The benefits of the earlier use of sacubitril/valsartan in de novo heart failure with reduced ejection fraction patients.

AIMS: We evaluated the clinical outcomes and trajectory of cardiac reverse remodelling according to the timing of sacubitril/valsartan (Sac/Val) use in patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Patients with de novo HFrEF who used Sac/Val between June 2017 and October 2019 were retrospectively enrolled. Patients were grouped into the earlier use group (initiation of Sac/Val < 3 months after the first HFrEF diagnosis) and the later use group (initiation of Sac/Val ≥ 3 months after the first HFrEF diagnosis). Primary outcome was a composite of HF hospitalization and cardiac death. Secondary outcomes were HF hospitalization, cardiac death, all-cause death, significant ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and echocardiographic evidence of cardiac reverse remodelling including left ventricular ejection fraction (LVEF) change during follow-up. Among 115 enrolled patients, 67 were classified in the earlier use group, and 48 were classified in the later use group. Mean period of HFrEF diagnosis to Sac/Val use was 52.1 ± 14.3 days in the earlier use group, and 201.8 ± 127.3 days in the later use group. During the median follow-up of 721 days, primary outcome occurred in 21 patients (18.3%). The earlier use group experienced significantly fewer primary outcome than the later use group (10.4% vs. 29.2%, P = 0.010). The Kaplan-Meier survival curve showed better event-free survival in the earlier use group than in the later use group (log rank = 0.017). There were no significant differences in cardiac death, all-cause death, and ventricular arrhythmia between two groups (1.5% vs. 2.1%, P = 0.811; 1.5% vs. 4.2%, P = 0.375; 3.0% vs. 0%, P = 0.227, respectively). Despite a significantly lower baseline LVEF in the earlier use group (21.3 ± 6.4% vs. 24.8 ± 7.9%, P = 0.012), an early prominent increase of LVEF was noted before 6 months (35.2 ± 11.9% vs. 27.8 ± 8.8%, P = 0.007). A delayed improvement of LVEF in the later use group resulted in similar LVEF at last follow-up in both groups (40.7 ± 13.4% vs. 39.4 ± 10.9%, P = 0.686). Although the trajectory of left ventricular remodelling showed similar pattern in two groups, left atrial (LA) reverse remodelling was less prominent in the later use group during the follow-up period (final LA volume index: 43.6 ± 14.3 mL/m2 vs. 55.2 ± 17.1 mL/m2 , P = 0.011). CONCLUSIONS: Earlier use of Sac/Val was related with better clinical outcome and earlier left ventricular reverse remodelling. Remodelling of LA was less prominent in the later use group implying delayed response in diastolic function.

Surveillance of adenosine stress myocardial contrast echocardiography following percutaneous coronary intervention.

BACKGROUND: The ability of adenosine stress myocardial contrast echocardiography (AS-MCE) to reveal decreased coronary blood flow or perfusion defects (PDs) has not been explored for clinical implications after coronary revascularization. This study sought to identify the prognostic value of PDs in asymptomatic patients following percutaneous coronary intervention (PCI). METHODS: We retrospectively analyzed 342 asymptomatic patients (67 years of mean age, 72% male) who underwent PCI with stents at least 9 months before AS-MCE between May 2019 and December 2020. Resting regional wall motion abnormality (rRWMA) and the patterns of PDs were assessed, and further PDs were classified as ischemic or fixed type. The primary endpoint was the composite of hospitalization for worsening heart failure, coronary revascularization, and cardiac death. RESULTS: In AS-MCE (median time interval following PCI: 17.4 months), PDs were present in 93 (27.2%) out of 342 patients; 70 of ischemic PD (75.3%), 58 of fixed PD (62.4%). Those with PD showed a higher frequency of rRWMA than those without PD (53.8 vs. 15.7%, p < 0.001). During the median follow-up of 22.6 months, 26 (7.6%) patients experienced more associated clinical outcomes with PD than rRWMA. Cox analysis revealed that the combined findings of rRWMA and PD, and specifically, ischemic PD of ≥ 2 segments were associated with a high increase in adverse outcomes. CONCLUSIONS: AS-MCE provided prognostic value in asymptomatic patients with prior PCI. PD might be complementary to rRWMA in risk stratification.

