Inducible Ventricular Arrhythmias Research Articles

Novel real-time automation of combined frequency and low voltage substrate mapping to guide ablation for Brugada syndrome: a case report

Abstract Background Brugada syndrome (BrS) is an inherited cardiac condition that increases the risk of sudden cardiac death (SCD) due to ventricular arrhythmias. Catheter ablation has been shown to effectively reduce recurrent ventricular fibrillation (VF) episodes through targeting of abnormal electrograms predominantly located within the anterior surface of the right ventricular outflow tract. Signal frequency mapping is an emerging concept that provides further definition of pathological ventricular substrate. Case summary A 66-year-old male with BrS was admitted to our institution with ICD shocks for VF. Electro-anatomical mapping (EAM) and ablation was performed utilising a novel automated frequency-based strategy. Combined automated frequency and low voltage maps were generated to define high frequency, low voltage (HF-LVo) depolarisation abnormalities within the QRS complex. Low frequency, low voltage (LF-LVo) regions from the QRS terminal notch to the T-wave offset were also identified. The combined HF-LVo and LF-LVo map areas totalled 12.4cm2, compared to the conventional low voltage and late potential map areas, which were 44cm2 and 27.8cm2 respectively. The ablation strategy targeted HF-LVo and LF-LVo regions only. Following ablation, re-mapping demonstrated near complete abolition of HF-LVo and LF-LVo regions, with no inducible ventricular arrhythmias during extra-stimulation testing. During follow-up, ECG normalisation was observed, with no further ventricular arrhythmias and a negative ajmaline challenge at 6 months. Discussion Catheter ablation for BrS utilising a novel automated combined frequency and low voltage EAM approach can objectively identify relevant substrate. The results demonstrate adequate substrate modification with comparable ablation target areas to previous studies and encouraging clinical outcomes.

Incidence and characteristics of premature ventricular beats in competitive athletes at preparticipation exercise testing

Abstract Introduction The European Society of Cardiology preparticipation screening (PPS) protocol for athletes includes history, physical examination and resting ECG only. However, adding exercise testing (ET) aimed at evaluating ventricular arrhythmias (VAs) inducibility may increase the chances to identify cardiac diseases at-risk of sudden death that would otherwise be missed. Recent studies showed that the risk that premature ventricular beats (PVBs) at ET are associated to an underlying disease depends not just on their number but on characteristics such as morphology and complexity. However, there are no data on the incidence of at-risk PVBs at ET, thus requiring further tests to rule-out a cardiac disease, in apparently healthy athletes. Aim To assess the incidence and characteristics of VAs in a cohort of apparently healthy athletes undergoing annual PPS including ET. Methods We included a consecutive series of 1431 (24±13 year-old, 75% males) competitive athletes who underwent PPS in 2023. According to the Italian law and national guidelines, PPS must include ET with a different protocol according to age: in athletes younger than 35 years (81% of the study group) a rapid constant-load ET target at evaluating VAs inducibility was performed while in athletes older than 35 years a standard incremental ET was carried out. PVBs recorded during ET were assessed in terms of morphology, complexity and response to exercise. Results the incidence of at least 1 PVB was 14.5%, with a statistically significant increase according to age (p<0.001, Figure). If only athletes with frequent (at least 5 isolated PVBs) or complex (at least 1 couplet/triplet/NSVT) VAs are considered, the incidence was 4.3%, still with a significant increase according to age. In particular, among athletes older than 35 years, the incidence of PVBs was 34.1% and of frequent/complex PVBs was 15.2%. As shown in the table and figure, more than half of athletes with PVBs showed at-risk features such as persistence/increase (rather than suppression) of VAs during exercise and an "uncommon" morphology (i.e. different than infundibular or fascicular). Conclusions PVBs during ET for preparticipation screening occurred in a sizeable proportion of athletes, particularly in those older than 35 years, and many showed at-risk features such as complexity, uncommon morphologies or exercise-inducibility. Despite VAs at ET may be the only sign of a disease at risk of sudden death, their high incidence may substantially impact on the need for further investigations after PPS. Hence, more efforts should be put to identify which PVBs characteristics are predictive for an underlying cardiac disease, particularly in master athletes.

