LAUSR

Dyspnoea is the cardinal manifestation of heart failure and remains its most perplexing feature. Those afflicted with chronic heart failure typically report both symptoms of dyspnoea and exercise intolerance, but does dyspnoea actually limit activities of daily living? It is maddeningly difficult to know if patients with heart failure stop exercising because they are short of breath or because they are limited for some other reason and incidentally report dyspnoea as an accompanying symptom. Although it may seem obvious that dyspnoea impairs quality of life in heart failure, it is time to question the obvious. Our thinking about dyspnoea in heart failure has long been heavily influenced by observations in patients with acute heart failure, particularly those who present with acute pulmonary oedema. This syndrome is characterized by abrupt and marked increases in cardiac filling and pulmonary venous pressures, which are accompanied by overwhelming dyspnoea at rest. Classically, patients exhibited pink frothy sputum upon coughing, the result of the transudation of fluid from the pulmonary capillaries into the alveoli. The presentation was so dramatic that it seemed reasonable to surmise that oxygen transport was impaired, and that the resulting hypoxaemia was responsible for the sensation of dyspnoea. However, most patients with acute heart failure following myocardial injury are not hypoxaemic, even though they are generally dyspnoeic. Furthermore, acute interventions may lead to relief of dyspnoea, but without any improvement in alveolar fluid, pulmonary rales, or oxygenation. Interestingly, when bedside cardiology was in its heyday, the most reliable objective finding that presaged the relief of dyspnoea in patients with acute pulmonary oedema was not measures of respiratory rate, blood oxygenation, or pulmonary function, but rather the cessation of diaphoresis. Dyspnoea was relieved when sympathetic drive dissipated, even though pulmonary function had not changed. Understanding dyspnoea became more difficult when we tried to decipher the genesis of the symptom in patients with chronic heart failure. An obvious explanation for dyspnoea in these individuals was that an increase in pulmonary venous pressures led to congestion-mediated changes in pulmonary compliance, alterations in alveolar fluid content, and impaired alveolar gas diffusion. Yet, many patients with chronic heart failure had markedly increased left ventricular filling pressures at rest (pulmonary wedge pressures >30 mmHg), but they did not complain of dyspnoea and did not exhibit tachypnoea, possibly because alveolar fluid transudation was prevented by heightened pulmonary lymphatic drainage. Additionally, in certain patients (i.e. those with mitral stenosis), the increase in pulmonary vascular resistance that accompanied progression of the disease led to a decrease in pulmonary blood flow and lessening of dyspnoea. As pulmonary artery pressures rose, exercise tolerance worsened, but patients often noted that dyspnoea was no longer a troublesome symptom and that fatigue had become the primary symptom that limited activities of daily living. Accordingly, an enhancement of transpulmonary blood flow could precipitate a rush of blood volume into the lungs, resulting in pulmonary oedema. These studies pointed to a role for pulmonary blood flow in the genesis of dyspnoea. Subsequent efforts to understand dyspnoea relied on cardiopulmonary exercise testing with simultaneous measurements of gas exchange and invasive assessments of cardiac pressures and blood flows. Studies of patients with chronic heart failure and left ventricular systolic dysfunction concluded that pulmonary venous congestion was not a critical factor in the genesis of dyspnoea. Patients with chronic heart failure experienced an excessive ventilatory response to CO2, but this was not related to exercise-induced increases in pulmonary venous pressures and could not be alleviated by pulmonary venous decongestion. Instead, the studies suggested a role for a low cardiac output as a mechanism for dyspnoea, based on the belief that a decrease in cardiac output (leading to poor pulmonary perfusion and ventilation–perfusion mismatching) might cause