External Cardioversion of Atrial Fibrillation Causes an Early Improvement of Cardiac Performance: A Longitudinal Strain Analysis Study

Introduction:

Atrial fibrillation (AF) is often associated with heart failure. Several studies have demonstrated that resumption of sinus rhythm (SR) improves cardiac output in the long-term. Aims of this study were to evaluate the acute variations of left ventricular (LV) performance, following successful external cardioversion (ECV) of persistent AF using longitudinal strain (LSt) analysis, and the influence of inflammation.

Materials and Methods:

We enrolled 48 patients with AF (age: 73 ± 12 years, men: 83.3%). A standard transthoracic echocardiographic evaluation was performed before the procedure and 6 h later; this included the analysis of LV endocardial peak LSt, a measure of myocardial deformation. In the last 32 patients, plasma concentration of interleukin-6 (IL-6) was also determined.

Results:

Restoration of SR led to the decrease of heart rate (HR) (74 ± 21 vs 64 ± 10 bpm, P < 0.001) and LV end-systolic volume (30 ± 16 vs 27 ± 17 mL/m², P = 0.001), and to the increase of LV end-diastolic volume (LVEDV) (56 ± 20 vs 60 ± 21 mL/m², P = 0.036) and ejection fraction (EF) (48 ± 10 vs 57 ± 11%, P < 0.001). Peak LSt improved in 43 (89.6%) patients (-12.9 ± 3.3 vs -18.0 ± 4.7%, P < 0.001). Multivariate analysis (R = 0.729, P < 0.001) showed that strain changes were directly correlated with basal HR and the appearance of atrial mechanical activity and inversely correlated with corrected thyroid dysfunction, LVEDV and the presence of a permanent pacemaker. Higher levels of IL-6 negatively affected LV performance improvement.

Conclusions:

Effective ECV of AF determines a significant and fast improvement of LV performance, which is readily captured by LSt analysis. Inflammatory status may impact the response to SR restoration.     

Myocardial work in hypertensive patients with and without diabetes: An echocardiographic study

We aimed to investigate myocardial performance using pressure‐strain loops in hypertensive patients with and without type 2 diabetes mellitus (DM). This cross‐sectional study included 165 subjects (55 controls, 60 hypertensive patients without DM, and 50 hypertensive patients with DM) who underwent complete two‐dimensional echocardiographic examination (2DE) including two‐dimensional speckle‐tracking echocardiography. Pressure‐strain curve was used to determine global myocardial work index, constructive work, wasted work, and work efficiency in all study participants. Left ventricular (LV) longitudinal and circumferential strains gradually reduced from controls throughout hypertensive subjects to patients with DM and hypertension. Global myocardial work index gradually increased from controls, throughout hypertensive patients to subjects with hypertension and DM (1887 ± 289 vs 2073 ± 311 vs 2144 ± 345 mm Hg%, P = .001). Constructive work increased in the same direction (2040 ± 319 vs 2197 ± 344 vs 2355 ± 379 mm Hg%, P < .001). Work efficiency and wasted work did not differ between three observed groups. Glycosylated hemoglobin and systolic blood pressure were associated with global myocardial work and constructive work independently of age, body mass index, LV structural and functional parameters in all hypertensive participants. In conclusion, pressure‐strain curve showed that myocardial work was significantly affected by hypertension and diabetes. Diabetes demonstrated an additional negative effect on myocardial work in hypertensive patients.     

Impact of Atrial Fibrillation Ablation on Left Ventricular Filling Pressure and Left Atrial Remodeling

Background

Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e'' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process.

Objective

To evaluate the impact of AF ablation on estimated LV filling pressure.

Methods

A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e'' and E/e'') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation.

Results

One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m² ± 10.6 mL/m² to 22.6 mL/m² ± 1.1 mL/m², p < 0.001) compared to the non-successful group (37.7 mL/m² ± 14.3 mL/m² to 37.5 mL/m² ± 14.5 mL/m², p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e'' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001).

Conclusion

Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure.     

