Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children, regardless of disease severity.

OBJECTIVE: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. METHODS: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. RESULTS: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0). CONCLUSION: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome.

Long-term cardiac outcomes of depression screening, diagnosis and treatment in patients with acute coronary syndrome: the DEPACS study.

BACKGROUND: To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS). METHODS: Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5-12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M). RESULTS: Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63-2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline. CONCLUSIONS: Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.

Molecular imaging-guided repair after acute myocardial infarction by targeting the chemokine receptor CXCR4.

AIMS: Balance between inflammatory and reparative leucocytes allows optimal healing after myocardial infarction (MI). Interindividual heterogeneity evokes variable functional outcome complicating targeted therapy. We aimed to characterize infarct chemokine CXC-motif receptor 4 (CXCR4) expression using positron emission tomography (PET) and establish its relationship to cardiac outcome. We tested whether image-guided early CXCR4 directed therapy attenuates chronic dysfunction. METHODS AND RESULTS: Mice (n = 180) underwent coronary ligation or sham surgery and serial PET imaging over 7 days. Infarct CXCR4 content was elevated over 3 days after MI compared with sham (%ID/g, Day 1:1.1 ± 0.2; Day 3:0.9 ± 0.2 vs. 0.6 ± 0.1, P < 0.001), confirmed by flow cytometry and histopathology. Mice that died of left ventricle (LV) rupture exhibited persistent inflammation at 3 days compared with survivors (1.2 ± 0.3 vs. 0.9 ± 0.2% ID/g, P < 0.001). Cardiac magnetic resonance measured cardiac function. Higher CXCR4 signal at 1 and 3 days independently predicted worse functional outcome at 6 weeks (rpartial = -0.4, P = 0.04). Mice were treated with CXCR4 blocker AMD3100 following the imaging timecourse. On-peak CXCR4 blockade at 3 days lowered LV rupture incidence vs. untreated MI (8% vs. 25%), and improved contractile function at 6 weeks (+24%, P = 0.01). Off-peak CXCR4 blockade at 7 days did not improve outcome. Flow cytometry analysis revealed lower LV neutrophil and Ly6Chigh monocyte content after on-peak treatment. Patients (n = 50) early after MI underwent CXCR4 PET imaging and functional assessment. Infarct CXCR4 expression in acute MI patients correlated with contractile function at time of PET and on follow-up. CONCLUSION: Positron emission tomography imaging identifies early CXCR4 up-regulation which predicts acute rupture and chronic contractile dysfunction. Imaging-guided CXCR4 inhibition accelerates inflammatory resolution and improves outcome. This supports a molecular imaging-based theranostic approach to guide therapy after MI.

Prognostic Value of Left Ventricular Dyssynchrony Assessed with Nuclear Cardiology in Patients with Known or Suspected Stable Coronary Artery Disease with Preserved Left Ventricular Ejection Fraction.

Left ventricular (LV) mechanical dyssynchrony assessed with phase analysis of electrocardiogram (ECG) -gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is useful for predicting major cardiac events (MCEs) in patients with cardiac dysfunction. However, there is no report on its usefulness in Japanese patients with known or suspected stable coronary artery disease (CAD) with preserved LV ejection fraction (LVEF).We retrospectively investigated 3,374 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin ECG-gated SPECT MPI and had preserved LVEF (≥ 45%), and followed them up to confirm their prognosis for three years. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris, and severe heart failure requiring hospitalization. LV mechanical dyssynchrony was evaluated with phase analysis with the Heart Risk View-F software to obtain the phase bandwidth and standard deviation.During the follow-up, 179 patients experienced MCEs: cardiac death (n = 42); non-fatal MI (n = 34); unstable angina pectoris (n = 54); and severe heart failure (n = 49). Results of the multivariate analysis showed age, a history of MI, diabetes mellitus, summed stress score, and stress phase bandwidth to be independent predictors for MCEs. In Kaplan-Meier analysis, prognoses were significantly stratified with the tertiles of stress phase bandwidth.LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for predicting a prognosis and stratifying the risk of MCEs in Japanese patients with known or suspected stable CAD with preserved LVEF.

