Publications by authors named "Maria Dorobantu"

104 Publications

Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).

Cardiovasc Res 2021 Sep 16. Epub 2021 Sep 16.

Department of Cardiology, 'Hippokration' General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between SARS-CoV-2 and ACE2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as "post-acute COVID-19" may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.
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http://dx.doi.org/10.1093/cvr/cvab298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500019PMC
September 2021

Arterial Hypertension and Serum Uric Acid in Elderly- SEPHAR III Study.

Arq Bras Cardiol 2021 08;117(2):378-384

University of Medicine and Pharmacy Victor Babes Timisoara - Department of Internal Medicine, Timisoara - Romênia.

Background: Hyperuricemia is a frequent finding in patients with arterial hypertension, and there is increasing evidence that this entity is also a risk factor for cardiovascular disease.

Objective: In the context of an aging population, this study aims to evaluate serum uric acid levels and arterial hypertension prevalence and control in a subgroup of Romanian adults (>65 years), concerning the influence of age on these parameters.

Method: The study sample consists of 1,920 adults included in SEPHAR III survey, of whom 447 were elderly patients (>65 years of age). During the two study visits, three blood pressure (BP) measurements were performed at 1-min intervals and serum uric acid levels, kidney function by estimated glomerular filtration rate, blood pressure, and intima media thickness measurements were conducted. Hypertension and controls were defined according to the current guidelines. Intima-media thickness evaluation was assessed by B-mode Doppler ultrasound evaluation. A significance level p < 0.05 was adopted for the statistical analysis.

Results: Adult patients had a significant lower serum uric acid levels, compared to elderly patients, regardless of glomerular filtration rate levels. Adult patients showed a significantly lower intima-media thickness levels, when compared to elderly patients.

Conclusion: Similar to previous studies, in the present study, age represented one of the factors contributing to the increased level of serum uric acid. An increasing prevalence of arterial hypertension with age, together with a poor control of blood pressure, was also obtained.
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http://dx.doi.org/10.36660/abc.20200004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395801PMC
August 2021

Molecular Research in Cardiovascular Disease.

Int J Mol Sci 2021 Jul 4;22(13). Epub 2021 Jul 4.

Department 4-Cardiothoracic Pathology, University of Medicine and Pharmacy Carol Davila, 8, Eroii Sanitari Bvd., 050474 Bucharest, Romania.

Cardiovascular diseases have attracted our full attention not only because they are the main cause of mortality and morbidity in many countries but also because the therapy for and cure of these maladies are among the major challenges of the medicine in the 21st century [...].
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http://dx.doi.org/10.3390/ijms22137199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267781PMC
July 2021

Body-mass index and diabetes risk in 57 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 685 616 adults.

Lancet 2021 07;398(10296):238-248

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings.

Methods: In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5-22·9 kg/m], upper-normal [23·0-24·9 kg/m], overweight [25·0-29·9 kg/m], or obese [≥30·0 kg/m]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region.

Findings: Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6-27·8), of obesity was 21·0% (19·6-22·5), and of diabetes was 9·3% (8·4-10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5-22·9 kg/m. Diabetes risk also increased steeply in individuals aged 35-44 years and in men aged 25-34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m among men in east, south, and southeast Asia to 28·3 kg/m among women in the Middle East and north Africa and in Latin America and the Caribbean.

Interpretation: The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines.

Funding: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.
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http://dx.doi.org/10.1016/S0140-6736(21)00844-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336025PMC
July 2021

Targeting Hypertension Screening in Low- and Middle-Income Countries: A Cross-Sectional Analysis of 1.2 Million Adults in 56 Countries.

J Am Heart Assoc 2021 07 2;10(13):e021063. Epub 2021 Jul 2.

Heidelberg Institute of Global Health Medical Faculty and University Hospital University of Heidelberg Germany.