Left atrial wall dyskinesia assessed during contractile phase as a predictor of atrial fibrillation recurrence after electrical cardioversion performed due to persistent atrial fibrillation

Direct current cardioversion (DCCV) is one of the basic methods for restoring sinus rhythm (SR) in patients with atrial fibrillation (AF). Left atrial (LA) strain is one of the parameters used to assess the risk of AF recurrence following DCCV. Assessing the strain also allows for the detection of segmental disorders of LA wall contractility, including dispersion or dyskinesia. In the present study, we determined the predictive value of LA wall dyskinesia in assessing the risk of AF recurrence after DCCV. We performed a comprehensive echocardiography in 89 patients with persistent AF following successful DCCV. We assessed the strain and strain rate in the reservoir (r), conduit, and contractile (ct) phases by using speckle tracking echocardiography. Dyskinesia was diagnosed when the strain rate of any segment of the LA wall displayed positive values during contraction. After 12 months, 47.2% of patients maintained SR. Patients who maintained SR had a significantly lower LA strain (LAS)r assessed in the apical 4-chamber view (4c) (11.38 ± 4.63 vs 14.54 ± 5.11; P = .004) and 2-chamber view (2c) (11.05 ± 4.1 vs 14.93 ± 6.82%; P = .006), LASct4c (2.51 ± 2.3 vs 5.09 ± 3.29%; P < .001), LASct2c (3.6 ± 2.98 vs 5.67 ± 4.23%; P = .008), peak strain rate (pLASR) ct4c (0.36 ± 0.24 s vs 0.62 ± 0.4⁻¹; P < .001) and pLASRct2c (0.49 ± 0.30 vs 0.79 ± 0.53 s⁻¹; P = .01). LA dyskinesia was observed less frequently in the 4c view in patients who maintained SR (59.57 vs 17.5%; P < .001). Multivariable logistic regression showed that the LASct4c (odds ratio (OR) 0.78; 95%CI 0.63–0.97; P = .027) and LA dyskinesia observed in the 4c view (OR 3.53; 95%CI 1.16–10.76; P = .027) were significant independent predictors of AF recurrence at 12 months. We conclude that LA dyskinesia observed in the 4c view and LASct4c are independent risk factors for AF recurrence following DCCV.     

PET/CT-Based Dosimetry in 90Y-Microsphere Selective Internal Radiation Therapy: Single Cohort Comparison With Pretreatment Planning on 99mTc-MAA Imaging and Correlation With Treatment Efficacy

⁹⁰Y PET/CT can be acquired after ⁹⁰Y-microsphere selective radiation internal therapy (SIRT) to describe radioactivity distribution. We performed dosimetry using ⁹⁰Y-microsphere PET/CT data to evaluate treatment efficacy and appropriateness of activity planning from ^99mTc-MAA scan and SPECT/CT.Twenty-three patients with liver malignancy were included in the study. ^99mTc-MAA was injected during planning angiography and whole body ^99mTc-MAA scan and liver SPECT/CT were acquired. After SIRT using ⁹⁰Y-resin microsphere, ⁹⁰Y-microsphere PET/CT was acquired. A partition model (PM) using 4 compartments (tumor, intarget normal liver, out-target normal liver, and lung) was adopted, and absorbed dose to each compartment was calculated based on measurements from ^99mTc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT, respectively, to be compared with each other. Progression-free survival (PFS) was evaluated in terms of tumor absorbed doses calculated by ^99mTc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT results.Lung shunt fraction was overestimated on ^99mTc-MAA scan compared with ⁹⁰Y-microsphere PET/CT (0.060 ± 0.037 vs. 0.018 ± 0.026, P < 0.01). Tumor absorbed dose exhibited a close correlation between the results from ^99mTc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT (r = 0.64, P < 0.01), although the result from ^99mTc-MAA SPECT/CT was significantly lower than that from ⁹⁰Y-microsphere PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy, P < 0.01). Absorbed dose to in-target normal liver was overestimated on ^99mTc-MAA SPECT/CT compared with PET/CT (62.6 ± 38.2 Gy vs. 45.2 ± 32.0 Gy, P = 0.02). Absorbed dose to out-target normal liver did not differ between ^99mTc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT (P = 0.49). Patients with tumor absorbed dose >200 Gy on ⁹⁰Y-microsphere PET/CT had longer PFS than those with tumor absorbed dose ≤200 Gy (286 ± 56 days vs. 92 ± 20 days, P = 0.046). Tumor absorbed dose calculated by ^99mTc-MAA SPECT/CT was not a significant predictor for PFS.Activity planning based on ^99mTc-MAA scan and SPECT/CT can be effectively used as a conservative method. Post-SIRT dosimetry based on ⁹⁰Y-microsphere PET/CT is an effective method to predict treatment efficacy.     

