Disclosures: The authors report no conflicts of interest regarding the content herein.

The authors can be contacted via Dr. Jon C. George at georgej@deborah.org.

Abstract

Percutaneous alcohol septal ablation has received more recent attention as an attractive alternative for drug-refractory hypertrophic obstructive cardiomyopathy and can be performed with excellent results and immediate clinical outcomes. We present herein a case of an exaggerated hemodynamic response in a patient with a very focal basal septum obstruction.

Case  

A 67-year-old Caucasian female with a recent diagnosis of hypertrophic obstructive cardiomyopathy (HOCM), mitral regurgitation (MR), and systemic hypertension, presented with a chief complaint of worsening dyspnea and chest pressure on exertion. She had rare palpitations associated with exertion, without dizziness or syncope. Her family history included premature coronary artery disease in her father and hypertrophic cardiomyopathy in a grandchild. On physical examination, she had a 2/6 systolic murmur along the left mid-sternal border that was augmented with bedside Valsalva maneuvers. Routine chemistries were unremarkable, with normal blood count and renal function. Her electrocardiogram (ECG) revealed normal sinus rhythm with an incomplete right bundle branch block and ST-segment flattening in the lateral leads with T-wave inversions in V5-V6 (Figure 1). She underwent diagnostic cardiac imaging with a trans-thoracic echocardiogram, which revealed a hyper-dynamic left ventricle and mild left ventricular hypertrophy of 1.0-1.1cm in the mid-anterior septum and posterior wall, but had focal basal septal hypertrophy of 1.7-1.8cm, mild MR, and a resting left ventricular outflow tract (LVOT) gradient of 80-90mmHg. Diagnostic cardiac catheterization revealed a dominant right coronary artery and only mild luminal irregularities in the left anterior descending artery (LAD) with two large-sized septal perforator arteries supplying the anterior septum. A 6 French dual lumen pigtail catheter (Vascular Solutions) was advanced across the aortic valve, measuring a dynamic resting LVOT gradient of 90mmHg. The catheter was manipulated against the left ventricular wall to induce premature ventricle contractions (PVCs), and a post-PVC gradient was measured at 180mmHg. The gradual pullback of the catheter revealed equalization of the systolic pressures across the aortic valve, confirming the absence of aortic stenosis.

The patient was treated medically with metoprolol 50mg orally twice daily, which was increased to 50mg three times daily since she had persistent symptoms with only minimal exertion. Regardless of the up-titration of the beta-blocker therapy, the patient continued to have New York Heart Association (NYHA) Class 3 exertional dyspnea and chest pressure, and Canadian Cardiovascular Society (CCS) Class 3 angina (CCS-3). She began to complain of generalized weakness and fatigue, presumed to be medication induced. Her symptoms affected her over the course of months, to the point of affecting her daily life activities. Within weeks, she progressed to NYHA Class 4 heart failure. At this point, she underwent a transesophageal echocardiogram (TEE) to evaluate her LVOT obstruction and mitral valve pathology. TEE confirmed similar findings as the previous transthoracic echocardiogram, including a focal basal septal hypertrophy of 1.8cm, normal tri-leafet aortic valve, mild posterior-directed MR with significant systolic anterior motion of the mitral valve, and a dynamic resting LVOT gradient of 90mmHg (Figure 2). At this point, she was referred back to the interventional cardiology team to be evaluated for alcohol septal ablation.

Repeat cardiac catheterization via a right femoral artery approach (15 months since her initial catheterization) showed no change in coronary anatomy, including two appropriate-sized septal perforators (Figure 3); however, the resting LVOT gradient was now 100mmHg (Figure 4A), with a post-PVC gradient of 192mmHg (Figure 4B). A decision was then made to proceed with percutaneous alcohol septal ablation.

A temporary right ventricular balloon-tipped pacing catheter was advanced via access in the right femoral vein and positioned within the right ventricular apex. A 6 French Extra Back Up Launcher 4.0 guide catheter (Medtronic) was placed in the left main coronary artery for support and a 0.014-inch PT-2 moderate support hydrophilic coronary wire (Boston Scientific) was advanced under fluoroscopic guidance into the second, large septal perforator (S2). A small 2.0 x 6mm over-the-wire balloon was advanced into the proximal portion of the S2 branch and inflated to nominal pressure. A soft injection of iso-osmolar, non-ionic contrast through the inflated balloon confirmed appropriate balloon position without any contrast reflux into the LAD. The wire was then removed and 2cc of 98% desiccated ethanol was delivered slowly through the inflated balloon over 2 minutes, with an additional minute of monitoring. No significant ECG changes occurred, aside from rare PVCs. This was repeated for the smaller, first proximal septal perforator (S1) with the same result. Final angiogram confirmed brisk flow into the LAD with obliteration of the S1 and S2 branches (Figure 5).

The 6 French dual lumen pigtail catheter was then re-advanced across the aortic valve, revealing a resting LVOT gradient <5mmHg (immediately pre-ablation was 100mmHg) (Figure 6A), and a provoked post-PVC gradient <40mmHg (immediately pre-ablation was 192mmHg) (Figure 6B). The patient tolerated the procedure well and was without bradycardia or high-grade electrical conduction blocks overnight in the intensive care unit. Post ablation troponin-I peaked at 28mcg/ml. An ECG post-ablation day 1 showed right bundle branch block morphology and a left axis deviation with ST-elevations in V1-V2 (Figure 7). The electrophysiology team evaluated the patient for possible bifascicular block and recommended a 48-hour outpatient telemetry monitor. Repeat transthoracic echocardiogram the following day showed a stunning of the basal segment of the anterior septum (Figure 8A), a resting peak LVOT gradient of 7mmHg by continuous wave Doppler interrogation (Figure 8B), and resolution of the posterior-directed MR jet (Figure 8C). The patient had an immediate and impressive reduction in her clinical symptoms from NYHA Class 4 to Class zero within 24 hours, with nearly complete resolution of her LVOT obstruction.

