Electrocardiographic predictors of atrial fibrillation in patients with cryptogenic stroke.

BACKGROUND: Empiric anticoagulation is not routinely indicated in patients with cryptogenic stroke without documentation of atrial fibrillation (AF). Therefore, identification of patients at increased risk of AF from this vulnerable group is vital. OBJECTIVES: To identify electrocardiographic (ECG) predictors of AF in patients with cryptogenic stroke or transient ischemic attack (TIA) undergoing insertion of an implantable cardiac monitor (ICM). METHODS: In this single-center study, 48 patients with cryptogenic stroke or TIA had an ICM implanted for detection of AF between January 2013 and September 2019. Patients with and without AF were compared in terms of p-wave duration and a novel index (MVP score). RESULTS: During a mean follow-up of 16 ± 14 months, AF was detected in seven patients (15%). Diagnosis of AF was made after a mean of 10 ± 14 months, with time to first AF detection ranging between 1 and 40 months. Patients with AF had a longer p-wave duration (136 ± 9 ms vs. 116 ± 10 ms; p = .0001) and a higher MVP score (4.5 ± 1.2 vs. 2.0 ± 0.9, p = .0001) than those without AF. Advanced interatrial block (IAB) was observed in 43% of patients with ICM evidence of AF and 0% of those without AF (p = .002). Age, LA size or LVEF were not predictors of AF. CONCLUSION: An increased p-wave duration, advanced IAB and high MVP score are associated with AF occurrence in patients with cryptogenic stroke. Identifying patients with these markers may be helpful as they may benefit from more exhaustive and prolonged monitoring.

Update on long QT syndrome.

Long QT syndrome (LQTS) is an inherited disorder characterized by a prolonged QT interval in the 12-lead electrocardiogram and increased risk of malignant arrhythmias in patients with a structurally normal heart. Since its first description in the 1950s, advances in molecular genetics have greatly improved our understanding of the cause and mechanisms of this disease. Sixteen genes linked to LQTS have been described and genetic testing had become an integral part of the diagnosis and risk stratification. This article provides an updated review of the genetic basis, diagnosis, and clinical management of LQTS.

Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site.

AIMS: Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits. METHODS AND RESULTS: Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II-III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II-III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II-III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise. CONCLUSION: The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II-III loop. This represents a 'mutation hotspot' in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.

Ambulatory ECG predictors of atrial fibrillation are ineffective in severe sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is strongly associated with atrial fibrillation (AF). Long-term ECG monitoring with implantable loop recorders facilitates the identification of undiagnosed AF in 20% of severe OSA cases. However, ambulatory ECG (AECG) monitoring is less resource intensive, and various parameters have been shown to predict AF. The aim of this study was to assess the efficacy of such AECG-based AF predictors in identifying patients with severe OSA most at risk. METHODS: Prospective observational study including patients with severe OSA and no history of AF. Patients had two 24-h AECG recordings, and if no AF was detected, implanted with a loop recorder (maximum 3 years). RESULTS: Of 25 patients implanted, AF ≥ 10 s was detected in 5 patients. None of the parameters from the AECG recordings were significantly different between patients who did and did not develop AF. CONCLUSIONS: AECG-based parameters were not effective for the prediction of AF in this severe OSA cohort.

Infrasound monitoring in non-traditional environments.

To date, the infrasound community has avoided deployments in noisy urban sites because interests have been in monitoring distant sources with low noise sites. As monitoring interests expand to include low-energy urban sources only detectable close to the source, case studies are needed to demonstrate the challenges and benefits of urban infrasound monitoring. This case study highlights one approach to overcoming urban challenges and identifies a signal's source in a complex acoustic field. One 38 m and one 120 m aperture infrasound arrays were deployed on building rooftops north of downtown Dallas, Texas. Structural signals in the recorded data were identified, and the backazimuth to the source determined with frequency-wavenumber analysis. Fourteen days of data were analyzed to produce 314 coherent continuous-wave packets, with 246 of these detections associated with a narrow range of backazimuth directions. Analyzing the backazimuths from the two arrays identified the Mockingbird Bridge as the probable source which was the verified with seismic measurement on the structure. Techniques described here overcame the constraints imposed by urban environments and provide a basis to monitor infrastructure and its conditions at local distances (0-100 km).

"Spontaneous Twiddler's" Syndrome: The Importance of the Device Shape.

