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Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE−/− mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery. RAS resulted in increased plasma angiotensin II levels, a mild, sustained increase in systolic blood pressure and increased aortic lipid deposition compared to sham-surgery. Surgically induced RAS led to the formation of atheroma in the infrarenal aorta and there was consistent and intense staining for Cyr61 within the atheroma. Treatment with irbesartan, aliskiren and amlodipine were associated with decreased aortic lipid deposition and decreased staining for Cyr61 in aortic atheroma. Serum levels of Cyr61 were not increased in mice or humans with RAS. In summary, Cyr61 expression in aortic atheroma but not serum is increased by RAS in ApoE−/− mice and is reduced by agents that lower blood pressure.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55–72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/

Introduction: Acute coronary syndrome (ACS) complicated by cardiac arrest (CA) has a heterogeneous presentation, and risk can be challenging to stratify. This study aimed to apply the SCAI cardiogenic shock stages to patients with ACS complicated by CA at early pivotal time intervals when prompt interventions may have a greater impact. Methods: Patients undergoing PCI presenting with CA were stratified according to the SCAI shock classification, retrospectively, on arrival to the cardiac catheterization laboratory (CCL) and on arrival to the intensive care unit (ICU). The primary end-point was in-hospital mortality. Secondary end-points were mortality stratified by the use of mechanical circulatory support or the level of vasopressor support used. Results: Between 01/2014 -08/2018, seventy-nine patients presented with ACS complicated by a CA. The mean age was 70 (SD ± 12) years, and 19 (24%) were females. On arrival to the CCL 17 (22%) were stage A, 6 (8%) were stage B, 31 (40%) were stage C, 19 (24%) were stage D, and 6 (8%) were stage E. In general, there was a stepwise increase in mortality with increasing stage (A 35% vs. B 16% vs. C 48% vs. D 68% vs. E 83%; p=0.05). There was a similar trend when stratified on arrival to the ICU (Figure 1), although of marginal statistical significance (P = 0.07). Presentation with shock stage D or E to the CCL was predictive of mortality (OR 3.7 CI 1.3-10.5; p=0.01) on logistic regression models. The use of mechanical support was not associated with increased mortality. However, the use of an Impella in patients requiring high vasopressor support at arrival to the CCL was associated with a trend towards decreased mortality (25% vs. 61%, p=0.18). Conclusion: Increasing SCAI shock stages on arrival to the CCL and ICU is associated with increased in-hospital mortality among patients who presented after a CA and underwent PCI. The SCAI classification at defined time points has the potential to serve as an important research tool.

Background Acute myocardial infarction (AMI) with left ventricular systolic dysfunction remains the largest cause for cardiogenic shock (CS) admissions. Aside for prompt revascularization few therapies have been shown to improve survival in this patient population. In the last decade, the use of mechanical circulatory support devices (MCS) for CS has increased, despite little evidence guiding their use. Purpose To explore for different baseline factors which may favor treatment with MCS vs pharmacological circulatory support (PCS) in AMI related CS. Methods Baseline clinical and procedural variables were retrospectively collected for all patient presenting to the cardiac cath lab with an AMI and CS at a large health care system. Patients were stratified by whether they received MCS or only PCS. The outcomes of interest were 30 day and one year mortality. Results Between 01/2014 andv08/2018, 205 patients presented to the cath lab with an AMI complicated by CS. The vast majority of cases were STEMIs (133/205, 65%). Overall mortality for the cohort at 30 days and one year were 41% and 50% respectively. There was no difference in 30 day or 1 year mortality between the MCS and PCS groups. A STEMI presentation was associated with increase 30 day mortality in the MCS group but the association was not seen at one year. Interestingly having a prior history peripheral vascular disease (PVD) and/or being on dialysis prior to the procedure was predictive of one year mortality in the MCS group (OR 3.8, 1.4–10.6, p=0.006) but not in the PCS. Conclusion Patients presenting with AMI complicated by CS have a high mortality despite successful revascularization. In our cohort having PVD and/or needing dialysis was predictive of mortality in patients receiving MCS. Patient selection is an important factor in choosing appropriate circulatory support, further prospective studies are needed. Figure 1 Funding Acknowledgement Type of funding source: None

Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE−/− mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery. RAS resulted in increased plasma angiotensin II levels, a mild, sustained increase in systolic blood pressure and increased aortic lipid deposition compared to sham-surgery. Surgically induced RAS led to the formation of atheroma in the infrarenal aorta and there was consistent and intense staining for Cyr61 within the atheroma. Treatment with irbesartan, aliskiren and amlodipine were associated with decreased aortic lipid deposition and decreased staining for Cyr61 in aortic atheroma. Serum levels of Cyr61 were not increased in mice or humans with RAS. In summary, Cyr61 expression in aortic atheroma but not serum is increased by RAS in ApoE−/− mice and is reduced by agents that lower blood pressure.

