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Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. Healthy young (N = 36; 19 women; age 25.4 ± 4.6 years) and older (N = 21; 12 women; age 62.4 ± 9.6 years) adults performed a supine 40 mmHg, 20 s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3 s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p

BACKGROUND In 2016, the American Society of Echocardiography (ASE) released guidelines for identifying left ventricular (LV) diastolic dysfunction (DD), but its ability to detect early hemodynamic abnormalities is not well established, especially in the setting of subclinical coronary artery disease (CAD). We hypothesize that the accuracy of ASE categorization of early LVDD is affected by knowledge of whether CAD history is present. METHODS We studied 34 patients (age 62 ± 7 years) with NYHA class I to II symptoms and with transthoracic echocardiography without findings suggesting myocardial disease (all with preserved LV ejection fraction), who underwent cardiac catheterization with high-fidelity LV pressure measurement. Echocardiographic images were evaluated for LVDD using ASE algorithm without and with knowledge of CAD history and angiography findings. CAD was considered as having DD for the algorithm. RESULTS CAD was identified in 22 patients at catheterization (65%). Using ASE guidelines without including history of CAD or angiographic results, 29 patients were DD-, 3 were DD+ (all grade II), and 2 were indeterminate. Inclusion of CAD history recategorized 59% (n = 20) patients to DD+ (all grade I) from DD- (P

Aims Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored. Methods and results The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT‐Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non‐fatal myocardial infarction (MI), cardiovascular mortality, non‐cardiovascular mortality, and all‐cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow‐up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT‐Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4–3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14–1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06–1.52). We also observed a greater incidence of HF hospitalization and non‐fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P 7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT‐Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non‐fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.

Using digital technology to share patient-generated health data has the potential to improve the self-management of multiple long-term health conditions. Sharing these data can allow patients to receive additional support from healthcare professionals and peer communities, as well as enhance their understanding of their own health. A deeper understanding of the concerns raised by those living with long-term health conditions when considering whether to share health data via digital technology may help to facilitate effective data sharing practices in the future. The aim of this review is to identify whether trust, identity, privacy and security concerns present barriers to the successful sharing of patient-generated data using digital technology by those living with long-term health conditions. We also address the impact of stigma on concerns surrounding sharing health data with others. Searches of CINAHL, PsychInfo and Web of Knowledge were conducted in December 2019 and again in October 2020 producing 2,581 results. An iterative review process resulted in a final dataset of 23 peer-reviewed articles. A thorough analysis of the selected articles found that issues surrounding trust, identity, privacy and security clearly present barriers to the sharing of patient-generated data across multiple sharing contexts. The presence of enacted stigma also acts as a barrier to sharing across multiple settings. We found that the majority of literature focuses on clinical settings with relatively little attention being given to sharing with third parties. Finally, we suggest the need for more solution-based research to overcome the discussed barriers to sharing.

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase‐contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P P P Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Graphical abstract, Highlights • LAIH may be a complication of blunt chest trauma. • Multimodality imaging with TEE and CMR can lead to the correct diagnosis. • Conservative management may be considered in hemodynamically stable patients.

The 2019 American College of Cardiology Scientific Sessions displayed innovation in many areas for the evaluation and management of cardiovascular disease from preventive evaluation and care to advanced interventions. Imaging played a central role in these developments with a highlight of the conference being the imaging research presented. This review will summarize key imaging studies which were presented at this scientific meeting which will lead to innovation in the evaluation and management of cardiovascular disease. Experts in nuclear imaging (DW/MA), echocardiography (MS), cardiac magnetic resonance (SL), and cardiac computed tomography (RB) selected abstracts which they found to be of particular interest to the multimodality imaging audience and were integrated into this review (LP).

Visual Abstract, Highlights • Extensive LA fibrosis is related to an increase in LA size and decrease in total LA EF. This supports the contention that the LA is not merely a bystander of MR but rather is actively involved in the pathophysiology of MR. • Chymase is plentiful in the human heart, especially in the LA, and correlates with extracellular matrix accumulation in primary MR. • Because of the unreliability of the LV ejection fraction in primary MR, future studies may consider LA size and total LA EF for timing of surgical intervention of asymptomatic moderate to severe MR., Summary Increasing left atrial (LA) size predicts outcomes in patients with isolated mitral regurgitation (MR). Chymase is plentiful in the human heart and affects extracellular matrix remodeling. Chymase activation correlates to LA fibrosis, LA enlargement, and a decreased total LA emptying fraction in addition to having a potential intracellular role in mediating myofibrillar breakdown in LA myocytes. Because of the unreliability of the left ventricular ejection fraction in predicting outcomes in MR, LA size and the total LA emptying fraction may be more suitable indicators for timing of surgical intervention.

BACKGROUND We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD). METHODS Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated. RESULTS In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively. CONCLUSIONS Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone.