Complement factor D deficiency ameliorates adverse cardiac remodelling by inhibiting C5a-C5aR mediated ISGs+ neutrophil activation post myocardial infarction

Abstract Background Exaggerated inflammatory response after myocardial infarction (MI) exacerbates myocardial injury and adverse cardiac remodeling, leading to heart failure. Current management of MI involves myocardial protection and antifibrotic therapy but do not target the inflammatory response per se. Complement factor D (CFD) is an upstream rate-limiting enzyme of complement system activation, which is the early event of inflammatory response post MI. We hypothesize that CFD can be an important modulator of the inflammation-remodeling cascade post MI, but the specific mechanism remains elusive. Purpose To investigate the role and mechanism of CFD in regulating inflammatory expansion and adverse remodeling post MI. Methods We generated Cfd-AKO (Cfdfl/fl Adipoq-cre) mice using the Cre-LoxP recombination system, as CFD is mainly secreted by adipocytes. Immune status and cardiac remodeling progress were assessed by cardiovascular magnetic resonance (CMR), histology, flow cytometry, immunofluorescence, and ELISA. Single cell RNA sequencing (scRNA-seq) analyzed non­cardiomyocytes isolated from Cfd-AKO and WT mice post MI or sham operation. Genetic ablation and co-culture experiments dissected the functional molecular properties and intercellular communication. An CFD inhibitor ACH-4471 was used to explore the role of CFD in ischemia-reperfusion (IR) injury. Results The survival of Cfd-AKO mice was strongly improved, while ventricular arrhythmia induction rates and number of episodes were significantly reduced compared with those of WT mice. CMR imaging showed that Cfd-AKO mice had higher ejection fraction and reduced left ventricular dilation than WTs. Masson trichrome and picrosirius red staining revealed that besides smaller infarct size, the extent of fibrosis in the border and distal remote area decreased in Cfd-AKO mice. Cfd loss reduced myocardial injury, inhibited the release of inflammatory factors, and limits the amplification of complement components C3a and C5a post MI. ScRNA-seq revealed that CFD modulated neutrophil chemotactic ability and pro-inflammatory function by inducing interferon-stimulated genes expressing (ISG+) neutrophil CXCL10 expression. Mechanistically, CFD activates the ISG transcriptional profile via the C5a/C5aR dependent STAT1/2-IRF9 pathway. Activated neutrophils promote myofibroblast transformation through IL1β/IL1R dependent intercellular communication, thus facilitating pathological fibrosis. Early pharmacological blocking of CFD in mice IR injury models inhibited inflammation, reduced infarct size and ameliorated cardiac dysfunction. Conclusions We demonstrate the crucial role of CFD in cardiac remodeling post MI. This process is critically regulated by C5a-C5aR, an important component of complement-inflammation cascade. This CFD-C5a mediated neutrophil pro-inflammatory and pro-fibrotic dual activity represents a novel pathway and an attractive therapeutic window for heart failure post MI.CFD in cardiac remodelling post MI

Long-term transcranial ultrasound stimulation regulates neuroinflammation to ameliorate post–myocardial infarction cardiac arrhythmia and remodeling

BackgroundSympathetic overactivation and neuroinflammation in the paraventricular nucleus (PVN) are crucial factors in post–myocardial infarction (MI) cardiac remodeling and ventricular arrhythmias (VAs). Prior study has indicated that low-intensity focused ultrasound stimulation could attenuate sympathetic neuroinflammation within the PVN to prevent the occurrence of VAs in an acute MI model. Meanwhile, the cGAS-STING pathway has shown potential to ameliorate the neuroinflammatory response. However, the effect and mechanisms of long-term transcranial ultrasound stimulation (LTUS) for modulating neuroinflammation in the chronic stage of MI remain unclear. ObjectiveThis study aimed to ascertain whether LTUS could mitigate post-MI neuroinflammation and improve cardiac arrhythmia and remodeling through the cGAS-STING pathway. MethodsThirty-six SD rats were equally randomized to the sham group (pseudo-MI modeling), chronic MI group (MI modeling), and LTUS group (MI modeling and long-term ultrasound stimulation). Transcranial ultrasound stimulation (15 min/d) was conducted on the PVN for 4 consecutive weeks. After 4-week intervention, echocardiography, electrophysiologic experiments, and histopathologic staining were performed to assess the role of LTUS on post-MI neuroinflammation and cardiac remodeling. ResultsThe results indicated that LTUS significantly facilitated microglial M1 to M2 polarization through the cGAS-STING signaling pathway within the PVN. Furthermore, LTUS inhibited MI-induced sympathetic neuroinflammation, thereby improving cardiac dysfunction, ameliorating cardiac remodeling, and reducing VA inducibility. ConclusionLong-term ultrasound stimulation of the PVN was found to alleviate post-MI neuroinflammation and to improve cardiac remodeling, which might inspire novel insights and clinical strategies for noninvasive neuromodulation and the treatment of post-MI VAs.

