Biventricular interaction and aortic function in adult patients with repaired tetralogy of Fallot: a two-dimensional-three-dimensional speckle-tracking echocardiographic study.

Aims: In patients late after correction of tetralogy of Fallot (TOF), the combined effects of pre-operative hypertrophy and hypoxia, ventricular interdependence, acquired post-operative lesions such as pulmonary or aortic regurgitation, and congenital vasculopathy may result in impaired right ventricular (RV) and left ventricular (LV) function. The aim of the present study was to investigate the interventricular interactions in repaired TOF (rTOF) and the impact of aortic function on biventricular performance using two-dimensional (2D-STE) and three-dimensional speckle-tracking echocardiography (3D-STE). Methods and results: Twenty-five adult patients with rTOF and 25 age- and gender-matched healthy controls were studied. LV and RV volumes were determined by 3D-STE and cardiac magnetic resonance. LV and RV longitudinal strains (LVLS and RVLS) and LV and RV area strains (LVAS and RVAS) and LV twist/rotation were calculated by 3D-STE. Ascending aorta circumferential strain (AAo-CS) was obtained using 2D-STE. LV 3D-STE parameters were decreased in rTOF patients compared with controls even in patients with normal ejection fraction. AAo-CS was decreased (6.7 ± 1.9 vs. 10.1 ± 2.6, P = 0.003) in rTOF patients compared with controls even in the presence of normal aortic dimensions and correlated with AAo diameter (r = -0.69, P = 0.0001), LV twist (r = 0.54, P = 0.004), LVAS (r = -0.56, P = 0.003), and RVLS (r = -0.39, P = 0.036). LVAS and AAo-CS were associated with disease severity (peak oxygen consumption and arrhythmia occurrence). Significant improvement in global χ 2 value was noted with RV 3D-STE parameters + LVAS + AAo-CS compared with RV dysfunction alone for detecting exercise capacity impairment (from 77.1 to 84.4 to 91.2, P = 0.003). Conclusion: Speckle-tracking echocardiography revealed subtle LV and AAo dysfunction in adults with rTOF. A correlation was observed between LV and RV strain changes and between AAo strain impairment and LV/RV dysfunction. LV and AAo changes had an incremental value in evaluating disease severity.

Commentary to Skudlik et al. (2023): why a scoping review and why only Germany?

This letter to the editor is a commentary on the scoping review by Skudlik et al. (2023) on the relocation of older people to nursing homes in Germany. In this commentary, we question certain methodological decisions that, in our view, particularly affect transferability of the results and give a partial picture of the phenomena studied by limiting the inclusion to German studies. We also have questions about the choice of knowledge synthesis method and why the concept of "nursing home" was not defined. We hope that this letter will open a constructive scientific discussion on an important topic that is understudied as the world's population ages.

Comprehensive echocardiographic assessment of right ventricular function, pulmonary arterial elastic properties and ventricular-vascular coupling in adult patients with repaired tetralogy of fallot: clinical significance of 3D derived indices.

We aimed to comprehensively analyze by three-dimensional speckle-tracking echocardiography (3DSTE) and Doppler echocardiography right ventricular (RV) performance, pulmonary arterial (PA) elastic properties and right ventricular-pulmonary artery coupling (RVPAC) in patients with repaired tetralogy of Fallot (rTOF) and assess the feasibility and clinical utility of related echocardiographic indices. Twenty-four adult patients with rTOF and twenty-four controls were studied. RV end-diastolic volume(3D-RVEDV), RV end-systolic volume(3D-RVESV), RV ejection fraction(3D-RVEF), RV longitudinal strain(3D-RVLS) and RV area strain(3D-RVAS) were calculated by 3DSTE. RV end-systolic area (RVESA) was obtained by planimetry. Pulmonary regurgitation (PR) was assessed as trivial/mild or significant by cardiac magnetic resonance (CMR) and color-Doppler. Pulmonary artery (PA) elastic properties were determined using two-dimensional/Doppler echocardiography. RV systolic pressure (RVSP) was measured using standard Doppler methods. RVPAC was assessed using various 3DSTE-derived parameters (3DRVAS/RVSP, 3DRVLS/RVESA, 3DRVAS/RVESV). Overall, 3DRVEF and 3DRVAS were impaired in rTOF patients compared with controls. PA pulsatility and capacitance were reduced (p = 0.003) and PA elastance was higher (p = 0.0007) compared to controls. PA elastance had a positive correlation with 3DRVEDV (r = 0.64, p = 0.002) and 3DRVAS (r = 0.51, p = 0.02). By ROC (receiver operating characteristics) analysis, 3DRVAS/RVESV, 3DRVAS/RVSP and 3DRVLS/RVESA cutoff values of 0.31%/mmHg, 0.57%/mmHg and 0.86%/mmHg, respectively, had 91%, 88% and 88% sensitivity and 81%, 81% and 79% specificity in identifying exercise capacity impairment. In rTOF patients increased 3DSTE-derived RV volumes and impaired RV ejection fraction and strain are associated with reduced PA pulsatility and capacitance and increased PA elastance. 3DSTE-derived RVPAC parameters using different afterload-markers are accurate indices of exercise capacity.