Effect of Elective Bentall Procedure on Left Ventricular Systolic Function and Functional Status: Long-Term Follow-Up in 90 patients

Because there are so few data on the long-term effects on left ventricular systolic function and functional status in patients who electively undergo Bentall procedures, we established a retrospective study group of 90 consecutive patients. This group consisted of 71 male and 19 female patients (mean age, 54 ± 10 yr) who had undergone the Bentall procedure to correct aortic valve disease and aneurysm of the ascending aorta, from 1997 through 2003 in a single tertiary-care center. We monitored these patients for a mean period of 117 ± 41 months for death, left ventricular ejection fraction and volume indices, and functional capacity as determined by New York Heart Association (NYHA) class.There were no operative deaths. The survival rate was 73.3% during follow-up. There were 10 cardiac and 13 noncardiac deaths, and 1 death of unknown cause. Echocardiography was performed before the index procedure and again after 117 ± 41 months. In surviving patients, statistically significant improvement in left ventricular ejection fraction, in comparison with preoperative values (0.49 ± 0.11 vs 0.41 ± 0.11; P <0.0001), was noted at follow-up. Similarly, we observed statistically significant reductions in left ventricular end-systolic (39.24 ± 28.7 vs 48.77 ± 28.62 mL/m²) and end-diastolic volumes (54.63 ± 6.97 vs 59.17 ± 8.92 mL/m²; both P <0.0001). Most patients (53/66 [80.3%]) progressed from a higher to a lower NYHA class during the follow-up period.The Bentall procedure significantly improved long-term left ventricular systolic function and functional status in surviving patients who underwent operation on a nonemergency basis.     

Pediatric cardiac catheterization procedure with dexmedetomidine sedation: Radiographic airway patency assessment

Aims:

The aim of the study was to measure airway patency objectively during dexmedetomidine sedation under radiographic guidance in spontaneously breathing pediatric patients scheduled for cardiac catheterization procedures.

Subjects and Methods:

Thirty-five patients in the age group 5–10 years scheduled for cardiac catheterization procedures were enrolled. All study patients were given loading dose of dexmedetomidine at 1 μg/kg/min for 10 min and then maintenance dose of 1.5 μg/kg/h. Radiographic airway patency was assessed at the start of infusion (0 min) and after 30 min. Antero-posterior (AP) diameters were measured manually at the nasopharyngeal and retroglossal levels. Dynamic change in airway between inspiration and expiration was considered a measure of airway collapsibility. Patients were monitored for hemodynamics, recovery time and complications.

Statistical Analysis:

Student paired t-test was used for data analysis. P < 0.05 was considered significant.

Results:

Minimum and maximum AP diameters were compared at 0 and 30 min. Nasopharyngeal level showed significant reduction in the minimum (6.27 ± 1.09 vs. 4.26 ± 1.03, P < 0.0001) and maximum (6.51 ± 1.14 vs. 5.99 ± 1.03, P < 0.0001) diameters. Similarly retroglossal level showed significant reduction in the minimum (6.98 ± 1.09 vs. 5.27 ± 1.15, P < 0.0001) and maximum (7.49 ± 1.22 vs. 6.92 ± 1.12, P < 0.0003) diameters. The degree of collapsibility was greater at 30 min than baseline (P < 0.0001). There was a significant decrease in heart rate (P < 0.0001), and the average recovery time was 39.86 ± 12.22 min.

Conclusion:

Even though airway patency was maintained in all children sedated with dexmedetomidine, there were significant reductions in the upper airway dimensions measured, so all precautions to manage the airway failure should be taken.     

Metabolic Syndrome,Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis

Background

Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (ε_CC) and longitudinal strain (ε_LL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders.

Objective

We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE.

Methods

We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components.

Results

Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower ε_CC and lower ε_LL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative ε_CC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative ε_LL after adjustment for ethnicity, LVEF, and creatinine.

Conclusion

Left ventricular ε_CC and ε_LL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.     

Myocardial function in Saudi adolescents with vitamin D deficiency: Tissue Doppler imaging study

