Temporal decline in defibrillation thresholds with an active pectoral lead system.

OBJECTIVES: The objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system. BACKGROUND: Ventricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown. METHODS: This study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 +/- 40 weeks) in 50 patients. RESULTS: The DFTs were 9.2 +/- 5.4 J at implantation, 8.3 +/- 5.8 J before discharge and 6.9 +/- 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (> or =15 J). No patient developed an inadequate safety margin (< 9 J) during follow-up. CONCLUSIONS: The DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs.

Influence of pregnancy on the risk for cardiac events in patients with hereditary long QT syndrome. LQTS Investigators.

BACKGROUND: The effects of pregnancy on women with the hereditary long QT syndrome are currently unknown. The appropriate medical management of pregnant patients with the long QT syndrome has not been established. METHODS AND RESULTS: The study was a retrospective analysis of the 422 women (111 probands affected with the long QT syndrome and 311 first-degree relatives) enrolled in the long QT syndrome registry who had one or more pregnancies. The first-degree relatives were classified as affected (QTc >0.47), borderline (QTc=0.45 to 0.47), and unaffected (QTc <0.45). Cardiac events were defined as the combined incidence of long QT syndrome-related death, aborted cardiac arrest, and syncope. The incidence of cardiac events was compared during equal prepregnancy, pregnancy, and postpartum intervals (40 weeks each). Multivariate logistic regression analysis was performed by use of a mixed-effects model to identify independent predictors of cardiac events among probands. The pregnancy and postpartum intervals were not associated with cardiac events among first-degree relatives. The postpartum interval was independently associated with cardiac events among probands (odds ratio [OR], 40.8; 95% confidence interval [CI], 3.1 to 540; P=.01); the pregnancy interval was not associated with cardiac events. Treatment with beta-adrenergic blockers was independently associated with a decrease in the risk for cardiac events among probands (OR, 0.023; 95% CI, 0.001 to 0.44; P=.01). CONCLUSIONS: The postpartum interval is associated with a significant increase in risk for cardiac events among probands with the long QT syndrome but not among first-degree relatives. Prophylactic treatment with beta-adrenergic blockers should be continued during the pregnancy and postpartum intervals in probands with the long QT syndrome.

ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients.

UNLABELLED: T-wave alternans (TWA) is a marker of myocardial electrical instability. We compared ECG features of microvolt TWA in coronary artery disease (CAD) and long QT syndrome (LQTS) patients. METHOD: The study populations consisted of 43 CAD and 39 LQTS patients. TWA was detected in resting Holter recordings using the new correlation method (CM). After preprocessing to adjust for RR variability and respiratory modulation, CM was used to quantify TWA amplitude (A(CM)), duration (N(CM)), and magnitude (MAG(CM); defined as the product of A(CM) and N(CM)). RESULTS: TWA was detected in 19 (44%) CAD and 17 (44%) LQTS patients. TWA was associated with longer RR intervals (P = 0.006) and had larger magnitudes (P = 0.067) in LQTS than CAD patients. The TWA was identified as transient (nonstationary) in 15 of 19 (79%) TWA-positive CAD patients, and in 8 of 17 (47%) TWA-positive LQTS patients (P = 0.047). CONCLUSIONS: The frequency of TWA detected with CM is similar in LQTS and CAD patients. TWA is larger in LQTS than in CAD patients, whereas TWA is more frequently transient (nonstationary) in LAD than LQTS patients. In LQTS patients, but not in CAD patients, a longer RR is associated with TWA, indicating different electrophysiologic mechanisms in the two pathologies.

Treatment of the neutropenia of Felty syndrome.

This review sets out to synthesize and critically evaluate the current reported data regarding therapeutic options for the neutropenia associated with Felty syndrome (Felty neutropenia). A MEDLINE search and bibliographies from recent reviews were used to identify trials and case reports that provided sufficient data to evaluate the effect of various interventions on both the neutropenia and the clinical course of patients with Felty syndrome. Data were obtained on baseline hematologic profiles, bone-marrow biopsies, and patient characteristics; length of follow-up; hematologic and clinical responses to the various interventions; and side-effect profiles. Treatment with hemopoietic growth factors or methotrexate can produce sustained hematologic and clinical responses with an acceptable side-effect profile. Splenectomy produces a long-term hematologic response in 80% of patients. Patients who do not respond hematologically have a higher incidence of non-fatal infections, but a significant minority (46%) do not experience any infections; the incidence of fatal infections is 12%, regardless of whether a hematologic response occurs. Of the patients who had infections prior to surgery, 55% did not experience further infections after splenectomy. Initial treatment of Felty neutropenia should consist of hemopoietic growth factors because of their rapid onset of action and relatively low incidence of side-effects. Splenectomy is a reasonable option if growth factors are ineffective and rapid amelioration of neutropenia is needed. Methotrexate offers a potentially promising alternative for the treatment of both the rheumatologic and the hematologic manifestations of Felty syndrome.

Type 1 diabetes mellitus: an imbalance between effector and regulatory T cells?

Abundant evidence now exists that autoimmunity plays a critical role in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. The non-obese diabetic (NOD) mouse is an extensively studied animal model of this T-cell-mediated autoimmune disease. Our laboratory has focused on isolating diabetogenic T cell clones from NOD mice as a means of elucidating the pathogenesis of type 1 diabetes. This experimental approach presupposes that type 1 diabetes in NOD mice results from the action of islet-reactive T cells that are not present in other mouse strains; the diabetogenic T cells would therefore represent "forbidden clones" which exist in NOD mice as a result of a failure of clonal deletion. While the inappropriate presence of diabetogenic T cells probably plays a central role in murine diabetes, it cannot explain all aspects of the disease. Type 1 diabetes is a chronic disorder with a lengthy preclinical stage; if the diabetogenic T cells acted in an unopposed fashion, one might expect to see a much more fulminant clinical course. This observation suggests that regulatory influences are likely to exist in this disease--a possibility supported by recent experimental data. If these regulatory influences could be identified and enhanced, specific immunotherapy for type 1 diabetes could be achieved.