Impact of arrhythmia on diagnostic performance of adenosine stress CMR in patients with suspected or known coronary artery disease.

BACKGROUND: The diagnostic performance of adenosine stress cardiovascular magnetic resonance (CMR) in patients with arrhythmias presenting for work-up of suspected or known CAD is largely unknown, since most CMR studies currently available exclude arrhythmic patients from analysis fearing gating problems, or other artifacts will impair image quality. The primary aim of our study was to evaluate the diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for 1) work-up of suspected coronary artery disease (CAD), or 2) work-up of ischemia in known CAD. METHODS: Patients with arrhythmia referred for work-up of suspected CAD or work-up of ischemia in known CAD undergoing adenosine stress CMR were included if they had coronary angiography within four weeks of CMR. RESULTS: One hundred fifty-nine patients were included (n = 64 atrial fibrillation, n = 87 frequent ventricular extrasystoles, n = 8 frequent supraventricular extrasystoles). Of these, n = 72 had suspected CAD, and n = 87 had known CAD. Diagnostic accuracy of the adenosine stress CMR for detection of significant CAD was 73 % for the entire population (sensitivity 72 %, specificity 76 %). Diagnostic accuracy was 75 % (sensitivity 80 %, specificity 74 %) in patients with suspected CAD, and 74 % (sensitivity 71 %, specificity 79 %) in the group with known CAD. For different types of arrhythmia, diagnostic accuracy of CMR was 70 % in the atrial fibrillation group, and 79 % in patients with ventricular extrasystoles. On a per coronary territory analysis, diagnostic accuracy of CMR was 77 % for stenosis of the left and 82 % for stenosis of the right coronary artery. CONCLUSION: The present data demonstrates good diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for work-up of suspected CAD, or work-up of ischemia in known CAD. This holds true for a per patient, as well as for a per coronary territory analysis.

Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis.

BACKGROUND: The diagnosis of myocarditis is challenging due to its varying clinical presentation. Since myocarditis can be associated with significant 5-year mortality, and postmortem data show myocarditis in almost 10% of all adults suffering sudden cardiac death, individual risk stratification for patients with suspected myocarditis is of great clinical interest. We sought to demonstrate that patients with clinically suspected myocarditis and a normal cardiovascular magnetic resonance (CMR) according to our definition have a good prognosis, independent of their clinical symptoms and other findings. METHODS: Prospective clinical long-term follow-up of consecutive patients undergoing CMR for work-up of clinically suspected myocarditis at our institution in 2007-2008. RESULTS: Follow-up was available for n=405 patients (all-comers, 54.8% inpatients, 38% outpatient referrals from cardiologists). Median follow-up time was 1591 days. CMR diagnosis was "myocarditis" in 28.8%, "normal" in 55.6% and "other pathology" in 15.6%. Normal CMR was defined as normal left ventricular (LV) volumes and normal left ventricular ejection fraction (LV-EF) in the absence of late Gadolinium Enhancement (LGE). The overall mortality was 3.2%. There were seven cardiac deaths during follow-up, in addition one aborted SCD and two patients had appropriate internal cardioverter defibrillator (ICD) shocks - all of these occurred in patients with abnormal CMR. Kaplan-Meier analysis with log-rank test showed significant difference for major adverse cardiac events (cardiac death, sudden cardiac death (SCD), ICD discharge, aborted SCD) between patients with normal and abnormal CMR (p=0.0003). CONCLUSION: In our unselected population of consecutive patients referred for CMR work-up of clinically suspected myocarditis, patients with normal CMR have a good prognosis independent of their clinical symptoms and other findings.

Atrial reverse remodeling: restitution of early tachycardia-induced alterations of atrial ion currents after termination of rapid atrial pacing in rabbits.

BACKGROUND AND PURPOSE: Studies report on the reversal of electrophysiological parameters altered by atrial tachycardia after cessation of the latter. However, there is no data concerning reversal of tachycardia-induced alterations of ion currents. Reverse remodeling of atrial ion currents (I(Ca,L), I(to), I(sus)) was studied in our rabbit model of tachycardia-induced electrical remodeling. METHODS: Three groups each with four animals were built. Rapid atrial pacing (600/min) for 5 days was applied in all groups. Thereafter, different time intervals (5, 10, 20 days) were awaited before the patch clamp experiments. RESULTS: Similar to I(to) remodeling in our model, within 20 days after cessation of atrial tachycardia, time course of I(to) reverse remodeling was also U-shaped. In contrast, there was no significant recovery of I(Ca,L) which was initially reduced by rapid atrial pacing. CONCLUSION: Relevance of a missing recovery of I(Ca,L) is likely as this current is closely linked with intracellular calcium handling.

