Search

Limited data are available on characteristics and long-term outcomes of patients with coronary artery bypass grafts (CABG) undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI). Between January 2000 to December 2014, we identified STEMI patients with prior CABG undergoing primary percutaneous coronary intervention from 3 sites. Kaplan-Meier methods to estimate survival and major adverse cardiac events (MACE) were employed and compared to a propensity matched cohort of non-CABG STEMI patients. Independent predictors of outcomes were analyzed with Cox modeling. Of the 3,212 STEMI patients identified, there were 296 (9.2%) CABG STEMI patients, having nearly similar frequencies of culprit graft (47.6%) versus culprit native (52.4%) as the infarct-related artery (IRA). At 10 years, the adjusted survival was 44% in CABG STEMI versus 55% in non-CABG STEMI (HR 1.26; 95%CI 0.86 to 1.87; p = 0.72). Survival free of MACE was lower for CABG STEMI (graft IRA, 37%; native IRA, 46%) as compared to non-CABG STEMI controls (63%) (p = 0.02). Neither CABG history nor IRA (native vs graft) was independently associated with death or MACE in multivariable analysis. Temporal trends showed no significant change in death or MACE rates of CABG STEMI patients over time. In conclusion, long term survival of CABG STEMI patients is not significantly different than matched STEMI patients without prior CABG; however, CABG STEMI patients were at significantly higher risk for MACE events.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was

Background: \ud Familial hypercholesterolemia is characterized by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. Monoclonal antibodies directed against proprotein convertase subtilisin–kexin type 9 (PCSK9) have been shown to reduce LDL cholesterol levels by more than 50% but require administration every 2 to 4 weeks. In a phase 2 trial, a twice-yearly injection of inclisiran, a small interfering RNA, was shown to inhibit hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholesterolemia.\ud Methods: \ud In this phase 3, double-blind trial, we randomly assigned, in a 1:1 ratio, 482 adults who had heterozygous familial hypercholesterolemia to receive subcutaneous injections of inclisiran sodium (at a dose of 300 mg) or matching placebo on days 1, 90, 270, and 450. The two primary end points were the percent change from baseline in the LDL cholesterol level on day 510 and the time-adjusted percent change from baseline in the LDL cholesterol level between day 90 and day 540.\ud Results: \ud The median age of the patients was 56 years, and 47% were men; the mean baseline level of LDL cholesterol was 153 mg per deciliter. At day 510, the percent change in the LDL cholesterol level was a reduction of 39.7% (95% confidence interval [CI], −43.7 to −35.7) in the inclisiran group and an increase of 8.2% (95% CI, 4.3 to 12.2) in the placebo group, for a between-group difference of −47.9 percentage points (95% CI, −53.5 to −42.3; P

To examine methods of assessing consent capacity in research protocols involving participants with impaired consent capacity, and examine instruments used to evaluate research consent capacity.A retrospective review of 330 active research protocols involving participants lacking capacity to consent over a 10-year period (January 1, 2009, through March 1, 2019) was conducted to collect protocol characteristics (medical specialty, level of risk and type of study, consent and assent procedures, and type of vulnerable or protected population). Methods to assess consent capacity are described, and instruments to assess consent capacity are summarized.The specialties most frequently involving participants with impaired consent capacity in research were Neurology (27.3%), Critical Care (16.7%), and Surgery (10%). Type of studies are observational (43.9%), clinical trials (33%), chart review (11.5%), biobank (6.1%), and biomarker (5.5%). Minimal risk (53.3%) outnumbered greater than minimal risk (46.7%) studies. Most obtained written informed consent (77%) and assent (40.9%). The most common method to assess consent capacity was direct assessment by investigators (32.7%). Only 86 (26%) studies used instruments to assess consent capacity. Of the 13 instruments used, the most common was the Evaluation of Decision-Making Capacity for Consent to Act as a Research Subject, and is the only instrument that assesses all four components of decisional capacity: understanding, appreciation, reasoning, and choice.Generally, there was lack of uniformity in determining capacity to consent to research participation. Very few studies used instruments to assess consent capacity. Institutional review boards can provide greater guidance for research consent capacity determination.

