Abstract The usefulness of post-mortem mRNA analysis and its potential applications in forensic casework is currently of interest, especially because of several factors affecting the quality of RNA ...samples that are not practically predictable. In fact, post-mortem RNA degradation is a complex process that has not been studied systematically. The purpose of this work is to establish whether RNA analysis from post-mortem heart tissue could be used as a forensic tool to investigate the cause of death, with special regard to those cases where a cardiac disease is suspected as the manner of death. We analysed heart tissue from 16 individuals with normal cardiac function, 9 with long post-mortem intervals (L-PMI) and 7 from organ donors with very short PMIs (S-PMIs). Right ventricle tissue was homogenised, and the RNA was isolated and reverse transcribed. The resulting cDNA was used in real-time PCR reactions to quantify the gene expression of beta-glucuronidase (GUSB), Nitric Oxide Synthase 3 (NOS3), Collagen 1 (COL1A1) and Collagen 3 (COL3A1). The percentage of samples with high-quality RNA was higher in samples with S-PMI (7 out of 7) than in samples with L-PMI (4 out of 9, p < 0.05). No differences in PMI time or cause of exitus were found between samples with degraded or non-degraded RNA in the L-PMI group. When comparing mRNA levels in samples with non-degraded RNA, we found similar values between the L-PMI and S-PMI groups for GUSB, COL1A1 and COL3A1. The NOS3 gene expression in the L-PMI subgroup was less than half that in the S-PMI. These results suggest that high-quality mRNA can be extracted from post-mortem human hearts only in some cases. Moreover, our data show that mRNA levels are independent from the PMI, even though there are mRNAs in which the expression levels are very susceptible to ischemia times. Clear knowledge about the relationship between mRNA integrity and expression and PMI could allow the use of several mRNAs as forensic tools to contribute to the determination of the cause of death with special regard to cardiovascular diseases.
Long-Term Trends in Newly Diagnosed Brugada Syndrome Casado-Arroyo, Ruben, MD, PhD; Berne, Paola, MD; Rao, Jayakeerthi Yoganarasimha, MD ...
Journal of the American College of Cardiology,
08/2016, Letnik:
68, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract Background A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population. Objectives This study sought to ...investigate the Brugada probands diagnosed from 1986 through the next 28 years. Methods We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group). Results There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients. Conclusions Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed.
Abstract Background Brugada syndrome is a cardiac disorder associated with a high risk of sudden cardiac death, especially in young subjects. The incidence and prevalence are likely underestimated. ...The diagnosis is based on a characteristic electrocardiography (ECG) pattern. The most commonly performed confirmatory test in cases of equivocal ECG is the intravenous ajmaline challenge. Although relatively safe, it carries the risk of ventricular arrhythmias that could potentially degenerate into a refractory electrical storm. Case report A 27-year-old man developed sustained ventricular fibrillation after ajmaline challenge. He was rescued on extracorporeal life support after 108 min of cardiopulmonary resuscitation. Extracorporeal life support allowed recovery of spontaneous circulation and resulted in a positive neurological outcome. < Learning objective: This case is an example of how extracorporeal life support was instituted after prolonged and unsuccessful cardiopulmonary resuscitation resulting in a positive central neurological outcome.>
A 52‐year‐old male was admitted with unstable angina and three‐vessel coronary artery disease. Electrocardiography (ECG) changes consistent with type‐1 Brugada ECG pattern were noted during ...admission. The patient was asymptomatic for syncope and had no family history of sudden cardiac death, ICD implantation, and Brugada syndrome. After coronary by‐pass graft the Brugada ECG pattern resolved, and ajmaline test did not elicit type‐1 ECG pattern, confirming the suspicion of Brugada phenocopy.
Background
Subcutaneous implantable cardioverter defibrillators (S‐ICDs) avoid complications secondary to transvenous leads, but inappropriate shocks (ISs) are frequent. Furthermore, IS data from ...patients with Brugada syndrome (BrS) with an S‐ICD are scarce.
Objective
We aimed to establish the frequency and predictors of IS in this population.
Methods
We analyzed the clinical and electrocardiographic characteristics, automated screening test data, device programming, and IS occurrence in adult patients with BrS with an S‐ICD.
Results
Thirty‐nine patients were enrolled (69% male, mean age at diagnosis 46 ± 13 years, mean age at implantation 48 ± 13 years). During a mean follow‐up of 26 ± 21 months, 18% patients experienced IS. Patients with IS were younger at the time of diagnosis (36 ± 8 vs. 48 ± 13 years, p = .018) and S‐ICD implantation (38 ± 9 vs. 50 ± 23 years, p = .019) and presented with spontaneous type 1 Brugada electrocardiogram pattern more frequently at diagnosis or during follow‐up (71% vs. 25%, p = .018). During automated screening tests, patients with IS showed lower QRS voltage in the primary vector in the supine position (0.58 ± 0.26 vs. 1.10 ± 0.35 mV, p = .011) and lower defibrillator automated screening score in the primary vector in the supine (123 ± 165 vs. 554 ± 390 mV, p = .005) and standing (162 ± 179 vs. 486 ± 388 mV, p = .038) positions. Age at diagnosis was the only independent predictor of IS (hazard ratio = 0.873, 95% confidence interval: 0.767–0.992, p = .037).
