Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

A Cost-Utility Analysis of the Syncope: Pacing or Recording in The Later Years (SPRITELY) Trial.

Background: The Syncope: Pacing or Recording in the Later Years (SPRITELY) trial reported that a strategy of empiric permanent pacing in patients with syncope and bifascicular block reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). Our objective was to determine the cost-effectiveness of using the ICM, compared with a pacemaker (PM), in the management of older adults (age > 50 years) with bifascicular block and syncope enrolled in the SPRITELY trial. Methods: SPRITELY was a pragmatic, open-label randomized controlled trial with a median follow-up of 33 months. The primary outcome of this analysis is the cost per additional quality-adjusted life-year (QALY). Resource utilization and utility data were collected prospectively, and outcomes at 2 years were compared between the 2 arms. A decision analytic model simulated a 3-year time horizon. Results: The mean cost incurred by participants randomized to the PM arm was $9918, compared to $15,416 (both in Canadian dollars) for participants randomized to the ICM arm. The ICM strategy resulted in 0.167 QALYs fewer than the PM strategy. Cost and QALY outcomes are sensitive to the proportion of participants randomized to the ICM arm who subsequently required PM insertion. In 40,000 iterations of probabilistic sensitivity analysis, the PM strategy resulted in cost-savings in 99.7% of iterations, compared with the ICM strategy. Conclusions: The PM strategy was dominant-that is, less costly and estimated to result in a greater number of QALYs. For patients with unexplained syncope, bifascicular block, and age > 50 years, a PM is more likely to be cost-effective than an ICM.

Contexte: L'essai SPRITELY ( S yncope: P acing or R ecording i n t h e L ater Y ears) a été mené auprès de patients ayant subi une syncope et un bloc bifasciculaire. Elle a montré qu'une méthode de stimulation électrique permanente et empirique du cœur permet de réduire les événements indésirables majeurs plus efficacement qu'une méthode reposant sur les résultats d'un moniteur cardiaque implantable. Notre objectif était de déterminer le rapport coût-efficacité de l'utilisation du moniteur cardiaque implantable par rapport à un stimulateur cardiaque dans la prise en charge de personnes âgées de plus de 50 ans présentant un bloc bifasciculaire et une syncope, inscrits à l'essai SPRITELY. Méthodologie: SPRITELY était un essai contrôlé ouvert et pragmatique à répartition aléatoire, dont le suivi médian était de 33 mois. Le paramètre d'évaluation principal de cette analyse était le coût supplémentaire par année de vie ajustée en fonction de la qualité (AVAQ). Les données sur l'utilisation des ressources et l'utilité ont été recueillies de manière prospective, et les résultats à deux ans ont été comparés entre les deux groupes. Un modèle décisionnel analytique a été utilisé pour simuler un horizon temporel de trois ans. Résultats: Le coût moyen pour les participants répartis aléatoirement dans le groupe utilisant un stimulateur cardiaque était de 9 918 $ CAN comparativement à 15 416 $ CAN pour ceux utilisant un moniteur cardiaque implantable. La stratégie du moniteur cardiaque implantable s'est traduite par une réduction de 0,167 du nombre d'AVAQ par rapport à la stratégie reposant sur le stimulateur cardiaque. Les résultats relatifs aux coûts et aux AVAQ sont sensibles à la proportion de participants répartis aléatoirement dans le groupe du moniteur cardiaque implantable qui ont par la suite dû recevoir un stimulateur cardiaque. Sur 40 000 itérations de l'analyse de sensibilité probabiliste, la stratégie du stimulateur cardiaque a occasionné des économies dans 99,7 % des itérations comparativement à la stratégie du moniteur cardiaque implantable. Conclusions: La stratégie du stimulateur cardiaque était dominante, autrement dit moins coûteuse et, selon les estimations, entraînerait un plus grand nombre d'AVAQ. Pour les patients de plus de 50 ans présentant une syncope idiopathique et un bloc bifasciculaire, un stimulateur cardiaque est plus susceptible d'être moins coûteux qu'un moniteur cardiaque implantable.

Clinical and Economic Outcomes Associated With Remote Monitoring for Cardiac Implantable Electronic Devices: A Population-Based Analysis.

