Showing papers by "Marmar Vaseghi published in 2022"

Myocardial infarction reduces cardiac nociceptive neurotransmission through the vagal ganglia

Abstract: Myocardial infarction causes pathological changes in the autonomic nervous system, which exacerbate heart failure and predispose to fatal ventricular arrhythmias and sudden death. These changes are characterized by sympathetic activation and parasympathetic dysfunction (reduced vagal tone). Reasons for the central vagal withdrawal and, specifically, whether myocardial infarction causes changes in cardiac vagal afferent neurotransmission that then affect efferent tone, remain unknown. The objective of this study was to evaluate whether myocardial infarction causes changes in vagal neuronal afferent signaling. Using in vivo neural recordings from the inferior vagal (nodose) ganglia and immunohistochemical analyses, structural and functional alterations in vagal sensory neurons were characterized in a chronic porcine infarct model and compared with normal animals. Myocardial infarction caused an increase in the number of nociceptive neurons but a paradoxical decrease in functional nociceptive signaling. No changes in mechanosensitive neurons were observed. Notably, nociceptive neurons demonstrated an increase in GABAergic expression. Given that nociceptive signaling through the vagal ganglia increases efferent vagal tone, the results of this study suggest that a decrease in functional nociception, possibly due to an increase in expression of inhibitory neurotransmitters, may contribute to vagal withdrawal after myocardial infarction.

Arrhythmias and Heart Failure in Pregnancy: A Dialogue on Multidisciplinary Collaboration

Abstract: The prevalence of CVD in pregnant people is estimated to be around 1 to 4%, and it is imperative that clinicians that care for obstetric patients can promptly and accurately diagnose and manage common cardiovascular conditions as well as understand when to promptly refer to a high-risk obstetrics team for a multidisciplinary approach for managing more complex patients. In pregnant patients with CVD, arrhythmias and heart failure (HF) are the most common complications that arise. The difficulty in the management of these patients arises from variable degrees of severity of both arrhythmia and heart failure presentation. For example, arrhythmia-based complications in pregnancy can range from isolated premature ventricular contractions to life-threatening arrhythmias such as sustained ventricular tachycardia. HF also has variable manifestations in pregnant patients ranging from mild left ventricular impairment to patients with advanced heart failure with acute decompensated HF. In high-risk patients, a collaboration between the general obstetrics, maternal-fetal medicine, and cardiovascular teams (which may include cardio-obstetrics, electrophysiology, adult congenital, or advanced HF)—physicians, nurses and allied professionals—can provide the multidisciplinary approach necessary to properly risk-stratify these women and provide appropriate management to improve outcomes.

Convergent cardiorespiratory neurons represent a significant portion of cardiac and respiratory neurons in the vagal ganglia

Abstract: Significant cardiorespiratory coordination is required to maintain physiological function in health and disease. Sensory neuronal “cross-talk” between the heart and the lungs is required for synchronous regulation of normal cardiopulmonary function and is most likely mediated by the convergence of sensory neural pathways present in the autonomic ganglia. Using neurotracer approaches with appropriate negative control experiments in a mouse model, presence of cardiorespiratory neurons in the vagal (nodose) ganglia are demonstrated. Furthermore, we found that convergent neurons represent nearly 50% of all cardiac neurons and approximately 35% of all respiratory neurons. The current findings demonstrate a pre-existing neuronal substrate linking cardiorespiratory neurotransmission in the vagal ganglia, and a potentially important link for cardiopulmonary cross-sensitization, which may play an important role in the observed manifestations of cardiopulmonary diseases.

Ionic remodelling following myocardial infarction explains phenotypic variability in ECG and arrhythmic substrate but not in ejection fraction

Abstract: Aims Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic remodelling, which are reflected as variable phenotypes. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with the post-MI electrophysiological heterogeneities are unknown. We aim to unravel how phenotypic ECG and EF variability in post-MI may be explained by the impact of ionic remodelling on spatio-temporal dispersion of repolarization using human biventricular electromechanical modelling and simulation. Methods and Results Multiple post-MI ECG phenotypes observed clinically were investigated using multi-scale modelling and simulation, calibrated and evaluated using experimental and clinical data. Acute stage T-wave inversion was caused by delayed repolarization in the epicardial border zone (BZ), and Brugada phenocopy was generated by repolarization delay and activation failure in the BZ. Upright tall T-waves in chronic MI represented large repolarisation dispersion between BZ and surrounding tissue, which promoted ectopic propagation at fast pacing. T-wave morphology alternans were present at fast-pacing due to prolonged refractoriness in the mid-myocardium. Post-MI ionic remodelling reduced EF through inhibition of calcium transient amplitude, but the EF at resting heart rate was not sensitive to the extent of repolarisation heterogeneity and the risk of repolarisation abnormalities at fast pacing. Conclusions In acute post-MI, ionic remodelling and its effect on refractoriness and propagation failure in the BZ have a strong impact on phenotypic ECG variability, whereas in chronic post-MI, the repolarisation dispersion across the BZ is crucial. T-wave and QT abnormalities are better indicators of repolarisation heterogeneities than EF in post-MI.

