Cardiac-disease-induced posttraumatic stress symptoms (CDI-PTSS) among cardiac patients' partners: A longitudinal study.

OBJECTIVE: Cardiac-disease-induced posttraumatic stress symptoms (CDI-PTSS) have been detected among a substantial number of cardiac patients. Even though patients' caregiving partners are also susceptible to CDI-PTSS, the research on cardiac partners' CDI-PTSS is scarce. Based on the ecological model of trauma and recovery, we investigated levels of partners' CDI-PTSS over time, and factors that potentially contribute to it. METHOD: During patients' hospitalizations, partners (N = 143) provided data regarding demographic variables and peritraumatic emotional distress (depression and anxiety). Four months later, partners' CDI-PTSS, their emotional distress, fear of patients' illness progression, and perceived social support were assessed. Eight months posthospitalization, partners filled out questionnaires tapping CDI-PTSS. Hypotheses were tested using structural equation modeling (SEM). RESULTS: A mild level of CDI-PTSS was detected among partners, 4 and 8 months after patients' cardiac event. Partners' distress as measured during patients' hospitalization, and their fear of patients' illness progression, contributed to the manifestation of CDI-PTSS over time. CONCLUSIONS: The findings shed light on potential risk factors for partners' CDI-PTSS. Interventions to ameliorate partners' distress and fear of illness progression should be designed toward reducing the development of CDI-PTSS among partners. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports.

AIM: There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID-19) pandemic. We analysed real-world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ-associated cardiovascular adverse events (CVAEs) in pre-COVID-19 reports. METHODS: We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014-9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 ). RESULTS: The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3-35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3-6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8-2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9-2.7], all IC025 > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ-associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). CONCLUSION: In a real-world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ-associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off-label indication, especially for patients with cardiac disorders.

Early Exposure to Cardiac Treatment and Distress Among Patients and Their Caregiving Partners.

Background: The experience of an acute coronary event (ACE), including early care and evaluation, can be a distressing and traumatic experience for patients and their romantic partners, who also act as caregivers. We hypothesized that, among partners who were present during the ACE, those who were also present during (1) transportation to the hospital and (2) initial medical treatment would experience greater (a) anxiety early post-event and (b) posttraumatic stress symptoms (PSS) related to the event 4 months later. The associations between partner presence with patient anxiety and PSS were also explored. Methods: Participants were ACE patients and their partners recruited between March 2015 and December 2016 from the Intensive Cardiac Care Unit (ICCU) of the Sheba Medical Center in Israel (N = 143; all patients were males and partners were females). Partners self-reported whether or not they were present during the cardiac event, the hospital drive, and initial care. Patients and partners self-reported anxiety in-hospital and PSS, keyed to the ACE, an average of 4 months later. Data were analyzed using General Estimating Equations (GEE) and Multilevel Modeling. Results: Neither patient anxiety nor PSS differed according to partner presence during the drive to the hospital. In contrast, partners had higher anxiety when they were not present at all (difference = 3.65, p = 0.019) and when present during the event and during the drive (difference = 2.93, p = 0.029) as compared to when they were present for the event but not for the drive. Partners who were present during the event, but not the drive, had lower PSS than those who were present for both the event and the drive (difference = -4.64, p = 0.026). Conclusions: Partners who accompany patients on the drive to the hospital may inadvertently put themselves at risk for greater distress following their loved one's cardiac event. Future research should enroll couples in an acute care context to inform couple-targeted tailored interventions to reduce distress in patients and their caregiving partners.

Data for a population based cohort study on abnormal findings of electrocardiograms (ECG), recorded during follow-up periodic examinations, and their association with long-term cardiovascular morbidity and all-cause mortality.

In this Data in Brief article, we provide data of the cohort and statistical methods of the research- "Incidental abnormal ECG findings and long-term cardiovascular morbidity and all-cause mortality: a population based prospective study" (Goldman et al., 2019). Extended description of statistical analysis as well as data of cohort baseline characteristics and baseline ECG incidental abnormal findings of 2601 Israeli men and women without known cardiovascular disease (CVD) is presented. The cohort is part of the Israel study of Glucose Intolerance, Obesity and Hypertension (GOH) (Dankner et al., 2007). Furthermore, we provide the data on the performance assessment of the 23 - year CVD-risk and the 31- year all-cause mortality prediction models, which includes Receiver Operating Characteristic (ROC) curves, reclassification-based measures and calibration curve.

