Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

BACKGROUND: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients. AIM OF THE STUDY: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients. METHODS: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory. RESULTS: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever. CONCLUSION: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.

Increased prevalence of early repolarization in electrocardiograms of psoriatic patients.

Psoriasis (Ps) is a chronic-relapsing, inflammatory, and proliferative condition of the skin: prior studies hypothesized a link between Ps and anomalies in ß-adrenergic tone. We therefore aimed to ascertain the prevalence of early repolarization pattern (ERP) in resting electrocardiograms (ECGs) of psoriatic patients compared with an appropriate control group. We performed a retrospective study of resting ECGs of 100 consecutive psoriatic patients and 100 healthy controls. The presence of ERP in at least two contiguous leads at rest ECG was recorded, and findings were also categorized according to the lead group where ERP was detected (anterior, lateral, inferior). An ERP in ≥ 2 contiguous leads occurred in 40 % of psoriatic patients, compared with 14 % of control subjects (p < 0.001). (36 vs 10 % in anterior leads, p < 0.001; 6 vs 3 % in inferior leads, p n.s.; 10 vs 2 % in lateral leads). After adjustment for sex, age, heart rate, and level of physical activity, the odds ratios for the presence of ERP were 8.6 (95 % CI, 2.1-35.2, p < 0.01), and 7.1 (95 % CI, 1.6-31.8, p < 0.05) in anterior leads. In a small case/control study, increased rates of ECGs showing ERP have been observed among psoriatic patients. Clinical significance of such finding needs to be assessed in further observational studies.

Catecholaminergic polymorphic ventricular tachycardia associated with sinus node dysfunction and junctional rhythm: Case report and literature review.

We report the case of a 38-year-old woman with history of syncope and polymorphic ventricular tachycardia; tachycardia was inducible at exercise stress test, not at electrophysiologic study. Phases of QT prolongation were found at ambulatory electrocardiogram monitoring. The woman came to our attention for periodic control of implantable loop recorder. Rest electrocardiogram at admission unexpectedly showed sinus bradycardia, junctional rhythm, and ventricular premature beats. Furthermore, loop recorder control revealed a short run of bidirectional tachycardia, not associated with syncope. Final diagnosis was catecholaminergic polymorphic ventricular tachycardia, and the patient was implanted with an ICD. We therefore report an unusual case of bidirectional ventricular tachycardia associated with sinus node dysfunction and junctional escape rhythm. We hypothesize that a diffuse dysfunction of cardiac conduction system, presumably based on diffuse disorder of calcium handling, may be responsible for both sinus node failure and ventricular tachycardia.

Investigation of a Large Kindred Reveals Cardiac Calsequestrin (CASQ2) as a Cause of Brugada Syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated with the risk of ventricular fibrillation (VF) and sudden cardiac death in a structurally normal heart. AIM OF THE STUDY: The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant Brugada syndrome. METHODS: Clinical and genetic studies were performed. Genetic analysis was conducted with NGS technologies (WES) using the Illumina instrument. According to the standard procedure, variants found by WES were confirmed in all available families by Sanger sequencing. The effect of the variants was studied by using in silico prediction of pathogenicity. RESULTS: The proband was a 52-year-old man who was admitted to the emergency department for syncope at rest. WES of the index case identified a heterozygous VUS CASQ2, c.532T>C, p.(Tyr178His). We studied the segregation of the variation in all pedigree members. All the patients were heterozygous for the variation CASQ2 p.(Tyr178His), whereas the remaining healthy individuals in the family were homozygous for the normal allele. Structural analysis of CASQ2 p.(Tyr178His) was performed and revealed an important effect of the missense variation on monomer stability. The CASQ2 Tyr180 residue is located inside the sarcoplasmic reticulum (SR) junctional face membrane interaction domain and is predicted to disrupt filamentation. CONCLUSIONS: Our data suggest that the p.Tyr178His substitution is associated with BrS in the family investigated, affecting the stability of the protein, disrupting filamentation at the interdimer interface, and affecting the subsequent formation of tetramers and polymers that contain calcium-binding sites.

A Novel DLG1 Variant in a Family with Brugada Syndrome: Clinical Characteristics and In Silico Analysis.

