Background ATP-sensitive potassium (KATP) cardiac channels consist of inward rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptor subunits SUR2A (encoded by ABCC9). Objective To examine the association of mutations in KCNJ8 with Brugada (BrS) and early repolarization (ERS) syndromes and elucidate the mechanism underlying the gain of function of KATP channel current (IK-ATP). Methods Direct sequencing of KCNJ8 and other candidate genes was performed on 204 BrS and ERS probands and family members. Whole-cell and inside-out patch clamp methods were used to study mutated channels expressed in TSA201 cells. Results The same missense mutation, p.Ser422Leu (c.1265C>T) in KCNJ8, was identified in 3 BrS and 1 ERS proband, but was absent in 430 alleles from ethnically-matched healthy controls. Additional genetic variants included CACNB2b-D601E. Whole cell patch clamp studies showed a two-fold gain of function of glibenclamide-sensitive IK-ATP when KCNJ8-S422L was co-expressed with SUR2A-wild type. Inside-out patch clamp evaluation yielded a significantly greater IC50 for ATP in the mutant channels (785.5±2 vs. 38.4±3 µM, n=5; p<0.01) pointing to incomplete closing of the KATP channels under normoxic conditions. Patients with a CACNB2b-D601E polymorphism displayed longer QT/QTc intervals, likely due to their effect to induce an increase in ICa-L. Conclusion Our results support the hypothesis that KCNJ8 is a susceptibility gene for Brugada and early repolarization syndromes and point to S422L as a possible hotspot mutation. Our findings suggest that the S422L-induced gain of function in IK-ATP is due to reduced sensitivity to intracellular ATP.

Severe pacemaker syndrome developed in nearly 20% of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode. Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients.

Left internal mammary artery (LIMA) angiography was performed with diagnostic coronary angiography in 130 cases for which the coronary findings made use of the LIMA as a bypass graft a consideration. In 98% of the cases the approach to LIMA angiography was femoral with a 5F LIMA catheter first directed into the proximal subclavian and then advanced over a guidewire placed into the distal subclavian well beyond the origin of the LIMA. After withdrawing the wire the catheter was brought proximally to selectively cannulate and visualize the LIMA with nonionic contrast media. The only complication was a single transient occipital visual field loss. LIMA caliber too narrow to permit use as a graft was found twice, LIMA occlusion unrelated to prior surgery was found once, and LIMA occlusion related to prior surgery was found twice. Subclavian and/or vertebral stenosis was present five times. Large proximal branches of the LIMA best identified prior to surgery were present 12 times. Based on this experience, LIMA angiography 1) can be performed safely with a high degree of success, 2) demonstrates significant findings in 15% of cases, and 3) should therefore be performed whenever coronary angiographic findings make it appropriate to consider LIMA to coronary artery bypass grafting.

To study the association between anxiety and neurocardiogenic syncope as determined by head-up tilt table testing (HUT) in men and women with presyncope or syncope, patients with unexplained syncope or presyncope undergoing HUT were asked to complete the Burns Anxiety Inventory (BAI), a validated inventory of 33 questions with responses graded from 0 to 3. HUT consisted of a 30-minute tilt to 60 degrees, which if negative, was repeated with an isoproterenol infusion. A positive HUT was defined as symptomatic hypotension and/or bradycardia. Of the 66 patients who completed the BAI and underwent HUT, 33 were men and 33 were women. The mean age was 57 +/- 18 years (17-91 years). Patients with a positive HUT had a higher BAI score than those with a negative HUT (22 +/- 12 vs 14 +/- 13, P = 0.017). This association was stronger in women with a BAI score of 24 +/- 11 in those with a positive HUT versus 13 +/- 8 in those with a negative HUT (P = 0.005). In contrast, the mean BAI score for men with a positive HUT was 19 +/- 13, as compared to 15 +/- 16 for a negative HUT (P = 0.5). In conclusion, the present study demonstrates a statistical association between anxiety (as determined by BAI) and HUT result. Gender-based analysis revealed a more statistically significant relationship between anxiety and HUT outcome for women as compared to men.

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