Statin therapy impact on Long-Term outcomes in acute heart Failure: Retrospective analysis of hospitalized patients.

Background: Statin therapy is well-established for treating hyperlipidemia and ischemic heart disease (IHD), but its role in Acute Decompensated Heart Failure (ADHF) remains less clear. Despite varying clinical guidelines, the actual utilization and impact of statin therapy initiation in patients with ADHF with an independent indication for statin therapy have not been thoroughly explored. Methods: We conducted a retrospective observational study on 5978 patients admitted with ADHF between January 1st, 2007, and December 31st, 2017. Patients were grouped based on their statin therapy status at admission and discharge. We performed multivariable analyses to identify independent predictors of short-term, intermediate-term, and long-term mortality. A sensitivity analysis was also conducted on patients with an independent indication for statin therapy but who were not on statins at admission. Results: Of the total patient cohort, 73.9% had an indication for statin therapy. However, only 38.2% were treated with statins at admission, and 56.1% were discharged with a statin prescription. Patients discharged with statins were younger, predominantly male, and had a higher prevalence of IHD and other comorbidities. Statin therapy at discharge was an independent negative predictor of 5-year all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.85). The sensitivity analysis confirmed these findings, demonstrating higher mortality rates in patients not initiated on statins during admission. Conclusions: The study highlights significant underutilization of statin therapy among patients admitted with ADHF, even when there's an independent indication for such treatment. Importantly, initiation of statin therapy during hospital admission was independently associated with improved long-term survival.

Sex-dependent outcomes of recanalization-treated acute ischemic stroke patients at Shamir (Assaf Harofeh) medical center, Israel, 2011-2020.

BACKGROUND/OBJECTIVES: Sex-based differences in incidence, etiologies, severity and recanalization treatment outcomes of patients with acute ischemic stroke (AIS) have been studied extensively. We set out to determine if there were sex-based differences in outcomes among AIS patients who received recanalization treatments at Shamir (Assaf Harofeh) Medical Center (SMC), Israel, between 2011 and 2020. METHODS: This was a single-center, retrospective chart review. The primary analysis compared outcomes for men and women, overall and stratifying by disease severity. We compared also demographics, risk factors and workflow data. RESULTS: Eight hundred and eleven patients received recanalization treatment between 2011 and 2020: 472 (58.1%) men and 339 (41.8%) women. Mean age, NIHSS score and proportion with an NIHSS score ≥ 6 were higher for women. Cerebrovascular risk factors were more prevalent in women, particularly atrial fibrillation, except that current smoking was more prevalent in men. Six hundred and twenty patients (78.1%) were treated with TPA alone, 89 (11.2%) with TPA and endovascular treatment (EVT), and 85 (10.7%) with EVT alone. Fifty percent of patients were discharged home, 41% to a rehabilitation hospital or nursing home, and 9% did not survive. Twenty-four patients (3%) sustained symptomatic bleeds. Outcomes were worse in patients with NIHSS score ≥ 6. Outcomes did not differ by sex. CONCLUSIONS: While treated women presented with more severe AIS and more risk factors, we did not find significant sex-related differences in outcomes. Meticulous adherence to risk factor modification remains the best strategy to reduce stroke incidence, morbidity, and mortality in women and in men.

Outcomes of Acute Coronary Syndrome Patients Who Presented with Cardiogenic Shock versus Patients Who Developed Cardiogenic Shock during Hospitalization.

Background: Cardiogenic shock (CS) continues to be a severe and fatal complication of acute coronary syndrome (ACS). CS patients have a high mortality rate despite significant progress in primary reperfusion, the management of heart failure and the expansion of mechanical circulatory support strategies. The present study addressed the clinical characteristics, management, and outcomes of ACS patients complicated with CS. Methods: We performed an observational study, using the 2000-2013 Acute Coronary Syndrome Israeli Surveys (ACSIS) database and identified hospitalizations of ACS patients complicated with CS. Patients' demographics and clinical characteristics, complications and outcomes were evaluated. We assessed the outcomes of ACS patients with CS at arrival (on the day of admission) compared with ACS patients who arrived without CS and developed CS during hospitalization. Results: The cohort included 13,434 patients with ACS diagnoses during the study period. Of these, 4.2% were complicated with CS; 224 patients were admitted with both ACS and CS; while 341 ACS patients developed CS only during the hospitalization period. The latter patients had significantly higher rates of MACEs compared with the group of ACS patients who presented with CS at arrival (73% vs. 51%; p < 0.0001). Similarly, the rates of in-hospital mortality (55% vs. 36%; p < 0.0001), 30-day mortality (64% vs. 50%; p = 0.0013) and 1-year mortality (73% vs. 59%; p = 0.0016) were higher in ACS patients who developed CS during hospitalization vs. ACS patients with CS at admission. There was a significant decrease in 1-year mortality trends during the 13 years of this study presented in ACS patients from both groups. Conclusions: Patients who developed CS during hospitalization had higher mortality and MACE rates compared with those who presented with CS at arrival. Further studies should focus on this subgroup of high-risk patients.

Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Analysis from the Acute Coronary Syndrome Israeli Survey.

INTRODUCTION: We aimed to compare the outcomes of acute coronary syndrome (ACS) patients undergoing in-hospital percutaneous coronary intervention treated with prasugrel versus ticagrelor. METHODS: Among 7,233 patients enrolled to the Acute Coronary Syndrome Israeli Survey (ACSIS) between 2010 and 2018, we identified 1,126 eligible patients treated with prasugrel and 817 with ticagrelor. Comparison between the groups was performed separately in ST-elevation myocardial infarction (STEMI) patients, propensity score matched (PSM) STEMI patients, and non-ST-elevation ACS (NSTE-ACS) patients. RESULTS: In-hospital complication rates, including rates of stent thrombosis, were not significantly different between groups. In PSM STEMI patients, 30-day re-hospitalization rate (p < 0.05), 30-day MACE (the composite of death, MI, stroke, and urgent revascularization, p = 0.006), and 1-year mortality rates (p = 0.08) were higher in the ticagrelor group compared to the prasugrel group; in NSTE-ACS patients, outcomes were not associated with drug choice. In Cox regression analysis applied on the entire cohort, prasugrel was associated with lower 1-year mortality in STEMI patients but not in NSTE-ACS patients (p for interaction 0.03). CONCLUSIONS: Compared to ticagrelor, prasugrel was associated with superior clinical outcomes in STEMI patients, but not in NSTE-ACS patients.

Could a Multi-Marker and Machine Learning Approach Help Stratify Patients with Heart Failure?

Half of the patients with heart failure (HF) have preserved ejection fraction (HFpEF). To date, there are no specific markers to distinguish this subgroup. The main objective of this work was to stratify HF patients using current biochemical markers coupled with clinical data. The cohort study included HFpEF (n = 24) and heart failure with reduced ejection fraction (HFrEF) (n = 34) patients as usually considered in clinical practice based on cardiac imaging (EF ≥ 50% for HFpEF; EF < 50% for HFrEF). Routine blood tests consisted of measuring biomarkers of renal and heart functions, inflammation, and iron metabolism. A multi-test approach and analysis of peripheral blood samples aimed to establish a computerized Machine Learning strategy to provide a blood signature to distinguish HFpEF and HFrEF. Based on logistic regression, demographic characteristics and clinical biomarkers showed no statistical significance to differentiate the HFpEF and HFrEF patient subgroups. Hence a multivariate factorial discriminant analysis, performed blindly using the data set, allowed us to stratify the two HF groups. Consequently, a Machine Learning (ML) strategy was developed using the same variables in a genetic algorithm approach. ML provided very encouraging explorative results when considering the small size of the samples applied. The accuracy and the sensitivity were high for both validation and test groups (69% and 100%, 64% and 75%, respectively). Sensitivity was 100% for the validation and 75% for the test group, whereas specificity was 44% and 55% for the validation and test groups because of the small number of samples. Lastly, the precision was acceptable, with 58% in the validation and 60% in the test group. Combining biochemical and clinical markers is an excellent entry to develop a computer classification tool to diagnose HFpEF. This translational approach is a springboard for improving new personalized treatment methods and identifying "high-yield" populations for clinical trials.

Association of Polycythemia with Outcomes of Acute Coronary Syndrome.

