A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

BACKGROUND: The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. METHODS: To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. RESULTS: We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. CONCLUSIONS: After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).

Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction: the ECCLIPSE-STEMI trial.

Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin. Recently, we demonstrated in healthy volunteers that the administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin. Loading dose of LA achieves platelet inhibition faster, and with less variability than aspirin. However, there are no data of this issue in patients with an ST-segment elevation myocardial infarction (STEMI). This is a prospective, randomized, multicenter, open platelet function study conducted in STEMI patients. Subjects were randomly assigned to receive a loading dose (LD) of intravenous LA 450 mg plus oral ticagrelor 180 mg, or LD of aspirin 300 mg plus ticagrelor 180 mg orally. Platelet function was evaluated at baseline, 30 min, 1 h, 4 h and 24 h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation (IPA) after arachidonic acid (AA) 0.5 mM at 30 min. Secondary endpoints were the IPA at 1, 4, and 24 h after AA, and non-AA pathways through the sequence (ADP and TRAP). A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 0.5 mM at 30 min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively (p = 0.001). This differential effect was observed at 1 h (p = 0.01), but not at 4 and 24 h. Subjects treated with LA presented less variability and faster inhibition of platelet aggregation wit AA compared with aspirin. The administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin on ticagrelor inhibited platelets in patients with STEMI. Loading dose of LA achieves an earlier platelet inhibition, and with less variability than aspirin.Trial Registration: Unique identifier: NCT02929888; URL: http://www.clinicaltrials.gov.

Diagnosis, prevention, and management of delirium in the intensive cardiac care unit.

Delirium is a frequent complication in patients admitted to intensive cardiac care units (ICCU) with potentially severe consequences including increased risks of mortality, cognitive impairment and dependence at discharge, and longer times on mechanical ventilation and hospital stay. Delirium has been widely documented and studied in general intensive care units and in patients after cardiac surgery, but it has barely been studied in acute nonsurgical cardiac patients. Moreover, delirium (especially in its hypoactive form) is commonly misdiagnosed. We propose a protocol for delirium prevention and management in ICCUs. A daily comprehensive assessment to improve detection should be done using validated scales (ie, confusion assessment method). Preventive measures are particularly relevance and constitute the basis of treatment as well, acting on reversible risk factors, including environmental interventions, such as quiet time, sleep promotion, family support, communication, and adequate treatment of pain and dyspnea. Pharmacological prophylaxis is not indicated with the exception of patients at risk of withdrawal syndrome but should only be used in patients with confirmed delirium. Dexmedetomidine is the drug of choice in patients with severe agitation, and those weaning from invasive mechanical ventilation. As the complexity of ICCUs increases, clinical scenarios posing challenges for the management of delirium become more frequent. Efforts should be done to improve the identification of patients at risk during admission in order to establish preventive interventions to avoid this complication. Patient-centered protocols will increase the awareness of the healthcare professionals for better prevention and earlier diagnosis and will positively impact on prognosis.

The Role of Frailty in Acute Coronary Syndromes in the Elderly.

BACKGROUND: Myocardial infarction (MI) patients are increasingly older, and common risk scores include chronological age, but do not consider chronic comorbidity or biological age. Frailty status reflects these variables and may be independently correlated with prognosis in this setting. OBJECTIVE: This study investigated the impact of frailty on the prognosis of elderly patients admitted due to MI. METHODS: This prospective and observational study included patients ≥75 years admitted to three tertiary hospitals in Spain due to MI. Frailty assessment was performed at admission using the Survey of Health, Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the composite of death or non-fatal reinfarction during a follow-up of 1 year. Overall mortality, reinfarction, the composite of death, reinfarction and stroke, major bleeding, and readmission rates were also explored. RESULTS: A total of 285 patients were enrolled. Frail patients (109, 38.2%) were older, with a higher score in the Charlson Comorbidity Index and with a higher risk score addressed in the GRACE and CRUSADE indexes. On multivariate analysis including GRACE, CRUSADE, maximum creatinine level, culprit lesion revascularization, complete revascularization, and dual antiplatelet therapy at discharge, frailty was an independent predictor of the composite of death and reinfarction (2.81, 95% CI 1.16-6.78) and overall mortality (3.07, 95% CI 1.35-6.98). CONCLUSION: Frailty is an independent prognostic marker of the composite of mortality and reinfarction and of overall mortality in patients aged ≥75 years admitted due to MI.

