The Association of Depression With QT Duration: A Comparison Between Individuals Younger or Older Than 65 Years.

OBJECTIVE: The electrocardiogram-derived corrected QT (QTc) interval is an indicator of cardiac autonomic activity that has been proposed as a biological measure to investigate the interplay between depression and cardiovascular diseases. This study assesses whether depression is associated with a longer QTc interval across age groups. METHODS: Assessment of depressive symptoms was performed in 1637 participants of the cross-sectional Corinthia study with the Zung Self-Rating Depression Scale in those younger than 65 years (group 1) and with the Geriatric Depression Scale in elderly individuals (≥65 years, group 2). The QT interval was obtained from electrocardiogram recordings and corrected for heart rate (QTc). RESULTS: Individuals in group 1 with depression were predominantly women and had a higher prevalence of coronary artery disease and diabetes mellitus. Group 1 individuals with depression had longer QTc duration (no depression versus depression, 389.3 [27.0] versus 401.1 [32.9] milliseconds; p < .001) and percentage of abnormal QTc (no depression versus depression, 2.0% versus 10.8%; p = .001) compared with those without depression. Elderly individuals (group 2) had similar values of QTc and percentage of abnormal QTc irrespective of depression status. Even after adjustment for known QT-prolonging factors, the presence of depression in younger individuals was associated with an increased QTc by 11.1 milliseconds and with an approximately 10.6-fold higher prevalence of abnormal QTc duration. CONCLUSIONS: Depression was associated with a longer QTc interval especially in individuals younger than 65 years. These findings may indicate an interrelationship between depression and autonomic dysregulation as potential risk factors for cardiovascular disease and sudden cardiac death.

Anti-interleukin-1 agents for pericarditis: a primer for cardiologists.

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1ß are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1ß (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1α and IL-1ß), and canakinumab (human monoclonal anti-IL-1ß antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low (<4%). The most common reported side effect is injection site reactions (>50% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years.

Incidence and Prevalence of Cardiac Arrhythmias in Pericardial Syndromes.

Arrhythmias in pericardial syndromes have been poorly investigated and available data are mainly obtained from relevant studies however having different endpoints from arrhythmias. Thus, the incidence and prevalence of any type of arrhythmias may be actually higher than generally considered. Atrial arrhythmias, mainly atrial fibrillation and flutter have been reported as the most common rhythm disturbances in the setting of acute pericarditis. Concerning pathophysiology of atrial arrhythmias, in contrast to earlier hypothesis that they occur exclusively in the presence of an underlying structural heart disease, recent data support an arrhythmogenic potential of acute pericardial inflammation regardless of the presence of heart disease. In cases of myopericarditis, namely primarily pericarditis with evidence of myocardial involvement (i.e., troponin elevation without however overt left ventricular dysfunction and/or segmental wall motion abnormalities), ventricular arrhythmias appear to prevail. With reference to the rest of pericardial syndromes data on arrhythmias development are even more sparce. In particular, in constrictive pericarditis atrial tachyarrhythmias are the most commonly detected and seem to be related to disease severity and possibly to the underlying etiology. In this review we have summarized the available information on the incidence and prevalence of arrhythmias in pericardial syndromes. We wish to emphasize that the clinical significance of arrhythmias in this setting in terms of prognosis and optimal medical treatment (including need and safety of anticoagulation in atrial fibrillation/flutter complicating acute pericarditis), should be further investigated.

The association of diabetes mellitus with carotid atherosclerosis and arterial stiffness in the Corinthia study.