BACKGROUND: Despite expert recommendations advocating use of remote monitoring (RM) of cardiac implantable electronic devices, implementation in routine clinical practice remains modest due to inconsistent funding policies across health systems and uncertainty regarding the efficacy of RM to reduce adverse cardiovascular outcomes. METHODS: We conducted a population-based cohort study of patients with de novo implantable cardioverter-defibrillators (ICDs) with or without cardiac resynchronization therapy (CRT-D), using administrative health data in Alberta, Canada, from 2010 to 2016. We assessed RM status as a predictor of all-cause mortality and cardiovascular (CV) hospitalization using Cox proportional hazards modelling, and direct health costs by generalized linear models. From this real-world data, we then constructed a decision-analytic Markov model to estimate the projected costs and benefits associated with RM compared with in-clinic visit follow-up alone. RESULTS: Among 2799 ICD and CRT-D patients, 1830 (63.4%) were followed by RM for a mean follow-up of 50.3 months. After adjustment for age, sex, and comorbidities, RM was associated with a lower risk of death (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.36-0.52; P < 0.001) and CV hospitalization (HR 0.76, 95% CI 0.64-0.91; P = 0.002). In the economic model, cost savings were observed over 5 years with an estimated savings of $12,195 per person (95% CI -$21,818 to -$4,790). The model estimated a cost-savings associated with RM strategy in 99% of simulations. CONCLUSIONS: These population data support more widespread implementation of RM technology to facilitate better patient outcomes and improve health system efficiency.

Remote Monitoring of Cardiovascular Implantable Electronic Devices in Canada: Survey of Patients and Device Health Care Professionals.

BACKGROUND: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. METHODS: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. RESULTS: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. CONCLUSIONS: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients.

INTRODUCTION: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d'un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d'optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L'objectif de la présente étude était d'examiner les obstacles réels et perçus à l'utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d'optimiser les modèles de soins à distance. MÉTHODES: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. RÉSULTATS: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d'uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l'utilisation optimale et l'adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l'ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d'information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. CONCLUSIONS: L'absence d'une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l'implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l'utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l'utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection.

AIMS: Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. METHODS AND RESULTS: Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). CONCLUSIONS: A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Postural orthostatic tachycardia syndrome is associated with significant employment and economic loss.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a debilitating form of chronic orthostatic intolerance that primarily affects women and causes substantial impairment in quality of life and function. Yet, there is minimal literature describing the employment and economic consequences of POTS. We explored these aspects of the POTS patient experience through a self-reported study designed using community-based participatory research principles. METHODS AND RESULTS: A comprehensive questionnaire, including employment and economic consequences, was developed in partnership with Dysautonomia International, a patient advocacy organization. The POTS community engaged in all stages of the research design and analysis. Participants were recruited through Dysautonomia International's website and social media channels. The analysis included 5,556 adult (age ≥18 years) participants with a physician-confirmed diagnosis of POTS. The majority of participants were female (95%). Forty-eight per cent of participants reported employment during the three months prior to the survey, and of these participants, 66.8% would work greater hours if not for illness limitations. Over two-thirds (70.5%) of participants have lost income due to POTS symptoms, with 36.0% of the total cohort losing more than $10,000 USD in the 12 months prior to the survey. Almost all (95%) participants reported POTS-related out-of-pocket medical expenses since diagnosis, with 51.1% of participants spending $10,000 USD or more. CONCLUSIONS: This is the largest study reporting the employment and economic challenges experienced by individuals with POTS. Exposure of these challenges emphasizes the need for earlier diagnosis and improved therapeutic strategies to reduce the negative individual and societal consequences of this disorder.

Assessment of dynamic cardiac repolarization and contractility in patients with hypertrophic cardiomyopathy.