Yield of left ventricular dyssynchrony by gated SPECT MPI in patients with heart failure prior to implantable cardioverter-defibrillator or cardiac resynchronization therapy with a defibrillator: Characteristics and prediction of cardiac outcome.

BACKGROUND: Mechanical left ventricular dyssynchrony (MLVD) might contribute in the therapeutic decision-making in patients with heart failure (HF) prior to cardiac resynchronization therapy (CRT). Our aim was to assess MLVD in patients with HF prior to implantable cardioverter-defibrillator (ICD) compared to patients with CRT-D. METHODS: In a prospective study, patients with LVEF ≤ 35% who were scheduled for ICD or CRT-D, underwent gated SPECT myocardial perfusion imaging with technetium 99m sestamibi within 3 months prior procedure. MLVD was measured by phase analysis. RESULTS: The study cohort consisted of 143 patients, 71 with ICD and 72 with CRT-D. Age 68.3 ± 11 and LVEF 24 ± 6%. Phase standard deviation (SD) was 62.5 ± 18 and 59.7 ± 20 (P = NS), respectively. During follow-up of 23.7 ± 12.1 months, there were 10 vs 14 cardiac death in ICD and CRT-D, respectively (P = NS), hospitalization for HF, in 34 vs 53 (P < .001). In multivariate analysis, Phase SD was the independent predictor for cardiac death [HR 2.66 (95% CI 1.046-6.768), P = .04]. Kaplan-Meier curves of phase SD of 60° significantly identified ICD patients with and without cardiac deaths and hospitalization for HF exacerbation. CONCLUSIONS: MLVD by phase SD can identify patients with cardiac events and predict cardiac death in patients treated with ICD.

Heart failure biomarkers in revascularized patients with stable coronary heart disease as clinical outcome predictors.

Introduction: The aim of this study was to investigate serum levels of galectin-3 (Gal-3) and N-terminal pro-brain Natriuretic Peptide (NT-proBNP) in patients with stable obstructive coronary artery disease, as well as their potential to predict clinical outcomes. Methods: This was a single-center cross-sectional cohort study. 168 patients were divided into three groups: percutaneous coronary intervention (PCI) group (N 64), coronary artery bypass graft surgery (CABG) group (N 57), and group with no coronary stenosis (N 47). Gal-3 and NT-proBNP levels were measured and the Syntax score (Ss) was calculated. Results: The mean value of Gal-3 was 19.98 ng/ml and 9.51 ng/ml (p < 0.001) in the study group and control group, respectively. Highest value of Gal-3 was found in the group of subjects with three-vessel disease (p < 0.001). The mean value of NT-proBNP in the study group was 401.3 pg/ml, and in the control group 100.3 pg/ml (p = 0.159). The highest value of NT-proBNP was found in the group of subjects with three-vessel disease (p = 0.021). There was a statistically significant association between Gal-3, NT-proBNP and occurrence of adverse cardiovascular event (p = 0.0018; p = 0.0019). Conclusion: Gal-3 and NT-proBNP could be used as an additional tool for diagnosis and severity assessment of stable obstructive coronary artery disease. Furthermore, it could help identify high-risk patients who could experience major adverse cardiovascular events.

Clinical profile and outcome of cardiac manifestations in patients presenting with multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection.

Multisystem inflammatory syndrome in children (MIS-C) can cause significant morbidity and mortality in children. This study was conducted to assess the pattern and outcome of cardiac abnormalities in MIS-C. This retrospective study was conducted in children with MIS-C between 1 month and 18 years. We enrolled 53 children with a mean age of 7.78 ± 4.62 years. Overall, 35.8% of children with MIS-C had cardiac manifestations in the form of coronary artery abnormalities (CAAs) or left ventricular (LV) dysfunction. Younger age (P 0.009) and high C-reactive protein at admission (P = 0.001) were significant predictors of cardiac involvement. CAAs were seen in 11.3% of children. On follow-up, 67% and 83% of children showed regression of CAA at 1 and 6 months, respectively. 24.5% of patients had presented with LV dysfunction. LV ejection fraction improved significantly at 1 month (P = 0.002) and 6 months (P = 0.001). Cardiac outcomes in MIS-C were favorable with timely identification and treatment.

