Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control

2021 ◽  
Author(s):  
Joseph Hadaya ◽  
Una Buckley ◽  
Nil Z. Gurel ◽  
Christopher A. Chan ◽  
Mohammed A Swid ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Therapeutic Potential ◽  
Distal Portion ◽  
Left Ventricular ◽  
Sympathetic Chain ◽  
Strong Correlations ◽  
Norepinephrine Release ◽  
Ventricular Activation ◽  
Current Block ◽  
The Right

Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart, and may be a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n=14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r=0.83-0.96, effect size d=1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.

scholarly journals Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients

2021 ◽  
Vol 10 (4) ◽  
pp. 822
Author(s):  
Luuk I.B. Heckman ◽  
Justin G.L.M. Luermans ◽  
Karol Curila ◽  
Antonius M.W. Van Stipdonk ◽  
Sjoerd Westra ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Activation Time ◽  
Ventricular Synchrony ◽  
Septal Pacing ◽  
Ventricular Activation ◽  
Qrs Morphology ◽  
Conversion Matrix ◽  
Qrs Duration ◽  
The Right ◽  
Electrophysiological Effects

Background: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). Objective: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction. Methods: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r’ morphology, LVSP and—in patients where left bundle branch (LBB) capture was achieved—LBBP. From the ECG’s QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined. Results: QRS area significantly decreased from 82 ± 29 µVs during RV septal pacing (RVSP) to 46 ± 12 µVs during LVSP. In the subgroup where LBB capture was achieved (n = 31), QRS area significantly decreased from 46 ± 17 µVs during LVSP to 38 ± 15 µVs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 ± 16 vs. 35 ± 19 µVs, respectively). The Azimuth significantly changed from RVSP (−46 ± 33°) to LVSP (19 ± 16°) and LBBP (−22 ± 14°). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman’s R = 0.58). Conclusions: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP.

Ventricular activation process and genesis of QRS complex in the goat

1961 ◽  
Vol 200 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Robert L. Hamlin ◽  
Allen M. Scher
Keyword(s):  
Interventricular Septum ◽  
Left Ventricular ◽  
Left Ventricular Cavity ◽  
Activation Process ◽  
Qrs Complex ◽  
Complex Activity ◽  
Single Burst ◽  
Ventricular Activation ◽  
The Right ◽  
Apical Area

The pathways of ventricular excitation in the interventricular septum and the free walls of the ventricles were determined in the goat. During the first 5 msec. of the QRS complex, activity occurs in a cup-shaped zone formed around the apex of the left ventricular cavity, consisting of the left endocardial portions of the septum and the endocardium of the free wall. Within the next 10 msec. of the QRS, the apical third of the septum is excited, simultaneously, from both the left and the right ventricular endocardial surfaces. Also, all of the ventricles, except the bases and a small epicardial apical area of the left ventricle, are excited with almost a single burst of depolarization. During the next 3–5 msec. the ventricular bases and the small apical epicardial area are excited along with the middle third of the interventricular septum. The final 15 msec. of the QRS and approximately 3 msec. of the following isoelectric period are inscribed during activation of the basilar third of the septum.

scholarly journals Bilateral Bundle Branch Area Pacing to Achieve Physiological Conduction System Activation

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Jinxuan Lin ◽  
Keping Chen ◽  
Yan Dai ◽  
Qi Sun ◽  
Yuqiu Li ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Right Bundle Branch Block ◽  
Left Ventricular ◽  
Conduction System ◽  
Conduction Delay ◽  
Activation Time ◽  
Bundle Branch Block ◽  
Ventricular Activation ◽  
Qrs Duration ◽  
The Right

