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Aims To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum. Methods and results The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson’s disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4). Of the AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC, and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs. Anaemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson, and depression were more prevalent in HF with preserved EF (HFpEF). The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anaemia 1.6 (1.4–1.8), diabetes 1.2 (1.1–1.4), kidney dysfunction 1.7 (1.5–1.9), COPD 1.4 (1.2–1.5), PVD 1.2 (1.1–1.4), stroke/TIA 1.3 (1.1–1.5), depression 1.2 (1.0–1.5), hepatic dysfunction 2.1 (1.8–2.5), malignancy 1.5 (1.2–1.8), sleep apnoea 1.2 (0.9–1.7), rheumatoid arthritis 1.5 (1.1–2.1), and Parkinson 1.4 (0.9–2.1). Anaemia, kidney dysfunction, COPD, and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA, and depression only in HF with reduced EF, and sleep apnoea and malignancy only in HFpEF. Conclusion Multiple NCCs conferred poor in-hospital and post-discharge outcomes. Ejection fraction categories had different prevalence and risk profile associated with individual NCCs.

Heart Failure (HF) is a multi-faceted and life-threatening syndrome characterized by significant morbidity and mortality, poor functional capacity and quality of life, and high costs. HF affects more than 64 million people worldwide. Therefore, attempts to decrease its social and economic burden have become a major global public health priority. While the incidence of HF has stabilized and seems to be declining in industrialized countries, the prevalence is increasing due to the ageing of the population, improved treatment of and survival with ischaemic heart disease, and the availability of effective evidence-based therapies prolonging life in patients with HF. There are geographical variations in HF epidemiology. There is substantial lack of data from developing countries, where HF exhibits different features compared with that observed in the Western world. In this review, we provide a contemporary overview on the global burden of HF, providing updated estimates on prevalence, incidence, outcomes, and costs worldwide.

Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online.

Aims Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. Methods and results Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. ‘Incident severe COVID-19’ was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19. Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. Conclusion SGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.

Large randomized controlled trials (RCTs) have led to major changes in the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) and these advances are included in the recent European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines issued in 2021 and 2022, respectively. According to both guidelines, treatment of patients with HFrEF is based on the administration of four classes of drugs that reduce the primary endpoint of cardiovascular death and HF hospitalizations in RCTs: angiotensin-converting enzyme or angiotensin receptor neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors. Specific sequences of treatment are not recommended but emphasis is given to reaching treatment with all four drugs as early as possible. Further treatments are considered in selected patients including ivabradine, hydralazine nitrates, digoxin, and the new agent vericiguat. Specific treatments, mostly new, for cardiovascular and non-cardiovascular comorbidities are also given. The aim of this article is to compare the two recent guidelines issued by the ESC and ACC/AHA/HFSA and show the few differences and the many consistent recommendations, now more numerous given the evidence available for many new treatments.

Patients discharged after an episode of acute heart failure have an increased risk of hospitalizations and deaths within the subsequent 3 months. This phase is commonly called the 'vulnerable period' and it represents a window of opportunity of intervention in order to improve longer term outcomes. Prompt identification of signs of residual haemodynamic congestion is a priority in planning for the out-of-hospital management strategies. Patients will also need to be screened for frailty and have a prioritization of the management of their comorbidities. Life-saving medications should be started together or in a short time and up-titrated (when needed) according to blood pressure, heart rate and concomitant comorbidities. Ideally, patients should be assessed by their general practitioner within 1 week of discharge and have a hospital/clinic follow-up within 4 weeks of discharge. Patients should progressively resume physical activities and adhere to an educational programme with appropriate lifestyle adjustments best implemented during a cardiac rehabilitation programme.