High density mapping guided partial antral ablation for a pulmonary vein isolation.

The muscular discontinuities at the pulmonary vein (PV)-left atrial (LA) junction are known. The high-density mapping may help to find the muscular discontinuity. This study evaluated the efficacy of a partial antral ablation for a pulmonary vein (PV) isolation using high density (HD) mapping. A total of 60 drug-refractory atrial fibrillation (AF) patients undergoing catheter ablation were enrolled. The detailed activation mapping of each PV and LA junction was performed using an HD mapping system, and each PV segment's activation pattern was classified into a "directly-activated from the LA" or "passively-activated from an adjacent PV segment" pattern. The antral ablations were performed at the directly-activated PV segments only when the PV had "passively-activated segments". If the PV did not contain passively-activated segments, a circumferential antral ablation was performed on those PVs. A "successful partial antral ablation" was designated if the electrical isolation of targeted PV was achieved by ablation at the directly-activated segments only. If the isolation was not achieved even though all directly-activated segments were ablated, a "failed partial antral ablation" was designated, and then a circumferential ablation was performed. Among 240 PVs, passively-activated segments were observed in 140 (58.3%) PVs. Both inferior PVs had more passively-activated segments than superior PVs, and the posteroinferior segments had the highest proportion of passive activation. The overall rate of successful partial antral ablation was 85%. The atrial tachyarrhythmia recurrence was observed in 10 patients (16.7%) at 1-year. HD mapping allowed the evaluation of the detailed activation patterns of the PVs, and passively-activated segments may represent muscular discontinuity. Partial antral ablation of directly-activated antral segments only was feasible and effective for a PVI.

Ablation of persistent atrial fibrillation based on high density voltage mapping and complex fractionated atrial electrograms: A randomized controlled trial.

INTRODUCTION: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. However, a PVI alone has been considered insufficient for persistent AF. This study aimed to evaluate the efficacy of persistent AF ablation targeting complex fractionated atrial electrogram (CFAE) areas within low voltage zones identified by high-resolution mapping in addition to the PVI. METHODS: We randomized 50 patients (mean age 58.4 ±â€Š9.5 years old, 86.0% males) with persistent AF to a PVI + CFAE group and PVI only group in a 1:1 ratio. CFAE and voltage mapping was performed simultaneously using a Pentaray Catheter with the CARTO3 CONFIDENSE module (Biosense Webster, CA, USA). The PVI + CFAE group, in addition to the PVI, underwent ablation targeting low voltage areas (<0.5 mV during AF) containing CFAEs. RESULTS: The mean persistent AF duration was 24.0 ±â€Š23.1 months and mean left atrial dimension 4.9 ±â€Š0.5 cm. In the PVI + CFAE group, AF converted to atrial tachycardia (AT) or sinus rhythm in 15 patients (60%) during the procedure. The PVI + CFAE group had a higher 1-year AF free survival (84.0% PVI + CFAE vs 44.0 PVI only, P = .006) without antiarrhythmic drugs. However, there was no difference in the AF/AT free survival (60.0% PVI + CFAE vs 40.0% PVI only, P = .329). CONCLUSION: Persistent AF ablation targeting CFAE areas within low voltage zones using high-density voltage mapping had a higher AF free survival than a PVI only. Although recurrence with AT was frequent in the PVI+CFAE group, the sinus rhythm maintenance rate after redo procedures was 76%.

Influence of Anatomical and Clinical Characteristics on Long-Term Prognosis of FFR-Guided Deferred Coronary Lesions.

