Heritable cardiac conduction and myocardial disease: from the clinic to the basic science laboratory and back to the clinic.

A close collaboration between the physicians-scientists of the Division of Cardiology, The Ohio State University and the basic scientists of the Department of Genetics, Harvard Medical School was essential to define the multiple phenotypic expressions and the genetic abnormalities in the heritable conduction and myocardial disease in a family from central Ohio (Family OSU). The Family OSU presents evidence of sequential hierarchical progression through multiple cardiac phenotypes (sinus bradycardia, atrioventricular conduction defects requiring pacemaker, supraventricular arrhythmias including atrial fibrillation, heart failure, and sudden cardiac death) on a decade-to-decade basis. In this setting, each phenotype may be mistakenly considered as a specific diagnosis by physicians working without a pedigree or long-term follow-up. Genetic analysis, however, confirms lamin A/C mutation. The role of the physician-scientist and the basic scientist for the study of heritable disorders is equally important but different. Only the physician-scientist, however, who is in constant contact with the patient understands the complexity of the disease. The physician-scientist with an interest in a particular disease can guide the basic scientist to define molecular mechanisms of that disease and by extension learn important lessons for other diseases.

Clinical Impact of Saline Volume Infused Through Irrigated-Tip Ablation Catheter in Low Acuity Paroxysmal Atrial Fibrillation Ablation Patients.

BACKGROUND: Radio-Frequency ablation (RFA) to achieve pulmonary vein isolation (PVI) remains mainstay therapy for symptomatic paroxysmal atrial fibrillation (PAF). The clinical consequences of large saline infusions during AF ablation have not been systematically studied. We utilized the differential flow-rates of the two commercially available ablation catheters (AC): 'ThermoCool' (TCAC) and 'Surround Flow' (SFAC) from Biosense-Webster to evaluate the clinical impact of the saline infused in the immediate post-ablation period. METHODS: Consecutive charts of PAF patients between 18 and 81 years who underwent RFA procedure at a tertiary care hospital were reviewed. RESULTS: Forty-seven patients were included in the study (33Males, 65±11years, LVEF 58±7% and left atrial diameter 44±7.5mm, 23TCAC-use). The saline volume infused through the AC was significantly higher with TCAC vs SFAC use (1277±316vs697±299 ml; p<0.001), with no difference in volume infused from other sources, total procedure or RFA times (p>0.05). This led to significant increase in post-ablation weight gain (96±23 vs 97.5±24kg; p=0.002), furosemide usage (39% vs 0%; p=0.0006), urine production (120±79 vs 63±31ml/hr; p=0.003) and post-RFA potassium reduction (4.4±0.42 vs 4±0.32mmol/l; p<0.001) with TCAC use. Significant post-RFA reduction in magnesium, calcium and creatinine, associated hyperchloremic metabolic acidosis and a modest QTc prolongation were also observed with use of both ACs albeit only moderate to weakly correlated with saline volume infused through the AC. No clinical adverse outcomes were encountered. CONCLUSIONS: Higher saline-volume infusing AC use in PAF ablation causes significant post-ablation weight gain despite higher furosemide use, larger urine production and associated post-RFA potassium reduction without increasing morbidity in lower acuity patients. Furthermore, an array of post-ablation electrolyte disturbances causes a modest and clinically insignificant QTc prolongation.

Volumetric cine CMR to quantify atrial structure and function in patients with atrial dysrhythmias.

PURPOSE: To implement a cardiac magnetic resonance (CMR)-based protocol to define atrial structure and function in individuals with paroxysmal atrial fibrillation (PAF), heritable cardiac conduction and myocardial disease with atrial dysrhtyhmias (HCCMD), and healthy controls. METHODS: Fifteen controls, 20 PAF, and 12 HCCMD subjects underwent CMR examination including: multislice short-axis cine, multislice horizontal long-axis cine, and gadolinium-enhanced coronal plane magnetic resonance angiography (MRA) for pulmonary vein analysis. We also assessed for ventricular myopathy with delayed myocardial enhancement (DME) acquisitions. RESULTS: Right and left ventricular measurements did not differ among the three groups. Seven heritable atrial dysrhythmia subjects and no control or PAF subjects demonstrated midmyocardial fibrosis of the basal interventricular septum by DME. Left atrial (LA) volume at the onset of atrial systole and minimal LA volume were significantly higher in PAF subjects compared to controls (p < 0.05 for both), LA percent emptying was significantly lower in PAF subjects (p < 0.01), and RA percent emptying was significantly lower in PAF subjects compared to controls (p < 0.01), though these differences were not significant when controlling for heart rate, age and gender. There was no significant difference in right atrial (RA) volumes among study groups. Atrial volumes and function did not differ significantly between heritable atrial dysrhtyhmia subjects and controls. PAF subjects had greater frequency of a right middle pulmonary vein (RMPV) than controls (6/20 vs. 3/15) that did not reach statistical significance. CONCLUSIONS: CMR can quantify atrial structure and function in patients with PAF compared to controls. This protocol could not detect abnormalities in atrial function in early affected patients with heritable cardiomyopathy and atrial premature beats.