Aleong, Ryan G.

AbstractIntroductionEsophageal injury is a well‐known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus.MethodsTo investigate temperature gradients across the tissue, we developed a porcine heart–esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10–15 g, 25–35 W, 30 s) or high‐power short duration (HPSD, 10–15 g, 40–50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed.ResultsIn total, five experiments were conducted each utilizing new porcine posterior LA wall‐esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus.ConclusionBoth SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.

Background— Brugada syndrome is a rare, autosomal-dominant, male-predominant form of idiopathic ventricular fibrillation characterized by a right bundle-branch block and ST elevation in the right precordial leads of the surface ECG. Mutations in the cardiac Na + channel SCN5A on chromosome 3p21 cause ≈20% of the cases of Brugada syndrome; most mutations decrease inward Na + current, some by preventing trafficking of the channels to the surface membrane. We previously used positional cloning to identify a new locus on chromosome 3p24 in a large family with Brugada syndrome and excluded SCN5A as a candidate gene. Methods and Results— We used direct sequencing to identify a mutation (A280V) in a conserved amino acid of the glycerol-3-phosphate dehydrogenase 1–like ( GPD1-L ) gene. The mutation was present in all affected individuals and absent in >500 control subjects. GPD1-L RNA and protein are abundant in the heart. Compared with wild-type GPD1-L, coexpression of A280V GPD1-L with SCN5A in HEK cells reduced inward Na + currents by ≈50% ( P <0.005). Wild-type GPD1-L localized near the cell surface to a greater extent than A280V GPD1-L. Coexpression of A280V GPD1-L with SCN5A reduced SCN5A cell surface expression by 31±5% ( P =0.01). Conclusions— GPD1-L is a novel gene that may affect trafficking of the cardiac Na + channel to the cell surface. A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na + current, and causes Brugada syndrome.