Incidental abnormal ECG findings and long-term cardiovascular morbidity and all-cause mortality: A population based prospective study.

BACKGROUND: The additional prognostic value of resting electrocardiogram (ECG) in long-term cardiovascular disease (CVD)-risk-assessment is unclear. We evaluated the association of incidental abnormal ECG findings with long-term CVD-risk and all-cause mortality, and assessed the additional prognostic value of ECG as a screening tool in adults without known CVD. METHODS: A cohort of 2601 Israeli men and women without known CVD were actively followed from 1976 to 1982 for 23-year cumulative CVD-incidence, and until May 2017 for all-cause mortality. At baseline and follow-up, participants underwent interviews, physical examinations, blood tests and ECG. RESULTS: At baseline, 1199 (46.1%) had incidental abnormal ECG findings (exposed-group). CVD cumulative incidence reached 31.6% among the 930 survivors who participated in the active follow-up (294/930). During a 31-year median follow-up, 1719 (66.1%) of the total cohort died. Incidental abnormal ECG findings were associated with 46% greater CVD-risk (odds ratio = 1.46, 95%CI = 1.09-1.97). The net reclassification improvement (NRI) of CVD-risk was 7.4% (95%CINRI = 1.5%-13.3%, p = 0.01) following the addition of ECG findings, but the C-index improvement was not statistically significant [C-index = 0.656 (0.619-0.694) vs. C-index = 0.666 (0.629-0.703), p = 0.14]. Multivariable Cox regression demonstrated an all-cause mortality hazard ratio (HR) of 1.18 (95%CI = 1.07-1.30) for exposed vs. unexposed individuals. Non-specific T-wave changes and left-axis deviation are the incidental ECG abnormalities that were associated with all-cause mortality [HR = 1.18 (95%CI = 1.05-1.33) and HR = 1.19 (95%CI = 1.00-1.42), respectively]. CONCLUSION: Incidental abnormal ECG findings, mainly non-specific T-wave changes and left-axis deviation, were associated with increased long-term CVD-risk and all-cause mortality among individuals without known CVD, and demonstrated net reclassification improvement for CVD-risk.

Participation in an Exercise-Based Cardiac Rehabilitation Program and Functional Improvement of Heart Failure Patients with Preserved Versus Reduced Left Ventricular Systolic Function.

BACKGROUND: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF. OBJECTIVES: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program. METHODS: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later. RESULTS: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3). CONCLUSIONS: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

Cardiac-disease-induced PTSD and Fear of illness progression: Capturing the unique nature of disease-related PTSD.

According to Edmondson's Enduring Somatic Threat (EST) Model of PTSD Due to Acute Life-Threatening Medical Events, the nature of PTSD in the context of illness may differ from the nature of "traditional" PTSD in that it includes future-oriented alongside past-related intrusive thoughts. Yet almost no empirical studies to date have assessed the putative future-oriented quality of cardiac-disease-induced PTSD (CDI-PTSD). In the current study, we assessed the hypothesized associations between CDI-PTSD and fear of illness progression (FoP) - a novel theoretical conceptualization of patients' future-related anxieties. We hypothesized that FoP would be positively associated with CDI-PTSD, and especially with its specific items of intrusive thoughts. Patients (N = 112) were interviewed three months post-hospitalization for an acute coronary event via use of the PSS-SR-5 (to assess PTSD symptomatology), the FoP-Q-SF (to assess fear of illness progression), and the HADS (to assess anxiety and depression levels). Results indicated a strong positive association between CDI-PTSD and FoP, even when controlling for anxiety and depression. As hypothesized, the concepts of CDI-PTSD and fear of illness progression were strongly associated both at the level of the clusters as well as at the level of the specific items. The current study provides an initial empirical validation of the EST Model, especially regarding the future-oriented nature of PTSD resulting from acute cardiovascular disease.

Trends in the management and outcomes of patients admitted with acute coronary syndrome complicated by cardiogenic shock over the past decade: Real world data from the acute coronary syndrome Israeli survey (ACSIS).

