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.

Preoperative evaluation of pulmonary hypertension in lung transplant candidates: echocardiography versus right heart catheterization.

BACKGROUND: Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the performance of echocardiographic PASP as an indicator of pulmonary hypertension in LT candidates, in order to assess the necessity of RHC. METHODS: From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015-2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods-echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. RESULTS: The mean value of PASP estimated by echocardiography was 49.5 ± 20.0 mmHg, compared to 42.5 ± 18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson's correlation: r = 0.609, p < 0.01). Echocardiography PASP measurements were moderately discriminative to diagnose PH, with an area under the curve (AUC) of 0.72 (95% CI 0.66-0.77). Echocardiographic overestimation of PASP of more than 10 mmHg was found in 35.0% of the patients, and underestimation was found in 11.6% of the patients. CONCLUSION: In the pre-surgical evaluation of LT candidates, echocardiographic estimation of PASP had moderate correlation and limited accuracy compared to the PASP measured by RHC. We thus recommend performing routine RHC to all LT candidates, regardless of the echocardiographic estimation of PASP.

Inferior ST-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere to Current Guidelines?

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital without pPCI capacity, and it is anticipated that pPCI cannot be performed within 120 min of first medical contact, fibrinolytic therapy is indicated (if there are no contraindications) (class I indication, level of evidence A). Our review of the pertinent literature shows that the current recommendation for inferior STEMI is based on the level of evidence lower than A. We can consider level B even C, supporting the recommendation for fibrinolytic therapy if pPCI is not available for inferior STEMI.

Characteristics Associated with Upper-Range Doses of Beta-Blockers and Angiotensin-Renin Inhibitors in Reduced Ejection Fraction.

BACKGROUND: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs). OBJECTIVES: To determine factors associated with attaining upper-range doses in patients with HFrEF. METHODS: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines. RESULTS: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65-78) and LVEF of 30% (IQR 25-35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05-1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m2/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34-5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13-0.90, P = 0.031). CONCLUSIONS: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

Prevalence of Carotid Artery Disease among Ambulatory Patients with Coronary Artery Disease.

BACKGROUND: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. OBJECTIVES: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. METHODS: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. RESULTS: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95% CI 1.403-7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95% CI 1.136-2.095, P = 0.005), and age at CAD onset (OR 1.028, 95% CI 1.002-1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. CONCLUSIONS: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD.

The proxy of renal function that most accurately predicts short- and long-term outcome after acute coronary syndrome.

AIMS: The aim of this study is to determine the most accurate renal function formula that predicts short- and long-term mortality in a wide spectrum of acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We analyzed 8,726 consecutive patients (46.3% ST-elevation myocardial infarction [STEMI] and 53.7% non-ST-elevation ACS [NSTE-ACS]) enrolled in the ACS survey in Israel. Renal function, assessed using 5 formulas as proxies of creatinine clearance or estimated glomerular filtration rate (Cockcroft-Gault, modification of diet in renal disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration, Mayo quadratic, and inulin clearance based), varied in applying the different formulas. For both STEMI and NSTE-ACS patients, the Mayo formula yielded the highest mean value (88.9 ± 27.7 and 81.4 ± 29.2 mL/min per 1.73 m(2), respectively) and Chronic Kidney Disease Epidemiology Collaboration the lowest (73.0 ± 23.1 and 67.0 ± 24.1 mL/min per 1.73 m(2), respectively). Using multivariate analysis, worse renal function was independently associated with increased mortality risk by 30% to 40% for each decrement of 10 U of creatinine clearance or estimated glomerular filtration rate in STEMI patients and by 25% to 30% for NSTE-ACS patients, using all 5 formulas. The only formula that more accurately predicted 1-year mortality than the MDRD formula was the Mayo quadratic formula with a 1-year net reclassification index of 0.26 and 0.14 for STEMI and NSTE-ACS patients, respectively, after multivariable adjustment. CONCLUSION: Worse renal function was an independent predictor for short- and long-term mortality using all 5 formulas in a broad spectrum of ACS patients, but only the Mayo quadratic formula had better accuracy in predicting mortality relative to the MDRD, suggesting that it may be the preferred prognosticator among ACS patients.

High Sensitivity Cardiac Troponin T Levels after Elective Cardioversion for Atrial Fibrillation/Flutter.

BACKGROUND: The kinetics of high sensitivity cardiac troponin T (hs-cTnT) levels after elective, biphasic, direct-current cardioversion for persistent atrial fibrillation/flutter remains unknown. METHODS: We examined hs-cTnT kinetics in 24 patients at baseline and at 2, 6 and 24 hours post-cardioversion, and again at 7 and 30 days. We also examined levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, brain natriuretic peptide (BNP), and high sensitivity C-reactive protein (hs-CRP). RESULTS: Median (25th, 75th interquartiles) baseline hs-cTnT concentration was 19.8 (10.4, 35.2) ng/L with 14 patients presenting with levels above the 99th percentile (13 ng/L). Hs-cTnT levels did not change significantly over time although they tended to decrease by 30 days, 18.8 ng/L (12.5, 23.3). There was no significant rise in other markers of myocardial injury. Similarly, BNP and hs-CRP levels were elevated at baseline and tended to decrease over time. CONCLUSIONS: Patients with persistent atrial fibrillation/flutter have elevated hs-cTnT levels, as part of a general rise in biomarkers such as BNP and hs-CRP, without a further rise after cardioversion. After cardioversion, there is a gradual non-significant decrease in biomarker levels over time, and thus a rise in hs-cTnT levels should not be attributed to cardioversion.

