The Elevated Inflammatory Status of Neutrophils Is Related to In-Hospital Complications in Patients with Acute Coronary Syndrome and Has Important Prognosis Value for Diabetic Patients.

Despite neutrophil involvement in inflammation and tissue repair, little is understood about their inflammatory status in acute coronary syndrome (ACS) patients with poor outcomes. Hence, we investigated the potential correlation between neutrophil inflammatory markers and the prognosis of ACS patients with/without diabetes and explored whether neutrophils demonstrate a unique inflammatory phenotype in patients experiencing an adverse in-hospital outcome. The study enrolled 229 ACS patients with or without diabetes. Poor evolution was defined as either death, left ventricular ejection fraction (LVEF) <40%, Killip Class 3/4, ventricular arrhythmias, or mechanical complications. Univariate and multivariate analyses were employed to identify clinical and paraclinical factors associated with in-hospital outcomes. Neutrophils isolated from fresh blood were investigated using qPCR, Western blot, enzymatic assay, and immunofluorescence. Poor evolution post-myocardial infarction (MI) was associated with increased number, activity, and inflammatory status of neutrophils, as indicated by significant increase of Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), fibrinogen, interleukin-1ß (IL-1ß), and, interleukin-6 (IL-6). Among the patients with complicated evolution, neutrophil activity had an important prognosis value for diabetics. Neutrophils from patients with unfavorable evolution revealed a pro-inflammatory phenotype with increased expression of CCL3, IL-1ß, interleukin-18 (IL-18), S100A9, intracellular cell adhesion molecule-1 (ICAM-1), matrix metalloprotease (MMP-9), of molecules essential in reactive oxygen species (ROS) production p22phox and Nox2, and increased capacity to form neutrophil extracellular traps. Inflammation is associated with adverse short-term prognosis in acute ACS, and inflammatory biomarkers exhibit greater specificity in predicting short-term outcomes in diabetics. Moreover, neutrophils from patients with unfavorable evolution exhibit distinct inflammatory patterns, suggesting that alterations in the innate immune response in this subgroup may exert detrimental effects on disease progression.

B-Type Natriuretic Peptide at Admission Is a Predictor of All-Cause Mortality at One Year after the First Acute Episode of New-Onset Heart Failure with Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) has been assessed extensively, but few studies analysed the predictive value of the NT-proBNP in patients with de novo and acute HFpEF. We sought to identify NT-proBNP at admission as a predictor for all-cause mortality and rehospitalisation at 12 months in patients with new-onset HFpEF. Methods: We analysed 91 patients (73 ± 11 years, 68% females) admitted for de novo and acute HFpEF, using the Cox proportional hazard risk model. Results: An admission NT-proBNP level above the threshold of 2910 pg/mL identified increased all-cause mortality at 12 months (AUC = 0.72, sensitivity = 92%, specificity = 53%, p < 0.001). All-cause mortality adjusted for age, gender, medical history, and medication in the augmented NT-proBNP group was 16-fold higher (p = 0.018), but with no difference in rehospitalisation rates (p = 0.391). The predictors of increased NT-proBNP ≥ 2910 pg/mL were: age (p = 0.016), estimated glomerular filtration rate (p = 0.006), left atrial volume index (p = 0.001), history of atrial fibrillation (p = 0.006), and TAPSE (p = 0.009). Conclusions: NT-proBNP above 2910 pg/mL at admission for de novo and acute HFpEF predicted a 16-fold increased mortality at 12 months, whereas values less than 2910 pg/mL forecast a high likelihood of survival (99.3%) in the next 12 months, and should be considered as a useful prognostic tool, in addition to its utility in diagnosing heart failure.

Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging.

