Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study.

BACKGROUND: Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure. METHODS: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms. RESULTS: Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P<0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P<0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment (P<0.01). CONCLUSIONS: We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03836079.

Left Ventricular Unloading Before Percutaneous Coronary Intervention is Associated With Improved Survival in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Left ventricular unloading with Impella may improve survival outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, the optimal timing to initiate left ventricular unloading has yet to be established. Therefore, we conducted a systematic review and meta-analysis to compare survival in patients with AMI-CS who were supported with Impella prior to PCI (pre-PCI) to those in whom support was initiated following PCI (post-PCI). METHODS: All studies that evaluated the impact of pre-PCI versus post-PCI Impella placement in patients with AMI-CS were included. Primary endpoints included in-hospital, 30-day, and 6-month survival rates. RESULTS: We identified five observational studies comparing outcomes in 432 patients with AMI-CS, of which 173 patients were treated with Impella pre-PCI and 259 patients post-PCI. Patients in the pre-PCI group had lower in-hospital mortality compared to patients in the post-PCI group (RR 0.62, 95% CI: 0.50-0.76, I2 = 0%). The lower mortality rate in the pre-PCI group remained evident at 30 days (HR 0.60, 95% CI: 0.47-0.78, I2 = 0%) and at 6 months (HR 0.66, 95% CI: 0.44-0.97, I2 = 0%). There was no difference in the risk of adverse events including reinfarction, stroke, major bleeding, acute ischemic limb, access site bleeding, and hemolysis. CONCLUSIONS: In this meta-analysis of studies evaluating survival among AMI-CS patients with left ventricular unloading initiated pre- versus post-PCI, Impella placement prior to PCI was associated with improved survival.

Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice: Translational Implications for Human Coronary Artery Disease.

[Figure: see text].

Incidence and clinical outcomes of bleeding complications and acute limb ischemia in STEMI and cardiogenic shock.

BACKGROUND: Bleeding complications and acute limb ischemia (ALI) are devastating vascular complications in patients with ST-segment elevation myocardial infarction (STEMI). Cardiogenic shock (CS) can further increase this risk due to multiorgan failure. In the contemporary era, percutaneous mechanical circulatory support is commonly used for management of CS. We hypothesized that vascular complications may be an important determinant of clinical outcomes for CS due to STEMI (CS-STEMI). OBJECTIVE: We evaluated 10-year national trends, resource utilization and outcomes of bleeding complications, and ALI in CS-STEMI. METHODS: We performed a retrospective cohort study of CS-STEMI patients from a large U.S. national database (National Inpatient Sample) between 2005 and 2014. Events were then divided into four different groups: no MCS, with intra-aortic balloon pump, percutaneous ventricular assist device includes Impella or Tandem Heart or extracorporeal membrane oxygenation. RESULTS: Bleeding complications and ALI were observed in 31,389 (18.2%) and 1,628 (0.9%) out of 172,491 admissions with CS-STEMI, respectively. Between 2005 and 2014, overall trends increased for ALI; however, the number of bleeding events decreased. ALI was associated with increased in-hospital mortality in comparison to those without any ALI. However, bleeding complications were not associated with increased in-hospital mortality. Compared to patients without complications, both bleeding and ALI were associated with increased length of stay (LOS) and hospitalization costs. CONCLUSIONS: Bleeding and ALI are common complications associated with CS-STEMI in the contemporary era. Both complications are associated with increased hospital costs and LOS. These findings highlight the need to develop algorithms focused on vascular safety in CS-STEMI.

Incidence and clinical outcomes of stroke in ST-elevation myocardial infarction and cardiogenic shock.