Background: \ud Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin–kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing.\ud Methods: \ud We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.\ud Results: \ud A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P

Objective: To investigate the pharmacodynamic properties of inclisiran, a small interfering RNA targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), in individuals with normal renal function and renal impairment (RI). Patients and Methods: The analysis included participants with normal renal function and mild, moderate, and severe RI from the phase 1 ORION-7 renal study (n=31) and the phase 2 ORION-1 study (n=247) who received 300 mg of inclisiran sodium or placebo. Results: In ORION-7, PCSK9 values were reduced at day 60 in the normal renal function group (68.1%±12.4%), mild RI group (74.2%±12.3%), moderate RI group (79.8%±4.9%), and severe RI group (67.9%±16.4%) (P

Supplemental Digital Content is available in the text., Grateful patients provide substantial philanthropic funding for health care institutions, resulting in important societal benefits. Although grateful patient fundraising (GPFR) is widespread, it raises an array of ethical issues for patients, physicians, development professionals, and institutions. These issues have not been described comprehensively, and there is insufficient guidance to inform the ethical practice of GPFR. Consequently, the authors convened a “Summit on the Ethics of Grateful Patient Fundraising,” with the goal of identifying primary ethical issues in GPFR and offering recommendations regarding how to manage them. Participants were 29 experts from across the United States who represented the perspectives of bioethics, clinical practice, development, law, patients, philanthropy, psychology, and regulatory compliance. Intensive discussions resulted in articulating ethical issues for physicians and other clinicians (discussions with patients about philanthropy; physician-initiated discussions; clinically vulnerable patients; conflicts of obligation and equity regarding physician’s time, attention, and responsiveness and the provision of special services; and transparency and respecting donor intent) as well as for development officers and institutions (transparency in the development professional–donor relationship; impact on clinical care; confidentiality and privacy; conflicts of interest; institution–patient/donor relationship; concierge services for grateful patients; scientific merit and research integrity; transparency in use of philanthropic gifts; and institutional policies and training in responsible GPFR). While these recommendations promise to mitigate some of the ethical issues associated with GPFR, important next steps include conducting research on the ethical issues in GPFR, disseminating these recommendations, developing standardized training for clinicians regarding them, and revising them as warranted.

Background: The ORION-1 trial (Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol [LDL-C]) demonstrated that inclisiran, an siRNA therapeutic that targets protease proprotein convertase subtilisin/kexin type 9 mRNA within hepatocytes, produces significant low-density lipoprotein cholesterol reduction. The effects of inclisiran on other lipids are less well described. Methods: ORION-1 was a phase 2 trial assessing 6 different inclisiran dosing regimens versus placebo. Participants with elevated low-density lipoprotein cholesterol despite receiving maximally tolerated statin therapy received a single-dose (200, 300, or 500 mg) or 2-dose starting regimen (100, 200, or 300 mg on days 1 and 90) of inclisiran or placebo. This prespecified analysis reports the percentage reductions in non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein (apo) B, very-low-density lipoprotein cholesterol, lipoprotein(a), triglycerides, HDL-C, and apo A1 at the primary efficacy time point (day 180) with mixed-effect models for repeated measures. Additional prespecified analyses report time course of changes from baseline at each visit to day 210, interindividual variation in response, and lipid goal attainment. Results: The mean age of the 501 participants was 63 years, 65% were male, 69% had atherosclerotic cardiovascular disease, 73% used statins, and mean low-density lipoprotein cholesterol was 128 mg/dL. A single dose of inclisiran reduced apo B, non–HDL-C, and very-low-density lipoprotein cholesterol over 210 days. A second dose of inclisiran provided additional lowering of these lipids. At day 180, non–HDL-C was lowered dose-dependently: by 25% from 148±43 to 110±45 mg/dL in the 200-mg single-dose group and by 46% from 161±58 to 91±58 mg/dL in the 2-dose 300-mg group. For the same dosing regimens, apo B was reduced by 23% from 101±23 to 78±29 mg/dL and by 41% from 106±31 to 65±33 mg/dL ( P Conclusions: Inclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting the synthesis of protease proprotein convertase subtilisin/kexin type 9 through siRNA may be a viable alternative to other approaches that target protease proprotein convertase subtilisin/kexin type 9. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02597127.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Objective To define the effect of a history of cancer on in-hospital and long-term mortality after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Patients and Methods In this retrospective cohort study of 2346 patients with STEMI enrolled in the Mayo Clinic PCI registry from November 1, 2000, through October 31, 2010, we identified 261 patients (11.1%) with a history of cancer. The in-hospital and long-term outcomes (median follow-up, 6.2 years; interquartile range=4.3-8.5 years), including cardiac and noncardiac death and heart failure hospitalization, of these patients were compared with those of 1313 cancer-negative patients matched on age, sex, family history of coronary artery disease, and date of STEMI. Results Patients with cancer had higher in-hospital noncardiac (1.9% vs 0.4%; P =.03) but similar cardiac (5.8% vs 4.6%; P =.37) mortality as matched controls. The group at highest acute mortality risk were those diagnosed as having cancer within 6 months before STEMI (hazard ratio [HR]=7.0; 95% CI, 1.4-34.4; P =.02). At 5 years, patients with cancer had similar cardiac mortality (4.2% vs 5.8%; HR=1.27; 95% CI, 0.77-2.10; P =.35) despite more heart failure hospitalizations (15% vs 10%; HR=1.72; 95% CI, 1.18-2.50; P =.01) but faced higher noncardiac mortality (30.0% vs 11.0%; HR=3.01; 95% CI, 2.33-3.88; P Conclusion One in 10 patients in this contemporary registry of patients undergoing primary PCI for STEMI has a history of cancer. These patients have more than a 3 times higher acute in-hospital and long-term noncardiac mortality risk but no increased acute or long-term cardiac mortality risk with guideline-recommended cardiac care.

