Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients.

In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of ß-adrenergic receptors, ß-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.

Cold, clumpy accretion onto an active supermassive black hole.

Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales. The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas. Recent theory and simulations instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds--a departure from the 'hot mode' accretion model--although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z = 0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma. Under the right conditions, thermal instabilities produce a rain of cold clouds that fall towards the galaxy's centre, sustaining star formation amid a kiloparsec-scale molecular nebula that is found at its core. The observations show that these cold clouds also fuel black hole accretion, revealing 'shadows' cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole, which serves as a bright backlight. Corroborating evidence from prior observations of warmer atomic gas at extremely high spatial resolution, along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it.

Diversity-Function Relationships in Natural, Applied, and Engineered Microbial Ecosystems.

The connection between ecosystem function and taxonomic diversity has been of interest and relevance to macroecologists for decades. After many years of lagging behind due to the difficulty of assigning both taxonomy and function to poorly distinguishable microscopic cells, microbial ecology now has access to a suite of powerful molecular tools which allow its practitioners to generate data relating to diversity and function of a microbial community on an unprecedented scale. Instead, the problem facing today's microbial ecologists is coupling the ease of generation of these datasets with the formulation and testing of workable hypotheses relating the diversity and function of environmental, host-associated, and engineered microbial communities. Here, we review the current state of knowledge regarding the links between taxonomic alpha- and beta-diversity and ecosystem function, comparing our knowledge in this area to that obtained by macroecologists who use more traditional techniques. We consider the methodologies that can be applied to study these properties and how successful they are at linking function to diversity, using examples from the study of model microbial ecosystems, methanogenic bioreactors (anaerobic digesters), and host-associated microbiota. Finally, we assess ways in which our newly acquired understanding might be used to manipulate diversity in ecosystems of interest in order to improve function for the benefit of us or the environment in general through the provision of ecosystem services.

Neurohormone levels remain elevated in continuous flow left ventricular assist device recipients.

INTRODUCTION: The levels of neurohormones were assessed in continuous-flow left ventricular assist device (CF-LVAD) recipients and compared to patients with heart failure (HF) and to healthy controls (HCs), and CF-LVAD recipients with closed or open aortic valves (AVs). METHODS: Aldosterone, norepinephrine, and renin levels were assessed in a total of 46 participants, including CF-LVAD recipients (n = 18), HF patients (n = 14), and HC individuals (n = 14). Echocardiographic assessments were performed to evaluate cardiac functions and aortic valve status and neurohormone levels were compared between CF-LVAD recipients with closed or open AVs. RESULTS: Aldosterone, norepinephrine, and renin levels were elevated to a similar extent in CF-LVAD recipients and HF patients, compared to HC individuals. In the CF-LVAD group, no differences were found between the levels of norepinephrine and aldosterone between recipients with AV opened or closed. With an open AVs, CF-LVAD recipients had higher levels of renin compared to recipients with closed AVs. However, an open AV was only a weak predictor of higher levels of renin. CONCLUSION: The findings that aldosterone, norepinephrine, and renin were elevated after restoration of hemodynamic functions during LVAD support suggest that the levels of neurohormones did not normalize. Future studies should investigate whether AV status in CF-LVAD recipients affects the levels of RAAS neurohormones and the mechanisms and clinical implications of elevated levels of neurohormones in CF-LVAD patients.

Reevaluating Modality of Cardiopulmonary Exercise Testing in Patients with Heart Failure and Resynchronization Therapy: Relevance of Heart Rate-Adaptive Pacing.

BACKGROUND: Chronotropic incompetence (CI) in heart failure (HF) patients with cardiac resynchronization therapy (CRT) and activity sensors may vary according to exercise modality. We hypothesized that chronotropic response and exercise capacity differ when HF patients with CRT and heart rate (HR) adaptive pacing are exercised on cycloergometer versus treadmill. METHODS AND RESULTS: This is a crossover study in which stable HF patients with CRT and HR-adaptive pacing triggered by activity sensors underwent maximal symptom-limited cardiopulmonary exercise testing on both a cycloergometer and treadmill. Adjusted percent of HR reserve (%HRR) was calculated as HRR/age-predicted HRR. CI was defined as ≤62% of age-predicted HRR. Among 16 patients (59 ± 10 years, ejection fraction 27 ± 12%, 87% on beta-blockers), prevalence of CI was high irrespective of exercise modality (87.5% on cycloergometer vs 62.5% on treadmill; P = .12). Chronotropic responses were better on the treadmill; %HRR was higher on a treadmill vs cycloergometer (61 ± 26% vs 22 ± 31%; P = .003). Peak oxygen consumption was increased by 24% on a treadmill vs cycloergometer (15.8 vs 12.7 mL/kg/min; P < .0001). CONCLUSIONS: In HF patients with CRT and HR-adaptive pacing, treadmill cardiopulmonary exercise testing enhances chronotropic response, HRR, and peak oxygen consumption compared with a cycloergometer. These findings may have implications in exercise prescription and thresholds for advanced therapies such as heart transplantation and ventricular assist devices.

