BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) provides an alternative to the transvenous implantable cardioverter-defibrillator (TV-ICD). Patients undergoing TV-ICD explantation may be eligible for reimplantation with an S-ICD; however, information on safety outcomes in this complex population is limited. OBJECTIVE: This analysis was designed to provide outcome and safety data from S-ICD patients who received their device after TV-ICD explantation. METHODS: Patients in the S-ICD IDE Study and EFFORTLESS Registry with a prior TV-ICD explantation, as well as those with no prior implantable cardioverter-defibrillator (ICD), were included. Patients were divided into 3 groups: those implanted with the S-ICD after TV-ICD extraction for system-related infection (n = 75); those implanted after TV-ICD extraction for reasons other than system-related infection (n = 44); and patients with no prior ICD (de novo implantations, n = 747). RESULTS: Mean follow-up duration was 651 days, and all-cause mortality was low (3.2%). Patients previously explanted for TV-ICD infection were older (55.5 ± 14.6, 47.8 ± 14.3 and 49.9 ± 17.3 years in the infection, noninfection, and de novo cohorts, respectively; P = .01), were more likely to have received the ICD for secondary prevention (42.7%, 37.2% and 25.6%; P < 0.0001) and had higher percentages of comorbidities, including atrial fibrillation, congestive heart failure, diabetes mellitus, and hypertension, in line with the highest mortality rate (6.7%). Major infection after S-ICD implantation was low in all groups, with no evidence that patients implanted with the S-ICD after TV-ICD explantation for infection were more likely to experience a subsequent reinfection. CONCLUSION: The S-ICD is a suitable alternative for TV-ICD patients whose devices are explanted for any reason. Postimplantation risk of infection remains low even in patients whose devices were explanted for prior TV-ICD infection.

• MeSH
• analýza přežití MeSH
• defibrilátory implantabilní * škodlivé účinky   statistika a číselné údaje   MeSH
• dospělí MeSH
• elektrická defibrilace přístrojové vybavení   metody   MeSH
• implantace protézy * škodlivé účinky   metody   mortalita   MeSH
• infekce chirurgické rány * diagnóza   epidemiologie   terapie   MeSH
• komorová tachykardie terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reoperace statistika a číselné údaje   MeSH
• selhání zařízení statistika a číselné údaje   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Patients with coronary artery disease (CAD) may have ventricular tachycardia (VT) from a separate nonischemic process. Catheter ablation in these patients can be misguided by abnormalities of coronary arteries. OBJECTIVE: To identify (1) the prevalence of unanticipated nonischemic VT in patients with known CAD presenting with VT and (2) the substrate and VT characteristics of this unique subset of patients. METHODS: We examined consecutive patients referred for VT catheter ablation who had a history of myocardial infarction and angiography documented CAD with presumed ischemic VT. Patients with low-voltage zones and/or VT origin inconsistent with CAD distribution were included for further analysis. RESULTS: Of 732 patients, 9 (1.2%) (7 men; median age 74 years; ejection fraction 30%) fulfilled inclusion criteria. Endocardial left ventricular scar inconsistent with CAD distribution was found in 8 patients. In 1 patient, only epicardial left ventricular scar was found. The distribution of low voltage (<1.5 mV) was predominantly around the aortic and mitral valves. Thirty-one VTs were induced in 8 patients. Most VTs had right bundle branch block (68%); of these VTs, 67% had an R/S transition zone later than lead V4 consistent with basal VT origin. Epicardial ablation was necessary in 2 patients. During follow-up (30 [25-39] months), 7 of 9 patients (78%) were free of recurrent VT. CONCLUSIONS: A small but important subgroup of patients with CAD and VT has a nonischemic substrate/etiology for VT. The presence of multiple VTs with basal origin suggests a potential nonischemic perivalvular substrate and possible need for epicardial VT ablation.

• MeSH
• kardiomyopatie komplikace   epidemiologie   patofyziologie   MeSH
• katetrizační ablace MeSH
• komorová tachykardie komplikace   epidemiologie   chirurgie   MeSH
• lidé MeSH
• mapování potenciálů tělesného povrchu MeSH
• následné studie MeSH
• nemoci koronárních tepen komplikace   diagnóza   patofyziologie   MeSH
• prevalence MeSH
• prognóza MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: Catheter ablation is an effective treatment of scar-related ventricular tachycardia (VT), but the overall complexity of the procedure has precluded its widespread use. Remote magnetic navigation (RMN) has been shown to facilitate cardiac mapping and ablation of VT in a retrospective series. STOP-VT is the first multicenter, prospective, single-arm and single-procedure study evaluating RMN-based mapping and ablation of post-infarction VT. METHODS: Patients with documented VT and prior MI, in whom an ICD was implanted either for primary or secondary prevention, were recruited from four EU and US centers. Either a transseptal (48 patients) or transaortic (5 patients) approach was employed to gain access for ventricular endocardial mapping/ablation during VT (entrainment mapping, activation mapping) and/or substrate mapping in sinus rhythm (elimination of fractionated/late potentials, variable extent of substrate modification) with RMN and irrigated RF ablation. The primary endpoints were as follows: (i) non-inducibility of the target VT or any other sustained VT; (ii) elimination of sustained VT/VF during ICD follow-up of up to 12 months. RESULTS: The cohort included 53 consecutive patients (median age 67 years, 49 men, median LVEF 31%). One hemodynamically unstable patient was excluded at the onset of mapping. Inducibility of sustained VT was achieved an average of 2.2 times per patient (1-8), with mean tachycardia cycle length (TCL) 374 milliseconds (179-510). Mean total procedure and fluoroscopy times were 223 minutes and 8.7 minutes, respectively; mean cumulative fluoroscopy time during mapping and ablation was 0.95 minutes; maximum power averaged 42.3 W with nominal saline 30 cc/min irrigation; mean cumulative RF time was 38 minutes. Non-inducibility of the target VT was achieved in 49/52 patients (94.2%) and non-inducibility of any VT was achieved in 38/52 patients (73.1%). A combination of RMN and manual ablation was performed in two patients, rendering one non-inducible. During the 12-month ICD follow-up period, freedom from any sustained VT/VF was observed in 30 patients (62%), of which 19 (63%) were off antiarrhythmic medications. Five patients expired during follow-up: one presented with a VT storm, but for the others, death was not related to VT/VF (MI-cardiogenic shock, pulmonary embolism, bronchogenic carcinoma, end stage heart failure). No procedural complications were reported. CONCLUSIONS: This first prospective, single-procedure, multicenter study indicates that remote magnetic navigation is a safe and effective method for catheter ablation of post-infarction VT.