Enhancing risk assessment in Chagas cardiomyopathy: Electrophysiology study stratified by Rassi score

BackgroundChagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. ObjectiveTo analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. MethodsThis prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. ResultsOf 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ± 4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15–3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21–4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). ConclusionEPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

Impaired Cardiac AMPK (5'-Adenosine Monophosphate-Activated Protein Kinase) and Ca2+-Handling, and Action Potential Duration Heterogeneity in Ibrutinib-Induced Ventricular Arrhythmia Vulnerability.

We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib-induced vulnerability to VA that can be modulated for cardioprotection remains unclear. The effects of ibrutinib on cardiac electrical activity and Ca2+ dynamics were investigated in Langendorff-perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca2+-handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls, P<0.002) and shorter action potential durations during pacing at various frequencies (P<0.05). Ibrutinib also decreased heart rate thresholds for beat-to-beat duration alternans of the cardiac action potential (P<0.05). Significant changes in myocardial Ca2+ transients included lower amplitude alternans ratios (P<0.05), longer times-to-peak (P<0.05), and greater spontaneous intracellular Ca2+ elevations (P<0.01). We also found lower abundance and phosphorylation of myocardial AMPK (5'-adenosine monophosphate-activated protein kinase), indicating reduced AMPK activity in hearts after ibrutinib treatment. An acute treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside ameliorated abnormalities in action potential and Ca2+ dynamics, and significantly reduced VA inducibility (37.1%±13.4% versus 72.2%±6.3% in the absence of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, P<0.05) in hearts from ibrutinib-treated rats. VA vulnerability inflicted by ibrutinib may be mediated in part by an impairment of myocardial AMPK activity. Pharmacological activation of AMPK may be a protective strategy against ibrutinib-induced cardiotoxicity.

Cryoablation of ventricular tachycardia using ultra-low temperature technology: acute success and insights from the post-interventional CMR

Abstract Background Radiofrequency catheter ablation (RFCA) has good acute and long-term success rates in idiopathic and ischemic ventricular arrhythmia (VA). Drawbacks of the RFCA are reversibility of the edema and limited penetration of the RF energy into the tissue which explain a worse effectiveness in midmyocardial substrates. In comparison to RFCA, the lesions produced by ultra-low temperature cryoablation (ULTC) which uses near-critical nitrogen cryogen at -1960C can be both deeper and irreversible, depending on the duration of the freeze. Purpose We aimed to evaluate the acute effectiveness of a new ULTC technology for VA by examining post-interventional cardiac magnetic resonance images (CMR) with late gadolinium enhancement (LGE), as a part of multi-center Cryocure-VT study. Methods Between December 2022 and May 2023, we ablated 6 patients (age 63±16%; 5 male) with sustained VA and structural heart disease. Three patients had previous myocardial infarction; 1 cardiac sarcoidosis, 1 LMNA/C dilated cardiomyopathy and 1 post-myocarditis VA. LGE-CMR was available in all patients before the ULTC. At first, electro-anatomical mapping and VA induction were performed followed by ULTC using transseptal access. Each application consisted of freeze-thaw-freeze cycle with freeze duration at operator’s discretion based on manufacturer-recommended duration-depth curve. At the end, induction protocol was repeated to assess the acute success. Additionally, LGE-CMR was performed after ablation as an attempt to visualize the cryo-lesions. Results Median of 6 applications (IQR 4.75-7.5) of cryo-energy were applied per patient. Median procedure time was 180 min (IQR 97-180), and median fluoroscopy time of 20 min (IQR 15-26). Septal VA exits were detected in 3/6 patients; in 1 the exit was at aorto-mitral continuity; in 2 – basal inferior. After ablation, no VAs were inducible in 5/6 (83%) patients. The only patient with failure to ablate all VAs had fewer applications (n=4) and shorter freeze duration of 30 sec., as compared to the rest. Post-procedural CMR revealed new LGE with up to 75% transmurality in 5/6 patients; microvascular obstruction in 4/6 patients. Only LV edema, but no LGE was observed in the patient with shortest freeze time, who also had intra-hospital recurrence. No complications occurred. Conclusions Cryoablation of VA using a new ultra-low temperature technology is effective and safe to ablate VT even in patients with mid-septal substrates. New LGE in result of ULTCA can be observed in CMR and the lesions depth depends on the duration of application.

