Congenital short QT syndrome (SQTS) is a rare inherited channelopathy without structural heart disease. It is an autosomal dominant primary electrical disorder with a low degree of penetrance. It has a characteristic clinical-electrocardiographic-electrophysiological phenotype consisting of irregular palpitations due to the frequent episodes of paroxysmal atrial fibrillation, dizziness and/or sudden cardiac death (SCD). Affected individuals usually have a positive family history of syncope or SCD in first-or second degree young relatives (younger than 40 years of age) with autopsy negative SCD. Resting electrocardiograms (ECGs) have very short and uniform QT/QTc intervals (QTc interval ≤330 ms with the exception of the calcium-dependent variants 4 and 5), absent or minimal ST segments, interval from J point to T wave peak (Jp-Tp) measured in the precordial lead with the T wave of greatest amplitude.

BACKGROUND:

This study sought to determine the feasibility and recommended phase 2 dose (RP2D) of the combination of cetuximab with chemoradiotherapy based on 5-fluorouracil (5-FU) and cisplatin (CP) in locally advanced anal canal carcinoma.

METHODS:

Cetuximab was administered on days 1, 8, 15, 29, 36, 43, and 50 (400 mg/m(2) initial dose, then 250 mg/m(2) /week) concurrent with total dose radiation of 55 to 59 Gy, both starting on day 1. Escalating doses of 5-FU (96-hour infusion) and CP (2-hour infusion), both on days 1 and 29, were administered according to the following design: starting dose level (0) 5-FU/CP = 800/60 mg/m(2) /day and up to dose level (+2) 5-FU/CP = 1000/80 mg/m(2) /day.

RESULTS:

Dose-limiting toxicity (DLT) events (uncontrolled diarrhea or febrile neutropenia) occurred in 3 of 14 assessable patients receiving escalated dose of 5-FU/CP, with 1 in dose level (0) and 2 in dose level (+2). The RP2D was 5-FU/CP = 800/80 mg/m(2) /day. Because of unexpected non-DLT treatment-related grade 3 (G3) adverse events (AEs) such as thrombosis/embolism, syncope, and infection occurring in ≥ 20% of patients, a safety expansion cohort with an additional 9 patients was investigated with the RP2D. The most frequent G3/G4 AEs evaluated in 23 patients were radiation dermatitis (12 patients), diarrhea (10 patients), thrombosis/embolism (6 patients), and infection (5 patients). The study was closed due to these severe AEs, although no G5 AEs occurred. Twenty of 21 patients (95%) achieved pathological complete response at primary tumor. With a median follow-up of 43.4 months, the 3-year locoregional control rate was 64.2%.

CONCLUSIONS:

Cetuximab could not be integrated with chemoradiotherapy-cisplatin-based therapy due to the high toxicity rate. However, efficacy is encouraging and further investigation of an epidermal growth factor receptor-targeted agent (other than cetuximab) concurrent with chemoradiation should be pursued. Cancer 2013. © 2013 American Cancer Society.

BACKGROUND:

-Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a cardiomyopathy characterized by ventricular arrhythmias and an abnormal right ventricle. Implantable cardioverter defibrillator (ICD) therapy may prevent sudden cardiac death (SCD) in patients with ARVD/C. Currently, an overview of outcomes, appropriate and inappropriate interventions, and complications of ICD therapy in ARVD/C is lacking.

METHODS AND RESULTS:

-A literature search was performed to identify studies reporting outcome and complications in patients with ARVD/C who underwent ICD implantation. Of 641 articles screened, 24 studies on 18 cohorts were eligible for inclusion. In case of >1 publications on a cohort, the most recent publication was included in the meta-analysis. There were 610 patients (mean age 40.4 years; 42% women), who had an ICD for primary or secondary prevention of SCD. Risk factors for SCD were presyncope (61%), syncope (31%), previous cardiac arrest (14%), ventricular tachycardia (58%), and ventricular fibrillation (6%). Anti-arrhythmic medication consisted mostly of beta-blockers (38%), amiodarone (14%), or sotalol (30%). During the 3.8-year follow-up, annualized cardiac mortality rate was 0.9%, annualized noncardiac mortality rate was 0.8%, and annualized heart transplant rate was 0.9%. The annualized appropriate and inappropriate ICD intervention rates were respectively 9.5% and 3.7%. ICD related complications consisted of difficult lead placement (18.4%), lead malfunction (9.8%), infection (1.4%), lead displacement (3.3%), and any complication (20.3%).

CONCLUSIONS:

-Cardiac and noncardiac mortality rates following ICD implantation in patients with ARVD/C are low. Appropriate ICD intervention occurred at a rate of 9.5%/year. Inappropriate ICD interventions and complications lead to considerable ICD related morbidity.