Utility of immune monitoring in heart transplant recipients on everolimus-based immune suppression.

BACKGROUND: Everolimus provides effective immune suppression (IS) after heart transplant (HTx). Its pharmacologic properties differentiate everolimus from other IS drugs. A non-invasive immune monitoring (IM) assay test appears to predict the immune state in HTx recipients on standard calcineurin-inhibitor-based IS. The utility of IM in HTx recipients on everolimus-based IS was evaluated. METHODS: Between June 2005 and June 2011, 34 adult HTx recipients followed up at our center received everolimus and had 381 IM assays that were performed at six months to 16-yr post-transplant. Results of the IM assay were correlated with infection and rejection episodes that occurred during the IM testing. RESULTS: In the everolimus-based IS group, there were 18 infectious episodes and four rejection episodes. The average IM score was significantly lower during infection than at steady state (188 ± 122 vs. 338 ± 137 ng/mL ATP, p < 0.001) and not significantly different during rejection when compared with steady state (430 ± 132 vs. 338 ± 137 ng/mL ATP, p = 0.5). CONCLUSIONS: The non-invasive IM assay predicts infectious risk in HTx recipients on everolimus-based IS. Its inconclusive association with rejection was probably due to the small number of rejections. Serial longitudinal IM may allow proper adjustment of everolimus doses.

Low plasma vitamin D levels and muscle-related adverse effects in statin users.

BACKGROUND: Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. OBJECTIVES: To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. METHODS: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. RESULTS: The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). CONCLUSIONS: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

[Large pericardial cyst in a young woman presenting with fever abdominal pain and diarrhea].

Pericardial cysts are rare mediastinal abnormalities occurring in 1 in 100,000 persons. Most pericardial cysts are congenital but may also be acquired. Their presence poses a diagnostic challenge, distinguishing them from other intracardiac and mediastinal lesions. We describe an unusual presentation of a large pericardial cyst which was diagnosed during the evaluation of prolonged fever, abdominal pain and diarrhea. This case emphasizes that the evaluation and treatment of a pericardial cyst should be based on clinical judgment and should be managed on a case by case basis.

Sex Differences in the Diagnosis, Management, and Outcomes of Suspected Non-ST-Elevation Acute Coronary Syndromes Meeting Rapid Rule-Out Criteria.

(1) Background: patients who meet current rapid rule-out criteria for myocardial infarction (MI) are considered low risk, yet their management remains nebulous, especially among women. We aimed to examine sex differences in the diagnosis, management, and outcomes of patients meeting the rapid rule-out criteria. (2) Methods: by simulating application of the rapid rule-out MI criteria, we analyzed consecutively triaged men and women with suspected NSTE-ACS who had high-sensitivity cardiac troponin T (hs-cTnT) values that met criteria (n = 11,477), in particular, those who were admitted (n = 3775). (3) Results: men constituted ~55% of triaged patients who met the rule-out criteria, whether admitted or discharged. Men were more likely to be admitted (33.7% vs. 31.9%, p = 0.04), more commonly with hs-cTnT values between level of detection (LOD, 5 ng/ml) and the 99th percentile (59.4% of all admissions vs. 40.5% for women), whereas women were more likely to be admitted with values < level of blank (LOB, 3 ng/mL; 22.9% vs. 9.2% for men). Thirty-day mortality (1 man and 1 woman) and in-hospital MI (9 men vs. 1 woman) were uncommon among admitted patients, yet resource utilization during 3-4 hospitalization days was substantial for both sexes, with men undergoing coronary angiography (6.8% vs. 2.9%) and revascularization (3.4% vs. 1.1%) more commonly. Long-term survival for both men and women, whether admitted or discharged, was significantly worse for hs-cTnT values between LOD and the 99th percentile, even after adjusting for age and cardiovascular comorbidities. (4) Conclusions: reporting actual hs-cTnT values < 99th percentile allows for better risk stratification, especially for women, possibly closing the sex gap.

Suspected Non-ST-elevation acute coronary syndrome meeting rapid rule-out criteria: resource utilization, diagnostic yield, and clinical outcomes of hospital admission.

