, median survival is 1 to 2 years if left untreated, with death often secondary to congestive heart failure or infective endocarditis.⁷

Surgery remains the preferred approach to the treatment of ruptured sinus of Valsalva aneurysm. Operative risk is reasonably low and long-term outcomes are good. The appropriate therapy for unruptured and asymptomatic sinus of Valsalva aneurysm remains less clear.

Successful transcatheter closure of ruptured sinus of Valsalva aneurysm has been described using Amplatzer devices, a procedure that avoids sternotomy and cardiopulmonary bypass. Despite advances in percutaneous techniques, open surgery with or without aortic valve replacement remains the current standard of care.⁸

BACK TO OUR PATIENT

In the case described above, the initial diagnostic study done to evaluate the patient’s dyspnea and murmur was transthoracic echocardiography, which demonstrated a relatively preserved ejection fraction with mild aortic regurgitation and an aneurysmal structure extending from the aortic root toward the right atrium.

Transesophageal echocardiography confirmed this finding (Figure 1). Cross-sectional imaging of the aortic valve (Figure 2) showed the aneurysm arising from the noncoronary cusp and communicating with the right atrium. Color flow Doppler (Figure 3) confirmed continuous flow between the aneurysmal sinus and right atrium throughout the cardiac cycle, consistent with the continuous murmur noted on physical examination.

The aneurysm was also noted on aortography (Figure 4) obtained before the patient underwent surgery to correct it. The surgery was successful, no complications occurred, and the murmur and associated dyspnea had completely resolved at subsequent follow-up.

This case highlights the importance of imaging studies such as echocardiography in diagnosing and managing sinus of Valsalva aneurysm, and also the importance of physical examination in guiding the diagnostic evaluation and differentiating this condition from other cardiac disorders.

A 45-year-old woman presents with shortness of breath that has been progressively worsening for 3 weeks. She has no history of medical conditions and is taking no medications. Her blood pressure is 132/68 mm Hg, pulse 90 beats per minute, respirations 14 per minute, and oxygen saturation 95% on room air by pulse oximetry.

Physical examination reveals clear lung fields and no jugular venous distention or peripheral edema. However, she has a grade 3 of 6 continuous murmur audible over the entire precordium that does not change in intensity with respiration.

1. Which of the following is the likely cause of this patient’s cardiac murmur?

• Ventricular septal defect
• Atrial septal defect
• Ruptured sinus of Valsalva aneurysm
• Aortic regurgitation
• Patent ductus arteriosus
• Pulmonic stenosis

Table 1 summarizes the characteristics of the murmurs caused by these various cardiac defects.

Ventricular septal defect causes murmurs that are characteristically holosystolic and heard best at the lower left sternal border with radiation to the right lower sternal border, which overlies the defect.

The murmur of restrictive ventricular septal defect is most often holosystolic because the pressure difference between the ventricles is generated almost instantly at the onset of systole with a left-to-right shunt continuing throughout ventricular contraction. In contrast, nonrestrictive ventricular septal defects generally do not generate a murmur, since pressure is equalized across the defect. This left-to-right shunting may lead to right ventricular volume overload, resulting in delayed closure of the pulmonary valve and a widely split S2. Irreversible pulmonary hypertension with shunt reversal may occur if the defect remains untreated.¹

Atrial septal defect. The most characteristic feature of atrial septal defect is a fixed split S2 resulting from right ventricular volume overload due to left-to-right atrial shunting of blood flow. As flow is shunted from the left to the right atrium and subsequently into the right ventricle, ejection of excess blood through the pulmonary valve produces a midsystolic flow murmur, heard best over the left upper sternal border, that may radiate to the back.

Ruptured sinus of Valsalva aneurysm. The pressure is higher in the aorta than in the right atrium throughout the cardiac cycle, and if a shunt is created between the two structures by a ruptured sinus of Valsalva aneurysm, the blood flow across this shunt throughout the cardiac cycle produces a continuous murmur. In contrast, if a sinus of Valsalva aneurysm ruptures into the right ventricle, the murmur is accentuated in diastole and attenuated in systole, and is often associated with pounding pulses and a thrill along either the left or right sternal border.¹

Aortic regurgitation causes a diastolic murmur as blood flows retrograde into the left ventricle through the incompetent aortic valve. This murmur is usually described as a blowing, decrescendo murmur heard best at the third left intercostal space.