OBJECTIVE: The authors sought to evaluate 10-year national trends, incidence and clinical outcomes of stroke in CS-STEMI. BACKGROUND: Stroke is a devastating complication among patients with ST-elevation myocardial infarction (STEMI). Concomitant cardiogenic shock (CS) may further increase the risk of stroke. Use of percutaneous mechanical circulatory support (pMCS) devices may further increase stroke risk in CS-STEMI. No studies have evaluated the risk of stroke in contemporary CS-STEMI. METHODS: We performed a retrospective cohort study of CS-STEMI patients from a large U.S. national database between 2005 and 2014. Previously validated codes for stroke were used to identify events of ischemic or hemorrhagic stroke. They were then divided into different groups: without MCS, with intra-aortic balloon pump, percutaneous ventricular assist device (PVAD, includes Impella or TandemHeart devices), or extracorporeal membrane oxygenation. RESULTS: In 172,491 admissions, stroke was noted in 5,613 (3.2%). Between 2005 and 2014, we observed an increase in the events of overall stroke from 3.1% in 2005 to 5.0% in 2014 (p for the trend <.001). The number of ischemic stroke events (2.4%) was higher than hemorrhagic stroke (0.1%) during the study period. Presence of stroke was associated with higher in-hospital mortality (40.6 vs. 29.8%, 95% CI adjusted odds ratio: 1.57, 1.44-1.67; p < .0001 among stroke vs. without stroke). CONCLUSIONS: The incidence of stroke events in CS-STEMI patients increased between 2005 and 2014, and is associated with higher in-hospital mortality, length of stay, and cost of hospitalization. The incidence of both hemorrhagic and ischemic stroke was higher with pMCS device use. Stroke prevention is a priority for CS-STEMI patients.

PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.

OBJECTIVE: Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention. Approach and Results: In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02-0.75); P=0.02. CONCLUSIONS: In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02561000.

First-in-human experience with occlusion of the superior vena cava to reduce cardiac filling pressures in congestive heart failure.

BACKGROUND: Acutely decompensated heart failure remains a major clinical problem. Volume overload promotes cardiac and renal dysfunction and is associated with increased morbidity and mortality in heart failure. We hypothesized that transient occlusion of the superior vena cava (SVC) will reduce cardiac filling pressures without reducing cardiac output or systemic blood pressure. The objective of this proof of concept study was to provide initial evidence of safety and feasibility of transient SVC occlusion in patients with acutely decompensated heart failure and reduced ejection fraction. METHODS AND RESULTS: In eight patients with systolic heart failure, SVC occlusion was performed using a commercially available occlusion balloon. Five minutes of SVC occlusion reduced biventricular filling pressures without decreasing systemic blood pressure or total cardiac output. In three of the eight patients, a second 10-minutes occlusion had similar hemodynamic effects. SVC occlusion was well-tolerated without development of new symptoms, new neurologic deficits, or any adverse events including stroke, heart attack, or reported SVC injury or thrombosis at 7 days of follow up. CONCLUSION: We report the first clinical experience with transient SVC occlusion as a potentially new therapeutic approach to rapidly reduce cardiac filling pressures in heart failure. No prohibitive safety signal was identified and further testing to establish the clinical utility of transient SVC occlusion for acute decompensated heart failure is justified.

Clinical outcomes following implantation of the ION™ paclitaxel-eluting platinum chromium coronary stent in routine clinical practice: Results of the ION U.S. post-approval study.

BACKGROUND: The ION Study assessed clinical outcomes for the thin-strut, ION™ (TAXUS Element) Paclitaxel-Eluting Platinum Chromium Coronary Stent System (Boston Scientific, Marlborough, MA) in unselected patients. METHODS: This prospective, open-label registry enrolled the first 1,120 consenting patients treated with the ION stent without clinical or angiographic inclusion criteria at 40 clinical sites. Follow-up was at discharge, 30 days, 180 days, 1 and 2 years. The primary endpoint, the 1-year rate of cardiac death or MI (CD/MI) in PERSEUS-like patients (i.e., patients similar to those enrolled in PERSEUS, the pivotal approval trial), was tested in patients pooled from the ION study (N = 316), the European TAXUS Element post-approval registry (TE-PROVE; N = 306 PERSEUS-like patients), and the PERSEUS WH/SV populations (N = 1,166); and then compared with a prespecified performance goal. Additional outcomes were examined in the overall ION patient population. RESULTS: A total of 1,111 (out of 1,120) enrolled patients received a study stent. Most patients were male (70%) and mean age was 64 years. At 1 year, the primary endpoint of CD/MI occurred in 2.1% (6/292) of PERSEUS-like patients in ION, and 2.3% (40/1,729) of patients in the combined analysis. The upper one-sided 95% confidence interval for the combined analysis was 2.9%, which was significantly less than the performance goal of 7.6% (P < 0.001). Within patients enrolled in the ION study (N = 1,111), the rate of CD/MI was 4.5% at 1 year and 7.5% at 2 years. Definite/probable stent thrombosis occurred in 2.1% of patients at 1 year and 2.5% at 2 years. CONCLUSIONS: The results of the ION Study confirm the mid-term safety and effectiveness of the ION stent for the treatment of coronary artery disease in everyday clinical practice.

Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

Noncanonical Matrix Metalloprotease 1-Protease-Activated Receptor 1 Signaling Drives Progression of Atherosclerosis.

OBJECTIVE: Protease-activated receptor-1 (PAR1) is classically activated by thrombin and is critical in controlling the balance of hemostasis and thrombosis. More recently, it has been shown that noncanonical activation of PAR1 by matrix metalloprotease-1 (MMP1) contributes to arterial thrombosis. However, the role of PAR1 in long-term development of atherosclerosis is unknown, regardless of the protease agonist. APPROACH AND RESULTS: We found that plasma MMP1 was significantly correlated (R=0.33; P=0.0015) with coronary atherosclerotic burden as determined by angiography in 91 patients with coronary artery disease and acute coronary syndrome undergoing cardiac catheterization or percutaneous coronary intervention. A cell-penetrating PAR1 pepducin, PZ-128, currently being tested as an antithrombotic agent in the acute setting in the TRIP-PCI study (Thrombin Receptor Inhibitory Pepducin-Percutaneous Coronary Intervention), caused a significant decrease in total atherosclerotic burden by 58% to 70% (P<0.05) and reduced plaque macrophage content by 54% (P<0.05) in apolipoprotein E-deficient mice. An MMP1 inhibitor gave similar beneficial effects, in contrast to the thrombin inhibitor bivalirudin that gave no improvement on atherosclerosis end points. Mechanistic studies revealed that inflammatory signaling mediated by MMP1-PAR1 plays a critical role in amplifying tumor necrosis factor α signaling in endothelial cells. CONCLUSIONS: These data suggest that targeting the MMP1-PAR1 system may be effective in tamping down chronic inflammatory signaling in plaques and halting the progression of atherosclerosis.

Quantitative assessment of myocardial perfusion using time-density curve analysis after elective percutaneous coronary intervention.

UNLABELLED: The aim of this study was to assess myocardial blush (MB) using a novel software algorithm that quantifies time-density curves (TDC) after percutaneous coronary intervention (PCI). METHODS: Thirty-two patients referred for elective PCI were enrolled. TDC curves were generated and mean maximal myocardial contrast density (Dmax) was calculated from 5 regions of interest in the PCI territory. Dmax was normalized to contrast injected in the proximal coronary artery (DI). RESULTS: Mean DI significantly increased after PCI in all subjects. Dmax correlated directly with subjective grading of Thrombolysis in Myocardial Infarction (TIMI) myocardial blush (R=0.47; P<.01). In 7 subjects referred for PCI of a chronic total occlusion (CTO), mean DI remained increased after PCI. Mean DI was lower in CTO versus non-CTO subjects; however, fold-improvement was higher after PCI of CTO lesions. CONCLUSION: Quantifying MB using TDC analysis is feasible and correlates with subjective MB grading. The clinical utility of MB quantitation after PCI requires further study.

Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism.