OBJECTIVES: The aim of this study was to evaluate the clinical and anatomical features to predict the long-term outcomes in patients with fractional flow reserve (FFR)-guided deferred lesions, verified by intravascular ultrasound (IVUS). BACKGROUND: Deferral of nonsignificant lesion by FFR is associated with a low risk of clinical events. However, the impact of combined information on clinical and anatomical factors is not well known. METHODS: The study included 459 patients with 552 intermediate lesions who had deferred revascularization on the basis of a nonischemic FFR (>0.80). Grayscale IVUS was examined simultaneously. The primary endpoint was patient-oriented composite outcome (POCO) (a composite of all-cause death, myocardial infarction, and any revascularization) during 5-year follow-up. RESULTS: The rate of 5-year POCO was 9.8%. Diabetes mellitus (hazard ratio: 3.50; 95% confidence interval [CI]: 1.86 to 6.57; p < 0.001), left ventricular ejection fraction ≤40% (hazard ratio: 4.80; 95% CI: 1.57 to 14.63; p = 0.006), and positive remodeling (hazard ratio: 2.04; 95% CI: 1.03 to 4.03; p = 0.041) were independent predictors for POCO. When the lesions were classified according to the presence of the adverse clinical characteristics (diabetes, left ventricular ejection fraction ≤40%) or adverse plaque characteristics (positive remodeling, plaque burden ≥70%), the risk of POCO was incrementally increased (4.3%, 13.6%, and 21.3%, respectively; p < 0.001). CONCLUSIONS: In patients with FFR-guided deferred lesions, 5-year clinical outcomes were excellent. Lesion-related anatomical factors from intravascular imaging as well as patient-related clinical factors could provide incremental information about future clinical risks.

Epidemiological and clinical characteristics of coronavirus disease 2019 in Daegu, South Korea.

OBJECTIVES: Two Coronavirus Disease 2019 (COVID-19) outbreaks simultaneously occurred at a church and a long-term care facility in Daegu, South Korea. This study aimed to investigate the epidemiological characteristics of COVID-19 and factors related to severe outcomes. METHODS: We enrolled all inpatients diagnosed with COVID-19 between February 21 and April 2, 2020, in Daegu Dongsan Hospital. We analyzed their clinical and demographic data, laboratory parameters, radiological findings, symptoms, and treatment outcomes. RESULTS: Of 694 patients, severe cases accounted for 19.7% (137 patients). No severe case was observed among patients aged ≤19 years. Hypertension was the most common comorbidity (27%), and cough was the most common symptom (59%). Asymptomatic patients accounted for 14.4% of cases. Lymphopenia, lactate dehydrogenase, C-reactive protein, and albumin were associated with severe outcomes. The first outbreak was mostly associated with younger age groups, and asymptomatic patients mostly showed mild progression. In the second outbreak involving a long-term care facility, both the number of severe patients and the mortality rate were higher. CONCLUSIONS: The overall mortality in Daegu was low, which might have resulted from large scale mass screening to detect patients and starting appropriate treatment, including hospitalization for severe cases, and quarantine for asymptomatic patients.

Long Term Clinical Outcomes in Patients with Moderate Aortic Stenosis.

BACKGROUND: While the surgical correction of moderate aortic stenosis (AS) can be deferred with a watchful waiting according to the present guideline, the clinical outcomes for moderate AS with comorbidity have not extensively been studied. We aimed to explore the factors that would contribute to the outcomes of moderate AS with at least five years of follow-up duration. METHODS: Medical records review identified patients with moderate aortic valve (AV) stenosis from January 2008 and December 2012. Echocardiographic data were gathered, and the final 5-year clinical outcomes, defined as the composite of cardiovascular (CV) death, admission for heart failure (HF) aggravation, and AV replacement, were evaluated. RESULTS: Among 148 patients (mean age, 69.3 years; mean AV area, 1.24 cm2), 79 had adverse outcomes (16 CV deaths, 32 AV replacements, and 31 HF cases), during a mean follow-up of 5.6 years. The event group showed worse dyspnea of NYHA III-IV and a higher frequency of diabetes mellitus (DM). They had a higher frequency of moderate or moderate-to-severe functional mitral regurgitation (MR) and smaller AV area. In the multivariate analysis, DM (HR 2.29, 95% CI 1.03-5.10), moderate or moderate-to-severe MR (HR 4.84, 95% CI 1.66-10.07), and NYHA III-IV (HR 3.84, 95% CI 1.72-8.56) independently were associated with adverse outcomes. CONCLUSIONS: The symptomatic patients with moderate AS had higher events than expected, and early intervention should be considered in case of concomitant MR and DM.

Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction.

