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The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Preventive Cardiology following peer review. The version of record Kavousi, Pisinger, Barthelemy, Smedt, Koskinas, Marques-Vidal, Panagiotakos, Prescott, Tiberi, Vassiliou, Løchen. Electronic cigarettes and health with special focus on cardiovascular effects: position paper of the European Association of Preventive Cardiology (EAPC). European Journal of Preventive Cardiology (EJPC). 2020:2047487320941993, is available online at: https://doi.org/10.1177/2047487320941993. Background - Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless. Discussion - The rapid evolution of the e-cigarette market has outpaced the legislator’s regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence. Conclusion - This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented.

This ESH Position Paper 2021 with updated proposed recommendations was deemed necessary after the publication of a set of new pivotal sham-controlled randomized clinical trials (RCTs), which provided important information about the efficacy and safety of endovascular device-based renal denervation (RDN) for hypertension treatment. RDN is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity. Five independent, fully completed, sham-controlled RCTs provide conclusive evidence that RDN lowers ambulatory and office blood pressure (BP) to a significantly greater extent than sham treatment. BP-lowering efficacy is evident both in patients with and without concomitant antihypertensive medication. The average decrease of 10mmHg in office BP is estimated to lower the incidence of cardiovascular events by 25-30%, based on meta-analyses of RCTs using pharmacological treatment. Neither peri-procedural, nor short-term or long-term adverse events or safety signals (available up to 3 years) have been observed. Implementing RDN as an innovative third option in the armamentarium of antihypertensive treatment requires a structured process that ensures the appropriate performance of the endovascular RDN procedure and adequate selection of hypertensive patients. The latter should also incorporate patients' perspective and preference that needs to be respected in a shared decision-making process.

Accurate office blood pressure measurement remains crucial in the diagnosis and management of hypertension worldwide, including Latin America (LA). Office blood pressure (OBP) measurement is still the leading technique in LA for screening and diagnosis of hypertension, monitoring of treatment, and long‐term follow‐up. Despite this, due to the increasing awareness of the limitations affecting OBP and to the accumulating evidence on the importance of ambulatory BP monitoring (ABPM), as a complement of OBP in the clinical approach to the hypertensive patient, a progressively greater attention has been paid worldwide to the information on daytime and nighttime BP patterns offered by 24‐h ABPM in the diagnostic, prognostic, and therapeutic management of hypertension. In LA countries, most of the Scientific Societies of Hypertension and/or Cardiology have issued guidelines for hypertension care, and most of them include a special section on ABPM. Also, full guidelines on ABPM are available. However, despite the available evidence on the advantages of ABPM for the diagnosis and management of hypertension in LA, availability of ABPM is often restricted to cities with large population, and access to this technology by lower‐income patients is sometimes limited by its excessive cost. The authors hope that this document might stimulate health authorities in each LA Country, as well as in other countries in the world, to regulate ABPM access and to widen the range of patients able to access the benefits of this technique.

[Abstract] The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described.

This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Preventive Cardiology following peer review. The version of record Piepoli, M.F., Abreu, A., Albus, C., Ambrosetti, M., Brotons, C., Catapano, A.L. ... Tiberi, M. (2020). Update on cardiovascular prevention in clinical practice: A position paper of the European Association of Preventive Cardiology of the European Society of Cardiology*. European Journal of Preventive Cardiology (EJPC), 27(2), 181-205 is available online at: https://doi.org/10.1177/2047487319893035. European guidelines on cardiovascular prevention in clinical practice were first published in 1994 and have been regularly updated, most recently in 2016, by the Sixth European Joint Task Force. Given the amount of new information that has become available since then, components from the task force and experts from the European Association of Preventive Cardiology of the European Society of Cardiology were invited to provide a summary and critical review of the most important new studies and evidence since the latest guidelines were published. The structure of the document follows that of the previous document and has six parts: Introduction (epidemiology and cost effectiveness); Cardiovascular risk; How to intervene at the population level; How to intervene at the individual level; Disease-specific interventions; and Settings: where to intervene? In fact, in keeping with the guidelines, greater emphasis has been put on a population-based approach and on disease-specific interventions, avoiding re-interpretation of information already and previously considered. Finally, the presence of several gaps in the knowledge is highlighted.

