Progression from paroxysmal to persistent atrial fibrillation (AF) has important clinical implications and is relevant to the management of patients with AF.
The purpose of this study was to define ...the long-term rate of progression from paroxysmal to persistent AF and the relevant clinical variables.
The Canadian Registry of Atrial Fibrillation enrolled patients after a first electrocardiographic diagnosis of paroxysmal AF. Associations between baseline characteristics and clinical outcomes were evaluated using a multivariable Cox proportional hazard model and a competing risk model accounting for death as a competing risk, where appropriate.
We enrolled 755 patients (61.7% men) aged between 14 and 91 years (mean age 61.2 ± 14.2 years). The median follow-up was 6.35 years (interquartile range 2.93-10.04 years), with a rate of progression to persistent AF at 1, 5, and 10 years was 8.6%, 24.3%, and 36.3%, respectively. All-cause mortality was 30.3% at 10 years. Factors associated with AF progression were increasing age (hazard ratio HR 1.40; 95% confidence interval CI 1.23-1.60, for each 10-year increment), mitral regurgitation (HR 1.87; 95% CI 1.28-2.73), left atrial dilatation (HR 3.01; 95% CI 2.03-4.47), aortic stenosis (HR 2.40; 95% CI 1.05-5.48), and left ventricular hypertrophy (HR .47; 95% CI 1.04-2.08). Factors associated with a lower rate of progression were a faster heart rate during AF (HR 0.94; 95% CI 0.92-0.96 per 5-beat/min increment) and angina (HR 0.54; 95% CI 0.38-0.77). After accounting for death as a competing risk, left ventricular hypertrophy and aortic stenosis were no longer significant.
Within 10 years of presenting with paroxysmal AF, >50% of patients will progress to persistent AF or be dead. Increasing age, mitral regurgitation, aortic stenosis, left ventricular hypertrophy, and left atrial dilatation were associated with progression to persistent AF.
Genetic testing is recommended in specific inherited heart diseases but its role remains unclear and it is not currently recommended in unexplained cardiac arrest (UCA). We sought to assess the yield ...and clinical utility of genetic testing in UCA using whole-exome sequencing (WES).
Survivors of UCA requiring external defibrillation were included from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes. A total of 228 UCA survivors (mean age at arrest 39 ± 13 years) were included. The majority were males (66%) and of European ancestry (81%). Following advanced clinical testing at baseline, the likely aetiology of cardiac arrest was determined in 21/228 (9%) cases. Whole-exome sequencing identified a pathogenic or likely pathogenic (P/LP) variant in 23/228 (10%) of UCA survivors overall, increasing the proportion of 'explained' cases from 9% only following phenotyping to 18% when combining phenotyping with WES. Notably, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy, in the absence of a diagnosis of cardiomyopathy at the time of arrest.
Genetic testing identifies a disease-causing variant in 10% of apparent UCA survivors. The majority of disease-causing variants was located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis. The present study supports the use of genetic testing including assessment of arrhythmia and cardiomyopathy genes in survivors of UCA.
Just as concerts emerge from the interaction of many instruments, so our understanding of Shakespeare is enriched by different approaches to him. Psychoanalysis assumes that creative writers have the ...need to both reveal and conceal their own inner conflicts in their works. They leave residues in their works that, if we pay attention, can become building blocks that reveal aspects of the unconscious. Readers may find that the questions raised add to the pleasure of reading Shakespeare and that they deepens their understanding of his plays. Topics covered include the pivotal position of Hamlet, the poet and his calling, the Oedipus complex, intrapsychic conflict, the battle against paranoia and the homosexual compromise. By using psychoanalytic techniques in analyzing his plays and characters, the author reveals more about Shakespeare's hidden motivations and mental health.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergically induced ventricular tachycardia (VT) associated with syncope and sudden death.
This study sought to ...characterize arrhythmias associated with CPVT with respect to provocation by exercise and drugs, electrocardiographic characteristics, and association with long-term outcomes; and to explore the relation between age and clinical presentation.
Seventy patients from 16 families were evaluated with exercise and selective adrenaline challenge, and screened for RyR2 mutations. CPVT was diagnosed in probands with symptoms and stress- or adrenaline-provoked VT, or in asymptomatic relatives with provoked VT or RyR2 mutations. Patients were followed up for recurrent syncope, VT, and sudden death.