BACKGROUND: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting. OBJECTIVE: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. METHODS: In the experimental group, a radio transmitter was implanted during the first sterile surgery to record nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. RESULTS: In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 µV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 µV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 µV (P<.039) and 2.14±0.50 µV (P<.001) at 4 and 8 weeks, respectively, after MI. In comparison, aSGNA at 4 and 8 weeks in dogs with MI but no ScNS was 8.26±6.31 µV (P=.005) and 10.82±7.86 µV (P=0002), respectively. Immunostaining showed confluent areas of remodeling in bilateral stellate ganglia and a high percentage of tyrosine hydroxylase-negative ganglion cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling was positive in 26.61%±11.54% of ganglion cells in the left stellate ganglion and 15.94%±3.62% of ganglion cells in the right stellate ganglion. CONCLUSION: ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac nerve sprouting after acute MI.

The impact of catheter ablation of atrial fibrillation on the left atrial volume and function: study using three-dimensional echocardiography.

PURPOSE: The exact correlation between the baseline left atrial (LA) volume (LAV) and atrial fibrillation (AF) radiofrequency catheter ablation (RFCA) outcomes and changes to the LA after AF RFCA has not yet been fully understood. We sought to evaluate the serial changes in the LAV and LA function after RFCA using 3D echocardiography. METHODS: Consecutive patients who received RFCA of paroxysmal (PAF) or persistent AF (PeAF) at our center between January 2013 and March 2016 were included. Real-time 3D apical full-volume images were acquired, and a 3D volumetric assessment was performed using an automated three-beat averaging method. The LAV index (LAVI) was calculated and the LA ejection fraction (LAEF) was calculated as [LAVmax - LAVmin]/LAVmax. RESULTS: Ninety-nine total patients were enrolled, and the mean age was 58.0 ± 8.2 years and 75 (74.7%) were male. There were 59 (59.6%) PAF patients and the remaining 40 (40.4%) had PeAF. AF recurred in 5 of 59 (8.5%) PAF and in 10 of 40 (25%) PeAF patients. The LAVImax increased on 1 day, decreased at 3 months, and then increased again at 1 year but was lower than that at baseline. The LAEF changes were similar to the volume changes but were more prominent in PeAF than PAF patients. The baseline 3D LAVImax was an independent predictor of AF recurrence after RFCA and the cut-off value was 44.13 ml/m2. CONCLUSION: In our study, even after 3 months of scar formation due to ablation, structural remodeling of the LA continued. The changes were more prominent in the non-recurrent, PeAF patients.

Implication of ultrasound contrast-enhancement of carotid plaques in prevalence of acute coronary syndrome and occurrence of cardiovascular outcomes.

PURPOSE: Ultrasonographic contrast enhancement of carotid plaque (CECP) has been used to detect neovascularization of vasa vasorum and plaque. However, it is uncertain whether CECP can provide risk stratification of coronary artery disease (CAD). This study aimed to evaluate the relationship between CECP and manifestations of acute coronary syndrome (ACS) in established CAD patients and to explore the prognostic implication of CECP for cardiovascular (CV) clinical outcomes. METHODS: A medical record review revealed that contrast-enhanced ultrasonography was performed to evaluate carotid atherosclerosis in 209 coronary artery-stented and 105 non-stented patients. The rate of ACS manifestations was compared depending on contrast uptake patterns: grade 0, absent; grade 1, dot; and grade 2, diffuse pattern. CV primary outcomes were assessed during a mean 7.6 months of follow-up. RESULTS: Male sex, smoking, history of old myocardial infarction, intensive medications, and a favorable lipid profile were common in the stented versus non-stented group. Patients with grade 2 CECP had a higher rate of ACS, greater plaque thickness, and class I-II of Gray-Weale plaque echogenicity. During follow-up, 10 coronary revascularizations (nine ACSs), six strokes, and four heart failures occurred. Grade 2 CECP was more closely related with CV primary outcomes and showed a tendency toward more acute CV outcomes. CONCLUSION: ACS manifestations were proportionate to CECP grade. Diffuse CECP uptake could be a risk factor for acute CV outcomes.

Prognostic Usefulness of Tricuspid Annular Diameter for Cardiovascular Events in Patients With Tricuspid Regurgitation of Moderate to Severe Degree.