OBJECTIVE: To ascertain whether temporal and geographic interest in seeking cardiovascular disease (CVD) information online follows seasonal and geographic patterns similar to those observed in real-world data. METHODS: We searched Google Trends for popular search terms relating to CVD. Relative search volumes (RSVs) were obtained for the period January 4, 2004, to April 19, 2014, for the United States and Australia. We compared average RSVs by month and season and used cosinor analysis to test for seasonal variation in RSVs. We also assessed correlations between state-level RSVs and CVD burden using an ecological correlational design. RESULTS: RSVs were 15% higher in the United States and 45% higher in Australia for winter compared with summer (P

Importance: Sustained reductions in low-density lipoprotein cholesterol (LDL-C) with lipid-lowering therapies that require frequent dosing are reliant on patient adherence, and poor adherence is associated with worse clinical outcomes. Objective: To determine whether inclisiran, a small interfering RNA, reduces mean LDL-C exposure with an infrequent dosing regimen. Design, Setting, and Participants: Prespecified analysis of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial. Participants were followed up monthly for LDL-C levels and proprotein convertase subtilisin-kexin type 9 (PCSK9) measurements as well as safety until their LDL-C levels had returned to within 20% of their change from baseline (maximum 360 days). The study included patients with elevated LDL-C despite maximally tolerated statin therapy. Data were analyzed between January 11, 2016, and June 7, 2017. Interventions: One dose (200, 300, or 500 mg on day 1) or 2 doses (100, 200, or 300 mg on days 1 and 90) of inclisiran sodium or placebo. Main Outcomes and Measures: Duration of time to return to within 20% of change from baseline for LDL-C levels and time-averaged LDL-C reductions over 1 year. Results: At baseline, among the 501 participants, 65% were men (n = 326 of 501), mean age was 63 years, 6% had familial hypercholesterolemia (n = 28 of 501), and 69% had established ASCVD (n = 347 of 501). Baseline LDL-C was 128 mg/dL among 501 randomized participants. The percentage of participants who were followed up to day 360 because their LDL-C levels had not returned to within 20% of their change from baseline ranged from 48.3% to 65.0% for those receiving a single dose and between 55.9% and 83.1% of those receiving 2 doses, with similar effects observed for PCSK9. Time-averaged reduction in LDL-C levels over 1 year after a single dose ranged from 29.5% to 38.7% (P

Patients with coronary artery disease (CAD) present clinically when their disease enters an unstable phase known as an acute coronary syndrome (ACS), in which the cap of a previously stable atheromatous coronary plaque ruptures or erodes, which in turn activates a thrombotic cascade that may lead to coronary artery occlusion, myocardial infarction (MI), cardiogenic shock, and patient death. There are nearly 2 million episodes of ACS in the United States annually; it is the most common reason for hospitalization with CAD and is the leading cause of death in the developed world. ACS patients include those with unstable angina (UA), non–ST segment elevation myocardial infarction (non-STEMI), and ST segment elevation myocardial infarction (STEMI) and patients who die suddenly of an arrhythmia precipitated by coronary occlusion. The distinction among various ACS subgroups reflects varying characteristics of clinical presentation (presence or absence of elevated cardiac biomarkers) and the type of electrocardiographic (ECG) changes manifested on the initial ECG at the time of hospitalization. This chapter focuses on UA and non-STEMI. A graph outlines mortality risks faced by patients with varying degrees of renal insufficiency. An algorithm describes the suggested management of patients admitted with UA or non-STEMI. Tables describe the risk stratification of the patient with chest pain, categories of Killip class, examination findings of a patient with high-risk ACS, diagnosis of MI, causes of troponin elevation other than ischemic heart disease, initial risk stratification of ACS patients, and long-term medical therapies and goals in ACS patients. This review contains 2 highly rendered figures, 11 tables, and 76 references.