Cardiovascular diabetology 21, 50 (2022). doi:10.1186/s12933-022-01481-0, Published by BioMed Central, London

To estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF)

Acute and chronic hyperkalemia (HK) is a frequent occurrence in patients with heart failure resulting from decreased renal function, dysfunctional homoeostatic mechanisms and the effect of cardiovascular drugs. Drugs such as renin-angiotensin-aldosterone system inhibitors (RAASi), angiotensin receptor-neprilysin inhibitor and beta-blockers can cause drug-induced HK by interfering with potassium excretion. Up until now therapies for acute and chronic HK have been limited to drugs that can be used in the acute and sub-acute phase. However, new therapeutic options for the acute and chronic therapy of HK have become available in recent years. Patiromer and sodium zirconium cyclosilicate are effective for both the acute and long-term treatment of HK in patients with cardio-renal syndrome and in those with heart failure. These medicines significantly reduce serum potassium in patients with HK on RAASi and enable the use and up-titration of RAASi in patients who are not optimally treated.

Medications with proven benefit in patients with heart failure with reduced ejection fraction are recommended, according to prospective large clinical trials, in the stable patient after careful up-titration in a strict sequential order. Although the relevance of careful clinical up-titration is unproven, there is evidence that after recompensation and shortly after hospital discharge, the rate of cardiovascular death and hospitalization is high. Clinical studies provided evidence that the onset of treatment effects is rapid, occurring within 28 days with most of these drugs used, and in some trials, early treatment after discharge or already started in the hospital has provided benefits. Therefore, early treatment without deferring it to the stable outpatient may be useful to reduce cardiac-related events further. This expert opinion proposes treatment layering according to individual patient phenotypes involving heart rate, blood pressure, impaired renal function, and electrolyte disturbances, as well as dedicated subgroups of patients with specific requirements for treatment initiation. This complements other approaches that suggest starting sequential treatment according to the size of treatment effects of drugs, specific cardiac diseases, and patient wishes. Patient phenotyping may guide personalized drug layering in heart failure with reduced ejection fraction that provides the best outcomes, whereas pragmatic clinical trials are warranted to scrutinize the effectiveness of these approaches.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB. © 2021 Elsevier Inc. and Journal of Cardiac Failure. [Published by Elsevier Inc.] All rights reserved.

Impaired glucose metabolism and diabetes are both very common in HF, and associated with worse functional status and prognosis. More lenient rather than strict glycaemic control is advised in patients with HF. In patients with diabetes and HF glycaemic control should be implemented gradually and moderately, giving preference to those drugs that have been shown to be safe and effective. SGLT2 inhibitors improve CV outcomes and reduce the risk of hospitalisations for heart failure, and are as a result the preferred glucose-lowering agents in T2DM patients at risk for, or with, established HF. Metformin is considered safe in HF with diabetes and is a preferred agent for glycaemic control in this setting. Sulfonylurea treatment seems to be associated with a higher risk of HF hospitalisation and is not indicated in patients with heart failure. GLP-1 receptor agonists have been proven to reduce macrovascular end points in patients with type II diabetes, however, they seem at most ineffective in patients with HF with reduced ejection fraction, and are not therefore the preferred agents in this patient population. DPP-4 inhibitors (gliptins) have only a limited effect on glucose control and no benefit on cardiovascular events and therefore do have compelling arguments for use in HF patients with type 2 diabetes.

The role and adverse effects of mineralocorticoid receptor overactivation in the pathophysiology of heart failure (HF) is wellrecognised. MR antagonists (MRAs) have been tested in HF and shown to be effective in improving outcomes. Steroid-type MRAs spironolactone and eplerenone, have been proven to reduce mortality in HFrEF. In patients with HFpEF, the TOPCAT trial found no significant benefits of spironolactone on cardiovascular outcomes. In order to overcome the limitations of existing steroidal MRAs, novel MRAs have been recently developed, finerenone and PF-03882845. These newer agents aim to optimise the benefits of MRAs and reduce their side-effects, especially hyperkalaemia.

Heart failure is associated with altered cardiac metabolism, in part, due to maladaptive mechanisms, in part secondary to comorbidities such as diabetes and ischaemic heart disease. The metabolic derangements taking place in heart failure are not limited to the cardiac myocytes, but extend to skeletal muscles and the vasculature causing changes that contribute to the worsening of exercise capacity. Modulation of cardiac metabolism with partial inhibition of free fatty acid oxidation has been shown to be beneficial in patients with heart failure. At the present, the bulk of evidence for this class of drugs comes from Trimetazidine. Newer compounds partially inhibiting free fatty acid oxidation or facilitating the electron transport on the mitochondrial cristae are in early phase of their clinical development.