BACKGROUND: Epidemiology data for lower-extremity arterial thromboembolism (LET) are limited and may result from either acute limb ischemia or an acute exacerbation of critical limb ischemia. Given marked changes in both diagnosis and therapy over the last 2 decades, we hypothesized that this time period would have witnessed reductions in both the incidence and in-hospital mortality of LET. METHODS AND RESULTS: Data from 1988 through 2007 from the National Hospital Discharge Survey were analyzed. All admissions for patients with LET were extracted, and the respective International Classification of Diseases, Ninth Revision, Clinical Modification codes were internally validated for both LET and acute limb ischemia. Descriptive statistics were used. The validity of the codes was good for identifying LET cases but poor for identifying acute limb ischemia cases because many of these acute presentations were attributable to critical limb ischemia. Over the 20-year span, there were 1.76 million cases of LET. The incidence of LET decreased significantly from 42.4 per 100 000 persons between 1988 and 1997 to 23.3 per 100 000 persons between 1998 and 2007. The in-hospital mortality for LET decreased significantly from 8.28% between 1988 and 1997 to 6.34% between 1998 and 2007, and male patients achieved greater mortality reduction compared with female patients. Treatments for acute limb ischemia showed decreasing use of surgical bypass and amputation and increasing rates of catheter-based thrombolysis. CONCLUSIONS: Over the 20-year study period, there have been significant reductions in both LET incidence and in-hospital mortality. Unfortunately, LET admissions extracted from an administrative database comprise a diverse group of individuals, including those with acute and chronic forms of limb ischemia and iatrogenic arterial injury, limiting the true assessment of ALI incidence.

Longitudinal stent deformation: quantitative coronary angiographic analysis from the PERSEUS and PLATINUM randomised controlled clinical trials.

AIMS: Recent reports have suggested susceptibility of novel thin-strut coronary stents to incur longitudinal stent deformation during or following deployment. This analysis assesses the incidence of longitudinal stent deformation in three stent platforms. METHODS AND RESULTS: Quantitative angiographic analysis (QCA) of 2,403 stents from the PERSEUS Workhorse (WH) and PLATINUM-WH trials was performed by an independent core laboratory. The distribution of QCA measured: nominal stent length ratios was compared between platforms to evaluate longitudinal stent deformation. Stent length ratio averaged 0.95 ± 0.07 in the TAXUS Express arm and 0.94 ± 0.06 in the ION (TAXUS Element) arm of the PERSEUS-WH trial (p=0.16). In the PLATINUM-WH trial, the mean ratio in the PROMUS cohort was slightly smaller (0.92 ± 0.09) than PROMUS Element (0.94 ± 0.08; p=0.004). Manual, blinded re-examination by the core laboratory of the angiograms corresponding to the 20 lowest and highest ratios in each trial did not identify any cases of stent deformation. CONCLUSIONS: Systematic analysis by an independent angiographic core laboratory of 2,403 stents implanted in patients enrolled in two large multicentre randomised trials demonstrated no stent deformation or meaningful differences in stent length ratios between ION and TAXUS Express or between PROMUS Element and PROMUS in the patient populations studied using the methodology employed.

The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction.