BACKGROUND: Polycythemia has not been extensively studied for its impact on acute coronary syndrome (ACS) outcomes. A previous study reported only 30-day outcomes to be worse in these patients. METHODS: Data from the ACS Israeli survey between 2000 and 2018 were utilized to compare between 3 groups of patients with ACS: anemic group (hemoglobin <12 g/dL for women and <12.5 g/dL for men), normal hemoglobin group, and polycythemic group (>16 g/dL and >16.5 g/dL, respectively). Measured outcomes included 30-day major adverse cardiac events (MACE comprising all-cause mortality, recurrent ACS, need for urgent revascularization, and stroke) and 1- and 5-year all-cause mortality. RESULTS: Of 14,746 ACS patients, 10,752 (72.9%) had normal hemoglobin levels, 3,492 (23.7%) were anemic, and 502 (3.4%) were polycythemic. In comparison with normal and anemic patients, polycythemic patients were younger (55.9 ± 10.5 vs. 61.9 ± 12.4 and 71.1 ± 12.2 for anemic, respectively, p < 0.001 for both), more frequently men (93.8% vs. 81.3% and 63.1%, respectively, p < 0.001), and less likely diabetic or hypertensive. Upon adjustment to baseline characteristics, compared with normal hemoglobin, polycythemia was not independently associated with 30-day MACE or 1-year mortality, but it was independently associated with higher risk for 5-year mortality (HR 1.76, 95% CI: 1.19-2.59, p = 0.005). Similar results were observed after propensity score matching. CONCLUSIONS: Although younger and with fewer comorbidities, polycythemic ACS patients are at increased risk for long-term all-cause mortality. Further study of this association is warranted to understand the causes and possibly to improve the outcomes of these patients.

The green man enigma: Unique presentation of toxicology in the emergency department.

We describe a case report of hypertensive crisis induced by a combination of amphetamine and Marwitt's Kidney Pills. Diagnosis was delayed because of nonspecific physical findings including chest pain, abdominal pain, coughing, and diarrhea. This was confounded by puzzling physical examination findings, including green-colored urine and fingernails. Diagnosis was aided with point-of-care ultrasound, which presented a picture of acute cardiac insufficiency, pulmonary congestion, and bilateral effusions. Laboratory values on admission indicated acute multiorgan injury. Detailed patient history revealed chronic consumption of "Kidney," an over-the-counter drug available in Thailand with the primary ingredient methylene blue and used for a myriad of renal and genitourinary conditions. The patient also had a history of amphetamine use, which ultimately initiated his acute presentation.

Idarucizumab (Praxbind®) for dabigatran reversal in patients undergoing heart transplantation: a cohort of ten patients.

BACKGROUND: Novel oral anticoagulants are used in atrial fibrillation. Idarucizumab has been approved for reversal of dabigatran in situations of life-threatening hemorrhage or emergency surgery. OBJECTIVES: We report a single center experience of ten patients on dabigatran therapy who were given idarucizumab prior to heart transplantation. METHODS & RESULTS: The mean plasma concentration of dabigatran prior to reversal was 139 ± 89 ng/ml. Hemoglobin, hematocrit and platelet levels were decreased after surgery. Surgical procedures were successfully performed with no increased risk, especially regarding bleeding complications. All patients were alive after 90 days. CONCLUSION: Dabigatran reversal with idarucizumab in contexts of emergency surgery/urgent procedures is an attractive and safe option to be taken into consideration for patients with end stage heart disease awaiting transplantation and indication of anticoagulant therapy.

Conception and bicentric validation of the proSCANNED score, a simplified bedside prognostic score for Heart Failure patients.

A simple and accurate prognostic tool for Heart Failure (HF) patients is critical to improve follow-up. Different risk scores are accurate but with limited clinical applicability. The current study aims to derive and validate a simple predictive tool for HF prognosis. French outpatients with stable HF of two university hospitals were included in the derivation (N = 134) or in the validation (N = 274) sample and followed up for a median of 23 months. Potential predictors were variables with known association with mortality and easily available. The proSCANNED risk score was derived using a parametric survival model on complete case data; it includes 8 binary variables and its values are 0-8. In the validation sample, the ability of the score to discriminate the 1-year vital status was moderate (AUC = 0.71, IC95% = [0.64-0.71]). However, the stratification of the score in three groups showed a good calibration for patients in the low- and medium-risk risk group. The proSCANNED score is an easy-to-use tool in clinical practice with a good discrimination, stability, and calibration sufficient to improve the medical care of patients. Other follow up studies are necessary to assess score applicability in larger populations, and its impact.

Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure.

AIMS: Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. METHODS AND RESULTS: Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. CONCLUSIONS: Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

STADE-HF (sST2 As a help for management of HF): a pilot study.

AIMS: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission. METHODS AND RESULTS: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate. CONCLUSIONS: Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.

sST2 as a value-added biomarker in heart failure.