Discussion  

Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by an abnormal thickening of the left ventricular walls, particularly the interventricular septum, causing a dynamic LVOT obstruction. Many phenotypes exist, with varying morphologies in the location and extent of left ventricular hypertrophy. HOCM has been associated with >14 different gene mutations and exists more commonly than previously recognized, with a prevalence of 1 in 500 people in the general population.¹ HOCM is likely to be under-recognized and under-diagnosed clinically.¹ Approximately 25% of patients affected with HOCM will have a resting LVOT obstruction defined as >30mmHg.^1,3

An additional 25-50% will have an LVOT obstruction induced with provocation (>40mmHg).^1-4 Typically, HOCM manifests with exertional dyspnea, angina, palpitations, pre-syncope, syncope, frank congestive heart failure, ventricular dysrhythmias, or even as sudden cardiac death.^1-6 Medical therapy initially includes adequate oral hydration and avoiding pre-load reducing medications. Ionotropic and chronotropic drugs are standards of care, and include beta-blockers and non-dihydropyridine calcium-channel blockers with maximal titration as clinically tolerated.^1-6 Additional negative ionotropy with agents like disopyramide is also considered.^1-6 Medical therapy with these negative ionotropes has been reported to improve symptoms in only 50% of patients affected with HOCM.2 Patients may also not tolerate high doses of negative ionotropic and chronotropic medications, and this, clinically, can be quite challenging.  

Percutaneous interventional techniques targeted at obliterating the LVOT obstruction include alcohol septal ablation, and ever since the endovascular technique was first reported in 1995, it has been increasingly applied as a definitive therapy for drug-resistant HOCM.⁷ Although traditionally performed via transfemoral artery access, transradial artery access cases have recently been reported with good technical and clinical success.⁸ Patient selection for alcohol septal ablation is a judicious process. Clinically, the patient should have persistent NYHA Class 3 or 4 heart failure symptoms, or CCS Class 3 or 4 angina on optimal medical therapy, or be limited by side effects of the drug classes or recurrent gradient-related syncope.^1,3 On echocardiography, basal septal hypertrophy should be >16mm and <30mm, and systolic anterior motion of the mitral valve as a product of the Venturi effect and posterior-directed MR are also common. If the mitral regurgitant jet is centrally or anteriorly directed, TEE may be helpful to exclude primary, degenerative mitral valve pathology. Angiographic criteria for alcohol septal ablation include a septal perforator of >1.5mm in diameter that subtends the targeted septal hypertrophy. Patients with a septal “bulge” or focal basal septal hypertrophy, and/or those with markedly provoked gradients, have been described as the best candidates for septal reduction therapy.¹ Approximately 20% of patients who are possible alcohol septal ablation candidates will not have an acceptable septal perforator artery for the ablation procedure.

Both resting and stimulated gradients are measured during cardiac catheterization. Provocation of the ventricle with the catheter induces PVCs, eliciting a provocable gradient as the PVC causes increased diastolic filling of the left ventricle. This allows stretching the myocardial fibers and augmentation of the post extra-systolic potentiation, resulting in markedly increased contractility, and greater obstruction and increased gradient of the LVOT in the heartbeat immediately following the PVC (Brockenbrough maneuver and phenomenon).⁵

Comparative analysis of alcohol septal ablation and surgical myomectomy in HOCM patients with age- and gradient-equivalent cohorts showed no significant difference in clinical outcomes.¹⁰ Hemodynamic and clinical functional improvement is observed in nearly 90% of carefully selected patients who undergo alcohol septal ablation, rivaling surgical myomectomy.^1,2 Reported procedural complications include complete heart block, myocardial infarction in unwanted territories, cerebral vascular accidents, or sudden cardiac death with mortality <1.5%. Permanent pacemaker implantation for complete heart block occurs in <5-10% of patients, particularly if there is a preexisting left bundle branch block.³ A right bundle branch block is seen more commonly post-ablation (>70% of patients), since the LAD supplies the right bundle branch).^1,3 Alcohol septal ablation typically infarcts and thins out the right ventricular side of the interventricular septum with an initial stunning of the basal septum, resumed contraction during the next 7 days, then, ultimately, thinning out of the infarcted basal septal myocardium over the following 3-4 weeks, relieving the LVOT obstruction and posterior MR.¹ Patients should be instructed to continue the negative ionotropic regimen until this final phase of the ablation occurs. Ultimately, due to the chaotic disarray of the interchanges of the myofibril architecture of hypertrophic cardiomyopathy, patients may remain at an elevated risk of sudden cardiac death, despite dissolution of the LVOT obstruction and clinical symptoms.^1-4,6,7

Summary  

Percutaneous alcohol septal ablation can be utilized for isolated symptomatic basal septal HOCM with profound reductions in LVOT obstruction and gradients, as well as excellent clinical outcomes. 

References

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