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.

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.

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.

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.

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.

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.

Contact-Force Guided Pulmonary Vein Isolation does not Improve Success Rate in Persistent Atrial Fibrillation Patients and Severe Left Atrial Enlargement: A 12-month Follow-Up Study.

BACKGROUND: Catheter ablation is a cornerstone treatment strategy in atrial fibrillation (AF). Left atrial (LA) size is one of the contributors in development of AF recurrences. The impact of contact-forced (CF) guided catheter ablation on the success rate of persistent AF patients with severe enlarged LA has not been investigated yet. METHODS: Sixty-six patients with diagnosis of longstanding persistent AF undergoing catheter ablation were enrolled. All patients underwent a standard transthoracic echocardiography according to the guidelines. LA size was considered severely enlarged when LA diameter was ≥ 50 mm. CF catheter ablation with a Tacticath Quartz catheter (St Jude Medical, St. Paul, MN, USA) was used in all patients. RESULTS: The mean age was 61.9 ± 9.9 years, and LAD 47.8 ± 11.6 mm. Among 66 patients with persistent AF, 32 (48%) patients were diagnosed with AF recurrences. Twenty-eight (42%) patients had severely enlarged LA. The recurrence of AF was comparable in patients with and without severe enlarged LA (47% vs. 42%, p=0.79). The recurrence of AF was lower in patients who underwent CF-guided ablation with a normal LA dimension (36 %, p=0.54). Procedure duration was longer in patients with severely enlarged LA. LA dimension was not significantly different between patients with and without AF recurrence (49.8 ± 7.9 mm vs. 45.9 ± 7.5 mm, p=0.15). LAD and was significantly correlated with the time to recurrence of AF (r:-0.60, p=0.02). CONCLUSION: Our preliminary findings have demonstrated that CF guided ablation does not improve the success rate in longstanding persistent AF patients with severe LA enlargement.

The Guideline-Policy Gap in Direct-Acting Oral Anticoagulants Usage in Atrial Fibrillation: Evidence, Practice, and Public Policy Considerations.

Atrial fibrillation has a high disease burden-both in prevalence and associated consequences. Despite anticoagulation being an effective treatment in atrial fibrillation, stroke prevention is slow to reflect evidence-based practice. Real-world data reveal a substantial portion of patients who would benefit from anticoagulation, yet do not receive it adequately or at all. A large part of this suboptimal treatment is due to the underutilization of direct oral anticoagulants (DOACs). In response to abundant evidence published over a short timeframe, international guidelines have adopted DOAC usage ahead of policy and fund holders. This paper reviews the evidence and values that influence published guidelines, patient-physician decision making, and policy framework on DOAC usage. An important factor is the access gap between patients who qualify for DOAC according to evidence-based guidelines and the subset of this cohort who are eligible for DOAC based on government funded policy. We analyse the Canadian health system in detail-including drug approval and funding process. Health care systems in other countries are explored, with emphasis on similar universal health care systems that may help overcome barriers common to Canada. We will discuss strategies to: (1) improve awareness of the risk and preventability of stroke; (2) enable physicians to provide evidence-based DOAC usage; (3) empower patients to improve adherence and persistence; (4) collect real-life data that encourages patient self-monitoring, physician outcomes auditing, and building evidence that is useful for policy makers; and (5) use postmarketing data in negotiating shared risk management between pharmaceuticals and government to improve access to DOACs.

Gold-tip versus contact-sensing catheter for cavotricuspid isthmus ablation: A comparative study.

OBJECTIVE: Radiofrequency (RF) ablation is a highly successful procedure for the management of typical atrial flutter (AFL), an abnormal heart rhythm originating within the atria. There is no strong evidence that the use of contact force (CF) has any impact on procedural duration or acute success in the management of cavotricuspid isthmus (CTI)-dependent AFL. The aim of this study was to compare acute procedural parameters using a non-CF, 4-mm, gold-tip, irrigated catheter and a CF-sensing catheter in patients with AFL. METHODS: This was a retrospective cohort study. Consecutive patients who underwent typical AFL catheter ablation with either a gold-tip or CF-sensing catheter were enrolled. The procedural parameters obtained were: time to achieve bidirectional block, time to terminate AFL, total duration of RF application, procedure duration, fluoroscopy time, acute reconnection within 20 minutes following the last RF application, and procedural complications. RESULTS: Of the 40 patients screened, 37 were included in the study. The procedural endpoint of bidirectional isthmus block was achieved in all patients. The use of gold-tip catheters was associated with a shorter length of time to achieve bidirectional block (median time: 20.0 minutes [interquartile range {IQR}: 12.0-28.0 minutes]) compared with a median time of 36.0 minutes (IQR: 12.0-53.0 minutes; p=0.048) in the CF group. Furthermore, there was a trend toward reduced procedural duration in favor of the gold-tip catheter (median goldtip: 74.0 minutes [IQR: 57.0-84.0 minutes]; median CF: 85.0 minutes [IQR: 57.0-107.0 minutes]; p=0.171). A greater requirement for the use of long sheaths was observed in cases where the CF catheter was employed for the procedure (CF: 11, 57.9 %; non-CF: 1, 5.6%; p=0.005). CONCLUSION: The time required to achieve bidirectional block, which is also reflected in the procedural time, was less when using a gold-tip catheter, and there was less need for the use of a long sheath. Further studies may be useful to evaluate this finding.

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).

High Voltage Guided Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation.

