A 17-gene stemness score for rapid determination of risk in acute leukaemia.

Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials. The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance. Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC+ and 89 LSC- cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.

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.

The E/e' Ratio-Role in Risk Stratification of Acute Heart Failure with Preserved Ejection Fraction.

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e' ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e' ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e' ratio as an independent predictor for HFR. An E/e' ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e' ratio < 13.80 (n = 39) and group 2 with an E/e' ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e' ratio is a useful discriminator between patients with acute HFpEF. An E/e' value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e' ratio.

Value of ejection fraction/velocity ratio in the prognostic stratification of patients with asymptomatic aortic valve stenosis.

BACKGROUND: The ejection fraction/velocity ratio (EFVR) is a simple function-corrected index of aortic stenosis severity with a good correlation with aortic valve area measured using the Gorlin formula at cardiac catheterization. It is calculated by dividing left ventricular ejection fraction (LVEF) to 4 × (peak jet velocity)2 . OBJECTIVE: Our aim was to evaluate the value of EFVR in predicting adverse events in patients with asymptomatic aortic stenosis. METHODS: We analyzed the clinical and echocardiographic data of 216 asymptomatic patients with at least moderate aortic stenosis (AVA ≤ 1.5 cm2 ). The primary end-point was cardiovascular death or aortic valve replacement. RESULTS: There were 119 (55%) men and mean age was 68 ± 10 years. The mean follow-up time was 4.2 ± 1.6 years (median 4.3 years). During follow-up, the composite end-point of death or aortic valve replacement was reached in 105 patients (49%). Using multivariate Cox regression analysis, EFVR and valvulo-arterial impedance emerged as independent variables associated with outcome (P < 0.001 and P = 0.001, respectively). In the subgroup of patients with severe aortic stenosis (AVA < 1 cm2 ), EFVR ≤ 0.9 was associated with an increased hazard ratio for the composite end-point of mortality and aortic valve replacement (HR 2.14, 95% CI: 1.15-4.0, P = 0.017), even after adjusting for aortic valve area. CONCLUSIONS: In patients with asymptomatic moderate to severe aortic stenosis, EFVR is useful for risk stratification. Our results suggest that incorporating EFVR in the evaluation of patients with asymptomatic aortic stenosis might help identify those who are most likely to benefit from early elective aortic replacement.

New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?

BACKGROUND: In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end-diastolic volume index has been recently proposed. AIM: To describe the prevalence of the newly identified remodeling patterns in patients with severe aortic stenosis and to evaluate their clinical relevance according to symptoms. METHODS: We analyzed 286 consecutive patients with isolated severe aortic stenosis. Current guidelines were used for echocardiographic evaluation. Symptoms were defined as the presence of angina, syncope, or NYHA class III-IV. RESULTS: The mean age was 75 ± 9 years, 156 patients (54%) were men, while 158 (55%) were symptomatic. According to the new classification, the most frequent remodeling pattern was concentric hypertrophy (57.3%), followed by mixed (18.9%) and dilated hypertrophy (8.4%). There were no patients with eccentric remodeling; only 4 patients had a normalLV geometry. Symptomatic patients showed significantly more mixed hypertrophy (P < .05), while the difference regarding the prevalence of the other patterns was not statistically significant. When we analyzed the distribution of the classic 4 patterns stratified by the presence of symptoms, however, we did not find a significant difference (P = .157). CONCLUSIONS: The new classification had refined the description of different cardiac geometric phenotypes that develop as a response to pressure overload. It might be superior to the classic 4 patterns in terms of association with symptoms.

Diagnosing diastolic dysfunction and heart failure with preserved ejection fraction in patients with atrial fibrillation: a clinical challenge.

