Hospitalized Acute Decompensated Heart Failure

The lifetime risk of developing HF from age 45 to age 95 is estimated to be between 20% and 45%. At this time, it is estimated that 50% of hospitalized HF cases will have an ejection fraction >40%.

Untreated left HF with preserved ejection fraction (HFpEF) has limited survival (only 35%), similar to that of HF with reduced ejection fraction (HFpEF). On the other hand, each hospitalization for HF increases the risk of mortality at 30 days and at one year. Therefore, it is imperative to accurately diagnose, categorize, and manage HF, given its increasing prevalence, cost, and high mortality rate.

Current evidence-based treatments can change the natural history of HF and offer hope for long-term success.

This opportunity usually begins during the index hospitalization for acute decompensation due to clinical congestion. A challenge for the medical community is to implement treatments while reducing hospitalizations and increasing survival.

Acute HF is a complex pathological state. It involves the interaction of neurohormonal activation, hypertension, salt and water retention, resulting in vasoconstriction and increased cardiac filling pressures, causing oxidative stress, inflammation, myocardial injury, deterioration of renal function and possible progressive organ damage.

Commonly, HF is divided into 4 hemodynamic profiles , depending on organ perfusion (cold or hot) and congestion (dry or wet). Patients admitted with decompensated HF usually have a warm and humid profile , where the pulmonary capillary wedge pressure is elevated, with a preserved cardiac index, ensuring intact organ perfusion. The warm-wet profile will be the primary focus of this article as opposed to the cold-wet profile , which reflects increased cardiac filling pressures and poor organ perfusion, or cardiogenic shock, which typically requires intensive care management.

Clinically, patients present with congestion, or are considered decompensated if they have evidence of weight-based volume overload; tachypnea; distention of the jugular vein; pulmonary, abdominal and peripheral edema with postural discomfort and dyspnea on exertion; nausea; early satiety and fatigue. Although hospitalizations are often thought to be due to a single event that portends congestion, acute HF is, in fact, not typically an acute process.

Hospitalizations for HF can be triggered by acute myocardial disease, ischemia, uncontrolled hypertension, arrhythmias, medication and non-adherence to diet, medications that cause negative inotropic activity or sodium retention, acute infections and/or even worsening of a heart valve disease.

In the Cardio-MEMS and CHAMPION studies, congestion was managed with an implantable hemodynamic sensor and the results were compared to the patient’s usual reactive responses to symptoms. A gradual increase in pulmonary pressures was observed over the days, before patients manifested symptoms of worsening congestion.

The 2017 update of the 2013 joint guidelines from the American College of Cardiology Foundation and the American Heart Association HF advises evaluating cardiac biomarkers to diagnose, prognosticate, and guide therapy of HF.

For the diagnosis or exclusion of HF, it is mainly recommended to determine the level of brain natriuretic peptide (BNP) or its precursor N-terminal pro BNP [NTproBNP] at hospital admission to compare it with baseline levels in patients. outpatients, since its excretion depends on myocardial stretching during congestion.

The recommendation to concomitantly compare natriuretic peptide levels at baseline and end of hospitalization to inform patient prognosis is often overlooked. A decrease of at least 30% heralds improved survival, rather than no change or an increase in levels. This finding is critical, since a decrease in natriuretic peptide as a therapeutic objective, at least for HFrEF, was shown to be useful to optimize fluid balance and stabilization of HF.

However, the authors highlight that subsequent studies evaluating the effect of natriuretic peptide-based treatment in high-risk hospitalized HFrEF patients did not find a decrease in HF hospitalizations or mortality compared with usual care.

Other emerging biomarkers predicting HF hospitalization and death are ST2 (tumurogenesis suppressor 2) and galectin-3, which may be complementary therapeutic targets to natriuretic peptides in the coming years. ST2 is a member of the IL-1 receptor family and is a marker of myocardial fibrosis and adverse cardiac remodeling. Galectin-3 is secreted by macrophages, mediates cardiac fibrosis, and can identify an advanced HF phenotype. Serial decreases in ST2, especially with a target value <35 ng/ml, are associated with better HF outcome, including survival, independent of natriuretic peptides.