Aim: CYP2C19 genotyping is used to guide antiplatelet therapy after percutaneous coronary intervention (PCI). This study evaluated the potential impact of CYP2C19 and multigene pharmacogenomics (PGx) testing on medications beyond antiplatelet therapy in a real-world cohort of PCI patients that underwent CYP2C19 testing. Methodology & results: Multiple medications with actionable PGx recommendations, including proton pump inhibitors, antidepressants and opioids, were commonly prescribed. Approximately 50% received a CYP2C19 metabolized medication beyond clopidogrel and 7% met criteria for a CYP2C19 genotype-guided intervention. A simulation analysis projected that 17.5 PGx-guided medication interventions per 100 PCI patients could have been made if multigene PGx results were available. Conclusion: This suggests that CYP2C19 and multigene PGx results could be used to optimize medication prescribing beyond antiplatelet therapy in PCI patients.

Introduction: Isolated systolic hypertension (ISH) is the most common form of hypertension in older people. However, accurate identification of ISH may be hindered because cuff blood pressure (BP) underestimates systolic BP (SBP) and overestimates diastolic BP (DBP). This study aimed to determine the influence of cuff BP accuracy on the identification of ISH. Methods: Cuff BP and invasive aortic BP were measured simultaneous (or near-simultaneously) in 1737 subjects (63 ± 12 years, 68% male) during coronary angiography. Data was derived from 32 studies, using 20 different cuff BP devices, from the Invasive Blood Pressure Consortium (INSPECT). ISH was defined as ≥140/

Background: Cuff blood pressure (BP) is intended to approximate central aortic BP and accuracy is paramount. Sex differences in BP physiology could influence the accuracy of cuff BP as an estimate of invasive aortic BP, but this has not been explored in-depth and was the aim of this study. Methods: Cuff and invasive aortic BP were measured in 1701 subjects (31.9% female, aged 63 ± 12) during coronary angiography from the INvaSive blood PressurE ConsorTium (INSPECT) database. Cuff accuracy was defined as cuff–invasive BP. In a sub-sample (n = 376, 27% female, aged 63 ± 11), invasive brachial BP was recorded to assess systolic (SBP) amplification (invasive brachial–aortic SBP). Results: Invasive aortic SBP was higher in females compared with males (mean [95% CI]: 141.8 mmHg [137.1, 146.3] versus 132.9 mmHg [129.4, 136.4], p < 0.001). Cuff SBP significantly underestimated invasive aortic SBP in females compared with males (−3.1 mmHg [−5.9, −0.2] versus 1.4 mmHg [−1.1, 4.0], p < 0.001 for difference). Sex differences remained after adjustment for age and height. In the sub-sample, aortic-to-brachial SBP-amplification was lower in females (7.1 mmHg [3.3, 10.8] versus 10.2 mmHg [5.1, 15.4], p = 0.0070). Sex, SBP-amplification, height and age were associated with cuff BP inaccuracy, but only SBP-amplification and age remained associated in multivariable analysis (p < 0.05). Conclusion: Females have greater propensity towards cuff BP inaccuracy through underestimation of aortic SBP. Both age and the magnitude of aortic-to-brachial SBP-amplification are related to cuff BP inaccuracy, which provide greater understanding of sex differences in BP physiology and may help improve the accuracy of cuff BP methods.

Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types.