Improving functional substrate delineation for ablation of ventricular tachycardia using high-density electroanatomic mapping and double ventricular extra stimuli protocol

Abstract Background A partial delineation of targets for ventricular tachycardia (VT) ablation may contribute to a suboptimal success rate. Abnormal electrograms (EGMs) with low-voltage near-field components might be concealed within high-amplitude far-field signals. Our hypothesis posited that acquiring functional mapping after double ventricular extrastimuli (S3 protocol) could reveal relevant areas of functional substrate overlooked during sinus or S1 mapping. Purpose To assess the benefit and feasibility of functional substrate mapping using a full ventricle S3 protocol and to evaluate its colocalization with conducting channels (CCs) identified in late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Methods (Figure 1) - An S3 mapping protocol with a drive train of S1 followed by S2 (effective refractory period (ERP) +30ms) and S3 (ERP+50ms) from the RV apex was conducted in 40 consecutive patients undergoing scar-related VT ablation. Deceleration zones (DZs) and areas of late potentials (LPs) were identified for all maps (S1, S2, and S3). Pre-procedural non-invasive substrate assessment was performed with LGE-CMR and post-processing using a commercially available system with automated CC identification. Results The S3 protocol was completed in 34 of the 40 procedures (85.0%). Repeated induction of ventricular arrhythmias prevented the full S3 protocol in 5 patients (15.0%). Functional substrate identified during S3 activation mapping was significantly more extensive than that identified using S2 and S1, including a higher number of DZs (2.94, 2.47, and 1.82, respectively; p&amp;lt;0.01) and a wider area of LPs (44.1cm2, 38.2cm2, and 29.4cm2, respectively; p&amp;lt;0.001). The percentage of CCs unmasked by DZs and LPs using S3 maps was significantly higher than the ones using S2 and S1 maps(78%, 65%, and 48%; p&amp;lt;0.001, and 88%, 81%, and 68%; p&amp;lt;0.01, repectively). After VT ablation based on an S3 protocol, 77.9% of patients have been VT free during a median follow-up of 13.6 months. Conclusions (Graphical abstract -Figure 2) - This novel substrate-based protocol for assessing functional substrate is feasible in most patients, enables better identification of ablation targets, and has the potential to improve patient prognosis post-ablation.Methods - The S3 protocolConclusion - Graphical abstract

The spatial ventricular gradient is associated with inducibility of ventricular arrhythmias during electrophysiology study