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.

Heart, COVID-19, and echocardiography.

Although clinical manifestations of coronavirus disease of 2019 (COVID-19) mainly consist of respiratory symptoms, a severe cardiovascular damage may occur. Moreover, previous studies reported a correlation of cardiovascular metabolic diseases with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and actually, many COVID-19 patients show comorbidities (systemic hypertension, cardio-cerebrovascular disease, and diabetes) and have a raised risk of death. The purpose of this review is to focus the cardiovascular effects of 2019-nCoV on the base of the most recent specific literature and previous learnings from SARS and MERS and analyze the potential role of echocardiography during the current critical period and short- and long-term follow-up.

Detection of Biofilm-associated Implant Pathogens in Cardiac Device Infections: High Sensitivity of Sonication Fluid Culture Even in the Presence of Antimicrobials.

INTRODUCTION: Sonication showed more sensitivity than traditional culture in the diagnosis of device infections. Aims of the study were to assess the role of sonication in the microbiological diagnosis and management of cardiac device infections (CDIs), to evaluate the sensitivity of sonication in patients on antimicrobial therapy at the time of device removal, and to analyze biofilm formation of the isolated strains. MATERIALS AND METHODS: A total of 90 devices (31 generators and 59 electrodes) collected from 31 patients with infection underwent sonication before culture. Devices were sonicated for 5 min and centrifuged at 3200 rpm for 15 min. Intraoperative traditional cultures were performed in 26 patients. Microorganisms were identified using conventional methods. Staphylococcal strains were tested for slime production. RESULTS: Microbiological diagnosis was achieved in 28 patients (90%). Sonicate fluid was positive in 68/90 (76%) of devices (27/31 [87%] generators and 41/59 [69%] electrodes), whereas intraoperative pocket swabs grew bacteria in 10/26 patients (38%, P = 0.0007). Among leads, 37/59 (62.7%) yielded bacteria even in the absence of vegetation. Coagulase-negative Staphylococci accounted for 83.8% (57/68) of the total; Staphylococcus aureus and Gram-negative bacilli were found in 4.4% (3/68) and 5.8% (4/68), respectively. Biofilm production was present in 15/22 (69%) staphylococcal strains. Overall, patients on therapy (n = 23) had a microbiological diagnosis in 20/23 (86.9%) and 7/22 (30.4%) through sonication and intraoperative cultures, respectively (P = 0.0002). DISCUSSION: Our data showed the high sensitivity of sonication in the diagnosis of CDIs, even in patients under antimicrobial therapy. CONCLUSION: Sonication represents an essential tool for both diagnosis and management of CDIs.

Mixed method exploration of the medical, service-related, and emotional reasons for emergency room visits of older cancer patients.

