The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth ...arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These results are related with the finding that overexpression of Gas1 in Hepa 1-6 cells arrests cell cycle before S phase, with a significant (p < 0.01) and concomitant reduction in the expression of cyclin E2 gene. In addition, a triangular analysis of microarray data shows that Gas1 overexpression restores the transcription levels of 150 genes whose expression was affected in the diethylnitrosamine-induced tumors, thirteen of which are involved in the hedgehog signaling pathway. Since the in vivo Gas1 gene delivery to livers of mice carrying hepatocellular carcinoma reduces the size and proliferating activity of tumors, partially restoring the transcriptional profile of the liver, the present study opens promising insights towards a therapeutic approach for hepatocellular carcinoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Brugada syndrome (BrS) has diagnostic challenges and controversial risk assessment. We aimed to investigate invasive and noninvasive parameters in symptomatic and asymptomatic patients ...from a Brazilian cohort of type‐1 BrS.
Methods
Patients with spontaneous and drug‐induced type‐1 BrS were classified into two groups, asymptomatic (n = 116, 84.1%) and symptomatic (n = 22, 15.9%; 13 with arrhythmogenic syncope, 9 with aborted sudden cardiac death). Genetic testing, EPS parameters, and electrocardiogram (ECG) parameters were analyzed.
Results
A total of 138 consecutive patients were eligible, 101 men (73.2%), mean 41.4 years, mostly probands (79%). Spontaneous pattern, observed in 77.5% of the patients, was associated with symptoms only if expressed in V1 and V2 standard position (not high precordial leads; p = .014). All symptomatic patients were probands. The presence of right ventricular outflow tract conduction delay (RVOTcd) signs, positive EPS, and SCN5A status was similar between symptomatic and asymptomatic subjects. During the mean 75‐month follow‐up, eight patients had appropriate therapies. All had spontaneous type‐1 ECG pattern and 2/8 (25%) were asymptomatic, with positive EPS. The overall LAE incidence of 1.1% per year dropped to 0.27% in asymptomatic patients. RVOTcd occurred more frequently in SCN5A carriers (QRS‐f 33.3% vs. 7.7%; p = .005, AVR sign 58.3% vs. 13.6%; p < .001; deep S in lead I 75% vs. 48.5%, p = .025%), as well as longer HV interval (66 vs. 49 ms; p < .001).
Conclusions
Spontaneous type‐1 Brugada pattern in standard leads and proband status were more frequent in symptomatic subjects. RVOTcd, more common in SCN5A carriers, did not predict symptoms in BrS patients. EPS exhibited limited prognostic value for this low‐risk population.
Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome ...data reported.
This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1.
Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis.
We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio HR: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years py) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00).
Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.
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Poor adherence to warfarin treatment is a contributor to poor quality of treatment, which increases the risk of bleeding and thromboembolic events. This study aims to evaluate the impact of adherence ...to warfarin therapy on anticoagulation quality during 12 weeks of pharmaceutical care and after 1 year of follow-up for patients with atrial fibrillation and with poor TTR. The Arrhythmia Unit of tertiary hospital in Brazil. We included 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR < 50%). Pharmacist-driven therapy management was performed for 12 weeks and patients were also evaluated 1 year after the end of the follow-up with a pharmacist. Adherence was classified into high adherence, medium adherence and low adherence. Impact of adherence to warfarin therapy after pharmaceutical care. Of the 262 patients, 160 were high adherence, 71 were medium adherence and 31 were low adherence. No statistically significant difference is found between adherence groups in demographic and clinical variables. The TTR basal means were not different among adherence groups (p = 0.386). However, the means of TTR 12 weeks and TTR 1 year after the end of protocol were statistically different among adherence groups (p < 0.001 and p = 0.002, respectively). When we compared TTR values at different times within the adherence group, we observed that there is a statistical difference between the three TTR means (basal versus 12 weeks versus 1 year after) within the adherence group (p < 0.001). Patients with poor anticoagulation control, who adhered to the treatment with warfarin during the pharmaceutical care had better anticoagulation quality compared to those who did not adhere to the therapy with warfarin.
Desde dezembro de 2019, observamos o rápido avanço da síndrome respiratória aguda grave causada pelo coronavírus 2019 (SARS-CoV-2). O impacto da evolução clínica de uma infecção respiratória é pouco ...conhecido em pacientes portadores de arritmias hereditárias, devido à baixa prevalência dessas doenças. Os pacientes que apresentam quadros infecciosos podem exacerbar arritmias primárias ocultas ou bem controladas, por diversos fatores, tais como febre, distúrbios eletrolíticos, interações medicamentosas, estresse adrenérgico e, eventualmente, o próprio dano miocárdico do paciente séptico. O objetivo desta revisão é destacar os principais desafios que podemos encontrar durante a pandemia pela Covid 19, especificamente nos pacientes com arritmias hereditárias, com destaque para a síndrome do QT longo congênito (SQTL), a síndrome de Brugada (SBr), a taquicardia ventricular polimórfica catecolaminérgica (TVPC) e a cardiomiopatia arritmogênica do ventrículo direito.
Mutations in the
) gene are commonly associated with cardiac manifestations, such as dilated cardiomyopathy (DCM) and conduction system disease. However, the overall spectrum and penetrance of rare
...variants are unknown. The present study described the presence of
in patients with "lone atrial fibrillation (AF)" as their sole clinical presentation.
One-hundred and one consecutive patients with "lone AF" criteria were initially screened by genetic testing. Genetic variants were classified according to the American College of Genetic and Genomic criteria. All subjects were evaluated through clinical and familial history, ECG, 24-h Holter monitoring, echocardiogram, cardiac magnetic resonance, treatment response, and the present relatives of
carriers. In addition, whole-exome data from 49,960 UK Biobank (UKB) participants were analyzed to describe the overall penetrance of rare
missense and loss of function (LOF) variants.
Three missense variants in
were identified in probands with AF as their first and unique clinical manifestation. Other five first-degree relatives, after the screening, also presented
gene variants. Among 49,960 analyzed UKB participants, 331 carried rare
missense or LOF variant. Participants who carried a rare
variant were significantly associated with higher odds of arrhythmic events and of an abnormal ECG in the per-protocol ECG exam (
= 0.03 and
= 0.05, respectively).
Although a rare occurrence, our findings emphasize the possibility of an initial presentation of apparently "lone AF" in
gene variant carriers.
Abstract
Aims
High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation ...marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG.
Methods and results
74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including ‘quick lay down’). For heart rate recovery (HRR) measurements and comparisons, a Student’s t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone.
Conclusion
Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.
Graphical Abstract
Graphical abstract
Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these ...events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist's warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient's INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2-3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014,
< 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015,
< 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.
The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role ...of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes.
The study included 28 patients from the Heart Institute of São Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR.
In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd (
= 0.018) and RVOT PSAX (
= 0.044), was significantly associated with arrhythmic outcomes. RV free wall longitudinal strain < 14.35% in absolute value was associated with arrhythmic outcomes (
= 0.033).
Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers.
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