Net clinical benefit of DOACs vs. usual anticoagulation treatment in venous thromboembolism and active cancer: systematic review and meta-analysis.

Patients with active cancer are at high risk of recurrent venous thromboembolism (VTE). Usual treatment includes low molecular weight heparin (LMWH), while vitamin K antagonists (VKAs) have also been used as substitutes for LMWH. Direct oral anticoagulants (DOACs) are considered a beneficial alternative to the usual treatment but are accompanied by an increased rate of bleeding compared to LMWH. We conducted a meta-analysis to evaluate the benefits and harms under a common denomination, namely the net clinical benefit (NCB), between DOACs and usual anticoagulation. The primary outcome was NCB-1, defined as non-fatal VTE, major non-fatal bleedings, and all-cause mortality). Co-primary outcomes were 1) NCB-2 (i.e., NCB-1 and clinically relevant non-major bleedings) and 2) NCB-3 (i.e., fatal or non-fatal VTE and major bleedings). A random-effects model was used to calculate outcome risk ratios and 95% confidence intervals (CI). Prospective Register of Systematic Reviews identification number CRD42021284238. We selected 8 studies (n = 4,4461 patients; mean follow-up, 6 months). The NCB-1 and -2 were not different between DOACs and usual anticoagulation, while the NCB-3 showed a reduction of 28% (95% CI, 10-42%), favoring DOACs. Recurrent VTE was reduced by 40% (95% CI, 25-53%) with DOACs than the usual treatment. Different bleeding outcomes and all-cause mortality were not different between treatments. All primary outcomes did not differ between DOACs and LMWH, while NCB-2 and NCB-3 were reduced with DOACs than VKAs. The NCB of DOACs was similar or more favorable to usual anticoagulation in patients with active cancer due to a substantial reduction of VTE and no bleeding excess.

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.

AIMS: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. METHODS AND RESULTS: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 µm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC. CONCLUSION: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: NCT03984123.

Cardiac imaging in cardiotoxicity: a focus on clinical practice.

Cancer therapeutics induced cardiotoxicity has emerged as an important factor of long-term adverse cardiovascular outcomes in survivors of various malignant diseases. Early detection of myocardial injury in the setting of cancer treatment is important for the initiation of targeted cardioprotective therapy, in order to prevent irreversible cardiac dysfunction and heart failure, while not withholding a potentially life-saving cancer therapy. Cardiac imaging techniques including echocardiography, cardiac magnetic resonance, and nuclear cardiac imaging are the main tools for the identification of cardiotoxicity. There is also growing evidence for the detection of subclinical cardiac dysfunction in cancer patients by speckle tracking echocardiography. In this review article, we focus on current and emerging data regarding the role of cardiac imaging for the detection of changes in myocardial function related with cancer treatment in clinical practice.

Advancements in the diagnostic workup, prognostic evaluation, and treatment of takotsubo syndrome.

Takotsubo syndrome (TTS) is an acute and mostly reversible cardiomyopathy that mimics an acute coronary syndrome with left ventricular (LV) systolic dysfunction without relevant obstructive coronary artery disease. Its prevalence is probably underestimated and reaches 1.2-2% in patients with acute coronary syndrome undergoing coronary catheterization. Although supraphysiological epinephrine levels have been associated with TTS, the detailed pathophysiology is incompletely understood. Chest pain is the most common clinical presentation; however, cardiac decompensation, cardiogenic shock, and sudden cardiac death due to ventricular fibrillation may also be the first clinical manifestations. Patients are mostly postmenopausal women, in whom the condition is commonly associated with emotional triggers; however, men have a higher prevalence of TTS being associated with physical triggers, which has a worse prognosis compared with TTS associated with emotional triggers. As a diagnosis of exclusion, TTS has no single definitive diagnostic test. According to the distribution of LV wall motion abnormalities, various morphological subtypes have been identified. The final diagnosis depends on cardiac imaging with left ventricular angiography during acute heart catheterization, as well as on echocardiography and cardiac magnetic resonance. Most patients recover completely, albeit several factors have been associated with worse prognosis. Management is based on observational data, while randomized multicenter studies are still lacking. This review provides a general overview of TTS and focuses on the hypothesized pathophysiology, and especially on current practices in diagnosis, prognosis, and treatment.