BACKGROUND: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated to sudden cardiac death. Overall, variants have been identified in eighteen genes encoding for ion channel subunits and seven genes for regulatory proteins. Recently, a missense variant in DLG1 has been found within a BrS phenotype-positive patient. DLG1 encodes for synapse associated protein 97 (SAP97), a protein characterized by the presence of multiple domains for protein-protein interactions including PDZ domains. In cardiomyocytes, SAP97 interacts with Nav1.5, a PDZ binding motif of SCN5A and others potassium channel subunits. AIM OF THE STUDY: To characterize the phenotype of an Italian family with BrS syndrome carrying a DLG1 variant. METHODS: Clinical and genetic investigations were performed. Genetic testing was performed with whole-exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using in silico prediction of pathogenicity. RESULTS: The index case was a 74-year-old man with spontaneous type 1 BrS ECG pattern that experienced syncope and underwent ICD implantation. WES of the index case, performed assuming a dominant mode of inheritance, identified a heterozygous variant, c.1556G>A (p.R519H), in the exon 15 of the DLG1 gene. In the pedigree investigation, 6 out of 12 family members had the variant. Carriers of the gene variant all had BrS ECG type 1 drug induced and showed heterogeneous cardiac phenotypes with two patients experiencing syncope during exercise and fever, respectively. The amino acid residue #519 lies near a PDZ domain and in silico analysis suggested a causal role for the variant. Modelling of the resulting protein structure predicted that the variant disrupts an H-bond and a likelihood of being pathogenic. As a consequence, it is likely that a conformational change affects protein functionality and the modulating role on ion channels. CONCLUSIONS: A DLG1 gene variant identified was associated with BrS. The variant could modify the formation of multichannel protein complexes, affecting ion channels to specific compartments in cardiomyocytes.

Lymphocyte subset characterization in patients with early clinical presentation of coronary heart disease.

This study aimed to investigate lymphocyte populations in non-diabetic patients with early clinical presentation of coronary heart disease (CHD). Twenty-five consecutive middle-aged (<55 years) out-patients with CHD (acute myocardial infarction in the previous 3 months) and stable clinical conditions (>1 month) underwent venous blood sampling in order to determinate CD3+ (T-lymphocytes), CD19+ (B-lymphocytes), CD4+ (helper/inducer lymphocytes) and CD8+ (suppressor/cytotoxic lymphocytes) populations. Patients with diabetes, heart failure symptoms, recent revascularization (<30 days) were excluded. Twenty-five patients matched for age, gender and risk factors were enrolled as controls. All patients with CHD previously underwent coronary angiography. CHD patients showed lower CD3+ levels (70.96 ± 4.72 vs. 74.12 ± 4.93 %, p < 0.05) and CD8+ (37.80 ± 7.15 vs. 46.36 ± 5.22 %, p < 0.001) but higher CD4+ (37.32 ± 7.99 vs. 31.64 ± 4.72 %, p < 0.01) and CD4+/CD8+ ratio (1.06 ± 0.43 vs. 0.69 ± 0.13, p < 0.001). Difference in CD19+ levels was not statistically significant. Subjects with an impaired (≤55 %) left ventricular ejection fraction were characterized by lower levels of CD8+ (33.23 ± 7.04 vs. 43.76 ± 7.40 %, p < 0.05) and higher levels of CD4+ (38.31 ± 8.23 vs. 32.73 ± 6.08 %, p < 0.05) and CD4+/CD8+ ratio (1.06 ± 0.38 vs. 0.79 ± 0.34, p < 0.05). CD8+ levels inversely related to severity of coronary atherosclerosis (r = -0.37, p < 0.01). In conclusion, subjects with early clinical presentation of CHD are characterized by an altered CD4+/CD8+ ratio and lower CD3+ levels.

Near zero vascular complications using echo-guided puncture during catheter ablation of arrhythmias: A retrospective study and literature review.

Background: Catheter ablation (CA) is routinely used for the treatment of arrhythmias. Vascular complications are the most common complications during these procedures. Previous data reported that ultrasound (US)-guided puncture is a useful method to avoid vascular complications. We reported our experience using US-guided puncture in patients undergoing CA for arrhythmias. Methods: A total of 273 patients (mean age 57 ± 17 years; 58% male) were referred to our center for CA of arrhythmias from January 2016 to December 2019. All procedures were performed by expert operators, and US-guided vascular access was performed on all patients. Doppler sonography was performed the day after the procedure on all patients. Results: Eighty-four patients (31%) underwent atrioventricular nodal reentrant tachycardia ablation, 49 patients (18%) atrioventricular reentrant tachycardia ablation, 14 patients (5%) atrial tachycardia ablation, 25 patients (9%) atrial flutter ablation, 63 patients (23%) atrial fibrillation ablation, and 38 patients (14%) ventricular tachycardia ablation. Vascular pseudo-aneurysms and arteriovenous fistula were defined as major complications; furthermore, venous thrombosis and inguinal hematomas were as defined minor complications. The percentage of major vascular complications was 0.3% (1 arteriovenous fistula) and the percentage of minor vascular complications was 0.3% (1 venous thrombosis). Discussion: Ultrasound-guided vascular puncture in patients undergoing CA is useful to improve procedural success and reduce complications.

Single- and multi-site pacing strategies for optimal cardiac resynchronization therapy: impact on device longevity and therapy cost.