This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.

In older adults without neurological diseases, walking limitations have been linked to age-related declines in both cerebral and peripheral systems. There is an urgent need to identify factors that can help compensate for these age-related multi-system declines, as there are currently no effective treatments available to reduce walking limitations in older age. Although effective mobility is the end result of the functional capacity of both central and peripheral systems, some adults appear resilient to these impairments in these systems and maintain higher mobility. We consistently observe up to 20% of older adults maintain fast walking speed in the presence of age-related cerebral small vessel disease and peripheral system impairments. In this symposium, we explore the potential neurobiological drivers of such apparent mobility resilience. We present data from different longitudinal epidemiological cohort studies of older age, including: Health Aging Body Composition Study, Mon-Yough Healthy Aging Team and the Central Control of Mobility in Aging. The studies presented here rely on multi-modal assessment of brain integrity, ranging from state of the art neurocognitive assessments to cutting-edge structural, functional, and molecular neuroimaging. Our results uncover distinct patterns of greater cortico-subcortical brain integrity as potential drivers of mobility resilience in older adults. The brain’s unique modulatory and adaptive capacity may provide clues for novel interventions to promote mobility and/or delay the onset of physical disability.

Heart failure (HF) is associated with metabolic changes that cause a progressive impairment of cardiac and skeletal muscle high-energy phosphate production. As a consequence of the impaired cardiac metabolism, other processes are activated in the failing heart that further exacerbate the progression of HF. The reduced production of high-energy phosphates has important implications for both systole and diastole in HF with both preserved and reduced left ventricular function. The aim of this review is to summarise the state-of-the-art on metabolic therapy in HF with a particular focus on trimetazidine. Metabolic agents optimise cardiac substrate metabolism without exerting negative haemodynamic effects. In particular, as studies with metabolic agents modulating cardiac metabolism have consistently demonstrated, this approach is effective in improving symptoms, functional capacity and prognosis in people with HF when added to optimal medical therapy. Therefore, the modulation of cardiac metabolism is an important therapeutic approach to the treatment of HF, especially in patients where it is of ischaemic or metabolic origin. Although further studies are needed, metabolic agents might be a new, effective strategy for the treatment of HF.

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF), but are underutilized. Hyperkalaemia may be one reason, but the underlying reasons for underuse are unknown. The aim of this study was to investigate the independent predictors of MRA underuse in a large and unselected HFrEF cohort.We included patients with HFrEF (ejection fraction40%), New York Heart Association (NYHA) class II-IV and heart failure (HF) duration ≥6 months from the Swedish HF Registry. Logistic regression analysis identified independent associations between 39 demographic, clinical, co-treatment, and socioeconomic predictors and MRA non-use. Of 11 215 patients, 27% were women; mean age was 75 ± 11 years; only 4443 (40%) patients received MRA. Selected characteristics independently associated with MRA non-use were in descending order of magnitude: lower creatinine clearance (60 mL/min), no need for diuretics, no cardiac resynchronization therapy/implantable cardioverter-defibrillator, higher blood pressure, no digoxin use, higher ejection fraction, outpatient setting, older age, lower income, ischaemic heart disease, male sex, follow-up in primary vs. specialty care, lower NYHA class, and absence of hypertension diagnosis. Plasma potassium and N-terminal pro B-type natriuretic peptide levels were not associated with MRA non-use.Mineralocorticoid receptor antagonists remain underused in HFrEF. Their use does not decrease with elevated potassium but does with impaired renal function, even in the creatinine clearance 30-59.9 mL/min range where MRAs are not contraindicated. MRA underuse may be further related to non-specialist care, milder HF and no use of other HF therapy.

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure.

