Year: 2024
Type: editorial
Abstract: This editorial refers to ‘Loop diuretic utilization with or without heart failure: impact on prognosis’, by J.M. Friday et al., https://doi.org/10.1093/eurheartj/ehae345. Heart failure represents the end-stage of many cardiac disorders which, if left untreated, results in elevated intracardiac pressures, with inadequate cardiac output at rest or during exercise. Congestion, the retention of water and salt, is a major feature of heart failure, causing the typical signs and symptoms of breathlessness, ankle swelling, and fatigue, varying only by degree and timing. In cases with rapid onset of various aetiologies or when resistant to treatment, the patient may deteriorate and die within hours. At the other end of the spectrum, there may be a very slow and gradual onset of symptoms, with dyspnoea which may be difficult to distinguish from the normal process of ageing or deconditioning from lack of activity. This may also be the case in the rapidly growing category with obesity, among many things a risk factor for heart failure and dilated cardiomyopathy in the young.1,2 The introduction of loop diuretics in the 1960s represented a major step forward in the treatment of acute decompensated heart failure.3 Loop diuretics offer rapid symptomatic relief, reducing anxiety and the very real fear of dying in patients literally drowning from volume overload. In chronic congestive heart failure with nocturnal dyspnoea and swollen legs, the beneficial effects are obvious. For a long time, diuretics were the mainstay in the treatment of congestive heart failure,4 with the potential addition of potassium-sparing diuretics. Restriction of physical activity and sodium intake topped the list of measures, with vasodilators and digitalis further down. Although loop diuretics are lifesaving in many clinical situations, they have not been proven to improve prognosis in chronic heart failure.5 Starting with from the publication of the CONSENSUS trial in 1987, there are at present at least four classes of drugs that effectively prolong life and reduce comorbidity,6 where the use of renin–angiotensin–aldosterone system (RAAS) inhibitors and beta-blockers has been established for a long time, with the more recent addition of sodium–glucose co-transporter 2 (SGLT2) inhibitors and the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan. With positive effects of SGLT2 inhibitors now also shown in patients with mildly reduced or preserved ejection fraction,7 these drugs have effectively changed the clinical landscape in chronic heart failure over the last decades, not only prolonging life but also adding improved quality of life. Not least, they have also reduced the need for and dosage of diuretics. Although diuretics are important in relieving symptoms of congestion in heart failure, they have many side effects and may be associated with shorter survival.8,9 Still, it is difficult to separate this risk from the negative prognostic effect of needing diuretics because of congestion in the first place. Administration of loop diuretics to patients with heart failure activates the RAAS and the sympathetic nervous system, both fundamental pathways in heart failure progression. These side effects are addressed by the administration of RAAS inhibitors and beta-blockers. Administration of loop diuretics to patients with heart failure may also result in a significant decrease in the glomerular filtration rate in some patients due to changes in renal blood flow and glomerular filtration pressure.10 Patients may also be inconvenienced by the need to pass water frequently, by thirst, by dizziness, or by other, less frequent symptoms. Importantly, loop diuretics are used not only in the treatment of heart failure but also for other disorders, such as types of fluid retention caused by, for example, renal disease or venous valve insufficiency, or as one of many antihypertensive drugs. In this issue of the European Heart Journal, Friday and colleagues add important information about associations between loop diuretics and outcomes in an observational study based on administrative data derived from multiple linked health records collected by the National Health Service of Greater Glasgow & Clyde Health Board.11 Among available records from 31 December 2009 to 31 December 2011, the authors selected four groups of patients with various vascular disorders (hypertension, coronary heart or peripheral vascular disease), in total nearly 200 000 people, who were divided into: (i) patients using loop diuretics without a recorded diagnosis of heart failure; (ii) patients with heart failure not using loop diuretics; (iii) patients with heart failure using loop diuretics; and (iv) patients with vascular disorders or medications without any recorded heart failure diagnosis and not using loop diuretics. The last category formed the reference group for comparisons. However, conditions such as atrial fibrillation, valvular disease, or venous thrombo-embolism were not included, unless patients were on a pre-defined list of medications used in