Significance of abnormal stress electrocardiography with normal cardiac imaging during stress testing-a meta-analysis.

BACKGROUND AND AIMS: Diagnostic testing for coronary artery disease frequently involves functional stress testing where imaging is often coupled with electrocardiogram (ECG) analysis. While decision-making is straightforward when both functional testing and ECG are either positive or negative, interpretation is challenging and prognostic importance uncertain with positive ECG and negative imaging since imaging is considered more sensitive. Prior studies have demonstrated mixed results. We sought to perform a meta-analysis of published studies to determine the significance of this particular type of discordant stress test result. METHODS AND RESULTS: PubMed, Cochrane, and Google Scholar were searched to identify studies reporting results of functional imaging (pharmacological exercise echocardiography or SPECT) and ECG analysis, along with the major adverse cardiovascular events (MACE) at patient follow-up. Studies were stratified based on functional imaging modality used. Primary outcome was a composite of all-cause death or myocardial infarction, and secondary outcome was the need for coronary revascularization. Random effects model was used to calculate risk ratios (RR), and heterogeneity among studies was assessed using the Higgins I2 value. Nine studies with a total of 23,715 patients were included. Primary end point was more common with discordant results with exercise stress echocardiography (RR 1.33, 95% confidence intervals [1.08-1.63]) or pharmacological SPECT (RR 6.53 95% CI [2.31-18.48]). CONCLUSIONS: Patients in the discordant exercise stress echocardiography and pharmacological SPECT groups were more likely to suffer the primary end point than those with a normal stress test. Discordant results should be interpreted carefully in the clinical context, given their prognostic impact based on the stress modality used.

Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association.

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

True relationship between tricuspid annular motion and velocity displacement components: Potential role in assessing right ventricular decoupling.

BACKGROUND: Although measures of longitudinal displacement of the tricuspid annulus measured by M-mode as tricuspid annular systolic plane excursion (TAPSE) and systolic velocity by tissue Doppler imaging (TA TDI s) are routinely used for assessment of right ventricular (RV) systolic function; these measures describe different phenomena and should not be used interchangeably. METHODS: Previously published data was used to determine the individual relationship between TAPSE and TA TDI s with increasing pulmonary artery systolic pressures (PASP). RESULTS: In this retrospective analysis, 488 patients were divided into 2 groups based on TAPSE (Group 1: <1.8 cm and Group 2: ≥1.8 cm). A robust correlation (R = .79) between TAPSE and TA TDI s noted for the entire population. However, a statistically lower correlation (R = .43) was seen between Group 1 and Group 2 (R = .65; p < .0047). With increasing pulmonary pressures, only PASP (p < .0001) and TA TDI s (p < .0001) discriminated between low and normal TAPSE/PASP values. Suggesting that a TA TDI s/PASP ratio would be most useful than TAPSE/PASP with a specificity of 80%. CONCLUSIONS: Significant differences exist between TAPSE and TA TDI s, particularly at low TAPSE values with increased PASP, were uncoupling occurs. Our data seems to suggest that TA TDI s/PASP would be most useful than TAPSE/PASP ratio. Future studies should address, if abnormalities in the material properties along the RV free wall account for these differences seen between TAPSE and TA TDI s.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. METHODS: PubMed/Medline, Embase, and Cochrane library were searched using the following terms: ("sglt2" and "acute heart failure") and ("sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. RESULTS: Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). CONCLUSION: Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects.

Impact of severity of baseline thrombocytopenia on outcomes after percutaneous coronary interventions: Analysis from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program.

