Case report: First-in-human combined low-dose whole-heart irradiation and high-dose stereotactic arrhythmia radioablation for immunosuppressive refractory cardiac sarcoidosis and ventricular tachycardia.

Background: Cardiac sarcoidosis is associated with heart failure, conduction abnormalities, and life-threatening arrhythmias including ventricular tachycardia (VT). Radiotherapy has been suggested as a treatment for extra-cardiac sarcoidosis in patients refractory to immunomodulatory treatment. Methods: The effectiveness and safety of low-dose whole-heart radiotherapy for therapy refractory cardiac sarcoidosis were evaluated in a pre- and post-intervention case report comparing the 54 months before and after treatment. Immunomodulatory low-dose whole-heart irradiation as sarcoidosis treatment consisted of a 2 × 2 Gy scheme. Additionally, high-dose single-fraction stereotactic arrhythmia radioablation of 1 × 20 Gy was applied to the pro-arrhythmic region to manage the ventricular tachycardia episodes. Cardiac sarcoidosis disease activity was measured by hypermetabolic areas on repeated fluorodeoxyglucose ([18F]FDG)-PET/computed tomography (CT) scans and by evaluating changes in ventricular tachycardia episodes before and after treatment. Results: One patient with therapy refractory progressive cardiac sarcoidosis and recurrent ventricular tachycardia was treated. The cardiac sarcoidosis disease activity showed a durable regression of inflammatory disease activity from 3 months onwards. The [18F]FDG-PET/CT scan at 54 months did not show any signs of active cardiac sarcoidosis, and a state of remission was achieved. The number of sustained VT episodes was reduced by 95%. We observed that the development of moderate aortic valve regurgitation was likely irradiation-related. No other irradiation-related adverse events occurred, and the left ventricular ejection fraction remained stable. Conclusion: We report here for the first time on the beneficial and lasting effects of combined immunomodulatory low-dose whole-heart radiotherapy and high-dose stereotactic arrhythmia radioablation in a patient with therapy refractory cardiac sarcoidosis and recurrent VT.

SCN5A overlap syndromes: An open-minded approach.

SCN5A overlap syndromes are clinical entities that express a phenotype combining aspects of different canonical SCN5A-related arrhythmia syndromes or a variable arrhythmic phenotype among individuals carrying the same SCN5A mutation. Here we review the literature addressing SCN5A overlap syndromes as well as the principal mechanisms currently proposed. Among others, a multifactorial determination encompassing an interaction between SCN5A variant(s), other genetic polymorphisms, and possibly environmental factors seems the most plausible hypothesis.

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES: We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS: We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS: The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS: We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results.

Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery.

Here we provide the correlation among different carotid ultrasound (US) variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray-Weale classification (GW) and measured by the greyscale median (GSM), a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present); CEUS_B a three-point scale (increasing IPNV from 1 to 3); CEUS_C a four-point scale (increasing IPNV from 0 to 3). We have also implemented a new simple quantification method derived from region of interest (ROI) signal intensity ratio as assessed by QLAB software. Further information is available in "Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016) [1].

Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis.