Vascular disease was for a long time considered a disease of the old age, but it is becoming increasingly clear that a cumulus of factors can cause early vascular aging (EVA). Inflammation plays a key role in vascular stiffening and also in other pathologies that induce vascular damage. There is a known and confirmed connection between inflammation and atherosclerosis. However, it has taken a long time to prove the beneficial effects of anti-inflammatory drugs on cardiovascular events. Diabetes can be both a product of inflammation and a cofactor implicated in the progression of vascular disease. When diabetes and inflammation are accompanied by obesity, this ominous trifecta leads to an increased incidence of atherothrombotic events. Research into earlier stages of vascular disease, and documentation of vulnerability to premature vascular disease, might be the key to success in preventing clinical events. Modulation of inflammation, combined with strict control of classical cardiovascular risk factors, seems to be the winning recipe. Identification of population subsets with a successful vascular aging (supernormal vascular aging-SUPERNOVA) pattern could also bring forth novel therapeutic interventions.

Phenotyping the Prediabetic Population-A Closer Look at Intermediate Glucose Status and Cardiovascular Disease.

Even though the new thresholds for defining prediabetes have been around for more than ten years, there is still controversy surrounding the precise characterization of this intermediate glucose metabolism status. The risk of developing diabetes and macro and microvascular disease linked to prediabetes is well known. Still, the prediabetic population is far from being homogenous, and phenotyping it into less heterogeneous groups might prove useful for long-term risk assessment, follow-up, and primary prevention. Unfortunately, the current definition of prediabetes is quite rigid and disregards the underlying pathophysiologic mechanisms and their potential metabolic progression towards overt disease. In addition, prediabetes is commonly associated with a cluster of risk factors that worsen the prognosis. These risk factors all revolve around a common denominator: inflammation. This review focuses on identifying the population that needs to be screened for prediabetes and the already declared prediabetic patients who are at a higher risk of cardiovascular disease and require closer monitoring.

Percutaneous closure of a large atrial septal defect in a child with severe dextroscoliosis: A case report.

In this study, we present the case of an 11-year-old child with cachexia, severe dextroscoliosis, pectus carinatum, secondary restrictive pulmonary disease, and an incidental finding of a large ostium secundum atrial septal defect (ASD) that was identified on preoperative assessment for surgical correction of the spinal deformity. Transthoracic and transesophageal echocardiography confirmed significant left-to-right shunting with a pulmonary blood flow to systemic blood flow ratio (Qp/Qs) of 3.18 through a 14 mm defect with good circumferential rims, larger than 5 mm. Despite significant left-to-right shunting, the defect was found prior to the development of pulmonary hypertension or right heart enlargement. The decision to close the atrial septal defect by percutaneous intervention was preferred over surgical closure, due to the restrictive pulmonary physiology and low body mass index (12.6 kg/m2). Percutaneous closure of the ASD was successfully performed under general anesthesia using an Occlutech Figulla Flex II ASD device, with no residual shunt. Surgical correction of the dextroscoliosis was subsequently performed with good results. A comprehensive clinical and echocardiographic evaluation is needed in patients with skeletal abnormalities in order to rule out associated congenital heart defects, which may impose therapeutic challenges.

The Onco-cardiologist Dilemma: to Implant, to Defer, or to Avoid Transcatheter Aortic Valve Replacement in Cancer Patients with Aortic Stenosis?

PURPOSE OF REVIEW: Aging is associated with an increased prevalence of both cancer and heart disease. The progression of aortic valve calcification to aortic stenosis may be accelerated by both cardiovascular risk factors and cancer treatments, such as radiotherapy with mediastinal involvement. Symptomatic aortic stenosis is occasionally diagnosed in cancer patients undergoing cardiovascular evaluation; likewise, cancer is often recognized during assessment preceding aortic valve interventions. In these complex cases, physicians face difficult treatment decisions. Due to a myriad of clinical presentations of cancer and valve disease, specific guidelines for this patient population are not currently in place. Management is currently based on clinical judgment, on an individual basis. RECENT FINDINGS: Patients with cancer in remission or with a favorable prognosis should be treated according to current cardiovascular guidelines. In these patients, aortic valve replacement can be performed either by surgery or transcatheter. Significant challenges arise in patients with active cancer, especially those receiving anti-cancer treatment. Recent data suggests that these patients can be offered aortic valve replacement, with a trend of favoring the transcatheter route in order to minimize perioperative risk and complications associated with major surgery. Patients with advanced cancer and severe aortic stenosis should be offered palliative care and can benefit from aortic balloon valvuloplasty if indicated. Modern cancer treatments associated with improved long-term prognosis may allow the appropriate cure of aortic stenosis. We discuss the protocol, outcomes, and evolving recommendations of aortic valve replacement in cancer patients with aortic stenosis.