Background: Left bundle branch pacing (LBBP) is a technique for conduction system pacing, but it often results in right bundle branch block morphology on the ECG. This study was designed to assess simultaneous pacing of the left and right bundle branch areas to achieve more synchronous ventricular activation. Methods: In symptomatic bradycardia patients, the distal electrode of a bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing (BBBP) was achieved by stimulating the cathode and anode in various pacing configurations. QRS duration, delayed right ventricular activation time, left ventricular activation time, and interventricular conduction delay were measured. Pacing stability and short-term safety were assessed at 3-month follow-up. Results: BBBP was successfully performed in 22 of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3±7.1 versus 118.4±5.7 ms, P <0.001). LBBP resulted in a paced right bundle branch block configuration, with a delayed right ventricular activation time of 115.0±7.5 ms and interventricular conduction delay of 34.0±8.8 ms. BBBP fully resolved the right bundle branch block morphology in 18 patients. In the remaining 4 patients, BBBP partially corrected the right bundle branch block with delayed right ventricular activation time decreasing from 120.5±4.7 ms during LBBP to 106.1±4.2 ms during BBBP ( P =0.005). Conclusions: LBBP results in a relatively narrow QRS complex but with an interventricular activation delay. BBBP can diminish the delayed right ventricular activation, producing more physiological ventricular activation. Graphic Abstract: A graphic abstract is available for this article.

scholarly journals Fusion Pacing with Biventricular, Left Ventricular-only and Multipoint Pacing in Cardiac Resynchronisation Therapy: Latest Evidence and Strategies for Use

2021 ◽  
Vol 10 (2) ◽  
pp. 91-100
Author(s):  
Peter H Waddingham ◽  
Pier Lambiase ◽  
Amal Muthumala ◽  
Edward Rowland ◽  
Anthony WC Chow
Keyword(s):  
Cardiac Resynchronisation Therapy ◽  
Left Ventricular ◽  
Bundle Branch Block ◽  
Response Dynamic ◽  
Av Conduction ◽  
Cardiac Resynchronisation ◽  
Ventricular Activation ◽  
Resynchronisation Therapy ◽  
Modifiable Factor ◽  
The Right

Despite advances in the field of cardiac resynchronisation therapy (CRT), response rates and durability of therapy remain relatively static. Optimising device timing intervals may be the most common modifiable factor influencing CRT efficacy after implantation. This review addresses the concept of fusion pacing as a method for improving patient outcomes with CRT. Fusion pacing describes the delivery of CRT pacing with a programming strategy to preserve intrinsic atrioventricular (AV) conduction and ventricular activation via the right bundle branch. Several methods have been assessed to achieve fusion pacing. QRS complex duration (QRSd) shortening with CRT is associated with improved clinical response. Dynamic algorithm-based optimisation targeting narrowest QRSd in patients with intact AV conduction has shown promise in people with heart failure with left bundle branch block. Individualised dynamic programming achieving fusion may achieve the greatest magnitude of electrical synchrony, measured by QRSd narrowing.

Risk factors for cardiovascular diseases and development of prehypertension

2018 ◽  
pp. 37-43
Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Left Ventricular ◽  
Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

Prevalence, Biochemical and Clinical Characteristics of Resistant Hypertension

2018 ◽  
Vol 69 (10) ◽  
pp. 2845-2849
Author(s):  
Daniela Gurgus ◽  
Elena Ardeleanu ◽  
Carmen Gadau ◽  
Roxana Folescu ◽  
Ioan Tilea ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Resistant Hypertension ◽  
Clinical Characteristics ◽  
Salt Intake ◽  
Target Organ Damage ◽  
Multivariate Logistic Regression Analysis ◽  
Organ Damage ◽  
Left Ventricular ◽  
High Salt Intake

The objectives of the present study were to evaluate the prevalence of resistant hypertension (RH) in primary care setting and to analyse its biochemical and clinical characteristics. After 3 months of treatment and evaluation, 721 (14.01%) of 5,146 patients with hypertension did not reach target office blood pressure of [ 140/90 mmHg. After exclusion of �white-coat effect� with ambulatory blood pressure, of secondary and pseudo- resistant hypertension, prevalence of RH was 6.74%. Lifestyle factors associated with RH were physical inactivity, obesity, high salt intake, smoking and excessive alcohol ingestion. Compared to controlled hypertension, RH patients presented higher incidence of family history of cardiovascular disease (38.90% vs 25.94%), diabetes mellitus (34.87% vs 19.01%), impaired fasting glucose (21.91% vs 19.07%), target organ damage (29.1% vs 15.95%), and cardiovascular disease (27.09% vs 17.06%). Dyslipidaemia (52.90% vs 42.03%), fasting plasma glucose (116.10�38.9 vs 107.80�37.2), HbA1c (6.41�1.42 vs 5.96�0.94), serum creatinine (1.09�0.27 vs 1.03�0.24) and microalbuminuria (21.90% vs 10.95%) were significantly higher in RH. Predictors of RH, determined by a multivariate logistic regression analysis were left ventricular hypertrophy (OD 2.14, 95% CI 1.32-3.69), renal impairment expressed as eGFR [ 60 ml/min/1.73m2 (OD 1.62, 95% CI 1.21-2.21) and the presence of cardiovascular disease (OD 1.48, 95% CI 1.02-2.16).