Highlights • Acute cardiovascular hospitalizations in NC declined after the state of emergency order. • Declines in rates were similar in both urban and rural counties, and older individuals experienced the most substantial declines. • After reopening measures, there was an abrupt rebound in acute cardiovascular hospitalizations. • Government orders closely correlate with health care seeking behavior in acute cardiovascular events., Objective Little is known about the effect of government-issued State of Emergency (SOE) and Reopening orders on health care behaviors. We aimed to determine the effect of SOE and Phase 1 of Reopening orders on hospitalizations for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF). Methods Hospitalizations for AMI and ADHF in the UNC Health system, which includes 10 hospitals in both urban and rural counties, were identified. An interrupted time series design was used to compare weekly hospitalization rates for eight weeks before the March 10th SOE declaration, eight weeks between the SOE order and Phase 1 of Reopening order, and the subsequent eight weeks. Results Overall, 3,792 hospitalizations for AMI and 7,223 for ADHF were identified. Rates before March 10th were stable. AMI/ADHF hospitalizations declined about 6% per week in both urban and rural hospitals from March 11th to May 5th. Larger declines in hospitalizations were seen in adults ≥65 years old (-8% per week), women (-7% per week), and White individuals (-6% per week). After the Reopening order, AMI/ADHF hospitalizations increased by 8% per week in urban centers and 9% per week in rural centers, including a significant increase in each demographic group. The decline and rebound in acute CV hospitalizations were most pronounced in the two weeks following the government orders. Conclusions AMI and ADHF hospitalization rates closely correlated to SOE and Reopening orders. These data highlight the impact of public health measures on individuals seeking care for essential services; future policies may benefit from clarity regarding when individuals should present for care., Graphical abstract Image, graphical abstract

Organizational models in the intensive care unit (ICU) have classically been described as either closed or open, depending on the presence or absence of a dedicated ICU team. Although a closed model has been shown to improve patient outcomes in medical and surgical ICUs, the merits of various care models have not been previously explored in the cardiac ICU (CICU) setting.From November 2012 to March 2014, data were prospectively collected on all admissions before and after transition from an open to closed CICU at our institution. Baseline clinical variables, illness severity, admission and discharge diagnoses, resource use, and outcomes were recorded. Anonymous surveys were also collected from nursing and resident trainee participants to evaluate the influence of unit structure on perceptions of care. Descriptive statistics were used, and logistic regression modeling was performed to examine the impact of unit structure on mortality.The study consisted of 670 patients, 332 (49.6%) of whom were admitted to the open CICU model and 338 (50.4%) of whom were admitted to the closed model. Neither CICU nor hospital mortality differed between the open and closed units, though length of stay was shorter in the closed CICU. Additionally, nurses and resident trainees reported that the closed CICU allowed for better communication, collaboration, and education.Although there was no significant impact of unit structure on patient outcomes in this single-center study, the closed CICU model was associated with better perceptions of care.

Objective To determine the ability of simple hemodynamic parameters obtained at the time of cardiac catheterization to predict in-hospital mortality following ST-elevation myocardial infarction (STEMI). Background Hemodynamic parameters measured at the time of primary percutaneous coronary intervention (PPCI) could potentially identify high-risk patients who would benefit from aggressive hemodynamic support in the Cardiac Catheterization laboratory. Methods This is a retrospective single-center study of 219 consecutive patients with STEMI. Left ventricular end-diastolic pressure (LVEDP), systolic blood pressure (SBP), and aortic diastolic blood pressure were obtained after successful revascularization. The prognostic ability of LVEDP, pulse pressure, and SBP/LVEDP ratio were compared to major mortality risk scores. Results Patients had a mean age of 60 ±14 years, were predominantly white (73%), male (64%), with anterior wall infarcts in 39%. Comorbidities included diabetes mellitus (27%), heart failure (9%), and chronic kidney disease (7%). In-hospital mortality was 9%. Patients with SBP/LVEDP ≤ 4 had increased risk of in-hospital death (32% vs. 5.3%, P 4. The area under curve (AUC) for SBP/LVEDP ratio for in-hospital mortality (0.69) was more predictive than LVEDP (0.61, P = 0.04) or pulse pressure (0.55, P = 0.02) but similar to Shock Index (ratio of heart rate to SBP) and Modified Shock Index (ratio of HR to mean arterial pressure). Conclusion An SBP/LVEDP ratio ≤ 4 identified a group of STEMI patients at high risk of in-hospital death. © 2017 Wiley Periodicals, Inc.