Registries and other cohorts have demonstrated that early revascularization improve the survival of patients presenting with Cardiogenic Shock (CS) completing Aute coronary syndrome (ACS). Our aim was to describe the change in the clinical characteristics of these patients and their management and their outcome. The study population comprised 224 patients who were admitted with ACS complicated by cardiogenic shock who were enrolled in the prospective biannual Acute Coronary Syndrome Israeli Surveys (ACSIS) between 2000 and 2013 (1.7% of all patients admitted with ACS during the study period). Survey periods were categorized as early (years 2000-2004) and late (year 2006-2013).The rate of cardiogenic shock complicated ACS declined from 1.8% between the years 2000-2004 to 1.5% during the years 2006-2013. The clinical presentation in both the early and late groups was similar. During the index hospitalization primary percutaneous coronary intervention (PPCI) was more frequently employed during the late surveys [31% vs. 58% (p<0.001)], while fibrinolysis therapy was not used in the late surveys group [27% vs. 0.0% (p=<0.001)]. Compared to patients enrolled in the early surveys, those enrolled in the late survey group experienced significantly lower mortality rates at 7-days (44% vs. 30%, respectively; p=0.03). However, this difference was no longer statistically significant at 30-days (52.8% vs. 46.4%, respectively, p=0.34) and 1-year (63% vs. 53.2%, respectively, p=0.14). Similarly, the rate of major adverse cardiac events (MACE) at 30-days was similar between the two groups (57.4% vs. 47.4%, respectively, p=0.13).Our findings indicate that patients admitted with ACS complicated by cardiogenic shock still experience very high rates of MACE and mortality during follow-up, despite a significant increase in the use of PPCI in this population over the past decade.

Caregiving styles and anxiety among couples: coping versus not coping with cardiac illness.

BACKGROUND AND OBJECTIVES: partners' caregiving efforts are not always beneficial to both recipient and provider. Bowlby's conceptualization of caregiving style as a stable predisposition may clarify such caregiving effects. The relationship between caregiving style (compulsive and sensitive) and anxiety among couples coping with cardiac illness and a matching control group not coping with cardiac illness were assessed. We hypothesized that one's compulsive caregiving would associate positively, and one's sensitive caregiving would associate negatively, with one's and one's partner's anxiety across contexts (cardiac and non-cardiac) and gender. DESIGN: A comparative design of 131 couples with a diagnosis of husbands' acute cardiac syndrome and 68 matched couples in the community was applied. METHODS: The Adult Caregiving Questionnaire and the Brief Symptoms Inventory were administered. RESULTS: Structural equation modeling revealed that one's compulsive caregiving was positively associated with one's anxiety, across most contexts. Multi-group analyses revealed that the associations between one's compulsive caregiving and one's partner's anxiety levels differed depending on gender and context. CONCLUSIONS: The distress which emerges in an individual who takes on a caregiving role and in his/her partner seems to result not only from the demands of the concrete caregiving situation but also from one's and one's partner's developmental history.

Cardiac Disease-Induced Post-traumatic Stress Symptoms (CDI-PTSS) Among Patients' Partners.

It is well established that a patient's partner can be deeply affected by the traumatizing nature of the patient's illness. Yet, no study to date has focused on post-traumatic stress symptoms (PTSS) among partners of patients coping with an acute coronary syndrome (ACS). The current study's main aims were to address this gap and to evaluate cardiac disease-induced (CDI) PTSS prevalence in partners of patients who experienced ACS. Patients who experienced ACS and their partners were interviewed by telephone 2 to 6 months after patients' hospitalization. All patients and partners were screened for CDI-PTSS. Demographic and medical variables as well as partners' level of exposure to the cardiac event were assessed. Prevalence of CDI-PTSS was higher among partners than among patients. Partners' number of CDI-PTSS was not significantly associated with patients' number of CDI-PTSS or with any of the other explanatory factors measured, except for education level. The preliminary results that arose from the current study point to the vast number of individuals who must act as caregivers for their ill partners while having to cope with their own PTSS. Much effort should be channelled into integrating partners into cardiac recovery programmes. Copyright © 2016 John Wiley & Sons, Ltd.

"It takes two to take": Caregiving style, relational entitlement, and medication adherence.

