Incidence and Predictors of Permanent Pacemaker Requirement after Transcatheter Aortic Valve Implantation with a Self‐Expanding Bioprosthesis

Background: Previous reports have suggested the occurrence of cardiac conduction disorders and permanent pacemaker (PPM) requirement after transcatheter aortic valve implantation (TAVI). Based on a single‐center experience, we aim to assess the incidence of postprocedural conduction disorders, need for PPM, and its determinants after TAVI with a self‐expanding bioprosthesis. Methods: From August 2007 to October 2009, 32 consecutive patients underwent TAVI with the Medtronic CoreValve (MCV) System (Medtronic Inc., Minneapolis, MN, USA). Three patients paced at baseline and two cases of procedure‐related mortality were excluded. We analyzed the 12‐lead electrocardiogram at baseline, immediately after procedure and at discharge. Requirements for PPM were documented and potential clinical, electrophysiological, echocardiographic, and procedural predictors of PPM requirement were studied. Results: After TAVI, eight patients (29.6%) required PPM implantation due to high‐grade atrioventricular (AV) block. The prevalence of left bundle branch block increased from 13.8% to 57.7% directly after implantation (P = 0.001). Need for PPM was correlated to the depth of prosthesis implantation (r = 0.590; P = 0.001). At a cutoff point of 10.1 mm, the likelihood of pacemaker could be predicted with 87.5% sensitivity and 74% specificity and a receiver operator characteristic curve area of 0.86 ± 0.07 (P = 0.003). Of the seven patients with preexisting right bundle branch block (RBBB), four (57.1%) required PPM implantation after TAVI. Conclusions: High‐grade AV block requiring PPM implantation is a common complication following TAVI and could be predicted by a deeper implantation of the prosthesis. Patients with preexisting RBBB also seem to be at risk for the development of high‐grade AV block and subsequent pacemaker implantation. (PACE 2010; 1364–1372)     

Radiofrequency Ablation of Symptomatic but Benign Ventricular Arrhythmias

Two cases are presented where ablation of severely symptomatic ventricular arrhythmias not responding to medical therapy was accomplished with radiofrequency current application. After a routine programmed stimulation protocol, a quadripolar ablation catheter with a 4-mm tip was advanced percutaneously into the left ventricle in one case and into the right ventricle in the second case; and after precise pace mapping, the arrhythmogenic focus was successfully ablated using radiofrequency current. The postablation ambulatory recording revealed virtual eradication of ventricular ectopy in both cases. In conclusion, in severely symptomatic cases of "benign" ventricular arrhythmias, radiofrequency ablation offers an effective therapeutic alternative.     

Sustained Monomorphic Ventricular Tachycardia: A Single Electrocardiographic Expression of Different Patterns of Reentry

Sustained monomorphic ventricular tachycardia (SMVT) can be the electrocardiographic expression of a reentrant impulse in the ventricles. In this study we analyzed the different types of reentry that might lead to SMVT, Methods: The pattern of activation of 73 episodes of SMVT induced in thin sheets of epicardium in 50 Langendorff perfused rabbit hearts were visualized with high resolution epicardial mapping (248 points). Results: Five different patterns of reentry resulting in SMVT were identified: (1) Single-loop reentry around a fixed obstacle (n = 40); (2) Single-loop reentry around a functional arc of conduction block (n = 17); (3) Double-wave reentry around a fixed obstacle (n = 9); (4) Figure-of-eight reentry around two areas of functional block (n = 5); and (5) Multiple synchronized circuits around multiple areas of functional block (n = 2), Conclusion: SMVT is a single electrocardiographic expression of different patterns of reentry. Accurate mopping is mandatory to identify the reentrant pathway and the pathophysiological substrate of the arrhythmia.     

Successful autografting in chronic myelogenous leukaemia using Philadelphia negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon

Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph¹ negative) progenitor cells for autografting. Recently, several studies have shown that Ph¹ negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.     

CYCLIN D1 AND RETINOBLASTOMA GENE EXPRESSION IN HUMAN BREAST CARCINOMA: CORRELATION WITH TUMOUR PROLIFERATION AND OESTROGEN RECEPTOR STATUS

Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically. Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinomas was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P=0·017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities. © 1997 John Wiley & Sons, Ltd.     

