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Background Valvular heart disease contributes to symptomatic heart failure, but its prevalence and prognostic significance in advanced heart failure is not well understood. Methods This retrospective population‐based cohort study included adult residents of Olmsted County, Minnesota, with advanced heart failure (2007–2018). Patients were classified by echocardiographic regurgitation and stenosis of aortic, mitral, tricuspid, and pulmonic valves at the time of advanced heart failure. We examined the associations of aortic stenosis, mitral regurgitation, and tricuspid regurgitation with risks of cardiovascular and all‐cause death through 2023 using Cox proportional hazards models. Results There were 936 patients with advanced heart failure (mean age, 76.9 years; 44.5% women, 43.4% with heart failure with preserved ejection fraction). Moderate or greater regurgitation was observed in 2.8% (n=26) of aortic, 26% (n=244) of mitral, 42% (n=389) of tricuspid, and 4.3% (n=40) of pulmonic valves, while moderate or greater stenosis was observed in 9.7% (n=91) of aortic and 1.8% (n=17) of mitral valves. No patients had clinically significant tricuspid or pulmonic stenosis. After adjustment for age, sex, left ventricular ejection fraction, right ventricular function, serum sodium, Charlson comorbidity index, body mass index, and systolic blood pressure, moderate and severe aortic stenosis were associated with increased cardiovascular death compared with patients without aortic stenosis (hazard ratio [HR], 1.42 [95% CI, 1.01–2.01]; and HR, 1.55 [95% CI, 1.02–2.36]), respectively. Conclusions Tricuspid regurgitation, mitral regurgitation, and aortic stenosis were the most observed valvular pathologies of moderate or greater severity in advanced heart failure. Only moderate or greater aortic stenosis was independently associated with cardiovascular death in advanced heart failure.

Abstract The sections in this article are: Pathogenesis of Type I Diabetes Effect of Type I Diabetes on Carbohydrate Metabolism Insulin Secretion and Action Postabsorptive and Postprandial Carbohydrate Metabolism Effects of Type I Diabetes and Its Treatment on Fatty Acid Metabolism Adipose Tissue Postabsorptive FFA Metabolism Postprandial FFA Availability Effects of Exercise on Adipose Tissue Lipolysis Regulation of Lipolysis During Hypoglycemia Effects Of Type I Diabetes on Protein Metabolism Regulation of Body Protein Mass, Amino Acid Levels and Nitrogen Balance Effect of Insulin on Protein Balance and Interaction of Insulin with Other Hormones and Substrates Effects of Insulin on Whole‐Body Protein Dynamics Effect of Insulin on Amino Acid Transamination Effect of Insulin on Regional Protein Dynamics Effect of Insulin on the Synthesis Rates of Specific Proteins Impact of Type I Diabetes on Protein Metabolism

Abstract The sections in this article are: Molecular Actions of Thyroid Hormone Thyroid Hormone Regulation of Growth and Development Extrahypothalamic Thyrotropin‐Releasing Hormone Metabolic Actions of Islet Cell Hormones Insulin Glucagon Amylin Calcitonin Gene‐Related Peptide Somatostatin Pancreatic Polypeptide Thyroid Hormone Regulation of Insulin Metabolic Actions Euthyroidism Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Glucagon Metabolic Actions Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Somatostatin Metabolic Actions Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Pancreatic Polypeptide Metabolic Actions Summary and Conclusions

