Should cardiologists who are not electrophysiologists be inserting implantable cardioverter-defibrillators (ICDs)? Curtis et al. performed a retrospective cohort study of patients who had an ICD fitted between January 2006 and June 2007. Patients were grouped according to whom had implanted their device: electrophysiologists, nonelectrophysiologist cardiologists, thoracic surgeons, and other specialists. The main outcome measures examined were the proportion of patients meeting the criteria for a defibrillator with cardiac resynchronization therapy (CRT-D) who received that device, and the in-hospital procedural complication rates.

111293 ICD implantations were included in the analysis. Overall, 70.9% were performed by electrophysiologists, 21.9% by nonelectrophysiologist cardiologists, 1.7% by thoracic surgeons, and 5.5% by other specialists. Patients who had an ICD inserted by anyone other than an electrophysiologist were found to be at an increased risk for complications both in unadjusted (p<0.001) and adjusted analyses (relative risk for nonelectrophysiologist cardiologists, 1.11; relative risk for thoracic surgeons, 1.44). Although 35841 patients met criteria for CRT-D, when a nonelectrophysiologist cardiologist or thoracic surgeon performed the procedure, patients were significantly less likely to receive the correct device (relative risk for nonelectrophysiologist cardiologists, 0.93; relative risk for thoracic surgeons, 0.81). The study also demonstrated that electrophysiologists were available in the majority of hospitals where thoracic surgeons and general cardiologist were performing their ICD insertions.

This study only looked at in-hospital outcomes, and it may be that long-term complications are equally as skewed; the same group is planning longer-term follow-up. Currently, no criteria exist for determining what procedures a physician may or may not perform; this paper demonstrates that this problem will become increasingly important as sub-specialisation in cardiology continues.

Curtis JP, Luebbert JJ, Wang Y, et al. Association of physician certification and outcomes among patients receiving an implantable cardioverter defibrillator. JAMA 2009; 301:1661-1670.

Coromilas J. Physician credentials and ICD implantation. JAMA 2009; 301:1713-1174.

The diagnosis and management of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) can be problematic – the disease has a highly variable clinical presentation, and cardiac arrhythmias and sudden cardiac death occur frequently. Currently the diagnosis is usually made clinically using criteria that have been defined by an international task force -whilst these are specific they are not very sensitive. Furthermore, the structural changes in ARVC generally spare the sub-endocardium and do not tend to involve the inter-ventricular septum and therefore the pathological features of ARVC may not be identified on conventional endomyocardial biopsy. Additionally, the pathological features are more pronounced in patients with severe disease, but may not be observed in patients with early disease.

Genetic testing offers an alternative method of diagnosis, and mutations in desmosomal proteins including desmoplakin, plakoglobin, plakophilin 2, desmocollin 2 and desmoglein 2 have been identified in approximately 40% of patients with ARVC. The authors of this paper had previously observed that levels of plakoglobin (also known as γ-catenin) were greatly reduced at intercalated disks in patients with rare recessive forms of ARVC. They further studied commoner forms of ARVC related to a variety of desmosomal genes and observed a decreased plakoglobin (a protein which links adhesion molecules at the intercalated disk to the cytoskeleton) signal level. Following this they sought to identify whether a decreased plakoglobin signal-level, identified at the myocardial cell-cell junctions was a sensitive and specific marker of ARVC using immunohistochemical techniques on human myocardial samples.

Myocardial samples from 11 patients with ARVC were tested for desmosomal gene mutations and of these 8 had the mutation. Myocardial autopsy samples from 10 patients with no evidence of clinical or pathological heart disease were used as a control. All ARVC samples but no controls demonstrated a marked reduction in levels of plakoglobin. Other desmosomal proteins showed variable changes but levels of the non-desmosomal adhesion molecule N-cadherin were normal in all patients with ARVC. In order to ascertain whether a decreased plakoglobin level was specific for ARVC, myocardial samples from 15 subjects with either dilated, ischaemic or hypertrophic cardiomyopathy were analysed. In all of these, N-cadherin and plakoglobin levels were indistinguishable from controls. Additionally, blinded immunohistochemical analysis of cardiac biopsy samples from the Johns Hopkins ARVC registry was performed. The correct diagnosis was made in 10/11 subjects with a definite diagnosis of ARVC on clinical criteria. The authors also ruled out ARVC in 10/11 subjects without ARVC, overall sensitivity 91%, specificity 82%, positive predictive value 83%, negative predictive value 90%. The plakoglobin level was diffusely reduced in ARVC samples including in those obtained from the left ventricle and inter-ventricular septum.

