Partners in Crime in the Setting of Recurring Cardiac Arrest

No previous reports are available about the potential dramatic effects resulting from the combination of acquired long QT interval not associated to bradycardia and myocardial ischemia. We report the case of a man that during acute necrotic pancreatitis presented QT interval prolongation without bradycardia, TdP, and two episodes of cardiac arrest. A coronary angiogram revealed a subocclusive stenosis of left anterior descending coronary artery, treated with a percutaneous coronary intervention. After myocardial revascularization, even in presence of long QT interval, no arrhythmic events occurred suggesting the key role of myocardial ischemia in triggering TdP in acquired long QT even without bradycardia. ECG performed six months later, after complete recovery from pancreatitis, showed a normal QT interval

VINYL: Variant prIoritizatioN bY survivaL analysis

Motivation: Clinical applications of genome re\uadsequencing technologies typically generate large amounts of data that need to be carefully annotated and interpreted to identify genetic variants associated with pathological conditions. In this context, accurate and reproducible methods for the functional annotation and prioritization of genetic variants are of fundamental importance, especially when large volumes of data \uad like those produced by modern sequencing technologies \uad are involved. Results: In this paper, we present VINYL, a highly accurate and fully automated system for the functional annotation and prioritization of genetic variants in large scale clinical studies. Extensive analyses of both real and simulated datasets suggest that VINYL show higher accuracy and sensitivity when compared to equivalent state of the art methods, allowing the rapid and systematic identification of potentially pathogenic variants in different experimental settings

Altered two-dimensional strain measures of the right ventricle in patients with Brugada syndrome and arrhythmogenic right ventricular dysplasia/cardiomyopathy

Aims: Brugada syndrome (BrS) is an inherited channelopathy that can be characterized by mild right ventricular (RV) abnormalities that are not detectable with conventional echocardiography. The aim of this study was to evaluate the presence of RV abnormalities in BrS patients when compared with controls and a group of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using two-dimensional (2D) strain analysis. Methods and results: We enrolled 25 BrS, 15 ARVD/C patients, and 25 controls. Right and left ventricular dimension and systo-diastolic function were evaluated by conventional echocardiography. Longitudinal systolic strain (sS) peak, systolic and early diastolic strain rate of lateral RV segments were evaluated by 2D speckle tracking analysis. Left ventricle global and segmental strain measures were also evaluated. A reduced basal or mid-RV lateral sS were the parameters mostly associated with both BrS and ARVD/C. In BrS patients the minimum sS observed in these segments was significantly lower than that of controls (-28.9±3.2% vs. -32.3±3.2%, P: 0.002) but significantly greater than that evaluated in ARVD/C patients (-24.6 ±6.7%, P < 0.001 both vs. BrS and controls). No differences were found between the BrS and the control group when left ventricular strain measures were analysed. Conclusion: By 2D strain technique it is possible to observe mild abnormalities in RV systolic and diastolic function of BrS patients that are less pronounced than those observed in ARVD/C patients. These results help to better define the phenotypic characteristics of BrS patients and represent the basis for future studies aimed at testing their clinical usefulness in BrS patients

Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies

Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30&nbsp;serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients’ sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1β IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70&nbsp;kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies

The practice of deep sedation in electrophysiology and cardiac pacing laboratories: Results of an italian survey promoted by the aiac (italian association of arrhythmology and cardiac pacing)