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.

Canadian Cardiovascular Society-Canadian Heart Failure Society Focused Clinical Practice Update of Patients With Differing Heart Failure Phenotypes.

A number of societies produce heart failure (HF) management guidelines, comprising official recommendations on the basis of recent research discoveries, but their applicability to specific situations encountered in daily practice might be difficult. In this clinical practice update we aim to provide responses to fundamental questions that face health care providers, like appropriate timing for the introduction and optimization of different classes of medication according to specific patient phenotypes, when second-line therapies and valvular interventions should be considered, and management of difficult clinical scenarios such as cardiorenal syndrome and frailty. A consensus-based methodology was used. Approaches to 5 different phenotypes are presented: (1) The wet HF phenotype is the easiest to manage, decongestion being performed alongside introduction of guideline-directed medical therapy (GDMT); (2) The de novo HF phenotype requires the introduction of the 4 pillars of GDMT, personalizing the order on the basis of the individuals' biological and physiological characteristics; (3) The worsening HF phenotype is a marker of poor prognosis, and therefore should motivate optimization of GDMT, start second-line therapies, and/or reevaluate goals of care/advanced HF therapies; (4) The cardiorenal phenotypes require correct volume assessment, because renal function usually improves with decongestion; and (5) The frail HF phenotype require special attention, careful drug titration, and consideration of cardiac rehabilitation programs. In conclusion, specific common HF phenotypes call for a personalized approach to improve adoption of the HF guidelines into clinical practice.

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

The evidence for pharmacist care in outpatients with heart failure: a systematic review and meta-analysis.

AIMS: Patients with heart failure (HF) have poor outcomes, including poor quality of life, and high morbidity and mortality. In addition, they have a high medication burden due to the multiple drug therapies now recommended by guidelines. Previous reviews, including studies in hospital settings, provided evidence that pharmacist care improves outcomes in patients with HF. Because most HF is managed outside of hospitals, we aimed to synthesize the evidence for pharmacist care in outpatients with HF. METHODS AND RESULTS: We conducted a systematic literature search in PubMed of randomized controlled trials (RCTs) and integrated the evidence on patient outcomes in a meta-analysis. We found 24 RCTs performed in 10 countries, including 8029 patients. The data revealed consistent improvements in medication adherence (independent of the measuring instrument) and knowledge, physical function, and disease and medication management. Sixteen RCTs were included in meta-analyses. Differences in all-cause mortality (odds ratio (OR) = 0.97 [95% CI, 0.84-1.12], Q-statistic, P = 0.49, I2  = 0%), all-cause hospitalizations (OR = 0.86 [0.73-1.03], Q-statistic, P = 0.01, I2  = 45.5%), and HF hospitalizations (OR = 0.89 [0.77-1.02], Q-statistic, P = 0.11, I2  = 0%) were not statistically significant. We also observed an improvement in the standardized mean difference for generic quality of life of 0.75 ([0.49-1.01], P < 0.01), with no indication of heterogeneity (Q-statistic, P = 0.64; I2  = 0%). CONCLUSIONS: Results indicate that pharmacist care improves medication adherence and knowledge, symptom control, and some measures of quality of life in outpatients with HF. Given the increasing complexity of guideline-directed medical therapy, pharmacists' unique focus on medication management, titration, adherence, and patient teaching should be considered part of the management strategy for these vulnerable patients.

Phase 0 Radiopharmaceutical-Agent Clinical Development.

The evaluation of antibody-targeted or peptide-targeted radiopharmaceuticals as monotherapy or in oncological drug combinations requires programmatic collaboration within the National Cancer Institute (NCI) clinical trial enterprise. Phase 0 trials provide a flexible research platform for the study of radiopharmaceutical-drug pharmacokinetics, radiation dosimetry, biomarkers of DNA damage response modulation, and pharmacodynamic benchmarks predictive of therapeutic success. In this article, we discuss a phase 0 clinical development approach for human antibody-targeted or peptide-targeted radiopharmaceutical-agent combinations. We expect that early-phase radiopharmaceutical-agent combination trials will become a more tactical and more prevalent part of radiopharmaceutical clinical development in the near-term future for the NCI Cancer Therapy Evaluation Program.

Association Between Neurohormone Levels and Exercise Testing Measures in Patients with Mechanical Circulatory Supports.