BACKGROUND AND AIMS: Evaluation of arterial stiffness and carotid atherosclerotic burden can provide important prognostic information regarding the risk of future cardiovascular events. The aim of this study was to assess these vascular properties in patients with diabetes mellitus (DM). METHODS AND RESULTS: In the context of the observational "Corinthia" study, we analyzed 1757 participants with determined DM status. Carotid ultrasonography was performed to evaluate intima-media thickness (cIMT) and carotid plaque burden. Arterial stiffness was estimated via assessment of carotid-to-femoral pulse wave velocity (cfPWV). Individuals with DM had increased mean cIMT, maximum cIMT, carotid plaque burden, and cfPWV compared to those without DM. After multivariable regression analysis, the presence of DM was still associated with significantly increased mean cIMT (by 0.074 mm, p = .004), maximum cIMT (by 0.134 mm, p = .007), cfPWV (by 0.929 m/s, p < .001), and a higher prevalence of carotid plaques (odds ratio 1.52, 95% confidence intervals 1.11, 2.10, p = .01). In a propensity score-matched cohort, mean cIMT, maximum cIMT, and carotid plaque burden were significantly higher in individuals with DM. Analysis according to territory of cIMT measurement displayed substantial differences in left (DM: 1.32 ± 0.78 mm vs. no DM: 1.20 ± 0.66 mm, p = .04) and right carotid bulbs (DM: 1.33 ± 0.82 mm vs. no DM: 1.18 ± 0.69 mm, p = .02) with respect to DM status while non-significant variations were observed in left (DM: 0.98 ± 0.49 mm vs. no DM: 0.91 ± 0.35 mm, p = .06) and right common carotid artery (DM: 0.95 ± 0.50 mm vs. no DM: 0.92 ± 0.40 mm, p = .36). CONCLUSIONS: Diabetes mellitus is associated with increased cfPWV and cIMT, with more pronounced lesions in the carotid bulb.

Acute Pericarditis: Update.

PURPOSE OF REVIEW: Since 2015, when ESC guidelines for the diagnosis and management of pericardial diseases were published, ongoing research has enhanced the current state of knowledge on acute pericarditis. This review is an update on the latest developments in this field. RECENT FINDINGS: In recurrent acute pericarditis, autoinflammation has been included among causative mechanisms restricting the vague diagnoses of "idiopathic" pericarditis. Cardiac magnetic resonance that detects ongoing pericardial inflammation may guide treatment in difficult-to-treat patients. Development of risk scores may assist identification of patients at high risk for complicated pericarditis, who should be closely monitored and aggressively treated. Treatment with IL-1 inhibitors has been proven efficacious in recurrent forms with a good safety profile. Finally, acute pericarditis has recently attracted great interest as it has been reported among side effects post COVID-19 vaccination and may also complicate SARS-CoV-2 infection. Recent advancements in acute pericarditis have contributed to a better understanding of the disease allowing a tailored to the individual patient approach. However, there are still unsolved questions that require further research.

Age- and sex-based differences in patients with acute pericarditis.

BACKGROUND: Acute pericarditis has a wide spectrum of clinical presentations largely depending on underlying aetiologies. We assessed the role of age and sex in the clinical features and outcome of acute pericarditis. MATERIALS AND METHODS: A total of 240 consecutive patients hospitalized with a first episode of acute pericarditis were included. At baseline demographics, clinical features, laboratory and imaging findings and medical therapy were recorded. Patients were followed up for at least 18 months for complications. Data comparisons were performed according to sex and age (≤60 or >60 years). RESULTS: The male/female ratio was 1.42, and 56% of patients were >60 years. Younger patients depicted more often chest pain (P = .001), fever and rubs (P < .001 for both), ST elevation and PR depression (P = .032 and .009, respectively), higher CRP values (P = .009) and less often dyspnoea (P = .046) and pericardial effusion (P = .036). Moreover, they received less often glucocorticoids (P < .001) and depicted less atrial fibrillation (P = .003) and a higher rate of recurrent pericarditis (P = .013). After multivariate adjustment for confounders, age >60 years remained an independent predictor for a lower risk of recurrent pericarditis (hazard ratio 0.60, 95% CI: 0.39-0.96, P = .033). Regarding sex, females were older (P = .007), showed less often ST elevation and PR depression (P < .001 and .002, respectively) and had a higher baseline heart rate (P = .02). Sex was not associated with recurrent pericarditis risk. CONCLUSIONS: Patients with acute pericarditis have distinct presenting clinical, biochemical and prognostic features according to age and sex. Awareness of such differences is important for clinical decision-making.

A risk score for pericarditis recurrence.

