A Novel Method for Patient‐Specific QTc—Modeling QT‐RR Hysteresis

Background: Cardiac repolarization adaptation to cycle length change is patient dependent and results in complex QT‐RR hysteresis. We hypothesize that accurate patient‐specific QT‐RR curves and rate corrected QT values (QTc) can be derived through patient‐specific modeling of hysteresis. Method and Results: Model development was supported by QT‐RR observations from 1959 treadmill tests, allowing extensive exploration of the influences of autonomic function on QT adaptation to rate changes. The methodology quantifies and then removes patient‐specific repolarization adaptation rates. The estimated average 95% QT confidence limit was approximately 1 msec for the studied population. The model was validated by comparing QT‐RR curves derived from a submaximal exercise protocol with rapid exercise and recovery phases, characterized by high hysteresis, with QT‐RR values derived from an incremental stepped protocol that held heart rate constant for 5 minutes at each stage of exercise and recovery. Conclusions: The underlying physiologic changes affecting QT dynamics during the transitions from rest to exercise to recovery are quite complex. Nevertheless, a simple patient‐specific model, comprising only three parameters and based solely on the preceding history of RR intervals and trend, is sufficient to accurately model QT hysteresis over an entire exercise test for a diverse population. A brief recording of a resting ECG, combined with a short period of submaximal exercise and recovery, provides sufficient information to derive an accurate patient‐specific QT‐RR curve, eliminating QTc bias inherent in population‐based correction formulas. Ann Noninvasive Electrocardiol 2011;16(1):3–12     

Diagnostic Performance of Various QTc Interval Formulas in a Large Family with Long QT Syndrome Type 3: Bazett's Formula Not So Bad After All …

Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS₃. The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene. Methods: The study group consisted of 101 adult family members: 57 carriers and 44 noncarriers (mean age 44.6 ± 14.6 and 40.3 ± 12.8 years, respectively). In all individuals a 12‐lead ECG, exercise ECG, and 24‐hour Holter ECG were obtained. Results: Correction for heart rate significantly improved the diagnostic performance of the QT interval. Diagnostic performance of the Bazett formula was similar to that of the newer formulas (Fridericia, Hodges, Framingham, and a logarithmic formula). At a cut‐off value of 440 ms, the Bazett corrected QT interval was associated with a sensitivity and specificity of 90% and 91%, respectively. Using the 24‐hour Holter ECG, a prolonged QTc at heart rates less than 60 beats/min was almost pathognomonic for genetic mutation (sensitivity and specificity both 99%), whereas the QTc calculated at the lowest heart rate using Bazett's formula provided full discrimination. Conclusion: In the present family, the resting ECG gave a good indication about the presence or absence of genetic mutation but a 24‐hour Holter recording was mandatory to ascertain the diagnosis. In the diagnosis of this form of LQTS₃, Bazett's formula was at least as good as other proposed corrections of the QT interval to heart rate.     

Cytapheresis—The Next 25 Years: Stem Cell Therapy

Abstract: Hemopoietic stem cell transplantation therapy has firmly established a role in the management of a range of malignant and nonmalignant disorders. Allogeneic bone marrow transplantation has been used as an adjunct in the treatment of acute leukemia with impressive results that have translated into long-term survival and cure. This experience has now extended to the management of other hematological malignancies and some solid tumors. With the ability to source hemopoietic stem cells from the peripheral blood by in vivo cytapheresis, there has been a rapid growth in the use of this form of therapy. The risks and benefits must be clearly appreciated and appropriate resources available with associated monitoring and quality assurance. There are few areas of medicine for which such close cooperation is necessary between medical, nursing, scientific, and allied health professionals to achieve successful outcomes. This paper addresses the logistical aspects of the provision of hemopoietic stem cell therapy in a routine clinical setting.     

Bioactive or Drug-Eluting Stents in 75 Years or Older Patients: The BIODES-75 Registry

BackgroundTiNO-coated BAS have demonstrated competitive outcomes compared to drug-eluting stents (DES). These devices allow short antiplatelet regimens and may be a good option for the growing elderly population undergoing percutaneous coronary intervention (PCI).MethodsMulticenter observational trial in routine clinical practice. A propensity-score matched analysis compared a prospective cohort of patients ≥ 75 years undergoing PCI with BAS, with a contemporary and retrospective cohort treated with last-generation DES. The co-primary endpoints of the study were the Target-Lesion-Failure (Cardiac death, non-fatal myocardial infarction, or target lesion revascularization) and Major Adverse Cardiovascular Events (total death, non-fatal myocardial infarction, stroke, or new revascularization) at 1 year.ResultsWhole population included 1000 patients, and 326 patients in each group were matched for analysis. No differences in primary endpoints were found: TLF 10.4% vs. 11% (HR 0.96 (Confidence Interval 95%, 0.36–1.7; p = 0.87)) and MACE 16.3% vs. 17.2% (HR 0.98 (Confidence Interval 95%; 0.3–1.5, p = 0.93)). Patients treated with BAS received shorter antiplatelets regimens (dual antiplatelet therapy at 1 year, 25.7% vs. 70.6%, p = 0.0001), and they presented lower incidence of bleeding (3.7% vs. 11.7%, HR 0.3 (IC 95% 0.16–0.6, p = 0.001)).ConclusionIn this real-life registry of patients ≥ 75 years, BAS were similar to the latest-generation DES in terms of efficacy and reduced the duration of the antithrombotic therapy, lowering bleeding events.     

Effectiveness and Safety of Golimumab for Patients ≥75 Years Old with Rheumatoid Arthritis

ObjectiveTreatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p＜0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p＜0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.     

Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome

The congenital long QT syndrome (LQTS) is an inherited disorder characterized by a prolonged cardiac action potential. This delay in cellular repolarization can lead to potentially fatal arrhythmias. One form of LQTS (LQT3) has been linked to the human cardiac voltage-gated sodium channel gene (SCN5A). Three distinct mutations have been identified in the sodium channel gene. The biophysical and functional characteristics of each of these mutant channels were determined by heterologous expression of a recombinant human heart sodium channel in a mammalian cell line. Each mutation caused a sustained, non-inactivating sodium current amounting to a few percent of the peak inward sodium current, observable during long (>50 msec) depolarizations. The voltage dependence and rate of inactivation were altered, and the rate of recovery from inactivation was changed compared with wild-type channels. These mutations in diverse regions of the ion channel protein, all produced a common defect in channel gating that can cause the long QT phenotype. The sustained inward current caused by these mutations will prolong the action potential. Furthermore, they may create conditions that promote arrhythmias due to prolonged depolarization and the altered recovery from inactivation. These results provide insights for successful intervention in the disease.