OBJECTIVES: The aim of this study was to evaluate the effect of the degree of severity of baseline thrombocytopenia (TCP) on outcomes after percutaneous coronary intervention (PCI) BACKGROUND: The association of TCP with clinical outcomes among patients undergoing coronary intervention has not been previously evaluated. METHODS: Using data from the US Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program, we identified patients undergoing PCI between October 1, 2007, to September 30, 2017. The cohort was then stratified by platelet count, as no TCP (platelet count >150,000/mcl), mild TCP (100-150,000/mcl), or moderate-severe TCP (<100,000/mcl) and this was associated with clinical outcomes. RESULTS: The cohort included 80,427 patients (98% male), of which 14.9% (13.2% mild, 1.7% moderate-severe) suffered from TCP at the time of PCI. Compared with mild or no TCP, moderate-severe TCP was associated with increased risk of post-PCI pericardiocentesis (0.6% vs. 0.2% vs. 0.2%, p = 0.018) and in-hospital mortality (1.5% vs. 0.7% vs. 0.7%) without a difference in postprocedure stroke (0.5% vs. 0.3% vs. 0.3%, p = 0.6). Over a median follow-up of 1729 days, time-to-repeat revascularization was significantly shorter in moderate-severe TCP (1080 vs. 1347 vs. 1467 days, p < 0.001) despite lower risk of revascularization. Both mild (adjusted HR: 1.11, 95% CI: 1.07-1.15, p < 0.001) and moderate-severe TCP (HR: 1.55, 95% CI: 1.43-1.69, p < 0.001) were associated with increased all-cause mortality compared with those without TCP. CONCLUSIONS: Thrombocytopenia was associated with increased short- and long-term adverse events among patients undergoing PCI. Any degree of TCP was associated with increased long-term all-cause mortality while moderate-severe TCP was also associated with increased risk of periprocedural adverse events.

Echo-Doppler measures of right ventricular systolic function are affected by reduced left ventricular systolic function.

BACKGROUND: Objective right ventricular (RV) systolic function assessment is attained using a series of well-described and validated echo-Doppler measurements. However, how left ventricular (LV) systolic function influences these RV functional measurements has not been previously studied. Consequently, we conducted a retrospective proof-of-concept analysis to answer this important question. METHODS: A total of 100 echocardiographic studies were included and patients were divided into two groups according to their LV ejection fraction (LVEF). The following RV variables were acquired including, tricuspid annular systolic plane excursion (TAPSE), velocity of the systolic motion (TA TDI s'), RV outflow tract velocity time integral (VTI), pulmonary vascular resistance (PVR), and the TAPSE to pulmonary artery systolic pressure (PASP) ratio. RESULTS: Not only TAPSE, TA DI s', RVOT VTI, PVR, and TAPSE/PASP were all significantly different between patients with normal versus abnormal LVEF; but most importantly, RVOT VTI (p < .0001) was the best discriminatory variable in assessing normal versus abnormal LVEF followed by TAPSE (p = .0001). Using receiver operating characteristic curve analysis, an RVOT VTI value > 11 identified patients with a normal LVEF with a sensitivity of 90% and specificity of 76%. CONCLUSION: Based on our results, reduced LVEF affects the RV, likely mediated by mechanisms of interventricular dependence. Therefore, RV analysis cannot be performed in isolation as it not only reflects intrinsic RV systolic function but also, is dependent on LV systolic function. In cases of reduced LVEF, additional measures of RV assessment should be used to provide better objective assessments.

Utility of the tricuspid annular tissue doppler systolic velocity and pulmonary artery systolic pressure relationship in right ventricular systolic function assessment: A pilot study.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio has been validated as a valuable noninvasive measure of right ventricular (RV) elastance and systolic function. However, the more reliable TA systolic (s') velocity measure of RV systolic function compared to TAPSE has not been previously studied. METHODS: We conducted a pilot study using several variables of RV function in 50 patients with the main aim to determine which numerical expression between TA TDI s'/PASP and TAPSE/PASP ratio was most useful. RESULTS: In a stepwise multiple regression analysis, TA TDI s'/PASP ratio (p < .0002); LVOT VTI/RVOT VTI ratio (p < .0002); RVOT VTI (p < .0047); TAPSE/PASP ratio (p < .0259) and TA TDI e' (p < .0292) were best in discriminating normal versus abnormal RV systolic function. Using receiver operator curve analysis, cut-off values for both TA TDI s'/PASP (>3.9 mm/c/mmHg) had 82.1% sensitivity and 77.3% specificity while the TAPSE/PASP (>.61 mm/mmHg) had 89.3% sensitivity and 68.2% specificity in identifying normal RV function in our studied population. CONCLUSION: Our results indicate that TA TDI s'/PASP is a better mathematical expression when examining the relationship between RV contractility and RV resistance relationship. Furthermore, we also found that inclusion of RVOT VTI, RV diastolic properties, and left ventricular systolic function are important determinants of RV systolic function assessments and should be routinely included. Additional prospective studies are now needed to confirm these results using hemodynamic data.

Significance of indeterminate and abnormal stress electrocardiography despite normal imaging in patients with suspected coronary artery disease - An analysis of the PROMISE trial.

BACKGROUND: Abnormal and indeterminate electrocardiographic (ECG) changes during cardiac stress imaging are not uncommon. While the prognostic importance of abnormal ECG despite normal imaging has been previously studied, prognosis of indeterminate stress ECG changes is uncertain. METHODS: We studied the prognostic value of stress ECG changes in symptomatic patients without known CAD and normal stress imaging from the PROMISE trial. Patients with normal ECG (concordant), indeterminate ECG and abnormal ECG (discordant) were identified among those with negative exercise imaging stress test (EIST) and negative vasodilator nuclear stress test (PIST). Outcomes of interest were major adverse cardiovascular endpoint (MACE, including all-cause mortality, myocardial infarction, and unstable angina hospitalization) and likelihood of coronary revascularization. RESULTS: In EIST, indeterminate stress ECG [1.1% vs. 0.2% adjusted hazard ratio (aHR) 4.2, (95% CI 1.11-15.6), p = 0.034] and discordant ECG [7.2% vs. 0.2% adjusted hazard ratio (aHR) 27.6, (95% CI 9.6-79.8), p < 0.0001] were associated with increased likelihood of revascularization compared to normal stress ECG. Similar findings were observed with PIST [indeterminate vs concordant [1.7% vs. 0.5% adjusted hazard ratio (aHR) 5.9, (95% CI 1.1-31.7), p = 0.041; discordant vs concordant 15.4% vs. 0.5% adjusted hazard ratio (aHR) 24.2, (95% CI 4.6-127.7), p = 0.0002]. MACE rates were similar between ECG subgroups, in both EIST and PIST. CONCLUSION: In symptomatic patients without known CAD undergoing stress imaging, indeterminate and discordant ECG changes results may indicate presence of obstructive CAD despite normal imaging results and predict increased likelihood of coronary revascularization despite no significant difference in MACE.

Effects of sodium-glucose cotransporter 1 and 2 inhibitors on cardiovascular and kidney outcomes in type 2 diabetes: A meta-analysis update.

In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome.

Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease. METHOD: Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. RESULTS: Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]). CONCLUSIONS: In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.

Exhaustion of coronary vasodilatory reserve in the resting state: Clinical characteristics and long-term outcomes after intervention.

OBJECTIVES/BACKGROUND: Resting coronary blood flow approximates flow with maximal vasodilation in very severe coronary stenosis. We studied the incidence of exhausted vasodilatory reserve by FFR, its clinical characteristics and long-term prognosis after FFR guided percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing FFR-guided PCI for coronary stenosis with reduced resting blood flow (baseline Pd/Pa < 0.8) were included. Basal maximal vasodilation (BMV) was defined as less than 5% difference between resting Pd/Pa and FFR, that is, FFR-baseline Pd/Pa < 0.05. RESULTS: Of 658 vessels that underwent FFR-guided PCI in 602 patients, 151 vessels had resting blood flow in the ischemic range (baseline Pd/Pa ≤ 0.8) and were included in the analysis. Of these, 28 lesions in 28 patients met criteria for BMV (4.25% of the entire registry and 18.5% of those with the reduced basal coronary flow). Stenosis severity was a significant predictor of the presence of BMV. In long term follow-up (median 106 ± 3.6 months), BMV was not associated with increased target vessel revascularization (TVR) or major adverse cardiac event compared to non-BMV(OR 1.9, 95% CI 0.7-4.8, p-value 0.2 and OR 1.3, 95% CI 0.75-2.5, p = 0.3, respectively). CONCLUSION: Low baseline Pd/Pa that approximates fractional flow reserve (exhausted vasodilatory reserve) defines a subgroup of patients with severe coronary artery stenosis. Prognosis, when treated with PCI along with medical therapy, appears similar to those with intact vasodilatory reserve.

Right ventricular free wall contractility in subcostal views: A proof-of-concept study to assess right ventricular systolic function.