Patients with diabetes mellitus have an increased risk of developing heart failure and diabetes mellitus is highly prevalent amongst patients with heart failure, especially those with HFpEF. Diabetic patients with heart failure have an increased mortality and an increased risk of hospitalisations and the use of certain anti- diabetic agents increase the risk of mortality and hospitalisation in heart failure. Conversely, newer therapeutic agents have shown a significant reduction of mortality, morbidity and risk of developing heart failure in diabetic patients with proven cardiovascular disease. This highly important area is reviewed in this paper.

This work examines associations of brain grey matter volumes (GMV) with physical and mental fatigability in older adults from a subsample (n=29; age=77.2 ± 5.5; 86% female) of LIFE Study participants. GMV for a priori identified brain regions were normalized to intracranial volume. Physical and mental fatigability were measured using the Pittsburgh Fatigability Scale and higher (HF) or lower (LF) fatigability were defined using established cut-points (Range: 0–50; HF physical:≥15 (65.5%); HF mental:≥13 (65.5%). We used an exploratory alpha level of p

Ahmad Haider,1 Aksam Yassin,2-4 Karim Sultan Haider,1 Gheorghe Doros,5 Farid Saad,4,6 Giuseppe MC Rosano7 1Private Urology Practice, Bremerhaven, 2Institute for Urology and Andrology, Segeberger Kliniken, Norderstedt, 3Department of Preventive Medicine, Men’s Health Program, Dresden International University, Dresden, Germany; 4Department of Urology, Gulf Medical University, Ajman, United Arab Emirates; 5Department for Epidemiology and Statistics, Boston University School of Public Health, Boston, MA, USA; 6Global Medical Affairs Andrology, Bayer Pharma AG, Berlin, Germany; 7Department of Cardiology, Centre for Clinical and Basic Science, San Raffaele-Roma, Rome, Italy Background/objectives: Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8years in hypogonadal men with a history of cardiovascular disease (CVD).Patients and methods: In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD. The effects of TTh on anthropometric and metabolic parameters were investigated for a maximum duration of 8years. Any occurrence of major adverse cardiovascular events was reported. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals.Results: In 77 hypogonadal men with a history of CVD who received TTh, we observed a significant weight loss and a decrease in waist circumference and body mass index. Mean weight decreased from 114±13kg to 91±9kg, change from baseline: −24±1kg and –20.2%±0.5%. Waist circumference decreased from 112±8cm to 99±6cm, change from baseline: −13±0.3cm. Body mass index decreased from 37±4 to 29±3, change from baseline: −8±0.2kg/m2. Cardiometabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure all improved significantly and sustainably. No patient suffered a major adverse cardiovascular event during the full observation time.Conclusion: In men with hypogonadism, TTh appears to be effective in achieving sustained improvements in all cardiometabolic risk factors and may be effective as an add-on measure in the secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. Keywords: testosterone, long-term testosterone therapy, cardiovascular risk, hypogonadism, secondary prevention

This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis.AF is quite prevalent in patients with HF.Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included. Each patient was defined as affected by HF according to the criteria of the trial in which the patient was enrolled. Pre-specified outcomes were the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular (CV) and all-cause death.A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and 28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin (median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE (relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68) and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95% CI: 0.81 to 0.91; p 0.01) and intracranial (RR: 0.74 95% CI: 0.63 to 0.88; p 0.01) bleeding but increased rates of all-cause (RR: 1.70 95% CI: 1.31 to 2.19; p 0.01) and CV death (RR: 2.05 95% CI: 1.66 to 2.55; p 0.01). NOACs, compared with warfarin significantly reduced SSE and major, intracranial, and any bleeding, regardless of the presence or absence of HF (pPatients with AF and HF had increased mortality but reduced rates of intracranial and any bleeding compared with the no-HF patients, with no differences in rates of SSE and major bleeding. NOACs significantly reduced SSE, major bleeding, and intracranial hemorrhage in HF patients. No interactions in efficacy and safety of NOACs were observed between AF patients with and without HF.