Vitamin D deficiency is a common health problem in Saudi Arabia especially in children and adolescents. Many studies have reported the relation between low 25-Hydroxyvitamin D (25(OH)D) levels with cardiovascular diseases risk factors as well as cardiovascular events, including stroke, myocardial infarction, and congestive heart failure. This study was conducted to evaluate the effect of 25(OH)D deficiency on the myocardial function and other echocardiographic variables in adolescent, using tissue Doppler imaging (TDI) and to correlate these parameters with 25(OH)D level. The study included 84 healthy adolescents, consecutively selected from adolescents attending the outpatient clinic of Saad Specialist Hospital, KSA between September 2013 and October 2014. The study population was classified into two groups; vitamin D deficient group with 25(OH)D level less than 20 ng/mL and normal vitamin D (control group) with 25(OH)D equal or more than 30 ng/mL. Both groups were subjected to measuring hemoglobin level, serum albumin, creatinine, total calcium, Phosphorous, intact parathyroid hormone (iPTH), B-type natriuretic peptide (BNP), and 25(OH)D levels. Both conventional and pulsed wave TDI were done for all participants. TDI measurements showed significant higher LV Tei Index and RV Tei index when compared to the control group (0.61 ± 0.11 Vs 0.32 ± 0.05 p < 0.0001), (0.54 ± 0.14 Vs 0.40 ± 0.06 p < 0.0001) respectively. Mitral and tricuspid annular systolic velocities were significantly lower in vitamin D deficient group (6.99 ± 1.92 Vs 10.69 ± 0.31 cm/sec p < 0.0001 and 12.30 ± 2.14 Vs 13.89 ± 0.29 p < 0.0001 respectively). The mitral and tricuspid E/Em ratio was significantly higher in vitamin D deficient group than control group (p < 0.0001, p 0.005) respectively. Left ventricular internal diameter at end-diastole (LVIDd) was significantly higher in vitamin D deficient group (44.72 ± 6.33 Vs 40.36 ± 6.21 p 0.003). Serum 25(OH)D level showed significant negative correlation with LV Tei index (r = −0.668, p < 0.0001), RV Tei index (r = −0.421, p < 0.0001). Vitamin D deficiency is associated with subtle systolic and diastolic myocardial dysfunction in Saudi adolescents. TDI is a useful tool for detecting early changes in the myocardium in this particular group.     

Cyclophosphamide induction dose and outcomes in ANCA-associated vasculitis with renal involvement: A comparative cohort study

Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m² vs 35 ± 26 mL/min/1.73 m², P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m² vs +6.0 ± 1.1 mL/min/1.73 m², P = .33). The 2.5–3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2−6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1–4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.     

A Comparison of Radiation Dose Between Standard and 3D Angiography in Congenital Heart Disease

Background

The use of three-dimensional rotational angiography (3D-RA) to assess patients with congenital heart diseases appears to be a promising technique despite the scarce literature available.

Objectives

The objective of this study was to describe our initial experience with 3D-RA and to compare its radiation dose to that of standard two-dimensional angiography (2D-SA).

Methods

Between September 2011 and April 2012, 18 patients underwent simultaneous 3D-RA and 2D-SA during diagnostic cardiac catheterization. Radiation dose was assessed using the dose-area-product (DAP).

Results

The median patient age and weight were 12.5 years and 47.5 Kg, respectively. The median DAP of each 3D-RA acquisition was 1093µGy.m² and 190µGy.m² for each 2D-SA acquisition (p<0.01). In patients weighing more than 45Kg (n=7), this difference was attenuated but still significant (1525 µGy.m² vs.413µGy.m², p=0.01). No difference was found between one 3D-RA and three 2D-SA (1525µGy.m² vs.1238 µGy.m², p = 0.575) in this population. This difference was significantly higher in patients weighing less than 45Kg (n=9) (713µGy.m² vs.81µGy.m², P = 0.008), even when comparing one 3D-RA with three 2D-SA (242µGy.m², respectively, p<0.008). 3D-RA was extremely useful for the assessment of conduits of univentricular hearts, tortuous branches of the pulmonary artery, and aorta relative to 2D-SA acquisitions.

Conclusions

The radiation dose of 3D-RA used in our institution was higher than those previously reported in the literature and this difference was more evident in children. This type of assessment is of paramount importance when starting to perform 3D-RA.     

Sudden cardiac death early after ST elevation myocardial infarction with and without severe left ventricular dysfunction

Introduction

There is high incidence of SCD in the early period following STEMI. We compared the temporal patterns and predictors of SCD amongst patients with LVEF ≤35% and LVEF >35%.

Methods

Data from STEMI patients was prospectively collected. SCD cases formed the study cohort and were categorized into 2 groups based on their LV function.