Partners' support has been associated with both patients' increased and decreased inclination toward health-promoting behaviors. Our hypothesis for understanding this enigma is that it is the interplay between partners' manner of care provision and patients' ability to accept these care efforts that may best predict patients' adherence. Thus, the current study's main goal was to examine the contribution of the interaction between caregivers' support style (sensitive and compulsive) and cardiac patients' sense of relational entitlement (restricted, excessive, assertive, entitlement expectations) to patients' medication adherence. The Adult Caregiving Questionnaire, the Sense of Relational Entitlement Scale, and the Medication Adherence Report Scale were administered to 114 cardiac patients and their partners, during patients' hospitalizations and 6 months later. The lowest levels of medication adherence were detected among patients high on restricted entitlement who were married to partners high on compulsive caregiving style. These findings strengthen our claim that it is the interaction between recipients' personality and providers' support style which explain self-regulatory processes that arise during times of family medical crises. (PsycINFO Database Record

A Three-Decade Survival Analysis of Intraventricular Conduction Delay in Adults Without Ischemic Heart Disease.

BACKGROUND: The prognosis of an incidental finding of intraventricular conduction delay in individuals without ischemic heart disease is debatable. Intraventricular conduction delay presents electrocardiographically as bundle branch block or nonspecific intraventricular conduction delay. We aimed to assess the long-term survival of an incidental intraventricular conduction delay finding in a cohort of individuals without ischemic heart disease, followed up for 3 decades. METHODS: A randomized stratified cohort of the adult Israeli population underwent medical examinations and electrocardiography between 1976 and 1982. Patients with ischemic heart disease were excluded, and the cohort was followed for all-cause mortality for a median of 30.4 years. Major intraventricular conduction delay was defined as having complete bundle branch block or nonspecific intraventricular conduction delay, and minor intraventricular conduction delay was defined as having incomplete bundle branch block. Cox proportional hazard model was performed, comparing individuals by electrocardiogram finding, adjusting for demographic, clinical, and electrocardiographic variables. RESULTS: Of 2465 subjects, 2385 (96.8%) were without intraventricular conduction delay, 38 (1.5%) had minor intraventricular conduction delay, and 42 (1.7%) had major intraventricular conduction delay. All-cause mortality rates were higher among minor and major intraventricular conduction delay groups (57.9% and 66.7%, P = .43 and P = .04, respectively) compared with no intraventricular conduction delay (52.1%). By controlling for sex, age, and body mass index, intraventricular conduction delay was not associated with all-cause mortality: hazard ratios, 0.82 (95% confidence interval, 0.52-1.25) and 1.06 (95% confidence interval, 0.72-1.54) for minor and major intraventricular conduction delay, respectively. CONCLUSIONS: Intraventricular conduction delay was not found to be an independent risk factor for all-cause mortality in individuals without ischemic heart disease.

Comparison of Noninvasively and Invasively Managed Patients, With or Without Revascularization in Non-ST Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey).

Patients with non-ST elevation myocardial infarction who are managed noninvasively at presentation or are catheterized but without revascularization represent a heterogeneous and understudied population. We evaluated the clinical characteristics, management strategies, and outcomes of patients with non-ST elevation myocardial infarction (NSTEMI) who were enrolled in the prospective biannual Acute Coronary Syndrome Israeli Surveys from 2004 to 2013. Patients were divided into 3 groups: no catheterization (no angio), catheterization with revascularization (angio-revascularized), and catheterization without revascularization (angio-nonrevascularized) groups. The study included 3,198 patients with NSTEMI. Coronary angiography was performed in 2,525 (79%) during the index hospitalization, of whom 1899 (59%) underwent revascularization. Evidence-based therapies were administered during the index hospitalization at a significantly higher rate to those in the angio-revascularized group compared with the other 2 groups. Multivariate analysis showed that compared with those in the angio-revascularized and angio-nonrevascularized groups, patients in the no angio group experienced a significantly higher risk for 1-year mortality (hazard ratio 2.04 [p ≤0.0001] and 1.21 [p = 0.01], respectively). The risk associated with no revascularized was consistent in each risk subset analyzed, including an older age, and increased creatinine levels. In conclusion, our data, from a large real-world contemporary experience, suggest that patients with NSTEMI who do not undergo coronary revascularization during the index hospitalization represent a greater risk and undertreated group with increased risk for long-term mortality.

Cardiac troponin elevation pattern in patients undergoing a primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: characterization and relationship with cardiovascular events during hospitalization.