Functional tricuspid regurgitation (TR) is frequently encountered. Current guidelines recommend the surgical correction of severe TR only at the time of left valve surgery despite emphasizing the enlarged tricuspid annulus (TA) dimension. We attempted to evaluate the relation between TA dimension and clinical outcomes of moderate or severe TR. A total of 213 patients (mean age 68 years, women 68%) with moderate or severe TR secondary to left-sided valve surgery, nonvalvular disease, or isolated primary TR were retrospectively identified and classified into tertiles of TA dimension. Cardiovascular (CV) outcomes were defined as a composite of hospitalization for worsening heart failure (HF), stroke, and CV death over a median follow-up of 3.4 years. Upper and lower tertiles of TA dimension had high frequencies of left-sided valve surgery and isolated primary TR, respectively. TA dimension was correlated with TR severity assigned as color Doppler grade and systolic tissue Doppler imaging of the tricuspid valve (TDI s'). During follow-up, there were 87 (41%) occurrences of primary outcomes: 65 HFs (31%), 13 CV deaths (6%), and 9 strokes (4%). There was a high frequency of adverse outcomes in the upper tertile. TA dimension and TDI s' were independently related to outcomes. An enlarged TA dimension was associated with outcomes irrespective of subgroups according to type or severity of TR and TDI s' (p = 0.21, p = 0.77, p = 0.15 for interaction). A cut-off value of 4.0 cm for TA dimension was best for CV event occurrence. When assessing clinical CV outcomes, TA dimension should be considered, even in moderate TR.

Incidence and predictors of silent embolic cerebral infarction following diagnostic coronary angiography.

BACKGROUND: Coronary angiography (CAG) is an invasive diagnostic procedure, which could lead to procedure related complications. One of the well known post-procedural complications is cerebral embolic infarction with or without symptoms. Silent embolic cerebral infarction (SECI) has clinical significance because it can progress to a decline in cognitive function and increase the risk of dementia in the long term. The aim of this study was to detect the incidence and predictors of SECI after diagnostic CAG using diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: A total of 197 patients with coronary artery disease who underwent DW-MRI for evaluation of intracranial vasculopathy before coronary artery bypass graft surgery were retrospectively enrolled in the present study. DW-MRI was performed within 48 h after diagnostic CAG. SECI was diagnosed as presence of focal bright high signal intensity in DW-MRI. Patients were divided into groups according to presence/absence of SECI (+ SECI vs. - SECI, respectively). The clinical and angiographic characteristics were analyzed and independent predictors were evaluated. RESULTS: Of the 197 patients, SECI occurred in 20 patients (10.2%) after diagnostic CAG. Age, female gender, frequency of underlying atrial fibrillation, extent of coronary disease, and fluoroscopic time during diagnostic CAG were not different between the + SECI and - SECI groups. Left ventricular ejection fraction was significantly lower in the + SECI group than in the - SECI group (45.9 ± 8.5% vs. 51.4 ± 13.1%, p=0.014) and performance rate of internal mammary artery (IMA) angiography was significantly higher in the + SECI group compared with the - SECI group (85% vs. 37.2%, p<0.001). By multivariate analysis, performing IMA angiography was the only predictor of SECI (OR=14.642; 95% CI=3.201 to 66.980, p=0.001). CONCLUSIONS: The incidence of SECI after diagnostic CAG was not infrequent. Diagnostic CAG with IMA angiography may increase the risk of SECI.

Pericardial approach for cardiac therapies: old practice with new ideas.

Treatment of cardiac disease via the epicardium fell under the domain of cardiac surgery due to the need for an open thoracotomy. Since an open thoracotomy is invasive in nature and has the potential for complications, a minimally invasive and percutaneous approach would be more attractive for suitable patients. The recent success of epicardial ablation of refractory arrhythmia via the percutaneous pericardial approach has increased the potential for delivery of epicardial therapies. Epicardial ablation has increased the success and safety since anti-coagulation and transseptal catheterization for left atrial arrhythmias is not required. The pericardial space has also been used to deliver therapy for several cardiac diseases. There are reports on successful delivery of drugs and their efficacy. Even though there was a wide range of efficacies reported in those studies, the reported complication rates are strikingly low, which suggests that direct delivery of drugs to the epicardium via the pericardial space is safe. Furthermore, recent animal studies have supported the feasibility of epicardial delivery of biological agents, including genes, cells, and even genetically engineered tissue for therapeutic purposes. In conclusion, percutaneous pericardial cannulation of closed pericardial space can play a significant role in providing non-surgical therapy for cardiovascular diseases. However, it requires skills and operator experiences. Therefore, there is need to further develop new tools, safer techniques, and effective procedure environment before generalizing this procedure.

