Severe aortic stenosis, critical coronary artery disease, and transfusion-dependent angiodysplasia – A management conundrum

Abstract

The combination of severe aortic stenosis, bleeding due to Heyde's syndrome and critical coronary artery disease presents a management challenge. We report the case of an 86-year-old who underwent percutaneous coronary intervention to the right coronary artery, simultaneous balloon aortic valvuloplasty to treat aortic stenosis and address bleeding from Heyde's syndrome, and subsequent staged transcatheter aortic valve implantation.

<Learning objective: The combination of severe aortic stenosis (AS), bleeding due to Heyde's syndrome and critical coronary artery disease presents a management challenge. This case demonstrated the efficacy of balloon aortic valvuloplasty in resolving gastrointestinal bleeding, with intravascular ultrasound-guided percutaneous coronary intervention with a bare metal stent and single anti-platelet therapy safely and effectively addressing critical coronary stenosis, allowing definitive treatment of AS by transcatheter aortic valve implantation to be performed as a staged procedure.>

Introduction

The association of severe aortic stenosis (AS) with gastro-intestinal (GI) bleeding due to a combination of intestinal angiodysplasia and von Willebrand factor dysfunction, known as Heyde's syndrome, is well described. Coronary artery disease is also prevalent in patients with severe AS, and revascularization in addition to aortic valve intervention may be indicated. Transcatheter aortic valve implantation (TAVI) is increasingly employed to treat patients with severe AS who are inoperable or high risk for surgical aortic valve replacement, with revascularization by percutaneous coronary intervention (PCI), most commonly prior to TAVI, if required. However, PCI is problematic in patients with Heyde's syndrome due to the requirement for dual anti-platelet therapy (DAPT) post-PCI and the consequent increased risk of GI bleeding. We report the case of an 86-year-old who presented with a management conundrum due to severe symptomatic AS with co-existent transfusion dependent angiodyplasia and critical right coronary artery (RCA) stenosis with associated refractory angina.

Case report

An 86-year-old previously independent female with no co-morbidity presented with a four-month history of exertional dyspnea and chest pain at rest. Auscultation revealed a harsh ejection systolic murmur radiating to the carotids, with an absent second heart sound, and mild pedal edema. Echocardiography demonstrated severe AS with a peak velocity of 4.7 m/s, mean pressure gradient of 55 mmHg, and valve area of 0.5 cm², mild-moderate concentric left ventricular (LV) hypertrophy, and good LV systolic function.

Routine blood tests revealed significant anemia with a hemoglobin (Hb) of 8.4 g/dl (normal range 1.5–16.0 g/dl), and low serum ferritin, iron level, and iron saturation, consistent with iron deficiency. Colonoscopy and gastroscopy found no source of bleeding. Fecal occult blood test was positive and a presumptive diagnosis of GI bleeding due to angiodysplasia was made. A 2 unit blood transfusion was administered, oral diuretic therapy instituted, and symptoms improved. Subsequent coronary angiography demonstrated critical focal stenosis in the mid RCA (Fig. 1A), with mild left-sided disease. Aortography demonstrated heavy calcification of the aortic root and ascending aorta. Coronary angiography was complicated by the development of acute pulmonary edema requiring intravenous morphine, furosemide and nitrates, and emergency hospital admission. Blood tests showed a further drop in hemoglobin from 8.9 to 8.0 g/dl.

Fig. 1.

(A) Mid right coronary artery (RCA) stenosis pre-percutaneous coronary intervention (PCI). (B) RCA post-PCI. (C) Aortogram post-transcatheter aortic valve implantation.

Pulmonary edema resolved with medical therapy but the patient experienced recurrent cardiac chest pain at rest while in hospital despite a further two unit blood transfusion. Troponin was not elevated. A cardiac surgical opinion was sought but the patient was deemed inoperable due to aortic calcification. Referral was made for consideration of TAVI +/− PCI.

Given the critical degree of stenosis of the RCA with chest pain at rest it was considered inappropriate to perform TAVI without prior PCI. However, the risks of GI bleeding on DAPT were substantial. We were also concerned about the risks of performing simultaneous PCI and TAVI in an unstable patient with myocardial ischemia at rest and active GI bleeding. We therefore elected to perform PCI to the RCA with simultaneous balloon aortic valvuloplasty (BAV) to treat aortic stenosis, in the hope that BAV would attenuate the tendency to bleeding from Heyde's syndrome. Following an abbreviated course of anti-platelet therapy TAVI could then be performed as a staged procedure.

