Radiofrequency catheter ablation of persistent atrial fibrillation by pulmonary vein isolation with or without left atrial posterior wall isolation: long-term outcomes of the CAPLA trial.

BACKGROUND AND AIMS: Posterior wall isolation (PWI) is commonly incorporated into catheter ablation (CA) strategies for persistent atrial fibrillation (AF) in an attempt to improve outcomes. In the CAPLA randomized study, adjunctive PWI did not improve freedom from atrial arrhythmia at 12 months compared with pulmonary vein isolation (PVI) alone. Whether additional PWI reduces arrhythmia recurrence over the longer term remains unknown. METHODS: In this multicenter, international, randomized study patients with persistent AF undergoing index CA using radiofrequency (RF) were randomized to PVI+PWI versus PVI alone. Patients underwent regular follow-up including rhythm monitoring for a minimum of 3 years post CA. AF burden at 3 years post-ablation was evaluated with either 28-day continuous ambulatory ECG monitoring, twice daily single-lead ECG or from cardiac implanted device. Evaluated endpoints included freedom from any documented atrial arrhythmia recurrence after a single procedure, AF burden, need for redo catheter ablation, rhythm at last clinical follow-up, healthcare utilisation metrics and AF-related quality of life. RESULTS: 333 of 338 (98.5%) patients (mean age 64.3±9.4 years, 23% female) completed 3-year follow-up, with 169 patients randomized to PVI+PWI and 164 patients to PVI alone. At a median of 3.62 years post-index ablation, freedom from recurrent atrial arrhythmia occurred in 59 patients (35.5%) randomized to PVI+PWI vs 68 patients (42.1%) randomized to PVI alone (HR 1.15, 95% CI 0.88-1.51, p=0.55). Median time to recurrent atrial arrhythmia was 0.53 years (IQR 0.34-1.01 years). Redo ablation was performed in 54 patients (32.0%) in the PVI+PWI group vs 49 patients (29.9%, p=0.68) in the PVI alone group. Pulmonary vein reconnection was present in 54.5% (mean number of reconnected PVs 2.2±0.9) and posterior wall reconnection in 75%. Median AF burden at 3 years was 0% in both groups (IQR 0-0.85% PVI+PWI vs 0-1.43% PVI alone, p=0.49). Sinus rhythm at final clinical follow-up was present in 85.1% with PVI+PWI vs 87.1% with PVI alone (p=0.60). Mean AF Effect On Quality-Of-Life (AFEQT) score at 3 years post-ablation was 88.0±14.8 with PVI+PWI vs 88.9±15.4 with PVI alone (p=0.63). CONCLUSIONS: In patients with persistent AF, the addition of PWI to PVI alone at index RF catheter ablation did not significantly improve freedom from atrial arrhythmia recurrence at long-term follow-up. Median AF burden remains low and AF quality of life high at 3 years with either ablation strategy.

Arrhythmias and Their Electrophysiological Mechanisms in Takotsubo Syndrome: A Narrative Review.

BACKGROUND: Takotsubo syndrome (TTS), an acute and usually reversible condition, is associated with both tachy- and bradyarrhythmias. Such arrhythmias can be life-threatening, e.g. ventricular tachycardia and fibrillation, and associated with cardiac arrest. Others, such as atrioventricular block, persist and require long-term device therapy. In this narrative review, we aim to provide a summary of the current literature on arrhythmias in TTS and their clinical sequelae. METHODS: PubMed and Medline databases were searched with various permutations of TTS, arrhythmias and beta-adrenoceptors. After application of exclusion criteria and review, 84 articles were included. RESULTS: Although there are no specific electrocardiograph (ECG) findings in TTS to differentiate it from ST-elevation myocardial infarction, suggestive patterns include small QRS amplitude, ST segment elevation without reciprocal ST depression and prolonged QT interval. Atrial tachyarrhythmias (incidence of 5-15%) are associated with a more unwell patient cohort. Ventricular arrhythmias (incidence 4-14%) are often associated with prolonged QT interval and are a cause of sudden death in TTS. Bradyarrhythmias are less common (incidence 1.3-2.5%), but have been reported with TTS, and usually persist beyond the acute phase. CONCLUSIONS: Takotsubo syndrome, though considered primarily a disease of the myocardium, carries multiple arrhythmic manifestations that affect short- and long-term prognosis. The management of such arrhythmias represents a constantly evolving area of research.

Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery.