BackgroundMyocardial electrical heterogeneity is critical for normal cardiac electromechanical function, but abnormal or excessive electrical heterogeneity is proarrhythmic. The spatial ventricular gradient (SVG), a vectorcardiographic measure of electrical heterogeneity, has been associated with arrhythmic events during long-term follow-up, but its relationship with short-term inducibility of ventricular arrhythmias (VAs) is unclear. ObjectiveThis study was designed to determine associations between SVG and inducible VAs during electrophysiology study. MethodsA retrospective study was conducted of adults without prior sustained VA, cardiac arrest, or implantable cardioverter-defibrillator who underwent ventricular stimulation for evaluation of syncope and nonsustained ventricular tachycardia or for risk stratification before primary prevention implantable cardioverter-defibrillator implantation. The 12-lead electrocardiograms were converted into vectorcardiograms, and SVG magnitude (SVGmag) and direction (azimuth and elevation) were calculated. Odds of inducible VA were regressed by logistic models. ResultsOf 143 patients (median age, 69 years; 80% male; median left ventricular ejection fraction [LVEF], 47%; 52% myocardial infarction), 34 (23.8%) had inducible VAs. Inducible patients had lower median LVEF (38% vs 50%; P < .0001), smaller SVGmag (29.5 vs 39.4 mV·ms; P = .0099), and smaller cosine SVG azimuth (cosSVGaz; 0.64 vs 0.89; P = .0007). When LVEF, SVGmag, and cosSVGaz were dichotomized at their medians, there was a 39-fold increase in adjusted odds (P = .002) between patients with all low LVEF, SVGmag, and cosSVGaz (65% inducible) compared with patients with all high LVEF, SVGmag, and cosSVGaz (4% [n = 1] inducible). After multivariable adjustment, SVGmag, cosSVGaz, and sex but not LVEF or other characteristics remained associated with inducible VAs. ConclusionAssessment of electrical heterogeneity by SVG, which reflects abnormal electrophysiologic substrate, adds to LVEF and identifies patients at high and low risk of inducible VA at electrophysiology study.

Distinct Electrogram Features and Ventricular Arrhythmia Induction Modes Between Repolarization and Conduction Heterogeneities

BackgroundRecent clinical studies have indicated the presence of localized electrical abnormalities in idiopathic ventricular fibrillation and J-wave syndrome patients. ObjectivesThis study aims to characterize the specific electrical signatures of localized repolarization and conduction heterogeneities and their respective role in vulnerability to arrhythmias. MethodsOptical mapping was performed in porcine right ventricles with local: 1) repolarization shortening; 2) conduction slowing; or 3) structural heterogeneity induced by locally perfusing: 1) pinacidil (20 μmol/L, n = 13); or 2) flecainide (2 μmol/L, n = 13) via an epicardial catheter; or 3) by local epicardial tissue destruction (9 radiofrequency lesions n = 12). Electrograms were recorded (n = 5 in each group) and spontaneous and induced arrhythmias were quantified and optically mapped. ResultsElectrograms were normal in (1) but showed local fragmentation in 40% of preparations in (2) with greater effects observed at high pacing frequencies dependent on the wavefront direction. In (3), the structural substrate alone increased the width and number of peaks in the electrograms, and addition of flecainide induced pronounced fragmentation (≥3 peaks and ≥70 ms) in all cases. Occurrence of spontaneous arrhythmias was significantly increased in (1) and (2) (P < 0.0001 and 0.05, respectively, vs baseline) and were triggered by ectopies. Vulnerability to arrhythmias at high pacing frequencies (≥2 Hz) was the lowest in (1) and greatest in (2). ConclusionsMicrostructural substrates have the most pronounced impact on electrograms, especially when combined with sodium channel blockers, whereas local action potential duration shortening does not lead to electrogram fragmentation even though it is associated with the highest prevalence of spontaneous arrhythmias.

Brugada syndrome: identification of subjects at risk and therapy.

Brugada syndrome mainly affects young subjects with structurally normal heart and can cause x syncope or sudden death due to ventricular arrhythmias, even as the first manifestation, in approximately 5-10% of cases. To date, two questions remain open: how to recognize subjects who will experience arrhythmic events and how to treat them. The guidelines suggest treating subjects with a previous history of cardiac arrest or arrhythmogenic syncope, while they are unconclusive about the management of asymptomatic patients, who represent ∼90% of Brugada patients. We recently demonstrated that in asymptomatic patients, the presence of spontaneous Brugada type 1 electrocardiogram (ECG) pattern and inducibility of ventricular arrhythmias at electrophysiological study allows us to identify a group of patients at greater risk who deserve treatment. Regarding treatment, there are three options: implantable cardioverter defibrillator, drugs, and epicardial transcatheter ablation. Recent studies have shown that the latter is effective and free from serious side effects, thus opening a new scenario in the treatment of Brugada patients at risk. Subjects who present drug-induced-only type 1 Brugada ECG pattern, in whom a spontaneous type 1 pattern has been ruled out with repeated ECGs and 12-lead 24-h Holter monitoring, represent a very low-risk group, provided they adhere to behavioural recommendations and undergo regular follow-up.