Early head growth: relation with IQ at 8 years and determinants in term infants of low and appropriate birthweight

Aim  To investigate the relation between head growth at different periods and IQ at 8 years, and to identify factors associated with more rapid head growth.
Method  Two parallel cohorts of term low birthweight (LBW) and appropriate birthweight (ABW) infants were enrolled at birth in northeast Brazil. Anthropometric measurements were made at birth, 2 months, 6 months, 12 months, 24 months, and 8 years. Cognition was assessed at 8 years ( n =164) with the Wechsler Intelligence Scale for Children. Multivariable analysis with a two-stage residual model was used to relate head growth between successive time points with IQ.
Results  Mean birthweight was 2.35kg (SD 0.15) in the LBW group (33 males, 50 females), and 3.21kg (SD 0.15) in the ABW group (28 males, 53 females). Mean gestational age was 38.8 weeks (SD 1.4) and 40.0 weeks (SD 1.3) respectively. In the LBW group, head growth from birth to 2 months and from 2 to 6 months, conditional on previous size, were significant independent predictors of IQ at 8 years. Conditional head growth from 6 months to 8 years and head size at birth were unrelated to IQ. In the ABW group there was no significant relation between conditional head growth and IQ for any period. Determinants of more rapid head growth from birth to 6 months in LBW infants were maternal height and rate of infant weight gain.
Interpretation  Head growth from birth to 6 months in term LBW infants is more important than prenatal or later postnatal head growth in predicting IQ at 8 years.     

Further Characterization of the Syndrome of Right Bundle Branch Block, ST Segment Elevation, and Sudden Cardiac Death

RBBB, ST Elevation, and SCD. We recently described a syndrome characterized by an ECG pattern of right bundle branch block and persistent ST segment elevation in leads V₁ to V₃ in patients suffering from aborted sudden cardiac death and not having demonstrable structural heart disease. We present new observations on this syndrome, especially those related to asymptomatic and intermittent forms. Forty-seven patients with the described ECG pattern were identified; 32 were symptomatic with syncope and sudden death aborted by cardiopulmonary resuscitation. Eleven patients received pharmacologic therapy, mainly amiodarone and/or beta-blocking agents, and 21 patients received an implantable defibrillator with or without pharmacologic therapy. Three of the 11 patients on pharmacologic therapy died suddenly during follow-up, while 9 of 21 patients with an implantable defibrillator used the device during follow-up. The remaining 15 patients were asymptomatic when first seen. Three patients died suddenly after 6 years, 3 months, and 2 months of follow-up without treatment. Another patient received an implantable defibrillator after syncope and had subsequent episodes of ventricular fibrillation terminated by the defibrillator. The other 11 patients remain asymptomatic without (6) or with (5) treatment with beta blockers. In 14 of the 47 patients, the ECG normalized momentarily during follow-up but later became abnormal again. During transient normalization of the ECG, administration of ajmaline or procainamide unmasked the described ECG pattern in six patients who received the drug. Long-term follow-up of survivors failed to show progression to any form of right or left ventricular cardiomyopatby.     

Cell-mediated immunity in localized cutaneous leishmaniasis patients before and after treatment with immunotherapy or chemotherapy

In previous studies of the treatment of localized cutaneous leishmaniasis (LCL) we demonstrated that the therapeutic efficiency of immunotherapy (BCG plus promastigotes of Leishmania mexicana) is equal to that of chemotherapy (Glucantime), without causing the serious side-effects of the drug treatment. In the present study, various aspects of cell-mediated immunity, including the lymphoproliferative response, and leucocyte subpopulations were evaluated both before treatment and after cure in 39 LCL patients who had received immunotherapy (IT), in 34 submitted to chemotherapy (CT), and in 14 patients cured by the administration of BCG alone. We demonstrated evident signs of T-cell activation in cured patients who had received either CT or IT. For example, an increased expression of IL-2 receptors was observed in such patients, compared to their pretreatment values. Also, a significant percentage of patients showed augmented in-vitro responses to mitogen, and both in-vitro and in-vivo reactivity to leishmanial antigen. No evidence was found for the development of an exaggerated immune response to Leishmania parasites in the IT group, because the final level of immunological reactivity was comparable to the CT group. Neither was there any difference in terms of the final immune response between the patients cured by BCG treatment alone and the other groups. However, the therapeutic efficiency of BCG was lower and the mean cure time was longer. We conclude that IT is very useful in the treatment of LCL patients because of its high efficiency, low propensity to produce side-effects, and the fact that it does not induce a state of hyper-reactivity.