In addition to serum biomarkers for assessing acute HF decompensation, the remote dielectric sensing vest ( Sensible Medical, Netanya, Israel ) for assessing lung fluid content has been shown to correlate well with invasive blood pressure measurements. pulmonary capillary wedge. Perhaps in the future, decreasing lung fluid content by using the remote dielectric sensing vest can serve as a therapeutic goal for hospitalized HF.

In order to rule out decompensated HF during the initial examination there are other means of assessing congestion, including portable point-of-care echocardiography , which may be more sensitive than biomarker analysis or chest radiographs alone.

Regardless of the strategies used to identify decompensated HF, whether physical examination, biomarkers, or remote dielectric sensing for point-of-care assessment, the DOSE ( Diuretic Optimization Strategies Evaluation ) trial showed that worsening Renal function may compensate for decongestion, but may not necessarily affect post-discharge outcomes, as long as there appear to be other objective signs of improvement and the increase is transient. On the other hand, there may be small increases in creatinine accompanied by the titration of renin-angiotensin system inhibitors or aldosterone antagonists (AA) and thus renal function is not a reliable biomarker to evaluate decongestion.

Lack of improvement or worsening of renal function, in the context of what appears to be worsening volume overload despite decongestion, may imply that patients are in a state of low cardiac output, i.e., cold. and wet , which can be confirmed by the use of a Swan-Ganz catheter to evaluate invasive hemodynamics, and the administration of intravenous vasodilators, inotropes and/or mechanical support would be necessary.

> Decongestion

For hot and humid patients , the mainstay of therapy is intravenous loop diuretics.

In case of severe volume overload, renal and splanchnic venous congestion, the effectiveness of the ambulatory diuretic dose established for the patient may decrease. Therefore, according to the DOSE trial, to achieve symptom relief, the indicated option upon admission to the hospital is to increase by 250% the total oral dose of the loop diuretic administered intravenously, in divided doses or as a continuous infusion.

Kidney injury from renal venous congestion may improve with diuretic administration because the kidneys are more likely to respond to high doses of diuretics if glomerular filtration rate is low.

If the patient does not respond to oral or intravenous loop diuretics, thiazide diuretics can be used to increase diuresis. In 2019, an expert consensus developed guidance for the target dose and route of administration when increasing loop and thiazide diuretics in hospitalized patients with decompensated HF. This guide also evaluates the risks, management and evolution of these patients. The goal is net fluid loss and weight loss, ideally at least 1 kg/day .

There is some limited data to suggest that tolvaptan (a vasopressin antagonist) may achieve similar weight loss at 48 hours, despite the lack of improvement in mortality and HF hospitalizations shown in the EVEREST trial.

If there is severe symptomatic hypervolemic hyponatremia, vasopressin antagonists can be used, with a natremia <125 mEq/dl, despite fluid restriction indicated to improve the morbidity of hospitalized HF.

Other theoretical strategies in the context of loop diuretic resistance include the adjuvant use of high-dose mineralocorticoid antagonists or even aliquots of hypertonic saline to combat renal sodium retention in the setting of hypochloremia, which may stimulate renin secretion or upregulate sodium chloride channels in the distal convoluted tubule.

> Complementary treatments

Diuresis assisted by parenteral inotropic vasodilators is not supported by clear evidence for warm and humid patients. The ROSE ( Renal Optimization Strategies Evaluation ) trial for acute HF found that the addition of low doses of dopamine or nesiritide improved congestion symptoms while preserving kidney function. However, no final benefit was found.

