The Spatial Ventricular Gradient is Associated with Inducibility of Ventricular Arrhythmias During Electrophysiology Study.

BACKGROUND: Myocardial electrical heterogeneity is critical for normal cardiac electromechanical function, but abnormal/excessive electrical heterogeneity is proarrhythmic. The spatial ventricular gradient (SVG), a vectorcardiographic measure of electrical heterogeneity, has been associated with arrhythmic events over long-term follow-up, but its relationship with short-term inducibility of ventricular arrhythmias (VAs) is unclear. OBJECTIVE: Determine associations between SVG and inducible VAs during electrophysiology study (EPS). METHODS: Retrospective study of adults without prior sustained VA, cardiac arrest, or implantable cardioverter-defibrillator (ICD), who underwent ventricular stimulation for evaluation of syncope, non-sustained VT, and/or risk-stratification prior to primary prevention ICD implantation. 12-lead ECGs were converted into vectorcardiograms and SVG magnitude (SVGmag) and direction (azimuth and elevation) were calculated. Odds of inducible VA were regressed using logistic models. RESULTS: Among 143 patients (median age 66, 80% male, median LVEF 47%, 52% myocardial infarction), 34 (23.8%) had inducible VAs. Inducible patients had lower median LVEF (38 vs 50%, p<0.0001), smaller SVGmag (29.5 vs 39.4mV*ms, p=0.0099), and smaller cosine SVG azimuth (cosSVGaz) (0.64 vs 0.89, p=0.0007). When LVEF, SVGmag, and cosSVGaz were dichotomized at their medians, there was a 39-fold increase in adjusted odds (p=0.002) between patients with all low LVEF, SVGmag, and cosSVGaz (65% inducible), compared to 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. CONCLUSION: Assessment of electrical heterogeneity via SVG, which reflects abnormal electrophysiological substrate, adds to LVEF and identifies patients at high and low risk of inducible VA at EPS.

P-wave alternans rebound following pulmonary vein isolation predicts atrial arrhythmia recurrence.

INTRODUCTION: Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. OBJECTIVE: We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. METHODS: This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. RESULTS: PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). CONCLUSION: A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.

Blind Spots in Development of Nanomedicines.

The field of nanomedicine demonstrates immense advantages and noteworthy expansion compared to conventional drug delivery systems like tablet, capsules, etc. Despite the innumerable advantages, it holds certain shortcomings in the form of blind spots that need to be assessed before the successful clinical translation. This perspective highlights the foremost blind spots in nanomedicine and emphasizes the challenges faced before the entry into the market, including the need for provision of safety and efficacy data by the regulatory agencies like FDA. The significant revolution of nanomedicine in the human life, particularly in patient well-being, necessitates to identify the blind spots and overcome them for effective management and treatment of ailments.

The Use of Local Activation Timing Histogram in Ablation of Focal and Re-Entrant Atrial Tachycardias.

BACKGROUND: Activation mapping is often used to differentiate focal from re-entrant arrhythmias. This can be challenging but is critical to ablation success. The local activation time (LAT) histogram, which depicts point distribution over isochronal segments, may help characterize arrhythmia mechanisms and identify an optimal ablation strategy. OBJECTIVES: This study aimed to investigate features of the LAT histogram associated with the focal vs re-entrant mechanism of atrial tachycardias (ATs) and the use of the LAT histogram in the identification of target ablation sites. METHODS: We retrospectively evaluated cases of focal and re-entrant ATs performed at a single academic tertiary care center for which activation mapping was performed using CARTO 3 version 7 software (Biosense Webster). Baseline patient, arrhythmia, and procedural characteristics as well as LAT histogram features were evaluated for each case. LAT histogram-guided ablation targets were also compared against actual ablation sites. RESULTS: Among 52 ATs assessed, 17 were focal, and 35 were re-entrant. Tachycardia cycle length was significantly shorter in re-entrant than in focal ATs (288.2 milliseconds [Q1-Q3: 250-306.5 milliseconds] vs 370 milliseconds [Q1-Q3: 285-400 milliseconds], respectively; P = 0.006). LAT histograms contained more "valleys" in re-entrant than in focal ATs (3 [Q1-Q3: 2-4] vs 1 [Q1-Q3: 1-1]; P < 0.001). No focal ATs contained >2 and no re-entrant ATs contained <1 LAT valley(s). All successful ablation sites correlated with LAT histogram-suggested sites. CONCLUSIONS: LAT histograms can help distinguish focal from re-entrant Ats and identify effective ablation sites.