BACKGROUND: Normal right ventricular (RV) function has been traditionally assessed from the apical window. However, in several patients the subcostal window is the only available acoustic. METHODS: Given the intricate functional and mechanical inter-dependence between longitudinal tricuspid annular (TA) displacement and RV free wall contractility (RVFW), we studied the utility of RVFW inward motion using both M-mode and velocity with tissue Doppler imaging (TDI) from the subcostal transthoracic view. RESULTS: If a TAPSE value ≥ 2 cm is used to identify normal RV function, an RVFW M-mode value > .8 cm, TA TDI s' velocity > .06 cm/s and TA TDI e' velocity value > .05 cm/s identify normal RV systolic function. Furthermore, ROC curve analysis for the RVFW M-mode showed an area under the curve (AUC) of .753 (95% CI: .604-.868) with a cut-off value > .8, sensitivity 75% and specificity 73%; for TA TDI s' AUC at .822 (95% CI: .681-.919) with a cut-off value > .06, sensitivity 75% and specificity 77% and for TA TDI e' the AUC was .771 (95% CI: .624-.882) with a cut-off value > .05, sensitivity 90% and specificity 46%. Reproducibility of repeat RVFW M-mode, TDI s' and e' measurements was good with strong inter-rater agreement (Kappa > .8). CONCLUSIONS: The subcostal window appears useful for assessing RV systolic function. Additional studies are now required to prospectively use these measures in the routine evaluation of RV systolic function particularly in patients with suboptimal apical windows.

Strain generation and right ventricular systolic function: The sum of all its parts.

BACKGROUND: Speckle-tracking echocardiography (STE) has provided a reliable means to enhance characterization and quantification of global right ventricular (RV) systolic function. The use of Automated Functional Imaging (AFI) software has been previously used to quantify RV longitudinal peak global strain (PGS) values during two-dimensional (2D) transthoracic echocardiographic examinations. However, there is a paucity of data regarding relative strain contribution of each individual regional segments when compared with global strain assessment. Consequently, our goal was to use AFI STE to examine the strain contribution of each regional segment when assessing RV function. METHODS: A retrospective analysis was performed on 107 patients that met our study criteria to correlate 2D TTE measures of RV systolic function to both RV AFI STE longitudinal peak global strain (PGS) and each individual regional RV free wall (RVFw) and inter-ventricular septum (IS) strain values. RESULTS: We found that TTE variables of RV systolic function only correlated with PGS (RVFAC; P < .0001, TAPSE; P < .0001, and TA TDI S'; P < .0001) but none of the six individual regional AFI strain values. When PGS was not included in the multivariate analysis, only the mid RVFw and mid IS strain regions correlated with measures of RV systolic function. CONCLUSIONS: Regional differences do exist with regards to strain generation along the RVFw and IS. These differences could be physiologically and anatomically explained based on our current understanding of RV muscle fiber arrangement. Further research is now needed to better characterize RV function in different clinical entities.

The sensitivity of graphic trends in differentiating sinus and supraventricular tachycardia.

BACKGROUND: The use of cardiac telemetry in the inpatient setting is widespread and has become integral in managing hospitalized patients. Telemetry is used to monitor patients with brady- and tachyarrhythmias. While most of the focus is on the rhythm strip data, a significant utility remains in analyzing the graphic heart rate trends. We specifically focused on the shape of the curve (rectangle or bell) of the heart rate over time to differentiate sinus tachycardia (ST) and supraventricular tachycardia (SVT). We hypothesized that identifying the shape of the graphic trend would improve the accuracy of diagnosis. METHODS: To demonstrate the simplicity of employing this method for improving the diagnosis of arrhythmia, we had senior medical students evaluate the telemetry strips and graphical trends. We gathered data from the medical student interpretation of 82 strips of in-hospital cardiac telemetry and asked them to differentiate ST and SVT based on the shape of the graphic trend. Each rhythm strip and the graphic trend was interpreted by two clinical cardiac electrophysiology attending physicians and confirmed on a 12­lead electrocardiogram. RESULTS: When students were asked to choose between ST and SVT based on the telemetry rhythm strip without graphic trends, 73% of their answers were correct. Diagnostic accuracy improved to 96% correct with the addition of the graphic trend. Depending on the telemetry rhythm strip alone, sensitivity to detect SVT was 75%, with 68% specificity. With the addition of the graphical trend, sensitivity improved to 98% and specificity 100%. CONCLUSION: Review of graphical trends, specifically the analysis of onset and offset, allows novice ECG readers to improve the ability to distinguish between ST and SVT.

Label-free optical biomarkers detect early calcific aortic valve disease in a wild-type mouse model.