Echocardiography in Autoimmune Rheumatic Diseases for Diagnosis and Prognosis of Cardiovascular Complications.

Autoimmune rheumatic diseases are systemic diseases frequently affecting the heart and vessels. The main cardiovascular complications are pericarditis, myocarditis, valvular disease, obstructive coronary artery disease and coronary microcirculatory dysfunction, cardiac failure and pulmonary hypertension. Echocardiography, including transthoracic two and three-dimensional echocardiography, Doppler imaging, myocardial deformation and transesophageal echo, is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases. Echocardiography is also important for monitoring the impact of drug treatment on cardiac function, coronary microcirculatory function, valvular function and pulmonary artery pressures. In this article we summarize established and evolving knowledge on the role of echocardiography for diagnosis and prognosis of cardiovascular abnormalities in rheumatic diseases.

Hypertrophic cardiomyopathy: an updated review on diagnosis, prognosis, and treatment.

Hypertrophic cardiomyopathy (HCM) represents a phenotype of left ventricular hypertrophy unexplained by abnormal loading conditions. The definition is based on clinical criteria; however, there are numerous underlying etiologic factors. The MOGE(S) classification provides a standardized approach for multimodal characterization of HCM. HCM is associated with increased morbidity and mortality, and especially the assessment of the risk of sudden cardiac death is of paramount importance. In this review, we summarize essential knowledge and recently published data on clinical presentation, diagnosis, genetic analyses, differential diagnosis, prognosis, and treatment options that are necessary for understanding and management of HCM.

Arterial stiffness and coronary artery disease.

PURPOSE OF REVIEW: The current traditional risk scores are not sufficient to predict the full incidence of cardiovascular disease. In this brief review, we discuss the pathophysiological mechanisms through which arterial stiffness affects cardiac function and the additive value of markers of arterial stiffness, to detect the presence of coronary artery disease (CAD) and predict adverse outcome in these patients. RECENT FINDINGS: Arterial stiffness causes early arrival of wave reflections in systole instead of diastole and, thus, increases systolic afterload and reduces diastolic coronary perfusion pressure. Abnormal collagen turnover, cytokines, and metalloproteinase activity are common biochemical links between vascular and myocardial stiffness. Pulse wave velocity, augmentation index, and central pressures measured by simple noninvasive methods are related to atheromatic plaque vulnerability, incidence, severity, and extent of CAD. Recent meta-analyses have shown the additive value of markers of arterial stiffness, and particularly of pulse wave velocity, to detect CAD, predict cardiovascular events, and reclassify patients to a higher cardiovascular risk. Studies assessing whether reduction of arterial stiffness is associated with improved prognosis are lacking. SUMMARY: Markers of arterial stiffness are useful tools to identify early atherosclerosis and adverse clinical outcomes in young adults and individuals with a modest risk factor profile. Assessing arterial stiffness may facilitate cardiovascular risk stratification beyond traditional risk scores.

Impairment in Right Ventricular-Pulmonary Arterial Coupling in Overweight and Obesity.