Children are defined as hypertensive when their blood pressure values equal or exceed the 95th percentile of the blood pressure value distribution in a pediatric population, according to gender, age and height. The population on which reference tables are based is of fundamental importance to establish the threshold values for the diagnosis of hypertension in pediatric age. Before 2017, both American and European guidelines used nomograms created in the same reference population which included children of all weight classes. Given the close and well-known association between hypertension and excess weight in childhood, the 2017 American guidelines proposed new reference nomograms excluding subjects with overweight and obesity from the “historical” reference population. Furthermore, the new American guidelines suggested a fixed cut-off of 130/80mmHg, starting from 13years and regardless of gender and height, to make the diagnosis of hypertension. In this document, the Italian Hypertension Society (SIIA) and the Italian Pediatric Society (SIP) jointly discuss a number of issues raised by the new American guidelines that involve the entire medical community, and also address the definition of arterial hypertension in the transition phase between childhood and adulthood.

Out-of-office blood pressure (BP) monitoring appears to be a very useful approach to hypertension management insofar it allows to obtain multiple measurements in the usual environment of each individual, allows the detection of hypertension phenotypes, such as white-coat and masked hypertension, and appears to have superior prognostic value than the conventional office BP measurements. Out-of-office BP can be obtained through either home or ambulatory monitoring, which provide complementary and not identical information. Home BP monitoring yields BP values self-measured in subjects' usual living environment; it is an essential method for the evaluation of almost all untreated and treated subjects with suspected or diagnosed hypertension, best if combined with telemonitoring facilities, also allowing long-term monitoring. There is also increasing evidence that home BP monitoring improves long-term hypertension control rates by improving patients' adherence to prescribed treatment. In Latin American Countries, it is widely available, being relatively inexpensive, and well accepted by patients. Current US, Canadian, Japanese, and European guidelines recommend out-of-office BP monitoring to confirm and refine the diagnosis of hypertension.

Introduction: Heterogenous sexual intercourse often produces a powerful orgasm that stimulates the pituitary function. Studies have suggested ejaculation frequency based on age. Materials and Methods: Semi-structured questionnaires were used to collect information from subjects. Semen samples were collected from sperm donors and sub-fertile men who presented for infertility challenges. Processing and analysis of semen samples were done according to World Health Organization (WHO) guidelines. Sperm deoxyribonucleic acid (DNA) fragmentation was evaluated using the Halosperm kit. Results: Among sperm donors, those aged χ2 = 0.09, P-value = 0.81, OR = 3.2, 95% CI: 0.23, 45.19) while among sub-fertile men those aged ≥40 years were approximately 2.3 times more likely to have very low frequency of MESI compared to aged χ2 = 2.11, P-value = 0.51, OR = 2.27, 95% CI: 0.74, 9.92). The frequency of all categories of MESI was highest among sub-fertile men aged χ2 = 0.03, P-value = 0.57, OR = 2.42, 95% CI: 0.41, 14.46). Sub-fertile men aged ≥40 with diastolic hypertension (≥90 mmHg) were approximately 6 times more likely to have a low (6 - 10) frequency of MESI compared to those aged χ2 = 1.97, P-value = 0.16, OR = 6.22, 95% CI: 0.69, 55.77). Overall mean fertilization rate was significantly higher (t-test = 2.44, P-value = 0.01) among sub-fertile men aged

Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause for heart failure is identified. Outcome varies from full recovery to residual left ventricular systolic dysfunction and even death. Many women return to their physician to acquire information on their long- term prognosis, to seek medical advice regarding contraception, or when planning a subsequent pregnancy. This position paper summarizes current evidence for long-term outcome, risk stratification of further pregnancies and overall management. Based on the best available evidence, as well as the clinical experience of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy members, a consensus on pre- and postpartum management algorithms for women undergoing a subsequent pregnancy is presented.