Management of Acute Coronary Syndromes in Geriatric Patients.

The mean age of patients presenting with acute coronary syndrome (ACS) has been increasing steadily in the last decades, so managing very old patients has become common practice. The oldest patients are under-represented in clinical trials, so specific evidence is scarce. Still, antithrombotic therapy and invasive strategy are the pillars of appropriate treatment even in the oldest patients. However, the elderly population is a heterogeneous group showing important divergences between chronological and biological age, which needs specific evaluation. Physical, and social function, geriatric syndromes, such as frailty or cognitive decline, and comorbidities must be taken into consideration for clinical decision-making but this requires evaluation beyond the traditional cardiologic approach. In general, elderly patients with ACS who are functional and independent should be treated with the same methods as younger patients although more cautiously. However, specific measures should be put in place to prevent functional decline and delirium, two of the most frequent and devastating specific complications in older patients. Multidisciplinary approaches are needed for that. In general, a new paradigm for the management of very old patients with ACS is warranted, in which evaluation of outcomes traditionally ignored by cardiologists should be considered.

Clinical profile, management and outcomes of patients with cardiogenic shock undergoing transfer between centers in Spain.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the clinical profile, management, and prognosis of ST segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) requiring interhospital transfer, as well as the prognostic impact of structural variables of the treating centers in this setting. METHODS: This study included patients with STEMI-CS treated at revascularization-capable centers from 2016 to 2020. The patients were divided into the following groups: group A: patients attended throughout their admission at hospitals with interventional cardiology without cardiac surgery; group B: patients treated at hospitals with interventional cardiology and cardiac surgery; and group C: patients transferred to centers with interventional cardiology and cardiac surgery. We analyzed the association between the volume of STEMI-CS cases treated, the availability of cardiac intensive care units (CICU), and heart transplant with hospital mortality. RESULTS: A total of 4189 episodes were included: 1389 (33.2%) from group A, 2627 from group B (62.7%), and 173 from group C (4.1%). Transferred patients were younger, had a higher cardiovascular risk, and more commonly underwent revascularization, mechanical circulatory support, and heart transplant during hospitalization (P<.001). The crude mortality rate was lower in transferred patients (46.2% vs 60.3% in group A and 54.4% in group B, (P<.001)). Lower mortality was associated with a higher volume of care and CICU availability (OR, 0.75, P=.009; and 0.80, P=.047). CONCLUSIONS: The proportion of transfers in patients with STEMI-CS in our setting is low. Transferred patients were younger and underwent more invasive procedures. Mortality was lower among patients transferred to centers with a higher volume of STEMI-CS cases and CICU.

Early approach to LDL-related risk after acute coronary syndrome: the OPTA project.

INTRODUCTION: Hyperlipidemia is the main underlying cause of atherosclerotic cardiovascular disease. Reducing low-density lipoprotein (LDL) cholesterol to recommended targets after an acute coronary syndrome (ACS) is of utmost importance as it is associated with a reduction of mortality and further cardiovascular events. Unfortunately, there are considerable gaps between guideline recommendations and clinical practice. In addition, the approach to treatment of this population is very heterogeneous, even in specialized cardiovascular units. Some easy-to-implement strategies may help to optimize the management of these patients. AREAS COVERED: The OPTA Project was developed to identify these gaps and to provide recommendations to improve and harmonize the management of patients with ACS, with a specific focus on lipids. EXPERT OPINION: Five areas of interest were defined: 1) evaluation of cardiovascular risk at admission, 2) development of a strategy to effectively and rapidly reduce LDL cholesterol levels, 3) determining LDL cholesterol goals (<55 mg/dL or stricter) and follow-up, 4) data collection during hospitalization, and 5) standardized discharge report. Specific recommendations are given to reduce inequalities, following the targets 'the lower, the better' and 'the earlier, the better.'

Prognosis of cardiogenic shock secondary to culprit left main coronary artery lesion-related myocardial infarction.

