J Am Coll Cardiol. 2009 May 5; 53(18): 1690-8Nieuwlaat R, Eurlings LW, Cleland JG, Cobbe SM, Vardas PE, Capucci A, López-Sendòn JL, Meeder JG, Pinto YM, Crijns HJOBJECTIVES: Our aim was to identify shortcomings in the management of patients with both atrial fibrillation (AF) and heart failure (HF). BACKGROUND: AF and HF often coincide in cardiology practice, and they are known to worsen each other's prognosis, but little is known about the quality of care of this combination. METHODS: In the observational Euro Heart Survey on AF, 5,333 AF patients were enrolled in 182 centers across 35 European Society of Cardiology member countries in 2003 and 2004. A follow-up survey was performed after 1 year. RESULTS: At baseline, 1,816 patients (34%) had HF. Recommended therapy for HF with left ventricular systolic dysfunction (LVSD) with a beta-blocker and either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker was prescribed in 40% of HF patients, while 29% received the recommended drug therapy for both LVSD-HF and AF, consisting of the combination of a beta-blocker, either ACEI or angiotensin II receptor blocker, and oral anticoagulation. Rate control was insufficient with 40% of all HF patients with permanent AF having a heart rate < or =80 beats/min. In the total cohort, HF patients had a higher risk for mortality (9.5% vs. 3.3%; p < 0.001), (progression of) HF (24.8% vs. 5.0%; p < 0.001), and AF progression (35% vs. 19%; p < 0.001) during 1-year follow-up. Of all recommended drugs for AF and LVSD-HF, only ACEI prescription was associated with improved survival during 1-year follow-up (odds ratio: 0.51 [95% confidence interval: 0.31 to 0.85]; p = 0.011). CONCLUSIONS: The prescription rate of guideline-recommended drug therapy for AF and LVSD-HF is low. Randomized controlled trials targeting this highly prevalent subgroup with AF and HF are warranted.

Circ Res. 2009 Apr 30; Remme CA, Scicluna BP, Verkerk AO, Amin AS, van Brunschot S, Beekman L, Deneer VH, Chevalier C, Oyama F, Miyazaki H, Nukina N, Wilders R, Escande D, Houlgatte R, Wilde AA, Tan HL, Veldkamp MW, de Bakker JM, Bezzina CRConduction slowing of the electric impulse that drives the heartbeat may evoke lethal cardiac arrhythmias. Mutations in SCN5A, which encodes the pore-forming cardiac sodium channel alpha subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable. We hypothesized that genetic modifiers underlie the variability in conduction slowing and disease severity. With the aim of identifying such modifiers, we studied the Scn5a(1798insD/+) mutation in 2 distinct mouse strains, FVB/N and 129P2. In 129P2 mice, the mutation resulted in more severe conduction slowing particularly in the right ventricle (RV) compared to FVB/N. Pan-genomic mRNA expression profiling in the 2 mouse strains uncovered a drastic reduction in mRNA encoding the sodium channel auxiliary subunit beta4 (Scn4b) in 129P2 mice compared to FVB/N. This corresponded to low to undetectable beta4 protein levels in 129P2 ventricular tissue, whereas abundant beta4 protein was detected in FVB/N. Sodium current measurements in isolated myocytes from the 2 mouse strains indicated that sodium channel activation in myocytes from 129P2 mice occurred at more positive potentials compared to FVB/N. Using computer simulations, this difference in activation kinetics was predicted to explain the observed differences in conduction disease severity between the 2 strains. In conclusion, genetically determined differences in sodium current characteristics on the myocyte level modulate disease severity in cardiac sodium channelopathies. In particular, the sodium channel subunit beta4 (SCN4B) may constitute a potential genetic modifier of conduction and cardiac sodium channel disease.