Twiddler's syndrome is caused by patient manipulation of the cardiac implantable device (CID) around its central axis within the pocket, resulting in retraction and dislocation of the electrodes. There are, however, some reports that Twiddler's syndrome may occur spontaneously without the patient's manipulation. This remains contentious as it may be argued that patients may not want to admit to manipulating the CID or may have been unaware of their actions. Recently, we have observed three very similar cases with a "spontaneous" Twiddler's syndrome resulting in lead displacement. All of the three patients denied device manipulation and were not prone to somnambulism or repetitive involuntary motor behaviors. It, therefore, seems highly unlikely that all patients could have manipulated the device in exactly the same way to result in the same postrotational position within the implant pocket. The fact is that the same device was implicated in all these cases in a relatively similar time sequence from implant to recognition of the implantable cardiac defibrillator rotation. We postulate that the unique elongated decision of the Fortify Assura (St. Jude Medical, Minneapolis, MN, USA) ICD makes this device prone to spontaneous rotation as is exemplified by our case series.

A luminous quasar at a redshift of z = 7.085.

The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS J1120+0641 is 1.9 megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS J1120+0641 exceeded 0.1.

Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long-term follow-up study.

BACKGROUND: Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet. OBJECTIVE: To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence. METHODS: Sixty-two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P-wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography. RESULTS: Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty-seven patients were male. During a mean follow-up period of 49.8 ± 22 months (range 12-60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12-9.93; p = .03). CONCLUSIONS: IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence.

Relation between perfluorooctanoic acid exposure and strokes in a large cohort living near a chemical plant.

BACKGROUND: A community around a chemical plant was exposed to perfluorooctanoic acid (PFOA) for over 50 years, primarily through drinking water. One cohort study of PFOA-exposed workers found a positive trend with stroke mortality. Other, cross-sectional, studies have found positive associations between serum PFOA and risk factors for stroke, including cholesterol, uric acid, and hypertension. OBJECTIVES: We examined the relation between PFOA exposure and incident strokes (including transient ischemic attacks) in community members, including plant workers. METHODS: Participants completed surveys in 2008-2011 regarding medical history, health-related behaviors, and demographics. Cox proportional hazards models were used to compare the hazard of stroke in relation to time-varying estimated cumulative PFOA serum levels, adjusting for confounders. RESULTS: Of 32,254 survey participants with exposure estimates, 1596 self-reported stroke, of whom 919 had their self-report validated by medical records review. After excluding subjects with strokes before age 20 and subjects born before 1920 or with missing covariate data, 825 cases remained. Compared with the lowest quintile of cumulative exposure, subsequent quintiles in the retrospective analysis had hazard ratios of 1.39 [95% confidence interval, 1.11-1.76], 1.36 [1.08-1.71], 1.45 [1.15-1.82], and 1.13 [0.90-1.44]. Tests for trend with linear or log-transformed cumulative dose were not significant (p=0.52 and 0.59, respectively). Neither an analysis with a 5-year lag, nor prospective analyses restricted to 2005-2011 (302 cases) found positive trends (p=0.44, positive trend; p=0.28, negative trend, respectively). CONCLUSIONS: Overall, our data provide only modest evidence of an association between PFOA and stroke incidence.

A randomized-controlled pilot study comparing ICD implantation with and without intraoperative defibrillation testing in patients with heart failure and severe left ventricular dysfunction: a substudy of the RAFT trial.

INTRODUCTION: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. METHODS: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. RESULTS: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all-cause mortality occurred in 10% of patients in the no-DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21-1.31, P = 0.14). CONCLUSIONS: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT.

Society position statement : Canadian Cardiovascular Society/Canadian Anesthesiologists' Society/Canadian Heart Rhythm Society joint position statement on the perioperative management of patients with implanted pacemakers, defibrillators, and neurostimulating devices.

PURPOSE: There are more than 200,000 Canadians living with permanent pacemakers or implantable defibrillators, many of whom will require surgery or invasive procedures each year. They face potential hazards when undergoing surgery; however, with appropriate planning and education of operating room personnel, adverse device-related outcomes should be rare. This joint position statement from the Canadian Cardiovascular Society (CCS) and the Canadian Anesthesiologists' Society (CAS) has been developed as an accessible reference for physicians and surgeons, providing an overview of the key issues for the preoperative, intraoperative, and postoperative care of these patients. PRINCIPAL FINDINGS: The document summarizes the limited published literature in this field, but for most issues, relies heavily on the experience of the cardiologists and anesthesiologists who contributed to this work. This position statement outlines how to obtain information about an individual's type of pacemaker or implantable defibrillator and its programming. It also stresses the importance of determining if a patient is highly pacemaker-dependent and proposes a simple approach for nonelective evaluation of dependency. Although the document provides a comprehensive list of the intraoperative issues facing these patients, there is a focus on electromagnetic interference resulting from electrocautery and practical guidance is given regarding the characteristics of surgery, electrocautery, pacemakers, and defibrillators which are most likely to lead to interference. CONCLUSIONS: The document stresses the importance of preoperative consultation and planning to minimize complications. It reviews the relative merits of intraoperative magnet use vs reprogramming of devices and gives examples of situations where one or the other approach is preferable.