Background The Accreditation Council for Graduate Medical Education (ACGME) has mandated revisions to residents' work hours to improve patient safety and enhance resident education and wellness. The impact on clinical outcomes on a national level is poorly understood. Objective We examined data from before and after the ACGME 2011 duty hour revision and looked for differences between teaching and nonteaching US hospitals. Methods A retrospective observational study of patients admitted to hospitals in the 2-year periods before and after the 2011 duty hour revision was conducted, utilizing a nationally representative data set. We compared patient and hospital characteristics using standardized differences. With nonteaching hospitals serving as the control group, we used multiple group interrupted time series segmented regression analysis to test for postrevision level and trend changes in mortality, length of stay (LOS), and costs. Results We examined more than 117 million hospitalizations. At teaching and nonteaching hospitals, trends in mortality and LOS in prerevision and postrevision periods were not significantly different (all P > .05). A significant monthly reduction in cost per hospitalization was noted postrevision at teaching hospitals (P = .019) but not at nonteaching hospitals (P = .62). In the 2 years following the 2011 revision, there was a monthly reduction in cost per hospitalization (–$52.28; 95% confidence interval –$116.90 to –$12.32; P = .026) at teaching relative to nonteaching hospitals. Conclusions There were no differences in mortality or LOS between teaching and nonteaching hospitals. However, there was a small decrease in cost per hospitalization at teaching hospitals following the 2011 revision.

PURPOSE: To assess trends in life support interventions and performance of the automated Acute Physiology and Chronic Health Evaluation (APACHE) IV model at mortality prediction compared with Oxford Acute Severity of Illness Score (OASIS) in a contemporary cardiac intensive care unit (CICU). METHODS AND MATERIALS: Retrospective analysis of adults (age ≥18 years) admitted to CICU from January 1, 2007, through December 31, 2015. Temporal trends were assessed with linear regression. Discrimination of each risk score for hospital mortality was assessed with use of area under the receiver operating characteristic curve (AUROC) values. Calibration was assessed with Hosmer-Lemeshow goodness-of-fit test. RESULTS: The study analyzed 10,004 patients. CICU and hospital mortality rates were 5.7% and 9.1%. APACHE IV predicted death had an AUROC of 0.82 (0.81–0.84) for hospital death, compared with 0.79 for OASIS (P

Background: Patients hospitalized for first acute coronary syndrome (ACS) are frequently discharged on multiple new medications. The short-term tolerability of these medications is unknown. Methods: This single-center cohort study assessed 30-day health-care utilization and how it may be impacted by medication prescribing trends. We included Olmsted County patients presenting with ACS and previously undiagnosed coronary artery disease in 2008 to 2009. All health-care contacts were reviewed 30 days after index hospital discharge for potential adverse medication effects including documented hypotension or bradycardia, or symptoms likely attributed to the medications. Results: The study included 86 patients; their mean age was 63 (standard deviation: 15.5 years). Antianginal or antihypertensive cardiovascular (CV) medications were prescribed to 98% of patients at discharge; 76% were prescribed 2 or more. There were 233 health-care contacts in 30 days; 90 (39%) of these contacts were unscheduled. More CV medications tended to be prescribed to patients with unscheduled contacts, both pre-ACS ( P = .045) and upon hospital discharge ( P = .051). Hypotension and/or bradycardia at follow-up occurred in 52 patients (60%). Surprisingly, there was no association between hypotension and/or bradycardia at follow-up and increased health-care utilization ( P = .12). Potential adverse drug effects were reported in 34 (40%) patients. These patients had significantly more total health-care contacts ( P < .001) and unscheduled health-care contacts (median 0 vs 1.5; P < .001). Conclusions: Symptoms of adverse drug effects were associated with more frequent health-care utilization after ACS. Clinicians need to consider this while striving to increase patient compliance with post-ACS medications and optimize care transitions.

The effectiveness of a pharmacoinvasive strategy consisting of fibrinolysis and transfer for percutaneous coronary intervention (PCI) compared to primary PCI (PPCI) in patients presenting to non-PCI-capable hospitals with ST-elevation myocardial infarction (STEMI) is not well defined. We analyzed data from the Mayo Clinic STEMI database of patients treated with a pharmacoinvasive strategy (favored in those presenting early after symptom onset) or PPCI in a regional STEMI network from 2004 to 2012. A total of 364 and 1,337 patients were included in the pharmacoinvasive and PPCI groups, respectively. Patients in the PPCI group were older and more frequently had cardiogenic shock at the time of presentation (12.1% vs 7.7%, p = 0.018). Death from any cause occurred in 58 (16%) and 314 (23%) patients in the pharmacoinvasive and PPCI groups, respectively (median follow-up 3.9 and 4.4 years, respectively). In multivariate analyses adjusting for age, gender, and other variables for which the 2 groups differed at baseline, there was no significant difference between the 2 strategies for 30-day (hazard ratio 0.66, 95% confidence interval 0.36 to 1.21) or overall mortality (hazard ratio 0.84, 95% confidence interval 0.63 to 1.12). Shorter door-to-balloon time was associated with increased effectiveness of PPCI (p for trend = 0.015), but there was no difference between the 2 strategies even when considering only the patients with door-to-balloon time in the lowest quartile. In conclusion, fibrinolysis followed by transfer for PCI represents a reasonable alternative when PPCI is not readily available especially in patients presenting early after symptom onset.

