Episode Care Costs Following Catheter-Directed Reperfusion Therapies for Pulmonary Embolism: A Literature-Based Comparative Cohort Analysis.

This analysis aimed to estimate 30-day episode care costs associated with 3 contemporary endovascular therapies indicated for treatment of pulmonary embolism (PE). Systematic literature review was used to identify clinical research reporting costs associated with invasive PE care and outcomes for ultrasound-accelerated thrombolysis (USAT), continuous aspiration mechanical thrombectomy (CAMT), and volume-controlled-aspiration mechanical thrombectomy (VAMT). Total episode variable care costs were defined as the sum of device costs, variable acute care costs, and contingent costs. Variable acute care costs were estimated using methodology sensitive to periprocedural and post-procedural resource allocation unique to the 3 therapies. Contingent costs included expense for thrombolytics, post-procedure bleeding events, and readmissions through 30 days. Through February 28, 2023, 70 sources were identified and used to inform estimates of 30-day total episode variable costs. Device costs for USAT, CAMT, and VAMT were the most expensive single component of total episode variable costs, estimated at $5,965, $10,279, and $11,901, respectively. Costs associated with catheterization suite utilization, intensive care, and hospital length of stay, along with contingent costs, were important drivers of total episode costs. Total episode variable care costs through 30-days were $19,146, $20,938, and $17,290 for USAT, CAMT, and VAMT, respectively. In conclusion, estimated total episode care costs following invasive treatment for PE are heavily influenced by device expense, in-hospital care, and post-acute care complications. Regardless of device cost, strategies that avoid thrombolytics, reduce the need for ICU care, shorten length of stay, and reduce post-procedure bleeding and 30-day readmissions contributed to the lowest episode costs.

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

BACKGROUND: Evidence supporting interventional pulmonary embolism (PE) treatment is needed. AIMS: We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. METHODS: FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. RESULTS: Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001).  Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

Percutaneous mechanical thrombectomy in a real-world pulmonary embolism population: Interim results of the FLASH registry.

OBJECTIVES: The FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH) is a prospective multi-center registry evaluating the safety and effectiveness of percutaneous mechanical thrombectomy for treatment of pulmonary embolism (PE) in a real-world patient population (NCT03761173). This interim analysis reports outcomes for the first 250 patients enrolled in FLASH. BACKGROUND: High- and intermediate-risk PEs are characterized by high mortality rates, frequent readmissions, and long-term sequelae. Mechanical thrombectomy is emerging as a front-line therapy for PE that enables immediate thrombus reduction while avoiding the bleeding risks inherent with thrombolytics. METHODS: The primary endpoint is a composite of major adverse events (MAE) including device-related death, major bleeding, and intraprocedural device- or procedure-related adverse events at 48 h. Secondary endpoints include on-table changes in hemodynamics and longer-term measures including dyspnea, heart rate, and cardiac function. RESULTS: Patients were predominantly intermediate-risk per ESC guidelines (6.8% high-risk, 93.2% intermediate-risk). There were three MAEs (1.2%), all of which were major bleeds that resolved without sequelae, with no device-related injuries, clinical deteriorations, or deaths at 48 h. All-cause mortality was 0.4% at 30 days, with a single death that was unrelated to PE. Significant on-table improvements in hemodynamics were noted, including an average reduction in mean pulmonary artery pressure of 7.1 mmHg (22.2%, p < 0.001). Patient symptoms and cardiac function improved through follow-up. CONCLUSIONS: These interim results provide preliminary evidence of excellent safety in a real-world PE population. Reported outcomes suggest that mechanical thrombectomy can result in immediate hemodynamic improvements, symptom reduction, and cardiac function recovery.

Supraclavicular Subclavian access for Sapien Transcatheter aortic valve replacement- a novel approach.

BACKGROUND: Within the trans-subclavian approach, procedural techniques can vary widely, and reported access generally refers to an infraclavicular axillary approach. We describe and report the use of a novel supraclavicular true subclavian approach for transcatheter aortic valve replacement (TAVR) exclusively for implantation of Sapien 3 valves. CASE PRESENTATION: We report our first five consecutive patients undergoing TAVR with a Sapien 3 valve using a standardized subclavian approach at a single center. In-hospital and 30-day complications were reported. The use of this approach resulted in successful implantation in 100% of patients in a safe manner with 0% mortality, stroke, and vascular injury during hospitalization and at 30 day follow-up. The in-hospital pacemaker implantation rate was 20%. The average length of stay was 3 days. CONCLUSIONS: TAVR with Sapien implant can be safely performed with a standardized supraclavicular subclavian approach in patients with unfavorable femoral access.

Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound.

OBJECTIVES: This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin. BACKGROUND: Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown. METHODS: In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period. RESULTS: Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non-warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 0.06; p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non-warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003). CONCLUSIONS: Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

Coronary atheroma progression rates in men and women following high-intensity statin therapy: A pooled analysis of REVERSAL, ASTEROID and SATURN.

BACKGROUND AND AIMS: High-intensity statin therapy (HIST) reduces cardiovascular events, however, sex-related differences in treatment effects are not well characterized. METHODS: A patient-level post hoc pooled analysis of 3 randomized trials utilizing serial coronary intravascular ultrasound was undertaken, testing the anti-atherosclerotic effects of HIST in coronary disease patients. Sex-related differences in changes (Δ) in coronary percent atheroma volume (PAV) were ascertained following 18-24 months of HIST (atorvastatin 80 mg or rosuvastatin 40 mg daily), and further characterized according to on-treatment lipid and lipoprotein levels. RESULTS: In women (n = 451) compared with men (n = 1190), on-treatment levels of LDL-C (68 ± 24 vs. 67 ± 22 mg/dl, p=0.62) and apoB (77 ± 23 vs. 76 ± 20 mg/dL, p=0.51) were similar; levels of HDL-C (53 ± 12 vs. 47 ± 11 mg/dl, p < 0.001), apoA1 (154 ± 26 vs. 140 ± 24 mg/dl, p < 0.001), triglycerides [122 (95, 158) vs. 114 (89, 154) mg/dl, p=0.012] and CRP [1.7 (0.9, 3.8) vs. 1.1 (0.6, 2.7) mg/l, p < 0.001] were higher; while the total cholesterol/HDL-C (TC/HDL-C) ratio was lower (2.9 ± 0.8 vs. 3.1 ± 0.8, p < 0.001). Compared with men, women harbored significantly lower baseline PAV (34.8 ± 8.7 vs. 38.3 ± 8.8%, p < 0.001), yet demonstrated significantly greater PAV regression (ΔPAV -1.07 ± 0.26 vs. -0.66 ± 0.23%, p=0.02). When achieved on-treatment levels of LDL-C were <64 mg/dl, apoB <73 mg/dl, non-HDL-C <88.8 mg/dl, and TC/HDL-C <2.99, women demonstrated significantly greater PAV regression than men. Multivariable analysis revealed female sex to independently associate with PAV regression (coefficient -0.66, p=0.02). CONCLUSIONS: Women demonstrate greater degrees of coronary plaque regression compared with men following long-term HIST, especially in the setting of lower achieved atherogenic lipoprotein levels.

Implications of Total to High-Density Lipoprotein Cholesterol Ratio Discordance With Alternative Lipid Parameters for Coronary Atheroma Progression and Cardiovascular Events.

The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio may quantify atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apolipoprotein B (apoB). We analyzed pooled data from 9 trials involving 4,957 patients with coronary artery disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and 2-year major adverse cardiovascular event (MACE) rates when TC/HDL-C levels were discordant with LDL-C, non-HDL-C, and apoB. Discordance was investigated when lipid levels were stratified by

Regression of coronary atheroma with statin therapy.

PURPOSE OF REVIEW: This article reviews coronary atheroma regression with statin therapy. RECENT FINDINGS: Unlocking the mechanisms of atherogenesis and plaque progression has been fundamental to understanding the means by which contemporary antiatherosclerotic therapies lower cardiovascular risk. The advent of intracoronary imaging has helped chart the natural course of coronary atherosclerosis and evaluate therapeutic strategies that modify its natural progression. From earlier intravascular ultrasonography studies using lower dose statins to recent clinical trials evaluating the long-term effects of high-intensity statin therapies, our understanding of the relationship between incremental low-density lipoprotein-cholesterol lowering and coronary atheroma progression-regression has evolved considerably, particularly in patients of varying cardiometabolic risk including those with diabetes mellitus and acute coronary syndromes. Evaluating the impact of novel therapies on coronary atheroma using imaging will continue to be integral in establishing their mechanistic benefit prior to embarking on large-scale, expensive, long-duration randomized trials powered for clinical end points. SUMMARY: Statins have remarkably impacted the natural course of coronary atherogenesis. Intravascular imaging has proven crucial in evaluating the mechanisms by which we can curb coronary atheroma progression and induce its regression. The insights gleaned from intravascular imaging trials evaluating statins have been complementary to the findings from large-scale trials powered for clinical end points.

Serial hemodynamic measurements in post-cardiac arrest cardiogenic shock treated with therapeutic hypothermia.