Left ventricular (LV) diastolic dysfunction, atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) share common risk factors and are closely related to each other and to adverse cardiovascular events. Exertional dyspnea in patients with AF should trigger comprehensive LV diastolic function evaluation since AF frequently precedes incident HFpEF. Echocardiographic assessment of LV diastolic function in patients with AF is challenging, mainly because of variability in cycle length, the absence of atrial contraction, and the frequent occurrence of LA enlargement regardless of LV filling pressures (LVFP). The algorithm of the 2016 recommendations for the evaluation of LV diastolic function cannot be directly applied in this setting. This review discusses the modalities available for diastolic function assessment and HFpEF diagnosis in patients with AF. Based on currently available data, a reasonable clinical target of diastolic function evaluation in AF would be to reach a binary conclusion: LVFP elevated or not. Recently, a two-step algorithm that combined several echocardiographic parameters plus inclusion of body mass index, has been proposed to differentiate normal from elevated LVFP in patients with AF. The echocardiographic evaluation must be complemented by a thorough clinical evaluation along with natriuretic peptides and cardiac catheterization in selected cases. If a diagnosis of HFpEF cannot be ascertained, a close follow up for timely identification of diastolic dysfunction markers along with monitoring and correction of modifiable risk factors are recommended.

Impact of associated significant aortic regurgitation on left ventricular remodeling and hemodynamic impairment in severe aortic valve stenosis.

OBJECTIVES: The left ventricular (LV) response to combined pressure and volume overload [aortic stenosis (AS) and aortic regurgitation (AR)] versus pressure overload (isolated AS)has not been systematically studied. We aimed to assess LV remodeling, functional and hemodynamic consequences inpatients with mixed aortic valve disease versus patients with isolated AS. METHODS: We enrolled 181 patients (67 ± 9 years,109 men) with severe AS (aortic valve area indexed to body surface area <0.6 cm 2 /m 2 ) who underwent preoperative cardiac catheterization and a complete echocardiogram. Pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure (LVEDP) and pulmonary artery pressure (PAP) were measured. RESULTS: One hundred and ten patients (group A)had isolated severe AS (AR 0­1) and 71 patients (group B)had mixed aortic valve disease (severe AS plus AR 2­3). Patients in group B were younger and in a higher New York Heart Association class (p < 0.01). Severity of AS was similar in both groups. Patients in group B had a higher indexed LV mass, a lower LV ejection fraction, and higher PCWP, LVED Pand PAP (all p ≤ 0.01). CONCLUSIONS: Patients with severe AS and significant AR are more symptomatic than patients with isolated severe AS. The increased burden due to the combined lesion induces pronounced LV remodeling and more severe hemodynamic consequences.

Ethical Issues in Long-term Care in Low-, Middle- and High-Income Countries During the COVID-19 Pandemic.

Long-term care (LTC) centers experienced an unprecedented emergency involving exponential mortality during the COVID-19 pandemic. Individuals residing in long-term care were particularly vulnerable to the effects of COVID-19, placing residents, staff, families, and organizations in a precarious position. Complex issues surrounding how to manage vulnerable populations during the pandemic have highlighted the importance of gathering information on ethical issues that require effective policy and decision-making. This project sought to identify the ethical issues faced in long-term care by residents, families, staff, and organizations from stakeholders themselves. A total of 305 participants from 45 countries responded, highlighting numerous ethical issues in long-term care during COVID-19. While numerous issues were mentioned, there was an overlap in the themes of responses between stakeholders. Visitation, isolation, harm, staff well-being, and the overall enforcement of policies during the pandemic represented the most often discussed issues. As a preliminary study of this issue, future research is necessary in order to effectively guide pandemic policymaking moving forward.

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.

A Practical Risk Score for Prediction of Early Readmission after a First Episode of Acute Heart Failure with Preserved Ejection Fraction.