BAV was performed with a 20 mm VACS-II (Osypka, Berlin, Germany) balloon with two separate inflations, reducing peak invasive gradient from 70 mmHg to 36 mmHg. Following this the RCA was engaged with an AL 0.75 guide catheter. Intravascular ultrasound (IVUS) guidance was employed to optimize stent deployment to allow single anti-platelet therapy post-PCI with minimization of the risk of stent thrombosis. The RCA was pre-dilated with a 2.5 mm × 8 mm Apex balloon (Boston Scientific, Marlborough, MA, USA) and then with a 3.0 mm × 10 mm Angiosculpt balloon (Angioscore, Fremont, CA, USA). A 4 mm × 15 mm Integrity (Medtronic, Minneapolis, MN, USA), bare metal stent was deployed at 11 atmospheres and post-dilated with a 4.5 mm × 8 mm Quantum Apex non-compliant balloon (Boston Scientific) to 18 atmospheres with a good angiographic result (Fig. 1B). Hb had dropped further at the time of BAV/PCI procedure from 9.6 g/dl to 7.2 g/dl and a further two units of blood was transfused. Recovery post-procedure was uncomplicated and the patient was discharged on day 3 on single anti-platelet therapy, aspirin 75 mg once daily.

At follow-up one month post-procedure she was pain-free, Hb was stable at 11.9 g/dl, with no further evidence of GI bleeding or requirement for transfusion.

TAVI was performed 2 months post-BAV. A 26-mm Core Valve (Medtronic) was deployed via a trans-femoral approach. Invasive gradient reduced from 45 mmHg to 0 mmHg with mild paravalvular aortic regurgitation (Fig. 1C). The patient was discharged on day 4 post-procedure on aspirin 75 mg once daily and clopidogrel 75 mg once daily. At the most recent follow-up, 3 months post-TAVI she was asymptomatic, with normal Hb, and no recurrence of GI bleeding.

Discussion

The association between AS and bleeding from intestinal angiodysplasia was first described by Edward J Heyde in 1958 [1] and is reported in approximately 3% of all patients with severe AS [2].

In the context of GI bleeding and severe AS there is a recommendation for aortic valve replacement as mucosal blood supply is improved and bleeding resolves [3] almost promptly [4]. Observational studies have demonstrated complete resolution of bleeding by correction of aortic stenosis by surgical aortic valve replacement in 80–95% of cases [3], [4]. Therefore it is imperative to screen patients with GI bleeding with severe AS as this condition is potentially reversible.

Fewer data exist describing the prevalence of Heyde's syndrome in patients undergoing TAVI, or the impact of TAVI on bleeding. In a retrospective analysis of 400 patients with severe AS undergoing TAVI the incidence of Heyde's syndrome was 1.7%. 37 patients were found to have associated gastrointestinal bleeding and within this cohort 7 patients were diagnosed with Heyde's syndrome. In all those patients who were treated successfully by TAVI bleeding had resolved fully [2].

Investigations for Heyde's syndrome include von Willebrand factor levels which tend to be reduced and colonoscopy. However, von Willebrand levels may be normal as multiple blood transfusions can interfere with the analysis [5]. In the presence of active bleeding colonoscopy may not be effective in the diagnosis of angiodysplasia, and angiography is a useful investigation in these cases [6].

In this paper, we report a case of severe aortic stenosis with transfusion-dependent anemia due to Heyde's syndrome in which BAV resulted in successful resolution of bleeding, with no further hemoglobin drops or transfusion requirement after treatment. While co-existent coronary artery disease (CAD) is found in 40–75% of patients undergoing TAVI, no clear data exist to inform decision-making around the need for revascularization [7].

Data on the effect of untreated CAD on outcomes of TAVI are conflicting, with most suggesting no adverse impact [8].

In the case reported here there was a clear indication for revascularization, but the conundrum presented was to perform PCI without exposing the patient to the risk of potentially life-threatening bleeding due to the additive effect of DAPT on pre-existing transfusion-dependent GI blood loss. We elected to perform PCI with a bare-metal stent and IVUS-guidance in order to facilitate a strategy of single antiplatelet therapy with aspirin alone with an acceptably low risk of stent thrombosis. A single anti-platelet was used as there was a potential risk of excess GI bleeding on DAPT since our patient had already required 6 units of blood in the absence of antiplatelets. The MUSIC trial has previously reported a stent thrombosis rate of only 1% with IVUS-guided optimization of BMS implantation [9]. Simultaneous BAV was performed to attenuate the impact of Heyde's syndrome to allow TAVI to be performed safely at a later date. An alternative strategy would have been to perform simultaneous TAVI and PCI, without bridging BAV, but we were concerned about performing TAVI in a patient with active GI bleeding and unstable symptoms, particularly given the recommendation for DAPT post-TAVI.

This strategy proved highly effective, with an uncomplicated course without adverse events following PCI and complete resolution of GI blood loss. TAVI was subsequently performed with an excellent result and clinical outcome.

Conflict of interest

The authors declare there is no conflict of interest.