AIMS: Mortality from cardiogenic shock complicating acute myocardial infarction (MI) remains high despite contemporary treatment. Therapeutic Hypothermia (TH) offers cardiovascular and systemic effects that may prove beneficial in this population, however, current data are limited. This study sought to evaluate the effect of therapeutic hypothermia on serial hemodynamics obtained in subjects with post-cardiac arrest cardiogenic shock. METHODS: We analyzed serial hemodynamics of 14 consecutive patients with cardiogenic shock after cardiac arrest treated with TH. Study inclusion required baseline hemodynamics obtained prior to initiation of TH confirming cardiogenic shock defined as cardiac index ≤2.2 L/min/m(2) with a systolic blood pressure of ≤90 mmHg, a vasopressor requirement, or need for mechanical circulatory support. RESULTS: In our 14 patients, the mean age was 58 ± 13.1 years, mean ejection fraction was 21 ± 8%, six had an acute MI, 12 required vasopressors, and 10 required mechanical support prior to initiation of TH. When compared to baseline, patients had significant improvements in Fick cardiac index, mixed venous O2 saturations, and serum lactate concentrations while heart rate was reduced following initiation of TH. There was no significant change in mean arterial pressure, however vasopressor requirement was reduced. CONCLUSIONS: In patients with cardiogenic shock following cardiac arrest, initiation of TH was associated with favorable changes in invasive hemodynamics suggesting safety in this population. Given potential for favorable hemodynamic and systemic effects of TH in cardiogenic shock, further prospective study of TH as a potentially novel adjunctive therapy to early reperfusion in post-MI cardiogenic shock should be considered.

High-intensity statin therapy alters the natural history of diabetic coronary atherosclerosis: insights from SATURN.

OBJECTIVE: Although statins can induce coronary atheroma regression, this benefit has yet to be demonstrated in diabetic individuals. We tested the hypothesis that high-intensity statin therapy may promote coronary atheroma regression in patients with diabetes. RESEARCH DESIGN AND METHODS: The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. This analysis compared changes in biochemistry and coronary percent atheroma volume (PAV) in patients with (n = 159) and without (n = 880) diabetes. RESULTS: At baseline, patients with diabetes had lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels but higher triglyceride and CRP levels compared with patients without diabetes. At follow-up, diabetic patients had lower levels of LDL-C (61.0 ± 20.5 vs. 66.4 ± 22.9 mg/dL, P = 0.01) and HDL-C (46.3 ± 10.6 vs. 49.9 ± 12.0 mg/dL, P < 0.001) but higher levels of triglycerides (127.6 [98.8, 163.0] vs. 113.0 mg/dL [87.6, 151.9], P = 0.001) and CRP (1.4 [0.7, 3.3] vs. 1.0 [0.5, 2.1] mg/L, P = 0.001). Both patients with and without diabetes demonstrated regression of coronary atheroma as measured by change in PAV (-0.83 ± 0.13 vs. -1.15 ± 0.13%, P = 0.08). PAV regression was less in diabetic compared with nondiabetic patients when on-treatment LDL-C levels were >70 mg/dL (-0.31 ± 0.23 vs. -1.01 ± 0.21%, P = 0.03) but similar when LDL-C levels were ≤70 mg/dL (-1.09 ± 0.16 vs. -1.24 ± 0.16%, P = 0.50). CONCLUSIONS: High-intensity statin therapy alters the progressive nature of diabetic coronary atherosclerosis, yielding regression of disease in diabetic and nondiabetic patients.

Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility?

Early observations of cardiogenic shock as a systemic clinical syndrome were first described in 1942. Today, cardiogenic shock remains the leading cause of death among patients hospitalized for myocardial infarction (MI). Mortality rates in post-MI cardiogenic shock approach 50% despite rapid revascularization, optimal medical care, and use of mechanical support. New therapeutic strategies with global systemic effects may offer advances in treatment and outcome in post-MI cardiogenic shock. Therapeutic hypothermia for post-MI cardiogenic shock has multiple potentially beneficial physiologic effects, including the potential to improve post-ischemic cardiac function and hemodynamics, decrease myocardial damage, and reduce end-organ injury from prolonged hypoperfusion. Available data in animal models of post-MI cardiogenic shock and ischemia/reperfusion injury and small case series of human patients with cardiogenic shock suggest its promise as a potential therapeutic strategy for cardiogenic shock in the post-MI setting. We hypothesize that systemic therapeutic hypothermia could decrease morbidity and mortality in post-MI patients with cardiogenic shock and warrants study a new treatment that could be widely available at hospitals worldwide.

Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus.

Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8(+) T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8+ T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K(b) and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection.