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Background: Cardiac resynchronization therapy (CRT) improves both morbidity and mortality in selected patients with heart failure and increased QRS duration. However, chronic kidney disease (CKD) may have an adverse effect on patient outcome. The aim of this systematic review was to analyze the existing data regarding the impact of baseline renal function on all-cause mortality in patients who underwent CRT. Methods: Medline database was searched systematically, and studies evaluating the effect of baseline renal function on all-cause mortality in patients who underwent CRT were retrieved. We performed three separate analyses according to the comparison groups included in each study. Data were analyzed using Review Manager software (RevMan version 5.3; Oxford, UK). Results: We included 16 relevant studies in our analysis. Specifically, 13 studies showed a statistically significant higher risk of all-cause mortality in patients with impaired baseline renal function who underwent CRT. The remaining three studies did not show a statistically significant result. The quantitative synthesis of five studies showed a 19% decrease in all-cause mortality per 10-unit increment in estimated glomerular filtration rate (eGFR) [HR: 0.81, 95% CI (0.73–0.90), p

Background. Intestinal mucosal barrier dysfunction in liver cirrhosis and its implicated mechanisms is of great clinical importance because it is associated with the development of serious complications from diverse organs through promotion of systemic endotoxemia.Aim. The present study was designed to investigate whether enterocytes’ proliferation, apoptosis and intestinal oxidative stress are altered in the intestinal mucosa of patients with compensated and decompensated liver cirrhosis.Material and methods. Twelve healthy controls (group A) and twenty four cirrhotic patients at a compensated (n = 12, group B) or decompensated condition (n = 12, group C) were subjected to duodenal biopsy. In intestinal specimens mucosal apoptotic and mitotic activity and their ratio were recorded by means of morphological assessment and mucosal lipid hydroperoxides were measured. Plasma endotoxin concentration, an index of gut barrier function, was also determined.Results. Cirrhotic patients presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0.001), whilst endotoxemia was higher in decompensated disease (P < 0.05 vs. compensated cirrhosis). Intestinal mucosal mitotic count was significantly lower in patients with compensated and decompensated cirrhosis compared to controls (P < 0.01, respectively), whilst a trend towards increased apoptosis was recorded. The mitotic/apoptotic ratio was significantly reduced in groups B (P < 0.05) and C (P < 0.01) as compared to controls. Intestinal lipid peroxidation was significantly increased in decompensated cirrhotics (P < 0.001 vs. groups A and B).Conclusions. The present study demonstrates for the first time that human liver cirrhosis is associated with decreased intestinal mucosal proliferation and proliferation/apoptosis ratio even at early stages of cirrhosis and increased intestinal oxidative stress in advanced liver disease.

Background: Cardiac resynchronization therapy (CRT) is an established therapeutic option for patients with heart failure (HF) and left ventricular ejection fraction (LVEF) =35 % who meet specific criteria according to current guidelines. However, up to 40 % of patients have no response to CRT. Our study aimed to investigate the association between different hematological and biochemical indices and response to CRT. Methods: Patients with HF due to ischemic or dilated cardiomyopathy referred to our hospital for CRT implantation from January 2013 to November 2017 were included in the study. Response to CRT was defined as an increase in LVEF =10 % or a decrease in left ventricular end-systolic volume (LVESV) =15 % at six months of follow-up. Results: A total of 48 patients (mean age: 66.2 ± 9.5 years, 81.3 % males) were included in the study. Of these HF patients, 29 (60.4 %) had ischemic cardiomyopathy, and 19 (39.6 %) had dilated cardiomyopathy. At six months of follow-up, 37 patients (77.1 %) had responded to CRT. Ten patients (20.8 %) had ventricular tachycardia (VT), 24 (50 %) patients were hospitalized, and two patients (4.2 %) died during the follow-up period. Multivariate analysis demonstrated that age (p =0.03) and creatinine levels (p =0.02) were independent predictors of the response to CRT. No significant associations between hematological markers (white blood cells, neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio, red blood cells distribution width) and CRT response were observed. Conclusions: A smaller increase in LVEF and a smaller decrease in LVESV were predictive for VT occurrence and hospitalizations in patients receiving CRT. No significant association between hematological markers and response to CRT was found. [ABSTRACT FROM AUTHOR]

