Hyperkalemia In Heart Failure Research Articles

Managing hyperkalemia in patients with heart failure on guideline-directed medical therapy: challenges and opportunities.

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium-glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate.

Epidemiology and risk factors for hyperkalaemia in heart failure.

Patients with heart failure (HF), particularly those with impaired renal function receiving renin-angiotensin-aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow-up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one-quarter to two-fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55-93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow-up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE-HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes.

Practical patient care appraisals with use of new potassium binders in heart failure and chronic kidney diseases.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure and in chronic kidney disease (CKD) patients due to the diseases themselves, which often coexist, the high co-presence of diabetes, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. Hyperkalaemia limits their administration or uptitration, thus impacting on mortality. New K+ binders, namely patiromer and sodium zirconium cyclosilicate (ZS-9), are an intriguing option to manage hyperkalaemia in heart failure and/or CKD patients, both to reduce its fatal effects and to let clinicians uptitrate RAAS inhibition. Even if their real impact on strong outcomes is still to be determined, we hereby provide a practical approach to favour their use in routine clinical practice in order to gain the correct confidence and provide an additive tool to heart failure and CKD patients' wellbeing. New trials are welcome to fill the gap in knowledge.

Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis

AimsHyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. Methods and resultsPubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4–26%), decreased hyperkalemia events by 29% (95% CI: 55–92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18–0.44) compared to placebo, maintaining a good safety profile. ConclusionNPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. Systematic Review registrationCRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811

Impact of Hyperkalemia in Heart Failure and Reduced Ejection Fraction: A Retrospective Study.

(1) Background: Hyperkalemia is a common finding in patients with heart failure and reduced ejection fraction (HFrEF), though its prognostic significance is controversial. There is no consensus on optimal potassium levels in these patients. The primary endpoint of this study was to determine the 5-year incidence of hyperkalemia in a cohort of patients with HFrEF. Secondary endpoints were to determine predictors of hyperkalemia and its impact on overall 5-year mortality; (2) Methods: retrospective, longitudinal, single-center observational study of patients with HFrEF followed-up in a specialized unit between 2011 and 2019. Hyperkalemia was considered as potassium concentration > 5.5 mEq/L; (3) Results: Hyperkalemia was observed in 170 (16.8%) of the 1013 patients. The 5-year hyperkalemia-free survival rate was 82.1%. Hyperkalemia was more frequent at the beginning of follow-up. Factors associated with hyperkalemia in the multivariate analysis were baseline potassium (HR 3.13, 95%CI 2.15-4.60; p < 0.001), creatinine clearance (HR 0.99, 95%CI 0.98-0.99; p = 0.013), right ventricular function (HR 0.95, 95%CI 0.91-0.99; p = 0.016) and diabetes mellitus (HR 1.40, 95%CI 1.01-1.96; p = 0.047). The overall survival rate at 5 years was 76.4%. Normal-high potassium levels (5-5.5 mEq/L) were inversely associated with mortality (HR 0.60, 95%CI 0.38-0.94; p = 0.025); (4) Conclusions: Hyperkalemia is a common finding in patients with HFrEF with an impact on the optimization of neurohormonal treatment. In our retrospective study, potassium levels in the normal-high range seem to be safe and are not associated with increased mortality.

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Management of Hyperkalemia in Heart Failure.

Hyperkalemia is a common electrolyte abnormality in heart failure (HF) that can cause potentially life-threatening cardiac arrhythmias and sudden cardiac death. HF patients with diabetes, chronic kidney disease and older age are at higher risk of hyperkalemia. Moreover, hyperkalemia is also often associated with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and sacubitril-valsartan. In clinical practice, the occurrence of hyperkalemia is a major concern among the clinicians and often limits RAASi use and/or lead to dose reduction or discontinuation, thereby reducing their potential benefits for HF. Furthermore, recurrent hyperkalemia is frequent in the long-term and is associated with an increase in hyperkalemia-related hospitalizations. Therefore, management of hyperkalemia has a special importance in HF patients. However, treatment options in chronic management are currently limited. Dietary restriction of potassium is usually ineffective with variable adherence. Sodium polystyrene sulfonate is commonly used, but its effectiveness is uncertain and reported to be associated with intestinal toxicity. New therapeutic options such as potassium binders have been suggested as potentially beneficial agents in the management of hyperkalemia. This document discusses prevalence, predictors and management of hyperkalemia in HF, emphasizing the importance of careful patient selection for medical treatment, uptitration of the doses of RAASi, regular surveillance of potassium and treatment options of hyperkalemia.

The importance of developing hyperkalaemia in heart failure during long-term follow-up

Background Hyperkalaemia is a potentially life-threatening condition. Furthermore, it is one of the main reasons for discontinuation and dose reduction of renin-angiotensin-aldosterone system inhibitors (RAASi) in clinical practice. However, exact data on the prevalence and consequences of occurrence of hyperkalaemia when taking RAASi in a dedicated heart failure care setting are scarce. Methods Consecutive patients diagnosed with heart failure from a single tertiary hospital between August 2000 and May 2017 were retrospectively evaluated. Primary endpoint was the development of hyperkalaemia (≥5.5 mmol/L) at any moment during follow-up. Results About 396 patients were included in the current analysis (mean follow-up 6.9 years). 26% (n = 104) and 12% (n = 46) of patients developed hyperkalaemia (≥5.5 mmol/L and ≥6.0 mmol/L, respectively). Diabetes mellitus (OR = 1.80, 95% CI = 1.03–3.19) and baseline creatinine (mg/dL) (OR = 2.37, 95% CI = 2.37–3.85) were independent risk factors for hyperkalaemia. Development of hyperkalaemia was associated with 6.5 higher odds for recurrence. Only 10% developed hyperkalaemia during up-titration of RAASi, while 90% developed during later follow-up on stable doses of RAASi. hyperkalaemia was not associated with worse outcome after multivariate adjustment for baseline co-morbidities. However, hyperkalaemia was associated with discontinuation and lower doses of MRAs during follow-up (p = 0.007). Discontinuation of MRA due to hyperkalaemia was associated with an increase in all-cause mortality in HFrEF patients (HR = 1.77, 95% CI = 1.05–2.99). Conclusions Approximately, one-fourth of patients developed hyperkalaemia during follow-up which was associated with a lower MRA dose during follow-up. Discontinuation of MRA, but not hyperkalaemia itself, was associated with an increased risk of all-cause mortality and heart failure admission in HFrEF patients.

Hyperkalemia in heart failure: current treatment and new therapeutic perspectives.

Hyperkalemia in heart failure is a condition that can occur with relative frequency because it is related to pathophysiological aspects of the disease, and favored by drugs that form the basis of chronic cardiac failure therapy. Often, associated comorbidities, such as kidney failure or diabetes mellitus can further adversely affect potassium levels. Hyperkalemia can result in acute and even severe clinical manifestations that put patients at risk. On the other hand, the finding of hyperkalemia in a chronic context can lead to a reduction in dosages or to suspension of drugs such as angiotensin-converting enzymes inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitor, and mineralcorticoid receptor antagonist, first line in the treatment of the disease, with negative effects in prognostic terms. Therapies for the correction of hyperkalemia have so far mainly concerned the treatment of acute clinical pictures. Newly developed molecules, such as patiromer or sodium zirconium cyclosilicate, now open new prospectives in the long-term management of hyperkalemia, and allow us to glimpse the possibility of a better titration of the cardinal drugs for heart failure, with consequent positive effects on patient prognosis. The aim of this review is to focus on the problem of hyperkalemia in the setting of heart failure, with particular regard to its incidence, its prognostic role, and the underlining pathophysiological mechanisms. The review also provides an overview of therapeutic strategies for correcting hyperkalemia in acute and chronic conditions, with a focus on the new potassium binders that promise to improve management of heart failure.

Hyperkalemia in heart failure: new solutions for an old problem

Potassium is the main intracellular ion and its homeostasis is finely regulated by the renal and gastrointestinal tract. Renal failure and hyperkalemia are conditions commonly found in patients with heart failure, the result of a complex interaction between heart and kidney (e.g. cardio-renal syndrome) and the side effects of drugs commonly used for treating heart disease (e.g. renin-angiotensin-aldosterone system inhibitors). Although hyperkalemia increases the risk of heart conduction disorders and life-threatening arrhythmias, its prognostic significance in heart failure is uncertain. Hyperkalemia and progression of renal damage are the main limitations to the introduction and titration of heart failure therapies. New drugs for the prevention and chronic treatment of hyperkalemia allow the introduction and modulation of anti-neurohormonal therapies in patients with heart failure otherwise excluded from these treatments due to excessively high serum potassium levels.This review illustrates the pathophysiological, epidemiological and prognostic aspects of hyperkalemia and analyses the possible treatments for this condition in heart failure patients.

Is hyperkalaemia in heart failure a risk factor or a risk marker? Implications for renin–angiotensin–aldosterone system inhibitor use

Is hyperkalaemia in heart failure a risk factor or a risk marker? Implications for renin–angiotensin–aldosterone system inhibitor use

What is the risk of hyperkalaemia in heart failure?

Introduction:Chronic heart failure (CHF) is the only major cardiovascular disease whose prevalence and incidence are thought to be increasing. Potassium balance may be lost both through the neurohormonal mechanisms involved in cardiovascular diseases and through the drugs used in their treatment. Avoiding both hypo- and hyperkalemia is difficult but beneficial in CHF.Areas covered:Aldosterone production is decreased in the elderly, diabetic patients, and those receiving drugs that block the production or action of renin and angiotensin II. As a result, these groups, as well as those with already impaired potassium excretion due to progressive age or disease-related decline in glomerular filtration rate, are particularly vulnerable to the development of hyperkalemia.Expert opinion:Evidence from several studies suggests that, in patients with CHF, serum potassium should be maintained between 4.0 and 5.5 mEq/L. To gain the maximum benefit from aldosterone antagonists it is necessary to individualize their use; it is also necessary to carefully monitor electrolytes.

Hyperkalemia in patients with heart failure: Incidence, prevalence, and management

Multilevel inhibition of neurohormonal activation using angiotensin-converting enzyme inhibitors, beta-blockers, angiotensin receptor blockers, and aldosterone antagonists is the cornerstone of modern heart failure treatment. Use of these agents in optimal doses is associated with significant improvements in heart failure-associated morbidity and mortality but also may increase serum potassium. Because potassium excretion already is impaired in many heart failure patients because of advanced age, diabetes, or chronic kidney disease, the risk of life-threatening hyperkalemia during treatment is significant. This review discusses the mechanisms, incidence, predictors, and management of hyperkalemia in heart failure, emphasizing the importance of careful patient selection for medical treatment and regular surveillance of potassium and creatinine.