AIMS: Many patients with suspected non-ST-elevation (NSTE) acute coronary syndromes (ACS) are admitted, even those with initial high-sensitivity cardiac troponins (hs-cTn) values who meet rapid rule-out criteria for myocardial infarction (MI). We examined the clinical outcomes, resource utilization, and diagnostic yield of suspected NSTE-ACS patients, who presented with hs-cTnT values meeting these criteria but were nevertheless hospitalized. METHODS AND RESULTS: Applying the 2020 European Society of Cardiology (ESC) rapid rule-out MI criteria, we identified consecutive patients with an initial value of hs-cTnT <5 ng/L or an initial value of ≥5 ng/L but <14 ng/L (99th percentile) and a small increment in a subsequent test, who were nevertheless admitted. The majority (85.4%) of patients presented to the emergency department (ED) with suspected NSTE-ACS had an initial hs-cTnT <99th percentile. We examined 3775 admitted patients out of 11 477 patients who were triaged and met MI rule-out criteria. Only 0.32% (12 patients) of admitted patients experienced index MI or overall death within 30 days. Resource utilization in terms of ED stay, hospital stay, noninvasive and invasive tests was substantial, yet revascularization was uncommon (2.5%). Multivariate adjustment for age, gender, and baseline cardiovascular risk factors demonstrates similar survival of admitted vs. discharged patients (P = 0.88). Initial hs-cTnT even below the 99th percentile provided a prognostic stratification for long term mortality. CONCLUSION: Our findings support a policy of ED discharge of suspected NSTE-ACS patients meeting rapid MI rule-out criteria and subsequent ambulatory evaluation, sparing resource-consuming admissions. In-hospital and ensuing prognosis were better with lower initial hs-cTnT values.

Do We Still Need Aspirin in Coronary Artery Disease?

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization.

Nutrigenetic impact of daily folate intake on plasma homocysteine and folate levels in patients with different methylenetetrahydrofolate reductase genotypes.

BACKGROUND: Elevated plasma homocysteine level is associated with coronary artery disease (CAD). Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is typically but inconsistently associated with hyperhomocysteinemia. We examined the impact of daily intake of folate, a co-factor in homocysteine metabolism, on plasma homocysteine and folate levels in CAD patients in relation with MTHFR genotypes. METHODS: Daily folate intake was assessed from 3-day food records in 99 patients with CAD: 35 with the T/T (homozygous mutant) genotype and 64 with the C/C or C/T (non-T/T) genotypes. RESULTS: Patients with the T/T genotype had higher fasting plasma homocysteine levels (18.4±1.9 vs. 12.6±0.6 µmol/l, P=0.01) and lower plasma folate levels (17.8±1.7 vs. 20.8±1.0 nmol/l, P=0.02). There were no differences between the genotype groups in energy-adjusted folate intake. In patients with the non-T/T genotypes, higher folate intake was associated with higher plasma folate levels and lower plasma homocysteine levels. In T/T homozygotes this association was weaker. Linear regression analysis showed that folate intake, the MTHFR genotype, plasma vitamin B12 levels, and the interaction between plasma folate level and MTHFR genotype, predicted homocysteine elevation. (folate intake, P=0.04, MTHFR genotype, P=0.03, plasma folate, P=0.02, and plasma B12 level, P=0.004). The model explained only 29% of the variance in log-transformed plasma homocysteine levels. CONCLUSION: T/T homozygotes are more sensitive to the combination of low folate intake, low plasma folate and vitamin B12 level, than patients with non-T/T genotypes. The variability in plasma homocysteine in T/T homozygotes is only partly explained by these variables.

Blood transfusion for acute decompensated heart failure--friend or foe?

BACKGROUND: In acute coronary syndromes (ACSs), blood transfusion (BT) has been associated with worse outcomes. The impact of BT among patients with acute decompensated heart failure (ADHF) remains unknown. METHODS: Propensity score analysis of patients with ADHF with and without BT in a national heart failure (HF) survey was used in this study. RESULTS: Of the 4,102 enrolled patients, 2,335 had ADHF, of whom 166 (7.1%) received BT. These patients were older (75.6% vs 73.6%, P = .04), more likely to be females (54.8% vs 43.9%, P = .007), more likely to have diabetes (59.0% vs 51.1%, P = .04) and renal dysfunction (59.0% vs 40.2%, P < .001), and more likely to receive inotropes (16.9% vs 8.0%, P < .001), but they had similar rates of ACS (41.0% vs 39.4%, P = .69) and prior HF (64.5% vs 70.0%, P = .23). Nadir hemoglobin levels were commonly <10 g/dL in BT patients (92.7% vs 8.0%); 15 BT patients had bleeding complications, of which 10 are major bleeding. Major predictors for BT were ACS (OR 1.85, 95% CI 1.15-2.96), inotropes use (OR 2.36, 95% CI 1.22-4.55), and nadir hemoglobin (OR 0.18 per 1 g/dL increase, 95% CI 0.14-0.22). In-hospital, 30-day, 1-year, and 4-year unadjusted mortality rates were higher for BT patients (10.8% vs 5.2%, P = .02; 11.0% vs 8.5%, P = .27; 39.6% vs 28.5%, P = .03; 69.5% vs 59.5%, P = .01, respectively). However, in 103 propensity-matched pairs (c-statistic 0.97), short-term mortality tended to be lower with BT (8.7% vs 14.6%, P = .20; 9.7% vs 18.4%, P = .08; 38.8% vs 42.7%, P = .59; and 72.8% vs 76.7%, P = .52, respectively). CONCLUSIONS: Acute decompensated HF patients receiving BT had worse clinical features and unadjusted outcomes, but BT per se seemed to be safe and perhaps even beneficial.