State of the art approach to managing angina and ischemia: tailoring treatment to the evidence.

Stable angina represents a chronic and often debilitating condition that affects daily activities and quality of life in patients with chronic coronary syndromes (CCS). Current European Society of Cardiology guidelines recommend a four-step approach for the medical treatment of patients taking into consideration hemodynamic variables (heart rate and blood pressure) and the presence or absence of left ventricular dysfunction. However, CCS patients often have several comorbidities and risk factors. Thus, a tailored approach that takes into consideration patient risk factors and comorbidities may have additional benefits beyond angina relief. This is a state of the art review of stable angina treatment based on the currently available evidence.

Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis?

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

The ESC 2019 CCS guidelines: Have we left our patients and scientific evidence behind?

The ESC CCS 2019 guidelines recognize that successful management of anginal symptoms relies on effective therapy tailored to individual patient characteristics but do not provide any specific advice or clarity on how to utilize pharmacotherapy in order to achieve these goals. In this review, we are going to summarize and discuss the main points of disagreement.

Polypill, hypertension and medication adherence: The solution strategy?

INTRODUCTION: Hypertension is an important global health challenge and a leading preventable risk factor for premature death and disability worldwide. In current cardiology practice, the main obstacles in the management of patients affected by hypertension are comorbidities and poor adherence to pharmacological treatments. The World Health Organization has recently highlighted increased adherence as a key development need for reducing cardiovascular disease. METHODS: Principal observational and clinical trial data regarding adherence, reductions in cardiovascular risk and safety of the polypill approach are summarized and reviewed. CONCLUSIONS: The polypill approach has been conclusively shown to increase adherence relative to usual care in all cardiovascular patients, furthermore, concomitant risk factor reductions have also been suggested. To date, the use of polypill could represent a solution strategy in patients affected by hypertension, comorbidities and non-adherence even though further studies, especially in the real-world settings, are needed in order to better understand its role in clinical practice.

Hemoperitoneum in peripartum: A case-series.

Hemorrhages are the first cause of perinatal deaths in French women. Thirteen percent of these deaths are not linked to obstetrical problems but rather to hemoperitoneum. These incidents are under-diagnosed and as a result, treatment is delayed and fetal and maternal mortality increases. We report three cases of patients, all White female in their last trimester of a non-problematic pregnancy presenting with hemoperitoneum and resulting in different outcomes. The analysis of published materials and of our cases leads us to infer that a diagnosis of hemoperitoneum must be considered in pregnant women when abdominal pain, symptoms of shock and a decrease in hemoglobin are associated. An immediate response and intensive care followed by hemostatic surgery give these patients the best chance to survive.

Cardiovascular disease in women, is it different to men? The role of sex hormones.

Cardiovascular disease in women differs in clinical presentation, pathophysiology and prognosis from that in men. The role of estrogens and androgens may help explain such sex dimorphisms, being involved in cardiac function, endothelial function and vascular tone. In particular, the cardioprotective effect of estrogen replacement therapy is observed in postmenopausal women in a time-dependent manner, i.e. when it is initiated at their first menopausal symptoms. Postmenopausal women, beyond aged men, may also benefit from testosterone supplementation therapy. Testosterone has been found to be an effective and safe therapy for elderly women with chronic heart failure. However, further studies are needed to clarify doses and routes of administration of androgens in postmenopausal women.

Gender differences in the effects of cardiovascular drugs.

Although sex-specific differences in cardiovascular medicine are well known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause, and pregnancy) and they present differences in drug pharmacokinetics (absorption, distribution, metabolism, and excretion) and pharmacodynamics, so that is not rare that they may respond differently to cardiovascular drugs. Furthermore, women are also less often treated with evidence-based drugs thereby preventing optimization of therapeutics for women of all ages, experience more relevant adverse drug reactions than men, and remain underrepresented in most clinical trials. Thus, current guidelines for prevention, diagnosis, and medical treatment for cardiovascular diseases are based on trials conducted predominantly in middle-aged men. A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarizes gender differences in the pharmacokinetics and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety.