Background: Though cardiovascular disease is an important cause of mortality in patients with end-stage renal disease, epidemiology of ST-elevation myocardial infarction (STEMI) is less well described in this population. Methods: This study included STEMI hospitalizations in patients aged ≥20 using Nationwide Inpatient Sample Database from 2006 to 2010. Primary outcomes were incidence and trends of STEMI hospitalizations based on renal function status. We also looked at utilization of revascularization procedures, all-cause-hospital mortality and predictors of mortality. Results: Of the estimated 882,447 STEMI hospitalizations, 11,383 were on maintenance dialysis and 1,076 had renal transplants. The incidence of STEMI was over 7 times in patients on maintenance dialysis and 1.73 times in renal transplant recipients compared to the general population. This incidence has however declined in those on maintenance dialysis (p for trend Conclusions: STEMI hospitalizations are more common in patients on maintenance dialysis and with renal transplants. The utilization of revascularizations procedures remains low and mortality high in these patients.

Patients with diabetes (DM) and metabolic syndrome (MS) have elevated risks for atherosclerotic cardiovascular disease. Aggressive LDL-C lowering reduces risks. Inclisiran, a new siRNA, lowers LDL-C and was evaluated in patients with type 2 diabetes (DM), metabolic syndrome (MS) without DM or

IMPORTANCE: Infusing a high-density lipoprotein mimetic containing apolipoprotein A-I Milano demonstrated potential atheroma regression in patients following an acute coronary syndrome. To our knowledge, the effect of infusing a new mimetic preparation (MDCO-216) with contemporary statin therapy is unknown. OBJECTIVE: To determine the effect of infusing MDCO-216 on coronary atherosclerosis progression. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, randomized clinical trial conducted in 22 hospitals in Canada and Europe compared the effects of 5 weekly intravenous infusions of MDCO-216 at a dose of 20 mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measures were the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patients who demonstrated plaque regression. Safety and tolerability were also evaluated. RESULTS: Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93 men [76.2%]; 61 [50.0%] with prior statin use; and a mean [SD] low-density lipoprotein cholesterol [LDL-C] level of 87.6 [40.5] mg/dL [to convert to millimoles per liter, multiply by 0.0259]), 113 (92.6%) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levels were comparable with the placebo and MDCO-216 (68.6 vs 70.5 mg/dL; difference, −2.5 mg/dL; 95% CI, −10.1 to 5.0; P = .51). A reduction in high-density lipoprotein cholesterol levels was observed in MDCO, but not placebo patients (−3.3 vs 3.0 mg/dL [to convert to millimoles per liter, multiply by 0.0259]; difference, −6.3 mg/dL; 95% CI, −8.5 to −4.1; P

OBJECTIVE To evaluate the efficacy and safety of inclisiran by diabetes status. RESEARCH DESIGN AND METHODS ORION-1 (ClinicalTrials.gov, NCT02597127) randomized 501 subjects with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents and high LDL cholesterol (LDL-C), despite maximally tolerated LDL-C–lowering therapies, to one or two doses of placebo or inclisiran. Levels of lipids and proprotein convertase subtilisin/kexin type 9 (PCSK9) at baseline and day 180 were compared. RESULTS Inclisiran was associated with marked declines in LDL-C (median −28% to −52%, P < 0.0001 and −28% to −55%, P < 0.005 for all doses in the without- and with-diabetes groups, respectively) and PCSK9. The inclisiran-treated groups also had lower apolipoprotein B, non-HDL cholesterol, and lipoprotein(a) but higher HDL cholesterol. Inclisiran had an adverse profile similar to that of placebo, and adverse events were proportionally balanced in the baseline with- and without-diabetes groups. CONCLUSIONS PCSK9-targeted siRNA-driven strategies may provide a novel therapeutic option for managing dyslipidemia in the presence and absence of diabetes.