Background As screening programs in low- and middle-income countries (LMICs) often do not have the resources to screen the entire population, there is frequently a need to target such efforts to easily identifiable priority groups. This study aimed to determine (1) how hypertension prevalence in LMICs varies by age, sex, body mass index, and smoking status, and (2) the ability of different combinations of these variables to accurately predict hypertension. Methods and Results We analyzed individual-level, nationally representative data from 1 170 629 participants in 56 LMICs, of whom 220 636 (18.8%) had hypertension. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or reporting to be taking blood pressure-lowering medication. The shape of the positive association of hypertension with age and body mass index varied across world regions. We used logistic regression and random forest models to compute the area under the receiver operating characteristic curve in each country for different combinations of age, body mass index, sex, and smoking status. The area under the receiver operating characteristic curve for the model with all 4 predictors ranged from 0.64 to 0.85 between countries, with a country-level mean of 0.76 across LMICs globally. The mean absolute increase in the area under the receiver operating characteristic curve from the model including only age to the model including all 4 predictors was 0.05. Conclusions Adding body mass index, sex, and smoking status to age led to only a minor increase in the ability to distinguish between adults with and without hypertension compared with using age alone. Hypertension screening programs in LMICs could use age as the primary variable to target their efforts.
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http://dx.doi.org/10.1161/JAHA.121.021063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403275PMC
July 2021

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease.

Ann Med 2021 12;53(1):1041-1047

Department of Cardiology, Clinical Emergency Hospital of Bucharest, Romania.

Introduction: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established.

Objectives: The study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group.

Results: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, =.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, =.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, =.02) and strongly with LVEF (rho= -0.8, =.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, =.01) and with the severity of coronary atherosclerosis (rho= -0.41, =.003).

Conclusions: CRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.
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http://dx.doi.org/10.1080/07853890.2021.1916070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245096PMC
December 2021

The prognostic value of right ventricular longitudinal strain and 3D ejection fraction in patients with dilated cardiomyopathy.

Int J Cardiovasc Imaging 2021 Nov 24;37(11):3233-3244. Epub 2021 Jun 24.

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

Several studies showed that right ventricular (RV) dysfunction is a powerful predictor in heart failure (HF). Advanced echocardiographic techniques such as speckle-tracking imaging and three-dimensional (3D) echocardiography proved to be accurate tools for RV assessment, but their clinical significance remains to be clarified. The aim of this study was to evaluate the role of two-dimensional (2D) RV strain and 3D ejection fraction (RVEF) in predicting adverse outcome in patients with non-ischemic dilated cardiomyopathy (DCM). We prospectively screened 81 patients with DCM and sinus rhythm, 50 of whom were enrolled and underwent comprehensive echocardiography, including RV strain and 3D RV volumetric assessment. Patients were followed for a composite endpoint of cardiac death, nonfatal cardiac arrest and acute worsening of HF requiring hospitalization. After a median follow-up of 16 months, 29 patients reached the primary endpoint. Patients with events had more impaired RV global longitudinal strain (- 10.5 ± 4.5% vs. - 14.3 ± 5.2%, p = 0.009), RV free wall longitudinal strain (- 12.9 ± 8.7% vs. - 17.5 ± 7.1%, p = 0.046) and 3D RVEF (38 ± 8% vs. 47 ± 9%, p = 0.001). By Cox proportional hazards multivariable analysis, RV global longitudinal strain and RVEF were independent predictors of outcome after adjustment for age and NYHA class. RVEF remained the only independent predictor of events after further correction for echocardiographic risk factors. By receiver-operating characteristic analysis, the optimal RVEF cut-off value for event prediction was 43.4% (area under the curve = 0.768, p = 0.001). Subjects with RVEF > 43.4% showed more favourable outcome compared to those with RVEF < 43.4% (log-rank test, p < 0.001). In conclusion, 3D RVEF is an independent predictor of major adverse cardiovascular events in patients with DCM.
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http://dx.doi.org/10.1007/s10554-021-02322-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223765PMC
November 2021

Acute inferior myocardial infarction in a young man with testicular seminoma: A case report.

World J Clin Cases 2021 Jun;9(16):4040-4045

Department of Cardio-Thoracic, University of Medicine and Pharmacy, Bucharest 050474, Romania.

Background: Atherosclerosis represents the main cause of myocardial infarction (MI); other causes such as coronary embolism, vasospasm, coronary-dissection or drug use are much rarely encountered, but should be considered in less common clinical scenarios. In young individuals without cardiovascular risk factors, the identification of the cause of MI can sometimes be found in the medical history and previous treatments undertaken.