Ventricular arrhythmia inducibility in porcine infarct model after stereotactic body radiation therapy

BackgroundVentricular arrhythmia (VA) is the primary mechanism of sudden death in patients with structural heart disease. Cardiac stereotactic body radiation therapy (SBRT) delivered to the scar in the left ventricle significantly reduces the burden of VA. ObjectiveThe goal of this study was to investigate the impact of SBRT on scar morphology and VA inducibility in a porcine infarct model. MethodsMyocardial infarction (MI) was created in 10 Yorkshire pigs involving the left anterior descending artery territory. Cardiac positron emission tomography and computed tomography were performed for targeted SBRT. Alternative pigs received SBRT at 25 Gy in a single fraction. The terminal experiment included endocardial mapping, programmed ventricular stimulation, and tissue harvesting. ResultsOf the 10 pigs infarcted, 2 died prematurely after MI and 8 (4 MI and 4 MI+SBRT) survived. Mean time from MI to SBRT was 48 ± 12 days, and mean time from SBRT to harvest was 32 ± 12 days. Scar was localized on intracardiac mapping in all pigs, and the scar was denser in the MI+SBRT compared with the MI-only group (33% ± 20% vs 14% ± 11%; P = .07). All 4 MI pigs had inducible VA during programmed stimulation, whereas only 1 of 4 pigs had inducible VA in the MI+SBRT arm (100% vs 25%; P = .07). No myocardial fibrosis was seen in the remote areas in either group. ConclusionSBRT reduced VA inducibility in pigs with scarring after MI. Endocardial mapping revealed denser scar in pigs receiving SBRT compared with those that did not, suggesting that SBRT suppresses VA inducibility through better scar homogenization.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

The effects of daily dose of intense exercise on cardiac responses and atrial fibrillation.

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia that is strongly associated with cardiovascular (CV) disease and sedentary lifestyles. Despite the benefits of exercise on overall health, AF incidence in high-level endurance athletes rivals that of CV disease patients, suggesting a J-shaped relationship with AF. To investigate the dependence of AF vulnerability on exercise, we varied daily swim durations (120, 180 or 240minday-1 ) in 7-week-old male CD1mice. We assessed mice after performing equivalent amounts of cumulative work during swimming (i.e. ∼700L O2 kg-1 ), as determined from O2 consumption rates ( ). The mean during exercise increased progressively throughout the training period and was indistinguishable between the swim groups. Consistent with similar improvements in aerobic conditioning induced by swimming, skeletal muscle mitochondria content increased (P=0.027) indistinguishably between exercise groups. Physiological ventricular remodelling, characterized by mild hypertrophy and left ventricular dilatation, was also similar between exercised mice without evidence of ventricular arrhythmia inducibility. By contrast, prolongation of daily swim durations caused progressive and vagal-dependent heart rate reductions (P=0.008), as well as increased (P=0.005) AF vulnerability. As expected, vagal inhibition prolonged (P=0.013) atrial refractoriness, leading to reduced AF vulnerability, although still inducible in the 180 and 240min swim groups. Accordingly, daily swim dose progressively increased atrial hypertrophy (P=0.003), fibrosis (P<0.001) and macrophage accumulation (P=0.006) without differentially affecting the ventricular tissue properties. Thus, increasing daily exercise duration drives progressively adverse atrial-specific remodelling and vagal-dependent AF vulnerability despite robust and beneficial aerobic conditioning and physiological remodelling of ventricles and skeletal muscle. KEY POINTS: Previous studies have suggested that a J-shaped dose-response relationship exists between physical activity and cardiovascular health outcomes, with moderate exercise providing protection against many cardiovascular disease conditions, whereas chronic endurance exercise can promote atrial fibrillation (AF). We found that AF vulnerability increased alongside elevated atrial hypertrophy, fibrosis and inflammation as daily swim exercise durations in mice were prolonged (i.e. ≥180minday-1 for 6weeks). The MET-hweek-1 (based on O2 measurements during swimming) needed to induce increased AF vulnerability mirrored the levels linked to AF in athletes. These adverse atria effects associated with excessive daily exercise occurred despite improved aerobic conditioning, skeletal muscle adaptation and physiological ventricular remodelling. We suggest that atrial-specific changes observed with exercise arise from excessive elevations in venous filling pressures during prolonged exercise bouts, which we argue has implications for all AF patients because elevated atrial pressures occur in most cardiovascular disease conditions as well as ageing which are linked to AF.