Aims: To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension., Methods: Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis., Results: In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = - 6.01 mmHg; 95% CI = [- 7.46, - 4.55] and MD = - 5.01 mmHg; 95% CI = [- 5.91, - 4.11], respectively). Moreover, resulted a similar reduction in systolic BP (MD = - 0.22 mmHg; 95% CI = [- 0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to the active comparator (MD = - 0.71 mmHg; 95% CI = [- 1.27, - 0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP., Conclusion: Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction., Competing Interests: Declarations. Authors contribution: Athanasios Manolis: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Paschalis Karakasis: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Visualization, Writing -original draft, Writing—review & editing. Dimitrios Patoulias: Conceptualization, Methodology, Investigation, Writing—original draft, Writing—review & editing. Michalis Doumas: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Manolis Kallistratos: Conceptualization, Methodology, Investigation, Writing—review & editing. Costas Thomopoulos: Conceptualization, Methodology, Investigation, Writing—review & editing. Maria Koutsaki: Investigation, Writing—review & editing. Guido Grassi: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. Giuseppe Mancia: Conceptualization, Methodology, Investigation, Project administration, Writing—review & editing. All authors read and approved the final manuscript. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for its design or conduction. Conflict of interest: The authors declare that they have no conflict of interest. Protocol: The study protocol was prepared a priori and registered in OSF ( https://osf.io/bm9cx/ ). Data availability: The data generated in this research will be shared on reasonable request to the corresponding author., (© 2024. The Author(s).)

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA 2 DS 2 -VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The conflict of interest declaration of authors are compiled into one file that can be found on the ESH website: https://www.eshonline.org/guidelines/2023-guidelines/. ESH received no financial support for the generation of this guidelines.

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension β-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown., Competing Interests: Disclosures G. Mancia has received honoraria from Astra Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier. M. Brunström reports lecture honoraria from Amarin, AstraZeneca and Medtronic. M. Burnier has received honoraria from Servier, Menarini, Cincor, Bayer, and Boehringer Ingelheim. G. Grassi has received lecture honoraria from Berlin-Chemie, Gedeon-Richter, Menarini, Merck Healthcare, and Servier. A. Januszewicz has received honoraria from Servier, Gedeon-Richter, Medtronic, KRKA, Novartis, AstraZeneca, Adamed, Bausch, Polfarma; Novartis; Berlin-Chemie; Termedia; ViaMedica; Medycyna Praktyczna. S.E. Kjeldsen reports lecture honoraria from Getz Pharma, J.B. Pharma, Merck Healthcare KGaA, Vector-Intas, and Zydus. M.L. Muiesan reports honoraria from Novartis and Merck-Serono. C. Thomopoulos reports lecture honoraria from Astra Zeneca, Menarini, Medtronic, Krka, Sanofi, and Servier. K. Tsioufis reports honoraria from Medtronic, St. Jude Medical, Bayer, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Chiesi, Pharmanel, Sanofi, Vianex, Win-Medica, Elpen, Recordati, Servier. R. Kreutz reports support for research by Bayer, honoraria for lectures from Bayer, Berlin-Chemie/Menarini, Daiichi Sankyo, Ferrer, Merck, Sanofi, and Servier.