Inclisiran, an investigational PCSK9-specific RNA silencing molecule with potential for a maintenance regimen of twice yearly dosing, significantly lowered LDL-C and PCSK9 in the dose-ranging ORION-1 trial. We report its efficacy and safety by diabetes status, and its impact on glycemia. ORION-1 randomized 501 persons with atherosclerosis (ASCVD) or ASCVD-risk equivalents, and high LDL-C despite maximally tolerated LDL-C lowering therapies, to inclisiran or placebo. Inclisiran significantly lowered LDL-C and PCSK9 similarly in persons with and without diabetes at day 180 (Table). Temporal A1C were similar in the placebo and incisiran arms (Figure). These data suggest that inclisiran is efficacious and does not worsen glycemia in persons with ASCVD or ASCVD-risk equivalents, regardless of their diabetes status, over 180 days. Disclosure L. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation. H. Teoh: None. D. Kallend: Employee; Self; The Medicines Company. R. Wright: Consultant; Self; Boehringer Ingelheim GmbH, The Medicines Company, Sanofi-Aventis, Eli Lilly and Company, Regeneron Pharmaceuticals, Inc. U. Landmesser: Advisory Panel; Self; Boehringer Ingelheim GmbH, Medicines Company, Sanofi. Speaker's Bureau; Self; Amgen Inc. P.L. Wijngaard: Employee; Self; The Medicines Company. Stock/Shareholder; Self; The Medicines Company. J.J. Kastelein: Consultant; Self; The Medicines Company. K.K. Ray: Consultant; Self; Amgen Inc., Sanofi. Research Support; Self; Sanofi. Consultant; Self; The Medicines Company. Research Support; Self; Amgen Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Esperion Therapeutics, Kowa Pharmaceuticals America, Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp..

Older adults account for an increasing number of cardiac intensive care unit (CICU) admissions. This study sought to determine the predictive value of illness severity scores for mortality in CICU patients ≥70 years of age. Adult patients admitted to the CICU from 2007 to 2015 at one tertiary care hospital were reviewed. Severity of illness scores were calculated on the first CICU day. Area under the receiver-operator characteristic curve (AUROC) values were used to assess discrimination for hospital mortality in patients ≥70 versus

BackgroundOptimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU.Methods and ResultsAdult patients admitted to theCICUfrom January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed.SOFAscores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)‐IIIandAPACHE‐IVscores were calculated onCICUday 1. Discrimination of hospital mortality was assessed using area under the receiver‐operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all‐cause hospital mortality was 9.0%. Day 1SOFAscore predicted hospital mortality, with an area under the receiver‐operator characteristic curve value of 0.83; area under the receiver‐operator characteristic curve values were similar for theAPACHE‐IIIscore, andAPACHE‐IVpredicted mortality (P>0.05). Mean and maximumSOFAscores over multipleCICUdays had greater discrimination for hospital mortality (PSOFAscore from day 1 and day 2 had higher mortality. Patients with day 1SOFAscore SOFAscore predicted higher long‐term mortality (PConclusionsThe day 1SOFAscore has good discrimination for short‐term mortality in unselected patients in the CICU, which is comparable toAPACHE‐IIIandAPACHE‐IV. Advantages of theSOFAscore overAPACHEinclude simplicity, improved discrimination using serial scores, and prediction of long‐term mortality.

The sword of Damocles, a term derived from Greek mythology, refers to the perpetual sense of fear and dread of death under which specific individuals, usually leaders, must live. According to the Greek myth, Damocles, a courtier, switched places with King Dionysius II, the ruler of Syracuse (modern

There are now more than 50,000 hospitalists working in the United States. Limited empiric research has been performed to characterize clinical excellence in hospital medicine. We conducted a qualitative study to discover elements judged to be most pertinent to excellence in clinical care delivered by hospitalists.The chiefs of hospital medicine at five hospitals were asked to identify their "clinically best" hospitalists. Data collection, in the form of one-on-one interviews, was directed by an interview guide. Interviews were transcribed verbatim, and the informants' perspectives were analyzed using editing analysis to identify themes.A total of 26 hospitalists were interviewed. The mean age of the physicians was 38 years, 13 (50%) were women, and 16 (62%) were non-white. Seven themes emerged that related to clinical excellence in hospital medicine: communicating effectively, appreciating partnerships and collaboration, having superior clinical judgment, being organized and efficient, connecting with patients, committing to continued growth and development, and being professional and humanistic.This qualitative study describes how respected hospitalists think about excellence in clinical care in hospital medicine. Their perspectives can be used to guide continuing medical education, so that offered programs can pay attention to enhancing the skills of learners so they can develop towards excellence, rather than using only competence as the desired target objective.