cardiovascular disease, including a loop diuretic. Of the patients (median age 65 years; 55% women), just over 80% neither took loop diuretics nor had recorded heart failure, 12% were taking loop diuretics but without heart failure, 4% had a record of heart failure, and were on loop diuretics, while 3% had heart failure but were not receiving loop diuretics. Accordingly, only one in four patients treated with loop diuretics had a diagnostic record of heart failure, with only 11.0% subsequently diagnosed with the condition over the following 5 years. Compared with vascular patients (without loop diuretics or heart failure diagnosis), 5-year mortality was only slightly higher for heart failure in the absence of loop diuretics, by ∼20%, while it was substantially higher, by 40%, among those with diuretics but no heart failure, and more than twice as high for heart failure treated with loop diuretics. As this is an observational study, causality cannot be determined. A large proportion were prescribed diuretics without a diagnosis, and they had worse prognosis than heart failure patients without loop diuretics. Potential explanations include that the diagnosis of heart failure may be missed in these cases, with need of diuretics serving as a signal of undiagnosed heart failure, or that loop diuretics are used for other conditions with poor prognosis, or that loop diuretic use increases mortality. As the authors indicate, all of these may be true. Overall, there were few recorded echocardiograms, with even fewer estimates of left ventricular function, although it is noted that many bedside echocardiograms would not have been included in the electronic health records. Even among those with a recorded diagnosis of heart failure, with or without loop diuretics, only about half had a record of an echocardiogram, and <40% of those with loop diuretics only. A potential diagnosis of heart failure with preserved ejection fraction could be missed on the basis of a normal ejection fraction, in particular if there was no measurement of natriuretic peptides. Uptake of either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the heart failure groups was ∼75% and of beta-blockers 64% and 69%, among those with and without loop diuretics, respectively, but lower for the group with loop diuretics only (49% for ARBs/ACE inhibitors and 36% for beta-blockers) although information on dosage and dose frequency was not available. The patients represent real-world data rather than clinical trials or registries, and patients with loop diuretics only represent miscellaneous cardiovascular diagnoses, mostly hypertension. The reason for their need for diuretics is not apparent from their records, nor was there information on if there had been any attempt at discontinuing diuretic treatment. The relatively favourable prognosis of patients with heart failure without loop diuretics could either mean that they were at an earlier stage of progressive disease or that the standard evidence-based treatment used during the inclusion period was sufficient to prevent water and salt retention, or both. To what extent the use of loop diuretics represents an unnecessary risk to patients cannot be concluded from this study, and the authors do not make any such claim. Various associations were explored, but further analyses of administrative datasets are unlikely to provide reliable answers. For this, randomized trials of initiation or withdrawal would be needed. With higher awareness of heart failure among clinicians, wider use of natriuretic peptides for diagnostic purposes, and with modern treatment, patients who do not need diuretics are likely to show a slightly different phenotype than in classical heart failure where congestion is a presenting feature. Importantly, their relatively favourable prognosis should lead to an increased awareness among clinicians about heart failure as a potential cause of vague and non-specific symptoms of fatigue, deconditioning, and palpitations, prompting a careful evaluation and laboratory tests, in particular in the presence of risk factors for heart failure such as coronary heart disease, hypertension, diabetes, or obesity. Among patients on loop diuretic treatment lacking a clear indication, their continuing use should be carefully evaluated, which in many cases could mean added diagnostic work-up. Also, because symptoms and signs may be both non-specific and at the same time not sensitive enough, it should be possible to identify as well as define heart failure at an earlier stage,12 through a more liberal use of measurements of natriuretic peptides, interpreted in the context of the clinical setting, and followed by cardiac imaging, if needed (Graphical Abstract). The author declares no disclosure of interest for this contribution. A.R. acknowledges support from the Swedish Research Council [2023-02144, 2019-00193], and the Swedish Heart and Lung Foundation.
Source: European Heart Journal
Author: Annika Rosengren
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Hjärt-Lungfonden, Vetenskapsrådet
OpenAlex ID: W4401700493