BACKGROUND: Multiple left ventricular pacing strategies have been suggested for improving response to cardiac resynchronization therapy (CRT). However, these programming strategies may sometimes entail accepting configurations with high pacing threshold and accelerated battery drain. We assessed the feasibility of predefined pacing programming protocols, and we evaluated their impact on device longevity and their cost-impact. METHODS: We estimated battery longevity in 167 CRT-D patients based on measured pacing parameters according to multiple alternative programming strategies: single-site pacing associated with lowest threshold, non-apical location, longest interventricular delay, and pacing from two electrodes. To determine the economic impact of each programming strategy, we applied the results of a model-based cost analysis using a 15-year time horizon. RESULTS: Selecting the electrode with the lowest threshold resulted in a median device longevity of 11.5 years. Non-apical pacing and interventricular delay maximization were feasible in most patients and were obtained at the price of a few months of battery life. Device longevity of > 10 years was preserved in 87% of cases of non-apical pacing and in 77% on pacing at the longest interventricular delay. The mean reduction in battery life when the second electrode was activated was 1.5 years. Single-site pacing strategies increased the therapy cost by 4-6%, and multi-site pacing by 12-13%, in comparison with the lowest-cost scenario. CONCLUSIONS: Modern CRT-D systems ensure effective pacing and allow multiple optimization strategies for maximizing service life or for enhancing effectiveness. Single- or multi-site pacing strategies can be implemented without compromising device service life and at an acceptable increase in therapy cost.

Delayed ventricular pacing failure and correlations between pacing thresholds, left ventricular ejection fraction, and QTc values in a male with Takotsubo cardiomyopathy.

BACKGROUND: Transient pacing failure caused by transient increased pacing threshold has been reported in patients with transient left ventricular apical dysfunction (Takotsubo cardiomyopathy [TC]). Normal pacing thresholds usually recover after normalization of systolic dysfunction. HYPOTHESIS: Pacing failure correlates with clinics of TC. METHODS: We report the case of a 76-year-old man with a dual chamber pacemaker, admitted for acute chest pain and dyspnea and final diagnosis of TC. One month after index admission, the patient came back complaining again of chest pain. Unexpectedly, admission electrocardiogram showed ventricular pacing failure and an increased pacing threshold. In the following weeks, pacing threshold gradually recovered with left ventricular ejection fraction and QTc values. RESULTS: Ventricular pacing threshold correlated directly to QTc values and inversely to left ventricular ejection fraction over time (P < 0.05). CONCLUSIONS: This is one of the first cases of delayed transient ventricular pacing failure in a male patient with transient left ventricular apical ballooning, in the presence of spared right ventricular function. Given the possibility of acute transient anomalies in myocardial impedance and pacing failure even in the subacute phase of TC several weeks after clinical onset of transient systolic dysfunction, pacing threshold should be carefully monitored in subjects with TC, both during the acute phase of the disease and in first months of follow-up after discharge. Ventricular pacing threshold correlated directly to QTc values and inversely to left ventricular ejection fraction over time.

Combined exogenous and endogenous catecholamine release associated with Tako-Tsubo like syndrome in a patient with atrio-ventricular block undergoing pace-maker implantation.

We report the case of a 65-year-old woman with complete atrio-ventricular block who underwent orciprenaline administration and pacemaker implantation. The intervention was complicated by pneumothorax and acute left ventricular systolic dysfunction with typical apical ballooning (Tako-Tsubo like syndrome). The patient was treated with diuretics and calcium-sensitizers and completely recovered. We speculate that both external and internal catecholamine triggered an acute left ventricular impairment with typical Tako-Tsubo features.

24 h and prolonged ambulatory ECG recording in patients with ventricular ectopy: Maybe 24 h are not enough?

AIM: To assess whether 24-h ambulatory ECG (AECG) recording underestimates arrhythmic risk in subjects with both ventricular ectopy and cardiovascular risk factors or history of coronary heart disease (CHD). METHODS: 29 consecutive patients with both ECG evidence of premature ventricular contractions (PVCs) and cardiovascular risk factors (n=14) or history of CHD (n=15) underwent 6 days prolonged AECG with an apposite device. Patients were divided according to number of PVCs, Lown's classification and evidence of non-sustained ventricular tachycardia (NSVT). Day by day data were compared with final findings at 6th day. RESULTS: Significant differences between findings at 24 h and those at 6th day were observed for all considered parameters. Differences became statistically not significant only at 4th day for number of PVCs and Lown's classes, at 5th day for NSVT. Results were significant both among patients with only risk factors and those with history of CHD. Sensitivity for NSVT significantly and progressively increased from 18% at 24 h, up to 82% only at 120 h. CONCLUSIONS: Twenty-four-hour AECG underestimates the risk of ventricular arrhythmias in patients with cardiovascular risk factors or history of CHD. Prolonged AECG might reduce this underestimation, particularly among patients at low risk. A careful cost-benefit assessment needs to be held in order to identify the most convenient AECG duration and subsets of patients most benefiting from prolonged AECG.