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia in man. Over the past years, importance of the renin-angiotensin-aldosterone system in AF pathophysiology has been recognized. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed with special regards concerning the effects on AF-induced structural remodeling. However, there is more and more evidence that MR antagonism also influences atrial electrophysiology and, respectively, AF-induced electrical remodeling, whereas the molecular mechanisms are almost unknown. The aim of this mini-review is to give an overview about the role of aldosterone in AF pathophysiology in principle and to summarize current available data concerning affection of cardiac ion channels by aldosterone and MR antagonism. Finally, as modulation of oxidative stress is discussed as one main therapy principle of "upstream" treatment of AF, potential mechanisms how modulation of oxidative stress by aldosterone and accordingly MR antagonism might alter atrial ion currents are delineated. Summarized, publications concerning potential mechanisms of aldosterone- and MR antagonism-modulated cardiac ion channels in various experimental settings are almost exclusively limited to the ventricular level and, partly, they are also contradictorily. Translation of these data to the atria is problematic because atrial and ventricular electrophysiology exhibit remarkable differences. It can be concluded that further research on the "atrial level" is needed in order to clarify the potential impact of the affection of atrial ion channels by aldosterone and accordingly MR antagonism in "upstream" therapy of AF.

Atorvastatin treatment affects atrial ion currents and their tachycardia-induced remodeling in rabbits.

AIMS: Atrial fibrillation (AF) leads to electrical atrial remodeling including alterations of various ion channels early after arrhythmia onset. The beneficial effects of statins in AF treatment due to their influence on oxidative stress and inflammation are discussed. Our hypothesis was that statins might also alter atrial ion currents and their early tachycardia-induced remodeling. MAIN METHODS: Effects of an atorvastatin treatment (7 days) on atrial ion currents and their tachycardia-induced alterations were studied in a rabbit model of tachycardia-induced electrical remodeling (rapid atrial pacing (600 min) for 24 and 120 h). Ion currents (L-type calcium channel [I(Ca,L)], transient outward current [I(to)]) were measured using whole cell patch clamp method and were compared with previous experiments in untreated but also tachypaced animals. KEY FINDINGS: Atorvastatin treatment alone decreased I(Ca,L) similar to rapid atrial pacing alone, currents were also further reduced by additional atrial tachypacing. I(to) and its pacing-induced down-regulation after 24 h were not influenced by atorvastatin treatment. However, I(to) was still reduced after 120 h in atorvastatin-treated animals and did not return to control values as expected. SIGNIFICANCE: The present study establishes that an atorvastatin treatment can affect atrial ion currents and their tachycardia-induced remodeling in a rabbit model. These results show that-amongst other positive effects on oxidative stress and inflammation-the impact of statins on ion currents and their tachycardia-induced alterations might also play a role in "upstream" treatment of AF with HMG-CoA reductase inhibitors.

Effects of selective mineralocorticoid receptor antagonism on atrial ion currents and early ionic tachycardia-induced electrical remodelling in rabbits.

Over the past years, the importance of the renin-angiotensin-aldosterone system in atrial fibrillation (AF) pathophysiology has been recognised. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed. Hypothesising that selective MR antagonism might also influence atrial ion currents (L-type calcium current [I (Ca,L)], transient outward potassium current [I (to)], sustained outward potassium current [I (sus)]) and their tachycardia-induced remodelling, the effects of an eplerenone treatment were studied in a rabbit model. Six groups each with four animals were built. Animals of the control group received atrial pacing leads, but in contrast to the pacing groups, no atrial tachypacing (600 per minute for 24 and 120 h immediately before heart removal) was applied. Animals of the eplerenone groups were instrumented/paced as the corresponding control/pacing groups, but were additionally treated with eplerenone (7 days before heart removal). Atrial tachypacing was associated with a reduction of I (Ca,L). I (to) was decreased after 24 h of tachypacing, but returned to control values after 120 h. In the absence of rapid atrial pacing, MR antagonism reduced I (Ca,L) to a similar extent as 120 h of tachypacing alone. Based on this lower "take-off level", I (Ca,L) was not further decreased by high-rate pacing. I (to) and its expected tachycardia-induced alterations were not influenced by MR antagonism. In our experiments, selective MR antagonism influenced atrial I (Ca,L) and its tachycardia-induced alterations. As changes of I (Ca,L) are closely linked with atrial calcium signalling, the relevance of these alterations in AF pathophysiology and, accordingly, AF treatment is likely and has to be further evaluated.