Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score.

BACKGROUND: Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses' malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability. METHODS: Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors. RESULTS: In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0-8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96-0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932; P=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (P<0.001; hazard ratio, 5.70) at follow-up. CONCLUSIONS: A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications.

Sex- and gender-related disparities in chest pain syndromes: the feminine mystique of chest pain.

Chest pain syndromes encompass a wide range of different clinical conditions, being coronary artery disease one of the most important and feared aetiology. Sex and gender disparities have been reported in pathophysiology, clinical presentations, diagnostic work-up and outcomes of patients admitted for chest pain. Biological differences in sexual hormones and neurological pain procession pathways have been proposed as contributors to disparities between men and women; however, gender-related disparities in socio-economic and psychological status have emerged as additional factors involved in these conditions. A better understanding of gender- and sex-related disparities will lead to improved clinical care and management of chest pain syndromes in both men and women. In this comprehensive review, we describe the existing knowledge regarding sex and gender-based differences in management and outcomes of chest pain syndromes in order to stimulate and promote the development of a more sex- and gender-oriented approach to these conditions.

Myocardial strain of the left ventricle by speckle tracking echocardiography: From physics to clinical practice.

Speckle tracking echocardiography (STE) is a reliable imaging technique of recognized clinical value in several settings. This method uses the motion of ultrasound backscatter speckles within echocardiographic images to derive myocardial velocities and deformation parameters, providing crucial insights on several cardiac pathological and physiological processes. Its feasibility, reproducibility, and accuracy have been widely demonstrated, being myocardial strain of the various chambers inserted in diagnostic algorithms and guidelines for various pathologies. The most important parameters are Global longitudinal strain (GLS), Left atrium (LA) reservoir strain, and Global Work Index (GWI): based on large studies the average of the lower limit of normality are -16%, 23%, and 1442 mmHg%, respectively. For GWI, it should be pointed out that myocardial work relies primarily on non-invasive measurements of blood pressure and segmental strain, both of which exhibit high variability, and thus, this variability constitutes a significant limitation of this parameter. In this review, we describe the principal aspects of the theory behind the use of myocardial strain, from cardiac mechanics to image acquisition techniques, outlining its limitation, and its principal clinical applications: in particular, GLS have a role in determine subclinical myocardial dysfunction (in cardiomyopathies, cardiotoxicity, target organ damage in ambulatory patients with arterial hypertension) and LA strain in determine the risk of AF, specifically in ambulatory patients with arterial hypertension.

Prognostic Role of Early Cardiac Magnetic Resonance in Myocardial Infarction With Nonobstructive Coronary Arteries.

BACKGROUND: Cardiac magnetic resonance (CMR) plays a pivotal diagnostic role in myocardial infarction with nonobstructive coronary arteries (MINOCA). To date, a prognostic stratification of these patients is still lacking. OBJECTIVES: This study aims to assess the prognostic role of CMR in MINOCA. METHODS: The authors assessed 437 MINOCA from January 2017 to October 2021. They excluded acute myocarditis, takotsubo syndromes, cardiomyopathies, and other nonischemic etiologies. Patients were classified into 3 subgroups according to the CMR phenotype: 1) presence of late gadolinium enhancement (LGE) and abnormal mapping (M) values (LGE+/M+); 2) regional ischemic injury with abnormal mapping and no LGE (LGE-/M+); and 3) nonpathological CMRs (LGE-/M-). The primary outcome was the presence of major adverse cardiovascular events (MACE). The mean follow-up was 33.7 ± 12.0 months and CMR was performed on average at 4.8 ± 1.5 days from the acute presentation. RESULTS: The final cohort included 198 MINOCA; 116 (58.6%) comprised the LGE+/M+ group. During follow-up, MACE occurred significantly more frequently in MINOCA LGE+/M+ than in the LGE+/M- and normal-CMR (LGE-/M-) subgroups (20.7% vs 6.7% and 2.7%; P = 0.006). The extension of myocardial damage at CMR was significantly greater in patients who developed MACE. In multivariable Cox regression, %LGE was an independent predictor of MACE (HR: 1.123 [95% CI: 1.064-1.185]; P < 0.001) together with T2 mapping values (HR: 1.190 [95% CI: 1.145-1.237]; P = 0.001). CONCLUSIONS: In MINOCA with early CMR execution, the %LGE and abnormal T2 mapping values were identified as independent predictors of adverse cardiac events at ∼3.0 years of follow-up. These parameters can be considered as high-risk markers in MINOCA.

Genomic Landscape Comparison of Cardiac versus Extra-Cardiac Angiosarcomas.