BACKGROUND: Ablation of the pulmonary vein (PV) antrum using an electroanatomic mapping system is standard of care for point-by-point pulmonary vein isolation (PVI). Focused ablation at critical areas is more likely to achieve intra-procedural PV isolation and decrease the likelihood for reconnection and recurrence of atrial fibrillation (AF). Therefore this prospective pilot study is to investigate the short-term outcome of a voltage-guided circumferential PV ablation (CPVA) strategy. METHODS: We recruited patients with a history of paroxysmal atrial fibrillation (AF). The EnSite NavX system (St. Jude Medical, St Paul, Minnesota, USA) was employed to construct a three-dimensional geometry of the left atrium (LA) and voltage map. CPVA was performed; with radiofrequency (RF) targeting sites of highest voltage first in a sequential clockwise fashion then followed by complete the gaps in circumferential ablation. Acute and short-term outcomes were compared to a control group undergoing conventional standard CPVA using the same 3D system. Follow-up was scheduled at 3, 6 and 12 months. RESULTS: Thirty-four paroxysmal AF patients with a mean age of 40 years were included. Fourteen patients (8 male) underwent voltage mapping and 20 patients underwent empirical, non-voltage guided standard CPVA. A mean of 54 ± 12 points per PV antrum were recorded. Mean voltage for right and left PVs antra were 1.7±0.1 mV and 1.9±0.2 mV, respectively. There was a trend towards reduced radiofrequency time (40.9±17.4 vs. 48.1±15.5 mins; p=0.22). CONCLUSION: Voltage-guided CPVA is a promising strategy in targeting critical points for PV isolation with a lower trend of AF recurrence compared with a standard CPVA in short-term period. Extended studies to confirm these findings are warranted.

Left Atrial Appendage characteristics in patients with Persistent Atrial Fibrillation undergoing catheter ablation (LAAPAF Study).

BACKGROUND: Despite technological and scientific efforts, the recurrence rate of persistent atrial fibrillation (AF) remains high. Several studies have shown that in addition to pulmonary vein (PV) isolation other non-PV triggers, particularly left atrial appendage may be the source of initiation and maintenance of AF. There are few studies showing the role of left atrial appendage (LAA) isolation in order to obtain higher success rate in persistent AF patients. OBJECTIVE: We analyzed the LAA volume, volume index and shape relative to the LA in patients with persistent AF undergoing AF ablation. METHODS: Fifty-nine consecutive patients with persistent AF who underwent catheter ablation were enrolled. Computerized tomography (CT) was performed in order to assess left atrial and PV anatomy including the LAA. Digital subtraction software (GE Advantage Workstation 4.3) was used to separate the LAA from the LA and calculate: LA volume (LAV), LA volume index (LAV/body surface area), LAA volume (LAAV), LAA volume index (LAA volume/LA volume), and LAA morphology [chicken wing (CW) or non-chicken wing (NCW)]. RESULTS: The mean age was 64.6 ± 9.8 years, 44 % male, and LA diameter 47.6 ± 7.8 mm. Median follow-up (FU) was 13 months. All patients had antral isolation of PVs and ablation of complex fractionation ± linear ablation (roof line/superior coronary sinus/mitral line). Among 59 patients with persistent AF, 26 (44 %) patients were diagnosed with AF recurrences. Mean LAV was 145.0 ± 45.9 ml, LAVI 68.9 ± 20.0 ml/m2, LAAV 10.3 ± 4.0 ml, and LAAVI 7.3 ± 2.7 ml/m2. LAA shape was non-chicken wing (NCW) in the majority of patients (51 %). LAA parameters were not significantly different between patients with and without AF recurrence (LAAV 11.0 ± 4.3 ml vs. 9.7 ± 3.8 ml, p=0.26; LAAVI 7.5 ± 3.0 ml/m2 vs. 7.2 ± 2.5 ml/m2, p=0.71; LAA shape of NCW 50 % vs 52 %, p=0.75, respectively). LAV was significantly correlated with the LAAV (r: o.47, p=0.009). The incidence of NCW LAA was significantly higher in patients with previous stroke/TIA (80 % vs. 20 %, p=0.04). CONCLUSION: The LAA anatomical characteristics (volume/volume index and the shape) were comparable in patients with/out AF recurrence post PVI. It remains to be determined if additional LAA isolation will impact outcomes in patients with persistent AF.

Single-entry models (SEMs) for scheduled services: Towards a roadmap for the implementation of recommended practices.

BACKGROUND: Long waiting times for elective services continue to be a challenging issue. Single-entry models (SEMs) are used to increase access to and flow through the healthcare system. This paper provides a roadmap for healthcare decision-makers, managers, physicians, and researchers to guide implementation and management of successful and sustainable SEMs. METHODS: The roadmap was informed by an inductive qualitative synthesis of the findings from a deliberative process (a symposium on SEMs, with clinicians, researchers, senior policy-makers, healthcare managers, and patient representatives) and focus groups with the symposium participants. RESULTS: SEMs are a promising strategy to improve the management of referrals and represent one approach to reduce waiting times. The SEMs roadmap outlines current knowledge about SEMs and critical success factors for SEMs' implementation and management. CONCLUSIONS: This SEM roadmap is intended to help clinicians, decision-makers, managers, and researchers interested in developing new or strengthening existing SEMs. We consider this roadmap to be a living document that will continue to evolve as we learn more about implementing and managing sustainable SEMs.

Extragalactic radio surveys in the pre-Square Kilometre Array era.

The era of the Square Kilometre Array is almost upon us, and pathfinder telescopes are already in operation. This brief review summarizes our current knowledge of extragalactic radio sources, accumulated through six decades of continuum surveys at the low-frequency end of the electromagnetic spectrum and the extensive complementary observations at other wavelengths necessary to gain this understanding. The relationships between radio survey data and surveys at other wavelengths are discussed. Some of the outstanding questions are identified and prospects over the next few years are outlined.

"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.