Continuous-flow left ventricular assist device (CF-LVAD) recipients exhibit impaired exercise capacity. Long-term continuous blood flow also elevates norepinephrine (NE) and aldosterone (Aldo) levels. However, the relationship between exercise capacity and neurohormonal activation has not been elucidated. Our study objective was to assess the association between cardiopulmonary exercise testing (CPT) measures and neurohormonal levels in CF-LVAD recipients. Symptom-limited CPT on a treadmill, using the modified Bruce protocol was performed in 15 CF-LVAD recipients. Norepinephrine and Aldo levels were measured, and the association between their levels and CPT measures were assessed. Peak VO2 (13.6 ml/kg/min) and percent age, sex predicted VO2 max (49.4%), and oxygen pulse (O2 pulse) (9.0 ± 4.0 ml/beat) were low, whereas minute ventilation/carbon dioxide output (VE/VCO2) slope (35) was elevated. In addition, VO2 at anaerobic threshold (VO2 AT), and O2 pulse values negatively correlated with NE levels. Norepinephrine levels positively correlated with chronotropic responses and heart rate (HR) recovery. Aldo levels in CF-LVAD recipients were not related to any CPT measures. Continuous-flow left ventricular assist device recipients exhibited impaired exercise capacity and chronotropic incompetence (CI). Despite the association of NE levels with chronotropic responses at peak exercise, neither NE levels nor chronotropic responses predicted peak VO2. This suggests that CI may not be the primary factor responsible for the low peak VO2. O2 pulse, which is a combined measure for stroke volume and peripheral oxygen extraction during exercise, was an independent predictor of peak VO2. Future studies should examine the contribution of peripheral factors to exercise capacity limitations.

Trying to succeed when the right ventricle fails.

PURPOSE OF REVIEW: Compared with the left ventricle, studies of right ventricular failure as a distinct clinical entity have lagged behind. Evolving appreciation of the prognostic significance of right ventricular dysfunction in the heart failure population and advances in noninvasive imaging have provided the impetus for recent investigation into the assessment and management of right ventricular failure. RECENT FINDINGS: Pulmonary hypertension and attendant right ventricular dysfunction are prevalent in patients with systolic and diastolic heart failure and are associated with poor survival. Simple echocardiographic and MRI indices of right ventricular function relate to prognosis and may also be useful in following response to therapy. Management of acute and chronic right ventricular failure is largely empiric and is focused on treating the underlying cause along with judicious use of diuretics and inotropes. The use of left ventricular assist devices to help treat pulmonary hypertension in heart failure is an emerging strategy in transplant-eligible patients. SUMMARY: Right ventricular failure is clinically significant and merits further dedicated study. Parameters of right ventricular dysfunction can be assessed noninvasively. An approach to the management of acute and chronic right ventricular failure should take into consideration novel pharmacologic and device-based therapies.

Acoustic fingerprints of dye-labeled protein submicrosphere photoacoustic contrast agents.

Dye-labeled protein microspheres, submicron in size and capable of producing thermoelastically generated ultrasound in response to laser stimulation, are presented as contrast agents for photoacoustic imaging. Incident laser energy absorbed by fluorescein isothiocyanate (FITC)-labeled elastin submicrospheres results in thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and a greater than two orders of magnitude increase in signal amplitude subsequent to converting FITC elastin into submicrospheres (despite a four orders of magnitude decrease in concentration). Evidence of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic imaging. Photoacoustic and ultrasound imaging of FITC-elastin submicrospheres in a water-filled phantom vessel shows enhanced contrast at low concentration and clear delineation of the phantom vessel wall.

Ventricular Standstill in a Patient With a Left Ventricular Assist Device.

A 58-year-old woman had medically refractory heart failure due to idiopathic dilated cardiomyopathy. She underwent tricuspid repair and left ventricular assist device implantation for inotropic-dependent heart failure. Because of severe right ventricular dysfunction, she experienced progressive bradycardia and ventricular asystole with electrocardiographic and echocardiographic standstill. Despite the lack of native cardiac activity, she maintained end-organ perfusion with inotropic support until she underwent successful transplantation. This report highlights a case of mechanical circulatory support with an isolated left ventricular assist device implantation even in the absence of native right ventricular function.