Angiosarcomas (ASs) are rare malignant vascular entities that can affect several regions in our body, including the heart. Cardiac ASs comprise 25-40% of cardiac sarcomas and can cause death within months of diagnosis. Thus, our aim was to identify potential differences and/or similarities between cardiac and extra-cardiac ASs to enhance targeted therapies and, consequently, patients' prognosis. Whole-transcriptome analysis of three cardiac and eleven extra-cardiac non-cutaneous samples was performed to investigate differential gene expression and mutational events between the two groups. The gene signature of cardiac and extra-cardiac non-cutaneous ASs was also compared to that of cutaneous angiosarcomas (n = 9). H/N/K-RAS and TP53 alterations were more recurrent in extra-cardiac ASs, while POTE-gene family overexpression was peculiar to cardiac ASs. Additionally, in vitro functional analyses showed that POTEH upregulation conferred a growth advantage to recipient cells, partly supporting the cardiac AS aggressive phenotype and patients' scarce survival rate. These features should be considered when investigating alternative treatments.

[Periprocedural myocardial injury and infarction after myocardial revascularization: incidence, clinical features and prognosis]. / Infarto e danno miocardico periprocedurali dopo rivascolarizzazione miocardica: incidenza, implicazioni cliniche e prognosi.

Myocardial revascularization, either percutaneous or surgical, is the cornerstone of chronic and acute ischemic coronary artery disease therapy. Periprocedural myocardial injury and infarction are possible complications of these procedures. Several pathogenetic mechanisms have been proposed in the setting of percutaneous (distal embolism, vasospasm, obstruction of a minor vessel) or surgical revascularization (prolonged ischemic time, early graft failure, arrhythmia or severe hypotension during the procedure). High-sensitivity cardiac troponins have emerged as the recommended biomarkers due to their important prognostic implications. However, data regarding diagnostic criteria, management and prognostic implications of these complications are lacking. The present review aims to provide an overview regarding the possible diagnostic criteria, management and prognostic role of periprocedural myocardial injury and infarction.

Performance of Prognostic Scoring Systems in MINOCA: A Comparison among GRACE, TIMI, HEART, and ACEF Scores.

Background: the prognosis of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not benign; thus, prompting the need to validate prognostic scoring systems for this population. Aim: to evaluate and compare the prognostic performance of GRACE, TIMI, HEART, and ACEF scores in MINOCA patients. Methods: A total of 250 MINOCA patients from January 2017 to September 2021 were included. For each patient, the four scores at admission were retrospectively calculated. The primary outcome was a composite of all-cause death and acute myocardial infarction (AMI) at 1-year follow-up. The ability to predict 1-year all-cause death was also tested. Results: Overall, the tested scores presented a sub-optimal performance in predicting the composite major adverse event in MINOCA patients, showing an AUC ranging between 0.7 and 0.8. Among them, the GRACE score appeared to be the best in predicting all-cause death, reaching high specificity with low sensitivity. The best cut-off identified for the GRACE score was 171, higher compared to the cut-off of 140 generally applied to identify high-risk patients with obstructive AMI. When the scores were tested for prediction of 1-year all-cause death, the GRACE and the ACEF score showed very good accuracy (AUC = 0.932 and 0.828, respectively). Conclusion: the prognostic scoring tools, validated in AMI cohorts, could be useful even in MINOCA patients, although their performance appeared sub-optimal, prompting the need for risk assessment tools specific to MINOCA patients.

Predictive value of Killip classification in MINOCA patients.

BACKGROUND: Killip classification is a practical clinical tool for risk stratification in patients with acute myocardial infarction (AMI). However, its prognostic role in myocardial infarction with non-obstructive coronary artery (MINOCA) is still poorly explored. Our purpose was to evaluate the prognostic role of high Killip class in the specific setting of MINOCA and compare the results with a cohort of patients with obstructive coronary arteries myocardial infarction (MIOCA). METHODS: This study included 2455 AMI patients of whom 255 were MINOCA. We compared the Killip classes of MINOCA with those of MIOCA and evaluated the prognostic impact of a high Killip class, defined if greater than I, on both populations' outcome. Short-term outcomes included in-hospital death, re-AMI and arrhythmias. Long-term outcomes were all-cause mortality, re-AMI, stroke, heart failure (HF) hospitalization and the composite endpoint of MACE. RESULTS: Killip class >1 occurred in 25 (9.8%) MINOCA patients compared to 327 (14.9%) MIOCA cases. In MINOCA subjects, a high Killip class was associated with a greater in-hospital mortality (p = 0.002) and, at long term follow-up, with a three-fold increased mortality (p = 0.001) and a four-fold risk of HF hospitalization (p = 0.003). Among MINOCA, a high Killip class was identified as a strong independent predictor of MACE occurrence [HR 2.66, 95% CI (1.25-5.64), p = 0.01] together with older age and worse kidney function while in MIOCA population also left ventricular ejection fraction and troponin value predicted MACE. CONCLUSIONS: Killip classification confirmed its prognostic impact on short- and long-term outcomes also in a selected MINOCA population, which still craves for a baseline risk stratification.

