The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of ...neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.
The progression of atrial fibrillation (AF) from paroxysmal to persistent forms remains a major clinical challenge. Abnormal sarcoplasmic reticulum (SR) Ca(2+) leak via the ryanodine receptor type 2 ...(RyR2) has been observed as a source of ectopic activity in various AF models. However, its potential role in progression to long-lasting spontaneous AF (sAF) has never been tested. This study was designed to test the hypothesis that enhanced RyR2-mediated Ca(2+) release underlies the development of a substrate for sAF and to elucidate the underlying mechanisms.
CREM-IbΔC-X transgenic (CREM) mice developed age-dependent progression from spontaneous atrial ectopy to paroxysmal and eventually long-lasting AF. The development of sAF in CREM mice was preceded by enhanced diastolic Ca(2+) release, atrial enlargement, and marked conduction abnormalities. Genetic inhibition of Ca(2+)/calmodulin-dependent protein kinase II-mediated RyR2-S2814 phosphorylation in CREM mice normalized open probability of RyR2 channels and SR Ca(2+) release, delayed the development of spontaneous atrial ectopy, fully prevented sAF, suppressed atrial dilation, and forestalled atrial conduction abnormalities. Hyperactive RyR2 channels directly stimulated the Ca(2+)-dependent hypertrophic pathway nuclear factor of activated T cell/Rcan1-4, suggesting a role for the nuclear factor of activated T cell/Rcan1-4 system in the development of a substrate for long-lasting AF in CREM mice.
RyR2-mediated SR Ca(2+) leak directly underlies the development of a substrate for sAF in CREM mice, the first demonstration of a molecular mechanism underlying AF progression and sAF substrate development in an experimental model. Our work demonstrates that the role of abnormal diastolic Ca(2+) release in AF may not be restricted to the generation of atrial ectopy but extends to the development of atrial remodeling underlying the AF substrate.
Methods LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF 5-year and PREVAIL 3-year patient-level data were aggregated and analyzed on an intent-to-treat basis.
Abstract Objectives The goal of this study was to evaluate the diagnostic performance of a comprehensive, multicomponent cardiac magnetic resonance (CMR) study for assessment of left atrial (LA) and ...left atrial appendage (LAA) thrombus. Background Pre-operative evaluation for pulmonary vein isolation (PVI) typically requires tomographic imaging to define pulmonary venous anatomy and transesophageal echocardiogram (TEE) to assess for the presence of LA/LAA thrombus. CMR is increasingly being used to define pulmonary venous anatomy before PVI. Limited data are available on the utility of a multicomponent CMR protocol in assessing LA/LAA thrombus. Methods We studied patients who underwent multicomponent CMR for evaluation of pulmonary venous anatomy before PVI and underwent TEE within 7 days. LA and LAA thrombi were evaluated by using CMR as follows: 1) cine-CMR; 2) contrast-enhanced magnetic resonance angiography; and 3) equilibrium phase delayed enhancement (DE) CMR with a long inversion time (TI) of 600 ms (long TI DE-CMR). Components of the CMR study were evaluated for diagnostic performance for detection of LA or LAA thrombus using TEE as the reference standard. Results During the study period, 261 patients were assessed. The median CHA2 DS2 VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 2, and 73.6% of patients were undergoing anticoagulation therapy. CMR and TEE were performed within 1.3 ± 2.3 days. LA/LAA thrombi were discovered in 9 patients (3.5%) by using TEE. Among the CMR techniques performed, long TI DE-CMR had the highest diagnostic accuracy (99.2%), sensitivity (100%), and specificity (99.2%), followed by contrast-enhanced magnetic resonance angiography (accuracy 94.3%; sensitivity 66.7%; and specificity 95.2%) and cine-CMR (accuracy 91.6%; sensitivity 66.7%; and specificity 92.5%). Conclusions In patients referred for PVI, CMR could be a single complete diagnostic study for assessment of pulmonary venous anatomy as well as presence of LA/LAA thrombi, thus reducing the number of pre-operative tests before PVI. Long TI DE-CMR has the best diagnostic performance and should be used for the detection of LA/LAA thrombi.
The arrhythmic role of the left atrial appendage (LAA) has been implicated in the maintenance of persistent atrial fibrillation. LAA isolation with catheter ablation has been successful but is ...limited by the risk of tamponade and electromechanical dissociation with the potential for LAA thrombus formation.
To assess whether LAA ligation results in LAA electrical isolation.
A total of 68 patients with contraindication or intolerance to oral anticoagulation therapy underwent LAA ligation with the LARIAT suture delivery device. Patients had unipolar n = 30(44%) or bipolar n = 38(56%) voltage measurements pre- and post-LAA ligation.
All 68 patients underwent successful LAA ligation. There was a statistically significant reduction in the mean LAA voltage from pre-ligation (unipolar pre-ligation voltage 1.1 ± 0.53 mV; bipolar pre-ligation voltage 4.7 ± 2.83 mV) to post-ligation (unipolar post-ligation voltage 0.3 ± 0.38 mV; bipolar post-ligation voltage 0.6 ± 0.27 mV). Ninety-four percent of the patients had a reduction in the LAA voltage after the closure of the snare, with 10 of 30 (33%) of the patients having complete elimination of LAA voltage with the initial tightening of the suture. Pacing from the LAA after the closure of the snare resulted in lack of capture of the left atrium in 28 of 31 patients.
The snare closure of the LAA using the LARIAT device produces an acute reduction in the LAA voltage and inhibits the capture of the left atrium during LAA pacing. Future studies are needed to determine whether LAA ligation affects atrial fibrillation burden.
The objective of this study was to examine prevalence and clinical implications of subclinical coronary artery disease (CAD) detected by coronary artery calcium score (CACS) testing in patients with ...atrial fibrillation (AF). CACS was assessed in patients without history of CAD undergoing catheter ablation of AF. Age- and gender-matched patients with normal sinus rhythm (NSR) presenting with chest pain served as controls. Predicted arterial age using the Multi-Ethnic Study of Atherosclerosis registry was also compared to the chronologic age. A total of 860 patients (430 AF and 430 NSR, age 63 ± 10 years, 65% men) were included. Subclinical CAD prevalence (CACS >0) was 74% (319 of 430) in the AF group. Compared to the patients with NSR, patients with AF had higher prevalence of Subclinical CAD (74% vs 63%; p <0.001). In multivariate analysis, AF was independently associated with Subclinical CAD (hazard ratio 1.60; p = 0.002) but only with persistent AF (hazard ratio 2.28; p <0.001). Predicted arterial age was greater than chronologic age in patients with AF (69 ± 12 vs 64 ± 9 years). CACS-diagnosed subclinical CAD identified new potential candidates for statin therapy (12%; 33 of 267) and for oral anticoagulation (19%; 40 of 206) by addition of subclinical CAD to the CHA2 DS2 -VASc scores. In conclusion, in patients without known history of CAD, prevalence of subclinical CAD was significantly higher in those with persistent AF than those with NSR. AF was associated with subclinical CAD independently and complimentarily to clinical risk factors. Identifying subclinical CAD has potential clinical indications for prevention of CAD progression and stroke.
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