Speech-induced atrial tachycardia: A narrative review of putative mechanisms implicating the autonomic nervous system.

Despite being uncommon, speech-induced atrial tachycardias carry significant morbidity and affect predominantly healthy individuals. Little is known about their mechanism, treatment, and prognosis. In this review, we seek to identify the underlying connections and pathophysiology between speech and arrhythmias while providing an informed approach to evaluation and management.

Procedural Adaptations to Avoid Haemodynamic Instability During Catheter Ablation of Scar-related Ventricular Tachycardia.

Classically, catheter ablation for scar-related ventricular tachycardia (VT) relied upon activation and entrainment mapping of induced VT. Advances in post-MI therapies have led to VTs that are faster and haemodynamically less stable, because of more heterogeneous myocardial fibrosis patterns. The PAINESD score is one means of identifying patients at highest risk for haemodynamic decompensation during attempted VT induction, who may, therefore, benefit from alternative ablation strategies. One strategy is to use temporary mechanical circulatory support, although this warrants formal assessment of cost-effectiveness. A second strategy is to minimise or avoid VT induction altogether by employing a family of 'substrate'-based approaches aimed at identifying VT isthmuses during sinus or paced rhythm. Substrate mapping techniques are diverse, and focus on the timing, morphology and amplitude of local ventricular electrograms - sometimes aided by advanced non-invasive cardiac imaging modalities. In this review, the evolution of VT ablation over time is discussed, with an emphasis on procedural adaptations to the challenge of haemodynamic instability.

Correlation Between Functional Substrate Mapping and Cardiac Computed Tomography-Derived Wall Thinning for Ventricular Tachycardia Ablation.

BACKGROUND: Functional substrate mapping during baseline rhythm can identify arrhythmogenic tissue during ventricular tachycardia (VT) ablation. Wall thinning and wall thickness channels (WTCs) derived from computed tomography angiography have been shown to correlate with low voltage and VT isthmuses. The correlation between functional substrate mapping, wall thinning, and WTCs in patients with infarct- or non-infarct-related cardiomyopathies (ICM and NICM, respectively) has not been previously described. OBJECTIVES: The purpose of this study was to correlate cardiac CTA-derived myocardial wall thinning with functional VT substrate mapping using isochronal late activation mapping. METHODS: In 34 patients with ICM or NICM undergoing VT ablation who had a preprocedure computed tomography angiography, myocardial wall thinning was segmented in layers of 1 to 5 mm. Areas of wall thinning and WTCs were then spatially correlated with deceleration zones (DZs) from registered left ventricular endocardial isochronal late activation maps. RESULTS: In 21 ICM patients and 13 NICM patients, ICM patients had greater surfaces areas of wall thinning (P < 0.001). In ICM patients, 94.1% of primary DZs were located on areas of wall thinning, compared to 20% of DZs in NICM patients overall but 50% if there was any wall thinning present. Fifty-nine percent of DZs in ICM patients and 56% of DZs in NICM patients were located near WTCs. The positive predictive value for WTC in localizing DZs was 22.5% and 37.8% in ICM and NICM patients, respectively. CONCLUSIONS: Wall thinning is highly sensitive for functional substrate in ICM patients. WTCs had modest sensitivity for functional substrate but low positive predictive value for identifying DZs in ICM and NICM patients. These findings suggest that wall thinning may facilitate more efficient mapping in ICM patients, but WTCs are insufficient to localize wavefront discontinuities.

Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation.

OBJECTIVE: Identification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone. The potential for increased risk for AF in patients with epilepsy is not well appreciated, despite recent evidence from a national survey of 1.4 million hospitalizations indicating that AF is the most common arrhythmia in people with epilepsy. METHODS: We analyzed inter-lead heterogeneity of P-wave morphology, a marker reflecting arrhythmogenic nonuniformities of activation/conduction in atrial tissue. The study groups consisted of 96 patients with epilepsy and 44 consecutive patients with AF in sinus rhythm before clinically indicated ablation. Individuals without cardiovascular or neurological conditions (n = 77) were also assessed. We calculated P-wave heterogeneity (PWH) by second central moment analysis of simultaneous beats from leads II, III, and aVR ("atrial dedicated leads") from standard 12-lead electrocardiography (ECG) recordings from admission day to the epilepsy monitoring unit (EMU). RESULTS: Female patients composed 62.5%, 59.6%, and 57.1% of the epilepsy, AF, and control subjects, respectively. The AF cohort was older (66 ± 1.1 years) than the epilepsy group (44 ± 1.8 years, p < .001). The level of PWH was greater in the epilepsy group than in the control group (67 ± 2.6 vs. 57 ± 2.5 µV, p = .046) and reached levels observed in AF patients (67 ± 2.6 vs. 68 ± 4.9 µV, p = .99). In multiple linear regression analysis, PWH levels in individuals with epilepsy were mainly correlated with the PR interval and could be related to sympathetic tone. Epilepsy remained associated with PWH after adjustments for cardiac risk factors, age, and sex. SIGNIFICANCE: Patients with chronic epilepsy have increased PWH comparable to levels observed in patients with AF, while being ~20 years younger, suggesting an acceleration in structural change and/or cardiac electrical instability. These observations are consistent with emerging evidence of an "epileptic heart" condition.