Background: Previous meta-analyses resurrected the debated statement "the lower, the better" following blood pressure (BP)-lowering treatment. We investigated the benefits of BP-lowering treatment at different BP targets by prevention category., Methods: The meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (CRD42022379249). The database included 115 BP-lowering or comparison trials from patients with (n=241 089) or without (n=198 937) previous cardiovascular events. Prevention disease groups were stratified by in-treatment achieved BP, drug class versus placebo, and drug class versus other classes. Risk ratios and 95% CIs of major adverse cardiovascular events were calculated., Results: Following a standard (10/5 mm Hg) BP reduction, major adverse cardiovascular event relative risk reductions were not different between prevention groups (primary, 25% [95% CI, 18%-31%]; secondary, 28% [95% CI, 20%-37%]). For achieved systolic BP of at least 140 mm Hg, between 130 and 140 mm Hg, and <130 mm Hg (nadir, 125 mm Hg), (1) risk ratios of major adverse cardiovascular events and absolute risk reductions were not different between prevention groups across systolic BP strata, and (2) residual risk, though 4.1× greater in secondary than primary prevention, decreased in primary prevention from higher to lower systolic BP targets. The effect of separate drugs versus others on the primary outcome was not different between prevention groups., Conclusions: BP-lowering treatment benefits did not differ by prevention group to a nadir of 125 mm Hg for systolic BP. Although residual risk in secondary prevention is higher than in primary prevention, it gradually decreases at progressively lower systolic BP targets in primary prevention., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022379249., Competing Interests: Disclosures C. Thomopoulos and K. Tsioufis have received speaker fees from Menarini, Sanofi, Medtronic, and Servier. C. Thomopoulos reports consulting fees from Sanofi and Menarini. The other authors report no conflicts.

The vast majority of antianginal drugs decrease heart rate and or blood pressure levels or the inotropic status of the left ventricle to decrease myocardial oxygen consumption (MVO2) and thus anginal symptoms. Ranolazine presents a completely different mechanism of action, which reduces the sodium-dependent calcium overload inhibiting the late sodium current. Current European Society of Cardiology (ESC) guidelines for the management of angina in patients with chronic coronary symptoms recommend the use of several drugs such as ranolazine, b-blockers, calcium channel blockers, long-acting nitrates, ivabradine, nicorandil and trimetazidine for angina relief. However, ranolazine, in addition to symptom relief properties, is an antianginal drug showing favorable effects in decreasing the arrhythmic burden and in ameliorating the glycemic profile of these patients. In this review, we summarize the available data regarding the antianginal and pleiotropic effects of this drug., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

There are scarce data on the comparative prognosis between patients with hypertensive emergencies (HE), urgencies (HU), and those without HU or HE (HP). Our study aimed to compare cardiovascular (CV) outcomes of HE, HU, and HP during a 12-month follow-up period. The population consisted of 353 consecutive patients presenting with HE or HU in a third-care emergency department and subsequently referred to our hypertension center for follow-up. After both groups completed scheduled follow-up visits, patients with HU were matched one-to-one by age, sex, and hypertension history with HP who attended our hypertension center during the same period. Primary outcomes were 1) a recurrent hypertensive HU or HE event and 2) non-fatal CV events (coronary heart disease, stroke, heart failure, or CV interventions), while secondary outcomes were 1) all-cause death, 2) CV death, 3) non-CV death, and 4) any-cause hospitalization. Events were prospectively registered for all three groups. During the study period, 81 patients were excluded for not completing follow-up. Among eligible patients(HE = 94; HU = 178), a total of 90 hospitalizations and 14 deaths were recorded; HE registered greater CV morbidity when compared with HU (29 vs. 9, HR 3.43, 95 % CI 1.7-6.9, p = 0.001), and increased CV mortality (8 vs. 1, HR 13.2, 95 % CI 1.57-110.8, p = 0.017). When opposing HU to HP, events did not differ substantially. Cox regression models were adjusted for age, sex, CV and chronic kidney disease, diabetes mellitus, and smoking. During 1-year follow-up, the prognosis of HU was better than HE but not different compared to HP. These results highlight the need for improved care of HU and HE., Competing Interests: Declarations of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Document Reviewers: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Non-pharmacological measures are recommended as the first-line treatment for individuals with high-normal blood pressure (BP) or mild hypertension. Studies directly comparing the BP effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) on a salt restriction background are currently lacking. Thus, our purpose was to assess the BP effects of a 3-month intensive dietary intervention