Results

There were 929 patients (mean age 55 ± 17 years) with a follow up of 41 ± 16 months. 154 pts (16.6%) had LVEF ≤35% (Group A, LVEF-29.9% ± 6%) and 775 pts had LVEF >35% (Group B, LVEF – 49% ± 14%). The two groups were similar with respect to sex distribution, age, prevalence of hypertension, and mean period of presentation. They differed in incidence of anterior wall MI (77.2% vs 55%), reperfusion (69% vs. 75%), prevalence of diabetes (50.6% vs 42%), and medication non-compliance (34% vs. 13%). The total SCD was 78 [Gp A, 25 (16.2%); Gp B, 53 (6.8%); p < 0.001]. The temporal cumulative SCD related mortality in the 2 groups was 1st month (8% vs. 4% p = 0.075), 3 months (14% vs. 5%, p < 0.001), 6 months (17% vs. 5%, p < 0.001), 1 year (18% vs. 6%, p < 0.001), at end of follow up (27% vs. 8%, p < 0.001). Multivariate predictors of SCD were medication compliance in the first month, and severe LV dysfunction with medication compliance beyond 1st month.

Conclusion

The incidence of SCD is high in first month after STEMI, irrespective of LV function. The number of SCD is higher in Group B patients. Algorithms to assess risk of SCD in early post STEMI period are urgently needed.     

The impact of atrial mechanical function on age‐dependent presentation of neurocardiogenic syncope

BackgroundThe contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive.HypothesisWe assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences.MethodsWe assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head‐up tilt test (HUTT).ResultsA total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m², p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05).ConclusionsPatients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.     

Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE)

Background

Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m²) the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group.

Objective

To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences.

Methods

4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3%) and non-obese (n = 3,105; 76.6%).

Results

There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67) and had a higher frequency of hypertension (75.2% vs. 57, 2%; p < 0.0001), diabetis mellitus (15.2% vs. 10.9%; p < 0.0001), dyslipidemia (59.5% vs 51.9%; p < 0.0001), family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023) and physical inactivity (71.4% vs. 52.9%, p < 0.0001). The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001), left atrium (3.97 vs. 3.72 cm; p < 0.0001) and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001). Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41). In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension.

Conclusion

Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese.     

Left Ventricular Synchrony and Function in Pediatric Patients with Definitive Pacemakers

Background

Chronic right ventricular pacing (RVP) induces a dyssynchronous contraction pattern, producing interventricular and intraventricular asynchrony. Many studies have shown the relationship of RVP with impaired left ventricular (LV) form and function.

Objective

The aim of this study was to evaluate LV synchrony and function in pediatric patients receiving RVP in comparison with those receiving LV pacing (LVP).

Methods

LV systolic and diastolic function and synchrony were evaluated in 80 pediatric patients with either nonsurgical or postsurgical complete atrioventricular block, with pacing from either the RV endocardium (n = 40) or the LV epicardium (n = 40). Echocardiographic data obtained before pacemaker implantation, immediately after it, and at the end of a mean follow-up of 6.8 years were analyzed.

Results

LV diastolic function did not change in any patient during follow-up. LV systolic function was preserved in patients with LVP. However, in children with RVP the shortening fraction and ejection fraction decreased from medians of 41% ± 2.6% and 70% ± 6.9% before implantation to 32% ± 4.2% and 64% ± 2.5% (p < 0.0001 and p < 0.0001), respectively, at final follow-up. Interventricular mechanical delay was significantly larger with RVP (66 ± 13 ms) than with LVP (20 ± 8 ms). Similarly, the following parameters were significantly different in the two groups: LV mechanical delay (RVP: 69 ± 6 ms, LVP: 30 ± 11 ms, p < 0.0001); septal to lateral wall motion delay (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0.0001); and, septal to posterior wall motion delay (RVP: 127 ± 33 ms, LVP: 58 ± 17 ms, p < 0.0001).

Conclusion

Compared with RV endocardium, LV epicardium is an optimal site for pacing to preserve cardiac synchrony and function.     

Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor-α-mRNA in isolated rat intrahepatic bile duct epithelial cells