The aim of this survey, which was open to all Italian cardiologists involved in arrhythmia, was to assess common practice regarding sedation and analgesia in interventional electrophysiology procedures in Italy. The survey consisted of 28 questions regarding the approach to sedation used for elective direct-current cardioversion (DCC), subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, atrial fibrillation (AF) ablation, ventricular tachycardia (VT) ablation, and transvenous lead extraction procedures. A total of 105 cardiologists from 92 Italian centres took part in the survey. The rate of centres where DCC, S-ICD implantation, AF ablation, VT ablation and lead extraction procedures were performed without anaesthesiologic assistance was 60.9%, 23.6%, 51.2%, 37.3%, and 66.7%, respectively. When these procedures were performed without anaesthesiologic assistance, the drugs (in addition to local anaesthetics) commonly administered were benzodiazepines (from 64.3% to 79.6%), opioids (from 74.4% to 88.1%), and general anaesthetics (from 7.1% to 30.4%). Twenty-three (21.9%) of the 105 cardiologists declared that they routinely administered propofol, without the supervision of an anaesthesiologist, in at least one of the above-mentioned procedures. In current Italian clinical practice, there is a lack of uniformity in the sedation/analgesia approach used in interventional electrophysiology procedures

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

Background: Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective: We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods: An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results: The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions: In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results

Does catheter ablation cure atrial fibrillation? Single-procedure outcome of drug-refractory atrial fibrillation ablation: A 6-year multicentre experience

Aims In the last decade, several approaches to ablating triggers and substrates of atrial fibrillation (AF) have been developed. However, most studies have reported data only on short- or medium-term follow-up. The aim of this study was to investigate whether the 1-year efficacy of catheter ablation for AF is predictive of long-term clinical success. Methods and results Between February 2001 and October 2003, 229 consecutive patients affected by drug-refractory paroxysmal or persistent AF underwent a single radiofrequency catheter ablation procedure (anatomical approach in 146 patients and electrophysiologically guided approach in 83 patients). Of these patients, 177 (mean age 59.1 \uc2\ub1 10.5 years, 57.6% with paroxysmal AF) were free from any atrial arrhythmia recurrence after 12 months. These 177 patients were subsequently followed up for at least another 24 months, by means of electrocardiogram and 24 h Holter monitoring. After a mean follow-up of 49.7 \uc2\ub1 13.3 months (range 36-83 months), 58.2% of the patients were free from any atrial arrhythmia recurrence (39.5% without antiarrhythmic drugs). The actuarial atrial arrhythmia recurrence rate was 13.0% at 2 years, 21.8% at 3 years, 35.0% at 4 years, 46.8% at 5 years, and 54.6% at 6 years. Atrial arrhythmia-free survival was similar in patients with paroxysmal or persistent AF, with and without antiarrhythmic drugs during the follow-up, who underwent electrophysiologically guided pulmonary vein (PV) isolation or anatomical PV ablation. Conclusion Even patients in whom catheter ablation prevents AF recurrence for 1 year should not be considered 'cured', since >40 of them will suffer AF recurrence over a long-term clinical follow-up

A Prospective Study of Key Correlates for Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2

Background: Randomized controlled trials evaluated monoclonal antibodies for the treatment (Study 2067) and prevention (Study 2069) of coronavirus disease 2019 (COVID-19). Household contacts of the infected index case in Study 2067 were enrolled in Study 2069 and prospectively followed; these cohorts provided a unique opportunity to evaluate correlates of transmission, specifically viral load. Methods: This post hoc analysis was designed to identify and evaluate correlates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, adjusting for potential confounding factors related to source SARS-CoV-2 viral load and risk of SARS-CoV-2 acquisition in this population. Correlates of transmission were evaluated in potential transmission pairs (any infected household member plus susceptible household contact). Results: In total, 943 participants were included. In multivariable regression, 2 potential correlates were determined to have a statistically significant (P <. 05) association with transmission risk. A 10-fold increase in viral load was associated with a 40% increase in odds of transmission; sharing a bedroom with the index participant was associated with a 199% increase in odds of transmission. Conclusions: In this prospective, post hoc analysis that controlled for confounders, the 2 key correlates for transmission of SARS-CoV-2 within a household are sharing a bedroom and increased viral load, consistent with increased exposure to the infected individual

Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection

Hepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

<p>Abstract</p> <p>Background -</p> <p>Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.</p> <p>Methods -</p> <p>We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.</p> <p>Results -</p> <p>During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ²= 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.</p> <p>Conclusion -</p> <p>In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.</p