Sex Differences in Heart Failure: What Do We Know?

Heart failure (HF) remains an important global health issue, substantially contributing to morbidity and mortality. According to epidemiological studies, men and women face nearly equivalent lifetime risks for HF. However, their experiences diverge significantly when it comes to HF subtypes: men tend to develop HF with reduced ejection fraction more frequently, whereas women are predominantly affected by HF with preserved ejection fraction. This divergence underlines the presence of numerous sex-based disparities across various facets of HF, encompassing aspects such as risk factors, clinical presentation, underlying pathophysiology, and response to therapy. Despite these apparent discrepancies, our understanding of them is far from complete, with key knowledge gaps still existing. Current guidelines from various professional societies acknowledge the existence of sex-based differences in HF management, yet they are lacking in providing explicit, actionable recommendations tailored to these differences. In this comprehensive review, we delve deeper into these sex-specific differences within the context of HF, critically examining associated definitions, risk factors, and therapeutic strategies. We provide a specific emphasis on aspects exclusive to women, such as the impact of pregnancy-induced hypertension and premature menopause, as these unique factors warrant greater attention in the broader HF discussion. Additionally, we aim to clarify ongoing controversies and knowledge gaps pertaining to the pharmacological treatment of HF and the sex-specific indications for cardiac implantable electronic devices. By shining a light on these issues, we hope to stimulate a more nuanced understanding and promote the development of more sex-responsive approaches in HF management.

Sex- and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA vs. MIOCA.

AIMS: The aim of the study is to evaluate the impact of sex on acute myocardial infarction (AMI) patients' clinical presentation and outcomes, comparing those with non-obstructive and obstructive coronary arteries (MINOCA vs. MIOCA). METHODS AND RESULTS: We enrolled 2455 patients with AMI undergoing coronary angiography from January 2017 to September 2021. Patients were divided according to the type of AMI and sex: male (n = 1593) and female (n = 607) in MIOCA and male (n = 87) and female (n = 168) in MINOCA. Each cohort was further stratified based on age (≤/> 70 years). The primary endpoint (MAE) was a composite of all-cause death, recurrent AMI, and hospitalization for heart failure (HF) at follow-up. Secondary outcomes included all-cause and cardiovascular death, recurrent AMI, HF re-hospitalization, and stroke. MINOCA patients were more likely to be females compared with MIOCA ones (P < 0.001). The median follow-up was 28 (15-41) months. The unadjusted incidence of MAE was significantly higher in females compared with males, both in MINOCA [45 (26.8%) vs. 12 (13.8%); P = 0.018] and MIOCA cohorts [203 (33.4%) vs. 428 (26.9%); P = 0.002]. Age was an independent predictor of MAE in both cohorts. Among MINOCA patients, females ≤70 years old had a higher incidence of MAE [18 (23.7%) vs. 4 (5.9%); P = 0.003] compared with male peers, mainly driven by a higher rate of re-hospitalization for HF (P = 0.045) and recurrence of AMI (P = 0.006). Only in this sub-group of MINOCA patients, female sex was an independent predictor of MAE (hazard ratio = 3.09; 95% confidence interval: 1.02-9.59; P = 0.040). MINOCA females ≤70 years old had worse outcomes than MIOCA female peers. CONCLUSION: MINOCA females ≤70 years old had a significantly higher incidence of MAE, compared with males and MIOCA female peers, likely due to the different pathophysiology of the ischaemic event. TRIAL REGISTRATION: Data were part of the ongoing observational study 'AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation' (ClinicalTrials.gov Identifier: NCT03883711).

The Role of Non-Invasive Multimodality Imaging in Chronic Coronary Syndrome: Anatomical and Functional Pathways.