Non-invasive cardiac activation mapping and identification of severity of epicardial substrate in Brugada Syndrome: a case report

IntroductionIt has recently been shown that electrocardiographic imaging (ECGi) can be employed in individuals undergoing an ajmaline test who have Brugada Syndrome (BrS), to evaluate the extent of substrate-involved arrhythmia in the right ventricular overflow tract (RVOT). For the first time, we stratify the risk of sudden cardiac death (SCD) in BrS during ajmaline testing using the dST-Tiso interval (a robust predictor of the inducibility of ventricular arrhythmias (VAs) in the presence of drug-induced BrS type-1 pattern) in combination with ECGi technology.Case presentationWe studied a 48-year-old man with BrS ECG type-2 pattern and presence of J-wave without a family history of SCD but with a previous syncope. Transthoracic echocardiography and cardiac magnetic resonance imaging were performed, showing normal results. The ECG was performed to assess the novel ECG marker “dST-Tiso interval.” The 3D epicardial mapping of the RVOT surface was performed with the support of a non-contact cardiac mapping system in sinus rhythm during ajmaline infusion. The examination of the propagation map unveiled the presence of multiple conduction blocks in this pathologic epicardial region, and the conduction blocks were identified within the central part and/or near the boundary separating the normal and slow conduction areas.ConclusionThe dST-Tiso interval, which lies between the onset and termination of the coved ST-segment elevation and serves as a robust predictor of VA inducibility in cases of drug-induced BrS type-1 pattern, was utilized in conjunction with ECGi technology (employed for the non-invasive confirmation and identification of the pathological substrate area). This combined approach was applied to stratify the risk of SCD in BrS during ajmaline testing, alongside clinical scores.

INDUCTION OF CARDIAC ARRHYTHMIAS DURING BICYCLE ERGOMETRY IN THE DIAGNOSIS OF CORONARY HEART DISEASE

HighlightsThe frequency of arrhythmias during bicycle ergometry was compared in patients with and without coronary heart disease. Their diagnostic significance in diagnosing this disease was analyzed separately for men and women. AbstractAim. To determine the diagnostic significance of exercise-induced cardiac arrhythmias (CAs) during bicycle ergometry (BEM) in patients with suspected coronary heart disease (CHD).Methods. For the retrospective study, 384 case histories of patients discharged from the cardiology department between 2011 and 2020 were selected according to the inclusion and exclusion criteria. The data of BEM and coronary angiography were studied. The correlation between the occurrence of induction of different types of CAs during BEM and the presence of coronary artery blood flow abnormalities was investigated. Indicators of the diagnostic significance of CAs in the diagnosis of coronary artery disease, such as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) results, were determined separately for men and women. The statistical significance of the results was assessed.Results. Statistically significant specificity and PPV for the induction of ventricular arrhythmias (VAs) without taking into account rare single monomorphic ventricular extrasystoles (VEs) in the diagnosis of CHD in men were 83.5% and 73.1%, respectively. The same indicators for VAs, excluding all single VEs, were 95.3% and 82.6% in men.Conclusion. The induction of VAs in men on BEM, with the exception of rare single monomorphic VEs, is diagnostically significant in the detection of CHD and allows us to qualify the result of BEM as “positive”. The induction of other CAs on BEM has not shown diagnostic significance in the detection of CHD.

Cardiac magnetic resonance predictors of ventricular arrhythmias inducibility before pulmonary valve replacement in patients with Tetralogy of Fallot

Cardiac magnetic resonance predictors of ventricular arrhythmias inducibility before pulmonary valve replacement in patients with Tetralogy of Fallot

Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction–induced ventricular arrhythmia

BackgroundOur previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. ObjectiveThis study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. MethodsFifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. ResultsCompared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain. ConclusionLIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

Prognosis of programmed ventricular stimulation in adult patients with syncope of unexplained origin: A historical cohort.

Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO). This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008-2021. In this interval, 575 patients underwent the procedure. Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow-up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all-cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter-defibrillator (ICD) implantation. At study follow-up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012). In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.