Twenty-seven patients including 16 probands were identified (median age 35 years, 67% female). Presentation was cardiac arrest in 33% and syncope in 56%, and 11% were asymptomatic. Polymorphic or bidirectional VT was provoked with exercise in 63% and adrenaline in 82%. The initiating beat of VT was late-coupled and wide (coupling interval 418 ± 42 ms; QRSd 131 ± 17 ms), and QRS morphology suggested an outflow tract origin in 59%. During follow-up of 6.2 ± 5.7 years, 2 patients died despite an implantable cardioverter-defibrillator (ICD), 4 patients received ICD therapy for VT, and 5 patients had inappropriate therapy for supraventricular tachycardia. Patients presenting with late-onset CPVT (age > 21; n = 10) were often female (80%) and less likely to have RyR2 (Ryanodine receptor type 2) mutations (33%), and fatal events were not observed during follow-up (4.1 ± 3.6 years).
Ventricular arrhythmia in CPVT is often initiated from the outflow tract region. Despite β-blocker therapy and selective ICD implantation, breakthrough arrhythmias occur and may be associated with adverse outcomes.
Characterizing patterns of animal movement is a major aim in population ecology, and yet doing so at an appropriate spatial scale remains a major challenge. Estimating the frequency and distances of ...movements is of particular importance when species are implicated in the transmission of zoonotic diseases. European badgers (Meles meles) are classically viewed as exhibiting limited dispersal, and yet their movements bring them into conflict with farmers due to their potential to spread bovine tuberculosis in parts of their range. Considerable uncertainty surrounds the movement potential of badgers, and this may be related to the spatial scale of previous empirical studies. We conducted a large‐scale mark–recapture study (755 km²; 2008–2012; 1935 capture events; 963 badgers) to investigate movement patterns in badgers, and undertook a comparative meta‐analysis using published data from 15 European populations. The dispersal movement (>1 km) kernel followed an inverse power‐law function, with a substantial ‘tail’ indicating the occurrence of rare long‐distance dispersal attempts during the study period. The mean recorded distance from this distribution was 2·6 km, the 95 percentile was 7·3 km and the longest recorded was 22·1 km. Dispersal frequency distributions were significantly different between genders; males dispersed more frequently than females, but females made proportionally more long‐distance dispersal attempts than males. We used a subsampling approach to demonstrate that the appropriate minimum spatial scale to characterize badger movements in our study population was 80 km², substantially larger than many previous badger studies. Furthermore, the meta‐analysis indicated a significant association between maximum movement distance and study area size, while controlling for population density. Maximum long‐distance movements were often only recorded by chance beyond the boundaries of study areas. These findings suggest that the tail of the badger movement distribution is currently underestimated. The implications of this for understanding the spatial ecology of badger populations and for the design of disease intervention strategies are potentially significant.
Swallowing-induced atrial tachycardia Mathew, Rebecca, MD; Green, Martin S., MD; Nery, Pablo B., MD
CMAJ. Canadian Medical Association journal,
04/2018, Letnik:
190, Številka:
16
Journal Article
Recenzirano
Odprti dostop
An 87-year-old woman presented at the emergency department with sudden and recurring episodes of lightheadedness that occurred while she was eating and drinking. The patient did not feel any chest ...pain or heart palpitation, and she had not experienced fainting, gastrointestinal distress, difficulty with or painful swallowing, nausea or heartburn. She had a history of rheumatic fever and bacterial endocarditis, which had been treated with a prolonged course of antibiotics given intravenously when she was an adolescent. On initial assessment, the patient was hemodynamically stable, with no substantial orthostatic change. The results of cardiac, respiratory and gastrointestinal examinations were normal. A gross neurologic screen was unremarkable. Laboratory investigations, including cell count and differential, serum chemistry, extended electrolytes, liver panel, coagulation profile and cardiac biomarkers, as well as chest radiography, were normal. Here, Mathew et al studying treatment on swallowing-induced atrial tachycardia of an 87-year-old woman.
We present results from a study of the dense circumnuclear molecular gas of starburst galaxies. The study aims to investigate the interplay between starbursts, active galactic nuclei and molecular ...gas. We characterize the dense gas traced by HCN, HCO+ and HNC and examine its kinematics in the circumnuclear regions of nine starburst galaxies observed with the Australia Telescope Compact Array. We detect HCN (1–0) and HCO+ (1–0) in seven of the nine galaxies and HNC (1–0) in four. Approximately 7 arcsec resolution maps of the circumnuclear molecular gas are presented. The velocity-integrated intensity ratios, HCO+ (1–0)/HCN (1–0) and HNC (1–0)/HCN (1–0), are calculated. Using these integrated intensity ratios and spatial intensity ratio maps, we identify photon-dominated regions (PDRs) in NGC 1097, NGC 1365 and NGC 1808. We find no galaxy which shows the PDR signature in only one part of the observed nuclear region. We also observe unusually strong HNC emission in NGC 5236, but it is not strong enough to be consistent with X-ray-dominated region chemistry. Rotation curves are derived for five of the galaxies and dynamical mass estimates of the inner regions of three of the galaxies are made.