Conclusion
IS was a frequent complication in patients with BrS with an S‐ICD. Younger age was independently associated with IS. A more thorough screening process might help prevent IS in this population.
This case emphasizes the need to use intravascular imaging to optimize stent implantation in the left main coronary artery. Despite recommendations, intravascular imaging is still widely ...under-utilized. The recently developed stent apposition OCT software (OPTIS Stent Optimization Software; Abbott Vascular) confirmed its usefulness in optimizing stent implantation in unprotected left main PCI.
Implantable cardioverter-defibrillator (ICD) indications for primary prevention in Brugada syndrome (BrS) are still debated.
The authors investigated the long-term outcome after ICD implantation in a ...large cohort of BrS patients.
Of a total of 370 patients with BrS in follow-up (age 43 ± 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors analyzed the long-term incidence of shocks and complications.
An ICD was implanted for secondary prevention in 10 patients (9.6%) and for primary prevention in 94 patients (90.4%). After a follow-up of 9.3 ± 5.1 years, 21 patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2 per 100 person-years). The rate of appropriate shocks was higher in secondary prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%) experienced appropriate ICD therapy, all with a spontaneous type 1 electrocardiogram and inducible ventricular arrhythmias. In the multivariable analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95% confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were significant predictors of appropriate therapy. Nine patients (8.7%) experienced 37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100 person-years). Three patients (2.9%) died (1 electrical storm and 2 noncardiovascular deaths).
ICD therapy is an effective therapy in high-risk patients with BrS. However, it is also associated with a significant risk of device-related complications. Special care during ICD implantation, adequate device programming, and regular follow-up may allow reducing the number of adverse events.
A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population.
This study sought to investigate the Brugada probands ...diagnosed from 1986 through the next 28 years.
We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group).
There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients.
Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed.
Abstract
Background and Aims
Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study ...was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes.
Methods
A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years.
Results
During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients 18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs). In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms hazard ratio (HR) 2.5, P = .001 and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs.
Conclusions
ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.
Structured Graphical Abstract
Structured Graphical Abstract
In our large cohort of 370 Brugada syndrome (BrS) patients from 18 international centers monitored continuously with an implantable loop recorder (ILR) for 3 years, 25.4% of the patients experienced an arrhythmic event (per-patient analysis). Specifically, 16% experienced an atrial arrhythmia, 5% a ventricular arrhythmia (VA), and 8% a bradyarrhythmia (per-event analysis). The occurrence of arrhythmic syncope in the whole cohort was 8.6% (32/370). The induction of ventricular fibrillation (VF) during an electrophysiological (EP) study emerged as the only predictor of VAs in this cohort. The clinical implications are detailed in the lower right part of the figure (SCD, sudden cardiac death; PM, pacemaker; ICD, implantable cardioverter-defibrillator; Drugs include anti-arrhythmic drugs and anticoagulants; CA, catheter ablation for atrial arrhythmias or VAs).
Background Chronic diseases have a negative impact on quality of life (QOL) and psychological health. There are limited related data regarding this topic in Brugada syndrome (BrS). We evaluated the ...effects of the diagnosis of BrS on health-related QOL and psychological status among patients and their relatives. Methods Patients with BrS and their relatives underwent psychological evaluation at diagnosis (T0), 1 and 2 years after diagnosis (T1 and T2) using questionnaires on mental QOL, anxiety, depression, stress, post-traumatic stress, and resilience resources. Results Sixty-one patients and 39 relatives were enrolled. Compared with controls, patients showed increased physical QOL (54.1 ± 6.5 vs. 50.1 ± 8.0, p = 0.014), reduced mental QOL (43.2 ± 11.8 vs. 49.6 ± 9.1, p = 0.018) and increased anxiety (9.9 ± 6.6 vs. 6.9 ± 7.7, p = 0.024) at T0; reduced resilience scores (3.69 ± 0.40 vs. 3.96 ± 0.55, p = 0.008) at T1; and reduced resilience (3.69 ± 0.35 vs. 3.96 ± 0.55, p = 0.019) and increased anxiety scores (16.4 ± 12.8 vs. 6.9 ± 7.7, p = 0.006) at T2. Relatives presented higher stress (17.63 ± 3.77 vs. 12.90 ± 6.0, p = 0.02) at T0 and higher anxiety scores at T0 (13.5 ± 7.6 vs. 6.9 ± 7.7, p < 0.001), T1 (12.0 ± 8.7 vs. 6.9 ± 7.7, p = 0.005), and T2 (16.4 ± 12.8 vs. 6.9 ± 7.7, p = 0.006) than controls. Female sex was significantly independently associated with worse mental QOL scores in patients at T0 (odds ratio = 0.10; 95% confidence interval = 0.05–0.94; p = 0.04). Conclusions The diagnosis of BrS impairs the QOL and psychological status of patients and their relatives. Female sex is independently associated with worse mental QOL in patients at diagnosis.
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