Prevalence and Localization of Hibernating Myocardium Among Patients with Left Ventricular Dysfunction

2019 ◽  
Vol 15 (9) ◽  
pp. 884-889
Author(s):  
Emine Acar ◽  
Ayşegül Aksu ◽  
Gökmen Akkaya ◽  
Gamze Çapa Kaya
Keyword(s):  
Scar Tissue ◽  
Left Ventricular ◽  
Hibernating Myocardium ◽  
Circumflex Artery ◽  
Irrigation Area ◽  
Left Circumflex Artery ◽  
Pet Ct ◽  
Perfusion Defects ◽  
The Right ◽  
Fdg Pet Ct

Objective: This study evaluated how much of the myocardium was hibernating in patients with left ventricle dysfunction and/or comorbidities who planned to undergo either surgical or interventional revascularization. Furthermore, this study also identified which irrigation areas of the coronary arteries presented more scar and hibernating tissue. Methods: At rest, Tc-99m MIBI SPECT and cardiac F-18 FDG PET/CT images collected between March 2009 and September 2016 from 65 patients (55 men, 10 women, mean age 64±12) were retrospectively analyzed in order to evaluate myocardial viability. The areas with perfusion defects that were considered metabolic were accepted as hibernating myocardium, whereas areas with perfusion defects that were considered non-metabolic were accepted as scar tissue. Results: Perfusion defects were observed in 26% of myocardium, on average 48% were associated with hibernation whereas other 52% were scar tissue. In the remaining Tc-99m MIBI images, perfusion defects were observed in the following areas in the left anterior descending artery (LAD; 31%), in the right coronary artery (RCA; 23%) and in the Left Circumflex Artery (LCx; 19%) irrigation areas. Hibernation areas were localized within the LAD (46%), LCx (54%), and RCA (64%) irrigation areas. Scar tissue was also localized within the LAD (54%), LCx (46%), and RCA (36%) irrigation areas. Conclusion: Perfusion defects are thought to be the result of half hibernating tissue and half scar tissue. The majority of perfusion defects was observed in the LAD irrigation area, whereas hibernation was most often observed in the RCA irrigation area. The scar tissue development was more common in the LAD irrigation zone.

scholarly journals Hemodynamic Support Using Percutaneous Transfemoral Impella 5.0 and Impella RP for Refractory Cardiogenic Shock

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Pratik K. Dalal ◽  
Amy Mertens ◽  
Dinesh Shah ◽  
Ivan Hanson
Keyword(s):  
Left Ventricle ◽  
Pulmonary Artery ◽  
Cardiogenic Shock ◽  
Ventricular Function ◽  
Standard Of Care ◽  
Left Ventricular ◽  
Biventricular Failure ◽  
Ventricular Support ◽  
The Right ◽  
Flow Pump

Acute myocardial infarction (AMI) resulting in cardiogenic shock continues to be a substantial source of morbidity and mortality despite advances in recognition and treatment. Prior to the advent of percutaneous and more durable left ventricular support devices, prompt revascularization with the addition of vasopressors and inotropes were the standard of care in the management of this critical population. Recent published studies have shown that in addition to prompt revascularization, unloading of the left ventricle with the placement of the Impella percutaneous axillary flow pump can lead to improvement in mortality. Parameters such as the cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi), obtained through pulmonary artery catheterization, can help ascertain the productivity of right and left ventricular function. Utilization of these parameters can provide the information necessary to escalate support to the right ventricle with the insertion of an Impella RP or the left ventricle with the insertion of larger devices, which provide more forward flow. Herein, we present a case of AMI complicated by cardiogenic shock resulting in biventricular failure treated with the percutaneous insertion of an Impella RP and Impella 5.0 utilizing invasive markers of left and right ventricular function to guide the management and escalation of care.

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

Sign in / Sign up

Export Citation Format

Share Document