Patent ductus arteriosus is a communication between the descending thoracic aorta and the pulmonary artery that fails to close at birth. The hallmark murmur associated with this defect is a continuous “machine-like” murmur located at the upper left sternal border, often radiating down the left side of the sternum into the back. Of note, increasing the systemic pressure by the Valsalva maneuver or handgrip exercise will increase the diastolic component of the continuous murmur associated with ruptured sinus of Valsalva aneurysm, helping to differentiate it from patent ductus arteriosus.²

Pulmonic stenosis causes a systolic murmur heard best at the second intercostal space along the left sternal border and having a crescendo-decrescendo intensity and harsh quality. As the right ventricle takes longer to eject its blood volume through the stenotic pulmonary valve, the delay in closure between the aortic and pulmonary valve is widened, resulting in a significant splitting of the S2. In addition, any maneuver that increases preload will also increase the intensity of the murmur.³

Our patient has a murmur that is continuous, is heard across the entire precordium, and has no respiratory variation. These features are most consistent with a sinus of Valsalva aneurysm that has ruptured into the right atrium.

The 2008 update of the joint American College of Cardiology and American Heart Association guidelines⁴ recommends further evaluation of diastolic or continuous murmurs with echocardiography, as these murmurs are most often signs of a pathologic condition. In addition, echocardiography is warranted to evaluate grade 3 or higher systolic murmurs and those that are holosystolic.⁴

SINUS OF VALSALVA ANEURYSM

Sinus of Valsalva aneurysm is rare, with an incidence of 0.09% to 0.15%. From 65% to 85% are in the right coronary cusp, 10% to 30% are in the noncoronary cusp, and fewer than 5% are in the left coronary cusp.⁵

This condition is most often congenital, accounting for up to 3.5% of congenital cardiac anomalies, though it can be acquired. Formation of the aneurysm is generally related to weakening of elastic fibers and muscular tissues that progresses over time.

Many cases of sinus of Valsalva aneurysm are associated with additional cardiac defects.¹ Ventricular septal defect is the most common coexisting congenital anomaly, occurring in up to 53% of patients and frequently associated with aneurysms involving the right coronary cusp and with sinus of Valsalva aneurysm.⁶ Other congenital anomalies often accompanying sinus of Valsalva aneurysm include pulmonary stenosis, atrial septal defect, bicuspid aortic valve, tetralogy of Fallot, patent ductus arteriosus, coarctation of the aorta, and subaortic stenosis. Another associated condition is aortic regurgitation, for which more than half of affected patients eventually require aortic valve replacement.²

Acquired sinus of Valsalva aneurysm can be the result of endocarditis, trauma, surgery, cardiac catheterization, or inflammatory or degenerative processes including, rarely, tertiary syphilis.³

Sinus of Valsalva aneurysm often remains asymptomatic, but symptoms may arise if the aneurysm ruptures, resulting in intracardiac shunting or aneurysm-associated compression of adjacent cardiac structures such as coronary arteries. Rupture may be spontaneous, secondary to chest trauma or excess exertion, or iatrogenic.

Imaging studies such as echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging are essential in diagnosing and managing sinus of Valsalva aneurysm and identifying coexisting cardiac anomalies.

Rupture occurs most commonly into the right ventricle, followed in frequency by the right atrium or left atrium. Once rupture occurs, median survival is 1 to 2 years if left untreated, with death often secondary to congestive heart failure or infective endocarditis.⁷

Surgery remains the preferred approach to the treatment of ruptured sinus of Valsalva aneurysm. Operative risk is reasonably low and long-term outcomes are good. The appropriate therapy for unruptured and asymptomatic sinus of Valsalva aneurysm remains less clear.