Eur J Cardiothorac Surg. 2009 Apr 28; Adluri RK, Singh AV, Skoyles J, Robins A, Hitch A, Baker M, Mitchell IMBackground: Hypothermic cardiopulmonary bypass is associated with low perfusion state causing a mismatch between demand and supply to various organs such as gut, kidneys and brain. The consequences are thought to be responsible for postoperative complications like systemic inflammatory response, renal failure, neurological injury, etc. Pharmacological agents like dopamine, dopexamine and dobutamine have been used in an attempt to reduce hypoperfusion and hence complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has recently been shown to be specific reno-splanchnic vasodilator in animal studies. We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood flow (HBF) during and after cardiopulmonary bypass and compared these with dopexamine. Methods: Ethics committee approval was obtained. Forty-two consecutive patients with good/moderate left ventricular function undergoing either elective/urgent coronary artery bypass grafting were included in the study. Patients were randomised to receive either fenoldopam (0.2mug/kgmin) (F; n=14) or dopexamine (2.0mug/kgmin) (Dx; n=14) normal saline (NS; n=14) continuously after induction of anaesthesia for 24h following completion of surgery. HBF was measured using the Indocyanine green dye disappearance rate method, before, during and after cardiopulmonary bypass. Data were collected pre-, intra- and postoperatively. Serum liver enzymes were measured during the perioperative period. Repeated measures ANOVA test was used to compare timed samples in both groups. Results: The study groups were comparable in pre- and intraoperative variables. In the fenoldopam and dopexamine groups there was a significant increase in heart rate 15min following the commencement of the infusion (NS:F:DX::-2.0+/-7.8beats/min:13.6+/-8.1beats/min (p=0.007):18.36+/-20.2beats/min (p=0.004)). However the change in mean arterial blood pressure was similar (NS:F:DX::-12.7+/-14.9:-4.0+/-23.1 (p=0.699):-2.6+/-22.3) (p=0.235). Cardiac index increased and systemic vascular resistance decreased (requiring noradrenaline infusion) in the fenoldopam group, however this did not reach statistical significance. Hepatic blood flow reduced during CPB and returned to near preoperative levels in all three groups with no statistical difference between groups. Conclusions: Fenoldopam infusion induced transient tachycardia, with no augmentation of hepatic blood flow whereas dopexamine induced tachycardia and did not augment hepatic blood flow. Fenoldopam and dopexamine may have hepato-protective effect.

Br J Radiol. 2009 Apr 27; Junqueira FP, Filho RM, Coutinho AC, Loureiro R, DE Pontes PV, Domingues RC, Dro Gasparetto ELIn this study we evaluated patients with pulmonary arterial hypertension (PAH) and impaired right ventricular function. We used cardiac MRI for the detection of myocardial delayed enhancement (MDE) and its possible association with other clinical variables. 20 patients (6 males and 14 females, aged 44.5+/-11 years; 15 New York Heart Association class III, 5 class IV) with known PAH (13 idiopathic, 7 resulting from chronic pulmonary embolism) were evaluated for the detection of MDE. Short-axis cine images of the heart were made for ventricular function assessment using a steady-state free precession sequence. For MDE evaluation, a short-axis phase-sensitive inversion recovery sequence was performed 10 min after intravenous administration of 0.2 mmol kg(-1) gadodiamide. Right ventricle (RV) systolic dysfunction, RV enlargement and RV hypertrophy were present in 20 patients (RV ejection fraction, 21.5+/-7.2 %; RV diastolic diameter, 5.97+/-0.79 cm; RV wall thickness, 0.73+/-0.10 cm). 13 of the 20 patients (65%) were positive for MDE (10 anterior, 12 inferior). All 13 positive patients with MDE demonstrated small hyperintense areas at the insertion points of the RV free wall in the interventricular septum. We found no significant correlation between MDE and ejection fraction or other haemodynamic variables. In this study MDE correlated positively only with the duration of disease. We found that septal MDE can be present in patients with PAH and impaired ventricular function. However, further studies are necessary to investigate this possible association and its prognostic implication.