AIMS: This study aimed to assess, in patients with cardiogenic shock secondary to unprotected left main coronary artery-related myocardial infarction (ULMCA-related AMICS), the incidence and predictors of no recovery of left ventricular function during the admission. METHODS AND RESULTS: This was an observational study conducted at two tertiary care centres (2012-20). The main outcome measured was death or requirement for heart transplantation (HT) or left ventricular assist devices (LVAD) during the admission. A total of 70 patients were included. Percutaneous coronary intervention (PCI) was successful in 53/70 patients (75.7%). The combined endpoint of death or requirement of HT or LVAD during the admission occurred in 41/70 patients (58.6%). The highest incidence of the primary endpoint was observed among patients with profound shock and occluded left main coronary artery (LMCA) (20/23, 87%, P < 0.001). Although a successful PCI reduced the incidence of the event in the whole cohort (51.9% vs. 82.4% in failed PCI, P = 0.026), this association was not observed among this last group of complex patients (86.7% vs. 87.5% in failed PCI, P = 0.731). The predictive model included left ventricular ejection fraction, baseline ULMCA Thrombolysis In Myocardial Infarction flow, and severity of shock and showed an optimal ability for predicting death or requirements for HT or LVAD during the admission (area under the curve 0.865, P < 0.001). CONCLUSIONS: ULMCA-related AMICS was associated with a high in-hospital mortality or need for HT or LVAD. Prognosis was especially poor among patients with profound shock and baseline occluded LMCA, with a low probability of recovery regardless of successful PCI.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

Interaction between VA-ECMO and the right ventricle.

BACKGROUND: The response of the right ventricle (RV) to the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is currently unpredictable. We hypothesized that the presence of uni- or bi-ventricular failure before implantation and the cannulation strategy may influence this interaction. We sought to assess the RV performance during VA-ECMO support and identify RV-related predictors of successful weaning. METHODS: Changes in RV size and function during VA-ECMO support by echocardiography were retrospectively analyzed in 87 consecutive adult patients between February 2008 and June 2017. Predictors of successful weaning due to myocardial recovery were evaluated by multivariable logistic regression. RESULTS: RV echocardiographic parameters did not vary significantly during VA-ECMO support and neither after stratification by the type of cannulation or the presence of isolated or biventricular failure. Successful weaning was conditioned by the absence of RV dysfunction before implantation (OR, 14.7; 95% CI, 13.3-140.3; p = 0.025) or in the last day of support (OR, 9.5; 95% CI, 1.6-54; p = 0.011) and was favored by a total or partial recovery of RV function during the assistance (OR, 6.2; 95%CI, 1.7-22.4; p = 0.005). RV improvement was more often observed in patients with acute RV failure and longer support, while VA-ECMO configuration, additional mechanical support, or pharmacological therapy had no effect. CONCLUSIONS: Preservation or improvement of RV function during VA-ECMO is essential for successful weaning. RV echocardiographic performance does not change significantly during VA-ECMO support and is not influenced by cannulation type or the presence of uni- or bi-ventricular failure before implantation.

Early detection of anthracycline- and trastuzumab-induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters.

AIMS: To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. METHODS AND RESULTS: Seventy-two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high-sensitivity cardiac troponin T, NT-proBNP, global longitudinal strain (GLS), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High-sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT-proBNP augmented after each anthracycline cycle (mean pre-cycle levels of 72 ± 68 pg/mL and post-cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post-anthracycline treatment and the decline in GLS was more pronounced (-17.6% vs. -21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02-1.24), odds ratio = 0.66 (0.44-0.92), P < 0.05] at 1 month post-anthracycline treatment. Neither high-sensitivity troponin T nor NT-proBNP was capable of predicting subsequent cardiotoxicity. CONCLUSIONS: One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab-induced cardiotoxicity.

Number of Antithrombotic Drugs Used Early and In-hospital Outcomes in Acute Coronary Syndromes.