The objective was to externally validate the ability of the San Francisco Syncope Rule (SFSR) to accurately identify patients who will experience a 7-day serious clinical event in an Asian population.This was a prospective cohort study, with a sample of adult patients with syncope and near-syncope enrolled. Patients 12 years old and below and patients with loss of consciousness after head trauma, a witnessed seizure, with known alcohol or illicit drug ingestion, and altered level of consciousness or persistent new neurologic deficits were excluded. The patients were evaluated for the presence of one or more of the five SFSR variables: shortness of breath, history of heart failure, hematocrit <30%, systolic blood pressure <90 mm Hg, and abnormal electrocardiogram (ECG). The patients were followed up by medical record review or telephone interview. Seven-day outcomes were death, arrhythmia, myocardial infarction, acute pulmonary edema, significant structural heart disease, pulmonary embolism, major cardiac procedure, stroke, subarachnoid hemorrhage, major bleeding, and anemia.A total of 1,250 patients from two centers were recruited. Fifty-six patients were excluded from primary analysis because of incomplete data (n = 55) and/or they were noncontactable for follow-up (n = 32). Of the 1,194 patients analyzed, 138 patients (11.6%) experienced adverse outcomes at 7 days. The rule performed with a sensitivity of 94.2% (95% confidence interval [CI] = 89.0% to 97.0%) and a specificity of 50.8% (95% CI = 47.7% to 53.8%).In this study, SFSR rule had a sensitivity of 94.2%. This suggests caution on the strict application of the rule to all patients presenting with syncope. It should only be used as an aide in clinical decision-making in this population.

PURPOSE:

Early postoperative mobilization is crucial for early ambulation to reduce postoperative pulmonary complications after lung resection. However, orthostatic intolerance (OI) may delay patient recovery, leading to complications. It is therefore important to understand the prevalence of and predisposing factors for OI following video-assisted thoracic surgery (VATS), which have not been established. This study evaluated the incidence of OI, impact of OI on delayed ambulation, and predisposing factors associated with OI in patients after VATS.

METHODS:

This retrospective cohort study consecutively analyzed data from 236 patients who underwent VATS. The primary outcome was defined as OI with symptoms associated with ambulatory challenge on postoperative day 1 (POD1), including dizziness, nausea and vomiting, feeling hot, blurred vision, or transient syncope. Multivariate logistic regression was performed to identify independent factors associated with OI.

RESULTS:

Of the 236 patients, 35.2 % (83) experienced OI; 45.8 % of these could not ambulate at POD1, compared with 15.7 % of patients without OI (P < 0.001). Factors independently associated with OI included advanced age [odds ratio 2.83 (1.46-5.58); P = 0.002], female gender [odds ratio 2.40 (1.31-4.46); P = 0.004], and postoperative opioid use [odds ratio 2.61 (1.23-5.77); P = 0.012]. Use of thoracic epidural anesthesia was not independently associated with OI [odds ratio 0.72 (0.38-1.37); P = 0.318].

CONCLUSION:

Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI.

Objective:

To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. Method: A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years.

Results:

A total of 24 living members were affected - QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only β-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period.

Conclusion:

Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.

Epinephrine administered intramuscularly is the treatment of choice for anaphylaxis, and more than 1 dose is occasionally required.To determine clinical background of anaphylaxis for improving the treatment, management, and prognosis of anaphylaxis.Children who had satisfied the diagnostic criteria for anaphylaxis according to the National Institute of Allergy and Infectious Disease Food Allergy and Anaphylaxis Network were selected from our hospital from April 1, 2009 to March 31, 2012.We analyzed 61 patients from the ages of 2 months to 14 years who satisfied the diagnostic criteria for anaphylaxis. Parents of 32 children (52.5%) reported that they had been administered single dose of epinephrine, and 3 children (4.9%) reported receiving multiple doses of epinephrine. The latter group experienced syncope more often (p = 0.049) than the former and suffered more often from comorbid allergic diseases (p = 0.043) that included either bronchial asthma, allergic rhinitis, or atopic dermatitis. Two (3.3%) children experienced biphasic reactions. Patients who experienced a biphasic reaction were more likely to have experienced syncope (p = 0.033), vomiting (p = 0.02), and administration of multiple doses of epinephrine (p = 0.0016).Our findings lead us to recommend that children receiving more than 1 injection of epinephrine should be observed for 24 hours, because it seems that children with requiring more than 1 injection of epinephrine might be have biphasic reactions.

We report an extremely rare case of thebesian vein microfistulae to both ventricles. A 65-year-old woman, with no major cardiovascular risk factors, presented with multiple episodes of chest pain. The resting electrocardiogram showed T-wave inversion in leads V1 -V4 . A Dipyridamole myocardial perfusion imaging revealed large and severe inferior defect with complete reversibility. Coronary angiography showed no coronary artery disease. On contrast injection, an exaggerated capillary blush from the distal portions of the right and left coronary artery systems was seen in both ventricles, mimicking the image of ventriculography. This appearance suggests prominent thebesian vessels, a congenital communication between the coronaries and the two ventricles. The clinical relevance of these myocardial sinusoids is still not well established. Although the majority of these fistulas are small in size and with no clinical significance, they can rarely present with chest pain, cardiac arrhythmia, syncope, myocardial infarction, and/or pulmonary hypertension. These fistulae when excessive can cause significant shunting of blood to the ventricles, leading to coronary steal phenomena and ischemia. This phenomenon is facilitated by the low resistance in these microfistulae as opposed to the higher resistance in the normal coronary circulation. Due to the diffuse nature of these microfistulae, neither surgery nor transcatheter therapy is feasible. This condition can only be managed medically; however, it should be noted that vasodilator agents, such as nitrates, can worsen the coronary steal phenomenon. Our patient was treated with ranolazine with significant improvement in her symptoms, which was not reported previously. Multiple coronary artery microfistulae could be an underestimated condition of angina in patient with normal coronaries.