Validation of Risk Stratification for Cardiac Events in Pregnant Women With Valvular Heart Disease.

BACKGROUND: Most risk stratification tools for pregnant patients with heart disease were developed in high-income countries and in populations with predominantly congenital heart disease, and therefore, may not be generalizable to those with valvular heart disease (VHD). OBJECTIVES: The purpose of this study was to validate and establish the clinical utility of 2 risk stratification tools-DEVI (VHD-specific tool) and CARPREG-II-for predicting adverse cardiac events in pregnant patients with VHD. METHODS: We conducted a cohort study involving consecutive pregnancies complicated with VHD admitted to a tertiary center in a middle-income setting from January 2019 to April 2022. Individual risk for adverse composite cardiac events was calculated using DEVI and CARPREG-II models. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis. RESULTS: Of 577 eligible pregnancies, 69 (12.1%) experienced a component of the composite outcome. A majority (94.7%) had rheumatic etiology, with mitral regurgitation as the predominant lesion (48.2%). The area under the receiver-operating characteristic curve was 0.884 (95% CI: 0.844-0.923) for the DEVI and 0.808 (95% CI: 0.753-0.863) for the CARPREG-II models. Calibration plots suggested that DEVI score overestimates risk at higher probabilities, whereas CARPREG-II score overestimates risk at both extremes and underestimates risk at middle probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 50%. CONCLUSIONS: In pregnant patients with VHD, DEVI and CARPREG-II scores showed good discriminative ability and clinical utility across a range of probabilities. The DEVI score showed better agreement between predicted probabilities and observed events.

Association of Coronary Computed Tomography Angiography and Stress Echocardiography with Long-Term Cardiac Outcome: A Comparison Study.

AIMS: This study aimed to assess which variables on coronary computed tomography angiography (CTA) and vasodilator stress-echocardiography (SE) are best associated with long-term cardiac outcome in patients presenting for suspected chronic coronary syndrome (CCS) who performed both tests. METHODS: We identified 397 patients with suspected CCS who, between 2007 and 2019, underwent both SE and CTA within 30 days. Coronary artery calcium score (CACS) and the number of coronary arteries with diameter stenosis >50% were assessed on CTA. The presence of reversible regional wall motion abnormalities (RWMA) and reduced Doppler coronary flow velocity reserve in the left-anterior descending coronary artery (CFVR) were assessed on SE. The association of SE and CTA variables with cardiac outcome (cardiac death or myocardial infarction) was evaluated using Fine and Gray competing risk models. RESULTS: During a median follow-up of 10 years, 38 (9.6%) patients experienced a nonfatal myocardial infarction and 19 (4.8%) died from a cardiac cause. RWMA (HR 7.189, p < 0.001) and a lower CFVR (HR 0.034, p < 0.001) on SE, along with CACS (HR 1.004, p < 0.001) and the number of >50% stenosed coronary vessels (HR 1.975, p < 0.001) on CTA, were each associated with cardiac events. After adjusting for covariates, only CACS and CFVR remained associated (both p < 0.001) with cardiac outcome. CONCLUSION: Our data suggest that only CFVR on vasodilatory SE and CACS on CTA are independently and strongly associated with long-term cardiac outcome, unlike RWMA or the number of stenosed coronary arteries, usually considered the hallmarks of coronary artery disease on each test.

Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients With Asymmetric Hypertrophic Cardiomyopathy.

Background Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long-term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long-term prognostic value of CFVR on clinical outcome in HCM population. Methods and Results We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients' clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow-up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P<0.001 vs. Group 1) adverse cardiac events. By Kaplan-Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event-free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log-rank 37.2, P<0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83-16.30, P<0.001), while CFVR PD was not significantly associated with outcome. Conclusions In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Impact of depression at early and late phases following acute coronary syndrome on long-term cardiac outcomes.

