233 - SELECTIVE BETA BLOCKADE FOR THE TREATMENT OF CORONARY VASOSPASM -ASSOCIATED POLYMORPHIC VENTRICULAR TACHYCARDIA

Case background: Long term medical management of patients with vasospastic angina usually includes vasodilators and calcium channel blockers (CCBs), however, this has been recently questioned in randomized controlled trials. Beta-blockers are relatively contraindicated due to the fear of unopposed alpha-adrenergic activities leading to further vasoconstrictions. However, this is only supported by small trials using propranolol. Nebivolol is a third-generation beta blocker with high selectivity for beta 1 receptor for vasodilation and restoration of endothelial function by activating beta 3 receptor to increase nitric oxide production. Likewise, allopurinol and colchicine are known to improve endothelial function and reduce oxidative stress.
Long-term prognosis of vasospastic angina is relatively favourable. However, cases with ventricular tachycardia (VT) and other complications are associated with poor prognosis. Unfortunately, there is a lack of tailored management for this subset of patients. In this case series, we will discuss the management of vasospastic angina complicated by polymorphic ventricular tachycardia.

Case 1 :
A 59-year-old female, with previously documented sinus bradycardia and sinus node dysfunction, presented to ER with three days of episodic chest tightness, presyncope, and dyspnea. Initial workups were unrevealing except sinus bradycardia with heart rate 37. Angiography identified no significant coronary artery disease (CAD). Diagnosis was confirmed with acetylcholine challenge revealing severe pain arterial spasm with 100 µg loading dose of acetylcholine (FFR = 0.78, IMR = 13, CFR = 3.3). There were episodes of transient ST elevation (STE, leads II, III, AVF, V3-V6) followed by polymorphic VT and PEA (Figure 1). She was discharged after receiving a dual-chamber pacemaker and initiating amlodipine 2.5 mg BID.
Her first device interrogation revealed nine episodes of polymorphic VT that spontaneously terminated, leading to an upgrade to an implantable cardioverter defibrillator (ICD), and she was switched to nebivolol 5 mg OD and colchicine 0.6 mg bid. At 3 months follow-up, she remained asymptomatic with no VT recurrence.

Case 2:
A 50-year-old female has a history of recurrent MINOCA (6 episodes), one of which resulted in prolonged ventricular fibrillation (VF) arrest and ICD implantation. In her 20s, she had multiple episodes of strokes secondary to recurrent carotid dissection. Investigations identified no evidence of fibromuscular dysplasia non-obstructive CAD on angiography (40% LAD lesion). However, she continued to have symptomatic episodes of chest pain that were suboptimally controlled with nitroglycerin.
During the acetylcholine challenge, only 20 µg of test dose resulted in STE, accompanied by diffused LAD vasoconstriction. She was started on nebivolol 2.5 mg bid and allopurinol 300 mg daily.
She remained asymptomatic and physically active for one year following changes to her medical therapy, with the exception of one transient episode of chest pain and diaphoresis, which she believed was triggered by stress.

Case 3:
A 52-year-old female survivor of out-of-hospital cardiac arrest secondary to VF, was found to have normal coronary arteries on angiography. She was discharged after receiving ICD and excluding all reversible causes for VF.
She was later hospitalized after a symptomatic episode with interrogation revealing polymorphic VT treated with appropriate shocks, and another episode in hospital was associated with dynamic inferio-lateral STE with reciprocal depression. Repeat angiography was unchanged and an electrophysiology study was performed with no inducible arrhythmia, leading to a high clinical suspicion of epicardial coronary spasm. Acetylcholine challenge later confirmed the diagnosis of diffuse vasoconstriction of LAD and RCA with 100 µg of acetylcholine (FFR = 0.91, IMR = 10, CFR = 5.8). Nebivolol 10 mg daily, allopurinol 100 mg daily, and colchicine 0.6 mg daily were commenced.
At three months follow-up, she had no further evidence of ventricular arrhythmias.

Case 4:
A 55-year-old female, with a high clinical suspicion of coronary artery vasospasm poorly controlled with amlodipine 5 mg PO, had a cardiac arrest with documented pulseless ventricular tachycardia and STE in the lateral leads, which led her to receive her first PCI (70% LAD lesion). She remained symptomatic for the next two years, and subsequently received her second PCI revealing 60% stenosis at the distal edge of the previous stent, possibly due to distal edge dissection secondary to vasospasm.
Diagnosis confirmed with acetylcholine challenge revealing severe spasm of LAD with 20 µg (Figure 2). She remained asymptomatic for the next two years after initiating allopurinol 300 mg OD and nebivolol 2.5 mg OD.

Management Challenges: Pathophysiology linking vasospasm and ventricular arrhythmia remains unclear. Interestingly, concurrent QT dispersion is significantly higher in cases complicated by cardiac arrest or syncope, explaining higher susceptibility to developing ventricular arrhythmia and poor prognosis. CCBs and ICD implantations remain the mainstays for these patients.

Takagi et al. demonstrated patients with out-of-hospital cardiac arrest had significantly lower survival rate compared to its control group, despite aggressive management with CCB and ICD implantation. EDIT-CMD is first randomized clinical trial of diltiazem in patients with ANOCA and no significant improvement in coronary vasomotor dysfunction, symptoms, and quality of life.

Traditionally, beta-blockers were avoided in the setting of coronary spasm for fear of Beta-2 blockade (which reduces beta-2 mediated vasodilation) leading to unopposed alpha-mediated vasoconstriction. Small randomized trials have questioned this convention and showed that beta blockers (atenolol and bisoprolol) tend to reduce anginal episodes and clinical events compared to vasodilators and CCBs.

Nebivolol is a beta blocker with a greater degree of selectivity for beta 1 adrenergic receptors than other agents, and a nitric oxide potentiating vasodilatory effect that can be of high utility in this patient population both in the prevention of coronary vasospasm and ventricular arrhythmia. To our knowledge, this is the first case series describing the use of Nebivolol in the treatment of ventricular arrhythmia in the setting of coronary vasospasm, showing the elimination of recurrent ventricular arrhythmia and device therapy.