Atrial fibrillation (AF) is an important and highly prevalent arrhythmia, which is associated with significantly increased morbidity and mortality, including a four- to five-fold increased risk for stroke,1,2 a two-fold increased risk for dementia,3,4 a three-fold risk for heart failure,2 a two-fold increased risk for myocardial infarction,5,6 and a 40–90% increased risk for overall mortality.2,7 The constantly increasing number of AF patients and recognition of increased morbidity, mortality, impaired quality of life, safety issues, and side effects of rhythm control strategies with antiarrhythmic drugs, and high healthcare costs associated with AF have spurred numerous investigations to develop more effective treatments for AF and its complications.8 Although AF treatment has been studied extensively, AF prevention has received relatively little attention, while it has paramount importance in the prevention of morbidity and mortality, and complications associated with arrhythmia and its treatment. Current evidence shows a clear association between the presence of modifiable risk factors and the risk of developing AF. By implementing AF risk reduction strategies aiming at risk factors such as obesity, hypertension, diabetes, and obstructive sleep ap-noea (OSA), which are interrelated, we impact upon the escalating incidence of AF in the population and ultimately decrease the healthcare burden of associated co-morbidities of AF. To address this issue, a Task Force was convened by the European Heart Rhythm Association and the European Association of Cardiovascular Prevention and Rehabilitation, endorsed by the Heart Rhythm Society and Asia-Pacific Heart Rhythm Society, with the remit to comprehensively review the published evidence available, to publish a joint consensus document on the prevention of AF, and to provide up-to-date consensus recommendations for use in clinical practice. In this document, our aim is to summarize the current evidence on the association of each modifiable risk factor with AF and the available data on the impact of possible interventions directed at these factors in preventing or reducing the burden of AF. While the evidence on AF prevention is still emerging, the topic is not fully covered in current guidelines and some aspects are still controversial. Therefore, there is a need to provide expert recommendations for professionals participating in the care of at-risk patients and populations, with respect to addressing risk factors and lifestyle modifications. Health economic considerations Atrial fibrillation is a costly disease, both in terms of direct, and indirect costs, the former being reported by cost of illness studies as per-patient annual costs in the range of US $2000–14200 in North America and of €450–3000 in Europe.9 In individuals with AF or at risk of developing AF, any effective preventive measure, intervention on modifiable risk factors or comorbidities, as well as any effective pharmacological or non-pharmacological treatment has the aim to reduce AF occurrence, thromboembolic events and stroke, morbidity and, possibly, mortality related to this arrhythmia. Apart from the clinical endpoints, achievement of these goals has economic significance, in terms of positive impact on direct and indirect costs and favourable cost–effectiveness at mid- or long-term, in the perspective of healthcare systems.10–12 In view of the epidemiological profile of AF and progressive aging of the population,13 an impressive increase of patients at risk of AF or affected by AF,14 also in an asymptomatic stage, is expected in the next decades, inducing a growing financial burden on healthcare systems, not only in Europe and North America, but also worldwide.15,16 In consideration of this emerging epidemiological threat due to AF, it is worth considering a paradigm shift, going beyond the conventional approach of primary prevention based on treatment of AF risk factors, but, instead, considering the potential for ‘primordial’ prevention, defined as prevention of the development of risk factors predisposing to AF in the first place.17 This approach, aimed at avoiding the emergence and penetration of risk factors into the population, has been proposed in general terms for the prevention of cardiovascular diseases17 and should imply combined efforts of policymakers, regulatory and social service agencies, providers, physicians, community leaders, and consumers, in an attempt to improve social and environmental conditions, as well as individual behaviours, in the pursuit of adopting healthy lifestyle choices.16 Since a substantial proportion of incident AF events can be attributable to elevated or borderline levels of risk factors for AF,18 this approach could be an effective way to reduce the financial burden linked to AF epidemiology. In terms of individual behaviour and adoption of a ‘healthy lifestyle’, it is worth considering that availability of full healthcare coverage (through health insurance or the healthcare system) may in some cases facilitate the unwanted risk of reducing, at an individual level, the motivation to adopt all the preventive measures that are advisable, in line with the complex concept of ‘moral hazard effect’.19 Patient education and patient empowerment are the correct strategies for avoiding this undesirable effect.

Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations, the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients undergoing non-cardiac surgery, pending the implementation of a “validity criteria checklist” before applying volume expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid volume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algorithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative morbidity and duration of hospital stay in high-risk surgical patients.