Background: The association of obesity with right ventricular function and the interplay between right heart and pulmonary circulation is incompletely understood. We evaluate the role of obesity as a determinant of right ventricular-pulmonary artery coupling (RVAC). Methods: We retrospectively studied consecutive subjects without overt cardiovascular or pulmonary disease. Subjects were stratified according to body mass index (BMI) as normal weight, overweight, or obese. A transthoracic echocardiographic study was used to assess left and right heart functional and structural parameters. RVAC was assessed using the ratio of peak systolic velocity of the tricuspid annulus to pulmonary artery systolic pressure (PASP). Results: A total of 145 subjects were enrolled with diabetes mellitus incidence higher in obese. There was no difference in left ventricular global longitudinal strain and in PASP or markers of right ventricular systolic function based on BMI. RVAC was significantly lower in the presence of obesity (normal weight: 0.52 (0.19) cm·(sec·mmHg)-1 vs. overweight: 0.47 (0.16) cm·(sec·mmHg)-1 vs. obese: 0.43 (0.14) cm·(sec·mmHg)-1, p = 0.03), even after adjustment for confounders (ß: -0.085, 95% confidence interval: -0.163, -0.009, p = 0.029). Conclusions: Our findings highlight the relationship between metabolic impairment and RVAC, suggesting additional mechanisms for heart failure development observed in obese subjects.

Practical guidance and clinical applications of transoesophageal echocardiography. A position paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for a wide spectrum cardiac and extra-cardiac diseases. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Cardiology Society to state the essential steps of the typical TOE exam performed in echo lab. This is an educational text, describing the minimal requirements and the preparation of a meticulous TOE examination. Most importantly, it gives practical instructions to obtain and optimize TOE views and analyses the implementation of a combined two-and multi-dimensional protocol for the imaging of the most common cardiac structures during a TOE. In the second part of the article a comprehensive review of the contemporary use of TOE in a wide spectrum of valvular and non-valvular cardiac diseases is provided, based on the current guidelines and the experience of the WG members.

Transoesophageal echocardiography beyond the Echo-Laboratory. An expert consensus paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established and valid imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for several specific diagnoses and recently a useful guide of an increasing number of catheter-based and surgical interventions. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Society of Cardiology to state the essential steps of the TOE exam performed beyond the echo lab: a) in the operating rooms intraoperatively during either transcatheter interventions, or cardiothoracic surgery and b) in the intensive care unit for critically ill patients' monitoring. This paper includes information and tips and tricks about the pre-procedural evaluation, the procedural echocardiographic guidance and post - procedural evaluation of the result and potential complications.

Peak exercise myocardial deformation indices during cardiopulmonary exercise testing are associated with exercise capacity and ventilatory efficiency in patients with dilated cardiomyopathy.

OBJECTIVE: Little is known about the exercise-induced changes in the multidimensional mechanical properties of the heart. We aimed to evaluate the myocardial deformation indices (MDI) at rest and their response at peak exercise during the same cardiopulmonary exercise testing (CPET) session, investigating their relationship to exercise capacity and ventilatory sufficiency in dilated cardiomyopathy (DCM) patients. METHODS: We evaluated left ventricular (LV) function using speckle tracking imaging (STI) at rest and peak exercise during the same CPET session in 57 idiopathic DCM patients in New York Heart Association (NYHA) I-II class [54 ± 12 years, 42 males, ejection fraction (EF) 33 ± 9%]. We measured global longitudinal strain (GLS), longitudinal strain rate at systole (LSRS) and diastole (LSRD), and circumferential strain rate (CircS). RESULTS: Resting GLS, LSRS, and LSRD were impaired compared with the predicted values but were improved at peak exercise (p < 0.001). All MDI at rest and/or at peak exercise were related to several CPET-derived parameters, including peak VO2, load, O2 pulse, and VE/VCO2 slope. Peak exercise LSRS > -1.10 sec-1 (AUC = 0.80, p < 0.001) and GLS > -13% (AUC = 0.81, p = 0.002) predicted impaired exercise capacity (peak VO2 < 20 ml/min/kg) and ventilatory inefficiency (VE/VCO2 slope>34). In multiple regression analysis, peak exercise LSRS and GLS were independently related to the peak VO2 (Beta = -0.39, p = 0.003) and VE/VCO2 slope (Beta = 0.35, p = 0.02), respectively. CONCLUSIONS: Peak exercise LSRS and GLS in NYHA I-II DCM patients subjected to CPET were associated with aerobic exercise capacity and ventilatory efficiency. Consequently, LSRS and GLS at peak exercise, through their association with CPET-derived CV risk indices, may underline the severity of heart failure and predict future CV events in this DCM population.