AIMS: Arrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy. METHODS: All participants had a cardiac implantable device capable of atrial pacing. Cases had clinical diagnosis of hypertrophic cardiomyopathy, controls were age-matched. Continuous electrocardiogram and blood pressure were recorded during and immediately after 30 second pacing trains delivered at increasing rates. RESULTS: Nine hypertrophic cardiomyopathy patients and 10 controls were enrolled (47% female, median 55 years), with similar baseline QRS duration, QT interval and blood pressure. Median septal thickness in hypertrophic cardiomyopathy patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak sub-aortic velocity >50mmHg. Ventricular ectopy occurred during or immediately after pacing trains in 4/9 hypertrophic cardiomyopathy patients and 0/10 controls (P = 0.03). During delivery of steady rate pacing across a range of cycle lengths, the QT-RR relationship was not statistically different between HCM and control groups; no differences were seen in subgroup analysis of patients with or without intact AV node conduction. Similarly, there was no difference between groups in the QT interval of the first post-pause recovery beat after pacing trains. No statistically significant differences were seen in surrogate measures for cardiac contractility. CONCLUSION: Rapid pacing trains triggered ventricular ectopy in hypertrophic cardiomyopathy patients, but not controls. This finding aligns with pre-clinical descriptions of excessive cardiomyocyte calcium loading during rapid pacing, increased post-pause sarcoplasmic reticulum calcium release, and subsequent calcium-triggered activity. Normal contractility at all diastolic intervals argues against clinical significance of altered length-dependent myofilament activation.

Remote-only monitoring for patients with cardiac implantable electronic devices: a before-and-after pilot study.

BACKGROUND: Outcomes for patients with cardiac implantable electronic devices are better when follow-up incorporates remote monitoring technology in addition to in-clinic visits. For patients with implantable devices, we sought to determine the feasibility, safety and associated health care utilization of remote-only follow-up, along with its effects on patients' quality of life and costs. METHODS: This multicentre before-and-after pilot study involved patients with new or existing pacemakers or implantable cardioverter defibrillators. The "before" phase of the study spanned the period October 2015 to February 2017; the "after" phase spanned the period October 2016 to February 2018. The exposure was remote-only follow-up in combination with Remote View, a service that facilitates access to device data, allowing device settings to be viewed remotely to facilitate remote programming. Outcomes at 12 months were feasibility (adherence to remote monitoring), safety (rate of adverse events) and health care utilization (remote and in-clinic appointments). We also assessed quality of life, using 3 validated scales, and costs, taking into account both health care system and patient costs. RESULTS: A total of 176 patients were enrolled. Adherence (defined as at least 1 successful remote transmission during follow-up) was 87% over a mean follow-up of 11.7 (standard deviation 2.2) months. There was a reduction in in-clinic visits at specialized sites among patients with both implantable defibrillators (26 v. 5, p < 0.001, n = 48) and pacemakers (42 v. 10, p < 0.001, n = 51). There was no significant change in visits to community sites for patients with defibrillators (13 v. 17, p = 0.3, n = 48). The composite rate of death, stroke, cardiovascular hospitalization and device-related hospitalization was 7% (n = 164). No adverse events were linked to the intervention. There was no change in quality-of-life scales between baseline and 12 months. Health care costs were reduced by 31% for patients with defibrillators and by 44% for those with pacemakers. INTERPRETATION: This pilot study showed the feasibility of remote-only follow-up, with no increase in adverse clinical outcomes and no effect on quality of life, but with reductions in costs and health care utilization. These results support progression to a larger-scale study of whether superior effectiveness and reduced cost can be achieved, with preservation of safety, through use of remote-only follow-up. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02585817.

Ambulance Use, Health Outcomes, and Costs for Emergency Department Visits for Primary Diagnosis of Syncope in Canada.

BACKGROUND: Syncope is a common presentation to the emergency department (ED), yet little is known regarding patient mode of arrival. METHODS: We identified patients ≥20 years old who presented to the ED with a primary diagnosis of syncope in Alberta and Ontario, Canada, between 2010 and 2016. Outcomes included 30-day in-hospital mortality, ED revisits, and rehospitalizations according to mode of arrival and discharge status. The estimated cost for ambulance use was calculated based on the provincial rates (Alberta CAD$385 and Ontario $240). RESULTS: A total of 271,601 syncope presentations to the ED were identified and 60.7% arrived by ambulance. A total of 76.3% (n = 125,793) of ambulance users and 87.0% of self-presenters (n = 92,845) were discharged from the ED. Regardless of mode of arrival, discharged patients were younger with fewer comorbidities. Compared with ambulance users admitted, those discharged had lower in-hospital mortality (0.2% vs 3.5%, P < 0.001), ED revisits (4.4% vs 10.4%, P < 0.001), and rehospitalizations (3.6% vs 10.7%, P < 0.001). Discharged self-presenters also had significantly lower outcomes (P < 0.001, for each outcome) compared with admitted self-presenters. The estimated cost for ambulance use among patients discharged from the ED was $33,137,735. CONCLUSION: A majority of syncope patients arrived to the ED by ambulance, and over 3 quarters were directly discharged home. Although discharged patients had a favourable short-term prognosis, they incurred high transportation costs. Strategies aimed at preventing unnecessary ambulance use are needed.