BACKGROUND: Currently the most widely accepted predictor of stroke risk in patients with carotid atherosclerosis is the degree of stenoses. Plaque echogenicity on ultrasound imaging (US) and intraplaque neovascularization (IPNV) are becoming recognized as factors of plaque vulnerability. Aim of the study was to investigate the correlation between the echogenicity of the carotid atherosclerosis by standard US and the degree of IPNV by contrast enhanced US (CEUS). METHODS: We recruited 45 consecutive subjects with an asymptomatic ≥50% carotid artery stenoses. Carotid plaque echogenicity at standard US was visually graded according to Gray-Weale classification (GW) and measured by the grayscale median (GSM), a semi-automated measurement performed by Adobe Photoshop©. On CEUS imaging IPNV was graded by different point scales according to the visual appearance of contrast within the plaque as follows: CEUS_A (1=absent; 2=present); CEUS_B (increasing IPNV from 1 to 3); and CEUS_C (increasing IPNV from 0 to 3). RESULTS: The correlation between echogenicity by GW and IPNV grading was as follows: CEUS_B (-0.130 p .423), CEUS_C (-0.108, p .509), CEUS_A (0.021, p .897). The correlation between echogenicity by GSM measurement and IPNV was as follows: using a CEUS_A (-0.125, p .444), CEUS_C (-0.021, p .897) (0.005, p .977). No correlation was found statistically significant. CONCLUSION: Our results display that there is no significant correlation between plaque echogenicity and IPNV. The small sample number and the multifaceted pathophysiology of the atherosclerotic plaque may explain the absence of statistically significantly correlation. Curtailing vulnerability explanation to either IPNV or echolucency may be misleading.

Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland) after smoking bans in enclosed public places--No Smoke Pub Study.

BACKGROUND: Second-hand smoke increases the risk of acute myocardial infarction. Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This offered the opportunity to assess the long-term impact of a smoking ban on the incidence of ST-elevation myocardial infarctions (STEMI) compared with a population where the law was not yet implemented. METHODS: We assessed the incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years before and after the ban application in CT and in Canton Basel City (CBC), where this law was not yet applied. Data were obtained from the codified hospital registry (ICD-10 codes). RESULTS: In CT, the mean incidence of STEMI admissions during the 3 pre-ban years (123.7) was significantly higher than the incidence of admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P <.024). Analysing population subsets, a post-ban reduction was observed among ≥65-year-old people of both sexes in each of the 3 post-ban years and in the <65-year age group during the first post-ban year (P = 0.02). Conversely, the mean incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same period. However, a significant long-term reduction in STEMI admissions was observed in CBC among the male group with ≥65 years (P < 0.01). CONCLUSION: Our work suggests a significant impact of the smoke-free policy on the number of annual STEMI. Specific population subsets (i.e. ≥65-year-old females) were particularly affected by the smoking ban, showing a significant reduction in STEMI hospitalizations.

Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome.

OBJECTIVES: The study assessed whether heart rate (HR) reduction following an exercise stress test (ExStrT), an easily quantifiable marker of vagal reflexes, might identify high- and low-risk long QT syndrome (LQTS) type 1 (LQT1) patients. BACKGROUND: Identification of LQTS patients more likely to be symptomatic remains elusive. We have previously shown that depressed baroreflex sensitivity, an established marker of reduced vagal reflexes, predicts low probability of symptoms among LQT1. METHODS: We studied 169 LQTS genotype-positive patients < 50 years of age who performed an ExStrT with the same protocol, on and off ß-blockers including 47 South African LQT1 patients all harboring the KCNQ1-A341V mutation and 122 Italian LQTS patients with impaired (I(Ks)-, 66 LQT1) or normal (I(Ks)+, 50 LQT2 and 6 LQT3) I(Ks) current. RESULTS: Despite similar maximal HR and workload, by the first minute after cessation of exercise the symptomatic patients in both I(Ks)- groups had a greater HR reduction compared with the asymptomatic (19 ± 7 beats/min vs. 13 ± 5 beats/min and 27 ± 10 beats/min vs. 20 ± 8 beats/min, both p = 0.009). By contrast, there was no difference between the I(Ks)+ symptomatic and asymptomatic patients (23 ± 9 beats/min vs. 26 ± 9 beats/min, p = 0.47). LQT1 patients in the upper tertile for HR reduction had a higher risk of being symptomatic (odds ratio: 3.28, 95% confidence interval: 1.3 to 8.3, p = 0.012). CONCLUSIONS: HR reduction following exercise identifies LQT1 patients at high or low arrhythmic risk, independently of ß-blocker therapy, and contributes to risk stratification. Intense exercise training, which potentiates vagal reflexes, should probably be avoided by LQT1 patients.