AIM: To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor α-mRNA (TNF-α-mRNA) with cultured rat intrahepatic bile duct epithelial cells.METHODS: By using fluorescent, immunohistochemical and in situ hybridization techniques, the uptake of Escherichia coli LPS and expression of TNF-α-mRNA with isolated rat intrahepatic bile duct epithelial cells were observed with confocal laser scanning microscopy.RESULTS: Positive reactions to LPS were found in the cytoplasm of isolated intrahepatic bile duct epithelial cells after incubation with LPS for 15 min and the FITC fluorescent intensity against LPS was significantly higher than that of the controls (121.45 μFI/μm² ± 15.62 μFI/μm² vs 32.12 μFI/μm² ± 9.64 μFI/μm², P < 0.01). After incubation with LPS for 3 h, fluorescein isocyanate (FITC) fluorescent intensities of the expression of TNF-α-mRNA with fluorescent in situ hybridization in the cytoplasm and nuclei of the cultured bile duct epithelial cells were significantly higher than those of the controls (189.15 μFI/μm² ± 21.33 μFI/μm² vs 10.00 μFI/μm² ± 8.99 μFI/μm², 64.85 μFI/μm² ± 14.99 μFI/μm² vs 21.20 μFI/μm² ± 2.04 μFI/μm², respectively (P < 0.01)). The increase of FITC fluorescent intensity of TNF-α-mRNA expression in the cytoplasm peaked at 6 h after incubation (221.38 μFI/μm² ± 22.99 μFI/μm²). At various time points after incubation with LPS, the increase of fluorescent intensities of TNF-α-mRNA in the cytoplasm were much higher than those in the nuclei (P < 0.01).CONCLUSION: LPS can act on and enter into isolated intrahepatic bile duct epithelial cells and stimulate the expression of TNF-α-mRNA.     

Endocrine cells in the ileum of patients with irritable bowel syndrome

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm² in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.     

Inhibitory effects of rapamycin on the different stages of hepatic fibrosis

AIM: To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.METHODS: We performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL⁺/Rapa^- group (un-treated control, n = 4), the BDL⁺/Rapa⁺ group (treated 14 d after BDL, n = 8), the BDL⁺/Rapa⁺⁺ group (treated on the day after BDL, n = 8), and the BDL^-/Rapa^- group (un-treated, sham -operated control, n = 4). The BDL⁺/Rapa⁺ and BDL⁺/Rapa⁺⁺ groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin.RESULTS: The liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL⁺/Rapa⁺⁺group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL⁺/Rapa⁺⁺group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001).CONCLUSION: The results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.     

Validation of methods to assess potential biomarkers in pediatric patients with esophageal eosinophilia

AIM: To validate methods for determining mast cell density, extracellular major basic protein content, and presence of fibrosis in esophageal eosinophilia.METHODS: Twenty specimens with > 20 eosinophils/high-power field (hpf) classified as high eosinophil density (HE) and 20 specimens with < 5 eosinophils/hpf classified as low esophageal density (LE) were identified. All 40 specimens underwent immunohistochemical staining and trichrome staining. Mast cell density, extracellular major basic protein (MBP) density, and presence of subepithelial fibrosis were assessed in a standardized manner. All specimens were evaluated by two separate observers and by a single observer on two separate occasions to evaluate reproducibility of the methods.RESULTS: A strong inter-observer correlation was noted for both peak and mean mast cell counts (r = 0.725, P < 0.0001 and r = 0.823, P < 0.0001). A strong intra-observer correlation also was noted for both peak and mean mast cell counts (r = 0.752, P < 0.0001 and r = 0.878, P < 0.0001). A very strong inter-observer correlation was noted for both peak (τ = 0.867, P < 0.0001) and mean extracellular MBP densities (r = 0.925, P < 0.0001). A very strong intra-observer correlation was noted for both peak (τ = 0.875; P < 0.0001) and mean extracellular MBP densities (r = 0.956, P < 0.0001). Excellent inter-rater reliability was found for fibrosis (κ = 0.887). Mast cell and MBP densities, as well as presence of fibrosis, were significantly increased in HE vs LE. The HE group had significantly higher intraepithelial mast cell peak (29.35 ± 21.61 vs 12.45 ± 8.26, P = 0.002) and mean (19.84 ± 15.81 vs 6.35 ± 4.5, P = 0.001) densities than the LE group. The HE group had significantly higher peak extracellular MBP (2.35 ± 0.67 vs 0.45 ± 0.61, P < 0.001) and mean extracellular MBP (1.95 ± 0.76 vs 0.20 ± 0.29, P < 0.0001) densities than the LE group. Seventy-three percent of patients with HE (11/15) had fibrosis, whereas only 10% of patients with LE (1/10) had fibrosis (P < 0.01). MBP performed the best in predicting classification of HE vs LE, with mean MBP demonstrating 100% sensitivity and 95% specificity at the optimal cut point.CONCLUSION: This study provides methodology and proof-of-concept for future evaluation of these biomarkers for differentiating esophageal eosinophilic diseases such as reflux esophagitis and eosinophilic esophagitis.     

Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p < 0.01 and p < 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (±3.71) × 10⁶ neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 10⁶ neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.