PURPOSE: When dealing with health issues, older cancer patients are likely to visit emergency rooms (ER), which are known to expose these patients to the risk of adverse outcomes. Little is known about the profile and reasons for such visits. The aim of this study is (1) to describe the profile of elderly cancer patients aged 70 years and older who visited the ER of a regional hospital in Québec, Canada, and (2) to explain the medical reasons and factors determining such visits from the patients' perspective. METHODS: A concurrent mixed method design was used. Descriptive analysis of administrative databases was conducted to describe the socio-demographic, clinical, and service utilization profile of 792 cancer patients aged 70 years and older. Content analysis of 11 semi-structured interviews of a sub-sample was subsequently performed to better understand the experience and meaning these patients attribute to this health behaviour. RESULTS: The sample of 792 older cancer patients made a total of 1572 ER visits. Most visits occurred during the daytime. More than half (53 %) of the patients were discharged, and close to 40 % were hospitalized. The most frequent reasons for consulting were respiratory (15.8 %), digestive (13.4 %), neurological (8.3 %), fever or infection-related (8.3 %), and cardiovascular (8.2 %). Content analysis of the qualitative data suggested that patients made ER visits mostly when other cancer care services were unavailable or because of a serious life-threatening health condition. CONCLUSIONS: The study suggests areas of improvement to prevent ER visits when health issues can be addressed by other care services.

Global and regional left ventricular strain indices in post-myocardial infarction patients with ventricular arrhythmias and moderately abnormal ejection fraction.

The aim of the study described here was to compare myocardial strains in ischemic heart patients with and without sustained ventricular tachycardia (VT) and moderately abnormal left ventricular ejection fraction (LVEF) to investigate which index could better predict VT on the basis of the analysis of global and regional left ventricular (LV) dysfunction. We studied 467 patients with previous myocardial infarction and LVEF >35%. Fifty-one patients had documented VT, and 416 patients presented with no VT. LV volumes and score index were obtained by 2-D echocardiography. Longitudinal, radial and circumferential strains were determined. Strains of the infarct, border and remote zones were also obtained. There were no differences in standard LV 2-D parameters between patients with and those without VT. Receiver operating characteristic values were -12.7% for global longitudinal strain (area under the curve [AUC] = 0.72), -4.8% for posterior-inferior wall circumferential strain (AUC = 0.80), 61 ms for LV mechanical dispersion (AUC = 0.84), -10.1% for longitudinal strain of the border zone (AUC = 0.86) and -9.2% for circumferential strain of the border zone (AUC = 0.89). In patients with previous myocardial infarction and moderately abnormal LVEF, peri-infarct circumferential strain was the strongest predictor of documented ventricular arrhythmias among all strain quantitative indices. Additionally, strain values from posterior-inferior wall infarctions had a higher association with arrhythmic events compared with global strain.

Intra-QT spectral coherence as a possible noninvasive marker of sustained ventricular tachycardia.

Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the q wave to the T wave peak (QTp) and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the QTp-Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without (0.508 ± 0.150 versus 0.607 ± 0.150, P < 0.05). Although the responsible mechanism remains conjectural, the QTp-Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias.

Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles.

BACKGROUND: We previously reported that IKAS are heterogeneously upregulated in failing rabbit ventricles and play an important role in arrhythmogenesis. This study goal is to test the hypothesis that subtype 2 of the small-conductance Ca(2+) activated K(+) (SK2) channel and apamin-sensitive K(+) currents (IKAS) are upregulated in failing human ventricles. METHODS AND RESULTS: We studied 12 native hearts from transplant recipients (heart failure [HF] group) and 11 ventricular core biopsies from patients with aortic stenosis and normal systolic function (non-HF group). IKAS and action potential were recorded with patch-clamp techniques, and SK2 protein expression was studied by Western blotting. When measured at 1 µmol/L Ca(2+) concentration, IKAS was 4.22 (median) (25th and 75th percentiles, 2.86 and 6.96) pA/pF for the HF group (n=11) and 0.98 (0.54 and 1.72) pA/pF for the non-HF group (n=8, P=0.008). IKAS was lower in the midmyocardial cells than in the epicardial and the endocardial cells. The Ca(2+) dependency of IKAS in HF myocytes was shifted leftward compared to non-HF myocytes (Kd 314 versus 605 nmol/L). Apamin (100 nmol/L) increased the action potential durations by 1.77% (-0.9% and 7.3%) in non-HF myocytes and by 11.8% (5.7% and 13.9%) in HF myocytes (P=0.02). SK2 protein expression was 3-fold higher in HF than in non-HF. CONCLUSIONS: There is heterogeneous upregulation of IKAS densities in failing human ventricles. The midmyocardial layer shows lower IKAS densities than epicardial and endocardial layers of cells. Increase in both Ca(2+) sensitivity and SK2 protein expression contributes to the IKAS upregulation.