The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has recently released the new cholesterol treatment guideline. This update was based on a systematic review of the evidence and replaces the previous guidelines from 2002 that were widely accepted and implemented in clinical practice. The new cholesterol treatment guideline emphasizes matching the intensity of statin treatment to the level of atherosclerotic cardiovascular disease (ASCVD) risk and replaces the old paradigm of pursuing low-density lipoprotein cholesterol targets. The new guideline also emphasizes the primacy of the evidence base for statin therapy for ASCVD risk reduction and lists several patient groups that will not benefit from statin treatment despite their high cardiovascular risk, such as those with heart failure (New York Heart Association class II-IV) and patients undergoing hemodialysis. The guideline has been received with mixed reviews and significant controversy. Because of the evidence-based nature of the guideline, there is room for several questions and uncertainties on when and how to use lipid-lowering therapy in clinical practice. The goal of the Mayo Clinic Task Force in the assessment, interpretation, and expansion of the ACC/AHA cholesterol treatment guideline is to address gaps in information and some of the controversial aspects of the newly released cholesterol management guideline using additional sources of evidence and expert opinion as needed to guide clinicians on key aspects of ASCVD risk reduction.

Objectives: This study sought to identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA).Background: Risk stratification for SCD, a major cause of mortality, i...

Cardiac arrest is the leading cause of death in Europe and the United States. Many patients who are initially resuscitated die in the hospital, and hospital survivors often have substantial neurologic dysfunction. Most cardiac arrests are caused by coronary artery disease; patients with coronary artery disease likely benefit from early coronary angiography and intervention. After resuscitation, cardiac arrest patients remain critically ill and frequently suffer cardiogenic shock and multiorgan failure. Early cardiopulmonary stabilization is important to prevent worsening organ injury. To achieve best patient outcomes, comprehensive critical care management is needed, with primary goals of stabilizing hemodynamics and preventing progressive brain injury. Targeted temperature management is frequently recommended for comatose survivors of cardiac arrest to mitigate the neurologic injury that drives outcomes. Accurate neurologic assessment is central to managing care of cardiac arrest survivors and should combine physical examination with objective neurologic testing, with the caveat that delaying neurologic prognosis is essential to avoid premature withdrawal of supportive care. A combination of clinical findings and diagnostic results should be used to estimate the likelihood of functional recovery. This review focuses on recent advances in care and specific cardiac intensive care strategies that may improve morbidity and mortality for patients after cardiac arrest.

Background The Effects of the P‐Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non‐ST‐Segment Elevation Myocardial Infarction ( SELECT ‐ ACS ) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P‐selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention ( PCI ). Methods and Results Patients (n=544) enrolled in the SELECT ‐ ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI ) were divided according to the time interval between study drug infusion and PCI . The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI . In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI , placebo‐adjusted geometric mean percent changes in troponin I, creatine kinase–myocardial band, and peak troponin I at 24 hours were −45.6% ( P =0.005), −30.7% ( P =0.01), and −37.3% ( P =0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI . Placebo‐adjusted geometric mean percent changes in troponin I and creatine kinase–myocardial band were −43.5% ( P =0.02) and −26.0% ( P =0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI , whereas the drug had no effect with longer intervals. Conclusions Inclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non– ST ‐segment elevation myocardial infarction, and benefits are larger when the infusion is administered PCI . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01327183.

Background Cardiac troponin is an independent predictor of cardiovascular mortality in individuals without symptoms or signs of cardiovascular disease. The mechanisms for this association are uncertain, and a role for troponin testing in the prevention of coronary heart disease has yet to be established. Objectives This study sought to determine whether troponin concentration could predict coronary events, be modified by statins, and reflect response to therapy in a primary prevention population. Methods WOSCOPS (West of Scotland Coronary Prevention Study) randomized men with raised low-density lipoprotein cholesterol and no history of myocardial infarction to pravastatin 40 mg once daily or placebo for 5 years. Plasma cardiac troponin I concentration was measured with a high-sensitivity assay at baseline and at 1 year in 3,318 participants. Results Baseline troponin was an independent predictor of myocardial infarction or death from coronary heart disease (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.4 to 3.7) for the highest (≥5.2 ng/l) versus lowest (≤3.1 ng/l) quarter of troponin (p < 0.001). There was a 5-fold greater reduction in coronary events when troponin concentrations decreased by more than a quarter, rather than increased by more than a quarter, for both placebo (HR: 0.29; 95% CI: 0.12 to 0.72 vs. HR: 1.95; 95% CI: 1.09 to 3.49; p < 0.001 for trend) and pravastatin (HR: 0.23; 95% CI: 0.10 to 0.53 vs. HR: 1.08; 95% CI: 0.53 to 2.21; p < 0.001 for trend). Pravastatin reduced troponin concentration by 13% (10% to 15%; placebo adjusted, p < 0.001) and doubled the number of men whose troponin fell more than a quarter (p < 0.001), which identified them as having the lowest risk for future coronary events (1.4% over 5 years). Conclusions Troponin concentration predicts coronary events, is reduced by statin therapy, and change at 1 year is associated with future coronary risk independent of cholesterol lowering. Serial troponin measurements have major potential to assess cardiovascular risk and monitor the impact of therapeutic interventions., Central Illustration