Soluble suppression of tumorigenicity-2 (sST2) is a biomarker widely investigated during the last few years. Its role has become clear in pathological conditions such as fibrosis and inflammation. From translational research to laboratory medicine, considerable efforts have been made to elucidate the features of sST2 biomarker and to consider its contribution to HF management. In this review, we summarized the results from recent works concerning sST2, and particularly we focused on the interest of sST2 in conditions for which classical biomarkers value interpretation is misleading. Indeed, despite other HF biomarkers, sST2 was proved to be independent from common comorbidities such as renal dysfunction and hypertension. Thus, sST2 showed promise for a combined strategy with natriuretic peptides, mainly for specific categories of patients. Particular attention was paid to findings on sST2 in HF with preserved ejection fraction (HFpEF), a form of HF for which reliable and specific biomarkers are awaited. Finally, a place is reserved to sST2 kinetics from basal to follow up values in order to improve clinical decision making and to customize patient treatments.

Management of advanced heart failure: a review.

INTRODUCTION: Heart failure (HF) has become a global pandemic. Despite recent developments in both medical and device treatments, HF incidences continues to increase. The current definition of HF restricts itself to stages at which clinical symptoms are apparent. In advanced heart failure (AdHF), it is universally accepted that all patients are refractory to traditional therapies. As the number of HF patients increase, so does the need for additional treatments, with an increased proportion of patients requiring advanced therapies. Areas covered: This review discusses extensive evidence for the effect of medical treatment on HF, although the data on the effect on AdHF is scare. Authors review the relevant literature for treating AdHF patients. Furthermore, mechanical circulatory devices (MCD) have emerged as an alternative to heart transplantation and have been shown to enhance quality of life and reduce mortality therefore authors also review the current literature on the different MCD and technologies. Expert commentary: More patients will need advanced therapies, as the access to heart transplantation is limited by the number of available donors. AdHF patients should be identified timely since the window of opportunities for advanced therapy is narrow as their morbidity is progressive and survival is often short.

Management of acute heart failure: Contribution of daily bedside echocardiographic assessment on therapy adjustment with impact measure on the 30-day readmission rate (JECICA).

There are currently one million heart failure (HF) patients in France and the rate is progressively increases due to population aging. Acute decompensation of HF is the leading cause of hospitalization in people over 65 years of age with a 25% re-hospitalization rate in the first month. Expenses related to the management of HF in France in 2013 amounted to more than one billion euros, of which 65% were for hospitalizations alone. The management of acute decompensation is a challenge, due to the complexity of clinical and laboratory evaluation leading to therapeutic errors, which in turn leads to longer hospitalization, high early re-hospitalization and complications. Therapeutic adjustment, especially diuretic, in the acute phase (during hospitalization) affects early re-hospitalization rates (within 30 days). These adjustments can be based on clinical estimation and laboratory parameters, but echocardiography has been shown to be superior in estimating filling pressures (FP) compared to clinical and laboratory parameters. We hypothesize that a simple daily bedside echocardiographic assessment could provide a reproducible estimation of FP with an evaluation of mitral inflow and the inferior vena cava (IVC). This could allow a more reliable estimate of the true blood volume of the patient and thus lead to a more suitable therapeutic adjustment. This in turn should lead to a decrease in early re-admission rate (primary endpoint) and potentially decrease six-month mortality and rate of complications.

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.

Routine Laboratory Indices as Predictor of Neurological Recovery in Post-Resuscitation Syndrome Patients Treated with Therapeutic Hypothermia.

BACKGROUND: Hypothermia is associated with improved outcome in selected survivors of cardiac arrest but no single metric enables proper prediction of neurological outcome. OBJECTIVES: To explored the association between routine laboratory indices of patients treated by hypothermia for cardiac arrest and their neurological outcome. METHODS: We retrospectively collected data from survivors of cardiac arrest treated with hypothermia for 24 hours and grouped them according to their neurological outcome to either "poor" or "favorable". Routine laboratory indices were collected at constant time intervals up to one week of admission. A comparison between the laboratory values in both groups was performed. RESULTS: Between May 2008 to November 2011, 41 consecutive patients with a mean age of 54.3 ± 16.7 years were included in this study. No significant correlation was found between routine laboratory indices and the neurological outcome. The temporal trend of decay in the serum glucose values and the ratio of polymorphonuclears to white blood cells during the first 72 hours after admission was steeper in the favorable outcome group (P for trend < 0.05). CONCLUSIONS: No single routine laboratory index was associated with neurological outcome of survivors of cardiac arrest treated with hypothermia. The temporal trends in both serum glucose and polymorphonuclear ratio signal a more intense inflammatory response associated with poor outcome.