Sonication of explanted cardiac implants improves microbial detection in cardiac device infections.

The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively; P = 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (P = 0.019) and uninfected (P = 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%; P = 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6 Staphylococcus epidermidis strains, 1 Staphylococcus hominis strain, 2 Corynebacterium striatum strains, and 1 Brevundimonas sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (P = 0.75 and P = 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices.

Autonomic nerve activity and the short-term variability of the Tpeak-Tend interval in dogs with pacing-induced heart failure.

BACKGROUND: In congestive heart failure (CHF), autonomic nervous system (ANS) activity is known to modulate arrhythmic risk through its effects on myocardial repolarization. An increased interval between the peak and the end of the T wave (T(peak)-T(end)) has been reported to increase the incidence of sudden cardiac death. However, the ANS influence on the T(peak)-T(end) interval remains unclear. OBJECTIVE: We directly measured ANS nerve activity in ambulatory dogs with pacing-induced CHF to test the hypothesis that ANS activity modulates the T(peak)-T(end) variability index (T(peak)-T(end)VI), the short-term variability of the T(peak)-T(end) interval obtained on 30 beats (T(peak)-T(end)STV(30)), and the short-term variability of the T(peak)-T(end) interval obtained on 5-minute ECG recording (T(peak)-T(end)STV(T)). METHODS: By using data previously recorded in 6 ambulatory dogs before and after pacing-induced CHF, we assessed ANS activity recorded with an implanted radiotransmitter that monitored integrated left stellate ganglion nervous activity (iSGNA), integrated vagus nerve activity (iVNA), and electrocardiogram (ECG). We selected for analysis 36 segments recorded at baseline and 36 after pacing-induced CHF with similar iSGNA. RESULTS: During CHF, T(peak)-T(end)STV(30) (P<.001) and T(peak)-T(end)STV(T) (P<.05) were significantly higher than those at baseline. The multiple linear mixed regression analysis disclosed a significant positive correlation between iSGNA and T(peak)-T(end)STV(T) (baseline: ß 2.92, P<.001; CHF: ß 1.13, P<.001) and a significant negative correlation between iVNA and T(peak)-T(end)STV(T) (baseline: ß-6.74, P<.001; CHF: ß-1.42, P< .001). CONCLUSIONS: In a canine model of pacing-induced CHF, iSGNA correlates positively while iVNA correlates negatively with T(peak)-T(end)STV(T). These findings suggest that SGNA increases while VNA decreases the dispersion of ventricular repolarization in ambulatory dogs with CHF.

Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.

INTRODUCTION: Myocardial infarction (MI) results in cardiac nerve sprouting in the myocardium. Whether or not similar neural remodeling occurs in the stellate ganglia (SGs) is unknown. We aimed to test the hypothesis that MI induces bilateral SG nerve sprouting. METHODS: Acute MI was created by coronary artery ligation in rabbits (n=12). Serum nerve growth factor (NGF) level was measured by enzyme-linked immunosorbent assay. The hearts and bilateral SGs were harvested for immunohistochemistry after 1 week in six rabbits and after 1 month in six rabbits. Immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), choline acetyltransferase (ChAT), and synaptophysin (SYN) was performed to determine the magnitude of nerve sprouting. Tissues from six normal rabbits were used as controls. Nerve density was determined by computerized morphometry. RESULTS: Myocardial infarction results in increased serum NGF levels at 1 week (1519.8±632.2 ng/ml) that persist up to 1 month (1361.2±176.3 ng/ml) as compared to controls (89.6±34.9 ng/ml) (P=.0002 and P=.0001, respectively). Immunostaining demonstrated nerve sprouting and hyperinnervation in both SGs after MI. The nerve densities (µm(2)/ganglion cell) in SG 1 week after MI and 1 month after MI and those in control groups, respectively, were as follows: GAP43: 278±96, 225±39, and 149±57 (P=.01); SYN: 244±152, 268±115, and 102±60 (P=.02); TH: 233±71, 180±50, and 135±68 (P=.047); ChAT: 244±100, 208±46, and 130±41 µm(2)/cell (P=.01). CONCLUSIONS: Myocardial infarction increases serum NGF levels and induces nerve sprouting and hyperinnervation in bilateral SGs for at least 1 month after MI. The hyperinnervation includes both adrenergic axons and cholinergic axons in the SG.

