Risk factors for recurrent syncope and subsequent fatal or near-fatal events in children and adolescents with long QT syndrome.

OBJECTIVES: We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS). BACKGROUND: Data regarding risk assessment in LQTS after the occurrence of the first syncope episode are limited. METHODS: The Prentice-Williams-Peterson conditional gap time model was used to identify risk factors for recurrent syncope from birth through age 20 years among 1,648 patients from the International Long QT Syndrome Registry. RESULTS: Multivariate analysis demonstrated that corrected QT interval (QTc) duration (≥500 ms) was a significant predictor of a first syncope episode (hazard ratio: 2.16), whereas QTc effect was attenuated when the end points of the second, third, and fourth syncope episodes were evaluated (hazard ratios: 1.29, 0.99, 0.90, respectively; p < 0.001 for the null hypothesis that all 4 hazard ratios are identical). A genotype-specific subanalysis showed that during childhood (0 to 12 years), males with LQTS type 1 had the highest rate of a first syncope episode (p = 0.001) but exhibited similar rates of subsequent events as other genotype-sex subsets (p = 0.63). In contrast, in the age range of 13 to 20 years, long QT syndrome type 2 females experienced the highest rate of both first and subsequent syncope events (p < 0.001 and p = 0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6- to 12-fold (p < 0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc duration. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events. CONCLUSIONS: Children and adolescents who present after an episode of syncope should be considered to be at a high risk of the development of subsequent syncope episodes and fatal/near-fatal events regardless of QTc duration.

Mutation-specific risk in two genetic forms of type 3 long QT syndrome.

The clinical course of patients with 2 relatively common long QT syndrome type 3 mutations has not been well described. In the present study, we investigated the mutational-specific risk in patients with deletional (DeltaKPQ) and missense (D1790G) mutations involving the SCN5A gene. The study population involved 50 patients with the DeltaKPQ mutation and 35 patients with the D1790G mutation. The cumulative probability of a first cardiac event (syncope, aborted cardiac arrest, or long QT syndrome-related sudden death) was evaluated using the Kaplan-Meier method. The Cox proportional hazards survivorship model was used to determine the independent contribution of clinical and genetic factors to the first occurrence of cardiac events from birth through 40 years of age. The Andersen-Gill proportional intensity regression model was used to analyze the factors associated with recurrent syncope. Patients with a DeltaKPQ mutation had a significantly greater probability of a first cardiac event from birth through 40 years of age (34%) than those with the D1790G mutation (20%; p <0.001). Multivariate analysis demonstrated an increased risk of cardiac events among DeltaKPQ carriers compared to D1790G carriers (hazard ratio 2.42, p <0.0001) after adjustment for gender and QTc duration. Patients with DeltaKPQ mutations also had an increased risk of recurrent syncope (hazard ratio 5.20, p <0.001). In conclusion, the clinical course of patients with long QT syndrome type with DeltaKPQ mutations was shown to be more virulent than those with D1790G mutations, and this effect was independent of QTc duration. The findings highlight the importance of knowing the specific mutation in risk stratification of patients with long QT syndrome type 3.

Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations.

BACKGROUND: Ethnic differences may affect the phenotypic expression of genetic disorders. However, data regarding the effect of ethnicity on outcome in patients with genetic cardiac disorders are limited. We compared the clinical course of Caucasian and Japanese long QT type-1 (LQT1) patients who were matched for mutations in the KCNQ1 gene. METHODS: The study population comprised 62 Caucasian and 38 Japanese LQT1 patients from the International LQTS Registry who were identified as having six identical KCNQ1 mutations. The biophysical function of the mutations was categorized into dominant-negative (> 50%) or haploinsufficiency (< or =50%) reduction in cardiac repolarizing IKs potassium channel current. The primary end point of the study was the occurrence of a first cardiac event from birth through age 40 years. RESULTS: Japanese patients had a significantly higher cumulative rate of cardiac events (67%) than Caucasian patients (39%; P = 0.01). The respective frequencies of dominant negative mutations in the two ethnic groups were 63% and 28% (P < 0.001). In multivariate analysis, Japanese patients had an 81% increase in the risk of cardiac events (P = 0.06) as compared with Caucasians. However, when the biophysical function of the mutations was included in the multivariate model, the risk associated with Japanese ethnicity was no longer evident (HR = 1.05; P = 0.89). Harboring a dominant negative mutation was shown to be the most powerful and significant predictor of outcome (HR = 3.78; P < 0.001). CONCLUSIONS: Our data indicate that ethnic differences in the clinical expression of LQTS can be attributed to the differences in frequencies of the specific mutations within the two populations.