Purpose Phase-contrast cardiovascular magnetic resonance (PC-CMR) quantification of intracardiac shunt (measuring the pulmonary to systemic flow ratio, Qp/Qs) is typically determined by measuring flow through planes perpendicular the pulmonary trunk (PA) and ascending aorta (Ao). This method is subject to error from presence of background velocity offsets and requires two scan acquisitions. We evaluated an alternate PC-CMR technique for quantifying Qp/Qs using a single modified plane that encompasses both the PA and Ao. Material and methods In 53 patients evaluated for intracardiac shunting, PC-CMR measurement in the individual Ao and PA planes and also in a single-acquisition plane was obtained and Qp/Qs calculated by each method. Bland-Altman analysis was performed to evaluate the agreement between the two methods. Results The 95% confidence limits of agreement ranged from -0.52 to +0.34 indicating good agreement between the two methods. There was excellent agreement on the clinically relevant threshold value of Qp/Qs ratio of 1.5 (representing criteria for surgical correction of shunt). Conclusions Qp/Qs determined from the single-acquisition approach agrees well with that of the individual PA and Ao method and offers potential improved accuracy (due to background velocity offset).

Background Half of U.S. adults have received at least one dose of the COVID-19 vaccines produced by either Pfizer, Moderna, or Johnson and Johnson, which represents a major milestone in the ongoing pandemic. Given the emergency use authorizations for these vaccines, their side effects and safety were assessed over a compressed time period. Hence, ongoing monitoring for vaccine-related adverse events is imperative for a full understanding and delineation of their safety profile. Case presentation An 22-year-old Caucasian male presented to our hospital center complaining of pleuritic chest pain. Six months prior he had a mild case of COVID-19, but was otherwise healthy. He had received his first dose of the Moderna vaccine three days prior to developing symptoms. Laboratory analysis revealed a markedly elevated troponin and multiple imaging modalities during his hospitalization found evidence of wall motion abnormalities consistent with a diagnosis of perimyocarditis. He was started on aspirin and colchicine with marked improvement of his symptoms prior to discharge. Conclusions We present a case of perimyocarditis that was temporally related to COVID-19 mRNA vaccination in an young male with prior COVID-19 infection but otherwise healthy. Our case report highlights an albeit rare but important adverse event for clinicians to be aware of. It also suggests a possible mechanism for the development of myocardial injury in our patient.

Background: Understanding data-sharing in HIV care is timely given the shift to remote consultations during COVID-19 and increasing expectations for self-management. We describe the 'data-sharing ecosystem' in HIV care by analysing HIV healthcare professional (HCP) beliefs and practices around sharing diverse types of service user and clinic-generated data across multiple contexts. Method: During February-October 2020, we conducted 14 semi-structured interviews with HCPs working in a large UK HIV outpatient service. Participants engaged in a card sorting task, sorting 33 data types routinely shared in HIV care into categories (comfortable/not comfortable/ not sure) across three data-sharing contexts: (a) from service users to HCPs in consultations;(b) HCPs to GPs;and (c) HCPs to non-HIV HCPs. Data were analysed thematically. Results: Over half (57%) of participants were female;57% were doctors. Participants had worked in HIV for 12 years on average. HCPs were comfortable with a wide range of data being shared with them by service users. Across all sharing contexts, HCPs were uncomfortable with sharing of service user photographs, perceiving them as not routinely shared, unnecessary, and potentially risking inadvertent sharing of inappropriate content. HCPs were comfortable sharing data with GPs and other non-HIV HCPs in two broad categories: (a) demographic data (e.g. age) and (b) non-sensitive data related to general health (e.g. sleep). HCPs were less comfortable sharing sensitive information about HIV status, sexual health, behaviour and identity, perceiving them as not relevant to care provided by other HCPs or as risking stigmatisation. Service user consent and relevance of data to sharing context were key determinants of data-sharing comfort. Conclusion: With a growing emphasis on self-management of HIV and on remote care provision, understanding the context of data-sharing in HIV care is increasingly important, particularly given the perceived durability of some current service changes as a result of COVID-19. We demonstrate the complex interplay of data types, relationship dynamics, and contexts of care provision that shape the data-sharing ecosystem in HIV care. Developing guidance on the sharing of service user and clinic-generated data in HIV care must account for these complexities.