Antithrombotic drug use for acute coronary syndromes (ACS) varies considerably. The number of antithrombotic drugs (excluding oral anticoagulants) used pre- and in-hospital was recorded in ACS survivors enrolled at hospital discharge in the long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients (EPICOR) registry ( NCT01171404 ), a prospective cohort study. Among 10,568 patients, the number of antithrombotic drugs used early/patient ranged from 0 to 8 (interquartile range = 3-4). Overall, 250 patients (2.4%) experienced ≥ 1 in-hospital ischemic event and 343 (3.2%) ≥ 1 non-fatal bleeding event. While there was no difference in the rate of ischemic events (p = 0.75 for-trend) according to the number of antithrombotic drugs, a significantly higher incidence of non-fatal bleeds was observed (p < 0.0001 for-trend), with OR = 1.68 (95%CI = 1.51-1.88) per additional antithrombotic drug, which remained after adjustment by patient characteristics. In conclusion, careful balancing of the short-term risks for ischemic and bleeding events should be considered when adding new antithrombotic drugs.

Temporal Trends in Mechanical Complications of Acute Myocardial Infarction in the Elderly.

BACKGROUND: Reperfusion therapy led to an important decline in mortality after ST-segment elevation myocardial infarction (STEMI). Because the rate of cardiogenic shock has not changed dramatically, the authors speculated that a reduction in the incidence or fatality rate of mechanical complications (MCs), the second cause of death in these patients, could explain this decrease. OBJECTIVES: This study sought to assess time trends in the incidence, management, and fatality rates of MC, and its influence on short-term mortality in old patients with STEMI. METHODS: Trends in the incidence and outcomes of MC between 1988 and 2008 were analyzed by Mantel-Haenszel linear association test in 1,393 consecutive patients ≥75 years of age with first STEMI. RESULTS: Overall in-hospital mortality decreased from 34.3% to 13.4% (relative risk reduction, 61%; p < 0.001). Although the absolute mortality due to MC decreased from 9.6% to 3.3% (p < 0.001), the proportion of deaths due to MC among all deaths did not change (28.1% to 24.5%; p = 0.53). The incidence of MC decreased from 11.1% to 4.3% (relative risk reduction 61%) with no change in their hospital fatality rate over time (from 87.1% to 82.4%; p = 0.66). The proportion of patients undergoing surgical repair decreased from 45.2% to 17.6% (p = 0.04), with no differences in post-operative survival (from 28.6% to 33.3%; p = 0.74). CONCLUSIONS: Although the incidence of MC has decreased substantially since the initiation of reperfusion therapy in elderly STEMI patients, this reduction was proportional to other causes of death and was not accompanied by an improvement in fatality rates, with or without surgery. MCs are less frequent but remain catastrophic complications of STEMI in these patients.

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry.

OBJECTIVES: This study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). BACKGROUND: TTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. METHODS: We analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. RESULTS: A total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of "a significant" left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). CONCLUSIONS: CS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning.

Planning secondary prevention: Room for improvement.

The prognosis of patients after acute coronary syndromes is still suboptimal, mainly due to the risk of recurrent adverse coronary events, which is greatest during the first year, but persists over one's lifetime. Meaningful progress in preventing cardiovascular events has been achieved. However, there remains much room for improvement by embracing innovative therapies and investing in multidisciplinary approaches. Pharmacological interventions focused on optimising antithrombotic and lipid-lowering therapies are both pillars of secondary prevention that have seen recent ground-breaking advances. Moreover, new approaches in diabetic patients with cardiovascular disease and new targets for anti-inflammatory treatment may significantly improve prevention strategies in the future. However, pharmacological treatments are expensive and can have significant side effects. Developing better tools in order to identify high-risk patients and promote more personalised strategies for each patient should be an absolute priority. Furthermore, adherence to medication is still low and represents a real challenge; several strategies to improve low adherence to treatment are currently under discussion. Non-pharmacological interventions are also essential. Improving communication with patients and advanced surveillance for those secondary risk factors that may negatively impact prognosis are crucial. Encouraging multidisciplinary teams that work effectively to optimise all aspects of secondary prevention, including a cardiac rehabilitation programme, is the optimal approach. Current secondary prevention strategies and suggestions for areas of improvement are discussed in this manuscript. However, the question remains: will research in secondary prevention continue to focus on stronger and more expensive drugs, or is it time for us to embrace a more patient-centred clinical and research model?

'Jamaican Stone': A potentially lethal remedy for delaying ejaculation.

Poisoning by ingestion of 'Jamaican Stone', a kind of cardioactive steroid, is extremely rare. However, mortality is very high. For this reason, when it occurs, an early and accurate diagnosis represents a critical challenge for clinicians. We present an unusual case of electrical storm caused by this substance.