BACKGROUND: Patterns of clinical symptoms and outcomes of perioperative myocardial infarction (PMI) in elderly patients after hip fracture repair surgery are not well defined. METHODS: A retrospective 1:2 case-control study in a cohort of 1212 elderly patients undergoing hip fracture surgery from 1988 to 2002 in Olmsted County, Minnesota. RESULTS: The mean age was 85.3 ± 7.4 years; 76% female. PMI occurred in 167 (13.8%) patients within 7 days, of which 153 (92%) occurred in first 48 hours; 75% of patients were asymptomatic. Among patients with PMI, in-hospital mortality was 14.4%, 30-day mortality was 29 (17.4%), and 1-year mortality was 66 (39.5%). PMI was associated with a higher inpatient mortality rate (odds ratio [OR], 15.1; confidence interval [CI], 4.6–48.8), 30-day mortality (hazard ratio [HR], 4.3; CI, 2.1–8.9), and 1-year mortality (HR, 1.9; CI, 1.4–2.7). CONCLUSION: Elderly patients, after hip fracture surgery, have a higher incidence of PMI and mortality than what guidelines indicate. The majority of elderly patients with PMI did not experience ischemic symptoms and required cardiac biomarkers for diagnosis. The results of our study support the measurement of troponin in postoperative elderly patients for the diagnosis of PMI, in order to implement in-hospital preventive strategies to reduce PMI-associated mortality. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine

Background Evidence suggests that metabolic syndrome (MbS) is associated with early senescence of bioprosthetic aortic valve prostheses. The purpose of this study was to determine whether MbS is also associated with accelerated failure of bioprosthetic valves prostheses in the mitral position. Methods Records of all patients undergoing bioprosthetic mitral valve replacement (MVR) from 1993 to 2000 were reviewed. Results Of 114 patients undergoing bioprosthetic MVR, 48 (42%) had MbS. Mean age was 73 years (vs. 74 years for no MbS). Patients underwent MVR for regurgitation (n = 97; 85%), stenosis (n = 12; 11%), or mixed lesions (n = 4; 4%). Etiology was degenerative (n = 35; 32%), rheumatic (n = 26; 24%), ischemic (n = 30; 28%), calcific (n = 9; 8%), and endocarditis (n = 8; 8%). Mean follow-up was 4.5 years. Overall survival at 5 and 10 years was 56% and 26%, respectively. Survival was similar between groups (p = 0.15). Five patients (2 MbS; 4% vs. 3 no MbS; 5%) required mitral reoperation at a mean of 3.8 years after initial MVR. The risk of prosthetic valve failure was not different between groups (p = 0.66). Despite no initial difference in transmitral gradients, gradients beyond five-year follow-up were greater for those with MbS (6.8 mmHg MbS vs. 4.7 mmHg no MbS, p = 0.007). Independent predictors of gradient progression beyond two years were MbS (p = 0.027) and female gender (p = 0.012). There were no significant differences in valve area, regurgitation, or ejection fraction. Conclusions Although overall survival following bioprosthetic MVR is challenging, MbS did not predict diminished survival or excess reoperative risk compared to non-MbS patients. The trend toward more rapid progression of transprosthetic gradients in MbS patients warrants further investigation.

Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Cynthia D. Adams, RN, PhD, FAHA; Elliott M. Antman, MD, FACC, FAHA; Charles R. Bridges, MD, ScD, FACC, FAHA[‡][1]; Robert M. Califf, MD, MACC; Donald E. Casey, Jr, MD, MPH, MBA, FACP[§][2]; William E. Chavey II, MD, MS[#][3]; Francis M. Fesmire, MD

Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Cynthia D. Adams, RN, PhD, FAHA; Elliott M. Antman, MD, FACC, FAHA; Charles R. Bridges, MD, ScD, FACC, FAHA[‡][1]; Robert M. Califf, MD, MACC; Donald E. Casey, Jr, MD, MPH, MBA, FACP[§][2]; William E. Chavey II, MD, MS[#][3]; Francis M. Fesmire, MD

Both acute kidney injury and chronic kidney disease (CKD) are associated with adverse outcomes in acutely ill cardiac patients. The effect of admission renal dysfunction on outcomes in cardiac intensive care unit (CICU) patients is not well-defined. Historical cohort study of 9431 patients admitted

Use of epinephrine (EPI) may be associated with higher mortality in patients with cardiogenic shock. Outcomes associated with EPI in unselected cardiac intensive care unit (CICU) patients remain uncertain. Historical cohort study of 9989 patients admitted to a single academic CICU from January 2007