Background Increasing service user demand and rising incidence of key sexually transmitted infections (STIs), alongside developments in diagnostics and digital health provision, at a time when services have faced fragmentation and reduction in funding, have resulted in a huge expansion in online postal sexually transmitted infection (STI) self-sampling services across some parts of the UK. This review aimed to explore who is accessing and using online postal self-sampling services in the UK, the acceptability of these services and whether they are exacerbating sexual health inequalities. Methods Following the PICO (Population Intervention Comparators Outcome) framework, a systematic search was conducted in nine databases in June 2020. Included studies were published between 01/2010–06/2020, in the English language, based on pre-agreed inclusion/exclusion criteria. A second reviewer carried out abstract and full text screening. 15 studies were included. Extracted data were analysed using descriptive statistics and thematic analysis. Results Study designs were heterogeneous, including quantitative, qualitative and mixed method analysis, and were therefore appraised using the Mixed Methods Appraisal Tool. Overall, studies were of good quality. However, the majority were either evaluating a single site/testing provider, were exploratory or observational. Few studies collected comprehensive demographic data. Individuals accessing online postal STI self-sampling services tended to be asymptomatic, white, women, over 20s, and from less deprived areas. These services tended to increase overall STI testing demand and access. There were varied results on whether services reduced time to treatment. Services were deemed highly acceptable if they were trustworthy, reliable, convenient, and improved patient choice. Conclusion Existing and new services must complete comprehensive evaluations to establish whether services are inclusive, accessible and address, rather than exacerbate, sexual health inequalities. Now is a critical time to identify the effectiveness of these digital health interventions given the wave of service expansions across the UK.

Background Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures. Objective We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures. Methods A prospective, observational study of neonates admitted with seizures to Tygerberg Hospital. Participants received crushed levetiracetam (diluted in saline) given orally or via naso-/orogastric tube. At steady-state, pharmacokinetic sampling was performed at pre-dose, 1.5, 2.5 and 4 h post-dose. Maximum concentration (Cmax), time to Cmax (Tmax), trough concentrations (Ctrough) and area under the concentration-time curve (AUC0–12) were calculated using non-compartmental analysis. Seizure termination and safety profiles were documented. Results Nineteen participants were grouped into three dosing ranges: (i) 5–15 mg/kg/12-hourly, (ii) 15–25 mg/kg/12-hourly and (iii) 25–35 mg/kg/12-hourly. Range 1 demonstrated AUC0–12 167.0 ± 45.6 h*μg/mL, Cmax 19.19 ± 4.12 μg/mL and Ctrough 9.99 ± 3.86 µg/mL. Range 2, AUC0–12 316.5 ± 108.4 h*μg/mL, Cmax 35.12 ± 10.54 µg/mL and Ctrough 19.25 ± 8.48 µg/mL. Range 3, AUC0–12 290.9 (range 176.14–405.59) h*μg/mL, Cmax 36.11 (range 27.58–44.64) µg/mL and Ctrough 13.03 (2.98–23.07) µg/mL. Seizures terminated in 17/19 (90%) neonates by day 3 and 19/19 (100%) by day 4 post-levetiracetam initiation. Conclusion Crushed levetiracetam has comparable pharmacokinetics to historical data. No pharmacokinetic differences were observed between oral vs. naso-/orogastric administration. Crushed levetiracetam tablets can be considered for neonates in low-resource settings where intravenous and syrup access is limited. LAY SUMMARY Intravenous preparations of antiepileptic medications are used in the management of neonatal seizures. Various established standard of care intravenous antiepileptic medicines are unavailable nationally and internationally due to reasons outside our control. This stock shortage included intravenous phenobarbitone which is the first-line treatment for paediatric seizures. Due to phenobarbital shortage, levetiracetam has been identified by the neonatologists at Tygerberg Hospital, Cape Town, South Africa, as a suitable treatment option due to its efficacy and safety profile. However, intravenous levetiracetam and oral syrup is not registered in South Africa. Levetiracetam tablets are being crushed, dissolved and administered to neonates. There are no data available on the absorption of crushed levetiracetam tablets administered to neonates via a nasogastric tube. This study characterized the pharmacokinetic profile of crushed levetiracetam administered to neonates. We selected neonates receiving levetiracetam from the neonatal wards at Tygerberg hospital and drew blood to analyse the levetiracetam concentrations at 4 different time points. We found that the overall exposure of crushed levetiracetam tablets were comparable to the exposures achieved in historical data of the unaltered formulations. We concluded that crushed levetiracetam tablets can be considered for neonates in low resource settings where intravenous and syrup access is limited.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.

A critical step in the clinical evaluation of postural tachycardia syndrome (PoTS) is the assessment of orthostatic tachycardia. Active stand testing (AST) and head up tilt table testing (HUT) can both be used to evaluate the presence of this tachycardia. Drugs that affect heart rate (HR), sympathetic nervous system activity, or blood volume should be withheld prior to the orthostatic test. There are several important methodological and physiological differences with HUT versus AST. Orthostatic heart rate is typically higher during HUT than with AST, and requires specialized equipment that is not available to all clinicians. Conversely, AST is convenient, cost-effective and can be performed in the primary care physician office. Reflex tachycardia specific to initial orthostatic hypotension may be greater in the initial minutes of AST, compared to HUT, and this should be considered in the evaluation of early AST HR responses. The AST has similar sensitivity and greater specificity than HUT. Overall, AST should be used as the first line diagnostic tool during assessment of orthostatic tachycardia in PoTS.

