Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy

Fallavollita, James A.; Dare, Jonathan D; Carter, Randolph L.; Baldwa, Sunil; Canty, John M.

doi:10.1161/circimaging.117.006446

Cited by 42 publications

(25 citation statements)

References 30 publications

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“…The adverse effects of obesity on cardiovascular haemodynamics, structure, impaired systolic and/or diastolic ventricular function, and increased risk of cardiac failure have been widely reported 24 , 25 . Increased obesity-related cardiac output, metabolic dysregulation, myocardial fatty infiltration all contribute to the eccentric and concentric hypertrophy characteristic of obesity-related cardiac failure 26 , which is also a cause of cardiogenic arrest 27 . Our results demonstrated a quasi-higher percentage of inotrope use in the overweight (76%) and obese patients (91%), as well as higher percentage of ECMO use (60%) in the obese patients.…”

Section: Discussionmentioning

confidence: 99%

Obese cardiogenic arrest survivors with significant coronary artery disease had worse in-hospital mortality and neurological outcomes

Sung

Chen

Chang

et al. 2020

Sci Rep

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Cardiogenic arrest is the major cause of sudden cardiac arrest (SCA), accounting for 20% of all deaths annually. The association between obesity and outcomes in cardiac arrest survivors is debatable. However, the effect of obesity on the prognosis of patients with significant coronary artery disease (CAD) successfully resuscitated from cardiogenic arrest is unclear. Thus, the association between body mass index (BMI) and outcomes in cardiogenic arrest survivors with significant CAD was investigated. This multicentre retrospective cohort study recruited 201 patients from January 2011 to September 2017. The eligible cardiogenic arrest survivors were non-traumatic adults who had undergone emergency coronary angiography after sustained return of spontaneous circulation and had significant coronary artery stenosis. BMI was used to classify the patients into underweight, normal-weight, overweight, and obese groups (< 18.5, 18.5–24.9, 25.0–29.9, and ≥ 30 kg/m2; n = 9, 87, 72, and 33, respectively). In-hospital mortality and unsatisfactory neurological outcomes (cerebral performance scale scores = 3–5) were compared among the groups. The obese group presented higher in-hospital mortality and unsatisfactory neurological outcome risks than the normal-weight group (in-hospital mortality: adjusted hazard ratio = 4.27, 95% confidence interval (CI) 1.87–12.04, P = 0.008; unsatisfactory neurological outcomes: adjusted odds ratio = 3.33, 95% CI 1.42–8.78, P = 0.009). Subgroup analysis showed significantly higher in-hospital mortality in the obese patients than in the others in each clinical characteristic. In cardiogenic arrest survivors with significant CAD, obesity was associated with high risks of mortality and unsatisfactory neurological recovery.

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Section: Discussionmentioning

confidence: 99%

Obese cardiogenic arrest survivors with significant coronary artery disease had worse in-hospital mortality and neurological outcomes

Sung

Chen

Chang

et al. 2020

Sci Rep

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“…Subsequent data analysis showed that while a larger LVEDVI, lack of angiotensin inhibition therapy, and elevated BNP enhanced the association of high-risk image findings with an arrhythmic event, a higher resting heart rate, older age, elevated creatinine, a larger left atrial volume index and a larger LVEDVI better predicted non-sudden cardiac death. 20 Thus, combining image data with cardiac and clinical parameters improves identification of patients likely to benefit from an ICD.…”

Section: Advantages Of Radionuclide Cardiac Autonomic Innervation Imamentioning

confidence: 99%

Importance of individual patient characteristics when assessing the ability of cardiac adrenergic imaging to guide ICD use

Travin

2022

Journal of Nuclear Cardiology

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“…Nerve sprouting may promote the heterogeneity of excitability and refractoriness, which was suggested to increase arrhythmia susceptibility in the reinnervated infarct border zone [8,9]. However, recent clinical studies [10,11] have shown that cardiac sympathetic denervation (rather than reinnervation) can lead to a higher risk of ventricular arrhythmias and arrhythmic death. Experimental and computational studies linked the beneficial effect of innervation to attenuation of infarct-induced vulnerability to repolarisation alternans via β-adrenergic activation [12,13] or to reduction of electrophysiological heterogeneity and calcium mishandling, which was present even when the nerves were not activated [14].…”

Section: Introductionmentioning

confidence: 99%

Optical interrogation of sympathetic neuronal effects on macroscopic cardiac monolayer dynamics

Burton

Tomek

Ambrosi

et al. 2019

Preprint

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Alterations in autonomic function are known to occur in cardiac conditions including sudden cardiac death. Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. Dissecting direct neural-cardiac interactions at the cellular level is technically challenging and understudied due to the lack of experimental model systems and methodologies. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiac monolayer dynamics to address research targets such as the effects of adrenergic stimulation via the release of neurotransmitters, the effect of neuronal numbers on cardiac wave behaviour and the applicability of optogenetics in mechanistic in vitro studies. We combine photo-uncaging or optogenetic neural stimulation with imaging of cardiac monolayers to measure electrical activity in an automated fashion, illustrating the power and high throughput capability of such interrogations. The methods described highlight the challenges and benefits of co-cultures as experimental model systems. RESULTS:1] Stellate Sympathetic Neurons make contacts with cardiomyocytes: Scanning electron microscopy of sympathetic neurons growing in co-culture with cardiomyocytes in vitro shows connections between neurite extension and cardiac syncytium (Figure 1 A). The neuron bodies and extensions clearly make physical contact with myocytes (Figure 1 B, C, D, E, F, G, H, I, J). Immuno staining of co-cultures shows co-localisation of Synpasin and Beta2 receptors (Figure 1 K), sympathetic neurons show positive staining for Th (Figure 1 L), and fibronectin contamination in the co-cultures was assessed by staining with Vimentin (Figure 1 M), which showed low abundance. 2] Pattern formation is affected by the presence of neurons: Using dye-free imaging (Figure 2 A, B, C), we investigated how neuronal activation modulates cardiac patterns of activation in monolayer culture. We chose experimental conditions that spontaneously yield a wide variety of wavefront topologies within the imaging system's 16 x 16 mm field of view. Introduction of an additional cell type can potentially introduce heterogeneities that would impact wave front stability. Surprisingly, co-cultures displayed fewer wave breaks than their monoculture counterparts at similar plating densities (Figure 2 D). We broadly classified wave dynamics as simple (periodic target waves and single spiral wave reentry, Figure 2 D top row), or complex (single dominant spirals with additional irregular waves and multiple equally sized wavelets, Figure 2 D bottom row). While monocultures frequently displayed complex dynamics, co-cultures rarely displayed this behavior (Figure 2 E, P<0.05, chi-square test). Indeed, we observed wavelet reentry in only one of the co-culture preparations (6 isolations, 20 preparations). 3] Conduction velocity in spontaneously active co-cultures is faster than myocyte monocultures:We measured conduction velocity in unstimulated co-cultures (n=19) and myocyte monocultures (n=9). Figure 2 F s...

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Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy

Cited by 42 publications

References 30 publications

Obese cardiogenic arrest survivors with significant coronary artery disease had worse in-hospital mortality and neurological outcomes

Obese cardiogenic arrest survivors with significant coronary artery disease had worse in-hospital mortality and neurological outcomes

Importance of individual patient characteristics when assessing the ability of cardiac adrenergic imaging to guide ICD use

Optical interrogation of sympathetic neuronal effects on macroscopic cardiac monolayer dynamics

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