implementing salt restriction either alone or in the context of the DASH, and the MedDiet compared to no/minimal intervention in adults with high normal BP or grade 1 hypertension., Methods: We randomly assigned never drug-treated individuals to a control group (CG, n = 60), a salt restriction group (SRG, n = 60), a DASH diet with salt restriction group (DDG, n = 60), or a MedDiet with salt restriction group (MDG, n = 60). The primary outcome was the attained office systolic BP difference among the randomized arms during follow-up., Results: A total of 240 patients were enrolled, while 204 (85%) completed the study. According to the intention-to-treat analysis, compared to the CG, office and 24 h ambulatory systolic and diastolic BP were reduced in all intervention groups. A greater reduction in the mean office systolic BP was observed in the MDG compared to all other study groups (MDG vs. CG: mean difference = -15.1 mmHg; MDG vs. SRG: mean difference = -7.5 mmHg, and MDG vs. DDG: mean difference = -3.2 mmHg, all P-values <0.001). The DDG and the MDG did not differ concerning the office diastolic BP and the 24 h ambulatory systolic and diastolic BP; however, both diets were more efficient in BP-lowering compared to the SRG., Conclusions: On a background of salt restriction, the MedDiet was superior in office systolic BP-lowering, but the DASH and MedDiet reduced BP to an extent higher than salt restriction alone., Competing Interests: Conflicts of Interest None related to the present work for all authors., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This paper reviews 11 current and previous international and some selected national hypertension guidelines regarding sex and gender-related differences. Those differences can be attributed to biological sex and to gender differences that are determined by socially constructed norms. All reviewed guidelines agree on a higher hypertension prevalence in men than in women. They also concur that evidence does not support different blood pressure thresholds and targets for treatment between men and women. Differences refer in addition to the differences in epidemiological aspects to differences in some morphometric diagnostic indices, e.g., left ventricular mass or the limits for daily alcohol intake. Concerning practical management, there are hardly any clear statements on different procedures that go beyond the consensus that blockers of the renin-angiotensin system should not be used in women of childbearing age wishing to become pregnant. Some further sex-specific aspects are related to differences in tolerability or drug-specific side effects of BP-lowering drugs. There is also a consensus about the need for blood pressure monitoring before and during the use of contraceptive pills. For management of pregnancy, several guidelines still recommend no active treatment in pregnant women without severe forms of hypertension, despite a wide consensus about the definition of hypertension in pregnancy. A disparity in treatment targets when treating severe and non-severe hypertension in pregnancy is also observed. Overall, sex-specific aspects are only very sparsely considered or documented in the evaluated guidelines highlighting an unmet need for future clinical research on this topic., (© 2023. The Author(s).)

The Coronavirus Disease 2019 (COVID-19) pandemic was declared in early 2020 after several unexplained pneumonia cases were first reported in Wuhan, China, and subsequently in other parts of the world. Commonly, the disease comprises several clinical features, including high temperature, dry cough, shortness of breath, and hypoxia, associated with findings of interstitial pneumonia on chest X-ray and computer tomography. Nevertheless, severe forms of acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are not limited to the respiratory tract but also may be extended to other systems, including the cardiovascular system. The bi-directional relationship between atherosclerosis and COVID-19 is accompanied by poor prognosis. The immune response hyperactivation due to SARS-CoV-2 infection causes an increased secretion of cytokines, endothelial dysfunction, and arterial stiffness, which promotes the development of atherosclerosis. Also, due to the COVID-19 pandemic, access to healthcare amenities was reduced, resulting in increased morbidity and mortality in patients at risk. Furthermore, as lockdown measures were largely adopted worldwide, the sedentary lifestyle and the increased consumption of processed nutrients or unhealthy food increased, and in the consequence, we might observe even 70% of overweight and obese population. Altogether, with the relatively low ratio of vaccinated people in many countries, and important health debt appeared, which is now and will be for next decade a large healthcare challenge. However, the experience gained in the COVID-19 pandemic and the new methods of patients' approaching have helped the medical system to overcome this crisis and will hopefully help in the case of new possible epidemics., Competing Interests: Annabelle Shor, Raluca Ecaterina Haliga, Viviana Onofrei Aursulesei and Oana Sirbu have the same contribution as the first author for this study. The authors report no conflicts of interest in this work., (© 2023 Ceasovschih et al.)