The 1, 2, 3, 4 of carcinoid heart disease: Comprehensive cardiovascular imaging is the mainstay of complex surgical treatment.

Carcinoid heart disease (CHD) is a rare complication of neuroendocrine tumors, most commonly involving the tricuspid and pulmonary valves. The mitral and aortic valves can also be affected, albeit rarely, in certain circumstances such as the presence of a patent foramen ovale. Transthoracic echocardiogram is generally considered the key imaging modality, but cardiac magnetic resonance can add valuable information, particularly in the assessment of pulmonary valve function or multivalvular disease. Previously, surgical management of CHD carried high mortality, as a result of less advanced surgical techniques and of late intervention, reserved for cases of severely symptomatic heart failure. Modern approaches are associated with significantly improved survival rates, even in multivalvular, complex cases. Valve replacement can provide survival benefits in patients with CHD, but the optimal timing for the intervention is uncertain, with data suggesting a trend of improved survival with earlier intervention. A comprehensive imaging assessment may contribute to establishing optimal surgical timing. This approach may shift the main driver of mortality from the cardiac involvement to the primary malignancy and lead to improved outcomes. We present a series of imaging findings in CHD patients who have successfully undergone simultaneous surgical replacement with bioprosthetic valves of 1 to 4 heart valves. The surgical decision in these patients was based on a multimodality cardiovascular approach, including transthoracic and transesophageal echocardiography and cardiac magnetic resonance. The patients had uncomplicated postoperative courses, significant symptomatic relief from heart failure symptoms, and there was no cardiovascular mortality. Early recognition of CHD with a multimodality approach may improve outcome, even in complex cases. Bioprosthetic valves are generally preferred in CHD due to decreased need for anticoagulation, despite concern for premature degeneration. A collaboration between the Oncology and Cardiology teams is essential for the long-term management of CHD patients.

Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases.

The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.

A Cancer Paradox: Machine-Learning Backed Propensity-Score Analysis of Coronary Angiography Findings in Cardio-Oncology.

OBJECTIVES: Cancer has been proposed as a cardiovascular risk factor. We aimed to assess the cardiovascular risk profile and coronary angiography (CA) findings of cancer patients and compare them to those of patients without cancer. METHODS: A retrospective case-control analysis was conducted on randomly enrolled cancer and non-cancer patients from a high-volume cardio-oncology center and a tertiary cardiology center, respectively, who underwent CA from April 2008 to June 2018. Baseline demographics, laboratory findings, cancer status and treatment, and current and prior CA findings were collected by chart review. Coronary artery disease (CAD) burden was assessed with machine-learning (neural-network) guided propensity-score adjusted multivariable regression, controlling for known CAD confounders. RESULTS: Of the 480 enrolled patients, a total of 240 (50%) had cancer. Fewer cancer vs non-cancer patients had clinically significant lesions on the left anterior descending artery (25.00% vs 39.17%, respectively; P<.01) and left circumflex artery (15.83% vs 30.00%, respectively; P<.001). Left main and right coronary artery disease prevalence was similar. Subjects with cancer were less likely to have multivessel CAD (odds ratio, 0.53; 95% confidence interval, 0.29-0.98; P=.04) and significant left circumflex artery lesions (odds ratio, 0.47; 95% confidence interval, 0.26-0.85; P=.01), independent of known CAD confounders. CONCLUSIONS: Patients with cancer have a lower burden of angiographically detected coronary atherosclerosis. Cancer patients are more likely than non-cancer patients to undergo CA for reasons other than suspicion of CAD. Further studies should prospectively analyze the impact of cancer on the development of CAD.