Dynamically shaped magnetic fields: initial animal validation of a new remote electrophysiology catheter guidance and control system.

BACKGROUND: To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed that provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described. METHODS AND RESULTS: A real-time, high-speed, closed-loop, magnetic RNS system (Catheter Guidance Control and Imaging) comprises 8 electromagnets that create unique dynamically shaped ("lobed") magnetic fields around the subject's torso. The real-time reshaping of these magnetic fields produces the appropriate 3D motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX 3D electroanatomic mapping system (St Jude Medical) and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm-tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by Catheter Guidance Control and Imaging. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 seconds to reach targets). At postmortem examination, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness. CONCLUSIONS: A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target radiofrequency ablation points within the pig left atrium. Validation of the system in clinical settings is under way.

Additive value of right ventricular dyssynchrony indexes in predicting the success of cardiac resynchronization therapy: a speckle-tracking imaging study.

BACKGROUND: The purpose of our study was to analyze the evolution of left and right ventricular (LV, RV) parameters before and after cardiac resynchronization therapy (CRT) using speckle-tracking imaging (STI). METHODS AND RESULTS: Eighty-one patients with dilated cardiomyopathy (New York Heart Association functional class III or IV), left bundle branch block (QRS ≥120 ms), and LV ejection fraction ≤35% were studied with STI echocardiography before and after CRT. LV longitudinal (LV-SD12-l), radial (LV-SD6-r), and circumferential (LV-SD6-c) intraventricular dyssynchrony and LV twist (LV-t) were determined. RV dyssynchrony (RV-SD6) was defined as the standard deviation of the 6 time to peak systolic strain values. At 6 months' follow-up after CRT, the degree of dyssynchrony correlated significantly with LV ejection fraction improvement and end-systolic volume reduction. In receiver operating characteristic curve analysis, the following variables predictive of successful CRT were obtained: LV-SD12-l (area under the curve [AUC] 0.69), LV-SD6-c (AUC 0.66), LV-SD6-r (AUC 0.79), LV-t (AUC 0.81), and RV-SD6+LV-SD6-r (AUC 0.83). By combining LV and RV intraventricular dyssynchrony (LV-SD12-l + LV-SD6-r + RV-SD6), the AUC was significantly improved to 0.89 (P < .005 compared with RV-SD6+LV-SD6-r; P < .001 compared with LV-t). CONCLUSIONS: Our data show that assessment of RV dyssynchrony parameters has an incremental value in the evaluation of candidates for CRT and may supplement LV dyssynchrony information.

Transient accelerated junctional rhythm late after para-Hisian accessory pathway cryoablation: a new phenomenon.

Transient junctional rhythm late after para-Hisian accessory pathway cryoablation occurred in two patients. Cryoablation was delivered using the 8 mm tip Freezor MAX™ catheter (Cryocath Technologies Inc., Montreal, Canada), 2 mm distal to the largest His potential. Transient symptomatic junctional rhythm occurred after 1 week. This benign, self-limiting rhythm is possibly caused by reversible cryoinjury to the His bundle periphery.

Histopathological substrate for chronic atrial fibrillation in humans.

BACKGROUND: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). OBJECTIVE: This study sought to examine the histological substrate of patients with chronic AF. METHODS: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. RESULTS: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% +/- 5.6% vs 7.4% +/- 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03). CONCLUSION: HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure.

BACKGROUND: Heart failure increases autonomic nerve activities and changes intracellular calcium (Ca(i)) dynamics. OBJECTIVE: The purpose of this study was to investigate the hypothesis that abnormal Ca(i) dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS: Simultaneous optical mapping of Ca(i) and membrane potential was performed in isolated Langendorff-perfused PV-left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 micromol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS: Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Ca(i), late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 +/- 0.6 beats/s (N = 4) to 6.5 +/- 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV-LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid-Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION: Ca(i) dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.