Optimal Strategy and Timing of Left Ventricular Venting During Veno-Arterial Extracorporeal Life Support for Adults in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Veno-arterial extracorporeal life support (VA-ECLS) is widely used to treat refractory cardiogenic shock. However, increased left ventricular (LV) afterload in VA-ECLS can worsen pulmonary congestion and compromise myocardial recovery. Our objectives were to explore the efficacy, safety, and optimal timing of adjunctive LV venting strategies. METHODS: A systematic search was performed on Medline, EMBASE, PubMed, CDSR, CCRCT, CINAHL, ClinicalTrials.Gov, and WHO ICTRP from inception until January 2019 for all relevant studies, including LV venting. Data were analyzed for mortality and weaning from VA-ECLS on the basis of timing of LV venting, along with adverse complications. RESULTS: A total of 7995 patients were included from 62 observational studies, wherein 3458 patients had LV venting during VA-ECLS. LV venting significantly improved weaning from VA-ECLS (odds ratio, 0.62 [95% CI, 0.47-0.83]; P=0.001) and reduced short-term (30 day; risk ratio [RR], 0.86 [95% CI, 0.77-0.96]; P=0.008) but not in-hospital (RR, 0.92 [95% CI, 0.83-1.01] P=0.09) or long-term (6 months; RR, 0.96 [95% CI, 0.90-1.03]; P=0.27) mortality. Early (<12 hours; RR, 0.86 [95% CI, 0.75-0.99]; P=0.03) but not late (≥12 hours; RR, 0.99 [95% CI, 0.71-1.38]; P=0.93) LV venting significantly reduced short-term mortality. Patients with LV venting spent more time on VA-ECLS (3.6 versus 2.8 days, P<0.001), and mechanical ventilation (7.1 versus 4.6 days, P=0.013). With the exception of hemolysis (RR, 2.18 [95% CI, 1.58-3.01]; P<0.00001), overall adverse events did not differ. CONCLUSIONS: LV venting, especially if done early (<12 hours), appears to be associated with an increased success of weaning and reduced short-term mortality. Future studies are required to delineate the importance of any or early LV venting adjuncts on mortality and morbidity outcomes.

Tau pathology in cognitively normal older adults.

INTRODUCTION: Tau pathology, a hallmark of Alzheimer's disease, is observed in the brains of virtually all individuals over 70 years. METHODS: Using 18F-AV-1451 (18F-flortaucipir) positron emission tomography, we evaluated tau pathology in 54 cognitively normal participants (mean age: 77.5 years, SD: 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between positron emission tomography signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status. RESULTS: Greater age, male sex, black race, and amyloid positivity were associated with higher 18F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (ß = -1.124, SE = 0.485, P = .025) and a steeper decline in memory performance (ß = -0.086, SE = 0.039, P = .029). DISCUSSION: Assessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer's disease.

Clinical risk scoring beyond initial troponin values: results from a large, prospective, unselected acute chest pain population.

BACKGROUND: Risk stratifying the diverse group of patients who present to hospital with chest discomfort remains challenging. Current clinical risk models, typically derived from selected populations, are limited by their relative complexity and the absence of a well-defined role of troponin. OBJECTIVE: To derive a simple clinical risk score from a large, unselected population of patients with chest discomfort and to delineate the prognostic value of an initial troponin measurement. METHODS: Prospective, consecutive data were collected from patients who presented to a tertiary care hospital. Multivariate analysis was used to identify variables predictive of the primary end point: death, nonfatal myocardial infarction or revascularization at 30 days. Integer values were assigned, generating a risk score to quantify individual patient risk. RESULTS: Among 1054 patients, predictor variables included ST-segment deviation (strongest predictor -- assigned two points), male sex, prior congestive heart failure, three or more cardiac risk factors and prior acetylsalicylic acid use (one point each). There was a progressive increase in events with increasing total score (P<0.0001), with a 15-fold gradient from scores of 0 to 4 and greater. Although a negative troponin measurement was associated with fewer events for all scores, patients with higher scores remained exposed to substantial risk. A negative initial troponin measurement conferred a negative predictive value of 97.3% (95% CI 93.7% to 99.1%) among patients with a risk score of 0. CONCLUSION: Significant 30-day events occurred in patients with elevated risk scores, despite negative initial troponin measurements, emphasizing the importance of clinical risk stratification. This simple clinical risk score, in conjunction with a single troponin I measurement, facilitates triage of patients who present to hospital with chest discomfort.

Mind the Gap: Current Challenges and Future State of Heart Failure Care.

The past decade has seen many advances in the management of heart failure (HF) that have improved survival and quality of life for patients living with this condition. A number of gaps remain in our understanding of the pathophysiology of HF, and the application of emerging treatment strategies is an exciting but daunting challenge. It is possible that advances in genetic evaluation of cardiomyopathy will provide a more refined approach to characterizing HF syndromes, whereas large-scale clinical trials on the horizon should further clarify the role of novel pharmacologic agents and invasive therapies. Cardiac repair and regeneration hold great promise, but a number of pragmatic issues will limit clinical application in the near term. Replacing cardiac function with ventricular assist devices represents significant progress in the management of advanced disease; however, unacceptable rates of complications and costs need to be addressed before broader use in the general HF population is feasible. The ability to personalize care is limited, and the optimal model of disease management in the Canadian context remains uncertain. The emergence of biomarker-guided management and remote monitoring technologies might facilitate a more personalized approach to care in an effort to maintain health and stability and to prevent worsening HF. Ultimately, a greater understanding of how and when to intervene in the setting of acute HF should translate into improved outcomes for the highest-risk subgroup of patients. This review highlights key challenges in the management of HF and highlights the progress toward an ideal future state.