Radiofrequency and microwave energy sources in surgical ablation of atrial fibrillation: a comparative analysis.

BACKGROUND: Due to its complexity and risk of bleeding, the Maze III procedure has been largely replaced by surgical ablation for atrial fibrillation (AF) using alternative energy sources. Radiofrequency (RF) and microwave (MW) are the most commonly used energy forms. In this study, we sought to compare these energy modalities in terms of clinical outcomes. METHODS: Two hundred five patients underwent surgical ablation of AF, from October 1999 to May 2004 at our institution via an endocardial approach. Patients were categorized into 2 groups: RF and MW. Baseline characteristics, operative details, and clinical outcomes were compared between the 2 groups. Rhythm success was defined as freedom from AF and atrial flutter as determined by postoperative electrocardiograms. RESULTS: One hundred twenty patients (58.5%) were ablated using RF, whereas 85 (41.5%) were ablated with MW. Most of the patients had persistent AF in both the RF and MW groups (85.7% versus 80.0%, respectively; P = .363). Intraoperative left atrial size was 6.4 +/- 1.7 cm for the RF group and 6.4 +/- 1.7 cm for the MW group (P = .820). Postoperative rhythm success at 6 and 12 months was 72.4% versus 71.4% (P +/- .611) and 75.0% versus 66.7% (P = .909) for the RF and MW groups, respectively. Hospital length of stay was comparable for both groups (15.4 +/- 14.0 versus 13.3 +/- 13.9 days; P = .307). Postoperative survival at 6 months, 1 year, and 3 years was 90.4%, 89.5%, and 86.1% for RF patients compared to 87.9%, 86.5%, and 84.4% for MW patients, respectively (log rank P = .490). CONCLUSIONS: RF and MW energy forms yield comparable postoperative rhythm success, hospital length of stay, and postoperative survival. Both sources are rapid, safe, and effective alternatives to "cut and sew" techniques for surgical treatment of AF.

Effect of diabetes on short- and long-term outcomes after left ventricular assist device implantation.

BACKGROUND: Diabetes mellitus (DM) is a frequent co-morbidity in patients with congestive heart failure (CHF). Implantation of LVADs is an acceptable option for diabetic patients with end-stage heart failure, yet no previous study has specifically examined the clinical outcomes of this patient population. METHODS: A retrospective analysis was performed on all patients who underwent LVAD insertion at a single institution from June 17, 1996 to April 14, 2004. Patients were divided into 2 groups: diabetics (DM) and non-diabetics (NDM). The groups were compared with regard to demographics, etiology of heart failure, body mass index (BMI), intensive care unit (ICU) stay, early mortality (< or =30 days), bridge-to-transplantation rate and post-LVAD and post-transplant survival. RESULTS: Two hundred one patients were identified. Of these, 49 (24.4%) had DM. Compared with the NDM group, DM patients had a higher mean body mass index (30.1 +/- 6.0 vs 26.1 +/- 4.8, p < 0.001) and a higher proportion of hypertension (57.4% vs 19.7%, p < 0.001). Although post-LVAD survival was similar, post-transplant survival in DM patients was significantly lower compared with NDM patients, with 1-, 3-, 5- and 7-year actuarial survival rates of 86.9%, 71.0%, 56.5% and 56.5% vs 90.5%, 88.4%, 83.0% and 80.7% (p = 0.020), respectively. CONCLUSIONS: Carefully selected diabetic patients can be successfully bridged to transplantation using LVADs with comparable outcomes to non-diabetic patients. Reasons for diminished post-transplant survival in this cohort are unclear and necessitate the conductance of multi-institutional studies to evaluate outcomes.