A diagnosis of Postural Tachycardia Syndrome (PoTS) requires a sustained increase in heart rate of 30 beats per minute or more (40 beats per minute if age 12–19 years) within 10 minutes of assuming upright posture, and in the absence of orthostatic hypotension (

Tendon geometry and tissue properties are important determinants of tendon function and injury risk and are altered in response to ageing, disease, and physical activity levels. The purpose of this study was to compare free Achilles tendon geometry and mechanical properties between trained elite/sub-elite middle-distance runners and a healthy control group. Magnetic resonance imaging (MRI) was used to measure free Achilles tendon volume, length, average cross-sectional area (CSA), regional CSA, moment arm, and T2* relaxation time at rest, while freehand three-dimensional ultrasound (3DUS) was used to quantify free Achilles tendon mechanical stiffness, Young’s modulus, and length normalised mechanical stiffness. The free Achilles tendon in trained runners was significantly shorter and the average and regional CSA (distal end) were significantly larger compared to the control group. Mechanical stiffness of the free Achilles tendon was also significantly higher in trained runners compared to controls, which was explained by the group differences in tendon CSA and length. T2* relaxation time was significantly longer in trained middle-distance runners when compared to healthy controls. There was no relationship between T2* relaxation time and Young’s modulus. The longer T2* relaxation time in trained runners may be indicative of accumulated damage, disorganised collagen, and increased water content in the free Achilles tendon. A short free Achilles tendon with large CSA and higher mechanical stiffness may enable trained runners to rapidly transfer high muscle forces and possibly reduce the risk of tendon damage from mechanical fatigue.

Although there are effective nucleoside analogs to treat HSV, VZV, and HCMV disease, herpesvirus infections continue to contribute to significant morbidity and mortality. Acyclovir is the drug of choice for HSV encephalopathy, yet there is an estimated 6-19% mortality rate with half of the survivors experiencing moderate to severe chronic neurological deficits. For VZV, current treatments are inadequate to prevent acute and persistent pain due to zoster. Treatment of HCMV with GCV requires close monitoring particularly in patients with impaired renal function and there are no approved treatments for congenital HCMV infections. New therapeutic options to control cytomegalovirus reactivation in bone marrow and stem cell transplant patients are needed to improve patient outcome. No successful chemotherapeutic options are available for EBV, HHV-6, 7, and 8. Drug resistance is a concern for HCMV, HSV, and VZV since approved drugs share common mechanisms of action. Targeting DNA encapsidation or capsid assembly provide additional options for the development of non-nucleoside, small molecule anti-herpesviral drugs.

This review summarizes key imaging studies that were presented at the American Heart Association Scientific Sessions 2018 in Chicago related to the fields of nuclear cardiology (including single photon emission computed tomography and positron emission tomography), cardiac computed tomography, cardiac magnetic resonance, and echocardiography. The aim of this bird's eye view is to inform readers of the various studies discussed at the meeting from these imaging modalities. While this review is directed to the benefit of those of us who were not able to attend the conference, we find that a general overview may also be useful to those that did since it is often difficult to get exposure to all abstracts at large meetings. Further, we hope that the presentation of multiple imaging studies in a single synthesized review will stimulate new ideas for future research in imaging.

In resource-restricted regions, respiratory distress syndrome (RDS) data are often underreported, making the determination of effective interventions and their outcome difficult. The combination of oxygen, nasal continuous positive airway pressure (CPAP) and surfactant therapy has the potential to prevent 42% of RDS-related deaths in sub-Saharan Africa, despite the financial implications. This article provides a brief overview on the status of RDS management, mainly nasal CPAP and surfactant therapy in very-low-birth-weight infants, in resource-restricted regions of sub-Saharan Africa. Data from the public health sector, as compared to the private health sector, of the Western Cape province, South Africa, are used to illustrate what RDS management strategies are able to accomplish in a resource-restricted region. Upscaling of all components (antenatal care, antenatal corticosteroids, prevention of hypothermia and RDS management strategies) are required to decrease premature infant mortality rates in resource-restricted areas.

Background Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left-sided radiation for breast cancer are associated with negative autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy. Subjects, Materials, and Methods Seventy-three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HRrest) and blood pressure were measured weekly during chemotherapy. HRrest, exercise heart rate recovery (HRrecovery), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment. Results During chemotherapy, HRrest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%–51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left-sided radiation individually predicted impairments of HRrest and HRrecovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice-weekly exercise attendance predicted improvement. By 10 weeks after treatment, HRrest and blood pressure were not different from prechemotherapy. Conclusion In this study, chemotherapy resulted in increased HRrest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left-sided radiation were associated with HRrest elevations and impairments of HRrecovery, but exercise training at least twice a week appeared to mitigate these changes. Implications for Practice This study characterized changes in clinically accessible measures with well-established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy-related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60-minute sessions of moderate-intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists.