Atherosclerotic renal artery stenosis (RAS) is associated with high mortality rates, but large randomized trials have not shown improvement in survival with renal artery stenting. These results suggest that factors other than ongoing renal hypoperfusion are important in determining survival in patients with RAS. Using logistic regression models, we performed a single-center, case-control study that included 188 patients with ≥70% RAS with an average age of 67 ± 10 years, 54% women, 20% black, and 70% smokers; 118 patients (63%) underwent renal artery stenting. A total of 89 patients (47%) died during an average follow-up of 5.1 years. Previous myocardial infarction (MI) (odds ratio 2.6 95% confidence interval [1.4 to 4.7]), left ventricular ejection fraction (LVEF) ≤35% (odds ratio 4.1 95% confidence interval [1.6 to 10.6]), and renal insufficiency were predictors of mortality in this study. The risk associated with LVEF ≤35% and previous MI were additive with mortality of 40%, 54%, and 85%, respectively, with 0, 1, or both these factors. Renal artery stenting was associated with a 43% reduction in mortality in patients with 0 or 1 mortality risk factors (defined as LVEF ≤35%, previous MI, and glomerular filtration rate ≤45 ml/min/1.73 m 2 ) but had no effect on mortality in patients with 2 or 3 mortality risk factors. Systolic blood pressure, diastolic blood pressure, or severity of RAS did not correlate with survival. In conclusion, this retrospective analysis suggests that clinical, in addition to anatomic and physiological, factors should be considered in future studies examining effects of renal artery stenting on survival.

Following primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction, microvascular perfusion is often impaired secondary to thrombotic embolization. Intracoronary (IC) fibrinolytic administration may reduce thrombotic burden and distal embolization. The ICE-T-TIMI-49 study evaluated the feasibility and safety of low-dose IC tenecteplase (TNK) during PPCI. The study randomized 40 PPCI patients to a volume matched bolus of IC TNK (4 mg) (n = 20) or IC saline placebo (n = 20) before and following PPCI. The primary end point was percent diameter stenosis of the culprit lesion following first bolus. The primary end point did not differ between IC placebo (median 100%, interquartile range [IQR] 83.0,100.0) and IC TNK (median 100% stenosis, IQR 91.0,100.0; p = 0.522). However, the proportion of patients with reduction in thrombus following first bolus tended to be greater with IC TNK (placebo: 12.5% vs IC TNK: 40.0%, p = 0.133). Following PPCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC) was lower (faster) with placebo (16.0 frames [IQR 12.0,24.0] vs 24.0 frames [22.0,32.0], p = 0.045) due to a trend towards greater frequency of hyperemia (cTFC14), a marker of distal embolization (50.0% vs 8.3%, p = 0.056). There was no difference in TIMI major bleeds and no intracranial hemorrhage. In conclusion, treatment with low-dose IC TNK appears safe and well tolerated during PPCI. Although IC TNK administration did not improve percent stenosis, a trend towards reduced thrombus burden was demonstrated with less hyperemia (a marker of distal embolization). Our findings provide support for a large randomized study.

Background: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex. Methods: The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years. Results: From 1995 to 2014, 28 732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trendP for trend Conclusions: The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

Current guidelines recommend dual antiplatelet therapy—a P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin—for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y 12 inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.

Objectives: Accurate blood pressure (BP) measurement is critical for appropriate hypertension diagnosis and management. Aortic BP represents pressure loading on vital organs and this can be approximated using upper arm cuff BP. With advancing age, cuff systolic BP (SBP) increases and diastolic BP (DBP) decreases (widening pulse pressure [PP]), but whether age may influence cuff BP compared with invasive BP is unknown and was the aim of this study. Methods: Cuff BP was measured simultaneously, or near-simultaneously, with invasive aortic BP during catheterization in 1696 individuals within the INSPECT consortium (an international collaboration comprising data from 31 studies and 19 different cuff BP devices [17 oscillometric, 2 mercury sphygmomanometry]). Differences in cuff and invasive BP were assessed using mixed models. Results: Subjects were aged 63.3 ± 10.6 years and 32% female. Cuff SBP overestimated invasive aortic SBP in those aged 40–49, but with increasing age there was a progressive increase in the underestimation of aortic SBP (Table). Conversely, cuff DBP systematically overestimated aortic DBP, increasingly with age. Thus, there was a progressively higher error (underestimation) in cuff PP with older age. Adjusting models for sex, mean arterial pressure, heart rate and catheter type did not alter the findings, and no interactions between these parameters and age were found. Conclusion: Cuff BP is progressively more biased with increasing age, exposing older people to greater chance for misdiagnosis of risk related to BP. The findings highlight the need to improve cuff BP methods to ensure all people receive appropriate diagnosis and management of hypertension.