The Q-Tc interval duration on the electrocardiogram is recognized to differ between the sexes. In vitro data and data from humans before and after puberty and menopause suggest that sex hormones play a role in the longer Q-Tc intervals in women, or conversely, the shorter Q-Tc intervals in men. Direct investigations of sex hormone effects on the Q-Tc interval in humans, however, are limited and reach conflicting conclusions. Our objective was to determine effects of testosterone on ECG Q-T intervals of older men and older women. ECG's from 84 older men and older women in double-blind placebo-controlled investigations of testosterone supplementation for the treatment of chronic heart failure (CHF) were analysed. Thirty men received 1000mg intramuscular long-acting testosterone undecanoate and 28 men received saline at 0, 6 and 12weeks. ECG's were recorded at baseline and 12weeks. Sixteen women received transdermal testosterone (33μg) and 10 women received matching placebo twice weekly for 24 weeks with ECG's at baseline and after 24weeks. Testosterone, but not placebo, shortened Q-T and Q-Tc intervals without heart rate changes. Q-T intervals decreased from 385±28 (mean±SD) to 382±28 ms (p

Although antianginal drugs are used over several months and through to years in stable angina, there is scant evidence regarding their influence on outcomes. The METRO (ManagEment of angina: a reTRospective cOhort) study sought to assess the independent effect of using these drugs on subsequent mortality risk in patients with stable angina.Consecutive patients with stable angina, receiving at least one antianginal drug (nitrates, beta-adrenoceptor antagonists, calcium channel antagonists, trimetazidine, or nicorandil), were selected if they were discharged alive from an intensive care unit following a myocardial infarction (MI). Their case-record data were used in a multivariate logistic regression model to examine the independent association of antianginal drug use prior to the MI with predicted post-discharge, 6-month, all-cause mortality risk.In 353 patients, of whom 287 (81.3%) were men, the mean (+/- SD) age was 55 (+/- 10.2) years and duration of treated stable angina was 27.2 (+/- 24.8) months. The odds ratios (95% CI) of 6-month, all-cause mortality after surviving an MI were: for treatment that included a beta-adrenoceptor antagonist, 0.63 (0.26, 1.52; p = 0.309); a calcium channel antagonist, 0.76 (0.12, 2.89; p = 0.638); a nitrate, 0.52 (0.26, 1.05; p = 0.070); nicorandil, 0.62 (0.29, 1.33; p = 0.221); and trimetazidine, 0.36 (0.15, 0.86; p = 0.022).The inclusion of trimetazidine in the antianginal treatment of stable angina is independently associated with a significant reduction in mortality after surviving an MI. This suggests that combining a metabolic agent with drugs that modulate oxygen supply and demand, early in the management of stable angina, may confer a survival benefit.

The diversity of bacterial communities of shallow (< or = 100 m depth) oil seep marine sediments from the southern Gulf of Mexico was evaluated. The geochemical properties of seep sediments were characterized as well as their microbial diversity in oil seep and control sediments. Bacteria were identified through molecular tools as belonging to the genera Marinobacter, Idiomarina, Marinobacterium, Frauteria and an unknown bacterium. Bacteria might be important components of microbial communities in Total Petroleum Hydrocarbon (TPH)-containing environments, displaying either facultative metabolism or able to grow only in petroleum-containing media. The identification of bacteria in shallow oil seep sediments could be used as indicators of marine hydrocarbons in southeastern Gulf of Mexico.

Objective Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). Methods In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. Results After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 ± 0.5 to 12.5 ± 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. Conclusions In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition. Diabet. Med. 25, 37–44 (2008)

Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P=0.0001), and improvements were maintained from 2 weeks after discontinuation (P

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P

Background: Elevated C-reactive protein (CRP) levels due to of heightened vascular inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels since during inflammation CRP production in the liver is induced by IL-6. It has been suggested that CRP may be a predictors of unfavourable outcome in postmenopausal women (PMW) receiving hormone replacement therapy. Because of the possible metabolic effect of hormone replacement therapy (HRT) on CRP, the relative predictive importance of CRP and IL-6 levels in PMW receiving HRT remains to be elucidated. Methods: We measured plasma levels of CRP and IL-6 levels in 346 consecutive PMW (mean age 66±9 years) with cardiovascular risk >20 in 10 years followed during a 36 month period. Women underwent measurement of inflammatory cytokines at baseline and were allocated to two groups according to the willingness to take hormone replacement therapy. All women underwent a further measurement of CRP and IL-6 at 3 and 6 months. Health status was assessed by out patient visits and hospital charts. Results: During 1 year follow up, three patient died, four had a major cardiovascular event, three had a unstable angina, two had a transient ischemic attack and two patients underwent PTCA. PMW with events had higher CRP levels compared with patients with no events (1.94±0.61 versus 1.43±0.21, P