Reduction in atrial and ventricular electrical heterogeneity following pulmonary vein isolation in patients with atrial fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) modulates the intrinsic cardiac autonomic nervous system and reduces atrial fibrillation (AF) recurrence. METHODS: In this retrospective analysis, we investigated the impact of PVI on ECG interlead P-wave, R-wave, and T-wave heterogeneity (PWH, RWH, TWH) in 45 patients in sinus rhythm undergoing clinically indicated PVI for AF. We measured PWH as a marker of atrial electrical dispersion and AF susceptibility and RWH and TWH as markers of ventricular arrhythmia risk along with standard ECG measures. RESULTS: PVI acutely (16 ± 8.9 h) reduced PWH by 20.7% (from 31 ± 1.9 to 25 ± 1.6 µV, p < 0.001) and TWH by 27% (from 111 ± 7.8 to 81 ± 6.5 µV, p < 0.001). RWH was unchanged after PVI (p = 0.068). In a subgroup of 20 patients with longer follow-up (mean = 47 ± 3.7 days after PVI), PWH remained low (25 ± 1.7 µV, p = 0.01), but TWH partially returned to the pre-ablation level (to 93 ± 10.2, p = 0.16). In three individuals with early recurrence of atrial arrhythmia in the first 3 months after ablation, PWH increased acutely by 8.5%, while in patients without early recurrence, PWH decreased acutely by 22.3% (p = 0.048). PWH was superior to other contemporary P-wave metrics including P-wave axis, dispersion, and duration in predicting early AF recurrence. CONCLUSION: The rapid time course of decreased PWH and TWH after PVI suggests a beneficial influence likely mediated via ablation of the intrinsic cardiac nervous system. Acute responses of PWH and TWH to PVI suggest a favorable dual effect on atrial and ventricular electrical stability and could be used to track individual patients' electrical heterogeneity profile.

Anterior vs. posterior position of dispersive patch during radiofrequency catheter ablation: insights from in silico modelling.

AIMS: To test the hypothesis that the dispersive patch (DP) location does not significantly affect the current distribution around the catheter tip during radiofrequency catheter ablation (RFCA) but may affect lesions size through differences in impedance due to factors far from the catheter tip. METHODS: An in silico model of RFCA in the posterior left atrium and anterior right ventricle was created using anatomic measurements from patient thoracic computed tomography scans and tested the effect of anterior vs. posterior DP locations on baseline impedance, myocardial power delivery, radiofrequency current path, and predicted lesion size. RESULTS: For posterior left atrium ablation, the baseline impedance, total current delivered, current distribution, and proportion of power delivered to the myocardium were all similar with both anterior and posterior DP locations, resulting in similar RFCA lesion sizes (< 0.2 mm difference). For anterior right ventricular (RV) ablation, an anterior DP location resulted in slightly higher proportion of power delivered to the myocardium and lower baseline impedance leading to slightly larger RFCA lesions (0.6 mm deeper and 0.8 mm wider). CONCLUSIONS: An anterior vs. posterior DP location will not meaningfully affect RFCA for posterior left atrial ablation, and the slightly larger lesions predicted with anterior DP location for anterior RV ablation are of unclear clinical significance.

Patient Selection, Techniques, and Complication Mitigation for Epicardial Ventricular Tachycardia Ablation.

