Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Do left ventricular assist device (LVAD) bridge-to-transplantation outcomes predict the results of permanent LVAD implantation?

Implantable left ventricular assist devices (LVADs) were designed for permanent implant, but we began their use for bridge-to-transplant (BTTx) to study their safety and effectiveness. We review our experience in order to compare the BTTx lessons learned with the outcomes and goals of permanent implants. From December 1991 until January 2002, 264 patients received 277 LVADs for BTTx. We analyzed temporal trends in pre-LVAD patient factors and device-specific time-related complications. Survival to transplant was 69%. Adverse event analysis demonstrated a high risk of infections (0.56, 1.28, and 1.88 per patient at 30 days and 3 and 6 months). HeartMate devices were more prone to infection than Novacor devices ( p < 0.0001). Cerebral infarctions occurred less commonly than infections (0.15, 0.25, 0.30 at 30 days and 3 and 6 months), were more common in Novacor than HeartMate ( p = 0.0001), and were decreased by the new Novacor Vascutek conduit ( p = 0.07), but these were still slightly higher than the HeartMate ( p = 0.04). Device failures occurred in 21 instances (all but one were in HeartMate devices [ p = 0.04 vs Novacor]), but have significantly decreased ( p < 0.0001) in HeartMate since 1998. Infections and device durability limit the chronic use of the HeartMate device, but device failures are decreasing. Novacor has fewer problems with infection and durability, and the new Vascutek conduit will reduce, but not eliminate, strokes

CT-based Diagnosis of Diffuse Coronary Artery Disease on the Basis of Scaling Power Laws

Diffuse coronary artery disease (CAD) without severe segmental stenosis is a substrate for plaque rupture (1–3). Hence, diffuse CAD is associated with unstable coronary syndromes or myocardial infarctions, which have significant clinical implications (4–6). In contrast to severe segmental stenosis, diffuse CAD is difficult to diagnose angiographically given the absence of a “normal” reference vessel (7). Although intravascular ultrasonography (US) has been used to visualize plaque burden in the vessel wall for the diagnosis of diffuse CAD (8,9), it is an interventional tool that requires an invasive procedure. Hence, there is a need for a noninvasive method with which to quantify diffuse CAD. There have been previous attempts at applying global morphologic features of the coronary artery tree in the assessment of diffuse CAD (7,10,11). Several experimental reports have also documented a direct relationship between coronary artery lumen size and heart weight or distal myocardial bed size (12–18) and between myocardial mass and the cumulative length of the arterial branches that perfuse the region (18,19). On the basis of the principle of minimum energy, we have recently deduced scaling power laws between length and volume and between length and cross-sectional area in an entire tree structure of various organs in different species (20,21). In particular, these scaling power laws have a self-similar nature (20–22), which implies that they can be clinically applied to a partial tree (eg, an epicardial coronary artery tree obtained with angiography, computed tomography [CT], or magnetic resonance [MR] imaging). Hence, we hypothesized that the length-volume scaling power law (ie, scaling relation and power law distribution for the sum of intravascular lengths and volumes in a tree) provides the signature of “normal” vasculature and deviations from which can be used to quantify the extent of diffuse CAD. The purpose of this study was to provide proof of concept for a diagnostic method to assess diffuse CAD on the basis of coronary CT angiography

CT-based Diagnosis of Diffuse Coronary Artery Disease on the Basis of Scaling Power Laws

Diffuse coronary artery disease (CAD) without severe segmental stenosis is a substrate for plaque rupture (1–3). Hence, diffuse CAD is associated with unstable coronary syndromes or myocardial infarctions, which have significant clinical implications (4–6). In contrast to severe segmental stenosis, diffuse CAD is difficult to diagnose angiographically given the absence of a “normal” reference vessel (7). Although intravascular ultrasonography (US) has been used to visualize plaque burden in the vessel wall for the diagnosis of diffuse CAD (8,9), it is an interventional tool that requires an invasive procedure. Hence, there is a need for a noninvasive method with which to quantify diffuse CAD. There have been previous attempts at applying global morphologic features of the coronary artery tree in the assessment of diffuse CAD (7,10,11). Several experimental reports have also documented a direct relationship between coronary artery lumen size and heart weight or distal myocardial bed size (12–18) and between myocardial mass and the cumulative length of the arterial branches that perfuse the region (18,19). On the basis of the principle of minimum energy, we have recently deduced scaling power laws between length and volume and between length and cross-sectional area in an entire tree structure of various organs in different species (20,21). In particular, these scaling power laws have a self-similar nature (20–22), which implies that they can be clinically applied to a partial tree (eg, an epicardial coronary artery tree obtained with angiography, computed tomography [CT], or magnetic resonance [MR] imaging). Hence, we hypothesized that the length-volume scaling power law (ie, scaling relation and power law distribution for the sum of intravascular lengths and volumes in a tree) provides the signature of “normal” vasculature and deviations from which can be used to quantify the extent of diffuse CAD. The purpose of this study was to provide proof of concept for a diagnostic method to assess diffuse CAD on the basis of coronary CT angiography

Bench repair of donor aortic valve with minimal access orthotopic heart transplantation.

While the number of people waiting heart transplantation increases, the number of organ donors decreases. This shrinking donor pool has prompted reassessment of donor selection for heart transplantation. Bench repair of a donor aortic valve was performed before minimal access orthotopic heart transplantation. Aortic insufficiency in the structurally normal tricuspid aortic valve was due to annular dilatation and was corrected with subcommissural annular plication. The postoperative period was uneventful. Follow-up at 4.5 years showed good results and no evidence of aortic regurgitation. (Ann Thorac Surg 2005;80:313–5

Trans1catheter mitral valve replacement with the NaviGate stent in a preclinical model

Aims: The aim of this study was to test the feasibility of transcatheter mitral valve implantation of the NaviGate device in acute and chronic preclinical models. Methods and results: We evaluated NaviGate valved stent implantation in the mitral position in an acute swine model (n=24, 645 days) through three different approaches - transatrial, transapical, and transseptal - and in a chronic swine model (n=12, >10 days) through a transatrial approach. The NaviGate implantation procedures were successful in 83% of the acute model studies (n=20) and 83% of the chronic model studies (n=10). Echocardiographic assessment showed low gradient across the valved stent (mean gradient <3 mmHg) and the left ventricular outflow tract (mean gradient <6 mmHg). Post implantation, there was no mitral regurgitation (MR) in 75% (n=15) of the acute studies and mild MR in 25% (n=5). In the chronic model, there was no MR in 60% (n=6) and mild MR in 40% (n=4). The implantation procedure was aborted in four acute studies due to inferior vena cava injury and in two chronic studies due to prosthesis-annulus mismatch. Conclusions: In preparation for clinical application, transcatheter mitral implantation of the NaviGate valved stent was proved feasible in acute and chronic preclinical models. The three featured delivery approaches are of particular value for high-risk patients with functional MR and challenging vascular access

Transcatheter Tricuspid Valve Implantation of NaviGate Bioprosthesis in a Preclinical Model

Patients with isolated functional or recurrent tricuspid regurgitation are often denied surgery because they are considered to be at high risk. Transcatheter valve therapy provides a less invasive alternative for tricuspid regurgitation associated with right heart failure. We have evaluated the feasibility of transcatheter tricuspid valve implantation of the NaviGate valved stent in a long-term swine model. The valved stent was successfully implanted through transjugular and transatrial approaches on the beating heart with excellent hemodynamic and valve performance. No conduction disturbance or coronary obstruction was observed. This technology could provide an alternative treatment for patients who are at high surgical risk with severe tricuspid regurgitation and compromised right ventricular function