Abstract 9547: Demographic Differences in Patients With Frequent PVCs and Cardiomyopathy in the General Population Receiving Ambulatory Holter Monitoring

Abstract: Introduction: A high burden of premature ventricular contractions (PVCs) has been associated with the development of cardiomyopathy (CM) and heart failure. However, the prevalence of high PVC burden and cardiomyopathy (CM) remain unclear. Hypothesis: The prevalence of high PVC burden (>5%) is underestimated in patients receiving Holter monitors and those with CM (LVEF <50%). Methods: A prospective multicenter clinical study of consecutive patients undergoing ambulatory Holter monitors (24 hours up to 2-weeks), between July 2018 through June 2020 were reviewed. Demographic data, PVC burden and LV function were collected within 6 months of Holter placement. Results: A total of 8 centers across the US provided a total of 6,808 patients with ambulatory Holter monitors. Four and 5% of patients undergoing Holter monitors had a PVC burden of 6-10% and >10%, respectively. A total of 3,938 patients had assessment of LVEF within 6 months of Holter, of which 634 (16%) had CM and 173 (4%) had both CM and PVCs > 5%. Males were more likely to have had LVEF assessment than females (58% vs. 55%, P=0.013). Table summarizes demographics in the overall population based on PVC burden and presence of CM. High PVC burden (>5%) was more prevalent in older, male, and White patients. In an ordinal logistic regression to assess PVC burden with gender separately for LVEF < or > 50%, females were found to have a higher PVC burden in the population with preserved LVEF (OR=1.59, 95% CI: 1.13, 2.22) but not with CM (LVEF < 50%, OR=1.13, 95% CI=0.97, 1.32). Females had a lower prevalence of high PVC burden (>5%) than males (7% vs. 11%; p<0.001), including among those with CM (23% vs. 29%, p=0.1). Conclusions: High PVC burden and CM are quite prevalent in the population undergoing Holter monitors. Older age is associated with higher PVC burden but no age difference is present between different PVC burdens in patients with CM. Females have a lower prevalence of high PVC burden (>5%) and combined high PVC burden and CM than males.

Ventricular Electrophysiological Effects of Vagal Nerve Stimulation in Humans With and Without Structural Heart Disease

Abstract: Clinical trials investigating the benefits of vagus nerve stimulation (VNS) in heart failure have shown mixed results. This variation maybe due to inconsistent stimulation parameters, which may fail to adequately stimulate cardiomotor fibers required for cardio‐protection. However, overstimulation of the vagus nerve may cause adverse off‐target effects. Thus, the aim of this study was to assess the beneficial effects of moderate frequency VNS in patients with structurally normal hearts (SNH) and those with cardiomyopathy (CM).

Abstract 11494: Electrophysiological Effects of Sympathoexcitation are Mitigated by Blockade of Neuropeptide Y Y2 Receptors on Cardiac Parasympathetic Nerve Terminals

Abstract: Introduction: Sympathetic activation releases both norepinephrine and co-transmitter neuropeptide Y (NPY). NPY can predispose to ventricular arrhythmias via receptors on cardiomyocytes. Ex vivo studies suggest that NPY may concomitantly reduce vagal tone via activation of NPY Y2 receptors (Y2R) on parasympathetic nerves, reducing acetylcholine release and further augmenting pro-arrhythmic sympathetic effects. We evaluated if parasympathetic Y2R blockade can prevent NPY-induced vagal inhibition, restore autonomic balance and stabilize cardiac electrophysiology. Methods: Yorkshire pigs (n = 12) underwent bilateral stellate ganglia stimulation (BSGS; 10 Hz, 4 ms) for 45 secs, before and after administration of selective Y2R antagonist BIIE0246 (BIIE; 32 nmol/kg bolus + 2 nmol/kg/min infusion). Hemodynamic and electrophysiological recordings were obtained with a left ventricular pressure (LVP) catheter, surface electrogram and a 56-electrode sock placed over the ventricles to measure activation recovery intervals (ARI), a surrogate of local action potential duration, from unipolar electrograms. Heart rate variability parameters, including low to high frequency ratio (LF/HF), were analyzed pre- and post-BIIE. Results: BSGS significantly increased heart rate (HR) and LVP, and shortened ventricular ARIs. BIIE significantly reduced both the rate of change and the maximal changes in HR and ARIs during BSGS. As anticipated, BSGS significantly increased LF/HF ratio, but this effect was abolished after BIIE. BIIE did not affect BSGS related increases in LVP. Conclusions: Cardiac effects of sympathetic activation are mediated, at least in part, by suppression of vagal tone through binding of NPY to parasympathetic Y2Rs. Blockade of this receptor partially counters pro-arrhythmic electrophysiological effects of BSGS and suggests a possible novel adjuvant role for Y2R blockade as a therapy for reducing consequences of sympatho-excitation.