Case Summary: We present the case of a 34-year-old man presenting acute inferior ST-elevation MI without classic cardiac risk factors. Seven years ago, he suffered from orchidopexy for bilateral cryptorchidism, and was recently diagnosed with right testicular seminoma for which he had to undergo surgical resection and chemotherapy with bleomycin, etoposide and cisplatin. Shortly after the first chemotherapy treatment, namely on day five, he suffered an acute MI. Angiography revealed a mild stenotic lesion at the level of the right coronary artery with suprajacent thrombus and vasospasm, with no other significant lesions on the other coronary arteries. A conservative treatment was decided upon by the cardiac team, including dual antiplatelets therapy and anticoagulants with good further evolution. The patient continued the chemotherapy treatment according to the initial plan without other cardiovascular events.

Conclusion: In young individuals with no cardiovascular risk factors undergoing aggressive chemotherapy, an acute MI can be caused by vascular toxicity of several anti-cancer drugs.
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http://dx.doi.org/10.12998/wjcc.v9.i16.4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180225PMC
June 2021

The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

Eur Heart J 2021 Jun 3. Epub 2021 Jun 3.

Robertson Center for Biostatistics, University of Glasgow, Boyd Orr Building University Avenue, Glasgow G12 8QQ, UK.

Aims: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population.

Methods And Results: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM.

Conclusion: In iron-deficient patients with HF and left ventricular ejection fraction ≤50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.
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http://dx.doi.org/10.1093/eurheartj/ehab234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370759PMC
June 2021

Right ventricular-arterial coupling - A new perspective for right ventricle evaluation in heart failure patients undergoing cardiac resynchronization therapy.

Echocardiography 2021 07 24;38(7):1157-1164. Epub 2021 May 24.

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Background: Right ventricular - arterial (RV-PA) coupling can be estimated by echocardiography using the ratio between (TAPSE) and pulmonary arterial systolic pressure (PASP). TAPSE/PASP ratio proved to be a prognostic parameter in patients with heart failure and reduced ejection fraction (HFrEF).

Objective: To evaluate the significance of RV-PA coupling in patients with HFrEF undergoing cardiac resynchronization therapy (CRT).

Methods: Patients undergoing CRT in our center between January 2017 and November 2019 were eligible. Response to CRT was defined by a reduction of more than 15% of left ventricle systolic volume (LVESV) one year after CRT. Primary endpoint was a composite of HF hospitalizations and death during follow-up.

Results: 54 patients (Age 64.0 ± 13.8 years; 58% male; left ventricular ejection fraction (LVEF) 28.4 ± 1.3%) were prospectively included. After a mean follow-up of 31 ± 12.9months, the primary endpoint had occurred in 18 (33.3%) patients. A lower TAPSE/PASP ratio was associated with baseline worse HF symptoms, lower LVEF and long-term less LV reverse remodeling (P < .05). After one year CRT improved RV systolic function (TAPSE, RV global longitudinal strain, P < .05), but not TAPSE/PASP ratio (P = .4). The ratio TAPSE/PASP (AUC=0.834) ≥ 0.58 mm/mm Hg showed good sensitivity (90%) and specificity (81.8%) for predicting response to CRT while a ratio <0.58 mm/mm Hg was associated with a higher risk of death and HF hospitalizations during the follow-up (HR 5.37 95%CI [1.6-18], P < .001).

Conclusion: RV-PA coupling evaluation using TAPSE/PASP ratio predicts CRT response. A lower TAPSE/PASP ratio is associated with a higher risk of adverse cardiovascular events.
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http://dx.doi.org/10.1111/echo.15096DOI Listing
July 2021

MicroRNAs in Acute ST Elevation Myocardial Infarction-A New Tool for Diagnosis and Prognosis: Therapeutic Implications.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Department of Cardiology, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients.
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http://dx.doi.org/10.3390/ijms22094799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124280PMC
April 2021

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy.

Diagnostics (Basel) 2021 Apr 30;11(5). Epub 2021 Apr 30.

Cardio-thoracic Department, University of Medicine and Pharmacy Carol Davila, Eroii Sanitari Bvd. 8, 050474 Bucharest, Romania.

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown.

Methods: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. LA 2D volumetric and STE parameters were analyzed in 86 LVH patients (43 HCM and 43 isolated HTN subjects) and 33 age- and sex-matched controls.