Hypertensive disorders are the most common medical complications in the peripartum period associated with a substantial increase in morbidity and mortality. Hypertension in the peripartum period may be due to the continuation of pre-existing or gestational hypertension, de novo development of pre-eclampsia or it may be also induced by some drugs used for analgesia or suppression of postpartum haemorrhage. Women with severe hypertension and hypertensive emergencies are at high risk of life-threatening complications, therefore, despite the lack of evidence-based data, based on expert opinion, antihypertensive treatment is recommended. Labetalol intravenously and methyldopa orally are then the two most frequently used drugs. Short-acting oral nifedipine is suggested to be used only if other drugs or iv access are not available. Induction of labour is associated with improved maternal outcome and should be advised for women with gestational hypertension or mild pre-eclampsia at 37 weeks’ gestation. This position paper provides the first interdisciplinary approach to the management of hypertension in the peripartum period based on the best available evidence and expert consensus.

The predictive value of vascular biomarkers such as pulse wave velocity (PWV), central arterial pressure (CAP), and augmentation index (AIx), obtained through pulse wave analysis (PWA) in resting conditions, has been documented in a variety of patient groups and populations. There are appropriate recommendations on their clinical use in clinical practice guidelines of various scientific societies. Operator-independent methods are currently available for estimating vascular biomarkers also in ambulatory conditions. The acceptable accuracy and reproducibility of ambulatory PWA makes it be a promising tool for evaluating vascular biomarkers in daily-life conditions. This approach may provide an opportunity to further improve the early cardiovascular screening in subjects at risk. However, there is no sufficient evidence to support the routine clinical use of PWA in ambulatory conditions at the moment. In particular, long-term outcome studies are needed to show the predictive value of ambulatory PWV, CAP and AIx values.

International audience; on behalf of Members of the ESH Working Group on Interventional Treatment of Hypertension This ESH update was deemed necessary with the publication of new results of sham-controlled randomized blinded prospective trials with renal denervation (RDN). Proof of concept studies and first randomized trials (some were sham-controlled) displayed discrepant results about the efficacy of RDN. Three sham-controlled randomized trials of the 2.0 generation yielded now similarity in the average blood pressure decrease following RDN. Reduction of ambulatory blood pressure was approximately 5 to 7 mmHg and of office blood pressure 10 mmHg. Such a decrease in blood pressure by pharmacologic therapy has been found to be associated with lower incidence of cardiovascular events in particular with respect to heart failure and stroke by roughly 25%. Nevertheless, some questions about renal denervation are unanswered. The heterogeneity of the blood pressure-lowering response point to the clinical need to identify predictors for efficacy, and questions on long-term safety could not have been answered due to the short duration of the sham-controlled randomized clinical trials.

Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.

The Pathophysiology of Aortic Cross-clamping and Unclamping. By Gelman S. ANesthesiology 1995; 82:1026–60. Reprinted with permission. Aortic cross-clamping (AoX) and unclamping are associated with severe hemodynamic disturbances in virtually all organs and systems. The main hemodynamic changes induced by AoX result from an increase in impedance to aortic flow, an increase in systemic vascular resistance and afterload, blood volume redistribution caused by collapse and constriction of venous vasculature distal to the aortic clamp, and a subsequent increase in preload. Preload may not increase if the aorta is clamped distal to the celiac artery; in that case, blood volume from distal venous vasculature may be redistributed to the splanchnic vasculature without associated increases in preload. Increases in afterload and preload demand an increase in contractility, which results in an autoregulatory increase in coronary blood flow. Without increases in coronary blood flow and myocardial contractility, decompensation may occur. Aortic cross-clamping is associated with the formation and release of many mediators which constitute a double-edged sword: they may mitigate or aggravate the harmful hemodynamic effects of AoX and unclamping. Injuries to the lungs, kidneys, spinal cord, or abdominal viscera are caused mainly by ischemia and reperfusion of organs distal to aortic cross-clamping. A clear understanding of the pathophysiologic mechanisms involved in these processes should help to promote rational, well-focused, and effective measures to prevent and treat homeostatic disturbances occurring during AoX and unclamping.