BACKGROUND: Right ventricular dysfunction (RVD) is a major cause of morbidity and mortality in the setting of acute inferior wall myocardial infarction (IWMI), and early detection may improve clinical outcomes. We defined a novel hemodynamic index, the pulmonary artery pulsatility index (PAPi), and explored whether the PAPi correlates with severe RVD in acute IWMI. METHODS: From 2008 to 2010, we identified 20 patients presenting with angiographically confirmed proximal right coronary artery occlusion and suspected RVD (sRVD) as defined by hemodynamic instability, profound bradycardia, or ST-elevation in lead V4R. Two controls groups were studied (1) 50 patients with nonobstructive coronary artery disease (Non-CAD) and (2) 14 patients presenting with acute coronary syndrome requiring left coronary stenting (ACS). Hemodynamic indices analyzed at the time of catheterization included: (1) the right atrial to pulmonary capillary wedge pressure ratio (RA:PCWP), (2) right ventricular stroke work (RVSW), and (3) the PAPi. Qualitative echocardiographic scores of RV systolic function were determined by two blinded investigators within 24 hr of catheterization. RESULTS: Among subjects with sRVD, 7 (35%) received a percutaneous RV support device (pRVSD) for medically refractory RV failure and 4 (20%) died prior to hospital discharge. Compared to Non-CAD and ACS controls, subjects with sRVD had a significantly lower PAPi (4.32 ± 3.04 vs. 5.52 ± 4.40 vs. 1.11 ± 0.57, respectively, P < 0.01) and a higher RA:PCWP ratio (0.48 ± 0.24 vs. 0.51 ± 0.26 vs. 0.81 ± 0.30, respectively, P < 0.05). Both the PAPi and RA:PCWP ratios correlated significantly with RVSW and qualitative echocardiographic grading. The PAPi demonstrated the highest sensitivity (88.9%) and specificity (98.3%) for predicting in-hospital mortality and/or requirement of a pRVSD. Using ROC curve derived cut-points, a PAPi ≤ 0.9 provided 100.0% sensitivity and 98.3% specificity (C-statistic: 0.998) for predicting these outcomes, exceeding the predictive value of the RA:PCWP ratio or RVSW. CONCLUSIONS: The PAPi is a simple, invasive hemodynamic measure that may help identify high-risk patients with acute IWMI with severe RVD. Earlier identification of this high-risk population may improve clinical outcomes.

The Occluded Artery Trial (OAT) Viability Ancillary Study (OAT-NUC): influence of infarct zone viability on left ventricular remodeling after percutaneous coronary intervention versus optimal medical therapy alone.

BACKGROUND: The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) versus optimal medical therapy (MED) in patients with persistent total occlusion of the infarct-related artery 3 to 28 days post-myocardial infarction. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ) viability is unknown. METHODS AND RESULTS: The OAT nuclear ancillary study hypothesized that (1) IZ viability influences left ventricular (LV) remodeling and that (2) PCI as compared with MED attenuates adverse remodeling in post-myocardial infarction patients with preserved viability. Enrolled were 124 OAT patients who underwent resting nitroglycerin-enhanced technetium-99m sestamibi single-photon emission computed tomography (SPECT) before OAT randomization, with repeat imaging at 1 year. All images were quantitatively analyzed for infarct size, IZ viability, LV volumes, and function in a core laboratory. At baseline, mean infarct size was 26% ± 18 of the LV, mean IZ viability was 43% ± 8 of peak uptake, and most patients (70%) had at least moderately retained IZ viability. There were no significant differences in 1-year end-diastolic or end-systolic volume change between those with severely reduced versus moderately retained IZ viability, or when compared by treatment assignment PCI versus MED. In multivariable models, increasing baseline viability independently predicted improvement in ejection fraction (P = .005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling. CONCLUSIONS: In the contemporary era of MED, PCI of the infarct-related artery compared with MED alone does not impact LV remodeling irrespective of IZ viability.

Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion.

OBJECTIVE: Early recognition of an acute coronary occlusion (ACO) improves clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium-derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated in ACO. METHODS AND RESULTS: Serum sFLT1 levels were measured by enzyme-linked immunosorbent assay in patients with ST-segment elevations and angiographically confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction, and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and in vitro human coronary artery endothelial cell injury were used. sFLT1 levels were increased in ACO compared with unstable angina/non-ST-elevation myocardial infarction, catheterized controls, or healthy volunteers (200.7±15.5 versus 70.7±44.0 versus 10.2±4.0 versus 11.7±1.7 pg/mL respectively, P<0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin I for ACO (100% versus 20% versus 20% respectively; P≤0.01 for each). Within 60 minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin increased sFLT1 levels within 15 minutes in human coronary artery endothelial cells. CONCLUSIONS: sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.

Usefulness of soluble endoglin as a noninvasive measure of left ventricular filling pressure in heart failure.