Objectives To determine the relationship between severity of stenosis and hemodynamic significance in calcified coronary arteries. Background Severity of stenosis is widely used to determine the need for revascularization but the effect of lesion calcification on hemodynamic significance is not well understood. Methods Two hundred consecutive patients undergoing fractional flow reserve (FFR) testing of an intermediate coronary lesion with a pressure wire and intravenous infusion of adenosine were studied. Coronary calcium was quantified based upon radiopacities at the site of the stenosis on cineangiography using the method of Mintz et al. (0 = none or mild calcium, 1 = moderate calcium, 2 = severe calcium). Results Mean age was 61 ± 11 years, 66% were males, 87.5% had hypertension, 44.5% had diabetes, and 20.5% were current smokers. The mean coronary stenosis by quantitative coronary angiography was 60 ± 12% and the mean FFR was 0.83 ± 0.08. There were 109, 45, and 46 patients classified as Calcium Score of 0, 1, or 2, respectively. Compared to those with no/mild or moderate calcification, patients with severe coronary calcium were older and more likely to have chronic kidney disease and pulmonary disease. The correlation between angiographic severity and FFR decreased as lesion calcification increased [calcium score = 0 (R2 = 0.25, P

Objectives Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI). Methods A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy. Results Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P

ST-segment elevation myocardial infarction (STEMI) is most commonly caused by an acute thrombotic occlusion of a coronary artery. For patients in whom the onset of STEMI occurs outside of hospital (outpatient STEMI), early reperfusion therapy with either fibrinolysis or primary percutaneous coronary intervention reduces complications and improves survival, compared with delayed reperfusion. STEMI systems of care are defined as integrated groups of separate entities focused on reperfusion therapy for STEMI, generally including emergency medical services, emergency medicine, cardiology, nursing, and hospital administration. These systems of care have been successful at reducing total ischaemia time and outpatient STEMI mortality. By contrast, much less is known about STEMI that occurs in hospitalized patients (inpatient STEMI), which has unique clinical features and much worse outcomes than outpatient STEMI. Inpatient STEMI is associated with older age, a higher female:male ratio, and more comorbidities than outpatient STEMI. Delays in diagnosis and infrequent use of reperfusion therapy probably also contribute to unfavourable outcomes for inpatient STEMI.

It is well established that the CYP2C19 nonfunctional *2 and *3 polymorphisms impair the bioactivation and antiplatelet effects of clopidogrel, and increase the risk of adverse cardiovascular events following percutaneous coronary intervention. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Recent studies have evaluated the impact of CYP2C19 genotype-guided selection of antiplatelet therapy on clinical outcomes and begun to close some of the gaps in knowledge and uncertainty that have impeded widespread clinical implementation of this precision medicine approach. This review will critically evaluate recent data and offer new insight into the potential clinical utility of genotype-guided antiplatelet therapy in the context of current clinical practice guidelines.

Challenges remain in predicting mortality and severe myocardial dysfunction in patients undergoing primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). Areas covered: Cardiogenic shock is associated with a high mortality rate. Less well characterized are patients who are not in cardiogenic shock but will die from pump failure as a result of a STEMI. There is a long history of using hemodynamics to risk stratify patients with acute MI with the Killip class being shown to provide prognostic information in the prereperfusion, thrombolytic and PPCI eras. Recent studies have identified low systolic blood pressure (SBP), elevated heart rate, elevated left ventricular end diastolic pressure (LVEDP), and low SBP/LVEDP ratio as hemodynamic parameters associated with early mortality in patients undergoing PPCI. Although infrequently used, prognostic information can be obtained from right heart catheterization in the setting of STEMI with the best-studied parameters being cardiac power, pulmonary capillary wedge pressure (PCWP), cardiac output, right atrial pressure/PCWP ratio, and pulmonary artery pulsatility index. Expert commentary: Hemodynamic parameters measured at the time of PPCI provide important prognostic information. Whether hemodynamics can be used to determine which patients benefit from early initiation of mechanical support remains to be determined.

Author(s): Dong, Olivia M; Li, Amy; Suzuki, Oscar; Oni-Orisan, Akinyemi; Gonzalez, Ricardo; Stouffer, George A; Lee, Craig R; Wiltshire, Tim | Abstract: AIM:To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing. MATERIALS a METHODS:A retrospective analysis was conducted with 122 cardiac catheterization laboratory patients undergoing angiography for eligibility of potential PGx-guided interventions that could have occurred if multigene PGx information was pre-emptively available at the time of the procedure. Medication data and presence of actionable at-risk genotypes were used to determine eligibility of a PGx intervention. RESULTS:20% of the study population (n = 24) would have qualified for at least one PGx-based medication intervention per US FDA or Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines within 6 months of their cardiac catheterization procedure. Commonly encountered gene-drug pairs for these interventions included: CYP2C19 for clopidogrel and antidepressants, CYP2D6 for antidepressants and codeine, SLCO1B1 for simvastatin, and VKORC1/CYP2C9 for warfarin. CONCLUSION:Pre-emptive use of a multigene PGx test in the cardiac catheterization laboratory offers potential to reduce adverse medication outcomes.