BACKGROUND: Currently, we remain uncertain about which patients are at increased risk for recurrent pericarditis. We developed a risk score for pericarditis recurrence in patients with acute pericarditis. MATERIALS AND METHODS: We prospectively recruited 262 patients with a first episode of acute pericarditis. Baseline patients' demographics, clinical, imaging and laboratory data were collected. Patients were followed up for a median of 51 months (interquartile range 21-71) for recurrence. Variables with <10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The final model performance was assessed by the c-index whereas model's calibration and optimism-corrected c-index were evaluated after 10-fold cross-validation. RESULTS: We identified six independent predictors for pericarditis recurrence, that is age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725-0.842), while the optimism-corrected c-index after cross-validation was 0.752. Based on these variables, we developed a risk score point system for recurrence (0-22 points) with equally good performance (c-index 0.740, 95% CI 0.677-0.803). Patients with a low score (0-7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence. The score was predictive of recurrence among most patient subgroups. CONCLUSIONS: A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.

The impact of sleeping duration on atherosclerosis in the community: insights from the Corinthia study.

PURPOSE: Sleep is an essential physiologic process whose disturbances have been regarded as a risk factor in various pathophysiologic processes, including atherosclerosis and cardiovascular disease. Although the negative influence of short sleep duration has been well-established, recent data suggest a possible harmful effect of prolonged sleeping pattern. METHODS: In the setting of the Corinthia cross-sectional study, self-reported night sleep duration was recorded in 1752 apparently healthy individuals and was classified as normal sleep duration (NSD, 7-8 h), short sleep duration (SSD, 6-7 h), very short sleep duration (VSSD, < 6 h), and long sleep duration (LSD, > 8 h). Carotid duplex ultrasonography was performed in order to measure the mean and maximum carotid intima-media thickness (cIMT) as a non-invasive marker of atherosclerosis. RESULTS: Subjects with LSD and VSSD had significantly higher mean cIMT (VSSD: 1.02 ± 0.45 mm, SSD: 0.95 ± 0.35, NSD: 0.96 ± 0.38 mm, LSD: 1.07 ± 0.52 mm; p < 0.001) and maximum cIMT (VSSD: 1.39 ± 0.9 mm, SSD: 1.25 ± 0.71 mm, NSD: 1.23 ± 0.76 mm, LSD: 1.41 ± 0.93 mm). Following a regression analysis adjusting for known cardiovascular risk factors, individuals with LSD and VSSD had higher mean cIMT by 0.054 mm and 0.067 mm respectively compared to those with NSD. CONCLUSION: A balanced sleeping duration of 6-8 h is associated with decreased mean and maximum IMT while both very short sleep duration and long sleep duration are associated with increased carotid intima-media thickness, a marker of subclinical atherosclerosis.

New Approaches to Management of Pericardial Effusions.

PURPOSE OF REVIEW: Pericardial effusion is a challenging pericardial syndrome and a cause of serious concern for physicians and patients due to its potential progression to life-threatening cardiac tamponade. In this review, we summarize the contemporary evidence of the etiology; diagnostic work-up, with particular emphasis on the contribution of multimodality imaging; therapeutic options; and short- and long-term outcomes of these patients. RECENT FINDINGS: In recent years, an important piece of information has contributed to put together several missing parts of the puzzle of pericardial effusion. The most recent 2015 guidelines of the European Society of Cardiology for the diagnosis and management of pericardial diseases are a valuable aid for a tailored approach to this condition. Actually, current guidelines suggest a 4-step treatment algorithm depending on the presence or absence of hemodynamic impairment; the elevation of inflammatory markers; the presence of a known or first-diagnosed underlying condition, possibly related to pericardial effusion; and finally the duration and size of the effusion. In contrast to earlier perceptions, based on the most recent evidence, it seems that in the subgroup of asymptomatic patients with large (> 2-cm end-diastolic diameter), chronic (> 3 months) C-reactive protein negative, idiopathic (without an apparent cause) pericardial effusion, a conservative approach is the most reasonable option. At present there is an increasing interest in the pericardial syndromes in general and pericardial effusions in specific, which has consistently expanded our knowledge in this "hazy landscape." Apart from general recommendations applied to all cases, an individualized, etiologically driven treatment is of paramount importance.