Progressive left ventricular (LV) dysfunction induces expression of the cytokine transforming growth factor-ß1. Endoglin (CD105) is a transforming growth factor-ß1 co-receptor that is released into the circulation as soluble endoglin (sEng). The objective of the present study was to assess the serum levels of sEng in patients with heart failure and to identify the predictive value of sEng for detecting elevated left ventricular end-diastolic pressures (LVEDPs). We measured the sEng levels in 82 consecutive patients with suspected LV dysfunction referred for determination of left heart filling pressures using cardiac catheterization. Among these subjects, the sEng levels correlated with the LVEDP (R = 0.689; p <0.0001), irrespective of the LV ejection fraction. Using a receiving operating characteristic curve, the sEng levels predicted an LVEDP of ≥16 mm Hg with an area under the curve of 0.85, exceeding the measured area under the curves for both atrial and brain natriuretic peptide, currently used biomarkers for heart failure diagnosis (atrial natriuretic peptide 0.68 and brain natriuretic peptide 0.65; p <0.01 vs sEng). In 10 subjects receiving medical therapy guided by invasive hemodynamic monitoring for heart failure, decreased a pulmonary capillary wedge pressure was associated with a reduced sEng level (R = 0.75, p = 0.008). Finally, compared to 25 healthy controls, the sEng levels were elevated in subjects with suspected LV dysfunction (3,589 ± 588 vs 4,257 ± 966 pg/ml, respectively, p <0.005) and correlated directly with the New York Heart Association class (R = 0.501, p<0.001). In conclusion, circulating levels of sEng are elevated in patients with increased LVEDP and New York Heart Association class, irrespective of the LV ejection fraction. sEng levels also decreased in association with a reduced cardiac filling pressure after diuresis. These findings have identified circulating sEng as a sensitive measure of elevated left heart filling pressures.

Conversion of infarction-associated atrial fibrillation by restoration of atrial perfusion.

We report a patient who presented with new onset atrial fibrillation in the setting of inferior ST-segment elevation myocardial infarction (STEMI). Cardiac catheterization revealed proximal occlusion of the left circumflex artery. Balloon angioplasty and stenting restored flow to a large left atrial branch, with prompt conversion of the rhythm to atrial flutter, and then to sinus rhythm. To our knowledge this represents the first demonstration of restoration of sinus rhythm by reversing left atrial ischemia in the setting of STEMI.

Intracardiac chloroma.

Chloromas are not frequently seen in patients with acute myelogenous leukemia and chloromas involving cardiac structures have only been rarely reported in the literature. We report a complete radiographic response to low-dose fractionated radiotherapy in a patient with an intracardiac chloroma.

Extended-release niacin reduces LDL particle number without changing total LDL cholesterol in patients with stable CAD.

BACKGROUND: The importance of the number of circulating low-density lipoprotein (LDL) cholesterol particles, in addition to total LDL level, has been increasingly recognized. The effects of extended-release niacin (ERN) on LDL particle numbers have not been studied. OBJECTIVE: To evaluate ERN's effects on LDL particle numbers. METHODS: Fifty-four patients with stable coronary artery disease (CAD) and well-controlled LDL levels were randomly assigned to 3 months of ERN (1 g/day) or placebo in addition to their baseline medications. Lipoprotein particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months. RESULTS: Compared to baseline, the addition of ERN had no significant effect on total LDL cholesterol levels; however, ERN decreased the number of medium and small LDL particles (P < .005). After 3 months, ERN decreased the number of medium and small LDL particles compared to placebo-treated patients (P < .05). ERN raised HDL cholesterol levels by 2.7%, significantly increased the number of large HDL particles (P < .001), and decreased the number of small HDL particles (P = .027) compared to placebo. There were no significant changes in lipid values or particle numbers in the placebo-treated patients. In patients with stable coronary artery disease and well-controlled LDL cholesterol levels, ERN reduced the number of circulating particles of the more atherogenic subtypes of LDL, despite having no effect on total LDL cholesterol levels. ERN also favorably altered the number of HDL particles. CONCLUSION: ERN-induced alterations in lipoprotein particle numbers may contribute to its anti-atherosclerotic effects, and these effects may not be evident from the standard lipid profile.