BACKGROUND: Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a diet-based, non-genetically modified mouse model for early CAVD progression, and explored the utility of two-photon excited fluorescence (TPEF) microscopy for early detection of CAVD progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with the potential to correlate with multiple stages of CAVD pathophysiology including calcium deposition, collagen remodeling and osteogenic differentiation. METHODS: Twenty-week old C57BL/6J mice were fed either a control or pro-calcific diet for 16 weeks and monitored via echocardiography, histology, immunohistochemistry, and quantitative polarized light imaging. Additionally, TPEF imaging was used to quantify tissue autofluorescence (A) at 755 nm, 810 nm and 860 nm excitation, to calculate TPEF 755-860 ratio (A860/525/(A755/460 + A860/525)) and TPEF Collagen-Calcium ratio (A810/525/(A810/460 + A810/525)) in the murine valves. In a separate experiment, animals were fed the above diets till 28 weeks to assess for later-stage calcification. RESULTS: Pro-calcific mice showed evidence of lipid deposition at 4 weeks and calcification at 16 weeks at the valve commissures. The valves of pro-calcific mice also showed positive expression for markers of osteogenic differentiation, myofibroblast activation, proliferation, inflammatory cytokines and collagen remodeling. Pro-calcific mice exhibited lower TPEF autofluorescence ratios, at locations coincident with calcification, that correlated with increased collagen disorganization and positive expression of osteogenic markers. Additionally, locations with lower TPEF autofluorescence ratios at 4 and 16 weeks exhibited increased calcification at later 28-week timepoints. CONCLUSIONS: This study suggests the potential of TPEF autofluorescence metrics to serve as a label-free tool for early detection and monitoring of CAVD pathophysiology.

Improved stent expansion with prolonged compared with short balloon inflation: A meta-analysis.

BACKGROUND: Despite evidence from individual studies suggesting that prolonged inflation improves coronary stent expansion, relatively shorter inflation times are commonly employed in clinical practice. METHODS: We performed an electronic search of PubMed, Web of Science, Cochrane, and CINAHL databases to retrieve outcome studies comparing prolonged versus short inflation times during stent deployment. Outcomes studied included minimal stent diameter (MSD) and minimal stent area (MSA). Standardized mean difference (SMD) was used to estimate the effect sizes for these continuous variables. RESULTS: Seven studies with a total of 341 patients (415 lesions; mean age 67.6 years; 82% male) were included. Drug-eluting stents were used in 89 ± 15% of coronary lesions. Prolonged stent inflation was associated with increased minimal stent diameter (2.93 ± 0.34 mm vs. 2.72 ± 0.28 mm; SMD = 0.42; 95% CI 0.25-0.59; P < 0.001) and minimal stent area (5.99 ± 1.21 mm2 vs. 5.17 ± 0.87 mm2 ; SMD = 0.46; 95% CI 0.19-0.73; P = 0.001) compared with shorter duration stent inflation. This difference remained significant in sensitivity analyses that excluded studies with very prolonged inflation duration or multiple stent balloon inflations. CONCLUSION: Despite differences in duration and methodology, prolonged stent inflation is associated with improved expansion compared with shorter duration. The effect of this optimization recommends randomized trials to determine whether long-term outcomes can be improved by this simple technical modification.

Two aortic valves in the parasternal long-axis view: Aortic dissection or artifact?

Refraction artifact produced the appearance of two aortic valves in the parasternal long axis view. Aortic dissection was ruled out by CT angiography.

Clinical Context and Detection of the Murmur of Advanced Aortic Stenosis.

OBJECTIVES: Auscultation is an important clue to the presence of aortic stenosis (AS). We sought to assess the effect of symptom status, prior knowledge of diagnosis, and other patient factors on murmur detection. METHODS: Patients with moderate-to-severe AS by echocardiography at a single center between June 2015 and June 2016 were included. Five consecutive patient encounters (inpatient and outpatient) within 12 months before the echocardiogram were analyzed. RESULTS: Ninety-five patients (418 different clinician encounters) were studied. The murmur of AS was identified by only 39% of clinicians. In multivariate analysis, significant determinants of murmur detection were examination in outpatient setting (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.75-6.61), known history of AS (OR 2.77, 95% CI 1.53-5.01), female sex (OR 1.97, 95% CI 1.07-3.60), and presence of symptoms (OR 1.91 95% CI 1.12-3.26). Compared with the murmur detection findings by clinicians in medicine, the findings of surgical specialty clinicians were significantly lower (OR 0.12, 95% CI 0.06-0.26, P < 0.001). CONCLUSIONS: In this real-world assessment, clinical context played an important role in the auscultation of AS murmur. The findings have important implications for the clinical diagnosis of asymptomatic advanced AS.

