Venous thromboembolism (VTE) is responsible for the hospitalization of >250 000 Americans annually and represents a significant risk for morbidity and mortality. Despite the publication of evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms, the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pulmonary embolism (PE), iliofemoral deep vein thrombosis (IFDVT),and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician.

Non-technical summary Exercise causes an increase in sympathetic activity which helps to redistribute blood flow while maintaining blood pressure. The exact mechanisms that regulate sympathetic activity and blood flow during exercise are not completely understood. By modulating the activity of a specific chemical receptor (the carotid chemoreceptor), we showed that this receptor contributes to the regulation of blood flow during exercise in healthy subjects. These findings demonstrate the importance of the carotid chemoreceptor in the regulation of blood flow during exercise in health.Abstract Carotid chemoreceptor (CC) inhibition reduces sympathetic nervous outflow in exercising dogs and humans. We sought to determine if CC suppression increases muscle blood flow in humans during exercise and hypoxia. Healthy subjects (N = 13) were evaluated at rest and during constant-work leg extension exercise while exposed to either normoxia or hypoxia (inspired O 2 tension, F IO 2 , ≈ 0.12, target arterial O 2 saturation = 85%). Subjects breathed hyperoxic gas (F IO 2 ≈ 1.0) and/or received intravenous dopamine to inhibit the CC while femoral arterial blood flow data were obtained continuously with pulsed Doppler ultrasound. Exercise increased heart rate, mean arterial pressure, femoral blood flow and conductance compared to rest. Transient hyperoxia had no significant effect on blood flow at rest, but increased femoral blood flow and conductance transiently during exercise without changing blood pressure. Similarly, dopamine had no effect on steady-state blood flow at rest, but increased femoral blood flow and conductance during exercise. The transient vasodilatory response observed by CC inhibition with hyperoxia during exercise could be blocked with simultaneous CC inhibition with dopamine. Despite evidence of dopamine reducing ventilation during hypoxia, no effect on femoral blood flow, conductance or mean arterial pressure was observed either at rest or during exercise with CC inhibition with dopamine while breathing hypoxia. These findings indicate that the carotid chemoreceptor contributes to skeletal muscle blood flow regulation during normoxic exercise in healthy humans, but that the influence of the CC on blood flow regulation in hypoxia is limited.

Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart failure (HF), and sensitivity is linked to greater mortality. This study aimed to determine the role of the peripheral chemoreceptor in cardiovascular control at rest and during exercise in HF patients and controls. Clinically stable HF patients (n = 11; ejection fraction: 39 ± 5%) and risk-matched controls (n = 10; ejection fraction: 65 ± 2%) performed randomized trials with or without dopamine infusion (2 μg·min(-1)·kg(-1)) at rest and during 40% maximal voluntary contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100% oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral chemoreceptor. At rest in HF patients, dopamine decreased ventilation (P = 0.02), decreased total peripheral resistance index (P = 0.003), and increased cardiac and stroke indexes (P ≤ 0.01), yet there was no effect of dopamine on these variables in controls (P ≥ 0.7). Hyperoxia lowered ventilation in HF (P = 0.01), but not in controls (P = 0.9), indicating suppression of the peripheral chemoreceptors in HF. However, no decrease of total peripheral resistance index was observed in HF. As expected, HG increased heart rate, ventilation, and brachial conductance of the nonexercising arm in controls and HF patients. During dopamine infusion, there were no changes in mean arterial pressure, heart rate, or ventilation responses to HG in either group (P ≥ 0.26); however, brachial conductance increased with dopamine in the control group (P = 0.004), but decreased in HF (P = 0.02). Our findings indicate that the peripheral chemoreceptor contributes to cardiovascular control at rest in HF patients and during exercise in risk-matched controls.

New knowledge about maleefemale differences in pathophysiology, diagnosis, and treatment is shifting the practice of medicine from a one-size-fits all approach to a more individualized process that considers sex-specific interventions at the point of care. In this article, we review how clinical practice guideline committees can incorporate a structured framework to determine whether sex-specific assessments of the quality of the evidence or the particular recommendations should be made. The process can be operationalized by societies who author clinical practice guidelines by developing formal policies to approach biological sex in a systematic way, and by ensuring that writing committees include an individual who will champion the formal appraisal of the literature for associations between sex and the outcomes of interest. Ongoing challenges are discussed, and solutions are provided for how to disaggregate the evidence, how to assess bias, how to improve search strategies, and what to do when the data are Sex Matters in Cardiovascular DiseaseCardiovascular medicine is arguably most advanced in its understanding of clinically significant biologic differences between the sexes, from prevention to treatment. 3,4 Risk factors for heart disease and stroke are known to vary between men and women. 5,6 Clinical presentations of acute coronary syndrome differ, men experience earlier onset disease, and

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