Successful transcatheter closure of ruptured sinus of Valsalva aneurysm has been described using Amplatzer devices, a procedure that avoids sternotomy and cardiopulmonary bypass. Despite advances in percutaneous techniques, open surgery with or without aortic valve replacement remains the current standard of care.⁸

BACK TO OUR PATIENT

In the case described above, the initial diagnostic study done to evaluate the patient’s dyspnea and murmur was transthoracic echocardiography, which demonstrated a relatively preserved ejection fraction with mild aortic regurgitation and an aneurysmal structure extending from the aortic root toward the right atrium.

Transesophageal echocardiography confirmed this finding (Figure 1). Cross-sectional imaging of the aortic valve (Figure 2) showed the aneurysm arising from the noncoronary cusp and communicating with the right atrium. Color flow Doppler (Figure 3) confirmed continuous flow between the aneurysmal sinus and right atrium throughout the cardiac cycle, consistent with the continuous murmur noted on physical examination.

The aneurysm was also noted on aortography (Figure 4) obtained before the patient underwent surgery to correct it. The surgery was successful, no complications occurred, and the murmur and associated dyspnea had completely resolved at subsequent follow-up.

This case highlights the importance of imaging studies such as echocardiography in diagnosing and managing sinus of Valsalva aneurysm, and also the importance of physical examination in guiding the diagnostic evaluation and differentiating this condition from other cardiac disorders.

For patients who have femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon achieves better 1-year patency than does using a standard balloon, according to a report published online June 24 in the New England Journal of Medicine.

Angioplasty initially restores blood flow in most patients with this type of PAD, but more than 60% develop restenosis from vessel recoil and neointimal hyperplasia within 1 year. The LEVANT2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) clinical trial assessed the performance of a drug-coated balloon (316 patients) against a standard balloon (160 patients) in participants treated at 54 sites in the U.S. and Europe, said Dr. Kenneth Rosenfield of Massachusetts General Hospital, Boston, and his associates.

The primary efficacy endpoint – the rate of patency of the target lesion at 1 year – was significantly higher with the paclitaxel-coated balloon (65.2%) than with the standard balloon (52.6%), the investigators said (N. Engl. J. Med. 2015 June 24 [doi:10.1056/NEJMoa1406235]).

However, secondary efficacy endpoints including the rates of event-free survival (86.7% vs. 81.5%), target-lesion revascularizations (12.3% vs. 16.8%), overall mortality (2.4% vs. 2.8%), amputation (0.3% vs. 0.0%) and thrombosis (0.4% vs. 0.7%) were not significantly different between the two study groups. Scores on a measure of walking distance improved significantly more with the paclitaxel-coated balloon, but ankle-brachial index and Rutherford scores measuring pain and symptoms of intermittent claudication did not differ significantly between the two study groups.

The primary safety endpoint – a composite of the proportion of patients free from perioperative death from any cause plus the proportion free from amputation, reintervention, or PAD-associated death at 1 year – was 83.9% with the paclitaxel-coated balloon and 79.0% with the standard balloon. This met the criterion for noninferiority.

“Our trial does not provide definitive guidance concerning the potential role of this paclitaxel-coated balloon in clinical practice. Although the findings are encouraging, long-term follow-up will be useful in determining whether the benefit of this intervention is sustained, increased, or attenuated over time,” Dr. Rosenfield and his associates said.

This study was funded by Lutonix-Bard, maker of the paclitaxel-coated balloon. Dr. Rosenfield reported ties to Lutonix/Bard, Cordis, Atrium, Abbott Vascular, and VIVA Physicians; his associates reported ties to numerous industry sources.

For patients who have femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon achieves better 1-year patency than does using a standard balloon, according to a report published online June 24 in the New England Journal of Medicine.

Angioplasty initially restores blood flow in most patients with this type of PAD, but more than 60% develop restenosis from vessel recoil and neointimal hyperplasia within 1 year. The LEVANT2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) clinical trial assessed the performance of a drug-coated balloon (316 patients) against a standard balloon (160 patients) in participants treated at 54 sites in the U.S. and Europe, said Dr. Kenneth Rosenfield of Massachusetts General Hospital, Boston, and his associates.