LifeShirt acquisition system to monitor ECG from ambulatory swine and the implementation of an arrhythmia detection algorithm.

A wearable cardiopulmonary monitoring system, a LifeShirt, was used to acquire continuous electrocardiograms (ECGs) from ambulatory swine. The animals received intracoronary injections of autologous mesenchymal stem cells, and the LifeShirt was used for long-duration ECG monitoring in pre-defined periods post cell infusion. The system used here was developed for measurements from non-human primates and canines; however, we demonstrated that it could be used to non-invasively measure ECGs from swine without creating undue stress or restricting movement. A MATLAB-based analysis algorithm was developed to automatically detect premature ventricular contractions (PVCs) that arose 8-10 hours after cell delivery with spontaneous resolution 2-3 days post-infusion. Template based cross-correlation was used to detect the PVCs and identify regions of consecutive ventricular rhythm. The final algorithm was highly specific and sensitive when tested on records from the MIT-BIH arrhythmia database. The algorithm was subsequently used to automatically identify and quantify PVCs from over 200 hours of ECG data obtained from nine ambulatory swine.

Comparison of long-term outcomes following sirolimus-eluting stent vs paclitaxel-eluting stent implantation in patients with long calcified coronary lesions.

BACKGROUND: Although previously reported studies on coronary calcification mainly focused on its presence or absence in discrete focal target lesions, calcified coronary lesions (CCL) angiographically present as diffuse long lesions in some patients. The aim of our study was to evaluate the long-term efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) on long CCL. METHODS: A total of 122 patients with 134 lesions (77 patients with 88 lesions for SES and 45 patients with 46 lesions for PES) were enrolled from 3 centers. Long CCL was defined visually as a culprit lesion with type B or C that was mainly due to coronary calcification with > 20 mm in total length by coronary angiography. Clinical follow-up was performed at 1 year and angiographic follow-up at 6 to 9 months after procedure. Major adverse coronary events (MACE) were defined as all-cause death, myocardial infarction (MI), and repeat target-lesion revascularization (TLR). RESULTS: There were no statistically significant differences in baseline, procedural, or angiographic characteristics and in 1-year rates of all-cause death, MI, and TLR between the 2 groups (all P = NS [not significant]). Likewise, the cumulative incidence of MACE at 1 year was similar between the 2 groups (7.8% of patients in the SES group vs 4.4% of patients in the PES group, respectively, P = NS). In patients who underwent follow-up angiography, the angiographic binary restenosis rate was 6.2% in the SES group vs 12.1% in the PES group, respectively (P = NS). CONCLUSION: In patients with long CCL, both SES and PES were comparably effective in either angiographic or clinical long-term outcomes.

Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a canine model of sudden death.

BACKGROUND: Little information is available on the temporal relationship between instantaneous sympathetic nerve activity and ventricular arrhythmia in ambulatory animals. OBJECTIVE: The purpose of this study was to determine if increased sympathetic nerve activity precedes the onset of ventricular arrhythmia. METHODS: Simultaneous continuous long-term recording of left stellate ganglion (LSG) nerve activity and electrocardiography was performed in eight dogs with nerve growth factor infusion to the LSG, atrioventricular block, and myocardial infarction (experimental group) and in six normal dogs (control group). RESULTS: LSG nerve activity included low-amplitude burst discharge activity (LABDA) and high-amplitude spike discharge activity (HASDA). Both LABDA and HASDA accelerated heart rate. In the experimental group, most ventricular tachycardia (86.3%) and sudden cardiac death were preceded within 15 seconds by either LABDA or HASDA. The closer to onset of ventricular tachycardia, the higher the nerve activity. The majority of HASDA was followed immediately by either ventricular arrhythmia (21%) or QRS morphology changes (65%). HASDA occurred in a circadian pattern. HASDA occurred twice as often in the experimental group than in the control group. Electrical stimulation of LSG increased transmural heterogeneity of repolarization (Tpeak-end intervals) and induced either ventricular tachycardia or fibrillation in the experimental group but not in the control group. Immunohistochemical studies revealed increased synaptogenesis and nerve sprouting in the LSG in the experimental group. CONCLUSION: Two distinct types of LSG nerve activity (HASDA and LABDA) are present in the LSG of ambulatory dogs. The majority of malignant ventricular arrhythmias are preceded by either HASDA or LABDA, with HASDA particularly arrhythmogenic.

