Diuretics in the Treatment of Patients Who Present Congestive Heart Failure and Hypertension
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Journal of Human Hypertension (2002) 16 (Suppl 1), S104–S113 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh Diuretics in the treatment of patients who present congestive heart failure and hypertension AJ Reyes Institute of Cardiovascular Theory, Montevideo, Uruguay The main operational objective of diuretic therapy in ment natriuresis in patients with congestive heart failure patients who present congestive heart failure and hyper- and hypertension. The state of renal function, the exis- tension is to reduce or to suppress excess bodily fluid. tence of certain co-morbid conditions, potential Effective diuretic therapy decreases cardiac size when untoward drug actions, and possible interactions of the heart is dilated, and it reduces lung congestion and diuretics with nutrients and with other drugs are some excess water. Consequently, external respiratory work of the factors that must be considered at the time of diminishes and cardiac output would be redistributed in deciding on the diuretic drug(s) and dose(s) to be pre- favour of systemic vascular beds other than that of the scribed. Spironolactone has been found to increase life respiratory muscles; dyspnoea decreases markedly and expectancy and to reduce hospitalisation frequency there is a slight reduction in fatigue. This clinical when added to the conventional therapeutic regimen of improvement and the fall in body weight caused by patients with advanced congestive heart failure and sys- diuretics entail an increase in effort capacity. Sub- tolic dysfunction. Therefore, spironolactone should be sequent exercise training ameliorates the abnormal ven- the drug of choice to oppose the kaliuretic effect of a tilatory response to physical effort and the skeletal mus- loop or of a thiazide-type diuretic. cle myopathy that occur in heart failure, and thereby it Journal of Human Hypertension (2002) 16 (Suppl 1), S104– attenuates dyspnoea and decreases fatigue further. S113. DOI: 10.1038/sj/jhh/1001354 Loop and/or thiazide-type diuretics may be used to aug- Keywords: congestive heart failure; diuretics; hypertension; hypokalaemia; hyponatraemia; spironolactone Introduction pulmonary circulation wedge pressure, and stroke volume and cardiac output decrease initially. Upon Congestive heart failure (CHF) and hypertension prolonged administration, the cardiac index may coexist in many patients. Coronary artery disease, stay below, equal or surpass its pre-treatment value, diabetes mellitus and/or renal insufficiency fre- but the magnitude of these changes is generally quently accompany the CHF-hypertension associ- low.7,8 There is a lack of correlation between vari- ation. Few investigative endeavours have addressed ables indicating effort capacity and cardiac output the effect of diuretic therapy in patients with CHF in patients suffering from chronic CHF, but we have and hypertension specifically, despite the fact that found that the NYHA functional class9 correlates diuretics are indicated for both conditions. Effective positively and that the 6-min mean walking velo- diuretic therapy is mandatory in patients with CHF, city10 correlates negatively with clinical (Figure 1) since no drug class other than diuretics can achieve and radiological11 increasing ordinal indicators of what diuretics can in terms of control of excess bod- the magnitude of lung congestion and pulmonary 1 ily fluid and its attendant symptom mitigation. water and with the cardiothoracic ratio.12 These findings strongly suggest that the beneficial effects The clinical and functional effects of of diuretics on the main symptoms of CHF are diuretics mainly due to the decrease in thoracic fluid that results from their diuretic action. Thus, lung conges- Effective diuretic therapy provides impressive tion and water and cardiac size should be con- symptomatic relief in patients with CHF.2–5 Haemo- sidered operational objectives of diuretic therapy dynamically, forced diuresis results in a decrease in in CHF. The substantial symptomatic relief produced by diuretics in patients with CHF is independent of Correspondence: AJ Reyes, Institute of Cardiovascular Theory, whether patients also present hypertension. How- Sotelo 3908, 11700 Montevideo, Uruguay ever, the blood pressure (BP) lowering effect of E-mail: [email protected] diuretics may result in improved cardiac pump Diuretics in heart failure and hypertension AJ Reyes S105 Figure 1 The 6-min walking test was carried out and the pulmonary congestion-and-water clinical score was evaluated in 59 ambulatory patients who presented NYHA functional class I-IV congestive heart failure after 1 month of stable pharmacotherapy. Thirty-nine patients also suffered from