Cancer is considered one of the leading causes of mortality worldwide. At the same time, hypertension is recognized as one of the most common comorbidities in cancer patients. Antineoplastic therapies, mainly tyrosine kinase and vascular endothelial growth factor inhibitors, have been associated with new-onset hypertension by activation of different pathophysiological pathways. However, the role of preexisting hypertension in cancer patients under treatment has not been thoroughly studied. According to this review, preexisting hypertension is an independent risk factor for increased blood pressure during anticancer therapy. Therefore, physicians should recognize hypertension and its phenotypes (i.e., masked hypertension) as an important modifiable risk factor that should be properly managed prior to the initiation of cancer therapy to avoid premature chemotherapy cessation. The development of onco-hypertension will help establish specific guidelines for managing hypertension in cancer patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: We determined the effect of ranolazine vs. placebo in angina patients on 1) selective measures of the ischemic burden, 2) cardiovascular outcomes, including atrial fibrillation incidence, 3) the in-treatment glycohemoglobin levels and the permanent discontinuations because of side effects, and 4) the achieved between-arms blood pressure and heart rate difference., Methods: PubMed and Cochrane Collaboration Library databases were searched for eligible trials until end of September 2020. Trial quality was assessed by the Rob2 tool. Risk ratios or achieved mean differences during follow-up and 95% confidence interval (CI) of categorical or continuous outcomes, respectively, were calculated (random-effects model). The relationship between discontinuation rates and ranolazine's mean dose was investigated by meta-regression analysis., Results: We selected 18 trials (n = 12,995 patients in patients with macro or microvascular coronary heart disease. Achieved blood pressure and heart rate at rest were not different between randomized arms. Ranolazine administration compared to placebo was associated with an increase of 1) total exercise duration by 30 seconds (95% CI, 18-42), 2) time to 1 mm ST-segment depression by 44 seconds (95% CI, 30-54), and 3) time to angina onset by 40 seconds (95% CI, 30-54). On average, the incidence of atrial fibrillation was reduced by 25% following ranolazine treatment compared to placebo, while glycohemoglobin showed a mean decrease of 0.4% (95% CI, 0.3-0.5%)., Discussion: Ranolazine remains an effective anti-ischemic drug, increases the angina-free exercise duration, delays the onset of ST-segment depression. The beneficial effects of ranolazine are extended to atrial fibrillation reduction rates and better glycemic control., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Current evidence on the prognosis of patients with a hypertensive crisis and predisposing factors is limited. We registered the clinical phenotype of patients with HC admitted to the emergency department, while those with a hypertensive emergency (HE) were hospitalized. One-year outcomes, i.e., composite of death or cardiovascular hospitalizations, were determined in patients with HE after hospital discharge. Out of 38,589 patients assessed in the emergency department, 256 hypertensive urgencies and 97 HE was registered. After stratification of the HE by sex, 48 men and 46 women completed the one-year follow-up. Men had more events than women (27 vs. 13, Ηazard Ratio 2.2, 95% Confidence Interval 1.03-4.7, p = 0.042) after adjustment for age, cardiovascular or chronic kidney disease, and diabetes mellitus. Our study raises the hypothesis that the male sex is an independent risk factor for cardiovascular outcomes in HE patients. CV Cardiovascular, BP blood pressure. The diagram presents the groups of comparison, men versus women in hypertensive emergencies that completed the 1-year follow-up for outcomes, in terms of hospitalizations or deaths., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The ideal treatment for patent foramen ovale (PFO) in patients with cryptogenic stroke remains controversial and is being evaluated. The objective of this study was to evaluate the net clinical benefit (NCB) between PFO closure and medical treatment., Methods: We searched three electronic databases from inception until January 2022. The primary outcomes were the NCB-1, defined as the cumulative incidence of stroke, major bleeding, atrial fibrillation/flutter, and serious procedural or device complications; the NCB-2 and NCB-3 were defined as NCB1 but using a weighted factor of 0.5 and 0.25 for atrial fibrillation/flutter events, respectively. We also evaluated each component outcome of NCB as