An update on the management and outcomes of cancer patients with severe aortic stenosis.

OBJECTIVES: We compared the outcomes of aortic valve replacement (AVR) by transcatheter (TAVR) and surgical (SAVR) routes with those of optimal medical management in patients with cancer and severe aortic stenosis (AS). BACKGROUND: Cancer therapy requires optimal cardiac output; however, the treatment of AS in cancer patients is not established. METHODS: Cancer patients with severe AS during January 2009 through February 2018 at a large cancer center were identified. Demographic and clinical characteristics including previous or active cancer diagnosis, history of chest radiotherapy, AS treatment, and survival were collected. Univariate Cox proportional hazards regression, the Kaplan-Meier analysis, and log-rank tests were used to compare overall survival (OS) between AS treatment groups. RESULTS: Sixty-five cancer patients with severe AS were identified; 28 received optimal medical treatment alone, 30 received TAVR, and seven received SAVR. The patients were predominantly male (n = 44, 68%) with a mean age of 71.17 years. The median OS was 9.87 months, and the most common cause of death was cancer (n = 29, 94% of deaths). AVR was associated with a lower risk of death than no AVR (hazard ratio [HR] 0.38, P = 0.007), and patients who underwent TAVR (HR 0.36, P = 0.01) had better survival than those with no AVR. Malignancy type, stage, and treatment were not associated with OS. CONCLUSIONS: Patients with cancer and severe AS who underwent AVR, predominantly TAVR, experienced better survival than those who had no AVR regardless of cancer type or cancer treatment. TAVR may be considered in patients with cancer and AS.

Diagnostic challenges in a patient with calciphylaxia - a case report.

Calciphylaxis is a condition with unclear etiopathogeny with vascular calcifications and thrombotic occlusion that lead to necrotic lesions. It is usually described in patients with end-stage renal disease (ESRD), but also in other conditions. The mortality rate is high, due to sepsis and internal organ failure. We present the case of a patient with multiple comorbidities (ESRD, diabetes, hypertension, Mönckeberg's sclerosis) with problems of differential diagnostic due to the necrotic lesions that mislead initially to systemic lupus erythematosus (SLE) with necrotizing vasculitis.

Stevens-Johnsons syndrome or drug-induced lupus - a clinical dilemma: A case report and review of the literature.

Tumor necrosis factor inhibitors are the first biological agents used in the treatment of rheumatoid arthritis (RA) to have yielded satisfactory results in terms of clinical improvement and radiologic progression, but they are also associated with the possibility of occurrence of a number of autoimmune systemic events [drug-induced lupus (DIL), vasculitis, sarcoidosis] and localized adverse events [uveitis, psoriasis, interstitial lung disease, erythema multiforme including the major form Stevens-Johnson syndrome (SJS)]. During treatment with TNF inhibitors, many patients develop positivity for antinuclear, antihistone and anti-double stranded DNA antibodies, though only a minority of patients will develop clinical manifestations and approximately less than 1% will fulfill the classification criteria for systemic lupus erythematosus. Mucocutaneous manifestations are the most frequent manifestations of DIL following treatment with TNF inhibitors, and can be severe and occasionally difficult to differentiate from erythema multiforme/SJS. Stopping the causative drug (the TNF inhibitor) and general supportive measures are usually sufficient in mild forms, but in moderate to severe forms, systemic glucocorticoids and sometimes immunosuppressive drugs are required. The present report presents the case of a patient with rheumatoid arthritis who developed severe recurrent cutaneous reactions and positive autoantibodies during TNF inhibitor treatment, with difficulties in differential diagnosis and treatment. A review of the literature is also presented.