The therapeutic and adverse effects of NSAIDs are secondary to their inhibition of prostaglandin synthesis. This inhibition causes a decrease in renal blood flow and compensatory sodium and water retention. By expanding the intravascular volume, NSAIDs blunt the response to diuretics, an important adjunct therapy in patients with HF. Prostaglandin depletion increases systemic vascular resistance, which may also augment symptoms of HF
Hemodynamic Profile Assessment The hemodynamic profiles of patients with advanced HF are shown above. The majority (90%) of patients presenting with ADHF are volume overloaded (wet). These patients may have a cardiac index that is unchanged or decreased. Most patients with a decreased cardiac index have SVR, although a minority have unchanged or low SVR. The signs and symptoms of congestion include orthopnea, jugular venous distention, and peripheral edema. Signs and symptoms of low perfusion include narrow pulse pressure, cool extremities, and decreased mental status. Stevenson LW. Eur J Heart Fail . 1999;1:251
Patient Selection and Treatment This quadrant diagram depicts hemodynamic profiles of patients with advanced HF. Signs and symptoms of congestion: orthopnea/paroxysmal nocturnal dyspnea, jugular venous distension, hepatomegaly, edema, rales (rare in chronic HF), elevated PA pressure, and valsalva square wave. Signs and symptoms of low perfusion: narrow pulse pressure, sleepy/obtunded, low serum sodium, cool extremities, hypotension with ACE inhibitor, renal dysfunction. The majority of patients with HF are volume overloaded or wet. These patients may have cardiac index that is unchanged or decreased. Most patients with decreased cardiac index have elevated systemic vascular resistance; however, a minority have unchanged or low SVR. Vasodilators can reduce filling pressures and improve cardiac output without risks of arrhythmia. Can transition to oral vasodilator regimen. Patients with signs of systemic hypoperfusion who are dry would be expected to have therapeutic benefits with volume loading and/or inotropic agents. Stevenson LW. Eur J Heart Fail . 1999;1:251
IV Agents for HF The relative benefits and possible limitations of IV HF therapies are summarized. Unlike other agents, including positive inotropes, nesiritide administration leads to a beneficial increase in cardiac output as well as decreases in PCWP and blood pressure, without affecting heart rate or rhythm. Young JB. Rev Cardiovasc Med . 2001;2(suppl 2):S19
Cardiac Medications “The Essentials” Kenneth Kenyon, PharmD, BCPS Assistant Clinical Professor Cardiology Clinical Pharmacist University of Washington Medical Center
Five days post-discharge the patient presents to her anticoagulation clinic for routine follow up and is referred to the ER due to an INR of 9.8 with no overt signs or symptoms of hemorrhage with the exception of increased bruising on her bilateral upper and lower extremities, but can remember injuring herself.
**Amiodarone, propafenone, flecainide, quinidine, diltiazem and verapamil
Antidepressants – fluoxetine, fluvoxamine
Statins – simvastatin, lovastatin, fluvastatin and rosuvastatin
Utilizing Vitamin K to Reverse INRs INR Clinical Setting Therapeutic Options < 5 No bleeding Hold warfarin until INR in therapeutic range ± vitamin K 2.5mg po Rapid reversal required Hold warfarin and give vitamin K 1mg IV infusion or 2.5mg po 5 – 8.9 No bleeding Hold warfarin until INR in therapeutic range ± vitamin K 2.5mg po Rapid reversal required Hold warfarin and give vitamin K 1-2mg IV infusion or 2.5mg po ≥ 9 No bleeding Hold warfarin until INR in the therapeutic range and give vitamin K 2.5-5mg po or 1-2mg IV infusion and repeat q24h PRN Rapid reversal required Hold warfarin and give vitamin K 1-10mg IV and may repeat q6-24h PRN Any INR Serious or life threatening bleeding Hold warfarin and give vitamin K 10mg IV infusion and supplement with FFP or PPC or recombinant factor VIIa and repeat as necessary guided by INR
How would your management of this patient differed if she presented with an STEMI?
Immediate treatment is the same as NSTEMI
MONA, UF Heparin or LMWH, clopidogrel
PCI: door-to-balloon within 90 minutes
GP IIb/IIIa therapy post-PCI at discretion of interventionalist – what do you need to know?
Fibrinolytic therapy: door-to-needle w/in 30 minutes of arrival if PCI not available
Streptokinase, Alteplase, Reteplase, Tenecteplase
Consideration for time from onset of chest pain and time of patient presentation (risk vs. benefit)
Presentation > 24 hrs from onset of chest pain – likely no benefit
81yo male is admitted to the Cardiology service for increased SOB, fatigue and malaise over the past 2 to 3 weeks. Of note his weight has increased 12 kg during this time. The patient reports he had been in his usual state of health, with the exception of a recent gout attack a few weeks ago, his pain was well controlled with colchicine and ibuprofen.
Hospital course: Patient was aggressively diuresed with IV diuretics, warfarin was held until INR within goal range, TEE-guided cardioversion failed, amiodarone was initiated and the patient remained in AF but achieved adequate rate control, patient’s HF symptoms improved significantly following 15-liter net negative diuresis and he was discharged home with clinic follow up in 2 weeks
Medication changes at d/c : ↑ torsemide to 80 daily, amiodarone 400mg daily
When do you consider utilizing intravenous agents such as vasodilators and inotropes in heart failure patients?
How do I know which agent to use?