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P =0.003) and had a greater proportion of women (75.0% versus 43%; P =0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m 2 ; P P =0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P

A 78-year-old black man presented to the Hypertension Clinic at the University of Alabama at Birmingham for uncontrolled blood pressure (BP). His BP remained uncontrolled (automated office, ≥135/85 mm Hg) from August 2011 to August 2016 in spite of use of 6 antihypertensive agents in adequate doses (Figure 1). During this time period, his average systolic BP was 167.1 mm Hg and average diastolic BP was 68.7 mm Hg. Figure 1. Blood pressure (BP) and antihypertensive medications before and after surgery. CABG indicates coronary artery bypass grafting. The patient was on 3 antihypertensive medications on initial presentation to University of Alabama at Birmingham in 2011, including an angiotensin receptor blocker (irbesartan), a calcium channel blocker (amlodipine), and a long-acting thiazide-like diuretic (chlorthalidone). Spironolactone was added as a fourth antihypertensive agent. Eventually, hydralazine—a vasodilator—and clonidine—a centrally acting sympatholytic—were added as the fifth and sixth antihypertensive agents. The patient’s BP remained uncontrolled on 6 different classes of antihypertensive medications (Figure 1). Comorbidities and secondary causes of hypertension were evaluated by biochemical analysis and imaging. ### Biochemical Analysis The patient was diagnosed with mild chronic kidney disease. Mean serum creatinine was 1.35 mg/dL with an estimated glomerular filtration rate of 58 mL/min per 1.73 m2. Diabetes mellitus was excluded (HbA1c was 5.5%), primary aldosteronism was excluded as the plasma aldosterone–renin ratio was

Background: Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform. Methods: In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch. Results: The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival. Conclusions: We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity.

This review summarizes key imaging studies that were presented in the American Heart Association Scientific Sessions 2017 related to the fields of nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. The aim of this bird's eye view is to inform readers about multiple studies reported at the meeting from these different imaging modalities. While such a review is most useful for those that did not attend the conference, we find that a general overview may also be useful to those that did since it is often difficult to get exposure to many abstracts at large meetings. The review, therefore, aims to help readers stay updated on the newest imaging studies presented at the meeting and will hopefully stimulate new ideas for future research in imaging.

In this paper, we propose a deformable mesh model (DMM) method for left-ventricular (LV) motion-estimation from cardiac-gated tagged magnetic resonance imaging (MRI). DMM starts by partitioning short-axis (SA) and long-axis (LA) images at end-diastole (ED) in a collection of non-overlapping mesh elements (triangles). Next, mesh elements are deformed attempting to track temporal changes in pixel intensities by minimizing an image-matching cost function from frame to frame. Finally, dense motion fields can be obtained at any frame from the displacement of mesh nodes, without any additional user interaction. For validation, 23 human tagged MRI studies were used, allocated as 7 normal, 9 hypertensive (HTN), and 7 with mitral regurgitation (MR). DMM end-systolic (ES) motion and strains were quantitatively compared to a “gold-standard” feature-based (FB) motion analysis method that includes manual tagline editing. DMM motion achieves subpixel average displacement error of SA landmarks with respect to FB. 3-D ES strains obtained from DMM correlate well with FB method ( $\rho $ ranging from 0.79 to 0.97). Finally, we show temporal curves for several DMM strain components, grouped according to the condition of patients (normal and diseased). These curves are qualitatively compared to a strain from unwrapped harmonic phase motion estimation algorithm. DMM produces robust temporal curves, which capture strain fluctuations reported in medical literature for HTN and MR conditions. This makes it a viable alternative to analyze motion from images at phases suffering from low contrast-to-noise ratio that may convey important information about the presence of certain cardiac pathologies.

Introduction Left ventricular (LV) hypertrophy in aortic stenosis (AS) becomes maladaptive over time, leading first to a reduction in global longitudinal strain (GLS) and in a later stage a reduction in ejection fraction (EF). The myocardial state of impaired GLS but preserved EF is a key remodeling turning point in AS, yet little is known about the coping mechanics of the LV at or around this sensitive juncture. Aim 1) To study the relationship between LV mass index (LVMi) increase and measures of LV function, including strain in AS; 2) To investigate whether augmentation of global myocardial radial and circumferential strain (GRS, GCS) compensates for the GLS reduction in AS patients with preserved EF. Methods One-hundred and eleven patients with varying degrees of AS, and 20 age- and gender-matched healthy volunteers were prospectively enrolled. transthoracic echocardiography with offline strain analysis was performed using TomTec software. Intra- and inter-observer variability of linear LV internal dimensions/thickness, EF and strain indices was tested on 20 randomly selected patients. Results Clinical and demographic characteristics of cases and controls are shown in Figure 1. GLS was impaired in AS patients compared to controls. In AS with preserved EF (>50%), as LVMi increased, GLS progressively improved up to a point, beyond which any further increase in LVMi appeared counter-productive with impairment of GLS (Figure 1). EF preservation in these AS patients was mediated by a compensatory supernormal augmentation of GRS and a smaller augmentation of GCS (Figure 1). We observed a significant inverse correlation between GRS and GLS (r = 0.3, p = 0.002), and a similar trend between GCS and GLS (r = 0.275, p = 0.004). Intraclass correlation coefficient was high for all measurements (0.7-0.9). Conclusion In patients with AS and preserved EF, progressive myocardial hypertrophy improves GLS up to a point beyond which GLS drops and GRS increase to compensate. This plasticity of myocardial mechanics, in particular the supranormal augmentation of GRS is what enables the pathologically hypertrophied AS ventricle to delay the otherwise inexorable decline in its global systolic function. Abstract 618 Figure 1