Perceptions of cardiac rehabilitation patients, specialists and rehabilitation programs regarding cardiac rehabilitation wait times.

BACKGROUND: In 2006, the Canadian Cardiovascular Society (CCS) Access to Care Working Group recommended a 30-day wait time benchmark for cardiac rehabilitation (CR). The objectives of the current study were to: (1) describe cardiac patient perceptions of actual and ideal CR wait times, (2) describe and compare cardiac specialist and CR program perceptions of wait times, as well as whether the recommendations are appropriate and feasible, and (3) investigate actual wait times and factors that CR programs perceive to affect these wait times. METHODS: Postal and online surveys to assess perceptions of CR wait times were administered to CR enrollees at intake into 1 of 8 programs, all CCS member cardiac specialists treating patients indicated for CR, and all CR programs listed in Canadian directories. Actual wait times were ascertained from the Canadian Cardiac Rehabilitation Registry. The design was cross-sectional. Responses were described and compared. RESULTS: Responses were received from 163 CR enrollees, 71 cardiac specialists (9.3% response rate), and 92 CR programs (61.7% response rate). Patients reported that their wait time from hospital discharge to CR initiation was 65.6 ± 88.4 days (median, 42 days), while their ideal median wait time was 28 days. Most patients (91.5%) considered their wait to be acceptable, but ideal wait times varied significantly by the type of cardiac indication for CR. There were significant differences between specialist and program perceptions of the appropriate number of days to wait by most indications, with CR programs perceiving shorter waits as appropriate (p < 0.05). CR programs reported that feasible wait times were significantly longer than what was appropriate for all indications (p < 0.05). They perceived that patient travel and staff capacity were the main factors negatively affecting waits. The median wait time from referral to program initiation was 64 days (mean, 80.0 ± 62.8 days), with no difference in wait by indication. CONCLUSIONS: Wait times following access to cardiac rehabilitation are prolonged compared with consensus recommendations, and yet are generally acceptable to most patients. Wait times following percutaneous coronary intervention in particular may need to be shortened. Future research is required to provide an evidence base for wait time benchmarks.

Prevalence of RPGR-mutated X-linked retinitis pigmentosa among males.

BACKGROUND: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease predominantly affecting males. MATERIALS AND METHODS: A comprehensive literature review was conducted to determine the prevalence of retinitis pigmentosa GTPase regulator (RPGR)-mutated XLRP. Identified studies were used to estimate four components among males: the prevalence of retinitis pigmentosa (RP), the proportion of RP that was X-linked, the proportion of misclassified inheritance type among RP cases, and the proportion of XLRP that was RPGR-mutated. Studies providing a direct estimate of XLRP prevalence were also included. The components' sample size-weighted averages were combined to determine an overall prevalence estimate. RESULTS: The prevalence of XLRP was estimated to be between 2.7-3.5 per 100,000 males in the US, Europe, and Australia. After correction for misclassification, the prevalence increased to 4.0-5.2 per 100,000 males. Finally, the proportion of XLRP cases due to RPGR mutations was applied, resulting in an RPGR-mutated XLRP estimate of 3.4-4.4 per 100,000 males. Studies from other countries were consistent with the results for the overall XLRP prevalence but were not included in the final calculation because of regional variations and lack of detailed information. CONCLUSIONS: These findings address an important gap in the understanding of RPGR-mutated XLRP by summarizing the global burden of this condition.

The obscuration by dust of most of the growth of supermassive black holes.

Supermassive black holes underwent periods of exponential growth during which we see them as quasars in the distant Universe. The summed emission from these quasars generates the cosmic X-ray background, the spectrum of which has been used to argue that most black-hole growth is obscured. There are clear examples of obscured black-hole growth in the form of 'type-2' quasars, but their numbers are fewer than expected from modelling of the X-ray background. Here we report the direct detection of a population of distant type-2 quasars, which is at least comparable in size to the well-known unobscured type-1 population. We selected objects that have mid-infrared and radio emissions characteristic of quasars, but which are faint at near-infrared and optical wavelengths. We conclude that this population is responsible for most of the black-hole growth in the young Universe and that, throughout cosmic history, black-hole growth occurs in the dusty, gas-rich centres of active galaxies.

A Systematic Review of the Risk of Motor Vehicle Collision in Patients With Syncope.

