Transcript Ventricular Tachycardia - Pitt Pharmacy Portfolio

Ventricular Tachycardia and the Role of
Ranolazine
Pam Lyons
PharmD Candidate 2014
Pharmacotherapy Scholars Program
University of Pittsburgh School of Pharmacy
Objectives
• Be able to explain the mechanism of action of
ranolazine
• Describe the role of ranolazine in ventricular
tachycardia and ischemic heart disease
• Understand the difference between premature
ventricular beats and ventricular tachycardia
• List the types of ventricular tachycardia
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DN – Presentation 7/31/13
CC: “I don’t feel well”
HPI: 61 yo male presented to ER with palpitations
and lightheadedness that had been occurring for ~1
week, mild cough
• Feels similar to how he usually feels when in VT.
• No orthopnea, CP, LE edema, fever, chills, n/v/d
• Claims compliance with all medications
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DN - Earlier that Morning…
• Saw his cardiologist the morning of 7/31/13 who
recommended an ablation
• 150 episodes of VT since 5/2013
– 10 episodes in the 24 hrs before appointment
– ICD had not fired
• In ER: Several runs of non-sustained VT
– ICD did not fire
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DN -PMH
• Mixed ischemic and non-ischemic
cardiomyopathy
• EF: 25-30% (5/2013)
• Inferior wall hypokinesis
• Ventricular Tachycardia
s/p radiofrequency ablation x2 (12/12,
2/13)
• DVT
• CKD
• COPD
• OSA
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DN - Social History
• Former smoker
• (-) EtOH, illicit drugs
• NKDA
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DN - Home Medications
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Ranolazine 1000 mg BID
Cavedilol 50 mg BID
Furosemide 40 mg BID
Simvastatin 20 mg daily
Valsartan 80 mg daily
Warfarin 4 mg q MWFSat
Sildenafil 20 mg TID
Albuterol 90 mcg/inhalation –
1 puff q 4 hr PRN
• Duoneb (albuterol-ipitropium)
3mg/0.5 mg – QID PRN
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• Advair 500/50mcg – 1 puff
BID
• Trazodone – 50 mg HS PRN
• Spirololactone 25 mg – ½ tab
BID
• Senna – 2 tabs HS
• Pantoprazone 40 mg daily
• Mulitvitamin daily
• Potassium Chloride ER 20
mEq daily
Vitals:
• BP: 106-141/54-81
• Pulse: 59-85 bpm
• RR: 16-18
• SaO2: 95-99%
• Temp: 37.2
Ht: 74 in Wt: 101 kg, BMI: 28.6
Exam:
• No JVD
• Warm and dry
• Diminished breath sounds
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DN - Labs
• Metabolic Panel:
– Na 137, K 4.0, Cl 102, CO2 28, BUN 34, Cr 2.8, Gluc 137
• CBC:
– WBC 4.8, Hgb 15.4, Hct 47.1, Plts 234
• Troponins (-)
• EKG:
– Atrial paced rhythm with prolonged PR interval and PVCs
– T wave inversions
– Same as previous EKGs
• CXR:
– Clear lungs with mild vascular congestion
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DN - Initial treatment
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IV metoprolol 5 mg
IV lidocaine 150 mg followed by drip at 2 mg/min
IV magnesium sulfate 2 g
Transferred to CCU
DN – Day 1 Plan (7/31/13)
• VT: likely secondary to previous infarct seen on stress test
in 4/12
– Continue lidocaine drip at 2 mg/min
• Check level in the morning
– Ranolazine 1000 mg PO BID
– Consider another ablation
• HF:
– Continue valsartan, lasix, carvedilol, simvastatin, sildenafil
• COPD
– Give O2 as needed
– Continue home medications
CCU– Day 1 Plan (7/31/13)
• DVT
– Warfarin
– Check INR tomorrow morning
• CKD
– Currently at baseline
• PPX
– On warfarin for DVT prophylaxis
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CCU - Day 2 (8/1/13)
• Pt reports no palpitations since transfer
• New epigastric pain and R sided CP
– Non-radiating
– Bloated feeling
• Lidocaine level: 3.8 ug/ml
– Goal: 1-5 ug/ml
• INR: 2.1
– Holding warfarin b/c of possible ablation