a secondary outcome. Risk ratios (RR) and 95% confidence intervals (CI) of each outcome were calculated (random-effects model)., Results: Our analysis included six RCTs (n = 3750 patients). The rates of NCB-1, NCB-2, and NCB-3 were not different between PFO closure and medical treatment. The heterogeneity between trials was low to moderate. Stroke showed a significant relative decrease of 44% (95% CI, 21-60%), favoring the PFO closure arm. Atrial fibrillation/flutter increased by 4.04 times (95% CI, 1.57-8.89) in the PFO closure compared with the medical treatment group. In a meta-regression analysis, the reduction in NCB-1 with PFO closure increased as the proportion of patients treated with the Amplatzer device increased (p = 0.02), and the reduction in NCB-1, NCB-2, and NCB-3 with PFO closure increased as the proportion of patients treated with substantial PFO size increased (p = 0.03)., Conclusion: The NCB between PFO closure and medical treatment was not different, suggesting individualized treatment to maximize benefit., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing rapidly worldwide, affecting 25-30% of the population. Fatty liver index (FLI) is a validated marker of NAFLD and can be used as a screening tool for hepatic steatosis. The purpose of the study was to evaluate the relationship between FLI and the risk of major cardiovascular events in never treated hypertensive patients. We included 903 hypertensive patients without a history of cardiovascular disease (mean age 52.7 ± 11.4 years; men 55%; baseline clinic BP 149.8 ± 15.2/95.5 ± 10.1 mmHg). Participants were prospectively evaluated for a mean follow-up period of 5.2 ± 3.2 years with at least one annual visit. Patients were also categorized into two groups using an FLI of 60 units. The incidence of cardiovascular events during follow-up was 8.5% (n = 77). Patients with FLI < 60 (n = 625) had a better BP control compared to their counterparts with FLI ≥ 60 (n = 278) during follow up (43% vs 33%, p = 0.02). Cox-regression analysis indicated that FLI (Hazard Ratio [HR], 1.05; 95% Confidence Interval [CI], 1.03-1.07, p < 0.001), FLI z-scores (HR, 3.66; 95% CI, 2.22-6.04) and high-risk FLI (HR, 7.5; 95% CI, 3.12-18.04) were independent determinants of the outcome after adjustment for baseline and follow-up variables. Stratification by diabetes mellitus indicated that FLI predicted the outcome to a greater extent in those with than those without diabetes (P-interaction < 0.001). In conclusion, FLI has an independent prognostic value for the incidence of cardiovascular events in newly diagnosed, never-treated hypertensive patients. Therefore, FLI might identify higher-risk patients in the primary prevention of hypertension., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We investigated whether blood pressure (BP) control measures, visit-to-visit BP variability, and time in therapeutic range (TTR) are associated with future cardiovascular outcomes in hypertensive patients., Materials and Methods: Among 1,408 hypertensive patients without cardiovascular disease, we prospectively evaluated the incident major cardiovascular events over 6 years. In newly diagnosed patients, antihypertensive drug treatment was initiated. We estimated two markers of on-treatment BP control, (1) visit-to-visit BPV as the coefficient of variation of office systolic BP (BP-CV), and (2) TTR calculated as the percentage of office systolic BP measurements within 120-140mmHg across visits., Results: The hypertensive cohort (672 males, mean age 60 years, 31% newly diagnosed) had a mean systolic/diastolic BP of 142/87 mmHg. The mean number of visits was 4.9 ± 2.6, while the mean attained systolic/diastolic BP during follow-up was 137/79 mmHg using 2.7 ± 1.1 antihypertensive drugs. The BP-CV and TTR were 9.1 ± 4.1% and 45 ± 29%, respectively, and the incidence of the composite outcome was 8.3% ( n  = 117). After adjustment for relevant confounders and standardization to z-scores, BP-CV and TTR were associated with a 43% (95% CI, 27-62%) increase and a 33% (95% CI, 15-47%) reduction in the outcome. However, the joint evaluation of TTR and BP-CV in a common multivariable model indicated that a standardized change of TTR was associated with the outcome to a greater extent than BP-CV (mean hazard ratios of 30% vs. 24%, respectively). When combined with the higher BP standardized-CV quartile, the lower TTR quartile predicted the outcome by 2.3 times (95% CI, 1.1-5.4) compared to the inverse TTR and BP-CV quartile pattern., Conclusion: High BP-CV or low TTR was associated with future cardiovascular events in a cohort of treated hypertensive patients. As a determinant, the extent of TTR value appears greater than BP-CV when these measures are considered in the same multivariable model.