A decade experience of cardiac retransplantation in adult recipients.

BACKGROUND: Cardiac retransplantation is considered to be the best therapeutic option for a failing cardiac allograft. However, poor outcomes with retransplantation have previously been reported, a factor that raises important ethical, logistic and financial issues given the limited organ donor supply. METHODS: Seven hundred sixty-six adult patients underwent cardiac transplantation for end-stage heart failure at our institution from 1992 to 2002. Of these, 41 (5.4%) were retransplants. Variables examined included recipient and donor demographics, indications for retransplant, comorbidities, cytomegalovirus (CMV) serology status, left ventricular assist device use before transplant, donor ischemic time, rate of early mortality (within 30 days), and post-transplantation survival rate. RESULTS: Indications for cardiac retransplant were transplant-related coronary artery disease in 37, acute rejection in 3, and other causes in 1. The mean interval between transplantation and retransplantation was 5.9 +/- 3.4 years. Baseline characteristics such as recipient age, gender, CMV serology status, and donor age were similar in the primary transplant and retransplant groups. Early mortality after transplantation was comparable between the 2 groups, but post-transplant survival was significantly lower in retransplant patients compared with primary transplants with 1-, 3-, 5-, and 7-year actuarial survival rates of 72.2%, 66.3%, 47.5%, and 40.7% vs. 85.1%, 79.2%, 72.9%, and 66.8%, respectively (p < 0.001). CONCLUSIONS: Cardiac retransplantation offers short-term outcomes similar to primary transplantation but lower long-term survival rates. Non-retransplant surgical options should also be considered in these patients. Careful patient selection and risk-assessment is necessary to govern appropriate allocation of limited donor organs.

Vibration anesthesia: a noninvasive method of reducing discomfort prior to dermatologic procedures.

In some dermatologic and cosmetic procedures, local anesthesia is not sufficient for relieving pain; often patients are averse to injections. We propose vibration anesthesia, the use of vibration delivered with commercially available inexpensive massagers to reduce discomfort. We find the analgesic effect of vibration helpful in minimizing pain in patients undergoing injections of botulinum toxin type A treatment for hyperhidrosis, injection of filler substances such as Restylane and Juvederm, laser therapy for leg veins, nail-fold injections, Q-switched laser treatment of tattoos, incision and drainage of abscesses, and cautery of facial warts, as well as facilitating anesthetic injections for needle-phobic patients. We expect that additional uses will be found as experience with this modality grows. Although the use of vibration anesthesia generally does not eliminate pain completely, it can serve to make the injection or procedure much more tolerable.

Treatment of HIV-associated facial lipoatrophy with Radiance FN (Radiesse).

HIV treatments frequently include the administration of Highly Active Antiretroviral Therapy (HAART) to combat the disease; although no conclusive evidence exists, it has been suggested that the HAART regimen may lead to facial lipoatrophy, exemplified by fat loss from facial areas, most notably the cheeks. Lipoatrophy can cause severe psychosocial consequences because it can be an identifying marker of HIV infection. Calcium hydroxylapatite (Radiance FN, recently renamed Radiesse) has been postulated to be a long-lasting, biocompatible filler that does not ossify, migratem or calcify. We present three patients with HIV-associated lipoatrophy who were treated with Radiance FN. Touch-up treatments were performed 1 month later for two patients. The percentage of improvement following the initial treatment ranged from 75 to 90 percent. Although there has been some loss of improvement over time, there has been significant persistence for up to 9 months. No complications have occurred, and patients were highly satisfied with treatment results. Our experience with Radiance FN has shown it to be a potentially valuable tool for treating facial lipoatrophy.