Intracoronary Beta Radiation for In-stent Restenosis in a Patient with Percutaneously Treated Hypertrophic Cardiomyopathy and Co

Atherosclerotic coronary artery disease (CAD) is seen in 25% patients with hypertrophic cardiomyopathy (HCM) aged more than 45 years1 and this association presents an intriguing problem to a clinician from both diagnostic and therapeutic standpoints. While myocardial ischemia leading to angina can occur in HCM by several other mechanisms, namely decreased coronary flow reserve, abnormal intramural arteries, inadequate capillary density, compression of septal perforators during systole, coronary spasm, diminished coronary perfusion pressure, and increased myocardial oxygen demand, the reliability of non-invasive tests in diagnosing CAD is especially low due to false-positive results. Coronary angiography remains the only reliable diagnostic tool in such a situation. Therapeutic decision-making also warrants meticulous planning. Drugs routinely used during medical therapy of CAD, such as nitrates and vasodilators, are harmful; surgical therapy, consisting of coronary artery bypass graft (CABG) surgery combined with myotomy-myectomy with or without plication of anterior leaflet of the mitral valve, or mitral valve replacement, are relatively high-risk procedures; and non-surgical techniques involving percutaneous coronary interventions with transcoronary ablation of septal hypertrophy (TASH) or A-V sequential pacing are still evolving. We describe a patient with coexistent HCM and CAD who was treated with novel percutaneous techniques. Case Report. A 67-year-old female with known obstructive HCM on maximally tolerated medical treatment (100 mg metoprolol, 120 mg verapamil and 100 mg aspirin) presented with progressively increasing dyspnea and angina pectoris. On catheterization, her resting gradient across the left ventricular outflow tract (LVOT) was 130 mmHg; on provocation with 400 µg intravenous nitroglycerin and the Valsalva maneuver, this gradient increased substantially and the patient experienced dizziness. Coronary angiography revealed a critical lesion in the proximal left anterior descending (LAD) coronary artery just before a large septal perforator (S1) (Figure 1). In view of the patient’s highly symptomatic state, we decided to perform percutaneous transluminal coronary angioplasty (PTCA) with stenting and TASH. A 5 French (Fr) pigtail and 4 Fr temporary pacing lead were introduced in the left and right ventricles, respectively, through the left femoral route. From the right femoral artery, a 7 Fr JL4 guiding catheter was selectively intubated in the left coronary artery. PTCA and stenting of the LAD lesion were done in the usual manner using a Galeo, High Flexible guidewire (Biotronik GmbH & Co., Berlin, Germany), a 3.0 x 20 mm Omnipass balloon (Cordis Corporation, Miami Lakes, Florida) and a 16 mm Jostent Flex Normal vessel stent (Jomed AB, Helsingborg, Sweden). A dissection was seen proximal to the stent and another 12 mm Jostent Flex Normal vessel stent was subsequently implanted. A second Hi-Torque Balance guidewire (Guidant Corporation, Santa Clara, California) was then negotiated into the S1. After extending this wire with a DOC extension (Guidant Corporation), a 2.5 x 10 mm Merlin over-the-wire balloon (B. Braun) was passed. After ensuring that the balloon was well within the proximal S1 at a safe distance from the LAD, it was inflated at 6 atmospheres to occlude the vessel. At 2 minutes post-inflation, the pressure gradient (between the left ventricular pressure through the pigtail catheter and the aortic pressure through the guiding catheter) decreased to 30 mmHg, thus confirming S1 as the target of alcohol ablation. A contrast injection was done in the LAD to further assess the balloon position. After withdrawing the HT Balance wire, contrast was injected into the S1 through the balloon shaft lumen to determine the supply area of the branch and to confirm that there was no spillover into the LAD. Thereafter, 2 ml of 96% alcohol was injected into the balloon port, followed by a vigorous saline flush. The balloon was deflated after 5 minutes. The gradient, however, increased to 70 mmHg after some time and angiography showed only partial occlusion of the S1. Another 2 ml of alcohol was injected into S1, after which the gradient settled at 30 mmHg. Final pictures revealed a tiny amount of flow in the septal branch and a good PTCA and stent result in the LAD (Figure 2). The patient was monitored at the Cardiac Care Unit for 2 days and discharged on the tenth day with an uneventful hospital stay. She was prescribed 100 mg metoprolol and 100 mg aspirin for long-term administration. The patient presented again after 7 months with recurrence of angina despite her compliance with the medication. The diagnostic angiogram exhibited significant in-stent restenosis (Figure 3), while the resting gradient across the LVOT was 20 mmHg. Brachytherapy was planned. An 8 Fr JL4 guiding catheter was engaged in the LAD. After the passage of a Hi-Torque Floppy Extra Support guidewire (Guidant Corporation) through the stenosis, the lesion was dilated