Type 2 diabetes is one of the leading pathologies that increases the risk of improper wound healing. Obesity has become a major risk factor for this disease that is now considered to be the 4th ...highest cause of preventable blindness according to the World Health Organization. The cornea is the most densely innervated structure in the human body and senses even the slightest injury. In diabetes, decreased corneal sensitivity secondary to diabetic peripheral neuropathy can lead to increased corneal abrasion, ulceration, and even blindness. In this study, a diet induced obesity (DIO) mouse model of pre-Type 2 diabetes was used to characterize changes in sensory nerves and P2X7, a purinoreceptor, a pain receptor, and an ion channel that is expressed in a number of tissues. Since our previous studies demonstrated that P2X7 mRNA was significantly elevated in diabetic human corneas, we examined P2X7 expression and localization in the DIO murine model at various times after being fed a high fat diet. Fifteen weeks after onset of diet, we found that there was a significant decrease in the density of sub-basal nerves in the DIO mice that was associated with an increase in tortuosity and a decrease in diameter. In addition, P2X7 mRNA expression was significantly greater in the corneal epithelium of DIO mice, and the increase in transcript was enhanced in the central migrating and peripheral regions after injury. Interestingly, confocal microscopy and thresholding analysis revealed that there was a significant increase in P2X7 distal to the injury, which contrasted with a decrease in P2X7-expressing stromal sensory nerves. Therefore, we hypothesize that the P2X7 receptor acts to sense changes at the leading edge following an epithelial abrasion, and this fine-tuned regulation is lost during the onset of diabetes. Further understanding of the corneal changes that occur in diabetes can help us better monitor progression of diabetic complications, as well as develop new therapeutics for the treatment of diabetic corneal dysfunction.
•The corneal epithelium from DIO murine model has an elevated expression of P2X7.•P2X7 expression is similar to that of corneas from humans with Type 2 diabetes.•The localization of P2X7 is enhanced distal from the leading wound edge.•The distinct pattern of sub-basal corneal nerves is lost after 15 weeks of enhanced diet.•There is an increase in tortuosity and a decrease in diameter of the corneal nerves.
The Wenckebach Phenomenon Hansom, Simon P; Golian, Mehrdad; Green, Martin S
Current cardiology reviews,
01/2021, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Medicine has many great pioneers, and in 1899, one such pioneer - Karel Frederik Wenckebach made a discovery which, even to this day, remains one of the fundamental concepts within electrophysiology.
...Since the Wenckebach Phenomenon was first described, the field of electrophysiology has developed at a rapid pace, allowing us to observe this behaviour, and its complexities, in many new ways. In a similar way, this chapter will illustrate Wenckebach behaviour across a spectrum of modalities from the 12 lead ECG, through to the intra-cardiac recordings from both electrophysiological studies and implantable cardiac devices. In doing so, we continue to shed light on the phenomenon first identified through Wenckebach’s meticulous attention to detail some 120 years ago.
Basal-like and triple-negative breast tumours encompass an important clinical subgroup and biomarkers that can prognostically stratify these patients are required.
We investigated two breast cancer ...tissue microarrays for the expression of calpain-1, calpain-2 and calpastatin using immunohistochemistry. The first microarray was comprised of invasive tumours from 1371 unselected patients, and the verification microarray was comprised of invasive tumours from 387 oestrogen receptor (ER)-negative patients.
The calpain system contains a number of proteases and an endogenous inhibitor, calpastatin. Calpain activity is implicated in important cellular processes including cytoskeletal remodelling, apoptosis and survival. Our results show that the expression of calpastatin and calpain-1 are significantly associated with various clinicopathological criteria including tumour grade and ER expression. High expression of calpain-2 in basal-like or triple-negative disease was associated with adverse breast cancer-specific survival (P=0.003 and <0.001, respectively) and was verified in an independent cohort of patients. Interestingly, those patients with basal-like or triple-negative disease with a low level of calpain-2 expression had similar breast cancer-specific survival to non-basal- or receptor- (oestrogen, progesterone or human epidermal growth factor receptor 2 (HER2)) positive disease.
Expression of the large catalytic subunit of m-calpain (calpain-2) is significantly associated with clinical outcome of patients with triple-negative and basal-like disease.
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