The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR). A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes. Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network’s opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation. The THOR Network’s consensus statement is, “In a casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components. As a part of this HR, the initial systolic blood pressure target should be 100 mm Hg. In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock” Postprint

Background Neurological injuries remain the leading cause of death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Adequate blood pressure is of paramount importance to optimize cerebral perfusion and to minimize secondary brain injury. Markers measuring global cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic variations after successful resuscitation are needed to assist a more individualized post-resuscitation care. Currently, no technique is available for bedside evaluation of global cerebral energy state, and until now blood pressure targets have been based on limited clinical evidence. Recent experimental and clinical studies indicate that it might be possible to evaluate cerebral oxidative metabolism from measuring the lactate-to-pyruvate (LP) ratio of the draining venous blood. In this study, jugular bulb microdialysis and immediate bedside biochemical analysis are introduced as new diagnostic tools to evaluate the effect of higher mean arterial blood pressure on global cerebral metabolism and the degree of cellular damage after OHCA. Methods/design This is a single-center, randomized, double-blinded, superiority trial. Sixty unconscious patients with sustained return of spontaneous circulation after OHCA will be randomly assigned in a one-to-one fashion to low (63 mm Hg) or high (77 mm Hg) mean arterial blood pressure target. The primary end-point will be a difference in mean LP ratio within 48 h between blood pressure groups. Secondary end-points are (1) association between LP ratio and all-cause intensive care unit (ICU) mortality and (2) association between LP ratio and survival to hospital discharge with poor neurological function. Discussion Markers measuring cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic changes after successful resuscitation are urgently needed to enable a more personalized post-resuscitation care and prognostication. Jugular bulb microdialysis may provide a reliable global estimate of cerebral metabolic state and can be implemented as an entirely new and less invasive diagnostic tool for ICU patients after OHCA and has implications for early prognosis and treatment. Trial registration ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03095742). Registered March 30, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3397-1) contains supplementary material, which is available to authorized users.

Item does not contain fulltext Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org).

The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies in relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib. An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome, the risk-benefit ratio of diagnostic and therapeutic tools and thereby to achieve myeloma response with novel combination approaches, while preventing CVAEs. Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment. A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions. This article is protected by copyright. All rights reserved.

Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers.We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points.Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P 0.0001).I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.

Medicine 95(36), e4446 (2016). doi:10.1097/MD.0000000000004446, Published by Lippincott Williams & Wilkins, Baltimore, Md.

The simple faint is secondary to hypotension and bradycardia resulting in transient loss of consciousness. According to Ohm's law applied to the circulation, BP = SVR × CO, hypotension can result from a decrease in systemic vascular resistance (SVR), cardiac output (CO), or both. It is important to understand that when blood pressure (BP) is falling, SVR and CO do not change reciprocally as they do in the steady state. In 1932, Lewis, assuming that decreased SVR alone accounted for hypotension, defined "the vasovagal response" along pathophysiologic lines to denote the association of vasodilation with vagal-induced bradycardia in simple faint. Studies performed by Barcroft and Sharpey-Schafer between 1940 and 1950 used volume-based plethysmography to demonstrate major forearm vasodilation during extreme hypotension and concluded that the main mechanism for hypotension was vasodilation. Plethysmographic measurements were intermittent and not frequent enough to capture rapid changes in blood flow during progressive hypotension. However, later investigations by Weissler, Murray, and Stevens performed between 1950 and 1970 used invasive beat-to-beat BP measurements and more frequent measurements of CO using the Fick principle. They demonstrated that CO significantly fell before syncope, and little vasodilation occurred until very late in the vasovagal reaction Thus, since the 1970s, decreasing cardiac output rather than vasodilation has been regarded as the principal mechanism for the hypotension of vasovagal syncope.

The trigeminocardiac reflex (TCR) has previously been described in the literature as a reflexive response of bradycardia, hypotension, and gastric hypermotility seen upon mechanical stimulation in the distribution of the trigeminal nerve. The diving reflex (DR) in humans is characterized by breath-holding, slowing of the heart rate, reduction of limb blood flow and a gradual rise in the mean arterial blood pressure. Although the two reflexes share many similarities, their relationship and especially their functional purpose in humans have yet to be fully elucidated. In the present review, we have tried to integrate and elaborate these two phenomena into a unified physiological concept. Assuming that the TCR and the DR are closely linked functionally and phylogenetically, we have also highlighted the significance of these reflexes in humans.