BACKGROUND: Methamphetamine abuse is a growing public health problem, and increasing numbers of patients are admitted with methamphetamine-associated cardiomyopathy (MAC). AIM: We sought to characterise the patterns of this disease and identify predictors of recovery. METHODS: We retrospectively studied consecutive patients diagnosed with MAC between January 2006 and July 2015. RESULTS: We identified 20 patients (14 males, 6 females) with mean age 35 ± 9 years. Most had very severe systolic dysfunction (mean left ventricular ejection fraction (LVEF) 19.7 ± 11.4%) at presentation with 14 requiring inotropes and 5 requiring mechanical support. The pattern of systolic dysfunction was global in 14 patients, while 6 patients had a 'reverse Takotsubo' (RT) pattern with severely hypokinetic basal-mid segments and apical preservation. RT patients were predominantly female, had a short history of methamphetamine abuse and had higher cardiac enzyme levels. Patients with global dysfunction tended to have mid-wall fibrosis on cardiac magnetic resonance imaging. On follow-up transthoracic echocardiography, 6 out of 19 (32%) had normalisation of LVEF (LVEF ≥ 50%) within 6 weeks. Smaller left ventricular and left atrial size, shorter duration of methamphetamine use and RT pattern appeared to predict early recovery. CONCLUSION: A subset of MAC patients, particularly those with a RT pattern and lesser ventricular dilatation have the potential for early recovery of ventricular function. By contrast, those with evidence of myocardial fibrosis and ventricular enlargement have limited scope for recovery.

Cardiac resynchronisation therapy in 2015: keeping up with the pace.

Despite improved understanding of the pathophysiology of heart failure (HF) and availability of better medical therapies, HF continues to grow as a cause of morbidity and mortality in Australia and worldwide. Over the past decade, cardiac resynchronisation therapy (CRT), or biventricular pacing, has been embraced as a powerful weapon against this growing epidemic. However, much has changed in our understanding of dyssynchrony in HF, and this has led to a change in guidelines to ensure more appropriate selection of CRT candidates to improve the 'non-response' rate. More data have also emerged about the use of CRT in atrial fibrillation and in pacemaker-dependent patients. There has also been a growing focus on multimodality imaging to guide patient selection and lead positioning. Exciting new lead technologies are also emerging, with the potential to improve CRT outcomes further.

Implementation and learning of laproscopic donor nephrectomy by a non-transplant general surgeon with advanced laparoscopic skills.

INTRODUCTION: Traditionally performed by vascular surgeons or urologists, laparoscopic nephrectomy for live kidney donor transplantation has emerged as a new effective and safe technique. This study examines the implementation of this technique at our centre, as performed by a single general surgeon with expertise in advanced laparoscopic surgery. METHODS: Patient records for 78 live donor transplants performed between February 2002 and September 2008 were divided into two groups (with 39 patients each) analyzed. A variety of outcome variables were compared. The same individual surgeon performed all laparoscopic donor nephrectomy (LDN) procedures. RESULTS: A significant advantage was noted for LDN with respect to hospital stay (LDN 5.1 ± 1.1 days vs open donor nephrectomy [ODN] 6.4 ± 2.6 days, P=0.01) while ODN had a significant advantage with respect to operative time (LDN 241.1 ± 55.7 min vs ODN 152.0 ± 27.7 min, P<0.01). Within the LDN group, we noted a significant shortening in the operation time with each case as experience increased (see graph; P<0.01). The total postoperative complication rate was similar in both groups (LDN: 31% vs ODN: 44%, P=0.25). There was a trend towards more respiratory complications in ODN (ODN 11/39 [28%] vs LDN 5/39 [13%], P=0.09). CONCLUSION: While implementing a new procedure may result in longer operative times initially, these improve with time, and our data demonstrates no compromise in patient safety or outcomes. The LDN procedure proved to be a desirable alternative to ODN, with shorter hospital stay and improved operator skills with each case, and without significant compromise in allograft recovery.

[Non-specific antitumoral activity of staphylococcal enterotoxins]. / Protivoopukholevaia nespetsificheskaia aktivnost' stafilokokkovykh énterotoksinov.

St. aureus enterotoxins A and B possess an antitumour effect. After intraperitoneal inoculation they decrease the size and in some cases prevent the development of the human hypernephroma in the cheek pouch of golden hamsters. The effect of enterotoxins may possibly consist in inducing the production of endogenous immune interferon which activates the host immune system and enhances the rejection of heterologous tumour cells.

[Genome expression of the DNA-containing human papovavirus in transformed human cells]. / Ekspressiia genoma DNK-soderzhasgchego virusa gruppy papova cheloveka v transformirovannykh kletkakh cheloveka.

In the course of study of the transformed cells of line 63 the phenomenon of cyclically repeated transitory infection of the level of separate cells accompanied by the periodically isolated DNA-containing virus has been shown. Virus reproduction was judged by the determination of the infectious and hemagglutinating activities and radioactivity. The application of activation methods (co-culturing, somatic hybridization and cells treatment with mytomycin C) led to the increase of virus synthesis in the transformed cells of line 63 during spontaneous production of it. We failed to express viral genome in refractor phase.