Diagnostic performance of electrocardiographic criteria in echocardiographic diagnosis of different patterns of left ventricular hypertrophy.

BACKGROUND: Electrocardiogram (ECG) is considered the initial screening method for the detection of left ventricular hypertrophy (LVH) despite its low sensitivity. However, there are no data on how ECG criteria for LVH perform in patients with concentric (cLVH) and eccentric LVH (eLVH). METHODS: In the setting of the Corinthia cross-sectional study, ECGs were analyzed in 1,570 participants of the study. Seven ECG LVH criteria were calculated (Sokolow-Lyon voltage, index, and product, sex-specific Cornell voltage and product, Lewis voltage, and the Framingham), whereas LVH was defined, based on echocardiographic data, as left ventricular mass indexed for body surface area (BSA) of at least 125 g/m2 in men and at least 110 g/m2 in women. RESULTS: Regarding the frequency encountered for each ECG LVH criterion, there was no difference between eLVH and cLVH. However, when ECG criteria were compared as continuous variables between LVH groups, Cornell voltage and product were higher in cLVH individuals, with a value of Cornell voltage >13.95 mV having 61% sensitivity and 62% specificity to differentiate cLVH from eLVH (p = .05). Even after adjustment for age, sex, body mass index, and hypertension, the occurrence of Cornell voltage or product increased the odds of cLVH by 1.6 times (p = .001). CONCLUSION: Cornell voltage and product criteria disclosed a superior discriminative ability for the detection of LVH via ECG. When further categorizing LVH as concentric and eccentric, Cornell product depicted the higher discriminative ability for cLVH.

Breakfast association with arterial stiffness and carotid atherosclerotic burden. Insights from the 'Corinthia' study.

BACKGROUND AND AIMS: The role of dietary patterns, in cardiovascular diseases has been challenged. The role of breakfast as an element of balance energy intake has gained research interest. However, the effects of dietary patterns related to breakfast consumption on vascular function are unknown. We explored the association of breakfast consumption habits with arterial wall elastic properties and carotid atherosclerosis. METHODS AND RESULTS: In this cross-sectional study we enrolled 2043 inhabitants of the Corinthia region in Greece. Carotid-femoral pulse wave velocity (cf-PWV) was used to assess arterial stiffness. Carotid intima-media thickness (cIMT) was measured and the mean and the maximum cIMT were calculated. According to food frequency questionnaires, breakfast contribution in total daily energy intake (>20%; 5-20% and <5%) was estimated. Subjects were categorized as high-energy breakfast consumers (HeBC), low-energy breakfast consumers (LeBC) and those skipping breakfast (SBf) respectively. From the study population 240 subjects were categorized as HeBC, 897 as LeBC, and 681 as SBf. The mean cf-PWV was significantly higher in subjects SBf compared to LeBC and HeBC (9.35 ± 2.82 m/s vs. 9.09 ± 2.77 m/s vs. 8.76 ± 2.69 m/s, p = 0.02). The mean cIMT was significantly higher in subjects SBf compared to LeBC and HeBC (1.04 ± 0.46 mm vs. 0.99 ± 0.43 mm vs. 0.92 ± 0.39 mm, p = 0.01). Even after adjustment for potential confounders and cardiovascular risk factors SBf subjects have significantly increased mean cIMT and cf-PWV. CONCLUSION: Skipping breakfast has an adverse effect on arterial stiffness and carotid atheromatic burden. Increased breakfast total energy intake may act protectively against atherosclerosis, a finding worth of further pathophysiologic exploration with potential clinical implications.

Arterial stiffness and subclinical aortic damage of reclassified subjects as stage 1 hypertension according to the new 2017 ACC/AHA blood pressure guidelines.