essential hypertension. The pulmonary congestion-and-water clinical score, which has a possible range of 0–24, equals the sum of the scores assigned to eight symptoms and four signs that denote pulmonary congestion and excess water in congestive heart failure. Some dots comprise more than one patient each. From AJ Reyes, G Crippa, MG Meny, E Sverzellati, RD Espinas and M Giorgi-Pierfranceschi: unpublished study. function and thus contribute to the clinical improve- upon exercise. Patients perceive these intense ment when hypertension coexists. Reductions in and/or rapid increases in respiratory work per dyspnoea, in systemic oedema and in BP have been minute as dyspnoea.26 found to progress in parallel over the first weeks of Elevations in respiratory work per minute imply monopharmacotherapy with a diuretic in patients that a high fraction of cardiac output should be with CHF and hypertension.13 addressed to the muscles of the external respiration, The processes giving place to the two cardinal to the detriment of the fraction that perfuses other symptoms that limit physical activity in heart fail- systemic vascular beds. This added underperfusion ure, namely dyspnoea and fatigue,14,15 have not been that affects the muscles of the limbs during physical fully unveiled.16 This paucity of information pre- effort is an immediate determinant of fatigue.27 cludes that the mechanism(s) of the symptom Resting and exercise local underperfusion and the attenuation brought about by forced diuresis in systemic functional shifts that occur in CHF would patients with CHF should be fully understood, account for the muscle waste and for the microana- mainly in view that diuretic therapy does not tomical, biochemical and functional unfavourable increase cardiac output to a great extent in most changes undergone by skeletal muscle in CHF. cases. We designed an hypothesis that focuses on These changes would constitute the basis of the the possible key role played by pulmonary conges- development of fatigue when physical activity aug- tion and water and by the respiratory muscles in this ments relative underperfusion. apparent paradox,17,18 and have been updating19–21 When treatment of chronic CHF with a diuretic is our construct while considering progress in research effective, ie when it increases diuresis to the sought and opinion.22 extent, pulmonary wedge pressure and lung water Pulmonary circulation wedge pressure is decrease,28 and therefore respiratory work per increased in CHF. In consequence, there is a net minute decreases. Cardiac output would undergo a passage of fluid from the pulmonary circulation to redistribution whereby a lower fraction is addressed the lung interstitium and to the small airway.23 to the respiratory muscles, which might be better Excess lung water and pulmonary circulation en- perfused than before the institution of diuretic ther- gorgement entail a decrease in pulmonary com- apy despite this reduction, and more blood would pliance and an increase in the airway resistance to reach other systemic regions, including the muscles air flow.24 These two changes determine an increase of the limbs. Additionally, cardiomegaly subsides, in the work done by the respiratory muscles per and body weight decreases. These favourable respiratory cycle. The rise in volumes and pressures changes result in an important reduction in in the heart, in the pulmonary circulation and per- dyspnoea and in a small decrease in fatigue, and haps in intrathoracic lymphatics, the decrease in therefore in an increase in the capacity to perform pulmonary compliance, and the underperfusion and physical activity.27 In the medium range, increased structural, biochemical and functional deterioration physical activity, particularly if it includes exercise that affects certain organs such as skeletal muscles,25 training, would improve the structure and function including the respiratory muscles, originate stimuli of skeletal muscle29–33 and would reduce excess ven- that increase (effort) ventilation inordinately in tilation,33–36 thereby mitigating dyspnoea and patients with CHF. Therefore, respiratory work per fatigue further. cycle and respiratory rate rise strikingly and quickly Diuretics provide the prime relief of the symp- Journal of Human Hypertension Diuretics in heart failure and hypertension AJ Reyes S106 toms that limit physical activity. In practice, excretory response to loop diuretics is quicker than patients with CHF should be treated with diuretics the responses to the diuretics of any other class. and with other drugs. Certain co-therapies may Furosemide, bumetanide and piretanide have an amplify the beneficial effects of diuretics. ancillary site of renal action in the proximal tubule of the nephron, where they inhibit carbonic anhyd- Modern diuretics rase. Ethacrynic acid