The results from this study demonstrate that reduced plakoglobin at intercalated disks is a consistent feature of ARVC and is not seen in other forms of heart muscle disease. It also shows that levels of the non-desmosomal adhesion molecule N-cadherin is normal in patients with ARVC or other forms of heart disease. Further validation studies will be necessary before this new test can be used clinically. In addition, it is also unknown whether all causes of ARVC result in decreased levels of plakoglobin at the intercalated disks – viral infection causing myocarditis has been associated with ARVC in some patients. This would suggest that acquired causes may also lead to the disease. Finally, although in ARVC myocardial degeneration and fibro-fatty replacement occur preferentially in the right ventricle, a diffuse reduction in plakoglobin levels was observed. This might suggest that it is not necessary to biopsy the heart in areas showing structural change to make the diagnosis. Moreover, it could be possible to obtain comparable information from more accessible tissues containing desmosomes such as hair follicles and buccal mucosa

· Asimaki A, Tandri H, Huang H et al. A New Diagnostic Test for Arrhythmogenic Right Ventricular Cardiomyopathy. N Engl J Med 2009;360:1075-84

Dronedarone is a benzofuran derivative with an electropharmacological profile similar to amiodarone but with different effects on individual ion channels. In two previous randomised controlled trials dronedarone was shown to be more effective than placebo in maintaining sinus rhythm and controlling ventricular rate during recurrences of AF.

The ATHENA (A Placebo Controlled Double Blind Parallel Arm Trial to Assess the Efficacy of Dronedarone 400mg bid for the Prevention of Cardiovascular Hospitalisation or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter) trial was a multicentre trial conducted in 37 countries and which involved 4628 patients. 2301 were randomised to receive dronedarone and 2327 were assigned to receive placebo. In light of the results from the ANDROMEDA trial (which looked at dronedarone in patients with advanced heart failure and was terminated because of an excess of deaths in the treatment arm) patients with recent decompensated heart failure or NYHA Class IV heart failure were excluded. The primary outcome was the first hospitalisation due to cardiac events or death from any cause. Secondary outcomes were death from any cause, death from cardiovascular causes and first hospitalisation due to cardiovascular events.

Patients were followed up for a mean of 21 +/-5 months. The study drug was discontinued prematurely in 30.2% of patients n the dronedarone arm an 30.8% in the placebo arm, mostly because of adverse events. The primary outcome occurred in 734 patients (31.9%) in the dronedarone group and 917 patients (39.4%) in the placebo group, hazard ratio for dronedarone 0.76 (95%CI 0.69-0.84, p<0.001). There were 116 deaths (5.0%) in the dronedarone group and 139 (6.0%) in the placebo group (HR 0.84, 95%CI 0.66-1.08, p=0.18). There were 63 deaths from cardiovascular causes (2.7%) in the dronedarone group and 90 (3.9%) in the placebo group (HR 0.71, 95%CI 0.51-0.98, p=0.03), predominantly due to a reduction of death from arrhythmia with dronedarone. Higher rates of bradycardia, QT-interval prolongation, nausea, diarrhoea, rash and increase in serum creatinine level occurred in the dronedarone group. Rates of thyroid and pulmonary related adverse events were not significantly different between the 2 groups although this should be interpreted with caution as the mean follow-up was 21 months and patients treated with amiodarone an develop such side effects >2 years from initiation of therapy.

It is likely that a combination of prevention of recurrence of AF and rate control during arrhythmic episodes were responsible for reducing the rates of hospitalization. The difference in outcome between ATHENA and ANDROMEDA is probably due to the differing enrollment criteria. It would appear that dronedarone increases cardiovascular mortality among patients with advanced and decompensated heart failure but reduces mortality among patients with less severe heart failure. The increase in creatinine level which was also seen in ANDROMEDA may not reflect a deterioration in renal function. It would appear that dronedarone reduces creatinine clearance without affecting glomerular filtration rate as a result of a specific partial inhibition of tubular organic-cation transporters. There was a relatively high rate of discontinuation of the study drug (30.2% in the dronedarone group) which may have underestimated both the benefit of dronedarone but also the likelihood of an increase in adverse events. The efficacy and tolerability of dronedarone and amiodarone as used to prevent the recurrence of AF are currently being evaluated in an ongoing clinical trial.