Results: The volumetric study showed that LA reservoir and conduit function were impaired in the HCM group compared to controls, while, in the HTN group, only LA conduit function was deteriorated. The HCM group had all three STE-derived LA functions impaired compared to controls. The HTN group, consistently with volumetric analysis, had solely LA conduit function reduced compared to controls. Ratios of LA booster-pump strain (S) and strain rate (SR) to interventricular septum (IVS) thickness were the most accurate parameters to discriminate between HCM and HTN. The subgroup harboring sarcomeric pathogenic (P)/likely pathogenic (LP) variants had reduced LA booster-pump S and SR compared with the genotype-negative subgroup.

Conclusions: LA reservoir, conduit, and pump functions are decreased in HCM compared to HTN patients with similar LVH. We report the ratios between LA contraction S/SR and IVS thickness as novel parameters with high accuracy in discriminating LVH due to HCM. The presence of P/LP variants in sarcomeric or sarcomeric-associated genes could be associated with more severe LA dysfunction.
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http://dx.doi.org/10.3390/diagnostics11050814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145163PMC
April 2021

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

Medicina (Kaunas) 2021 Apr 13;57(4). Epub 2021 Apr 13.

Cardiothoracic Pathology Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.

: 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. : 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. : 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%, < 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 ( = 0.003) and a shorter time to first HFR ( = 0.002). However, this parameter did not influence all-cause mortality within six months ( = 0.84). : 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.
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http://dx.doi.org/10.3390/medicina57040375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070491PMC
April 2021

Forgotten No More-The Role of Right Ventricular Dysfunction in Heart Failure with Reduced Ejection Fraction: An Echocardiographic Perspective.

Diagnostics (Basel) 2021 Mar 19;11(3). Epub 2021 Mar 19.

Department of Cardiology, Carol Davila University of Medicine and Pharmacy, 050513 Bucharest, Romania.

During the last decade, studies have raised awareness of the crucial role that the right ventricle plays in various clinical settings, including diseases primarily linked to the left ventricle. The assessment of right ventricular performance with conventional echocardiography is challenging. Novel echocardiographic techniques improve the functional assessment of the right ventricle and they show good correlation with the gold standard represented by cardiac magnetic resonance. This review summarizes the traditional and innovative echocardiographic techniques used in the functional assessment of the right ventricle, focusing on the role of right ventricular dysfunction in heart failure with reduced ejection fraction and providing a perspective on recent evidence from literature.
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http://dx.doi.org/10.3390/diagnostics11030548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003573PMC
March 2021

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

Diagnostics (Basel) 2021 Jan 29;11(2). Epub 2021 Jan 29.

Cardiothoracic Pathology Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.

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) ( = 0.07), hemoglobin ( = 0.04), left ventricle end-diastolic diameter (LVEDD) ( = 0.07), E/e' ratio ( = 0.004), left ventricle outflow tract velocity-time integral (LVOT VTI) ( = 0.045), and diabetes mellitus ( = 0.06). Three of the variables were used to generate a risk score for HFR: LVED, /e', LVOT VT - Score = 28.763 4.558 × log (LVED (mm)) 1.961 × log (e' ratio) 1.759 × log (LVOT VT (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.
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http://dx.doi.org/10.3390/diagnostics11020198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911435PMC
January 2021

Variation in the Proportion of Adults in Need of Blood Pressure-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1 037 215 Individuals From 50 Nationally Representative Surveys.

Circulation 2021 03 8;143(10):991-1001. Epub 2021 Feb 8.

Division of Primary Care and Population Health, Department of Medicine, Stanford University, CA (P.G.).

Background: Current hypertension guidelines vary substantially in their definition of who should be offered blood pressure-lowering medications. Understanding the effect of guideline choice on the proportion of adults who require treatment is crucial for planning and scaling up hypertension care in low- and middle-income countries.

Methods: We extracted cross-sectional data on age, sex, blood pressure, hypertension treatment and diagnosis status, smoking, and body mass index for adults 30 to 70 years of age from nationally representative surveys in 50 low- and middle-income countries (N = 1 037 215). We aimed to determine the effect of hypertension guideline choice on the proportion of adults in need of blood pressure-lowering medications. We considered 4 hypertension guidelines: the 2017 American College of Cardiology/American Heart Association guideline, the commonly used 140/90 mm Hg threshold, the 2016 World Health Organization HEARTS guideline, and the 2019 UK National Institute for Health and Care Excellence guideline.

