The role of transforming growth factor-beta in Marfan syndrome

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fi brillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact onthe tissue homeostasis of microfibrils, and elastic fi bers. We also investigate current data onthe extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Togetherthese factors, by the destruction of the connective tissue fi bers, may play an important role inthe development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for thetreatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease

Bentall procedure: quarter century of clinical experiences of a single surgeon

BACKGROUND: We retrospectively analyzed 25 years of experiences with the button Bentall procedure in patients with aortic root pathologies. Even though this procedure has become widespread, there are only a few very long term follow-ups available in the clinical literature, especially regarding single surgeon results. METHODS: Between 1988 and 2013, a total of 147 patients underwent the Bentall procedure by the same surgeon. Among them there were 62 patients with Marfan syndrome. At the time of the surgery the mean age was 46.5 +/- 17.6 years. The impact of surgical experience on long-term survival was evaluated using a cumulative sum analysis chart. RESULTS: The Kaplan-Meier estimated overall survival rates for the 147 patients were 91.8 +/- 2.3 %, 84.3 +/- 3.1 %, 76.3 +/- 4.9 % and 59.5 +/- 10.7 % at 1,5,10 and 20 years, respectively. Multivariate Cox regression analysis identified EuroSCORE II over 3 % (OR 4.245, 95 % CI, 1.739-10.364, p = 0.002), acute indication (OR 2.942, 95 % CI, 1.158-7.480, p = 0.023), use of deep hypothermic circulatory arrest (OR 3.267, 95 % CI, 1.283-8.323, p = 0.013), chronic kidney disease (OR 6.865, 95 % CI, 1.339-35.189, p = 0.021) and early complication (OR 3.134, 95 % CI, 1.246-7.883, p = 0.015) as significant risk factors for the late overall death. The survival rate for freedom from early complication was 94.3 +/- 2.2 %, 88.0 +/- 3.3 %, 82.9 +/- 4.7 % and 69.2 +/- 8.4 % at 1,5,10 and 20 years. The main pathological findings of the aortic wall were cystic medial degeneration in 75 %, fibrosis in 6 %, atherosclerosis in 13 % and no pathological alteration in 6 % of the samples. The overall survival rate was significantly lower in patients operated in first 15 years compared to patients operated in the last decade (log-rank p = 0.011). CONCLUSION: According to our long-term follow-up the Bentall operation provides an appropriate functional result by resolving the lesions of the ascending aorta. Based on our results, 25-30 operations done is necessary to gain such a level of confidence and experince to aquire better results on long-term survival. In addition, we discussed that there were no co-morbidities affecting on the survival of Marfan patients and prophylactic aortic root replacement ensures a longer survival among patients with Marfan syndrome

Anatomical characteristics of the left atrium and left atrial appendage in relation to the risk of stroke in patients with versus without atrial fibrillation

Background: The left atrial appendage (LAA) has been regarded as an important source of cardiac thrombus formation and appears important in the contribution to thromboembolism in patients with atrial fibrillation (AF). Our aim was to evaluate the relationship between LAA morphology and previous stroke or transient ischemic attack in 2 large and distinct patient cohorts with and without known AF. Methods: The study population consisted of patients with and without drug-refractory AF who underwent computed tomography before transcatheter AF ablation or clinically indicated for suspected coronary artery disease. The computed tomography data were used for volumetric assessment of the left atrium and LAA and to determine LAA morphology. The LAA was classified by 3 readers in consensus as chicken wing, swan, cauliflower, or windsock, based on predefined morphology classification criteria. Results: In total, 1813 patients (mean age 59 +/- 11 years, 42% female) who underwent computed tomography were included in this analysis (908 patients with AF and 905 patients without known AF). Swan LAA morphology was independently associated with prior stroke/transient ischemic attack in the overall study population (odds ratio, 3.40, P<0.001), and in patients with (odds ratio, 2.88, P=0.012) and without known AF (odds ratio, 3.96, P=0.011). Conclusions: Swan morphology of the LAA is independently associated with prior stroke or transient ischemic attack in patients with known AF, as well as in patients not previously diagnosed with AF.Cardiolog

Coronary computed tomography angiography investigation of the association between left main coronary artery bifurcation angle and risk factors of coronary artery disease

To explore the association between the left main coronary artery bifurcation angle and common atherosclerotic risk factors with regard to the development of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA). A retrospective review of 196 CCTA cases (129 males, 67 females, mean age 58 ± 10.5 years) was conducted. The bifurcation angle between the left anterior descending (LAD) and left circumflex (LCx) was measured on two-dimensional (2D) and three-dimensional (3D) reconstructed images and the type of plaque and degree of lumen stenosis was assessed to determine the disease severity. An association between bifurcation angle and patient risk factors [gender, body mass index (BMI), hypertension, cholesterol, diabetes, smoking and family history] of CAD was also assessed to demonstrate the relationship between these variables. The mean bifurcation angle between the LAD and LCx was 79.40° ± 22.97°, ranging from 35.5° to 178°. Gender and BMI were found to have significant associations with bifurcation angle. Males were at 2.07-fold greater risk of having a >80° bifurcation angle and developing CAD than females (P = 0.003), and patients with high BMI (>25 kg/m2) were 2.54-fold more likely to have a >80° bifurcation angle than patients with a normal BMI (P = 0.001) and thus were at greater risk of developing CAD. There is a direct relationship between the left main coronary artery bifurcation angle and patient gender and BMI. Measurement of the bifurcation angle should be incorporated into clinical practice to identify patients at high risk of developing CAD

Possible extracardiac predictors of aortic dissection in Marfan syndrome

BACKGROUND: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. METHODS: A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-beta (TGF-beta) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. RESULTS: Among patients with aortic dissection, TGF-beta serum level was elevated (43.78 +/- 6.51 vs. 31.64 +/- 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2alpha = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. CONCLUSIONS: We found three easily measurable parameters (striae atrophicae, TGF-beta serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR

Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation

Introduction There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. Methods AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. Results In total, 561 AF patients (61.9 +/- 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. Conclusion The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.Cardiovascular Aspects of Radiolog

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection