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Ify R Mordi,1,2 Athar A Badar,2 R John Irving,2 Jonathan R Weir-McCall,1 J Graeme Houston,1 Chim C Lang1,2 1Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK; 2Department of Cardiology, Ninewells Hospital and Medical School, Dundee, UK Abstract: The aim of this review was to discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20 years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In this review, we examine the current state-of-the-art in noninvasive imaging to provide an up-to-date analysis of current investigation and management options. Keywords: angina, noninvasive imaging, SPECT, stress echo, cardiovascular magnetic resonance, CT coronary angiography

Jagdeep SS Singh, Chim C Lang Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. Keywords: heart failure, angiotensin receptor-neprilysin inhibitor, heart failure with preserved ejection fraction, nesiritide, candoxatril, omapatrilat, hypertension, renal impairment, myocardial infarction

Here, we report on new multi-wavelength radio observations of the unusual point source "N3" that appears to be located in the vicinity of the Galactic Center (GC). VLA observations between 2 and 50 GHz reveal that N3 is a compact and bright source (56 mJy at 10 GHz) with a non-thermal spectrum superimposed upon the non-thermal radio filaments (NTFs) of the Radio Arc. Our highest frequency observations place a strict upper limit of 65 × 28 mas on the size of N3. We compare our observations to those of Yusef-Zadeh & Morris and Lang et al., and conclude that N3 is variable over long timescales. Additionally, we present the detection of a compact molecular cloud located adjacent to N3 in projection. CH3CN, CH3OH, CS, HC3N, HNCO, SiO, SO, and NH3are detected in the cloud, and most transitions have FWHM line widths of ∼20 km s-1. The rotational temperature determined from the metastable NH3transitions ranges from 79 to 183 k depending on the transitions used. We present evidence that this molecular cloud is interacting with N3. After exploring the relationship between the NTFs, molecular cloud, and N3, we conclude that N3 likely lies within the GC. We are able to rule out the H ii region, young supernova, active star, AGN, and micro-quasar hypotheses for N3. While a micro-blazar may provide a viable explanation for N3, additional observations are needed to determine the physical counterpart of this mysterious source.

We present new observations of the quiescent giant molecular cloud GCM0.253+0.016 in the Galactic center, using the upgraded Karl G. Jansky Very Large Array. Observations were made at wavelengths near 1 cm, at the K (24-26 GHz) and Ka (27 and 36 GHz) bands, with velocity resolutions of 1-3 km s-1 and spatial resolutions of ∼0.1 pc, at the assumed 8.4 kpc distance of this cloud. The continuum observations of this cloud are the most sensitive yet made, and reveal previously undetected emission which we attribute primarily to free-free emission from external ionization of the cloud. In addition to the sensitive continuum map, we produce maps of 12 molecular lines: 8 transitions of NH3-(1, 1), (2, 2), (3, 3), (4, 4), (5, 5), (6, 6), (7, 7), and (9, 9), as well as the HC3N (3-2) and (4-3) lines, and CH3OH 4-1-30, the latter of which is known to be a collisionally excited maser. We identify 148 CH3OH 4-1-30 (36.2 GHz) sources, of which 68 have brightness temperatures in excess of the highest temperature measured for this cloud (400 K) and can be confirmed to be masers. The majority of these masers are concentrated in the southernmost part of the cloud. We find that neither these masers nor the continuum emission in this cloud provide strong evidence for ongoing star formation in excess of that previously inferred by the presence of an H2O maser.

At a distance of 8 kpc, the center of our Galaxy is the nearest galacticnucleus, and has been the subject of numerous key projects undertaken by greatobservatories such as Chandra, Spitzer, and Herschel. However, there are stillno surveys of molecular gas properties in the Galactic center with less than30" (1 pc) resolution. There is also no sensitive polarization survey of thisregion, despite numerous nonthermal magnetic features apparently unique to thecentral 300 parsecs. In this paper, we outline the potential the VLASS has tofill this gap. We assess multiple considerations in observing the Galacticcenter, and recommend a C-band survey with 10 micro-Jy continuum RMS andsensitive to molecular gas with densities greater than 10^4 cm^{-3}, covering17 square degrees in both DnC and CnB configurations ( resolution ~5"),totaling 750 hours of observing time. Ultimately, we wish to note that theupgraded VLA is not just optimized for fast continuum surveys, but has apowerful correlator capable of simultaneously observing continuum emission anddozens of molecular and recombination lines. This is an enormous strength thatshould be fully exploited and highlighted by the VLASS, and which is ideallysuited for surveying the center of our Galaxy.