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact. Currently, various guidelines and recommendations have been published about chronic coronary syndromes (CCS). According to the recent European Society of Cardiology guidelines on chronic coronary syndrome, a multimodal imaging approach is strongly recommended in the evaluation of patients with suspected CAD. Today, in the current practice, non-invasive imaging methods can assess coronary anatomy through coronary computed tomography angiography (CCTA) and/or inducible myocardial ischemia through functional stress testing (stress echocardiography, cardiac magnetic resonance imaging, single photon emission computed tomography-SPECT, or positron emission tomography-PET). However, recent trials (ISCHEMIA and REVIVED) have cast doubt on the previous conception of the management of patients with CCS, and nowadays it is essential to understand the limitations and strengths of each imaging method and, specifically, when to choose a functional approach focused on the ischemia versus a coronary anatomy-based one. Finally, the concept of a pathophysiology-driven treatment of these patients emerged as an important goal of multimodal imaging, integrating 'anatomical' and 'functional' information. The present review aims to provide an overview of non-invasive imaging modalities for the comprehensive management of CCS patients.

Sex-Related Disparities in Cardiac Masses: Clinical Features and Outcomes.

BACKGROUND: Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. PURPOSE: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. MATERIAL AND METHODS: The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. RESULTS: Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p < 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. CONCLUSIONS: In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses.

Echocardiographic Markers in the Diagnosis of Cardiac Masses.

BACKGROUND: The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown. The aim of this study was to identify and integrate the echocardiographic features of CMs that can accurately predict malignancy. METHODS: An observational cohort study was conducted among 286 consecutive patients who underwent standard echocardiographic assessment for suspected CM at Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histologic examination or, in the case of cardiac thrombi, with radiologic evidence of thrombus resolution after appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of six echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numeric score, ranging from 0 to 6, with a cutoff of ≥3 balancing sensitivity and specificity with respect to the histologic diagnosis of malignancy. Classification tree analysis was used to determine the ability of echocardiographic parameters to discriminate subgroups of patients with differential risk for malignancy. RESULTS: Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (P < .001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (P < .001). Infiltration, moderate to severe pericardial effusion, nonleft localization, sessile implantation, polylobate shape, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted score of ≥3 was very high (>0.90) and similar to that of the previously published weighted score. Classification tree analysis generated an algorithm in which infiltration was the best discriminator of malignancy, followed by nonleft localization and sessile implantation. The percentage correctly classified by classification tree analysis as malignant was 87.5%. Agreement between observer readings and CM histology ranged between 85.1% and 91.5%. The presence of at least three echocardiographic parameters was associated with lower survival. CONCLUSIONS: In the approach to CMs, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

[Cardiac masses: classification, clinical features and diagnostic approach]. / Classificazione, caratteristiche cliniche e strategie diagnostiche delle masse cardiache.

The term cardiac mass refers to benign or malignant cardiac tumors and cardiac metastases but also to pseudotumors, which is a heterogeneous group consisting of thrombi, vegetations and normal variant structures. While primitive cardiac tumors are rare, metastases and pseudotumors are relatively common. The non-invasive diagnostic approach has not been well established in the literature yet. The first-line non-invasive approach consists of echocardiography, which provides good diagnostic accuracy for masses like thrombi, vegetations and some tumors (mainly myxoma and fibroelastoma). In contrast, for other masses, it does not provide information about the potential malignancy because of poor tissue characterization. Second-line (cardiac computed tomography and cardiac magnetic resonance) or third-line (positron emission tomography-computed tomography) evaluations have been validated in the diagnostic approach to cardiac masses by many studies. In fact, a comprehensive diagnostic approach may establish the diagnosis of malignancy without histological report, which is pivotal for the subsequent therapeutic strategy.The aim of this narrative review is to describe the commonly available non-invasive diagnostic techniques for cardiac masses, their potential and limitations and to suggest a diagnostic pathway for common practice.

Genetics and clinical phenotype of Erdheim-Chester disease: A case report of constrictive pericarditis and a systematic review of the literature.

Background: Erdheim-Chester disease (ECD) is a rare form of histiocytosis. An increasing number of genetic mutations have been associated with this syndrome, confirming its possible neoplastic origin. Recently, a connection between the BRAF mutational status and a specific phenotype was described; however, no studies have yet evaluated the correlations between other mutations and the clinical features of the disease. Objectives: This study aims to clarify the association between the clinical phenotype and genetic mutations identified in the neoplastic cell lines of ECD. Methods: We describe a case of ECD characterized by pericardial involvement and a KRAS mutation shared with chronic myelomonocytic leukemia. Hence, through a meta-analysis of individual participant data of all genetically and clinically described cases of ECD in the literature, we aimed to elucidate the association between its clinical phenotype and baseline genetic mutations. Results: Of the 760 studies screened, our review included 133 articles published from 2012 to April 2021. We identified 311 ECD patients whose genotype and phenotype were described. We found five main genes (BRAF, KRAS, NRAS, PIK3CA, and MAP2K1) whose mutation was reported at least three times. Mutation of BRAF led to a neurological disease (183 of 273 patients, 67%; p < 0.001); KRAS- and NRAS-mutated patients mainly showed cutaneous (five of six patients, 83.3%, p < 0.004) and pleural (four of nine patients, 44%, p = 0.002) involvement, respectively; PIK3CA was not associated with specific organ involvement; and MAP2K1 mutations caused the disease to primarily involve the peritoneum and retroperitoneum (4 of 11, 36.4%, p = 0.01). Conclusion: This work implies a possible influence of baseline mutation over the natural history of ECD, underscoring the importance of a thorough genetic analysis in all cases with the ultimate goal of identifying a possible targeted therapy for each patient.