BACKGROUND: The first admission for acute heart failure with preserved ejection fraction (HFpEF) drastically influences the short-term prognosis. Baseline characteristics may predict repeat hospitalization or death in these patients. METHODS: A 103 patient-cohort, admitted for the first acute HFpEF episode, was monitored for six months. Baseline characteristics were recorded and their relation to the primary outcome of heart failure readmission (HFR) and secondary outcome of all-cause mortality was assessed. RESULTS: We identified six independent determinants for HFR: estimated glomerular filtration rate (eGFR) (p = 0.07), hemoglobin (p = 0.04), left ventricle end-diastolic diameter (LVEDD) (p = 0.07), E/e' ratio (p = 0.004), left ventricle outflow tract velocity-time integral (LVOT VTI) (p = 0.045), and diabetes mellitus (p = 0.06). Three of the variables were used to generate a risk score for HFR: LVEDD, E/e', LVOT VTI -DEI Score = - 28.763 + 4.558 × log (LVEDD (mm)) + 1.961 × log (E/e' ratio) + 1.759 × log (LVOT VTI (cm)). Our model predicts a relative amount of 20.50% of HFR during the first 6 months after the first acute hospitalization within the general population with HFpEF with a DEI Score over -0.747. CONCLUSIONS: We have identified three echocardiographic parameters (LVEDD, E/e', and LVOT VTI) that predict HFR following an initial acute HFpEF hospitalization. The prognostic DEI score demonstrated good accuracy.

Aminoglycoside-mediated partial suppression of MECP2 nonsense mutations responsible for Rett syndrome in vitro.

Rett syndrome is a pediatric neurological condition that affects primarily girls. Approximately 30% of Rett syndrome cases arise from point mutations that introduce a premature stop codon into the MECP2 gene. Several studies have now shown that certain aminoglycosides can facilitate read-through of some types of nonsense mutations in a context-dependent manner and allow the generation of a full-length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study, we tested whether the common premature terminating mutations of MECP2 seen in Rett syndrome cases can be partially suppressed by aminoglycoside administration. Our results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK293 cells, but with differing levels of efficiency. In addition, we also show that aminoglycosides increased the prevalence of full-length MeCP2 protein in a dose-dependent manner in a lymphocyte cell line derived from a Rett syndrome girl with the R255X mutation. This study helps to establish the "proof of principle" that some nonsense mutations causing Rett syndrome can be at least partially suppressed by drug treatment.

Role of advanced left ventricular imaging in adults with aortic stenosis.

This review focuses on the available data regarding the utility of advanced left ventricular (LV) imaging in aortic stenosis (AS) and its potential impact for optimising the timing of aortic valve replacement. Ejection fraction is currently the only LV parameter recommended to guide intervention in AS. The cut-off value of 50%, recommended for decision-making in asymptomatic patients with AS, is currently under debate. Several imaging parameters have emerged as predictors of disease progression and clinical outcomes in this setting. Global longitudinal LV strain by speckle tracking echocardiography is useful for risk stratification of asymptomatic patients with severe AS and preserved LV ejection fraction. Its prognostic value was demonstrated in these patients, but further work is required to define the best thresholds to aid the decision-making process. The assessment of myocardial fibrosis is the most studied application of cardiac magnetic resonance in AS. The detection of replacement fibrosis by late gadolinium enhancement offers incremental prognostic information in these patients. Clinical implementation of this technique to optimise the timing of aortic valve intervention in asymptomatic patients is currently tested in a randomised trial. The use of T1 mapping techniques can provide an assessment of interstitial myocardial fibrosis and represents an expanding field of interest. However, convincing data in patients with AS is still lacking. All these imaging parameters have substantial potential to influence the management decision in patients with AS in the future, but data from randomised clinical trials are awaited to define their utility in daily practice.

Type I Kounis Syndrome after Protracted Anaphylaxis and Myocardial Bridge-Brief Literature Review and Case Report.

The term allergic angina, introduced for the first time by Nicholas Kounis in 1991, initially referred to the coexistence of acute coronary syndromes with allergy or hypersensitivity. At present, it is believed that Kounis syndrome is a particular case of systemic disease, with multiorgan arterial involvement generated during immediate hypersensitivity reactions. Myocardial bridging (MB), a condition that can induce coronary artery spasm, has long been regarded as a benign condition. Since both pathologies are associated with arterial spasm, Kounis syndrome and MB are considered to be confounding pathologies for acute coronary syndromes, and their association is quite a rare finding. To date, there are no precise data on the epidemiology, and the population affected by Kounis syndrome seems to be highly heterogeneous. Since this is a rare disease, even less is known about possible different phenotypes, including MB overlap. We report a case of type I variant Kounis syndrome associated with MB with no evidence of coronary artery disease, occurring as late presentation, following a severe systemic reaction (anaphylaxis) induced by a Hymenoptera sting. At present, only two other cases of type I and one case of type II Kounis syndrome occurring in patients with myocardial bridging have been described.