• Carvedilol decreased to 25 mg BID from 50 mg BID
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CCU - Day 3 (8/2/13)
• Pt had HA overnight
– Decrease lidocaine drip to 1 mg/min
– Level: 4.1 ug/ml
• BP: 126-155/64-107
– Increase carvedilol from 25mg BID  37.5 mg BID
– Increase valsartan from 40 mg BID  80 mg BID
• Plan for ablation next week
– Holding Coumadin
• INR 2.2
– Start heparin drip
CCU - Day 4 (8/3/13)
• Stable  just waiting for ablation
– No more VT
– BP: 80-123/42-75, Pulse: 71-81
• Lidocaine changed to PO mexilitine 150 mg q8hr
• Transferred to Pavillion
Pavillion - Day 5 (8/4/13)
• Heart failure improving
– Euvolemic, NYHA II
• Holding Lasix
• Development of AKI on CKD
– Scr 3.0
– Possibly due to increase in valsartan – hold it
– 250 NS bolus
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Pavillion – Day 5 Lab Trends
7/31
8/1
8/2
8/3
8/4
Na
137
137
136
131
135
Scr
2.8
2.5
2.6
3.0
3.0
BUN
34
35
33
37
41
Mg
2.1
2.7
2.4
2.3
2.2
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Pavillion - Day 6 (8/5/13)
• VT
– >90 short runs
– Continue ranolazine
– D/c mexilitine after tonight
• Heart Failure Stable
– Euvolemic
• +695 ml from yesterday
• Holding lasix
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• AKI on CKD
– Not improving from yesterday
– Scr 3.3 – up from 3.0
– UA normal
– Hold valsartan until Scr
improves
• DVT
– Holding warfarin – ablation
planned for 8/7
– INR – 1.3
Pavillion - Day 7 (8/6/13)
• VT worsening
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Frequent episodes of longer duration
Continue mexiletine today, then hold for ablation
Transferred to CCU
Restart lidocaine 100 mg IV once
• Then drip 2 mg/min
– Awaiting ablation tomorrow
– Sympotmatic
• AKI improving
– Scr down to 2.7
• Hemodynamically stable
• All other lab WNL
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CCU – Day 8 (8/7/13) – Ablation Day
• Ablation
– Found scar on the LV – possible cause for VT
– Multiple ablations to the midapex of the inferoseptal wall
• Back in the CCU:
– DN complains of substernal CP
• Non-radiating, non-pleuritic, not reproducible
– No further palpitations
– 2 episodes of Altered Mental Status – resolved spontaneously
– Starting to get frustrated
• Vitals:
– BP: 151-165/83-102, pulse 59-63
• Scr improving – 2.4
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CCU – Day 9 (8/8/13)
• Stable overnight
– Had some low BP: 80-110/40-50
• Decrease Coreg from 37.5 BID to 25 BID
• VT
– Pain from ablation improving
– No further runs of VT
• Lidocaine drip d/ced
• Continue mexiletine and ranolazine
• HF
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Restart valsartan 40 mg BID
Restart lasix 40 mg BID
Start spironolactone 12.5 mg daily
Continue sildenafil 20 mg TID
CCU – Day 9 (8/8/13)
• DVT
– D/c warfarin completely
• CKD
– AKI improving
– Scr = 2.2
• At baseline
– Monitor Scr closely
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CCU - Day 10 (8/9/13)
• Stable – only 1 run of VT overnight
• New toe pain
– Suspected gout
– Avoiding colchicine b/c of CKD
– Start prednisone 30 mg
• Transferred to 4D
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Ventricular Tachycardia
Goldberger: Clinical Electrocardiography, 8th ed.
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Premature Ventricular Beats
• What is it?
– Premature = before the beat
– Appear as a wide QRS wave
• T wave and QRS waves point in opposite directions
• Prevalence
– Extremely common at all ages
– Healthy and sick people
• Etiology
– Ventricular pacemakers take over
• Caffeine, stress, cocaine, stimulants, digoxin, electrolyte
imbalances
– In heart disease
• Ischemia, fibrosis, scarring, from previous MI
Goldberger: Clinical Electrocardiography, 8th ed.