BACKGROUND: Depression has been associated with worse cardiac outcomes in patients with acute coronary syndrome, while no study has investigated trajectory of depression and ACS prognosis. This study investigated associations of depressive disorder within 2 weeks (early) and at 1 year (late) after ACS with major adverse cardiac event (MACE). METHOD: In 757 ACS patients recruited in 2007-2012 and evaluated for depressive disorder at the two time-points, 5-12 year follow-up for MACE was conducted. RESULTS: MACE incidence was significantly higher in patients with depressive disorder at early or late phase of ACS than those without, regardless of status at the other time point; however, highest incidence was found following depression at both time points. LIMITATION: The follow-up for depressive disorder was made at only one point. CONCLUSION: Depression evaluation thus needs consideration both early and late post-ACS.

NT-proBNP Level Predicts Extent of Myonecrosis and Clinical Adverse Outcomes in Patients with ST-Elevation Myocardial Infarction: A Pilot Study.

BACKGROUND AND HYPOTHESIS: The initial assessment of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) reflects cardiac damage and is an important prognostic factor in patients with acute ST-elevation myocardial infarction (STEMI). N-Terminal prohormone of brain natriuretic peptide (NT-proBNP) is released following cardiomyocytes injury. However, the relationship between NT-proBNP levels, myocardial damage and clinical outcomes after STEMI has not been well defined. METHODS: Plasma levels of NT-proBNP, troponin I and creatinine kinase (CK) were assessed in 75 patients with STEMI. Echocardiography and CMR were performed prior to hospital discharge. Cardiac damage was quantified using peak biomarker levels and LGE. Patients were followed for a median of 975 days (IQR 823-1098 days) for major adverse cardiac events (MACE) (all-cause mortality, recurrent myocardial infraction, unplanned recurrent revascularization and recurrent hospitalization for heart failure). RESULTS: Plasma levels of NT-proBNP increased following STEMI to peak at 24 hours. The dynamic changes in plasma NT-proBNP were similar to those noted with troponin I and its delayed peak but not those observed with plasma CK levels. Peak NT-proBNP levels correlated positively with indices of myocardial damage such as peak troponin I (R2 =0.38, P <0.001), peak CK (R2 =0.22, P = 0.01) and LGE examination (R2 = 0.46, P <0.001). Peak plasma level of NT- proBNP was strongly predictive of MACE during the follow-up period. CONCLUSIONS: Peak levels of NT-proBNP following STEMI are predictive of the extent of myocardial damage and clinical outcomes. These results suggest an important prognostic role for NT-proBNP assessment in STEMI patients.

Long-Term Prognostic Value of Coronary Computed Tomography Angiography in an Asymptomatic Elderly Population.

Background The prognostic value of coronary computed tomographic angiography (CCTA) for evaluating coronary artery disease in asymptomatic older adults is controversial. We investigated the prognostic value of CCTA in community-dwelling elderly Koreans. Methods and Results Participants (n=470; mean age: 75.1±7.3 years) who underwent CCTA were enrolled from KLoSHA (Korean Longitudinal Study on Health and Aging), a community-based prospective cohort. Using CCTA, coronary artery disease was classified as normal, nonobstructive, or obstructive according to the presence of 0%, <50%, or ≥50% stenosis, respectively. Coronary artery calcium scores were investigated together with Framingham risk score, atherosclerotic cardiovascular disease score, and individual risk factors. Major adverse cardiac events (MACE) were defined as a composite of cardiac event-related death or nonfatal myocardial infarction. During a median follow-up of 8.2 years (interquartile range: 7.7-10.1 years), MACE occurred in 24 participants (5.1%). Compared with the normal group, participants in the obstructive group showed higher incidence of MACE (hazard ratio: 5.65; 95% CI, 1.22-26.16; P=0.027), whereas there were no significant differences in MACE between the normal and nonobstructive groups. The 8-year event-free survival rates were 98.1±1.1%, 94.9±1.6%, and 81.7±4.8% in the normal, nonobstructive, and obstructive groups, respectively. Compared with the Framingham risk score and coronary artery calcium score model, CCTA improved risk prediction by C-index (from 0.698 to 0.749) and category-free net reclassification index (0.478; P=0.022). Conclusions CCTA showed better long-term prognostic value for MACE than coronary artery calcium score in this asymptomatic older population.