HYPOTHESIS: We aimed to describe the kinetics and associated prognostic implications of the cardiac troponin release curve after a primary percutaneous coronary intervention (PPCI) in patients presenting with ST-segment elevation myocardial infarction (STEMI). PATIENTS AND METHODS: We prospectively determined, in a prespecified timely manner, serial cardiac troponin I levels and obtained clinical, ECG, and echocardiographic data from 175 consecutive patients hospitalized with STEMI who underwent PPCI. The median peak troponin levels and time until troponin peaking were determined. RESULTS: The troponin elevation curve following PPCI was single peaked, with a median value measuring 715 times the upper normal limit and a median peaking time of 8 h. Later-peaking troponin levels were associated with a TIMI flow grade of 0/1 at the initiation of angiography and with lack of at least 70% regression in the ST-elevation on the first post-PPCI ECG. Higher peak values were similarly associated with these two parameters as well as with a lower blush score and with distal embolization during PPCI. Both higher peak values and later peaking of troponin were associated independently with higher occurrence of the combined adverse cardiovascular event outcomes consisting of death, congestive heart failure, and recurrent infarction. CONCLUSION: The cardiac troponin elevation curve following PPCI for STEMI shows a single peak and is affected by the adequacy of myocardial reperfusion. This method can serve as a simple surrogate for risk stratification of patients with STEMI who undergo PPCI.

[A snapshot: the causes of admission and complications to an acute coronary care unit in a tertiary center in Israel].

BACKGROUND: The reasons for admission to the Acute Coronary Care Unit (ACCU) have changed in the past few years. The classical cause of acute coronary syndrome sets aside the causes of acute heart failure and post-procedural complications. There is also a change in the demographic characteristics and co-morbidities of the admitted patients. OBJECTIVES: The aim of this study is to illustrate the current causes of admission and complications during hospitalization in a tertiary center. METHOD: We compiled a computerized prospective registry during the months of January to March 2014. The registry includes the cause of admission, demographic characteristics, co-morbidities, interventions and clinical outcomes. RESULTS: A total of 257 patients were admitted to the ACCU with a calculated sum of 937 hospitalization days. The average age was 67 ± 15; a third of the patients were above the age of 75 and a third were female; 100 patients have presented with other co-morbidities such as COPD, chronic renal failure, CVA or malignancy; and 46% of the patients were admitted due to acute coronary syndrome (ACS). Other causes were acute heart failure, shock and post-procedural complications. The average length of hospitalization was 2.9 ± 1.7 days for ACS patients compared to 4.3 ± 5 days due to other causes. Approximately 25% had developed acute heart failure during their hospital stay; most of them were older with higher rates of co-morbidities. The duration of hospitalization was longer in those patients, 5.5 ± 5 days, compared to 3.2 ± 4 (p < 0.005); 20% of the patients needed mechanical ventilation; 8.3% had acute renal failure; 4.7% acquired infection while hospitalized; 3.1% had major bleeding and 1.9% had arrhythmias. The total mortality rate was 2.3%. Patients who presented with ACS had a mortality rate of 1% compared to patients who were admitted due to heart failure or shock who had a mortality rate of 10.4% in this period. CONCLUSION: We have presented the current trend of admission to the ACCU with a shift from ACS to other cardiac causes such as acute heart failure, shock or peri-procedural complications. The rate of co-morbidities and hospital complications is increasing as the patients' age increases. This shift of patients' characteristics requires a re-examination of the role of the medical staff in this new era. There is a need to increase funding for acquiring new technology, staff education and reinforcing current staff.

Clinical outcomes and cost effectiveness of accelerated diagnostic protocol in a chest pain center compared with routine care of patients with chest pain.

AIMS: The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department. METHODS AND RESULTS: Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14-0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)]. CONCLUSION: An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.

Thrombophilic state in young patients with acute myocardial infarction.