BACKGROUND: Drivers at risk of sudden incapacitation from syncope pose a potential threat to themselves and to society. The purpose of this systematic review is to synthesize the risk of motor vehicle collisions (MVCs) for patients with a history of syncope. METHODS: We systematically searched Medline (1946-2019) as well as Cinahl, Embase, Psychinfo, and the Transportation Research Information Documentation (1806-2017) for articles on MVCs and drivers with vasovagal syncope (VVS), arrhythmic syncope, or syncope not yet diagnosed (NYD). Quality ratings were assigned by team consensus. RESULTS: Eleven studies of moderate quality were included (n = 42,972). Compared with the general populations of Canada, the United States, and the United Kingdom (0.49%-2.29% per driver-year), the prospective MVC risk was lower for VVS (0.0%-0.31% per driver-year; 3 studies; n = 782) and higher for arrhythmic syncope (1.9%-3.4% per driver-year; 2 studies; n = 730). The results were more variable for syncope NYD (0.0%-6.9% per driver-year prospectively; 6 studies; n = 41,460). Patients with syncope NYD had an almost 2-fold increased MVC risk in the largest study, although the smaller studies showed contradictory findings. CONCLUSIONS: VVS patients appear to be at very low risk for MVCs, supporting current guidelines which do not recommend driving suspension for these patients in most cases. Although the data for other forms of syncope are too limited for definitive conclusions and must be improved, arrhythmic syncope appears to be associated with nontrivial risk.

Canadian Registry of ICD Implant Testing procedures (CREDIT): current practice, risks, and costs of intraoperative defibrillation testing.

BACKGROUND: There is uncertainty about the proper role of defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion. METHODS: A prospective registry was conducted at 13 sites in Canada between January 2006 and October 2007. OBJECTIVES: To document the details of DT, the reasons for not conducting DT, and the costs and complications associated with DT. RESULTS: DT was conducted at implantation in 230 of 361 patients (64%). DT was more likely to be conducted for new implants compared with impulse generator replacements (71% vs 32%, P = 0.0001), but was similar for primary and secondary prevention indications (64% vs 63%, P = NS). Among patients not having DT, the reason(s) given were: considered unnecessary (44%); considered unsafe, mainly due to persistent atrial fibrillation (37%); lack of an anesthetist (20%); and, patient or physician preference (6%). When performed, DT consisted of a single successful shock > or = 10J below maximum device output in 65% of cases. A 10J safety-margin was met by 97% of patients, requiring system modification in 2.3%. Major perioperative complications occurred in 4.4% of patients having DT versus 6.6% of patients not having DT (P = NS). ICD insertion was $844 more expensive for patients having DT (P = 0.16), largely due to increased costs ($28,017 vs $24,545) among patients having impulse generator replacement (P = 0.02). CONCLUSIONS: DT was not performed in a third of ICD implants, usually due to a perceived lack of need or relative contraindication.

Deactivation of Implantable Cardioverter Defibrillator in Patients With Terminal Diagnoses.

Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. However, in patients with terminal illnesses, these devices may disrupt the dying process. This study was undertaken to review our current strategies surrounding device deactivation. A retrospective chart review was performed at Kingston Health Sciences Centre of patients with an ICD who died from 2015 to 2018. Data collected included patient demographics, clinical details surrounding device implantation, patient co-morbidities leading to deactivation, time to deactivation, physical place of deactivation, and device programming information. Ethics approval was obtained from the Queen's University Health Sciences Research Ethics Board. A total of 49 patients were included for analysis. Mean age at the time of death was 77.5 years (range: 57 to 94 years) and 12.2% (6/49) were women. The indications for ICD implantation were primary prevention of sudden cardiac death in 69.4% (34/49) and secondary prevention in 30.6% (15/49). Deactivation as part of end-of-life care was performed in 32.7% of patients (16/49). Deactivations occurred in clinic in 6.1% (3/49) of patients, on hospital inpatient wards in 12.2% (6/49) of patients, and in critical care settings in 14.2% (7/49) of patients. The remaining 67.3% (33/49) of patients died with fully functioning devices in place. The most prevalent terminal diagnoses were metastatic cancer (22.4%) and end-stage congestive heart failure (20.4%). On average, patients had their devices deactivated 13 months (range: 0 to 62 months) after their terminal diagnosis was established. Once a patient was documented as Do Not Resuscitate (DNR), deactivation was discussed and carried out within a mean time of 38 days (range: 0 to 400 days). Seven patients had their device active for more than 1 month after being documented as DNR. Ten patients (20.4%) received ICD shocks after their terminal diagnosis, 9 received shocks in the month before death, and 2 received shocks after formal DNR orders were in place. Approximately one-third of patients with ICDs received deactivation of their cardioversion/defibrillation therapies as part of their end-of-life care plan. A relatively high proportion of patients (20%) received an ICD shock in the last month of life. In conclusion, addressing device programming needs, including deactivation of cardioversion/defibrillation therapies, should be considered in the context of a patient's goals of care in every patient with an ICD who has a co-existing life-limiting diagnosis.