Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES: This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND: Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed. METHODS: Eighty-five patients with end-stage HF, QRS duration >120 ms, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up. RESULTS: Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs. 35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony >/=65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ms (p < 0.001). CONCLUSIONS: Patients with LV dyssynchrony >/=65 ms respond to CRT and have an excellent prognosis after CRT.     

Polymerase chain reaction-based differential diagnosis of Ancylostoma duodenale and Necator americanus infections in humans in northern Ghana

We evaluated a two-step semi-nested polymerase chain reaction (PCR)-based approach for the specific detection of Ancylostoma duodenale DNA in human faeces. The test was used to determine to what extent this species of hookworm is present in the regions of Bolgatanga and Garu of northern Ghana. Initially, the sensitivity and specificity of the PCR were tested using a range of well-defined control samples. Subsequently, a total of 378 human faecal DNA samples from Bolgatanga and Garu were subjected to the PCR. The results were compared with those obtained using a previously established PCR for the specific detection of Necator americanus DNA in human faeces. Infection with A. duodenale was recorded in 74 (19.6%) samples and N. americanus in 278 (73.5%), of which 64 (16.9%), represented co-infections with both species. While A. duodenale was predominantly detected in the samples from Bolgatanga, infections in Garu related almost exclusively to N. americanus. The results showed that the present PCR approach is a valuable complementary tool for the diagnosis of A. duodenale infection in humans in Ghana, having implications for epidemiological studies and for the monitoring of the success of control programmes in regions in Africa.     

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular ejection fraction <35%, left bundle branch block, and QRS >120 ms). The presence of left ventricular dyssynchrony is needed to result in improvement after cardiac resynchronization therapy.     

Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias

Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A. These reconstructions, made from serial sections of mouse embryos, show that from the outset of atrial development, the systemic and pulmonary veins are directly connected to the atrium. Relative to the systemic junctions, however, the pulmonary venous junction appears later. Our experience shows that three-dimensional reconstructions have three advantages. First, they provide clear access to the combined morphological and molecular data, allowing clarification and verification of morphogenetic concepts for nonmorphological experts and setting the scene for further discussion. Second, they demonstrate that, from the outset, the myocardium surrounding the pulmonary veins is distinct from that clothing the systemic venoatrial junctions. Third, they reveal an anatomical and molecular continuity between the entrance of the systemic venous tributaries, the internodal atrial myocardium, and the atrioventricular region. All these regions are derived from primary myocardium, providing a molecular basis for the observed nonrandom distribution of focal right atrial tachycardias.     

Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy.

AIMS: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. CONCLUSION: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT.     

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia

The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fc gamma receptor--bearing phagocytes. In 2 experimental models for ITP, it is shown that the therapeutic efficacy of IVIG preparations is related to the IgG dimer content present in these preparations. A rat monoclonal antibody (mAb; MWReg30) directed to the murine platelet-specific integrin alpha(IIb)beta(3) (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3 hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-Fc gamma RII/III mAb 2.4G2 or IVIG greatly reduced platelet clearance. With continuous infusion, platelet numbers reached a steady state after 4 days, at approximately 25% of control. This reduction in platelets was, however, not observed in mice deficient for the FcR gamma-chain, lacking Fc gamma RI, Fc gamma RIII, and Fc gamma RIII(-/-) mice. Infusion of a single dose of IVIG with a high IgG dimer content on the 4th day--ie, mimicking therapeutic administration--resulted in a platelet increase for several days. IVIG predominantly consisting of monomeric IgG had no effect on platelet numbers. In conclusion, continuous infusion of MWReg30 induces thrombocytopenia in mice by enhancing Fc gamma receptor--mediated clearance of platelets. In this model, it is shown that IgG dimers present in IVIG preparations are responsible for the increase in platelet counts. (Blood. 2001;98:1095-1099)     

How salient is the silent period? The role of the silent period in the prognosis of upper extremity motor recovery after severe stroke.

Transcranial magnetic stimulation (TMS) has been successful in the prediction of motor recovery in acute stroke patients with initially severe paresis or paralysis of the upper extremity. Motor evoked potentials (MEP) appear to have a high specificity but a rather low sensitivity with regard to motor recovery. The silent period (SP) has been proposed as an additional factor to the MEP for predicting motor recovery that might optimize the sensitivity of TMS. The authors reviewed the literature and case series focusing on the additional value of the SP to the MEP for predicting poststroke hand motor recovery. Studies that have analyzed the SP for predicting poststroke motor recovery have rather inconsistent results and suffer from heterogeneity in technical methods, methodology, and patient characteristics. In most studies, prolonged SPs have been found immediately after stroke, whereas in the (sub)acute phase thereafter, different patterns of SP duration have been found. These differences are thought to be related to stroke localization, though contraction-induced reduction phenomena and recovery-related intracortical phenomena may also be responsible. Although the SP might be used to identify clinically silent or minor strokes, in acute stroke patients with initial severe paresis or paralysis, the SP seems to have no additional value to MEP for predicting poststroke motor recovery. Nevertheless, the SP (poststroke-reduced SPs and contraction-induced inhibitory phenomena) has been proposed as a prognostic factor for poststroke spasticity. This review emphasizes the significance of the SP in predicting poststroke motor recovery and spasticity. Although the relation among the SP, recovery-related intracortical phenomena, and spasticity remains unclear, a neurophysiologic model underlying the SP is discussed. However, more research is needed on the value of the SP for predicting poststroke spasticity.     

Acute facial paralysis: a virological study

A serological study using the complement fixation reaction for herpes zoster virus (HZV) and herpes simplex virus (HSV) was carried out on 120 patients with Bell's palsy and 5 with Ramsay-Hunt syndrome. Three Bell's palsy patients (2.5%) showed a significant HZV antibody titre rise. In no case was a rise of HSV antibody titre observed. Two Ramsay-Hunt patients showed a significant rise of HZV antibody titre. Rise of HSV antibody titre was not observed in this group either. The Monosticon test to exclude infectious mononucleosis, proved to be negative in all cases of Bell's palsy. In 2 cases of Bell's palsy, a biopsy specimen for virus isolation was obtained during a decompression operation. No virus could be cultured from the epineurium of the first patient. That of the second patient was found to contain HSV type I. There was no serological evidence of a HSV antibody titre rise.