New and old roles of the peripheral and brain renin-angiotensin-aldosterone system (RAAS): Focus on cardiovascular and neurological diseases.

It is commonly accepted that the renin-angiotensin-aldosterone system (RAAS) is a cardiovascular circulating hormonal system that plays also an important role in the modulation of several patterns in the brain. The pathway of the RAAS can be divided into two classes: the traditional pathway of RAAS, also named classic RAAS, and the non-classic RAAS. Both pathways play a role in both cardiovascular and neurological diseases through a peripheral or central control. In this regard, renewed interest is growing in the last years for the consideration that the brain RAAS could represent a new important therapeutic target to regulate not only the blood pressure via central nervous control, but also neurological diseases. However, the development of compounds able to cross the blood-brain barrier and to act on the brain RAAS is challenging, especially if the metabolic stability and the half-life are taken into consideration. To date, two drug classes (aminopeptidase type A inhibitors and angiotensin IV analogues) acting on the brain RAAS are in development in pre-clinical or clinical stages. In this article, we will present an overview of the biological functions played by peripheral and brain classic and non-classic pathways of the RAAS in several clinical conditions, focusing on the brain RAAS and on the new pharmacological targets of the RAAS.

Androgens and cardiovascular disease in postmenopausal women: a systematic review.

Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within physiological levels is associated with overall well-being. However, a definitive explanation as to how androgens have an impact on cardiovascular health in postmenopausal women and whether they may be used for cardiovascular treatment has yet to be established. With these aims, a systematic review of the existing studies on the link between androgens and cardiovascular disease and the effects of testosterone therapy on cardiovascular outcomes in postmenopausal women has been conducted. The few existing studies on cardiovascular outcomes in postmenopausal women indicate no effect or a deleterious effect of increasing androgens and increased cardiovascular risk. However, there is evidence of a favorable effect of androgens on surrogate cardiovascular markers in postmenopausal women, such as high density lipoprotein cholesterol, total cholesterol, body fat mass and triglycerides. Further studies are therefore needed to clarify the impact of therapy with androgens on cardiovascular health in postmenopausal women. The cardiovascular effect of testosterone or methyltestosterone with or without concomitant estrogens needs to be elucidated.

Changes in serum uric acid levels and cardiovascular events: a meta-analysis.

BACKGROUND AND AIMS: The association between serum uric acid (SUA) levels and cardiovascular (CV) risk or all-cause death has been repeatedly reported. However, it has not been assessed whether reduction of SUA levels is associated with reduced CV risk. The aim of the current study was to evaluate the relationship between changes of SUA levels and CV events as well as all-cause death. METHODS AND RESULTS: Randomised trials reporting SUA at baseline and at the end of follow-up and clinical end-points (all-cause death, myocardial infarction (MI), stroke, heart failure (HF) and CV death) were included in the study. Meta-regression analysis was performed to test the relationship between SUA changes and clinical end-points. Eleven trials enrolling 21,373 participants followed up for 2.02 ± 1.76 years and reporting 4533 events were included. In meta-regression analysis, no relationship between SUA changes from baseline to end of follow-up and the composite outcome including CV death, stroke, MI and HF was found (change in Tau(2) (t) = -0.64; p Tau (p) = 0.541). Similarly, no relationship was found between SUA changes and single components of the composite outcome (MI: t = -0.83; p = 0.493; stroke: t = 0.46; p = 0.667; HF: t = 2.44; p = 0.162; CV death: t = -0.54; p = 0.614) and all-cause death (t = -0.72; p = 0.496). Results were confirmed by sensitivity analysis. No heterogeneity among studies or publication bias was detected. CONCLUSIONS: Changes in SUA levels observed during pharmacologic treatments do not predict the risk of all-cause death or CV events. As SUA levels are associated with increased CV risk, additional studies with direct xanthine-oxidase inhibitors are requested.

Cardiovascular health in the menopausal woman: impact of the timing of hormone replacement therapy.