• MeSH
• internacionalita * MeSH
• katetrizační ablace metody   MeSH
• kohortové studie MeSH
• komorová tachykardie diagnóza   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetické jevy * MeSH
• následné studie MeSH
• prospektivní studie MeSH
• roboticky asistované výkony metody   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION: Following myocardial infarction (MI), left ventricular function is determined by cardiac remodeling occurring in both infarcted and noninfarcted myocardium (NIM). Unipolar voltage mapping may detect remodeling changes in NIM that are associated with the left ventricular ejection fraction (LVEF). We aimed to identify (1) unipolar voltage characteristics in patients with chronic MI, and (2) association of voltage abnormalities with degree of left ventricular dysfunction (LVD). METHODS AND RESULTS: Two groups of patients with ischemic cardiomyopathy (ICM) who underwent LV endocardial mapping during catheter ablation for ventricular tachycardia (VT) between January 2010 and December 2012 were studied. The first group (19 males) had mild to moderate LVD (M-LVD, LVEF >35%) and was matched for age, sex, infarction size, and infarction location with 10 males who had severe LVD (S-LVD, LVEF <35%). Both bipolar and unipolar endocardial abnormal voltage areas were measured and compared between groups. Abnormal bipolar area was comparable in both groups (30 ± 8% in the S-LVD group vs 28 ± 8% in the M-LVD group; P = 0.5). Total abnormal unipolar voltage area was significantly larger in the S-LVD group (57 ± 14% vs 43 ± 13%; P = 0.02). The abnormal unipolar voltage area within the normal bipolar voltage area was greater in the S-LVD group (26 ± 11% vs 15 ± 16%; P = 0.03). In receiver operating characteristic curve analysis, an 18.0% cut-off value for abnormal unipolar area within NIM identified severe LVD, with 90% sensitivity and 79% specificity (area under the curve 0.821). CONCLUSIONS: Patients with ICM and severe LVD have larger areas of unipolar voltage abnormality in the noninfarcted tissue than patients with M-LVD.

• MeSH
• dysfunkce levé srdeční komory diagnóza   patofyziologie   chirurgie   MeSH
• ischemická choroba srdeční diagnóza   patofyziologie   chirurgie   MeSH
• kardiomyopatie diagnóza   patofyziologie   chirurgie   MeSH
• katetrizační ablace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování potenciálů tělesného povrchu metody   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• gastroezofageální reflux farmakoterapie   MeSH
• kyselina chlorovodíková antagonisté a inhibitory   farmakologie   MeSH
• žaludeční kyselina sekrece   MeSH
• žaludeční šťáva účinky léků   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• gastroenterologie

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. METHODS AND RESULTS: All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

• MeSH
• akční potenciály MeSH
• časové faktory MeSH
• centra terciární péče MeSH
• elektrofyziologické techniky kardiologické MeSH
• funkce levé komory srdeční * MeSH
• katetrizační ablace * MeSH
• komorová tachykardie diagnóza   mortalita   patofyziologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• podpůrné srdeční systémy * škodlivé účinky   MeSH
• recidiva MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční selhání diagnóza   mortalita   patofyziologie   terapie   MeSH
• studie proveditelnosti MeSH
• tepový objem MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

• MeSH
• Alzheimerova nemoc * genetika   patologie   MeSH
• celogenomová asociační studie MeSH
• kognitivní dysfunkce * psychologie   MeSH
• lidé MeSH
• proteiny tau genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

• MeSH
• Alzheimerova nemoc * genetika   MeSH
• histokompatibilita - antigeny MeSH
• HLA antigeny MeSH
• HLA-DRB1 řetězec * genetika   MeSH
• lidé MeSH
• Parkinsonova nemoc * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• Publikační typ
• tisková chyba MeSH

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

• MeSH
• Alzheimerova nemoc epidemiologie   genetika   patologie   MeSH
• amyloidový prekurzorový protein beta genetika   metabolismus   MeSH
• apolipoproteiny E genetika   MeSH
• celogenomová asociační studie MeSH
• datové soubory jako téma MeSH
• genetická predispozice k nemoci MeSH
• heterozygot MeSH
• hodnocení rizik metody   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• multifaktoriální dědičnost * MeSH
• následné studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• validační studie MeSH