A novel stent inflation protocol improves long-term outcomes compared with rapid inflation/deflation deployment method.

BACKGROUND: High-pressure inflation for coronary stent deployment is universally performed. However, the duration of inflation is variable and does not take into account differences in lesion compliance. We developed a standardized "pressure optimization protocol" (POP) using inflation pressure stability rather than an arbitrary inflation time or angiographic balloon appearance for stent deployment. Whether this approach improves long-term outcomes is unknown. METHODS AND RESULTS: 792 patients who underwent PCI using either rapid inflation/deflation (n = 376) or POP (n = 416) between January 2009 and March 2014 were included. Exclusion criteria included PCI for acute myocardial infarction, in-stent restenosis, chronic total occlusion, left main, and saphenous vein graft lesions. Primary endpoint was target vessel failure [TVF = combined end point of target vessel revascularization (TVR), myocardial infarction, and cardiac death]. Outcomes were analyzed in the entire cohort and in a propensity analysis. Stent implantation using POP with a median follow-up of 1317 days was associated with lower TVF compared with rapid inflation/deflation (10.1 vs. 17.8%, P < 0.0001). This difference was driven by a decrease in TVR (7 vs. 10.6%, P = 0.0016) and cardiac death (2.9 vs. 5.8%, P = 0.017) while there was no difference in myocardial infarction (1 vs. 1.9%, P = 0.19). In the Cox regression model, deployment using POP was the only independent predictor of reduced TVF (HR 0.43; 0.29-0.64; P < 0.0001). In the propensity analysis (330 patients per group) TVF remained lower with POP vs. rapid inflation/deflation (10 vs. 18%, P < 0.0001). CONCLUSIONS: Stent deployment using POP led to reduced TVF compared to rapid I/D. These results recommend this method to improve long-term outcomes. © 2017 Wiley Periodicals, Inc.

Xanthine Oxidase Induces Foam Cell Formation through LOX-1 and NLRP3 Activation.

PURPOSE: Xanthine oxidase catalyzes the oxidation of xanthine to uric acid. This process generates excessive reactive oxygen species (ROS) that play an important role in atherogenesis. Recent studies show that LRR and PYD domains-containing protein 3 (NLRP3), a component of the inflammasome, may be involved in the formation of foam cells, a hallmark of atherosclerosis. This study was designed to study the role of various scavenger receptors and NLRP3 inflammasome in xanthine oxidase and uric acid-induced foam cell formation. METHODS AND RESULTS: Human vascular smooth muscle cells (VSMCs) and THP-1 macrophages were treated with xanthine oxidase or uric acid. Xanthine oxidase treatment (of both VSMCs and THP-1 cells) resulted in foam cell formation in concert with generation of ROS and expression of cluster of differentiation 36 (CD36) and oxidized low density lipoprotein (lectin-like) receptor 1 (LOX-1), but not of scavenger receptor A (SRA). Uric acid treatment resulted in foam cell formation, ROS generation and expression of CD36, but not of LOX-1 or SRA. Further, treatment of cells with xanthine oxidase, but not uric acid, activated NLRP3 and its downstream pro-inflammatory signals- caspase-1, interleukin (IL)-1ß and IL-18. Blockade of LOX-1 or NLRP3 inflammasome with specific siRNAs reduced xanthine oxidase-induced foam cell formation, ROS generation and activation of NLRP3 and downstream signals. CONCLUSIONS: Xanthine oxidase induces foam cell formation in large part through activation of LOX-1 - NLRP3 pathway in both VSMCs and THP-1 cells, but uric acid-induced foam cell formation is exclusively through CD36 pathway. Further, LOX-1 activation is upstream of NLRP3 activation. Graphical Abstract Steps in the formation of foam cells in response to xanthine oxidase and uric acid. Xanthine oxidase stimulates LOX-1 expression on the cell membrane of macrophages and vascular smooth muscle cells (VSMCs) and increases generation of ROS, which activate NLRP3 inflammasome and downstream pro-inflammatory mediators such as Caspase-1, IL-1ß and IL-18. Xanthine oxidase also induces CD36 expression. Activation of both LOX-1 and CD36 (LOX-1> > CD36) participates in the transformation of macrophages and VSMCs into foam cells. Uric acid formed from xanthine-xanthine oxidase interaction stimulates CD36 expression and triggers foam cell formation independent of NLRP3 activation.