Hemodynamic Profile Assessment Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. Congestion at Rest Low Perfusion at Rest No No Yes Yes Warm & Dry Warm & Wet Cold & Wet Cold & Dry
Possible evidence of low perfusion
Narrow pulse pressure
Low serum sodium
Hypotension with ACE inhibitor
Renal dysfunction (one cause)
Patient Selection and Treatment Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. Congestion at Rest Yes No Warm & Dry PCWP normal CI normal (compensated) Cold & Wet PCWP elevated CI decreased Cold & Dry PCWP low/normal CI decreased Vasodilators Nitroprusside Nitroglycerin Inotropic Drugs Dobutamine Milrinone Normal SVR High SVR Low Perfusion at Rest No Yes Warm & Wet PCWP elevated CI normal Natriuretic Peptide Nesiritide or
Intravenous Agents for Heart Failure increase; decrease; + effect (number of and qualitatively associated with degree of effect); 0 no effect Reference: Adapted from Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19. Therapy CO PCWP BP HR Arrhythmia Shorter Onset Longer Offset Dopamine (ng/kg/min) Low (<3) Mod (3 –7) High (7–15) +++ +++ +++ 0 0 0 Dobutamine +++ 0 Milrinone + ++ Nitroglycerin +++ 0 Nesiritide ++ ++ Nitroprusside ++++ 0
Patient was initially given 5mg IV metoprolol x 2 without adequate rate control, then received diltiazem 25mg IV x1 followed by a continuous infusion at 5mg/min with adequate rate control. She was also initiated on heparin via continuous infusion.
The following morning the patient underwent TEE-guided cardioversion, which was unsuccessful as a LAA thrombus could not be ruled out, so cardioversion was cancelled.
The patient was converted from IV to oral diltiazem and later discharged home still in atrial fibrillation but with adequate rate control
How symptomatic is the patient and is there sequela (ischemia, acute pulmonary edema)
Risk vs. benefit of immediate cardioversion
Symptoms uncomfortable but immediately tolerable
Initial therapy should be based on drugs that slow conduction and increase refractoriness of the AV node
Consider etiology of atrial fibrillation/flutter
Precipitated by high states of adrenergic tone (e.g. thyrotoxicosis
So which antiarrhythmic do I choose? Depends – what is the goal of therapy? Rate or rhythm control? Depends – what type of patient are we talking about – age, cardiac history, acuity? † - denotes predominate ion channel interaction, most agents have a multitude of effects responsible for their antiarrhythmic potential Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Disopyramide, Procainamide, Quinidine Lidocaine, Mexilitine Propafenone, Flecainide, Moricizine Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class II Metoprolol, Esmolol, etc. Beta-adrenergic blockade A/V Class III Amiodarone, Sotalol, Dofetilide, Ibutilide Dronedarone (pending FDA approval) Potassium channel blockade A/V Class IV Diltiazem, Verapamil Ca++ channel blockade A Misc. Adenosine, Digoxin, Magnesium Agent specific A/V
Class Specific Antiarrhythmic Agents Mechanism of Action† Class II Metoprolol, Esmolol, etc. Beta-adrenergic blockade Class IV Diltiazem, Verapamil Ca++ channel blockade Misc. Adenosine (SVT), Digoxin (AF. AFL) Agent specific
Select agents with proven role in atrial arrhythmias
Significant considerations for side-effects and tolerability
Concurrent disease states
Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Disopyramide, Procainamide, Quinidine Lidocaine, Mexilitine Propafenone, Flecainide, Moricizine Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class III Amiodarone, Sotalol, Dofetilide, Ibutilide Dronedarone (pending FDA approval) Potassium channel blockade A/V
Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Side effects preclude long-term use No efficacy in atrial arrhythmias Propafenone, Flecainide Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class III Amiodarone, Sotalol, Dofetilide Dronedarone (pending FDA approval) Potassium channel blockade A/V
Intravenous Antiarrhythmic Dosing Drug Clinical Situation Dose Amiodarone Recurrent VT/VF Cardiac Arrest 150 mg IVPB x 1 over 10 minutes, then 1 mg/min x 6 hrs, then 0.5 mg/min infusion x 18+ hours 150-300mg IV bolus repeated PRN Diltiazem PSVT; rate control AF 0.25 mg/kg IV bolus (may repeat x 1 with 0.35 mg/kg bolus) then 5-15 mg/hr infusion Ibutilide Termination AF 1 mg/10min IVPB, may repeat x 1 Lidocaine VT/VF 100 mg IV push (may repeat x 2), then 2-4 mg/min infusion (1-2 mg/min in HF or liver disease) Magnesium Torsades, VT/VF 1-2 grams in 10ml NS IV push (MR x 2) Procainamide AF (WPW), VT 15-18 mg/kg at 20-50 mg/min IV load, then 1-6 mg/min infusion Verapamil PSVT; rate control AF 5mg IV push (may repeat up to 20mg), then 5-15 mg/hr infusion
4) Nitrates – PDE inhibitors (e.g. Viagra) Synergistic reduction in venous tone resulting in significant hypotension. Avoid combination 5) Warfarin - Rifampin Induces warfarin metabolism – often requires significant increases in warfarin doses by 50-100% within 7-14 days
Top 10 Drug-Drug Interactions in Cardiology Drugs Consequence/Suggested Action 6) Amiodarone – Beta-blockers Potential for bradycardia (and arrhythmias) especially on initiation, monitor for bradycardia 7) Amiodarone – Diltiazem/Verapamil Additive reduction in heart rate and myocardial contraction – monitor for bradycardia or signs of CO 8) Diltiazem/Verapamil - Statins Similar to amiodarone-statin interaction, try to avoid simvastatin, and lovastatin 9) Spironolactone – ACE Inhibitors/ARBs & KCl supplements Clinically indication concomitant therapy in HF, but carries high risk for hyperkalemia, especially with SCr – monitor closely, within 3 to 5 days of initiation or dose escalation 10) Propafenone - Warfarin Increased warfarin effect due to inhibition of metabolism – monitor INRs more closely x 2 weeks, dose reduce PRN