Background: CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention. The feasibility, sustainability, and clinical impact of using CYP2C19 genotype–guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. Methods: A single-center observational study was conducted in 1193 patients who underwent percutaneous coronary intervention and received DAPT after implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation end points. Risk of major adverse cardiovascular or cerebrovascular and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. RESULTS: CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing ( P P =0.001) varied over time. Risk for major adverse cardiovascular or cerebrovascular was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio, 4.65; 95% confidence interval, 2.22–10.0; P P =0.347). Bleeding event rates were similar across groups (log-rank P =0.816). Conclusions: Implementing CYP2C19 genotype–guided DAPT is feasible and sustainable in a real-world setting but challenging to maintain at a consistently high level of fidelity. The higher risk of major adverse cardiovascular or cerebrovascular associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.

Background: The optimal anticoagulation strategy for percutaneous coronary interventions (PCIs) remains debated. We report outcomes after switching from a bivalirudin-first to an unfractionated heparin (UFH)-first strategy for PCIs in a large academic center. Methods: Patients undergoing PCI from June 1 st 2013–May 31 st , 2015 were identified through the National Cardiovascular Data Registry (NCDR), and divided into the “bivalirudin era” (June 2013–July 2014) and the “UFH era” (October 2014–May 2015). Bleeding outcomes were compared using multivariable logistic regression adjusted for potential confounders. Results: A total of 1,145 patients were identified (bivalirudin era =752, UFH era =393). Radial access for PCI increased over time, and was lower in the bivalirudin era (26% vs. 34%, P

Background The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction ( MI ) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non–ST‐segment–elevation myocardial infarction ( NSTEMI) . We aim to evaluate the impact of type 2 MI on hospital‐level NSTEMI metrics and discuss the implications for quality and public reporting. Methods and Results We conducted a single‐center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI . Weighted Kaplan–Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI . Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P P MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67–7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44–2.73) after discharge. Type 2 MI was also associated with a lower 30‐day cardiovascular‐related readmission (risk ratio: 0.49; 95% confidence interval, 0.12–2.06). Conclusions NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI . Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics.

Importance In-hospital ST-segment elevation myocardial infarction (STEMI) is a unique clinical entity with epidemiology, incidence, and outcomes distinct from that of out-of-hospital STEMI and has only within the past 10 years begun to receive increased attention and research. Patients with in-hospital STEMI are older, have more comorbidities, and more frequently have coagulopathies and contraindications for anticoagulation and fibrinolytic therapy. A standardized clinical definition of in-hospital STEMI is lacking. The objectives of this special communication are to (1) summarize the knowledge base regarding in-hospital STEMI; (2) review the challenges of diagnosis and treatment of patients with in-hospital STEMI; (3) present a standardized clinical definition for in-hospital STEMI; and (4) provide a quality improvement protocol to improve diagnosis, triage, and treatment of patients with in-hospital STEMI. Observations Patients with in-hospital STEMI less frequently present with typical angina symptoms, and an electrocardiogram is often obtained owing to changes in clinical status, changes on telemetry, or a finding of elevated cardiac biomarker. The frequent nontypical presentations often lead to substantial delays in the diagnosis of STEMI. Only 34% to 71% of patients with in-hospital STEMI undergo diagnostic catheterization, and only 22% to 56% undergo percutaneous coronary intervention. Even in contemporary reports, some studies report in-hospital mortality in the range of 31% to 42%. Three areas of delay in the treatment of patients with in-hospital STEMI that merit particular attention are (1) delays in electrocardiogram acquisition, (2) delays in electrocardiogram interpretation, and (3) delays in activation of existing STEMI systems of care. Conclusions and Relevance Treatment of patients with in-hospital STEMI is more complex and challenging than treatment of patients who develop out-of-hospital STEMI, leading to delays in diagnosis and triage and less frequent use of reperfusion therapy. Quality improvement programs targeted at decreasing delays and streamlining treatment of such patients may improve treatment and outcome.

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. Particulate matter-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/−) mice which possess decreased anti-oxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/− mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/− mouse aortas, and relaxation was significantly reduced in young SOD2+/− compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/− mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of anti-oxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/− mice.