Impact of admission hyperglycemia on short and long-term prognosis in acute myocardial infarction: MINOCA versus MIOCA.

BACKGROUND: The prognostic role of hyperglycemia in patients with myocardial infarction and obstructive coronary arteries (MIOCA) is acknowledged, while data on non-obstructive coronary arteries (MINOCA) are still lacking. Recently, we demonstrated that admission stress-hyperglycemia (aHGL) was associated with a larger infarct size and inflammatory response in MIOCA, while no differences were observed in MINOCA. We aim to investigate the impact of aHGL on short and long-term outcomes in MIOCA and MINOCA patients. METHODS: Multicenter, population-based, cohort study of the prospective registry, designed to evaluate the prognostic information of patients admitted with acute myocardial infarction to S. Orsola-Malpighi and Maggiore Hospitals of Bologna metropolitan area. Among 2704 patients enrolled from 2016 to 2020, 2431 patients were classified according to the presence of aHGL (defined as admission glucose level ≥ 140 mg/dL) and AMI phenotype (MIOCA/MINOCA): no-aHGL (n = 1321), aHGL (n = 877) in MIOCA and no-aHGL (n = 195), aHGL (n = 38) in MINOCA. Short-term outcomes included in-hospital death and arrhythmias. Long-term outcomes were all-cause and cardiovascular mortality. RESULTS: aHGL was associated with a higher in-hospital arrhythmic burden in MINOCA and MIOCA, with increased in-hospital mortality only in MIOCA. After adjusting for age, gender, hypertension, Killip class and AMI phenotypes, aHGL predicted higher in-hospital mortality in non-diabetic (HR = 4.2; 95% CI 1.9-9.5, p = 0.001) and diabetic patients (HR = 3.5, 95% CI 1.5-8.2, p = 0.003). During long-term follow-up, aHGL was associated with 2-fold increased mortality in MIOCA and a 4-fold increase in MINOCA (p = 0.032 and p = 0.016). Kaplan Meier 3-year survival of non-hyperglycemic patients was greater than in aHGL patients for both groups. No differences in survival were found between hyperglycemic MIOCA and MINOCA patients. After adjusting for age, gender, hypertension, smoking, LVEF, STEMI/NSTEMI and AMI phenotypes (MIOCA/MINOCA), aHGL predicted higher long-term mortality. CONCLUSIONS: aHGL was identified as a strong predictor of adverse short- and long-term outcomes in both MIOCA and MINOCA, regardless of diabetes. aHGL should be considered a high-risk prognostic marker in all AMI patients, independently of the underlying coronary anatomy. Trial registration data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711.

Impact of Admission Hyperglycemia on Heart Failure Events and Mortality in Patients With Takotsubo Syndrome at Long-term Follow-up: Data From HIGH-GLUCOTAKO Investigators.

OBJECTIVE: To investigate admission hyperglycemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). RESEARCH DESIGN AND METHODS: In patients with TTS and hyperglycemia (n = 28) versus normoglycemia (n = 48), serum norepinephrine and 123I-labeled metaiodobenzylguanidine (MIBG) cardiac scintigraphy were assessed. Heart failure (HF) occurrence and death events over 2 years were evaluated. RESULTS: At hospitalization, those with hyperglycemia versus normoglycemia had higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Glucose values correlated with norepinephrine levels (R 2 = 0.39; P = 0.001). In 30 patients with TTS, 123I-MIBG cardiac scintigraphy showed lower late heart-to-mediastinum ratio values in the acute phase (P < 0.001) and at follow-up (P < 0.001) in those with hyperglycemia. Patients with hyperglycemia had higher rates of HF (P < 0.001) and death events (P < 0.05) after 24 months. In multivariate Cox regression analysis, hyperglycemia (P = 0.008), tumor necrosis factor-α (P = 0.001), and norepinephrine (P = 0.035) were independent predictors of HF events. CONCLUSIONS: Patients with TTS and hyperglycemia exhibit sympathetic overactivity with a hyperglycemia-mediated proinflammatory pathway, which could cause worse prognosis during follow-up.