Coronary Microvascular Dysfunction in Asymptomatic Patients with Severe Psoriasis.

Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.

Additive prognostic value of longitudinal myocardial deformation to SCORE2 in psoriasis.

Aims: Psoriasis has been associated with increased cardiovascular (CV) risk. We investigated whether markers of CV function and their change after treatment have a prognostic value for adverse outcomes. Methods and results: In a prospective study, at baseline and after 6 months of treatment with biological agents, we assessed in 298 psoriasis patients (i) left ventricular global longitudinal strain (GLS) and (ii) carotid-femoral pulse wave velocity (PWV), to evaluate their prognostic value for major adverse cardiovascular events (MACEs), including coronary artery disease, stroke, hospitalization for heart failure, and all-cause death over a 4-year follow-up period. During follow-up, 26 (8.7%) MACEs were recorded. By univariate analysis, decreasing absolute GLS values [hazard ratio (HR): 0.73, P < 0.001], decreasing GLS change after treatment (HR: 0.53, P = 0.008), and increasing PWV values (HR: 1.16, P = 0.049) were associated with adverse outcomes. Baseline GLS and its change post-treatment remained independent predictors of adverse events after adjusting for several confounders (P < 0.05). The addition of baseline GLS and its absolute change post-treatment to SCORE2 increased Harrell's C from 0.882 to 0.941. By multivariable analysis, for each 1% increase in absolute baseline GLS values, the risk of MACE decreased by 33% and for each 1% absolute increase of GLS post-treatment compared with the baseline value, the risk of MACE decreased by 58%. Conclusion: Global longitudinal strain has an independent and additive prognostic value to SCORE2 for adverse CV events in psoriasis, providing timely decision-making for intensive anti-inflammatory treatment and aggressive modification of risk factors to reduce CV risk.

Fagerstrom score predicts smoking status six months after hospitalization for acute myocardial infarction: a prospective study.

BACKGROUND: Fagerstrom score is a validated marker of nicotine addiction in smokers. METHODS: In a prospective study, we investigated a) the predictive value of Fagerstrom score for the smoking status in patients early after acute myocardial infarction (AMI) and b) the effectiveness of medically assisted smoking cessation programs in the prevention of relapsing to smoking post discharge. In 103 smokers (58 ± 12 years, 79.6% males), we assessed Fagerstrom score during hospitalization for AMI. Patients filled a dedicated questionnaire including data on family, marital and educational status, habits related to smoking and were followed-up at 3 and 6 months after discharge. RESULTS: Twenty-eight patients (27.2%) did not quit smoking throughout the 6-months follow-up period (Fagerstrom score:8.1 ± 1.6), 39 patients (37.8%) ceased smoking at 3 months but relapsed to smoking at 6 months (score:6.8 ± 2.1), and only 34 patients (33%) had ceased smoking for 6 consecutive months (score:5.2 ± 2 p < 0.05 for all comparisons between subgroups). By multivariate analysis, Fagerstrom score remained a significant predictor of smoking cessation at 6 months (OR: 0.72, 95%CI: 0.60--0.86, p < 0.001). Out of 73 patients who abstained from smoking for the first 3 months post-AMI, those who participated in a smoking cessation program displayed lower rate of relapsing to smoking compared with those who opted to cease smoking without any support (33.3% vs 61.8% p = 0.012). CONCLUSION: Fagerstrom score is a useful predictor of smoking cessation 6 months post-AMI. Patients participating in a smoking cessation program display lower relapse rates post-discharge suggesting the need of well-organized smoking cessation clinics for secondary prevention of heart disease.

Apremilast Improves Endothelial Glycocalyx Integrity, Vascular and Left Ventricular Myocardial Function in Psoriasis.