The prevalence of thrombophilia and dyslipidemia among young survivors of acute coronary syndrome has not been clearly defined. The purpose of the current study was to investigate the prevalence of multiple markers of thrombophilia and dyslipidemia in a cohort of consecutive young survivors of acute coronary syndrome. The study cohort included 156 consecutive young patients (men <45 and women <50 years), admitted to the intensive cardiac care unit with newly diagnosed acute coronary syndrome. Analysis included baseline, clinical and epidemiological characteristics, angiographic coronary anatomy, echocardiographic evaluation, extensive lipid and thrombophilia laboratory profiles, and in-hospital and 1-year clinical outcomes for all patients. Acute myocardial infarction was diagnosed in 142 (92 %) patients, of whom 108 (72 %) had ST-segment elevation. Eighteen (12 %) patients had no traditional risk factors. Low levels of high-density lipoprotein (<40 mg/dL) were found in 101 (65 %) patients, and 49 (34 %) patients had elevated levels of lipoprotein(a) (Lp(a)) (>30 mg/dL). Eighteen (12 %) patients were diagnosed with antiphospholipid antibody syndrome (APS), and 73 (47 %) had at least one laboratory finding consistent with thrombophilia. Patients with APS had significantly higher levels of Lp(a) (46 ± 32 vs. 29 ± 31 mg/dL, p = 0.005). APS is a common prothrombotic state found in young survivors of acute coronary syndrome. Lp(a) levels are elevated among APS patients who present with premature acute coronary syndrome.

Evaluation of platelet response to different clopidogrel dosing regimens in patients with acute coronary syndrome in clinical practice.

High-post clopidogrel platelet reactivity in acute coronary syndrome (ACS) patients is associated with adverse outcomes and may be related to clopidogrel dosing. Clinical studies evaluating different clopidogrel doses have resulted in conflicting conclusions. Clopidogrel dosing regimens have evolved over time, enabling us to evaluate platelet reactivity in real-life ACS patients undergoing percutaneous coronary intervention and treated with three different clopidogrel doses. Platelet reactivity was assessed with light transmitted aggregometry on the third day post clopidogrel loading in 404 consecutive ACS patients. Of them, 198 were treated with a standard regimen (300 mg loading, 75 mg/day maintenance dose), 95 with a high loading regimen (600 mg loading, 75 mg/day maintenance dose) and 111 with a high loading/high maintenance regimen (600 mg loading, 150 mg/day maintenance). Compared with the standard regimen, the high loading regimen resulted in significantly lower mean platelet reactivity to adenosine diphosphate (ADP) with a lower proportion of patients exhibiting clopidogrel non-responsiveness (11% vs. 28%, p = 0.004). Compared with the high loading regimen, the high loading/high maintenance regimen resulted in significantly lower mean platelet reactivity to ADP, but without a further drop in the number of non-responders (8.1% vs. 11%, p = 0.16). In conclusion, greater overall inhibition can be achieved with higher loading and maintenance doses in ACS patients. However, despite high clopidogrel doses, a sizable proportion of patients remained "resistant" to the effects of clopidogrel.

Acute coronary syndromes are associated with a reduction of VLA-1+ peripheral blood T cells and their enrichment in coronary artery plaque aspirates.

Memory T cells producing interferon (IFN)γ and expressing very late antigen-1 (VLA-1) integrin collagen receptors are found in carotid atherosclerotic plaques, suggesting their involvement in coronary artery disease (CAD) as well. To determine the role of VLA-1+ T cells in CAD percent of CD3+ T cells binding monoclonal antibodies (mAb) to VLA-1 in peripheral blood (PB), and in coronary plaque material aspirated during coronary arterography and arterial blood, were analyzed in a cohort of 117 patients with CAD and 34 controls without CAD. % VLA-1+ T cells in PB was 0.63 ± 0.09% in controls compared to 0.96 ± 0.95% in patients with CAD (p<0.009). The increase was due to a marked elevation of % VLA-1+ T cells in stable CAD (1.6 ± 0.27%) whereas % VLA-1+ T cells during acute coronary syndromes (ACS) and in patients with ischemia by thalium SPECT scan had significantly lower levels. % VLA-1+ T cells in coronary artery plaque material aspirated during therapeutic angiography in patients with ACS was significantly higher than in arterial blood (1.39 ± 0.96% vs 0.75 ± 0.84%, p<0.035, n=3). Thus, % VLA-1+ T cells increases in the PB during stable CAD but decreases in ACS. The finding of their enrichment in coronary blood containing atherosclerotic plaque aspirates suggests that a shift of VLA-1+ T cells from blood to atherosclerotic plaques may play a role in plaque instability in patients with ACS.

Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial.

IMPORTANCE: The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE: To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS: Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS: Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE: Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01076764.