Percutaneous epicardial ventricular tachycardia ablation can decrease implanted cardioverter defibrillator shocks and hospitalizations; proper patient selection and procedural technique are imperative to maximize the benefit-risk ratio. The best candidates for epicardial ventricular tachycardia will depend on history of prior ablation, type of cardiomyopathy, and specific electrocardiogram and cardiac imaging findings. Complications include hemopericardium, hemoperitoneum, coronary vessel injury, and phrenic nerve injury. Modern epicardial mapping techniques provide new understandings of the 3-dimensional nature of reentrant ventricular tachycardia circuits across cardiomyopathy etiologies. Where epicardial access is not feasible, alternative techniques to reach epicardial ventricular tachycardia sources may be necessary.

Esophageal Perforation Following Radiofrequency Catheter Ablation for Atrial Fibrillation: A Conservative Approach.

Esophageal perforation following radiofrequency catheter ablation of atrial fibrillation (AF) is a rare and potentially deadly complication. Here, we report a case with successful conservative management of esophageal perforation following AF ablation demonstrating how surgery is not always required in properly selected patients.

Limitations of Baseline Impedance, Impedance Drop and Current for Radiofrequency Catheter Ablation Monitoring: Insights from In silico Modeling.

Background: Baseline impedance, radiofrequency current, and impedance drop during radiofrequency catheter ablation are thought to predict effective lesion formation. However, quantifying the contributions of local versus remote impedances provides insights into the limitations of indices using those parameters. Methods: An in silico model of left atrial radiofrequency catheter ablation was used based on human thoracic measurements and solved for (1) initial impedance (Z), (2) percentage of radiofrequency power delivered to the myocardium and blood (3) total radiofrequency current, (4) impedance drop during heating, and (5) lesion size after a 25 W−30 s ablation. Remote impedance was modeled by varying the mixing ratio between skeletal muscle and fat. Local impedance was modeled by varying insertion depth of the electrode (ID). Results: Increasing the remote impedance led to increased baseline impedance, lower system current delivery, and reduced lesion size. For ID = 0.5 mm, Z ranged from 115 to 132 Ω when fat percentage varied from 20 to 80%, resulting in a decrease in the RF current from 472 to 347 mA and a slight decrease in lesion size from 5.6 to 5.1 mm in depth, and from 9.2 to 8.0 mm in maximum width. In contrast, increasing the local impedance led to lower system current but larger lesions. For a 50% fat−muscle mixture, Z ranged from 118 to 138 Ω when ID varied from 0.3 to 1.9 mm, resulting in a decrease in the RF current from 463 to 443 mA and an increase in lesion size, from 5.2 up to 7.5 mm in depth, and from 8.4 up to 11.6 mm in maximum width. In cases of nearly identical Z but different contributions of local and remote impedance, markedly different lesions sizes were observed despite only small differences in RF current. Impedance drop better predicted lesion size (R2 > 0.93) than RF current (R2 < 0.1). Conclusions: Identical baseline impedances and observed RF currents can lead to markedly different lesion sizes with different relative contributions of local and remote impedances to the electrical circuit. These results provide mechanistic insights into the advantage of measuring local impedance and identifies potential limitations of indices incorporating baseline impedance or current to predict lesion quality.

Influence of the early-life gut microbiota on the immune responses to an inhaled allergen.

Antibiotics, among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity. We hypothesized that early-life microbiome alterations would lead to increased susceptibility to allergy and asthma. To test this, mouse pups between postnatal days 5-9 were orally exposed to water (control) or to therapeutic doses of azithromycin or amoxicillin. Later in life, these mice were sensitized and challenged with a model allergen, house dust mite (HDM), or saline. Mice with early-life azithromycin exposure that were challenged with HDM had increased IgE and IL-13 production by CD4+ T cells compared to unexposed mice; early-life amoxicillin exposure led to fewer abnormalities. To test that the microbiota contained the immunological cues to alter IgE and cytokine production after HDM challenge, germ-free mice were gavaged with fecal samples of the antibiotic-perturbed microbiota. Gavage of adult germ-free mice did not result in altered HDM responses, however, their offspring, which acquired the antibiotic-perturbed microbiota at birth showed elevated IgE levels and CD4+ cytokines in response to HDM, and altered airway reactivity. These studies indicate that early-life microbiota composition can heighten allergen-driven Th2/Th17 immune pathways and airway responses in an age-dependent manner.

Wide Complex Tachycardia and Cardiac Arrest During Endoscopy.

A 59-year-old man presented for implantable cardioverter-defibrillator placement after a wide QRS complex tachycardia cardiac arrest at an outside hospital. In this case report, we discuss the differential diagnosis of this patient's tachyarrhythmia and the electrophysiological studies that established the diagnosis and guided management. (Level of Difficulty: Intermediate.).