Abstract The sections in this article are: Regulation of the Upper Airway During Exercise Anatomy and Physiology of the Upper Airway Contractile Properties and Endurance of Upper Airway Muscles Changes in Upper Airway Flow Resistance During Exercise Upper Airway Muscle Activities during Exercise Oronasal Distribution of Respiratory Airflow Effects of Exercise on Passive Respiratory Mechanics Elastic Properties Total Lung Capacity Expiratory Flow Rates, Vital Capacity, and Residual Volume Breathing Pattern During Exercise Mechanical Breathing Pattern Methods of Assessment of Respiratory Muscle Contraction Pattern of Respiratory Muscle Contraction Influence of Sensory Feedback on Breathing Pattern Influence of Respiratory Mechanics on Breathing Pattern Influence of Duration of Exercise on Breathing Pattern Influence of Mode of Exercise on Breathing Pattern Breathing Pattern during Recovery from Exercise Physiological Implications of Exercise Breathing Pattern Importance of Respiratory Load in Regulation of Exercise Hyperpnea Helium‐Oxygen Unloading Unloading with Pressure Assist Conclusion Locomotor‐Respiration Interdependence Entrainment—the Most Obvious Locomotor‐Respiratory Interaction How Does Entrainment Effect Ventilation? Is there Stronger Evidence to Support a Significant Biomechanical Effect of Locomotion on Respiration in Dogs? Are Biomechanical Effects Important in Entrainment in Humans? Locomotory: Respiratory Interactions, Independent of Entrainment Conclusion Respiratory Muscle Perfusion and Energetics Oxygen Cost of Hyperpnea Respiratory Muscle Blood Flow Exercise‐Induced Respiratory Muscle Fatigue Respiratory System Design Assessment of Diaphragm Fatigue in Animal Models Glycogen Depletion Fiber Type Recruitment Definition of Fatigue Task Failure vs. Objective Assessment of Fatigue Contractile Changes with Fatigue Predicting Respiratory Muscle Fatigue During Exercise Application of Resting Tests to Respiratory Muscle Function During Exercise Assessment of Respiratory Muscle Fatigue in Humans Volitional Tests Volitional Tests Applied to Exercise Nonvolitional Tests Bilateral Phrenic Nerve Stimulation ( BPNS ) Characteristics of Diaphragm Fatigue High‐ vs. Low‐Frequency Fatigue Sites and Mechanisms of Respiratory Muscle Fatigue Central Fatigue in Humans Neurotransmission Fatigue Bilateral Phrenic Nerve Stimulation Applied to Exercise Short‐Term Exercise Endurance Exercise Factors Contributing to the Decline in Twitch Pdi Following Exercise Role of Diaphragmatic Force Output in Fatigue Consequences of Exercise‐Induced Diaphragmatic Fatigue Fatigue vs. Task Failure Does Training of Respiratory Muscles Affect Exercise Performance? Altered Respiratory Muscle Recruitment with Fatigue Physical Training Effects on Respiratory Muscles Respiratory Muscle Morphology and Contractile Properties Whole‐Body Training: Effects on Rodent Respiratory Muscles Whole‐Body Exercise: Effects on Human Respiratory Muscle Performance Specific Respiratory Muscle Training Respiratory Sensation During Exertion Mechanisms of Respiratory Sensations during Exercise Methods of Assessing Respiratory Sensations Respiratory Movements An Urge to Breathe A Sense of Respiratory Effort Respiratory Sensation as a Respiratory Controller during Exercise Respiratory Sensation as a Limiting Factor during Exercise Conclusions Summary—Pulmonary System Limitations and Their Effects on Exercise Performance Absence of Pulmonary System Limitations in the Normally Fit Contrasting Adaptabilities: Demand vs. Capacity Alveolar Capillary Diffusion Surface of the Lung Ventilatory Limitations/Constraints Inadequate Alveolar Ventilation and Limitations Endurance Exercise Performance Special Circumstances Favoring Pulmonary Limitations to Exercise Performance in Health Hypoxia of High Altitudes Aging Effects on Pulmonary Limitations

Abstract The sections in this article are: Effects of Anesthesia on the Chest Wall Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Effects of Anesthesia on FRC Effects of Anesthesia on Pressure‐Volume Relationships Total Respiratory System Lungs Chest Wall Mechanisms for Changes in Pressure‐ Volume Relationships Effects of Anesthesia on Pressure‐Flow Relationships Effects of Anesthesia on Intrapulmonary Inspired‐Gas Distribution Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Conclusions

Abstract The sections in this article are: Basic Concepts—Review of Muscle Mechanics Muscle Fiber Types Mechanics of Muscle Electrical Properties of Skeletal Muscle Individual Respiratory Muscles and Their Properties General Considerations Diaphragm Intercostal Muscles Sternocleidomastoid and Scalenus Muscles Abdominal Muscles Other Respiratory Muscles Altered Respiratory Muscle Mechanical Properties in Disease Obstructive Lung Disease Diseases Characterized by Stiff Lungs Neuromuscular Diseases Severe Obesity

Abstract The sections in this article are: Mechanism of Expiratory Flow Limitation Wave‐Speed Limitation Viscous Flow Limitation Computational Model Measurement and Analysis Volume‐Time Flow‐Volume Relative Merits of Presentations Volume‐Time Flow‐Volume Additional Considerations Volume and Time History Effects of Changing Gas Properties Dysanaptic Growth Axial Bronchial Tension Thoracoabdominal Mechanics

Abstract The sections in this article are: Why is Stress Distribution Nonuniform? Why is it Important to Know Stress Distribution? Simplifications Introduced to Analysis of Stress Distribution Relationship Between Microscopic Structure and Macroscopic Properties Material Properties of Lung Parenchyma Meaning of Other Elastic Constants Implications of Relative Magnitudes of Bulk and Shear Moduli Macroscopic Lung Stress Distribution Local Stress Distribution

Abstract The sections in this article are: Equation of Motion Application of Equation of Motion to a Model Determination of Resistance and Compliance Inertance and Reactance Impedance Time Constant Nonlinear Resistance and Hysteresis Application of Equation of Motion to the Respiratory System Applied Pressures Relationship to Lung Volume Tidal Breathing Opposing Pressures Flow Resistance Maximal Expiratory Flow Gas Compression and Measurement of Flow‐Volume Curves Dynamics of Breathing Breathing at Rest and During Exercise Factors Affecting Respiratory Dynamics

Abstract The sections in this article are: Lung Volumes Volume‐Pressure Relations of Respiratory System During Relaxation Total Respiratory System Chest Wall and Lung Effects of Gravity and Posture Changes Throughout Life Span Volume‐Pressure Relations of Respiratory System During Static Muscular Efforts Alveolar Pressure Abdominal and Thoracic Pressures Factors Limiting Volume Extremes Upper Volume Extreme Lower Volume Extreme