Lamin A/C Missense Mutation R216C Pinpoints Overlapping Features Between Brugada Syndrome and Laminopathies

A 31-year-old man experienced at-rest cardiac arrest. After successful resuscitation, the baseline ECG demonstrated sinus rhythm with concave ST segment elevation in right precordial leads (V1–V3) followed by a negative and symmetrical T-wave. Neither coronary artery disease nor electrolytes’ imbalances were detected. In the following days, ECG showed a spontaneous type 1 Brugada ECG pattern (Figure [A1]), more evident with right precordial leads in II and III intercostal spaces. Transthoracic echocardiography (Figure [A2]) failed to show any cardiomyopathy. Cardiac MRI showed normal chambers dimension, wall thickness, volume, and function (left ventricular end diastolic volume, 67.7 mL/m2; IVS, 1 cm; left ventricular end fraction, 59.7%). Late gadolinium enhancement sequences were negative; adipose and fibrous tissue infiltration were excluded. The patient was implanted with a transvenous single chamber cardioverter defibrillator (Medtronic). Several appropriate ICD interventions on VT and ventricular fibrillation were recorded in the following years. Family history (Figure [B]) was positive for sudden cardiac death: the maternal grandfather died at age 45 years, aII degree maternal cousin died during sleep at age 40 years. The proband’s mother showed a first degree atrioventricular block (PR interval=280 ms) and right bundle branch block (Figure [A3]). A neurological examination in the index case and his mother was negative and creatine phosphokinase levels were normal in both. Informed written consent was obtained from all family members. Study was approved by the Local Ethics Committee (152/2013/O/Oss, June 1, 2013). Molecular genetic analysis was performed by next generation sequencing using PED MASTR Plus assay comprising 52 cardiac electrical disorders related genes, SCN5A included (www.agilent.com)

Attualità e nuove prospettive in tema di cardiogenetica

In recent years, cardiogenetics is emerging as a major discipline for the study of many pathologies, with immediate clinical effects for patients who were previously managed by the cardiologist alone. Recent acquisitions have allowed significant improvements in terms of diagnostic characterization, prognostic stratification and guidance for treatment for both patients with genetic disease and their family members. At present, cardiogenetics has an important role for the clinical management of patients with cardiomyopathies and channelopathies. We present an updated review of the literature and a proposal of organizational model

Heart Rate Variability Relates with Competition Performance in Professional Soccer Players

Background: Heart rate variability (HRV) is widely used in professional soccer players as a tool to assess individual response to training load. Different devices and methods are available for HRV assessment. The relationship between HRV and competitive soccer matches performance is not documented. Methods: We monitored HRV in professional soccer players throughout a game season. Measurements were performed with a portable lightweight device in weekly 5 min sessions from which we obtained the value of the square root of the mean squared differences of successive beat-to-beat intervals (rMSSD). Game parameters of run and velocity were collected. Results: Twenty-seven players were monitored with a total of 121 observations. The rMSSD significantly related with the total distance covered (p = 0.036) and with the distance covered running at >15 km/h (p = 0.039) during soccer games. Conclusions: HRV was associated with competition performance in professional soccer players

Standard ECG in Brugada Syndrome as a Marker of Prognosis: From Risk Stratification to Pathophysiological Insights

Background The 12‐lead ECG plays a key role in the diagnosis of Brugada syndrome (BrS). Since the spontaneous type 1 ECG pattern was first described, several other ECG signs have been linked to arrhythmic risk, but results are conflicting. Methods and Results We performed a systematic review to clarify the associations of these specific ECG signs with the risk of syncope, sudden death, or equivalents in patients with BrS. The literature search identified 29 eligible articles comprising overall 5731 patients. The ECG findings associated with an incremental risk of syncope, sudden death, or equivalents (hazard ratio ranging from 1.1–39) were the following: localization of type 1 Brugada pattern (in V2 and peripheral leads), first‐degree atrioventricular block, atrial fibrillation, fragmented QRS, QRS duration >120 ms, R wave in lead aVR, S wave in L1 (≥40 ms, amplitude ≥0.1 mV, area ≥1 mm2), early repolarization pattern in inferolateral leads, ST‐segment depression, T‐wave alternans, dispersion of repolarization, and Tzou criteria. Conclusions At least 12 features of standard ECG are associated with a higher risk of sudden death in BrS. A multiparametric risk assessment approach based on ECG parameters associated with clinical and genetic findings could help improve current risk stratification scores of patients with BrS and warrants further investigation. Registration URL: https://www.crd.york.ac.uk/prospero/. Unique identifier: CRD42019123794

Antibiotic prophylaxis based on individual infective risk stratification in cardiac implantable electronic device: the PRACTICE study

none12Aims: In patients undergoing cardiac implantable electronic device (CIED) intervention, routine pre-procedure antibiotic prophylaxis is recommended. A more powerful antibiotic protocol has been suggested in patients at high risk of infection. Stratification of individual infective risk could guide the prophylaxis before CIED procedure. Methods and results: Patients undergoing CIED surgery were stratified according to the Shariff score in low and high infective risk. Patients in the 'low-risk' group were treated with only two antibiotic administrations while patients in the 'high-risk' group were treated with a prolonged 9-day protocol, according to renal function and allergies. We followed-up patients for 250 days with clinical outpatient visit and electronic control of the CIED. As primary endpoint, we evaluated CIED-related infections. A total of 937 consecutive patients were enrolled, of whom 735 were stratified in the 'low-risk' group and 202 in the 'high-risk' group. Despite different risk profiles, CIED-related infection rate at 250 days was similar in the two groups (8/735 in 'low risk' vs. 4/202 in 'high risk', P = 0.32). At multivariate analysis, active neoplasia, haematoma, and reintervention were independently associated with CIED-related infection (HR 5.54, 10.77, and 12.15, respectively). Conclusion: In a large cohort of patients undergoing CIED procedure, an antibiotic prophylaxis based on individual stratification of infective risk resulted in similar rate of infection between groups at high and low risk of CIED-related infection.noneMalagù, Michele; Vitali, Francesco; Brieda, Alessandro; Cimaglia, Paolo; De Raffele, Martina; Tazzari, Enea; Musolino, Cristina; Balla, Cristina; Serenelli, Matteo; Cultrera, Rosario; Rapezzi, Claudio; Bertini, MatteoMalagù, Michele; Vitali, Francesco; Brieda, Alessandro; Cimaglia, Paolo; De Raffele, Martina; Tazzari, Enea; Musolino, Cristina; Balla, Cristina; Serenelli, Matteo; Cultrera, Rosario; Rapezzi, Claudio; Bertini, Matte

Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention

Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients with ST-Segment-Elevation Myocardial Infarction and Multivessel Disease

Background - The nonculprit lesion (NCL) management in ST-segment-elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario. Methods and Results - The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n=31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n=45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3-4 days later) procedures (r=0.98; 95% confidence interval, 0.96-0.99; mean difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was κ=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99). Finally, in cohort C, we identified 110 ST-segment-elevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value ≤0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2-4.5; P=0.01). Conclusions - In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment-elevation myocardial infarction patients