• Hohnloser SH, Crijns HJGM, Van Eickels M et al. Effect of dronedarone on Cardiovascular Events in Atrial Fibrillation. N Engl J Med 2009; 360:668-78

Although amiodarone maintains sinus rhythm in 45% to 70% of patients during 12 to 54 months follow-up, it is also associated with many serious non-cardiac side effects.  To investigate if episodic treatment with amiodarone could still be effective in preventing atrial fibrillation (AF), but without causing significant side-effects, Ahmed et al. randomised 209 patients with recurrent symptomatic persistent atrial fibrillation to either episodic (drug stopped four weeks after cardioversion and restarted only if patient symptomatic) or continuous amiodarone treatment.

After a median follow-up of 2.1 years, 51 (48%) of those receiving episodic treatement vs 64 (62%) of those receiving continuous treatment had sinus rhythm (P=.05).  AF recurred in 85 patients (80%) of patients treated episodically, compared to 56 (54%) of those treated contuously (p<.001).  No significant difference was noted in the primary composite endpoint of major adverse events related to underlying heart disease or amiodarone (35% vs 33%).  Nonstatistically significant differences in the incidence of amiodarone-related major events (19% episodic vs 24% continuous) and underlying heart disease-related major events (16% vs 9%) were noted.  All-cause mortality and cardiovascular hospital admissions were higher among those receiving episodic treatment (53% vs 34%).

Although the number of patients in this trial is small, the message appears to be that there is no role for PRN amiodarone in the treatment of atrial fibrillation.  If amiodarone side-effects are of concern, then lowering the dose, rather than interrupting therapy, is the preferred strategy.

• Ahmed S, Rienstra M, Crijns HJGM et al.  Continuous vs episodic prohylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial. JAMA 2008; 300:1784-1792.

Atrio-ventricular node ablation has been used to treat symptomatic atrial fibrillation with poor rate control although these studies have contained few subjects with low ejection fractions. Biventricular pacing has recently been shown to be superior to right ventricular pacing following atrio-ventricular node ablation.

The Pulmonary Vein Antrum Isolation (PVI) versus AV Node Ablation with Biventricular Pacing for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure (PABA-CHF) trial aimed to compare pulmonary vein isolation with atrioventricular node ablation and biventricular pacing in patients with an ejection fraction <40%, symptomatic atrial fibrillation and NYHA Class II-III heart failure. This was a prospective multicentre randomised controlled trial.  The primary end-point was a composite of ejection fraction, distance on a 6 minute walk test and Minnesota Living with Heart Failure Questionnaire (MLWHF) score.  Follow up was performed with a loop event monitor that patients wore from months 2-6 post-procedure. Patients recorded any symptoms and recorded at least 2-3 transmissions/week, even if they were asymptomatic.

41 patients underwent PVI and 40 AV node ablation with biventricular pacing.  The composite primary end point favoured patients undergoing PVI with an improved questionnaire score at 6 months (p<0.001), a longer 6 minute walk test (340m vs 297m, p<0.001) and a higher ejection fraction (35% vs 28%, p<0.001). 88% of patients receiving anti-arrhythmic drugs in the PVI group, and 71% not receiving these agents, were free of atrial fibrillation at 6 months. In the PVI population, 2 patients developed pulmonary stenosis, 1 a pericardial effusion and 1 pulmonary oedema. In the AV node ablation and biventricular pacing arm, lead displacement occurred in 1 patient and 1 had a pneumothorax.

The AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) Trial was a landmark study that has been argued to show a benefit of rate control over a rhythm control strategy. However subsequent analysis of the data demonstrated that rhythm control with restoration of sinus rhythm conferred survival benefit. PVI ( arguably a form of rhythm control) in this trial had a good success rate and resulted in superior morphological and functional outcomes when compared to the optimal rate control strategy (AV node ablation and biventricular pacing). 100% of patients in the AV node ablation and pacing arm had atrial fibrillation at 3 and 6 months – an unexpected finding.

Although this study is limited by the short follow-up data and the fact that the procedures were all performed in very experienced centres, it nonetheless provides strong support for PVI in centres with the appropriate experience.

• Khan MN, Jais P, Cummings J et al. Pulmonary-Vein Isolation for Atrial Fibrillation in Patients with Heart Failure. N Engl J Med 2008;359:1778-85