Clinical and Economic Value of Routine Pathological Examination of Hernia Sacs and Scheduled Clinic Follow-Ups After Inguinal Hernia and Hydrocele Repair in a Canadian Tertiary Care Children's Hospital.

BACKGROUND: The clinical and economical value of routine submission of hernia sacs for pathological examination and scheduled clinic follow-ups after inguinal hernia and hydrocele repair has been questioned. Herein, we assessed the institutional variability in these routine practices. METHODS: We retrospectively reviewed patients who underwent unilateral or bilateral inguinal hernia and/or hydrocele repair, open or laparoscopically, at our institution from 2015 to 2018. RESULTS: 1181 patients were included (1074 inguinal hernias and 157 hydroceles). Of 531 specimens obtained from 446 (38%) patients, 515 (97%) were normal. 16 (3%) abnormal pathological findings included 7 with mesothelial hyperplasia, 5 with nonfunctional genital ductal remnants, 3 with ectopic adrenal cortical tissues, and 1 epidydimal structure which was not recognized at the time of surgery. 418 (35%) patients had scheduled clinic follow-ups 65 (IQR 46-94) days postoperatively. 44 (4%) patients with unexpected postoperative Emergency Department visits within 30 days of surgery were identified. Only one patient required inpatient treatment, and the rest did not require intervention or admission. The total direct cost of analyzing specimens during the study period was $30,798 CAD ($10,266/year). The average cost to detect a potentially significant finding was $1924.88/specimen and $2053.20/patient. CONCLUSIONS: Routine pathological examination of hernia sacs and scheduled clinic follow-ups were associated with significant costs and predominantly nonsignificant findings. They should therefore be reserved for patients with a high clinical suspicion of injuries/abnormalities or risk factors for potential complications. LEVEL OF EVIDENCE: This is a level III evidence study.

Acute Myocardial Infarction Mortality Rates and Trends in Romania between 1994 and 2017.

Introduction: The current study aimed to assess recent acute myocardial infarction (AMI) mortality rates and trends in Romania between 1994 and 2017. This dataset is a necessity in the context of the current improvement of emergency protocols, medical addressability, and modernization of hospital infrastructure. Materials and Methods: The study is a retrospective analysis of an anonymized mortality database containing all deaths registered in Romania during 1994-2017. AMI crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated using the European Standard Population. Poisson regression was used for calculating the annual percentage change (APC) in mortality, subsequently used to make mortality predictions through the year 2030. Results: There were 197,152 AMI deaths in women (39.3% of total AMI), and 304,644 (60.7%) in men. Mortality rates were higher in men as compared with women for the entire time covered by the study. Based on the 1994-2017 ASMR dynamics, predictions for the year 2030 showed an overall AMI ASMR of 70.9 (95% CI 69.9-71.9), with gender analysis showing 46.8 (95% CI 45.8-47.9) in women and 104.1 (95% CI 102.3-105.8) in men. Conclusion: Acute myocardial infarction age-standardized mortality rates decreased significantly in Romania between 1994 and 2017 in close correlation to the implementation of national healthcare programs.

Clinical, histological and therapeutic modern approach of Ledderhose disease.