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Premature Ventricular Beats
• Symptoms
– Usually none
– Severe palpitations
• Treatment
– None
– Possibly Beta blockers for symtomatic PVB
• Frequent VPB requires further workup
Goldberger: Clinical Electrocardiography, 8th ed.
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Ventricular Tachycardia
• Three or more PVB in a row = Ventricular Tachycardia
– Rate >100 BPM
• Causes
– Reentrant
– Focal
• Length of Arrhythmia
– Sustained
• >30 seconds or requiring defibrillation
– Non-sustained
• <30 sec
• Appearance on EKG
– Monomorphic
– Polymorphic
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Goldberger: Clinical Electrocardiography, 8th ed.
Krannert Institute for Cardiology.. Cardiol Clin 26. 2008:459–479
Torsades de Pointes
• Type of polymorphic VT
• Causes
– QT prolongation
• Congenital
• Acquired
– Class Ia AAD, sotalol, dofetilide, phenothiazines, TCAs,
erythromycin, etc
– Electrolyte imbalances: hypomagnesemia, hypokalemia
– Severe bradyarrhythmias
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Goldberger: Clinical Electrocardiography, 8th ed.
ACLS Guidelines for the treatment of VT
• Drug of Choice:
– Amiodarone: 150 mg over 10 minutes  1mg/min drip x 6hrs 
0.5mg/min drip
• Second line:
– Lidocaine: 1.5 mg/kg repeated q 3-5 minutes
• Maintenance dose: 1-4 mg/min
• Third line:
– Procainamide 30 mg/min
• Maintenance dose: 1-4 mg/min
• Polymorphic VT
– Magnesium Sulfate 1-2 g IV over 10 minutes
Goldman L et al. Goldman’s Cecil Maedicine. 2012
Mizzi A et al. Anesthesiol Clin. 2011;29(3): 535-45
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Ranolazine: Place in Treatment
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Ranolazine
• Indication:
– Chronic Stable Angina
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Ranolazine Mechanism
Ranolazine
Ranolazine
Ranolazine package insert
Bunch, JT. PACE. 2011;34:1600-6
Scirica BM et al. Circulation. 2007;116:1647-52
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Role of Ranolazine in Ventricular
Tachycardia
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Ranolazine for Ventricular Tachycardia
MERLIN-TIMI 36 Trial
6560 Patients with NSTEMI
IV Ranolazine then Oral
Ranolazine
Placebo
Primary Outcome: Effect of ranolazine on the compostie of CV
death and ischemia
Scirica BM et al. Circulation. 2007;116:1647-52
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MERLIN –TIMI 36 Patients
• 6351 patients with valid EKGs
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Mean age: 63 years
Females: 33.8-36.3%
HTN: 73.4-74%
Smoker: 26.5-24.3%
Prior heart failure: 16.5-17.2%
Prior ventricular arrhythmia: 3.8-3.9%
Prior MI: 34%
• Median duration of EKG = 6.8 days
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Scirica BM et al. Circulation. 2007;116:1647-52
Effects of Ranolazine on Heart Rhythm
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Scirica BM et al. Circulation. 2007;116:1647-52
Effect of Ranolazine in Refractory Patients: Case Series
• Patients:
– 12 patients with VT refractory to other treatments
• All on a Class III anti-arrhythmic and with an ICD
– Frequent shocks
• 6 patients had failed a previous Class III
• 2 patients on IV anti-arrhythmic
• 6 on either lidocaine or mexilitine
• 5 with previous ablations
• 2 being referred for ablation
– 10 had ischemic heart disease
– Average EF: 34% +/- 0.13
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Bunch TJ et al. PACE. 2011;34:1600-6.
Effect of Ranolazine in Refractory Patients: Case Series
12 patients with refractory VT
Ranolazine 1000mg BID
for 6 months
Reduction in VT in 11 of 12 patients
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Effect of Ranolazine in Refractory Patients: Case Series
• Negatives:
– QRS increased non-significantly
– No benefit to 2 patients
• Arrhythmogenic right ventricular
cardiomyopathy/dysplasia
• nonischemic cardiomyopathy
– GI side effects limited use in 2 patients
– 4 hospitalizations
– May lower blood glucose and A1c
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Questions?
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