Pulmonary hypertension (PH) is a clinical condition characterised by elevation of pulmonary arterial pressure (PAP) above normal range due to various aetiologies. While cardiac right-heart catheterisation (RHC) remains the gold standard and mandatory for establishing the diagnosis of PH, noninvasive imaging of the heart plays a central role in the diagnosis and management of all forms of PH. Although Doppler echocardiography (ECHO) can measure a range of haemodynamic and anatomical variables, it has limited utility for visualisation of the pulmonary artery and, oftentimes, the right ventricle. Cardiovascular magnetic resonance (CMR) provides comprehensive information about the anatomical and functional aspects of the pulmonary artery and right ventricle that are of prognostic significance for assessment of long-term outcomes in disease progression. CMR is suited for serial follow-up of patients with PH due to its noninvasive nature, high sensitivity to changes in anatomical and functional parameters, and high reproducibility. In recent years, there has been growing interest in the use of CMR derived parameters as surrogate endpoints for early-phase PH clinical trials. This review will discuss the role of CMR in the diagnosis and management of PH, including current applications and future developments, in comparison to other existing major imaging modalities.

The first literary reference to persistent pulmonary hypertension (PH) of the newborn (PPHN) can be found in 1969 by Gersony et al., who described it as persistence of physiologic characteristics of the fetal circulation in the absence of disease. Defined as a failure of normal circulatory transition at birth, or more specifically as failure of the pulmonary vasculature to relax after birth, with continued shunting of non-oxygenated blood into the systemic circulation via fetal channels (ductus arteriosus and foramen ovale), it remains a challenging neonatal emergency to manage. Term and nearterm infants are most commonly affected, but PPHN can occur in premature infants.

Asymptomatic patients may exhibit symptoms during objective exercise testing, but whether symptoms are due to the obstructively of the valve (typified by the mean gradient) or underlying ventricular function remains unknown. While the mean gradient is an easy parameter to measure no consensus about the measurement of contractile reserve exists. Longitudinal abnormalities may occur in the presence of a normal ejection fraction and the augmentation of these parameters is poorly described. To obtain an objective regarding patients exercise ability is best determined using cardiopulmonary exercise testing. We therefore examined echocardiographic predictors of exercise ability during cardiopulmonary exercise testing.24 asymptomatic patients with moderate to severe or severe aortic stenosis and preserved ejection fraction underwent stress echocardiography with simultaneous cardiopulmonary exercise testing. The primary assessment of exercise ability was the VO2peak and OUES. Echocardiography was measured at rest and during maximal exercise (defined as RER > 1)OUES and VO2peak showed a poor relationship with conventional parameters of severity including peak and mean gradients, AVA and dimensionless index, resting systolic function (by EF and TDI). During exercise systolic augmentation had a good relationship with exercise ability but the exercise mean gradient and exercise LVEF did not.Longitudinal systolic function and particularly systolic augmentation is the strongest predictor of exercise ability when compared to conventional measures of severity.VO2peakOUESS' exerciseRho=0.69 (p=0.001)R= 0.71 (p=0.001)S' restRho=0.52 (p=0.01)R= 0.44 (p=ns)Rest AV max VRho= 0.09 (p=ns)R= -0.08 (p=ns)Rest AV mean PGRho= 0.34 (p=ns)R=-0.10 (p=ns)Exercise AV max VRho=0.43 (p=0.05)R=0.23 (p=ns)Exercise AVmean PGRho= 0.51 (p=0.001)R=0.26 (p=ns)Rest AVARho=0.40 (p=ns)Rho=0.46 (p=0.04)Dimensionless indexRho=0.15 (p=ns)R=0.13 (p=ns)LVEF restRho=-0.18 (p=ns)R=-0.32 (p=ns)LVEF exerciseRho=0.18 (p=ns)R=0.17 (p=ns)S' - systolic velocity; V - velocity; AV - aortic valve; AVA- aortic valve area; LVEF - left ventricular ejection fraction.