The primary efficacy endpoint – the rate of patency of the target lesion at 1 year – was significantly higher with the paclitaxel-coated balloon (65.2%) than with the standard balloon (52.6%), the investigators said (N. Engl. J. Med. 2015 June 24 [doi:10.1056/NEJMoa1406235]).

However, secondary efficacy endpoints including the rates of event-free survival (86.7% vs. 81.5%), target-lesion revascularizations (12.3% vs. 16.8%), overall mortality (2.4% vs. 2.8%), amputation (0.3% vs. 0.0%) and thrombosis (0.4% vs. 0.7%) were not significantly different between the two study groups. Scores on a measure of walking distance improved significantly more with the paclitaxel-coated balloon, but ankle-brachial index and Rutherford scores measuring pain and symptoms of intermittent claudication did not differ significantly between the two study groups.

The primary safety endpoint – a composite of the proportion of patients free from perioperative death from any cause plus the proportion free from amputation, reintervention, or PAD-associated death at 1 year – was 83.9% with the paclitaxel-coated balloon and 79.0% with the standard balloon. This met the criterion for noninferiority.

“Our trial does not provide definitive guidance concerning the potential role of this paclitaxel-coated balloon in clinical practice. Although the findings are encouraging, long-term follow-up will be useful in determining whether the benefit of this intervention is sustained, increased, or attenuated over time,” Dr. Rosenfield and his associates said.

This study was funded by Lutonix-Bard, maker of the paclitaxel-coated balloon. Dr. Rosenfield reported ties to Lutonix/Bard, Cordis, Atrium, Abbott Vascular, and VIVA Physicians; his associates reported ties to numerous industry sources.

For patients who have femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon achieves better 1-year patency than does using a standard balloon, according to a report published online June 24 in the New England Journal of Medicine.

Angioplasty initially restores blood flow in most patients with this type of PAD, but more than 60% develop restenosis from vessel recoil and neointimal hyperplasia within 1 year. The LEVANT2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) clinical trial assessed the performance of a drug-coated balloon (316 patients) against a standard balloon (160 patients) in participants treated at 54 sites in the U.S. and Europe, said Dr. Kenneth Rosenfield of Massachusetts General Hospital, Boston, and his associates.

The primary efficacy endpoint – the rate of patency of the target lesion at 1 year – was significantly higher with the paclitaxel-coated balloon (65.2%) than with the standard balloon (52.6%), the investigators said (N. Engl. J. Med. 2015 June 24 [doi:10.1056/NEJMoa1406235]).

However, secondary efficacy endpoints including the rates of event-free survival (86.7% vs. 81.5%), target-lesion revascularizations (12.3% vs. 16.8%), overall mortality (2.4% vs. 2.8%), amputation (0.3% vs. 0.0%) and thrombosis (0.4% vs. 0.7%) were not significantly different between the two study groups. Scores on a measure of walking distance improved significantly more with the paclitaxel-coated balloon, but ankle-brachial index and Rutherford scores measuring pain and symptoms of intermittent claudication did not differ significantly between the two study groups.

The primary safety endpoint – a composite of the proportion of patients free from perioperative death from any cause plus the proportion free from amputation, reintervention, or PAD-associated death at 1 year – was 83.9% with the paclitaxel-coated balloon and 79.0% with the standard balloon. This met the criterion for noninferiority.

“Our trial does not provide definitive guidance concerning the potential role of this paclitaxel-coated balloon in clinical practice. Although the findings are encouraging, long-term follow-up will be useful in determining whether the benefit of this intervention is sustained, increased, or attenuated over time,” Dr. Rosenfield and his associates said.

This study was funded by Lutonix-Bard, maker of the paclitaxel-coated balloon. Dr. Rosenfield reported ties to Lutonix/Bard, Cordis, Atrium, Abbott Vascular, and VIVA Physicians; his associates reported ties to numerous industry sources.