Results: The proportion of adults in need of blood pressure-lowering medications was highest under the American College of Cardiology/American Heart Association, followed by the 140/90 mm Hg, National Institute for Health and Care Excellence, and World Health Organization guidelines (American College of Cardiology/American Heart Association: women, 27.7% [95% CI, 27.2-28.2], men, 35.0% [95% CI, 34.4-35.7]; 140/90 mm Hg: women, 26.1% [95% CI, 25.5-26.6], men, 31.2% [95% CI, 30.6-31.9]; National Institute for Health and Care Excellence: women, 11.8% [95% CI, 11.4-12.1], men, 15.7% [95% CI, 15.3-16.2]; World Health Organization: women, 9.2% [95% CI, 8.9-9.5], men, 11.0% [95% CI, 10.6-11.4]). Individuals who were unaware that they have hypertension were the primary contributor to differences in the proportion needing treatment under different guideline criteria. Differences in the proportion needing blood pressure-lowering medications were largest in the oldest (65-69 years) age group (American College of Cardiology/American Heart Association: women, 60.2% [95% CI, 58.8-61.6], men, 70.1% [95% CI, 68.8-71.3]; World Health Organization: women, 20.1% [95% CI, 18.8-21.3], men, 24.1.0% [95% CI, 22.3-25.9]). For both women and men and across all guidelines, countries in the European and Eastern Mediterranean regions had the highest proportion of adults in need of blood pressure-lowering medicines, whereas the South and Central Americas had the lowest.

Conclusions: There was substantial variation in the proportion of adults in need of blood pressure-lowering medications depending on which hypertension guideline was used. Given the great implications of this choice for health system capacity, policy makers will need to carefully consider which guideline they should adopt when scaling up hypertension care in their country.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940589PMC
March 2021

Gender Disparities in the Prevalence, Awareness, Treatment, and Control of High Blood Pressure.

Curr Pharm Des 2021;27(29):3173-3179

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

The gender effects in arterial hypertension (HT) epidemiology remain poorly clarified to date. We present an up-to-date review of the data regarding gender disparities in HT's prevalence, awareness, treatment, and control. Based on the data from three consecutive national-representative SEPHAR (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania) surveys conducted between 2005 and 2016, we provide insights into gender differences in HT's epidemiology and their 11- years the evolutionary trend in a high-CV risk European country. Our data displays gender effects in different age-dependent epidemiological patterns in terms of hypertension prevalence, awareness, treatment, and control, mainly due to hormonal status. Hypertension's prevalence is higher in younger men and older women. Although women are more often aware of their hypertensive condition and receive more often antihypertensive treatment, BP control is lower in older women compared to men of the same age, mainly due to a higher treatment side-effect rate. There is no solid evidence that different antihypertensive drugs exhibit different effects in lowering BP values between genders. In high CV risk European countries like Romania, if all the influencing conditions remain similar to those in the past 11 years, gender discrepancies in terms of HT's prevalence will diminish over time, awareness and treatment of hypertension will continue to be higher in females than in men, with an upward trend of BP control predicted only for women, while in men HT treatment control rate is expected to stagnate.
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http://dx.doi.org/10.2174/1381612827666210125154749DOI Listing
October 2021

Sex Differences in Ischemic and Bleeding Outcomes in Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights From the TAO Trial.

Circ Cardiovasc Interv 2021 01 12;14(1):e009759. Epub 2021 Jan 12.

Université de Paris, AP-HP, FACT, FHU APOLLO, Hôpital Bichat, Inserm U-1148, Paris, France (G.D., Y.E., P.G.S.).

Background: Previous studies have observed poorer outcomes in females with myocardial infarction, but older age and lower use of percutaneous coronary intervention in females are factors that potentially explain the worse outcome. This study sought to determine if female sex is an independent factor of ischemic and bleeding outcomes in non-ST-segment-elevation acute coronary syndrome treated with a systematic invasive approach.

Methods: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with non-ST-segment-elevation acute coronary syndrome treated invasively to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, the primary ischemic end point (all-cause death, myocardial infarction within 180 days) and the primary safety end point (Thrombolysis in Myocardial Infarction major or minor bleeding within 30 days) were analyzed according to sex.