CONTEXTE: La syncope est une manifestation courante chez les patients qui se présentent au service des urgences; pourtant, on en sait peu sur la façon dont ces patients arrivent à l'hôpital. MÉTHODOLOGIE: Nous avons examiné les dossiers de patients âgés de 20 ans ou plus qui se sont présentés au service des urgences d'hôpitaux de l'Alberta et de l'Ontario, au Canada, et qui ont reçu un diagnostic de syncope entre 2010 et 2016. Les issues évaluées comprenaient la mortalité hospitalière à 30 jours, les nouvelles visites au service des urgences et les réadmissions à l'hôpital en fonction du mode d'arrivée et du statut au moment de la sortie de l'hôpital. Le coût estimatif des services d'ambulance a été calculé à partir des tarifs provinciaux (385 $ en Alberta et 240 $ en Ontario). RÉSULTATS: En tout, 271 601 cas de syncope ont été recensés dans les services des urgences; dans 60,7 % des cas, le patient est arrivé en ambulance. Au total, 76,3 % (n = 125 793) des patients arrivés en ambulance et 87,0 % des patients qui se sont présentés d'eux-mêmes (n = 92 845) ont reçu leur congé du service des urgences. Quel que soit leur mode d'arrivée, les patients qui ont reçu leur congé étaient plus jeunes et présentaient moins d'affections concomitantes. Chez les patients arrivés en ambulance, ceux qui ont reçu leur congé ont affiché des résultats inférieurs à ceux qui ont été admis à l'hôpital quant à la mortalité hospitalière (0,2 % vs 3,5 %, p < 0,001), aux nouvelles visites au service des urgences (4,4 % vs 10,4 %, p < 0,001) et aux réadmissions à l'hôpital (3,6 % vs 10,7 %, p < 0,001). Dans le cas des patients qui se sont présentés d'eux-mêmes, l'incidence des issues évaluées était aussi plus faible chez ceux qui ont reçu leur congé (p < 0,001 pour chaque issue) que chez ceux qui ont été admis à l'hôpital. Le coût estimatif du recours aux services d'ambulance par les patients qui ont reçu leur congé du service des urgences se chiffrait à 33 137 735 $. CONCLUSION: La majorité des patients subissant une syncope sont arrivés au service des urgences en ambulance, et plus des trois quarts ont reçu directement leur congé à la maison. Bien que le pronostic à court terme des patients ayant reçu leur congé du service des urgences ait été favorable, ces patients ont dû payer des frais de transport élevés. Des stratégies visant à prévenir le recours inutile aux services d'ambulance s'imposent.

Canadian Cardiovascular Society Clinical Practice Update on the Assessment and Management of Syncope.

Syncope is a symptom that occurs in multiple settings and has a variety of underlying causes, ranging from benign to life threatening. Determining the underlying diagnosis and prognosis can be challenging and often results in an unstructured approach to evaluation, which is ineffective and costly. In this first ever document, the Canadian Cardiovascular Society (CCS) provides a clinical practice update on the assessment and management of syncope. It highlights similarities and differences between the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society and the 2018 European Society of Cardiology guidelines, draws on new data following a thorough review of medical literature, and takes the best available evidence and clinical experience to provide clinical practice tips. Where appropriate, a focus on a Canadian perspective is emphasized in order to illuminate larger international issues. This document represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific advice. The primary writing panel wrote the document, followed by peer review from the secondary writing panel. The CCS Guidelines Committee reviewed and approved the statement. The practice tips represent the consensus opinion of the primary writing panel authors, endorsed by the CCS. The CCS clinical practice update on the assessment and management of syncope focuses on epidemiology, the initial evaluation including risk stratification and disposition from the emergency department, initial diagnostic work-up, management of vasovagal syncope and orthostatic hypotension, and syncope and driving.

Quality of life improves in vasovagal syncope patients after clinical trial enrollment regardless of fainting in follow-up.

BACKGROUND: Frequent syncope is linked to poorer health-related quality of life (HRQoL). Recurrent syncope has been observed to reduce in all groups after seeing a syncope expert and enrolling in a clinical trial. It is unknown if HRQoL improves with this reduction in syncope recurrence. OBJECTIVES: We examined the change in HRQoL over time in vasovagal syncope (VVS) patients seen by a syncope expert and enrolled in a trial. We also explored whether change differed with treatment or the frequency of fainting during follow up. METHODS: The Short Form Health Survey (SF36) was completed at baseline (BL), 6 m, and 12 m post-enrollment by VVS patients in the 1st and 2nd Prevention of Syncope Trials, which were multi-centered, randomized, placebo-controlled trials of metoprolol (POST) and fludrocortisone (POST2). Differences in HRQoL at BL, 6 m, and 12 m were analyzed and compared by faints in follow-up and randomization group. RESULTS: Complete study data were available for 143 VVS patients (40 ±â€¯17 years, 62% F). Over 12 months, patients reported improvement in all SF36 dimensions except for bodily pain. Post hoc analyses indicated that differences first occurred between BL and 6 m for all but general health. Fainting in follow-up or drug randomization group did not diminish the improvements. The baseline syncope burden was not different whether patients' HRQoL improved or not. CONCLUSION: HRQoL of VVS patients improves over time after enrolling in a clinical trial, even with recurrent faints or randomization to placebo. Improvements may result from alternative factors, such as interaction with experts or patient adjustment.

Alternative Approaches to the Assessment of the Systemic Circulation and Left Ventricular Performance: A Proof-of-Concept Study.

BACKGROUND: The purpose of this article is to examine the systemic circulation and left ventricular (LV) performance by alternative, nonconventional approaches: systemic vascular conductance (G SV ) and the head-capacity relation (ie, the relation between LV pressure and cardiac output), respectively; in so doing, we aspired to present a novel and improved interpretation of integrated cardiovascular function. METHODS: In 16 open-chest, anaesthetized pigs, we measured LV pressure (P LV ), central aortic pressure (P Ao ), and central venous pressure (P CV ) and aortic flow (Q Ao ). We calculated heart rate (HR), stroke volume, cardiac index (CI = cardiac output/body weight), mean PLV ( P ¯ LV ) , and the average arteriovenous pressure difference ( Δ P = P ¯ Ao - P ¯ CV ); G SV  = CI/( P ¯ Ao - P ¯ CV ). We studied the effects of changing loading conditions with the administration of phenylephrine (Δ P ¯ Ao ≥ +25 mm Hg), isoproterenol (ΔHR ∼+25%), sodium nitroprusside (Δ P ¯ Ao ≥ -25 mm Hg), and proximal aortic constriction (to maximize developed P LV and minimize Q Ao ). RESULTS: Sodium nitroprusside and isoproterenol increased G SV compared with phenylephrine and constriction. A maximum head-capacity curve was derived from pooled data using nonlinear regression on the maximum P ¯ LV values in Q Ao bins 12.5 mL/min/kg wide. The head-capacity relation and the plots of conductance were combined using CI as a common axis, which illustrated that CI is the output of the heart and the input of the circulation. CONCLUSIONS: Thus, at a given CI, G SV determines the driving pressure and, thereby, P Ao . We also demonstrated how decreases in G SV compensate for arterial hypotension by restoring the arteriovenous pressure difference and arterial pressure.