The cardiovascular effects of hormone replacement therapy (HRT) have been the subject of much debate since the initial findings from the Women's Health Initiative (WHI) were reported. However, re-analyses of WHI results have suggested that the association between HRT use and cardiovascular risk is influenced by several factors and that, among these, age and time since menopause may play a key role. Preclinical and human studies have shown differential effects of estrogen on the vasculature of healthy subjects compared with those with existing atherosclerosis. Indeed, while HRT has shown no protective effects in the presence of established atherosclerotic disease, it may have beneficial or neutral effects on healthy vasculature or early atherosclerosis. However, the final cardiovascular effects of estrogens in non-hysterectomized women are influenced by the type, dosage, and route of administration of the progestin used in association. The results of ongoing studies on the timing of HRT initiation will help women make better informed decisions regarding their menopausal health. Current treatment guidelines recommend initiation of HRT in recently postmenopausal women for the relief of vasomotor symptoms.

[Maxillary sinus septa. Prevalence and anatomy]. / Les septums du sinus maxillaire. Prévalence et anatomie au travers d'une revue de la littérature de 1980 à 2009.

BACKGROUND: Maxillary sinus septa may complicate sinus elevation procedures, especially when they are not diagnosed prior to surgery. The authors had for aim to review published data, to analyze the etiology, the prevalence, the localization, and the size of maxillary sinus septa, and to determine what were the best preoperative radiological examinations. PATIENTS AND METHODS: The Medline search was made with keywords such as "maxillary sinus anatomy, maxillary sinus augmentation, maxillary sinus septa, sinus graft/complications, dental implants". The search was limited to studies published in English from 1980 to January 2009. RESULTS: Twenty-two articles were analyzed. The prevalence of maxillary sinus septa ranged between 14.3% and 33.3%. There was no specific geographic distribution within the sinuses. The mean heights of septa ranged between 2.8 and 8.1 mm. DISCUSSION: It is recommended to systematically use preoperative CT or CBCT scan imaging because of the prevalence, the variable anatomy, and the bad contribution of conventional X-rays.

Morphological features of the maxillary incisors roots and relationship with neighbouring anatomical structures: possible implications in endodontic surgery.

The purpose of this study was to investigate the relationship between the root apex of the upper incisors and neighbouring anatomical structures as well as the morphology of the root-end foramen after apicoectomy. Fifty-seven patients requiring endodontic surgical treatment for a maxillary anterior root were enrolled. A preoperative diagnostic computed tomography (CT) scan was analysed to determine: the distance between the anterior wall of the nasopalatine duct and the central (CI-ND) incisor root 4mm from the apex; and the distance between the floor of the nasal cavity and the tip of either the central (CI-NF) or the lateral (LI-NF) incisor root. After apicoectomy, root-end foramen endoscopic pictures were taken in order to characterize their morphology. Fifty-nine central and 26 lateral incisors were evaluated. The average CI-ND was 4.71 ± 1.26 (SD) mm. The average CI-NF was 10.62 ± 2.25 mm. The average LI-NF was 13.05 ± 2.43 mm. The foramen shape after apicoectomy was ovoid to circular in about 90% of cases in both central and lateral incisors. A sound knowledge of the anatomical relationships at the surgical site is essential for the clinician to perform a safe endodontic surgical procedure.

Effects of testosterone on the Q-T interval in older men and older women with chronic heart failure.

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<0.002) and Q-Tc intervals decreased from 398±26 to 392±27 (p<0.006) in men on testosterone. In women, Q-T intervals decreased from 400±25 to 397±23ms (p=0.06) and Q-Tc intervals from 415±26 to 409±27ms (p=0.3) on testosterone. Q-T intervals were longer in women compared with men under all conditions (p<0.03). The data support a direct effect of testosterone to shorten Q-T intervals in older men and older women in the absence of HR changes or hypogonadal status. Mean decreases are small and unlikely to affect risks of arrhythmic events in patients receiving Q-T prolonging medications.