Results: Of 13 229 randomized patients, 3980 (30.1%) were females and 9249 (69.9%) were males. Females were older (64.8±11.0 versus 60.7±11.1 years), had more comorbidities, received less peri-procedural antithrombotic therapy, and underwent less frequently revascularization. Overall, females experienced a higher risk of ischemic (10.2% versus 9.1%; odds ratio [OR], 1.15 [1.01-1.30]) and bleeding events (4.2% versus 3.4%; OR, 1.23 [1.02-1.49]) than males. After multivariate analysis, the risk of ischemic outcomes (OR, 1.04 [0.90-1.19]), death (OR, 1.00 [0.75-1.23]), or bleeding (OR, 1.05 [0.85-1.28]), were similar between females and males. Only, noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding were increased in females (OR, 1.69 [1.11-2.56]).

Conclusions: In patients with non-ST-segment-elevation acute coronary syndrome with systematic invasive management, ischemic outcomes, bleeding events, and mortality were higher in females. After multivariate analyses, female sex was not an independent predictor of ischemic and bleeding events although noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding was higher in females. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009759DOI Listing
January 2021

Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy.

Diagnostics (Basel) 2020 Dec 7;10(12). Epub 2020 Dec 7.

Department of Cardiology, Clinical Emergency Hospital of Bucharest, Calea Floreasca 8, 014461 Bucharest, Romania.

Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM).

Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM.

Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel.

Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.
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http://dx.doi.org/10.3390/diagnostics10121061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762332PMC
December 2020

The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry. Rationale, design and objectives.

J Hum Hypertens 2021 11 25;35(11):1029-1037. Epub 2020 Nov 25.

Servicios y Tecnología Cardiovascular de Guatemala. Cardiosolutions, Guatemala City, Guatemala.

Hypertension is a major risk factor for the development of heart failure with preserved ejection fraction (HFPEF) and blood pressure (BP) in itself is an important marker of prognosis. The association of BP levels, and hemodynamic parameters, measured by ambulatory blood pressure monitoring (ABPM), with outcomes, in patients with HFPEF is largely unknown. Patients with HFPEF have a substantial burden of co-morbidities and frailty. In addition there are marked geographic differences in HFPEF around the world. How these difference influence the association between BP and outcomes in HFPEF are unknown. The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry aims to assess the relevance of BP parameters, measured by ABPM, on the outcome of HFPEF patients worldwide. Additionally, the influence of other relevant factors such as frailty and co-morbidities will be assessed. Stable HFPEF patients with a previous hospitalization, will be included. Patients should be clinically and hemodynamically stable for at least 4 weeks before study inclusion. Specific data related to HF, biochemical markers, ECG and echocardiography will be collected. An ABPM and geriatric and frailty evaluation will be performed and the association with morbidity and mortality assessed. Follow up will be at least one year.
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http://dx.doi.org/10.1038/s41371-020-00446-8DOI Listing
November 2021

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

Lancet 2020 12 13;396(10266):1895-1904. Epub 2020 Nov 13.

Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.

Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed.

Findings: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.

Interpretation: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

Funding: Vifor Pharma.
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http://dx.doi.org/10.1016/S0140-6736(20)32339-4DOI Listing
December 2020

High-normal blood pressure and related cardiovascular risk factors prevalence in the Romanian adult population: insights from the SEPHAR III study.

J Hum Hypertens 2021 10 25;35(10):884-895. Epub 2020 Sep 25.

University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.

High normal blood pressure (HNBP) is associated with an increased risk of incident high blood pressure (HBP) and of cardiovascular diseases (CVD). To estimate the prevalence of HNBP and related cardiovascular risk factors, a representative sample of 1970 Romanian adults was enrolled in SEPHAR III survey (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania). All were evaluated for blood pressure values and by a 71-item questionnaire, anthropometric measurements, together with extensive evaluation for target organ damage, blood, and urine sample collection. Prevalence of HNBP was 11% [45.1% had HBP, 43.9% normal BP (NBP)]. HNBP individuals were older (51.14 ± 17.13 years) than subjects with NBP (40.5 ± 15.96 years) but younger than those with HBP (55.79 ± 15.68 years), p < 0.0001 (95% CI 18-85, respectively 18-91). Values of weight, waist circumference, body mass index, total and LDL cholesterol, triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), uric acid, serum creatinine, glomerular filtration rate estimate by CKD-EPI equation, urinary albumin to creatinine ratio, intimae-media thickness, arterial stiffness measurements and diastolic dysfunction, indexed left ventricular mass, interventricular septum and posterior left ventricle wall thickness, left atrial volume, and LA dilatation were significantly higher in HNBP subjects than in NBP. Our study showed that individuals with HNBP represent ~11% and most of them had an elevated total cardiovascular risk. It is essential to educate the public and health care providers to be aware of these individuals and of steps that should be taken to treat modifiable cardiovascular risk factors.
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http://dx.doi.org/10.1038/s41371-020-00417-zDOI Listing
October 2021

The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies.

