Impaired HRT, abnormal TWA, and an EF <0.50 beyond 8 weeks after MI reliably identify patients at risk of serious events. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; http://www.clinicaltrials.gov/ct/show/NCT00399503?order=1; NCT00399503).

CSH is associated with a significantly increased risk of infection requiring hospitalization within 1 year following cardiac implantable electronic device surgery. Strategies aimed at reducing hematomas may decrease the long-term risk of infection. (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial [BRUISE CONTROL]; NCT00800137).

The expression of calreticulin, a Ca 2+ -binding chaperone of the endoplasmic reticulum, is elevated in the embryonic heart, and because of impaired cardiac development, knockout of the Calreticulin gene is lethal during embryogenesis. The elevated expression is downregulated after birth. Here we have investigated the physiological consequences of continued high expression of calreticulin in the postnatal heart, by producing transgenic mice that overexpress the protein in the heart. These transgenic animals exhibit decreased systolic function and inward I Ca,L , low levels of connexin43 and connexin40, sinus bradycardia, and prolonged atrioventricular (AV) node conduction followed by complete heart block and sudden death. We conclude that postnatal downregulation of calreticulin is essential in the development of the cardiac conductive system, in particular in the sinus and AV nodes, when an inward Ca 2+ current is required for activation. This work identifies a novel pathway of events, leading to complete heart block and sudden cardiac death, which involves high expression of calreticulin in the heart. G AC TAC AG C T C G T C C T T G G C C T G T C TAG -CATAGTCAGGAACATCATATGGGTAC-3′were annealed to create double strand DNA fragmentepitope is underlined followed by KDEL ER retrieval signal). cDNA encoding calreticulin was synthesized by a PCR-driven amplification (8) and cloned into SalI site of a plasmid containing the 5.5-kb mouse cardiac α-myosin heavy chain (α-MHC) (Figure 1a). Linearized pBS-α-MHC-CRT-HA was microinjected into the fertilized oocytes, which were transferred into the oviduct of pseudopregnant FVB/N mice. Transgenic mice were identified by PCR analysis of tail genomic DNA using a forward primer corresponding the 5′ end of the mouse the α-MHC promoter sequence (MHCf: 5′-TATCTCCCCCATAAGAGTTT-3′) and a reverse primer corresponding to the 5′ end of the calreticulin cDNA sequence (CRT-N3A: 5′-GTCAATCTTCACCTCAT-ACG-3′) (Figure 1a). Founder mice were identified, bred with wild-type FVB/N mice, and maintained in a pathogen-free environment.SDS-PAGE and Western immunoblotting. Proteins from mouse tissues including heart, brain, lung, liver, kidney, and thymus were lysed, separated by SDS-PAGE followed by immunoblotting (9). Protein assays were carried out using DC Protein Assay kit (Bio-Rad Laboratories Inc., Hercules, California, USA). Blots were probed with rabbit anti-HA antibodies, goat or rabbit anti-calreticulin antibodies (9, 10), rabbit anti-calnexin (Stress Gene, Victoria, British Columbia, Canada; 1:500 dilution), rabbit anti-BiP (1:2,000 dilution), rabbit anti-PDI (9) (1:500 dilution), rabbit anti-calsequestrin (10) (1:300 dilution), rabbit anti-Cx43 (1:20,000 dilution), or rabbit anti-SERCA2 antibodies (11) (1:1,000 dilution). Antibody binding was detected with appropriate peroxidase-conjugated secondary antibodies followed by a standard enhanced chemiluminescence development reaction.Northern blot analysis. Northern blot analysis was carried out as described elsewhere (10). The following c...

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