Clinical Relevance of Baseline TCP in Transcatheter Aortic Valve Replacement

AIMS: To investigate the influence of baseline thrombocytopenia (TCP) on short-term and long-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 732 consecutive patients with severe, symptomatic aortic stenosis undergoing TAVR from January 2012 to December 2015 were included. Primary outcomes of interest were the relationship of baseline TCP with 30-day and 1-year all-cause mortality. Secondary outcomes of interest were procedural complications and in-hospital mortality in the same subgroups. The prevalence of TCP (defined as platelet count <150 × 109/L) at baseline was 21.9%, of whom 4.0% had moderate/severe TCP (defined as platelet count <100 × 109/L). Compared to no or mild TCP, moderate/severe TCP at baseline was associated with a significantly higher 30-day mortality (23.3% vs 2.3% and 3.1%, respectively; P<.001) and 1-year mortality (40.0% vs 8.3% and 13.4%, respectively; P<.001). In Cox regression analysis, moderate/severe baseline TCP was an independent predictor of 30-day and 1-year mortality (hazard ratio [HR], 13.18; 95% confidence interval [CI], 4.49-38.64; P<.001 and HR, 5.90; 95% CI, 2.68-13.02; P<.001, respectively). CONCLUSIONS: In conclusion, baseline TCP is a strong predictor of mortality in TAVR patients, possibly identifying a specific subgroup of frail patients; therefore, it should be taken into account when addressing TAVR risk

Assessment of the Severity of Paravalvular Regurgitation and its Role on Survival After Transcatheter Aortic Valve Replacement

Background: To evaluate the impact of various measurements of paravalvular regurgitation (PVR) on survival after transcatheter aortic valve replacement (TAVR). PVR can be difficult to grade and both its incidence and impact on survival may be decreasing as TAVR evolves. Methods: This retrospective study included 911 patients undergoing TAVR in two institutions. PVR was graded according to the 3-grade scheme proposed by the guidelines (PVR grade), and subsequently grade 2 and 3, and grade 0 and 1 were lumped together. PVR was also graded as a composite score (PVR score), based on 6 commonly used metrics. PVR grade, PVR score and its six individual components were tested against the risk of both 1-year and longer term mortality after TAVR. Results: Patients with moderate/severe PVR had a higher Society of Thoracic Sugeons (STS) score, higher levels of serum creatinine and larger left atria compared to patients with none/mild PVR. Moderate/severe PVR was more frequent with self-expandable and larger valves. After adjusting for American College of Cardiology (ACC) TAVR risk score, neither PVR grade, PVR score nor its six components were associated with an increased risk of mortality at 1-year (severe PVR adjusted HR: 0.75, 95% Confidence Interval [CI]: 0.19, 3.01, p = 0.50). However, intervention for clinically severe PVR increased the risk of mortality by more than 7-fold (adjusted hazard ratio [HR]: 7.6, 95% CI: 2.4, 23.5, p < 0.0001). Conclusions: In the contemporary era, moderate-severe PVR is uncommon. However, re-intervention for PVR portends a poor prognosis. This highlights the crucial importance of clinical judgment over imaging alone

Clinical applications of transesophageal echocardiography

Detailed formal protocol with illustrations and extensive bibliography.UT Southwestern--Internal Medicin

Pre-operative evaluations of the risk of cardiac events in patients undergoing non-cardiac surgery

Detailed formal protocol with illustrations and extensive bibliography.UT Southwestern--Internal Medicin

Clinical assessment of myocardial viability

Detailed formal protocol with illustrations and extensive bibliography.UT Southwestern--Internal Medicin

The Evolving Concept of Secondary Mitral Regurgitation Phenotypes

Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response

Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1

Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation or β-cell regeneration. The pancreas, not the liver, is the ideal organ for islet regeneration, because it is the natural milieu for islets. Since islet mass is known to increase during obesity and pregnancy, the concept of stimulating pancreatic islet regeneration in vivo is both rational and physiologic. This paper proposes a novel approach in which non-viral gene therapy is targeted to pancreatic islets using ultrasound targeted microbubble destruction (UTMD) in a non-human primate model (NHP), the baboon. Treated baboons received a gene cocktail comprised of cyclinD2, CDK, and GLP1, which in rats results in robust and durable islet regeneration with normalization of blood glucose, insulin, and C-peptide levels. We were able to generate important preliminary data indicating that gene therapy by UTMD can achieve in vivo normalization of the intravenous (IV) glucose tolerance test (IVGTT) curves in STZ hyperglycemic-induced conscious tethered baboons. Immunohistochemistry clearly demonstrated evidence of islet regeneration and restoration of β-cell mass

Clinical and Echocardiographic Outcomes of Transcatheter Tricuspid Valve Interventions: A Systematic Review and Meta-Analysis.

peer reviewedBACKGROUND: Medically managed tricuspid regurgitation (TR) has detrimental outcomes. Transcatheter tricuspid valve interventions (TTVIs) represent an alternative to surgery in high-risk patients; however, only early experiences exist. AIM: The aim of this study was to analyze the clinical and echocardiographic outcomes of TTVI. METHODS: MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to June 2021. Studies reporting data on outcome post-TTVIs were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was all-cause mortality at 30-day and 1-year post-TTVI. RESULTS: Out of 2,718 studies, 27 were included. Notably, 30-day and 1-year all-cause mortalities were 5% (95% confidence interval [CI]: 4-8%, p < 0.001) and 25% (95% CI: 12-45%, p = 0.016). Procedural success was associated with a 58% risk reduction in 1-year mortality vs. lack thereof (odds ratio 0.42, 95% CI: 0.27-0.66, p < 0.001). TTVI is associated with a significant reduction in TR severity (TR EROA, mean difference [MD] 0.31 cm(2); 95% CI: 0.23-0.39 cm(2), p < 0.001; regurgitant volume, MD 23.54 ml; 95% CI: 17.4-29.68 ml, p = 0.03) and increase in forward stroke volume (FSV, MD 3.98 ml; 95% CI: 0.11-7.86 ml, p = 0.04). CONCLUSION: TTVI significantly reduces TR severity and increases FSV and is associated with improved survival at 1 year compared with patients without procedural success. Long-term outcomes compared with medical therapy await the results of ongoing pivotal trials; nonetheless, TTVIs appear to be a promising alternative to surgery for TR

Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model

Background Non-human primate (NHP) diabetic models using chemical ablation of b-cells with STZ have been achieved by several research groups. Chemotherapeutic STZ could lead to serious adverse events including nephrotoxicity, hepatotoxicity, and mortality. Methods We implemented a comprehensive therapeutic strategy that included the tether system, permanent indwelling catheter implants, an aggressive hydration protocol, management for pain with IV nubain and anxiety with IV midazolam, moment-by-moment monitoring of glucose levels post-STZ administration, and continuous intravenous insulin therapy. Results A triphasic response in blood glucose after STZ administration was fully characterized. A dangerous hypoglycemic phase was also detected in all baboons. Other significant findings were hyperglycemia associated with low levels of plasma leptin, insulin and C-peptide concentrations, hyperglucagonemia, and elevated non-esterified fatty acids (NEFA) concentrations. Conclusions We successfully induced frank diabetes by IV administering a single dose of pharmaceutical-grade STZ safely and without adverse events in conscious tethered baboons

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options