J Clin Med 2020 Jul 4;9(7). Epub 2020 Jul 4.

Department of Cardiology, Clinical Emergency Hospital of Bucharest, Floreasca Street 8, 014461 Bucharest, Romania.

Pediatric inherited cardiomyopathies (CMPs) and channelopathies (CNPs) remain important causes of death in this population, therefore, there is a need for prompt diagnosis and tailored treatment. Conventional evaluation fails to establish the diagnosis of pediatric CMPs and CNPs in a significant proportion, prompting further, more complex testing to make a diagnosis that could influence the implementation of lifesaving strategies. Genetic testing in CMPs and CNPs may help unveil the underlying cause, but needs to be carried out with caution given the lack of uniform recommendations in guidelines about the precise time to start the genetic evaluation or the type of targeted testing or whole-genome sequencing. A very diverse etiology and the scarce number of randomized studies of pediatric CMPs and CNPs make genetic testing of these maladies far more particular than their adult counterpart. The genetic diagnosis is even more puzzling if the psychological impact point of view is taken into account. This review aims to put together different perspectives, state-of-the art recommendations-synthetizing the major indications from European and American guidelines-and psychosocial outlooks to construct a comprehensive genetic assessment of pediatric CMPs and CNPs.
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http://dx.doi.org/10.3390/jcm9072111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408669PMC
July 2020

The ESC Working Group on Coronary Pathophysiology and Microcirculation.

Eur Heart J 2020 06;41(23):2150-2151

Institut für Physiologie, Universität zu Lübeck, Lübeck, Germany and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck.

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http://dx.doi.org/10.1093/eurheartj/ehaa386DOI Listing
June 2020

Combined right and left ventricular mechanical dispersion enhance the arrhythmic risk stratification in hypertrophic cardiomyopathy.

J Cardiol 2020 10 3;76(4):364-370. Epub 2020 Jun 3.

Department of Cardiology, Clinical Emergency Hospital of Bucharest, Bucharest, Romania; University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.

Background: Ventricular arrhythmias are the most frequent cause of sudden cardiac death in individuals with hypertrophic cardiomyopathy (HCM). In the present study we investigated if combined left ventricular (LV) and right ventricular (RV) mechanical dispersion (MD) are correlated with ventricular arrhythmias. We aimed also to analyze if MD enhances the arrhythmic risk stratification in HCM.

Methods: The cohort included 47 subjects with HCM and 36 healthy individuals. All the studied population underwent clinical, 24-h electrocardiographic (ECG) monitoring for detection and description of non-sustained ventricular tachycardia (NSVT) in terms of number of events, maximal rate and length and comprehensive transthoracic echocardiography, including strain rate imaging. MD was calculated as standard deviation of time from the peak of R wave on ECG to maximum LV or RV shortening in 17 LV and 3 RV segments.

Results: HCM subjects with NSVT on ECG monitoring had increased LVMD (81±18ms vs 42±8ms) and RVMD (52±26 vs 25±23ms) compared with the HCM group without NSVT or compared with the healthy controls. On receiver operating characteristic curves the cut-off values associated with optimal specificity and sensitivity were 62ms for LVMD and 39ms for RVMD. LVMD (OR=1.86, 95% CI 1-1.06, p=0.01) and RVMD (OR=1.04, 95% CI 1.01-1.07, p=0.003) were the only independent variables that correlated with longer and faster NSVT and furthermore improved the risk stratification of NSVTs.

Conclusions: In a cohort of subjects with HCM, LVMD and RVMD correlates with the presence of NSVT on ECG monitoring. Combined LVMD and RVMD may improve the risk stratification of HCM with NSVT.
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http://dx.doi.org/10.1016/j.jjcc.2020.04.009DOI Listing
October 2020

Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis.

Cardiovasc Res 2021 01;117(1):29-42

Department of Infection, Immunity and Cardiovascular Disease, Bateson Centre & INSIGNEO Institute, University of Sheffield, Sheffield S10 2RX, UK.

Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.
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http://dx.doi.org/10.1093/cvr/cvaa085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797212PMC
January 2021
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