Aortic valve disease (AVD) is the most common form of valvular heart disease in the western world. The only proven therapy for severe AVD is open aortic valve replacement, with trans-catheter aortic valve implantation emerging as a promising modality to treat severe aortic stenosis in a selected group of patients. AVD has a long asymptomatic phase with symptoms occurring late in the disease and once symptoms develop, prognosis is poor. There is a growing appreciation that aortic valvular heart disease incorporates a disease process that extends beyond the valve itself leading to an aortic valvular 'heart' disease. The renin-angiotensin system is known to modulate adverse left ventricular remodeling and myocardial fibrosis, which could be caused by increased load caused by the AVD. In this review, the authors explore evidence that suggest that drugs that target the renin-angiotensin system may have a potential therapeutic role in AVD. [ABSTRACT FROM AUTHOR]

Background: Right ventricular apical pacing can cause dyssynchronous activation of the ventricles, increase sympathetic activation, cause abnormalities in myocardial perfusion, worsen cardiac output and endothelial function, and may be associated with adverse cardiovascular effects. The use of rennin-angiotensin system blockers (RASBs) may be beneficial in counteracting these potentially harmful effects of right ventricular pacing. Objective: To explore the impact of RASB use on the outcome in patients with right ventricular pacemakers implanted for complete atrioventricular (AV) block. Methods: Patients implanted with right ventricular pacemakers for complete AV block between 1994 and 2009 were identified from the Tayside Pacing Registry. Cox proportional hazards model was used to assess differences in all-cause mortality and congestive heart failure hospitalizations for those receiving RASB during follow-up, adjusted for confounding variables. We also performed 2 sensitivity analyses--a propensity score-matched analysis and time-dependent analyses--to minimize bias. Results: Eight hundred twenty patients (57% men; median age 73 years; range 22-103 years) received pacemakers for complete AV block between 1994 and 2008 (54% dual-chamber pacemaker and 46% ventricular demand pacemaker). Two hundred seventy-eight (34%) patients had received RASBs. Mean follow-up was 4.9 ± 4.6 years, with 540 (65%) deaths. RASB use was independently associated with significantly reduced mortality (adjusted hazard ratio 0.67; 95% confidence interval 0.47-0.94; P = .017) and reduced heart failure hospitalization (adjusted hazard ratio 0.42; 95% confidence interval 0.17-0.92; P <.001). Conclusions: This study suggests that RASBs may confer outcome benefits in patients with right ventricular pacemakers implanted for complete AV block. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to demonstrate in patients with moderate to severe heart failure that exertional dyspnea can be alleviated by improving muscle function.Background: Dyspnea is a frequent limiting symptom in patients with chronic heart failure (CHF). This sensation may originate from activation of receptors in the musculature rather than the lung.Methods: To investigate whether dyspnea could be alleviated by selective changes in leg muscle function, we performed isolated lower-limb training in 17 patients with severe CHF. Eight patients learned guided imagery relaxation techniques and served as an active control group. Exercise training consisted of three months of low-level bicycle and treadmill exercise such that minute ventilation was <25 l/min. Leg calisthenics were also performed. Maximal and submaximal exercise performance, respiratory and quadriceps muscle strength and endurance and quality-of-life and dyspnea scales were measured before and after each intervention. Metabolic stress testing (VO(2)), pulmonary function tests and isokinetic strength testing were also performed.Results: In the active control group, no changes in leg muscle function, pulmonary function, maximal and submaximal exercise performance or quality-of-life questionnaires were observed. In the training group, peak torque of leg flexors (pre: 39 +/- 15 ft-lb; post: 50 +/- 13 ft-lb; p < 0.002) increased and the fatigue ratio decreased, indicating improved strength and endurance of the leg muscles. Maximal inspiratory and expiratory mouth pressures and maximum voluntary ventilation were unchanged. Peak VO(2) was increased (pre:12 +/- 2.2 ml/kg/min; post: 14 +/- 2.6 ml/kg/min) as well as the duration of exercise at 70% peak VO(2) increased (pre: 11.5 +/- 3.1 min; post: 21.5 +/- 5.4 min; p < 0.003). Perceived dyspnea during the submaximal testing was decreased. Minnesota Living with Heart Failure Score, Guyatt Dyspnea Scale, and the Transitional Dyspnea Index were all improved with training (all p < 0.05).Conclusions: We concluded that improvement of limb muscle function alleviates dyspnea and improves exercise performance in patients with CHF. [ABSTRACT FROM AUTHOR]