Background The extra-renal effects of aldosterone on left ventricular (LV) structure and function are exacerbated by increased dietary sodium in persons with hypertension. Previous studies demonstrated endothelial dysfunction and increased oxidative stress with high salt diet in normotensive salt-resistant subjects. We hypothesized that increased xanthine oxidase (XO), a product of endothelial cells, is related to 24-h urinary sodium and to LV hypertrophy and function in patients with resistant hypertension (RHTN). Methods The study group included persons with RHTN (n = 91), defined as a blood pressure > 140/90 mmHg on ≥ 3 medications at pharmacologically effective doses. Plasma XO activity and 24-h urine were collected, and cardiac magnetic resonance imaging (MRI) was performed to assess LV function and morphology. Sixty-seven normotensive persons on no cardiovascular medications served as controls. A subset of RHTN (n = 19) received spironolactone without salt restriction for six months with follow-up XO activity measurements and MRI analyses. Results XO activity was increased two-fold in RHTN vs. normal and was positively correlated with LV mass, LV diastolic function, and 24-h urinary sodium. In RHTN patients receiving spironolactone without salt restriction, LV mass decreased, but LV diastolic function and XO activity did not improve. Baseline urinary sodium was positively associated with rate of change of LV mass to volume ratio and the LV E/A ratio. Conclusions These results demonstrate a potential role of endothelium-derived oxidative stress and excess dietary salt in the pathophysiology of LV hypertrophy and diastolic dysfunction in persons with RHTN unaffected by the addition of spironolactone.

Background: Left ventricular (LV) remodeling and diastolic properties are affected by both underlying cardiovascular disease/cardiovascular disease risk factors (CVDRFs) and corresponding medication therapy. However, these effects may not be apparent in patients with multiple CVDRFs. We evaluated the effect of medication classes on hemodynamics in a patient cohort with normal LV dimensions and systolic function. Methods: In 38 participants (61 ± 7 years, 64 ± 9% LV ejection fraction) undergoing coronary angiography, LV pressure measurement and cardiac magnetic resonance imaging was performed. The effects of coronary artery disease (CAD), CVDRFs and their corresponding medication therapy on LV parameters were analyzed considering the number of CAD/CVDRFs and ‘adequacy’ of medication therapy to address each existing condition with specific indication-based medication classes. Results: Of the patients studied, 68% had CAD, 87% had hypertension, 87% had dyslipidemia, and 45% had diabetes. Neither individual or total number of CAD/CVDRFs were associated with overall differences in LV diastolic parameters. However, those without (n = 20) and with (n = 18) ‘adequate’ medication therapy for underlying CAD/CVDRFs differed in values of LV end diastolic pressure (17 ± 4 vs. 11 ± 5 mm Hg, P

Background. A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world’s largest LM outbreak to date. Methods. We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 2017 - 31 January 2018). Current epidemic LM cases were compared with a historical cohort of sporadic neonatal LM cases at our institution (2006 - 2016). The global literature on epidemic neonatal LM outbreaks (1 January 1978 - 31 December 2017) was reviewed. Results. Twelve neonates (median gestational age 35 weeks, median birth weight 2 020 g) were treated for confirmed LM bacteraemia in 2017/18, presenting at a median age of 0.5 days. In 5 cases, neurolisteriosis was suspected. Three neonates died (25.0%) v. 8/13 neonatal deaths (61.6%) in the sporadic listeriosis cohort (2006 - 2016) ( p =0.075). The institution’s neonatal LM infection incidence increased significantly in 2017 from a historical rate of 0.17/1 000 live births to 1.4/1 000 ( p

Background Pulmonary artery ( PA ) stiffness is associated with increased pulmonary vascular resistance ( PVR ). PA stiffness is accurately described by invasive PA impedance because it considers pulsatile blood flow through elastic PA s. We hypothesized that PA stiffness and impedance could be evaluated noninvasively by PA velocity transfer function ( VTF ), calculated as a ratio of the frequency spectra of output/input mean velocity profiles in PA s. Methods and Results In 20 participants (55±19 years, 14 women) undergoing clinically indicated right‐sided heart catheterization, comprehensive phase‐contrast and cine‐cardiac magnetic resonance imaging was performed to calculate PA VTF , along with right ventricular mass and function. PA impedance was measured as a ratio of frequency spectra of invasive PA pressure and echocardiographically derived PA flow waveforms. Mean PA pressure was 29.5±13.6 mm Hg, and PVR was 3.5±2.8 Wood units. A mixed‐effects model showed VTF was significantly associated with PA impedance independent of elevation in pulmonary capillary wedge pressure ( P =0.005). The mean of higher frequency moduli of VTF correlated with PVR (ρ=0.63; P =0.003) and discriminated subjects with low (n=10) versus elevated PVR (≥2.5 Wood units, n=10), with an area under the curve of 0.95, similar to discrimination by impedance (area under the curve=0.93). VTF had a strong inverse association with right ventricular ejection fraction (ρ=−0.73; P P =0.02). Conclusions VTF , a novel right ventricular– PA axis coupling parameter, is a surrogate for PA impedance with the potential to assess PA stiffness and elevation in PVR noninvasively and reliably using cardiac magnetic resonance imaging.

