Person:

Hauser, Thomas

OBJECTIVE: Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated (ENPP1) K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals. RESEARCH DESIGN AND METHODS: A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; (n) = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; (n) = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database ((n) = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients ((n) = 169 from Italy, n = 170 from the U.S.). RESULTS: Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80–2.70) in GHS, 2.31 (95% CI 1.22–4.34) in TVAS, and 1.36 (95% CI 0.88–2.10) in CREED, and 1.56 (95% CI 1.15–2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, (P) = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients ((P) = 0.035 for interaction). CONCLUSIONS: The (ENPP1) K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.

Background: The relationship between pulmonary vein (PV) anatomy and successful catheter ablation of atrial fibrillation (AF) is poorly understood Methods: First-pass contrast enhanced PV magnetic resonance angiography was performed in 71 consecutive patients prior to PV isolation. PV diameter and cross-sectional area (CSA) were measured prior to PV isolation. Any symptomatic or asymptomatic AF >10s was considered a recurrence. Early recurrence was defined as recurrent AF ≤30 days after PV isolation, while late recurrence of AF was defined as recurrent AF >30 days after. Results: At 1 year, 57 % had any recurrence of AF while 41 % had late recurrence of AF. Study subjects with one or more PV diameter in the top 10th percentile had trend toward more early recurrent AF (HR 1.99, p = 0.053). Study subjects with one or more PV CSA in the top 10th percentile had more late recurrent AF (HR 2.25, p = 0.039) and a trend toward more early recurrent AF (HR 1.94, p = 0.064). With multivariate analysis, PV size was not associated with early recurrent AF, but late recurrent AF was associated with one or more large PV, increased left atrial size, and non-paroxysmal AF. Study subjects with all three of these risk factors had a 100 % rate of late recurrent AF at 1 year, while those with none had a 7 % rate of late recurrent AF. Conclusions: Larger PV size is independently associated with more late recurrent AF after PV isolation. Determination of PV size prior to PV isolation may predict procedural success.

Background: Anatomic atrial enlargement is associated with significant morbidity and mortality. However, atrial enlargement may not correlate with clinical measures such as electrocardiographic (ECG) criteria. Past studies correlating ECG criteria with anatomic measures mainly used inferior M-mode or two-dimensional echocardiographic data. We sought to determine the accuracy of the ECG to predict anatomic atrial enlargement as determined by volumetric cardiovascular magnetic resonance (CMR). Methods: ECG criteria for left (LAE) and right atrial enlargement (RAE) were compared to CMR atrial volume index measurements for 275 consecutive subjects referred for CMR (67% males, 51 (\pm) 14 years). ECG criteria for LAE and RAE were assessed by an expert observer blinded to CMR data. Atrial volume index was computed using the biplane area-length method. Results: The prevalence of CMR LAE and RAE was 28% and 11%, respectively, and by any ECG criteria was 82% and 5%, respectively. Though nonspecific, the presence of at least one ECG criteria for LAE was 90% sensitive for CMR LAE. The individual criteria P mitrale, P wave axis < (30^\circ), and negative P terminal force in V1 (NPTF-V1) > 0.04(s{\cdot}mm) were 88–99% specific although not sensitive for CMR LAE. ECG was insensitive but 96–100% specific for CMR RAE. Conclusion: The presence of at least one ECG criteria for LAE is sensitive but not specific for anatomic LAE. Individual criteria for LAE, including P mitrale, P wave axis < (30^\circ), or NPTF-V1 > 0.04(s{\cdot}mm) are highly specific, though not sensitive. ECG is highly specific but insensitive for RAE. Individual ECG P wave changes do not reliably both detect and predict anatomic atrial enlargement.