Ledderhose disease or plantar fibromatosis is a rare hyperproliferative disorder of the plantar aponeurosis, clinically characterized by nodules situated especially on the medial border of the foot. It is histopathologically associated with Dupuytren's disease. This disease has some risk factors, like old age, alcohol or nicotine abuse, liver dysfunction, trauma or exposure to vibrations and autoimmune disorders, but the exact etiology is still unknown. Even though it is benign, the local manifestations can be aggressive, leading to debilitating deformities and contractures of the toes. Ultrasound and magnetic resonance imaging are used to confirm the diagnosis and to eliminate other disorders. Whenever is possible, the conservative therapies are recommended. Having a high recurrence, Ledderhose disease can be hard to treat, needing multiple surgical interventions. This paper aims to cover all the important aspects of this disease for daily medical practice, from history to clinical manifestations, diagnostic methods and histopathological features, to conservative and surgical treatment modalities.

Obesity, Cardiac Remodeling, and Metabolic Profile: Validation of a New Simple Index beyond Body Mass Index.

AIM: The body mass index (BMI), the most used anthropometric index of obesity, has an important limitation, not taking into consideration the distribution of body fat. We developed a new simple index: the waist-corrected BMI (wBMI), calculated as waist circumference (WC) × BMI. The study aim was to assess the role of wBMI, compared to BMI, WC, and Waist-to-Height Ratio (WHtR) in predicting abnormal cardiac geometry, insulin resistance, increased arterial stiffness, and dyslipidemia. METHODS: This was a cross-sectional study that included 805 patients referred to our Department of Preventive Cardiology for risk factors evaluation and treatment. Eleven echographic and laboratory parameters were determined, and receiver operating characteristic (ROC) curves were derived. Areas under ROC curves (AUC) were used to assess the accuracy of the four indexes to identify unfavorable characteristics. RESULTS: There were 29% overweight, 59% obese, and 77% hypertensive patients. Of 11 echographic and laboratory parameters, wBMI, BMI, WHtR, and WC had the largest AUC for identifying 3, 1, 6, and 1 parameters, respectively, but with overlapping 95% confidence intervals. wBMI had the largest AUC for increased arterial stiffness and insulin resistance; also, it was superior to BMI for increased left atrial volume, relative wall thickness, and triglyceride level. CONCLUSIONS: In a large population with a high prevalence of obesity and hypertension, all four indexes were associated with unfavorable characteristics. wBMI has the theoretical advantage of taking into account simultaneously the global fat mass and distribution and might be useful for a better cardiovascular risk assessment.

Left atrial dysfunction as a determinant of pulmonary hypertension in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

In patients with severe aortic stenosis (AS), the presence of pulmonary hypertension (PH) has been linked to a poor prognosis. We aimed to assess the main determinants of PH in patients with severe AS and preserved left ventricular ejection fraction (LVEF). We prospectively enrolled 108 consecutive patients with isolated severe AS (indexed aortic valve area <0.6 cm2/m2) and LVEF >50%, in sinus rhythm. Left atrial (LA) function was assessed using longitudinal deformation parameters (by speckle tracking echocardiography). PH (defined as systolic pulmonary artery pressure >40 mmHg) was present in 20 patients. Patients with severe AS and PH were older (p = 0.05), had higher BNP values (p = 0.05) and a greater degree of LV diastolic dysfunction: higher E/e' and E/A ratios and lower EDT values (p < 0.03 for all) compared to patients without PH. There were no differences between groups regarding AS severity and LV systolic function parameters. Patients with PH had a more impaired LA function: lower septal and lateral late diastolic peak velocity a' (p < 0.001 and p = 0.04 respectively) and lower LA peak longitudinal strain and strain rate parameters (p ≤ 0.005 for all). In multivariable analysis, LA late diastolic longitudinal strain rate was the only independent correlate of PH in our patients (p = 0.04). Patients with isolated severe AS, preserved LVEF and PH had larger LA volumes, a more impaired LA function, and higher LV filling pressures compared to those without PH. LA booster pump function, reflected by late diastolic longitudinal strain rate, emerged as an independent correlate of PH in these patients.

Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients.

There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL2 and HDL3 were isolated from CAD patients' plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL2 or HDL3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL2 and HDL3, 35% augmented apoAII in HDL2, and in HDL3 increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL2 or HDL3 from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15-20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL3 from ACS) and can discriminate between these two groups of CAD patients.