Background: The 2017 ACC/AHA blood pressure (BP) guidelines generated controversies due to the new proposed BP cut-off values defining hypertension. We aimed to assess aortic stiffness of subjects who are reclassified as stage 1 hypertensive according to the new guidelines and compare them with the subjects of "elevated BP" category. Patients and methods. Data from the "Corinthia" study, an observational, cross-sectional survey of 2,043 participants were analyzed. Subjects were classified into 4 groups: group A: systolic pressure (SBP) 120-129 and diastolic pressure (DBP) < 80 mmHg, group B: SBP 130-139 or DBP 80-89 mmHg, group B1: SBP 130-139 and DBP < 80 mmHg and group B2: SBP 130-139 and DBP 80-89 mmHg. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity (PWV). A value of PWV > 10m/s was consider indicative of asymptomatic organ damage while values of PWV exceeded the 90 % percentile for each age group were consider as abnormal. Results: Groups B, B1 and B2 have significantly increased PWV compared to group A, independently from age and other risk factors (PWV: 9.2 ± 2.8 vs 9.4 ± 2.7 vs 8.6 ± 2.5 vs 8.1 ± 2.3 m/s, p < 0.01, respectively). The prevalence of PWV > 10 m/s and abnormal PWV values in group A was significantly lower than the corresponding prevalence in randomly selected, age-matched subjects from group B (13.5 % vs 24.4 %, p = 0.027 and 5.6 % vs 14.2 %, p = 0.022, respectively). Conclusions: The reclassified subjects as stage 1 hypertensive by the new guidelines have a significantly increased aortic stiffness and greater prevalence in asymptomatic aortic damage compared to subjects with elevated BP. This finding may indirectly explain the increased cardiovascular risk of this group.

The Role of Epicardial Fat in Pericardial Diseases.

PURPOSE OF REVIEW: Despite the recent advancements in diagnostic modalities and therapeutic options available, the pathophysiology of pericardial syndromes remains poorly understood. In this review article, we explore the possible links between cardiac adiposity and pericardial syndromes. RECENT FINDINGS: Over the last years, the notion of cardiac adipose tissue has radically changed, and its pivotal role in myocardial diseases has been acknowledged. Recent evidence suggests a cross-talk between epicardial fat and the heart. Imaging of epicardial and pericardial adipose tissue has an independent predictive/prognostic value in cardiovascular disease. Recent data suggests that imaging of epicardial adipose tissue may also provide prognostic information on the clinical course of patients with acute pericarditis. Evidence from clinical and translational studies suggests possible links between epicardial fat and pericardial diseases, which need to be further explored. Epicardial adipose tissue could have a role both as a prognostic biomarker in pericardial syndromes and as potential therapeutic target for pericardial diseases. The findings of future research in the field are eagerly anticipated.

Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular vs. blood oxidative stress.

AIMS: Experimental evidence suggests that telomere length (TL) is shortened by oxidative DNA damage, reflecting biological aging. We explore the value of blood (BTL) and vascular TL (VTL) as biomarkers of systemic/vascular oxidative stress in humans and test the clinical predictive value of BTL in acute myocardial infarction (AMI). METHODS AND RESULTS: In a prospective cohort of 290 patients surviving recent AMI, BTL measured on admission was a strong predictor of all-cause [hazard ratio (HR) [95% confidence interval (CI)]: 3.21 [1.46-7.06], P = 0.004] and cardiovascular mortality (HR [95% CI]: 3.96 [1.65-9.53], P = 0.002) 1 year after AMI (for comparisons of short vs. long BTL, as defined by a T/S ratio cut-off of 0.916, calculated using receiver operating characteristic analysis; P adjusted for age and other predictors). To explore the biological meaning of these findings, BTL was quantified in 727 consecutive patients undergoing coronary artery bypass grafting (CABG), and superoxide (O2.-) was measured in peripheral blood mononuclear cells (PBMNC). VTL/vascular O2.- were quantified in saphenous vein (SV) and mammary artery (IMA) segments. Patients were genotyped for functional genetic polymorphisms in P22ph°x (activating NADPH-oxidases) and vascular smooth muscle cells (VSMC) selected by genotype were cultured from vascular tissue. Short BTL was associated with high O2.- in PBMNC (P = 0.04) but not in vessels, whereas VTL was related to O2.- in IMA (ρ = -0.49, P = 0.004) and SV (ρ = -0.52, P = 0.01). Angiotensin II (AngII) incubation of VSMC (30 days), as a means of stimulating NADPH-oxidases, increased O2.- and reduced TL in carriers of the high-responsiveness P22ph°x alleles (P = 0.007). CONCLUSION: BTL predicts cardiovascular outcomes post-AMI, independently of age, whereas VTL is a tissue-specific (rather than a global) biomarker of vascular oxidative stress. The lack of a strong association between BTL and VTL reveals the importance of systemic vs. vascular factors in determining clinical outcomes after AMI.