The phosphodiesterase 4 inhibitor apremilast is used for the treatment of psoriasis. We investigated the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. One hundred and fifty psoriatic patients were randomized to apremilast (n = 50), anti-tumor necrosis factor-α (etanercept; n = 50), or cyclosporine (n = 50). At baseline and 4 months post-treatment, we measured: (1) Perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter 5-25 µm using a Sidestream Dark Field camera (GlycoCheck). Increased PBR indicates damaged glycocalyx. Functional microvascular density, an index of microvascular perfusion, was also measured. (2) Pulse wave velocity (PWV-Complior) and (3) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Compared with baseline, PBR5-25 µm decreased only after apremilast (-12% at 4 months, p < 0.05) whereas no significant changes in PBR5-25 µm were observed after etanercept or cyclosporine treatment. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of functional microvascular density (+14% versus +1% versus -1%) and in a higher reduction of PWV. Apremilast showed a greater increase of GLS (+13.5% versus +7% versus +2%) than etanercept and cyclosporine (p < 0.05). In conclusion, apremilast restores glycocalyx integrity and confers a greater improvement of vascular and myocardial function compared with etanercept or cyclosporine after 4 months.

Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease.

Psoriatic disease is associated with vascular and myocardial dysfunction. We aimed to evaluate endothelial glycocalyx barrier properties and microvascular perfusion in psoriatic patients, as well as their correlation with carotid intima-media thickness (cIMT) and markers of left ventricular (LV) myocardial deformation. We examined 297 psoriatic patients and 150 controls, adjusted for age, sex, and atherosclerotic risk factors. The severity of psoriatic disease was estimated using the psoriasis area and severity index (PASI). Perfused boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter 5-25 µm using Sidestream Dark Field camera (Microscan, GlycoCheck). Increased PBR indicates reduced glycocalyx thickness. Indexes of microvascular perfusion, including red blood cells filling (RBCF) and functional microvascular density, were also calculated. We measured cIMT, coronary flow reserve (CFR) and markers of myocardial deformation by speckle-tracking imaging, namely global longitudinal strain (GLS) and percentage changes between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO). Compared to controls, psoriatic patients had higher PBR5-25µm (2.13 ± 0.29µm versus 1.78 ± 0.25µm, p < 0.001) and lower RBCF and functional microvascular density (p < 0.001). Increased PASI was associated with elevated PBR and more impaired cIMT and GLS (p < 0.05). There was an inverse association of PBR with RBCF and functional microvascular density (p < 0.001). In psoriatic population, increased PBR was related to increased cIMT, reduced CFR, impaired GLS and decreased %dpTw-UtwMVO (p < 0.001). Glycocalyx thickness is reduced in psoriatic patients, which in turn impairs microvascular perfusion, and is associated with carotid IMT and impaired coronary and myocardial function.Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT02144857.

Updated knowledge and practical implementations of stress echocardiography in ischemic and non-ischemic cardiac diseases: An expert consensus of the Working Group of Echocardiography of the Hellenic Society of Cardiology.

Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training-which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease.

Investigating the Link between Psoriasis and Cardiovascular Disease: Current Evidence, Therapeutic Implications and Perspectives.

Psoriasis; a chronic inflammatory disease is characterized by symmetric hyperkeratotic plaques affecting any part of the body. Psoriasis is nowadays considered as a systemic inflammation linked with several comorbidities as metabolic syndrome, depression, anxiety and increased prevalence of cardiovascular (CV) disease. The hypothesis that psoriasis is an independent CV risk factor leading to atherosclerosis via inflammation is now widely accepted. Deciphering the underlying mechanisms interconnecting psoriasis and CV disease may have significant implications in treatment decisions. Accumulating evidence suggests that systematic therapies and recently introduced biologic agents, that control psoriasis by suppressing the chronic and systemic inflammation, may alter the progression of CV disease. We herein attempt a review of current evidence analysing the relationship between psoriasis and CV comorbidities, comment on the mechanisms underlying this association and investigate the consequences for the management of psoriasis.