with a 3 x 10 mm Cutting Balloon (IVT). After obtaining adequate dilatation, the balloon catheter was removed and the Beta-Rail delivery catheter (Novoste, Norcross, Georgia) was advanced over the guidewire and positioned across the balloon treatment site. Following a non-active Transfer Device run, a 40 mm radiation source train (containing 16 sealed Strontium-90, beta-radiation emitting sources) was administered hydraulically to the treatment site (Figure 4). After a dwell time of 3 minutes and 6 seconds, and a dose delivery of 18.4 Gy, the source train was hydraulically retrieved from the coronary artery and positioned back into the Transfer Device. The delivery catheter was then removed. Check pictures revealed vessel spasm, which disappeared after a liberal dose of intracoronary nitroglycerin. Final pictures displayed a successful procedure (Figure 5). The patient was discharged after 2 days of observation on 100 mg metoprolol and 100 mg aspirin. During follow-up, the patient continued in New York Heart Association class II with the above-mentioned medical management. Her coronary angiograms at 6 months (Figures 6 and 7) and 1 year (Figures 8 and 9) after brachytherapy showed a good intervention result. The hemodynamic values recorded during the last invasive examination were impressive. While the resting gradient across the LVOT was 10 mmHg, the pulmonary artery pressures were 28/19 mmHg (mean, 22 mmHg) compared to an initial pre-TASH pressure of 58/28 mmHg (mean, 36 mmHg). The mean pulmonary capillary wedge pressure was 18 mmHg compared to an initial pressure of 26 mmHg and the left ventricular end-diastolic pressure was 16 mmHg compared to 35 mmHg at initial presentation. As far as possible, uniformity was maintained in the loading conditions during both the first and last catheterization. While the patient fasted overnight in both instances, no intravenous administrations were given during the baseline examination. However, the patient was taking metoprolol plus verapamil before the initial catheterization and only metoprolol during the last examination. Discussion. Management of obstructive HCM associated with significant CAD has been described in the literature. Before the 1990s, the usual method of treatment was either medical therapy or surgical myotomy-myectomy with bypass grafting.2,3 With the advent of percutaneous treatment of obstructive HCM, catheter-based approaches for both disease entities seem to be possible. Seggewiss et al. were the first to report simultaneous TASH and coronary stenting in a patient with coexisting obstructive HCM and CAD.4 Another report described balloon dilatation and stenting for CAD and A-V sequential pacemaker implantation for HCM.5 We describe the clinical course of an elderly symptomatic female who was treated with PTCA and stenting for CAD as well as TASH for obstructive HCM during the same procedure. Half a year after the combined procedure, she developed in-stent restenosis for which brachytherapy was administered. At 6-month and 1-year post-brachytherapy follow-up, she was symptomatically well controlled and the angiography and catheterization data demonstrated good brachytherapy and TASH results. To the best of our knowledge, this is the first report of intracoronary beta radiation therapy in a patient with obstructive HCM who was also treated with alcohol septal ablation. Brachytherapy was feasible and effective in the presence of HCM. Moreover, it did not adversely affect the results of TASH and improved hemodynamic parameters were seen after 1 year. This might be an important observation in light of the fact that percutaneous coronary interventions can adversely affect HCM, as was apparent from a report by Kerker et al., who observed a rapid progression of septal hypertrophy in an adult after excimer laser coronary angioplasty.6 The reason cited was the mutagenic effect of the XeCl excimer laser. Proliferative effects of radiation have also been described. Myocardial hypertrophy has been reported after radiation therapy,7 and the susceptibility of the heart to adverse effects of radiation increases in the presence of hypertrophy.8 Moreover, low doses of endovascular ionizing radiation are shown to have a paradoxical stimulatory effect on cell proliferation.9–11 Because low-dose exposure, were it to occur in the myocardium, would be expected during intracoronary radiation therapy, a hyperplastic myocardial response might occur that could negate the results of TASH. Therefore, the possibility of an adverse interaction, albeit theoretical, does exist in a patient with TASH undergoing brachytherapy. Though low-dose myocardial exposure may not be an issue with beta brachytherapy because of its limited penetration (Conclusion. A 1.5-year clinical and invasive follow-up of a symptomatic patient with coexisting obstructive HCM and CAD is presented. The patient was initially treated with simultaneous TASH and coronary stenting, and later with brachytherapy for in-stent restenosis. Brachytherapy was effective and feasible and did not adversely affect the results of TASH.

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