Spontaneous chordae rupture of tricuspid valve in patient with chronic renal failure.

Spontaneous chordae rupture of the tricuspid valve is relatively rare, unlike the mitral valve. We present a 27-year-old male with chronic renal failure on hemodialysis therapy for treatment of parathyroid adenoma. The echocardiography showed the severe tricuspid regurgitation with chordae rupture which was not noted 1 year ago. In addition, the papillary muscle of both mitral and tricuspid valve was shortened and calcified extensively. However, in his clinical history, the specific causes for chordae rupture, such as chest trauma or endocarditis, were not disclosed. It was presumed that dilated right ventricle with volume or pressure overloading and secondary hyperparathyroidism are probably responsible for the chordae rupture of tricuspid valve.

Ischemic esophageal necrosis secondary to traumatic aortic transection.

Esophageal necrosis with perforation secondary to traumatic aortic transection is extremely rare but usually fatal. A 47-year-old man complained of sudden swallowing difficulty 6 days after blunt trauma. Computed tomography showed a ruptured aorta and the midesophagus shifted to the right side with luminal obliteration because of the ruptured aorta. After primary repair of the partially transected aorta, unexpected mediastinitis because of esophageal perforation was noted. Upper endoscopy showed midesophageal ulceration, necrosis, and perforation. Biopsy samples were consistent with ischemia. The possibility of direct esophageal trauma or intraoperative esophageal injury was ruled out. Esophageal exclusion with thoracoscopic decortication and multiple antibiotics were ineffective, and the patient eventually died. Ischemic esophageal necrosis caused by mechanical compression can occur in a traumatic aortic transection. Dysphagia, when present with radiologic signs, indicates a displaced and compressed esophagus. In spite of aggressive surgical and medical treatment for a perforated esophagus, the prognosis remains poor.

Analysis of proteome and transcriptome of tumor necrosis factor alpha stimulated vascular smooth muscle cells with or without alpha lipoic acid.

Vascular smooth muscle cells (VSMCs) play an important role in the development and progression of atherosclerosis. Tumor necrosis factor alpha (TNFalpha), a cytokine secreted by VSMCs and macrophages in atherosclerotic lesions, regulates a variety of cellular functions of inflammatory cells and VSMCs by promoting cell growth and motility, which are critical for the initiation and progression of vascularlesions. Alpha lipoic acid (ALA), a well known antioxidant, acts as a pyruvate dehydrogenase cofactor in mitochondrial metabolism. Recently, we reported that ALA has many beneficial effects on vascular cells in atherosclerosis. The aim of the current study was to examine VSMCs, treated for 24 hours with TNFalpha (10 ng/mL) in the presence or absence of ALA (2 mM), for differential protein and genes expression using two-dimensional gel electrophoresis (2-DE) and DNA microarray analysis, respectively. Using 2-DE, we identified proteins whose expression changed by at least 2.5-fold after TNFalpha stimulation. Proteins up-regulated by TNFalpha that were subsequently down-regulated in the presence of ALA were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as plasminogen activator inhibitor-2, fetal liver LKB-interacting protein, osteoblast-specific factor 2, glucosidase II, cyclin-dependent kinase 3, endoplasmin precursor and glutathione synthetase. TNFalpha down-regulated proteins that were up-regulated in the presence of ALA were keratin 19, eukaryotic translation elongation factor and Rho GDP dissociation inhibitor alpha. Gene expression analysis using DNA microarray tools confirmed the up-regulation or down-regulation of some, but not all, of the proteins observed in ALA challenged, TNFalpha-treated cells. This data should provide valuable information about the underlying mechanisms of atherosclerosis.