• 
• 

Three Part Question

In a patient with [recent onset atrial fibrillation and left ventricular failure], can [diltiazem] [control the ventricular rate without worsening left ventricular function]?

Clinical Scenario

A 72-year-old woman with a past history of untreated hypertension presents with palpitations, shortness of breath and ankle swelling for the past 72 h. Examination shows that she has atrial fibrillation with a ventricular rate of 162 bpm, a blood pressure of 146/78 mm Hg and signs of mild left ventricular failure (LVF), both clinically and on the chest x ray. ECG shows atrial fibrillation with a ventricular rate of 160 bpm and voltage criteria for left ventricular hypertrophy. You decide that ventricular rate control is the most appropriate therapy for her. You have been told recently that the chronotropic effects of digoxin are of slow onset and amiodarone runs the risk of cardioversion. You wonder therefore whether diltiazem, a calcium antagonist, may be of use.

Search Strategy

Medline 1966 to week 4 April 2009 using Ovid interface:
{[Exp atrial fibrillation or atrial fibrillation.mp or AF.mp] AND [exp calcium channel blockers or calcium channel blocker.mp or exp diltiazem or diltiazem.mp] AND [exp heart failure or congestive heart failure.mp or congestive cardiac failure.mp or left ventricular failure.mp or exp pulmonary edema or pulmonary edema.mp or pulmonary oedema.mp]}.

The search was repeated in EMBASE 1980 to 2009 week 18 and the Cochrane database.

Search Outcome

The Medline search found 78 papers. Two papers were relevant to the question and are detailed in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Goldenberg et al, 1994, USA	37 Patients with atrial fibrillation or flutter and moderate to severe LVF randomly assigned to placebo or iv diltiazem, 0.25 mg/kg over 2 minutes Those randomly assigned to the placebo group who did not respond then received iv diltiazem at 0.25 mg/kg over 2 minutes Any patient who did not respond to iv diltiazem received a further iv dose of diltiazem at 0.35 mg/kg LVF was defined as patients with NYHA class III or IV disease as well as pulmonary congestion on clinical exam and on CXR	Multicentre, randomised double blind placebo controlled trial with an open-label phase for placebo non-responders	Ventricular rate control as defined by a HR <100 bpm, >20% decrease in HR compared with baseline or conversion to sinus rhythm	18/22 Patients randomly assigned to diltiazem arm achieved reduction in ventricular rate within 5 minutes, with a further three patients responding to a further higher dose of diltiazem None of the 15 patients in the placebo arm achieved a therapeutic response with placebo but all had a therapeutic response when given open label iv diltiazem	Severe chronic heart failure with ejection fraction <25% present in 9/37 (24%) of patients 23/37 were NYHA class III 14/37 were NYHA class IV Digoxin prescribed for 59% of patients pre-study. Small numbers only. Not performed in the ED. Uncertain whether atrial fibrillation was of acute onset
			Worsening of heart failure	There was no worsening of congestive heart failure in any patient
			Patient reported symptoms	54% of Patients in the initial blinded diltiazem arm reported an improvement in their symptoms, none in the placebo arm
Heywood et al, 1991, USA	Nine patients with atrial fibrillation and acute congestive cardiac failure (JVP >9 cm, rales, S3, CXR evidence of LVF) given 0.25 mg/kg iv diltiazem followed by 0.3 mg/kg if ventricular rate reduction <10% Excluded if SBP <90 mm Hg, recent MI or PaO2 <45 mm Hg in air	Uncontrolled study	Control of ventricular rate Change in haemodynamic parameters Side effects	All patients achieved significant rapid control of ventricular rate with no side-effects (mean 142 bpm to 114 bpm) Significant increase in cardiac output and stroke volume but significant decrease in blood pressure, systemic vascular resistance and pulmonary artery systolic pressures Pulmonary capillary wedge and right atrial pressures did not change	Small observational study Significant congestive heart failure (34%, SD 18%) No other drugs given before administration of diltiazem Studied in a CCU but patients recruited from the ED

Comment(s)

Atrial fibrillation and cardiac failure share common risk factors and frequently co-exist. The onset of atrial fibrillation with a rapid ventricular rate may cause an acute deterioration of cardiac function. Control of the ventricular rate, an important determinant of left ventricular function, is therefore necessary. However, trials of drugs for the control of ventricular rate in patients with acute atrial fibrillation normally exclude patients with significant LVF.

There are no emergency department randomised trials of drug therapy for the control of rapid ventricular rates in patients with acute atrial fibrillation and significant LVF.

Editor Comment

bpm, beats per minute; CCU, coronary care unit; CXR, chest x ray; ED, emergency department; HR, heart rate; iv, intravenous; JVP, jugular venous pressure; LVF, left ventricular failure; MI, myocardial infarction; NYHA, New York Heart Association; PaO2, arterial oxygen tension; SBP, systolic blood pressure.

Clinical Bottom Line

There is some low-quality evidence suggesting that diltiazem is beneficial when used for the acute treatment of atrial fibrillation and LVF. However, it should not be used in this way until further evidence is forthcoming.

References

1. Goldenberg IF, Lewis WR, Dias VC, Heywood JT, Pederson WR. Intravenous diltiazem for the treatment of patients with atrial fibrillation or flutter and moderate to severe congestive cardiac failure. Am J Cardiol 1994;74:884-9.
2. Heywood JT, Graham B, Marias GE, Jutzy KR. Effects of intravenous diltiazem on rapid atrial fibrillation accompanied by congestive cardiac failure. Am J Cardiol 1991;67:1150-2.