Citations

Background—Current clinical diagnosis of long-QT syndrome (LQTS) includes genetic testing of family members of mutation-positive patients. The present study was designed to assess the clinical course of individuals who are found negative for the LQTS-causing mutation in their families.Methods and Results—Multivariate Cox proportional hazards model was used to assess the risk for cardiac events (comprising syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) from birth through age 40 years among 1828 subjects from the LQTS Registry who were found negative for their family LQTS-causing mutation. The median QTc of study subjects was 423 ms (interquartile range, 402–442 ms). The cumulative probability of a first syncope through age 40 years was 15%. However, only 2 patients (0.1%) had ACA, and none died suddenly during follow-up. Independent risk factors for syncope in genotype-negative subjects included female sex (hazard ratio [HR], 1.60;P=0.002), prolonged QTc (HR=1.63 per 100 ms increment,P=0.02), family history of ACA or SCD (HR=1.89,P=0.002), and LQT2 versus LQT1 family mutation (HR=1.41,P=0.03). Subgroup analysis showed that the presence of theK897Tpolymorphism in the LQT2 gene in an affected family was associated with an 11-fold (P=0.001) increase in the risk of recurrent syncope in genotype-negative subjects.Conclusions—Our findings suggest that cardiac events among genotype-negative family members of LQTS patients are dominated by nonfatal syncopal episodes without occurrence of sudden cardiac death. The risk for nonfatal events in this population may be mediated by the presence of common polymorphisms in LQTS genes.

Background—Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population.Methods and Results—We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38;P=0.005) and the postmenopausal period (hazard ratio, 8.10;P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19;P=0.05;P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause.Conclusions—The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.

Background— Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied. Methods and Results— The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] ≥470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc <440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.65 ( P <0.001) in the age range of 41 to 60 years and 1.23 ( P =0.31) in the age range of 61 to 75 years. The clinical course of study subjects displayed gender differences: Affected LQTS women experienced a significantly higher cumulative event rate (26%) than borderline (16%) and unaffected (12%) women ( P =0.001), whereas event rates were similar among the 3 respective subgroups of men (29%, 26%, and 27%; P =0.16). Recent syncope (<2 years in the past) was the predominant risk factor in affected subjects (hazard ratio 9.92, P <0.001), and the LQT3 genotype was identified as the most powerful predictor of outcome in a subset of 871 study subjects who were genetically tested for a known LQTS mutation (hazard ratio 4.76, P =0.02). Conclusions— LQTS subjects maintain a high risk for life-threatening cardiac events after age 40 years. The phenotypic expression of affected subjects is influenced by age-specific factors related to gender, clinical history, and the LQTS genotype.

Background— The congenital long-QT syndrome (LQTS) is an important cause of sudden cardiac death in children without structural heart disease. However, specific risk factors for life-threatening cardiac events in children with this genetic disorder have not been identified. Methods and Results— Cox proportional-hazards regression modeling was used to identify risk factors for aborted cardiac arrest or sudden cardiac death in 3015 LQTS children from the International LQTS Registry who were followed up from 1 through 12 years of age. The cumulative probability of the combined end point was significantly higher in boys (5%) than in girls (1%; P <0.001). Risk factors for cardiac arrest or sudden cardiac death during childhood included corrected QT interval [QTc] duration >500 ms (hazard ratio [HR]; 2.72; 95% confidence interval [CI], 1.50 to 4.92; P =0.001) and prior syncope (recent syncope [<2 years]: HR, 6.16; 95% CI 3.41 to 11.15; P <0.001; remote syncope [≥2 years]: HR, 2.67; 95% CI, 1.22 to 5.85; P =0.01) in boys, whereas prior syncope was the only significant risk factor among girls (recent syncope: HR, 27.82; 95% CI, 9.72 to 79.60; P <0.001; remote syncope: HR, 12.04; 95% CI, 3.79 to 38.26; P <0.001). β-Blocker therapy was associated with a significant 53% reduction in the risk of cardiac arrest or sudden cardiac death ( P =0.01). Conclusions— LQTS boys experience a significantly higher rate of fatal or near-fatal cardiac events than girls during childhood. A QTc duration >500 ms and a history of prior syncope identify risk in boys, whereas prior syncope is the only significant risk factor among girls. β-Blocker therapy is associated with a significant reduction in the risk of life-threatening cardiac events during childhood.

AbstractWe have reviewed 108 cases of bacterial endocarditis treated surgically since 1968. The mean age of the patients was 47.7±15.6 years (± SD) (range, 14–79 yr). Seventy‐seven percent were male. The most common causative organisms were staphylococci (46%), streptococci viridans group (25%), and other streptococci (20%). Forty‐five percent, 25%, and 13% of patients had native aortic valve, native mitral valve, or native double valve (AV/MV) involvement, respectively. Eighteen patients had prosthetic valve endocarditis. No patient underwent surgery for tricuspid valve endocarditis. Seventy‐three patients were considered to have active endocarditis (AE) (positive blood or tissue cultures and/or annular abscesses). The 35 remaining patients had healed endocarditis (HE). Preoperative complications in patients with either AE or HE were stroke (11%, 11%), renal failure (33%, 3%;p<0.001), pulmonary edema (83%, 34%;p<0.001), anemia (36%, 8%;p<0.01), and inotrope dependence (22%, 6%;p<0.05). Hospital mortality for native valve AE was 19.6% (11/56), and for healed endocarditis, 5.7% (2/35). Independent predictors of hospital mortality were inotrope dependence (p<0.001), annular abscess (p<0.01), pulmonary edema (p<0.01), and staphylococcal infection (p<0.05). The 5‐year actuarial survival for operative survivors was 68.4±7.5% (AE) and 78.3±9.2% (HE). We conclude that the operative mortality for patients with continuing sepsis is high and that surgery should be undertaken early in staphylococcal endocarditis. If surgery is successful, then the long‐term prognosis is good.