[Pathogenic properties of the human papovavirus in the golden hamster model]. / Izuchenie patogennykh svoistv papovavirusa cheloveka na modeli zolotistykh khomiachkov.

Human papovavirus isolated from human malignant paraganglioma was found to have pathologic relevance to golden hamsters of varying age inducing sarcomas in adults, when given intracerebrally, and lesions of central nervous system in newborns inoculated subcutaneously. T-antigen, immunologically related to that of SV40 was detected in tumor cells. Infectious papovavirus, identical to human one, was isolated from brain tissues of sick hamsters.

[Stable cell line from a malignant human paraganglioma and its virological study]. / Stabil'naia kletochnaia liniia iz zlokachestvennoi paragangliomy cheloveka i ee virusologicheskoe izuchenie.

Under in vitro cultivation of 14 soft tissue malignant human tumors there were obtained two cell lines: from cells of hypernephroma (Hn-7) and malignant paraganglioma (Par-1). The transfer of the cultured Par-1 cells medium to recipient cells CET enabled obtaining the transformed cell line 63. This line possesses all the features of in vitro growing tumor cells: it results in tumor growth in young Syrian hamsters, when injected retrobuccally, and in newborn animals injected percutaneously, also it yields cell colonies growth in semiliquid agar. The cultured line 63 ran through more than 100 passages, its isoenzymic assay indicates that it belongs to a human type and differs from cells HeLa, the karyotypic pattern shows the number of chromosomes to be close to the dyploid number in man. In the cell line 63 there is the synthesis of two viruses: RNA-containing one belonging to the orthomixo-group and DNA-containing one belonging to human oncoviruses of the Papova group.

[Properties of viruses isolated from human fibroblasts culture treated by paraganglioma culture filtrate]. / Svoistva virusov, vydelennykh iz kul'tury fibroblastov cheloveka, obrabotannoi fil'tratom kul'tury paragangliomy.

In the human fibroblasts culture, transformed by the material from malignant paraganglioma culture, there was found the RNA- and DNA containing virus synthesis. The RNA-containing virus with a buoyant density of 1.16--1.18 g/ml shows no hemagglutinating activity, it fails to infect newborn Syrian hamsters, and produces no transformation-destruction changes in mammalian tissue culture. The DNA-containing virus with a buoyant density of 1.24--1.28 g/ml would agglutinate the guinea-pig and group 0 human erythrocytes, produces lesions in newborn Syrian hamsters, and cytodestructive changes in the culture of rat and mice embryonal cells and in cells of a transplantable line Vero. In terms of its properties it may be referred to human viruses of the Papova group. A combined action of DNA- and RNA-containing viruses produces a transformation effect on embryonal hamster cells and the cells of a transplantable line Vero.

[Preparative isolation and some properties of SV40 T-antigen]. / Preparativnoe vydelenie i nekotorye svoistva T-antigena virusa SV 40.

SV40 T-antigen was isolated from hamster tumors and purified about 1600-fold by the procedure including successive ammonium sulfate precipitation, chromatography on DEAE-cellulose, preparative polyacrylamide gel electrophoresis and elimination of the bulk of contaminating cell proteins by the interaction with antibodies to the tissues of normal hamsters. The resulting preparation was not quite homogenous being contaminated with some of cell proteins left. T-antigen in the tumor extract was revealed at least in three distinct forms with molecular weight of 100 000, 200 000, and 400 000. It is proposed that these forms correspond to mono-, di-, and tetramers of the basal protein of T-antigen, although the alternative explanation, the existence of complex of T-antigen with cell proteins, cannot be ruled out.

[Study of DNA melting in the region of the inversion of relative stability of AT and GC pairs]. / Issledovanie plavleniia DNK v oblasti inversii otnositel'noi stabil'nosti AT- i GC-PAR

Systematic data on the dependence of the melting curve parameters of DNA from different organisms on the concentration of salt (C2H5)5NBr have been obtained. The melting curves were studied by spectrophotometric as well as by microcalorimetric methods. The DNA melting range width is shown to pass through the minimum value delta0T = 0.6 +/- 0.1 degrees at the point of inversion of relative stability of AT and GC pairs that corresponds to the concentration of (C2H5)4NBr equal to 2.9 +/- 0.1 M. This concentration, as well as the value of delta0T, are the same for different DNA's of common chemical structure. The T2 and T4 DNA containing hydroxymethylated and glucosylated cytosine residues show an anomalous behaviour. The enthalpy of melting falls very slowly as the salt concentration increases. The possible causes of the observed value of delta0T are discussed. A conclusion is drawn that the main factor which governs the DNA melting process in the region of inversion of the relative stability of AT and GC pairs is the heterogeneity of stacking interaction between different base pairs.