Although the number of heart transplants performed in North America has been relatively stable over the last decade, median survival has steadily improved, according to the ISHLT Transplant Registry. Likewise, the number of continuous flow left ventricular assist devices (LVADs) implanted each year in the United States has more than quintupled in 5 years, reaching a total of 2,420 implanted in 2013, according to the Sixth INTERMACS annual report. The number of heart failure patients therefore is growing considerably, and so is the prevalence of the advanced therapies which require close and continuous monitoring and management. In this issue of the Journal, Gupta et al have provided a broad and comprehensive yet succinct survey of the most recent literature describing multiple imaging modalities as they relate to the transplant and LVAD populations. Although imaging choice tends to lean heavily on what techniques are available or on institutional expertise, it is important to stay informed of the status and developments in other imaging modalities as research and patient care progresses at an unparalleled rate. Transplant recipients face certain challenges related to the therapeutic window wherein the degree of immunosuppression to suppress rejection must be balanced with the short-term risk for infection and long-term risk for malignancy, each of which are represented in the leading causes of death in this population. Monitoring the function of the transplanted heart is most easily done with standard echocardiography techniques. Gupta et al also touch on cardiac magnetic resonance (CMR), which can provide additional information that echo cannot accurately determine, such as presence of myocardial scar and right ventricular end diastolic volume index, which appear to be independent predictors of cardiovascular outcomes. Cardiac allograft vasculopathy is another significant cause of morbidity and mortality in post-transplant patients that has led to needed, and often impressive, investigation into the accurate and early detection of this potentially reversible condition. The current gold standard, invasive coronary angiography, has limitations related to the nature of the disease. Allograft vasculopathy and coronary atherosclerosis are distinct entities, the former thought to be driven by, among other things, non-self major histocompatibility complexes, e.g. HLADR, and the failure of outward remodeling as compensation for neointimal hyperplasia due to expansion of vascular smooth muscle cells. Allograft vasculopathy is diffuse, involving large epicardial and smaller intramyocardial arteries, and its course is unpredictable, and often clinically silent due to denervation. Approximately 10% of patients die in the 12 months following a diagnosis of cardiac allograft vasculopathy. Yet, there are available therapies such as pharmacologic inhibition/modulation of cellular proliferative signaling, which have been associated with reduced incidence and slower progression; thus the need for early and accurate detection is paramount. Invasive catheter-based conventional coronary angiography has long been the See related article, pp. 617–638

During the past decade, the IODP (International Ocean Discovery Program) has fostered a significant increase in deep biosphere investigations in the marine sedimentary and crustal environments, and scientists are well-poised to continue this momentum into the next phase of the IODP. The goals of this workshop were to evaluate recent findings in a global context, synthesize available biogeochemical data to foster thermodynamic and metabolic activity modeling and measurements, identify regional targets for future targeted sampling and dedicated expeditions, foster collaborations, and highlight the accomplishments of deep biosphere research within IODP. Twenty-four scientists from around the world participated in this one-day workshop sponsored by IODP-MI and held in Florence, Italy, immediately prior to the Goldschmidt 2013 conference. A major topic of discussion at the workshop was the continued need for standard biological sampling and measurements across IODP platforms. Workshop participants renew the call to IODP operators to implement recommended protocols.

A large number of studies were presented at the 2014 American Heart Association Scientific Sessions. In this review, we will summarize key studies in nuclear cardiology, computed tomography, echocardiography, and cardiac magnetic resonance imaging. This brief review will be helpful for readers of the Journal who are interested in being updated on the latest research covering these imaging modalities.

Noradrenergic deficits have been described in the hippocampus and the frontal cortex of Alzheimer's disease brains, which are secondary to locus coeruleus degeneration. Locus coeruleus is the brain stem nucleus responsible for synthesis of noradrenaline and from where all noradrenergic neurons project. In addition, it has been suggested that noradrenaline might play a role in modulating inflammatory responses in Alzheimer's disease. In this study we aimed to investigate the effect of various agonists and antagonists for adrenergic receptors on amyloid precursor protein processing. Among them, we found that prazosin, an α(1)-adrenoceptor antagonist, was able to reduce the generation of amyloid β in N2a cells. Treatment of transgenic APP23 mice with prazosin prevented memory deficits over time. Although prazosin did not influence amyloid plaque load, it induced astrocytic proliferation and increased the release of apolipoprotein E and anti-inflammatory cytokines. These findings suggest that chronic treatment with prazosin leads to an anti-inflammatory response with potential beneficial effects on cognitive performance.