CONTEXTE: Le présent article examine l'efficacité de la circulation générale et la fonction ventriculaire gauche à l'aide de paramètres de rechange non conventionnels, soit la conductance vasculaire systémique (G VS ) pour l'une et la relation pression-volume (c.-à-d. la relation entre la pression ventriculaire gauche et le débit cardiaque) pour l'autre, dans le but de présenter une interprétation nouvelle et améliorée de la fonction cardiovasculaire intégrée. MÉTHODOLOGIE: Chez 16 porcs anesthésiés, nous avons mesuré à thorax ouvert la pression ventriculaire gauche (P VG ), la pression aortique centrale (P AC ), la pression veineuse centrale (P VC ) et le flux aortique (Q A ). Nous avons établi la fréquence cardiaque (FC), le volume d'éjection systolique, l'index cardiaque (IC; rapport entre le débit cardiaque et le poids corporel), la P VG moyenne ( P ¯ VG ) et la différence de pression artérioveineuse moyenne ( Δ P = P ¯ A C − P ¯ V C ); G VS  = IC/( P ¯ AC − P ¯ VC ). Nous avons aussi étudié les effets d'une modification des conditions de charge cardiaque provoquée par l'administration de phényléphrine (Δ P ¯ AC ≥ + 25 mmHg), d'isoprotérénol (ΔFC d'environ + 25 %) ou de nitroprussiate de sodium (Δ P ¯ AC ≥ − 25 mmHg) et par la constriction de l'aorte proximale (pour maximiser la P VG développée et réduire le plus possible le Q A ). RÉSULTATS: Le nitroprussiate de sodium et l'isoprotérénol ont augmenté la G VS comparativement à la phényléphrine et à la constriction. Une courbe de la relation pression-volume maximale a été dérivée à partir des données groupées, au moyen d'une régression non linéaire sur les valeurs maximales de la P ¯ VG réparties dans des classes de Q A de 12,5 ml/min/kg d'amplitude. La courbe de la relation pression-volume et le tracé de la conductance ont été superposés en utilisant l'IC comme axe commun, ce qui a permis de constater que l'IC correspond au débit cardiaque et au volume entrant dans la circulation. CONCLUSIONS: Pour un IC donné, la G VS détermine la pression motrice et donc, la P AC . Nous avons aussi démontré comment une diminution de la G VS compense l'hypotension artérielle en rétablissant la différence de pression artérioveineuse et la pression artérielle.

Status of Early-Career Academic Cardiology: A Global Perspective.

Early-career academic cardiologists, who many believe are an important component of the future of cardiovascular care, face myriad challenges. The Early Career Section Academic Working Group of the American College of Cardiology, with senior leadership support, assessed the progress of this cohort from 2013 to 2016 with a global perspective. Data consisted of accessing National Heart, Lung, and Blood Institute public information, data from the American Heart Association and international organizations, and a membership-wide survey. Although the National Heart, Lung, and Blood Institute increased funding of career development grants, only a small number of early-career American College of Cardiology members have benefited as funding of the entire cohort has decreased. Personal motivation, institutional support, and collaborators continued to be positive influential factors. Surprisingly, mentoring ceased to correlate positively with obtaining external grants. The totality of findings suggests that the status of early-career academic cardiologists remains challenging; therefore, the authors recommend a set of attainable solutions.

Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5).

BACKGROUND: Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a ß-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. STRUCTURE OF STUDY: The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis. POWER CALCULATIONS: A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. IMPLICATIONS: This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients.

Rationale for the prevention of syncope trial IV: assessment of midodrine.

BACKGROUND: Vasovagal syncope is a common problem associated with a poor quality of life, which improves when the frequency of syncope is reduced. Effective pharmacological therapies for vasovagal syncope have been elusive. Midodrine is a pro-drug whose primary metabolite is an alpha-1 adrenoreceptor agonist. A few studies have suggested that it may be beneficial in syncope, but all have had significant methodological limitations. A placebo-controlled clinical trial of midodrine for the prevention of vasovagal syncope is needed. STRUCTURE OF STUDY: The prevention of syncope trial IV (POST 4) is a multicenter, international, randomized, placebo-controlled study of midodrine in the prevention of vasovagal syncope. The primary end point is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive midodrine 10-30 mg/day or matching placebo, and followed for 1 year. Secondary end points include syncope frequency, presyncope, and quality of life. Primary analysis will be performed with an intention-to-treat approach, with a secondary on-treatment analysis. POWER CALCULATIONS: A total sample size of 112, split equally between the two groups, achieves 85 % power to detect a 50 % relative risk reduction when the event rates are 55 and 27.5 % in the placebo and midodrine arms. Allowing for 20 % dropout, we propose to enroll 140 patients. REGISTRATION: POST 4 is registered with http://www.clinicaltrials.gov (NCT01456481). IMPLICATIONS: This study will be the first adequately powered trial to determine whether midodrine is effective in preventing vasovagal syncope. If it is effective, then midodrine may become the first-line pharmacological therapy for this condition.