Frailty is a complex clinical syndrome associated with ageing and chronic illness, resulting from multiple organ impairment; physiological reserves decrease and vulnerability to stressors increase. The role of frailty in cardiovascular disease has become increasingly recognised. Up to 79% of patients with heart failure are frail. Moreover, frailty is associated with a worse quality of life and poor prognosis. This review summarises the available literature on frailty in HF and highlights indications for its management.

Heart failure (HF) is characterised by exercise intolerance, which substantially impairs quality of life (QOL) and prognosis. The aim of this review is to summarise the state of the art on pharmacological interventions that are able to improve exercise capacity in HF. Ivabradine, trimetazidine and intravenous iron are the only drugs included in the European Society of Cardiology HF guidelines that have consistently been shown to positively affect functional capacity in HF. The beneficial effects on HF symptoms, physical performance and QOL using these pharmacological approaches are described.

Desde 1987 a 2000 se ha reportado gran mortalidad (>70%) de tortugas marinas del género Lepidochelys en la playa La Escobilla, en Oaxaca, México. Aunque la causa de tal mortalidad se debe a factores diversos, algunos autores la atribuyen mayormente a la depredación de embriones y crías que hace un escarabajo de la familia Trogidae. La revisión taxonómica confirmó que el escarabajo presente en La Escobilla es Omorgus suberosus Fabricius. Este escarabajo habita también otras playas de anidación de tortugas marinas del Pacífico, pero no del Atlántico. El presente trabajo, basado en la revisión y síntesis de la literatura publicada sobre el tema, describe la interacción Omorgus-tortugas marinas (Lepidochelys) y cuestiona el papel depredador de O. suberosus. No se encontró evidencia suficiente de que Omorgus sea un depredador especialista en embriones de tortugas marinas; por el contrario, parece ser un necrófago- saprófago facultativo muy eficiente en la remoción de materiales orgánicos en playas de anidación de tortugas marinas.

Background: Various strategies have been proposed to improve diagnosis and triage of patients with chest pain at low risk, but uncertainty still exists on the optimal combination of diagnostic tools that should be used in this subset of patients. Hypothesis: The aim of this study was to evaluate the incremental benefit of continuous 12-lead ST-segment monitoring over that provided by conventional diagnostic tools in patients with chest pain. Methods: Of 232 consecutive patients referred because of chest pain, 52 were classified as low-risk according to the Agency for Health Care Policy and Research unstable angina guidelines and observed for 12 h with serial cardiac enzymes and electrocardiograms (ECG) (every 3 h). All patients also underwent both echocardiography at entry and continuous 12-lead ST-segment monitoring during the observation period. Results: During a mean hospital stay of 3.7 days (range 1-14 days), a benign outcome was observed in 37 patients (71%), whereas 15 patients (29%) had major cardiac events or recurrence of chest pain of ischemic origin. Addition of ST-segment monitoring findings to baseline clinical data as well as to serial enzymes and ECG features added significant incremental prognostic value (p < 0.001). Multivariate analysis showed reproduction of pain by chest pressure (p < 0.05) and presence of ST-segment changes (≥ 0.1 mV) during 12-lead ST-segment monitoring (p < 0.001) as independent predictors of a benign or unfavorable outcome. Conclusions: In low-risk patients with chest pain, continuous 12-lead ST-segment monitoring provides significant incremental diagnostic and prognostic information to currently used clinical, enzymatic, and ECG data, and is helpful in identifying the subset of patients with a worse in-hospital outcome.