Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

Variation in the Amount of Hemoglobin S in a Patient with Sickle Cell Trait and Megaloblastic Anemia

A patient with sickle cell trait and nutritional megaloblastic anemia wasfound to have a much smaller proportion of hemoglobin S during the megaloblastic phase than after recovery. This observation suggests preferential synthesis of hemoglobin A by megaloblastic bone marrow in the presence of theA-S trait.

Submitted on July 30, 1962 Accepted on November 9, 1962     

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.     

Molecular Genetic Basis of Hypertrophic Cardiomyopathy:

Genetics of SCD in HCM. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric proteins. The disease is characterized by left ventricular hypertrophy in the absence of an increased external load, and myofibrillar disarray. A large number of mutations in genes coding for the β-myosin heavy chain (β-MyHC), cardiac troponin T (cTnT), cardiac troponin I, α-tropomyosin, myosin binding protein C (MyBP-C), and myosin light chain 1 and 2 in patients with HCM have been identified. Genotype-phenotype correlation studies have shown that mutations carry prognostic significance. The Gly²⁵⁶Glu, Val⁶⁰⁶Met, and Leu⁹⁰⁸Val mutations in the μ-MyHC are associated with a benign prognosis. In contrast, Arg⁴⁰³Gln, Arg⁷¹⁹Trp, and Arg⁴⁵³Cys mutations are associated with a high incidence of sudden cardiac death (SCD). Mutations in cTnT are associated with a mild degree of hypertrophy, but a high incidence of SCD. Mutations in MyBP-C are associated with mild hypertrophy and a benign prognosis. However, it has become evident that factors other than the underlying mutations, such as genetic background and possibly environmental factors, also modulate phenotypic expression of HCM.     

Encainide for the Treatment of Refractory Ventricular Tachycardia in Patients Undergoing Programmed Electrical Stimulation

Encainide was evaluated in 26 patients undergoing programmed electrical stimulation (PES) for ventricular arrhythmias. These patients had inducible symptomatic ventricular tachyarrhythmias during baseline PES and had previously failed a mean of 3.2 antiarrhythmic agents. Encainide was discontinued in six patients prior to PES because of spontaneous ventricular tachycardia (VT) (five patients) and adverse effect (one patient). Encainide increased, the PR, QRS, QTc intervals, and right ventricular effective refractory period (RVERP) significantly from baseline (P < 0.05) in 16 patients who were extensive metabolizers. Encainide, at a mean dose of 110 ± 28 mg/day increased the ventricular tachycardia cycle length (VTCL) from 278 ± 77.1 msec to 334 ± 68.8 msec (P < 0.05). Encainide alone was effective (< 15 beats induced) or partially effective (converting inducible sustained VT to < 15 beats asymptomatic nonsustained VT or increasing the VTCL < 100 msec with no symptoms) in two and seven patients respectively. In seven patients, encainide was also reevaluated at a higher dose (mean dose 148 ± 22 mg/day), but this dose did not significantly alter the overall response or measured parameters. Seven patients were subsequently evaluated on combination of encainide and another antiarrhythmic agent. The combination was effective in three patients and partially effective in three patients. Serum concentrations were measured during each testing period; a moderate correlation was observed between the PR and RR intervals and total concentrations in patients who were extensive metabolizers. Eleven patients who were effective or partially effective during acute testing were placed on long-term encainide therapy (three patients alone and eight patients on combination therapy). In a mean follow-up of 8.9 months (1–25 months) encainide was discontinued in five patients (two patients due to nonsudden cardiac death, one patient due to recurrent nonfatal VT, and two patients due to side effects of combination therapy.) Conclusion: Encainide alone is minimally effective (7.7%) for preventing inducible ventricular tachycardia, but partially effective in 38.9%. Retesting at a higher dose does not offer any additional benefit. However, encainide in combination with another antiarrhythmic agent may improve the response in patients who remain inducible on encainide alone. Further studies are needed to verify this observation.     

Ki-ras MUTATIONS IN ADENOMAS: A CHARACTERISTIC OF CANCER-BEARING COLORECTAL MUCOSA

Activating mutations in the Ki- ras 2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki- ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki- ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki- ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.