Prognostic implications of epicardial fat volume quantification in acute pericarditis.

BACKGROUND: The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis. MATERIALS AND METHODS: Fifty (n = 50) patients with first diagnosis of acute pericarditis were enrolled in this study. Patients underwent a cardiac computerized tomography (CT) scan to quantify EFV on a dedicated workstation. Patients were followed up in hospital for atrial fibrillation (AF) development and up to 18 months for the composite clinical endpoint of development of constrictive, recurrent or incessant pericarditis or poor response to nonsteroidal anti-inflammatory drugs. RESULTS: Patients presenting with chest pain had lower EFV vs. patients without chest pain (167·2 ± 21·7 vs. 105·1 ± 11·1 cm3 , respectively, P < 0·01); EFV (but not body mass index) was strongly positively correlated with pericardial effusion size (r = 0·395, P = 0·007) and associated with in-hospital AF. At follow-up, patients that reached the composite clinical endpoint had lower EFV (P < 0·05). After adjustment for age, EFV was associated with lower odds ratio for the composite clinical endpoint point of poor response to NSAIDs or the development of constrictive, recurrent or incessant pericarditis during follow-up (per 20 cm3 increase in EFV: OR = 0·802 [0·656-0·981], P < 0·05). CONCLUSIONS: We report for the first time a significant association of EFV with the clinical features and the outcome of patients with acute pericarditis. Measurement of EFV by CT may have important prognostic implications in these patients.

Different Prognostic Significance of Cardiac Troponin at Presentation and Peak Cardiac Troponin in Patients with Non-ST Segment Elevation Myocardial Infarction.

OBJECTIVES: Non-ST elevation myocardial infarction (NSTEMI) is one of the most common manifestations of acute coronary syndromes (ACS). We evaluated the prognostic role of cardiac troponin I (cTnI) at presentation and peak cardiac troponin I in patients with NSTEMI. METHODS: We consecutively enrolled 215 subjects presenting with NSTEMI. Subjects were followed up for 1 year. cTnI at presentation and the peak value of cTnI were measured. The primary end point was defined as cardiovascular death, readmission to hospital with heart failure and new ACS. RESULTS: The subjects who presented the primary end point (49 subjects) had significantly increased values of peak cTnI compared to subjects free of cardiovascular events [7.19 (2.97-21.32) vs. 4.09 (1.18-11.85) ng/l; p = 0.002]. Nevertheless, cTnI at presentation did not differ between subjects who presented the primary end point and those free of events (p = 0.39). Multivariate Cox regression analysis after adjustment for confounders revealed by the univariate analysis showed that for an increase in peak cTnI from 1 to 10 ng/l, there is a 60% anticipated increase in the relative risk to present the primary end point (p = 0.04). CONCLUSION: These findings documented the different prognostic significance of cTnI at presentation and peak cTnI in patients presenting with NSTEMI, and highlighted the importance of monitoring the levels of cTnI in this high-risk population.

Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial.

Importance: Anakinra, an interleukin 1ß recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Objective: To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Design, Setting, and Participants: The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with ≥3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. Interventions: Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. Main Outcomes and Measures: The primary outcomes were recurrent pericarditis and time to recurrence after randomization. Results: Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06% of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of -1.95% (95% CI, -3.3% to -0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P <.001). During anakinra treatment, 20 of 21 patients (95.2%) experienced transient local skin reactions: 1 (4.8%) herpes zoster, 3 (14.3%) transaminase elevation, and 1 (4.8%) ischemic optic neuropathy. No patient permanently discontinued the active drug. No adverse events occurred during placebo treatment. Conclusion and Relevance: In this preliminary study of patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of anakinra compared with placebo reduced the risk of recurrence over a median of 14 months. Larger studies are needed to replicate these findings as well as to assess safety and longer-term efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02219828.