If decongestion attempts are not successful with strategies for the administration of intravenous diuretics, ultrafiltration can be applied , in selected patients and in collaboration with nephrology. With ultrafiltration, water and solute are mobilized from the plasma, through a semipermeable membrane, while intravascular volume is maintained. This is possible if there is central venous access and nursing and anticoagulation services.

Hospitalizations for acute decompensated HF are an opportunity to address comorbid noncardiac diseases that may improve the quality of life of HF patients. The 2017 focused update of the HF guidelines incorporated the best available data to make recommendations on the management of anemia and sleep-disordered breathing in patients with HF.

The New York Heart Association [NYHA] endorses intravenous iron for chronic iron deficiency anemia (ferritin <100 ng/ml or 100–300 ng/ml if transferrin saturation is <20% in patients with IC functional class II and III), but based on few trials. Ferric carboxymaltose was also tested to improve NYHA functional class and the 6-minute walk distance test. Clinical trials are being carried out with new formulations of intravenous iron to improve morbidity and evaluate the impact on mortality.

On the other hand, if sleep-related breathing disorders are suspected in patients with NYHA functional class II-IV HF, formal sleep testing is indicated, which is performed in hospitalized or outpatient patients. A sleep study can differentiate between central and obstructive sleep apnea, and facilitate the initiation of continuous positive airway pressure to improve sleep quality and nocturnal oxygenation.

> Guideline-based treatment for heart failure with reduced ejection fraction

Among patients with an ejection fraction <40% hospitalized for HF, it is imperative to continue guideline-directed medical therapy (GDMT) for HF to maintain neurohormonal antagonism .

On the other hand, as patients approach clinical euvolemia during the decongestion phase of an HF hospitalization, it is crucial to uptitrate or initiate GDMT because it provides the opportunity to optimize dosing regimens that can often take a long time. considerable amount of time in outpatients, and improve outcomes after discharge.

Recent data from CHAMP-HF ( Change in the Management of Patients with Heart Failure ) suggest that <1% of patients receive target doses of GDMT over a 12-month period in the outpatient setting. This finding implies a need for treatment of patients with chronic HFrEF, which may begin in the hospital, before discharge.

For many years, the mainstay of chronic HFrEF management was based on a 3-pronged, evidence-based approach to neurohormonal antagonism to improve mortality: The 2019 American College of Cardiology expert consensus recommendations for patients hospitalized for ICs highlight initiation or dose optimization of these agents before hospital discharge.

The PARADIGM-HF trial established that sacubitril/valsartan is superior to enalapril in patients with HF with ejection fraction <35% in reducing cardiovascular death and HF with hospitalizations.

If minimal doses of ACEIs or ARBs are hemodynamically tolerated, transition to a neprilysin receptor inhibitor (NRI) is preferable to achieve such a mortality benefit. The recommendation to initiate or transition to an IRN is reflected in guidelines for HF and consensus statements for its management.

Hospitalization for acutely decompensated HF provides the opportunity to change the needle in transitioning from ACEIs or ARBs to an NRI before hospital discharge. Among hospitalized patients, the PIONEER-HF study argues for greater sustained decreases in NTproBNP in patients who initiated an NRI vs. ACE inhibitors during and after hospitalizations. The push to initiate this transition to an IRN as soon as possible is further reinforced by the PROVE-HF study demonstrating improvements in reverse cardiac remodeling and myocardial structure as NTproBNP levels are reduced with exposure to an IRN.

Optimizing GDMT during an index or subsequent HF hospitalization also provides the opportunity to address medication adjustments in select populations. Based on the A-HEFT study of selected African Americans, the addition of hydralazine and isosorbide dinitrate to an optimal dose of ACEIs and β-blockers is recommended. This finding reflects a relative risk reduction in mortality and the number needed to treat 21 to prevent 1 death, compared with placebo.

The 2013 HF guidelines also recommend combining hydralazine and isosorbide dinitrate instead of an ACEI or an ARB, in any individual who cannot tolerate such drugs due to drug intolerance, renal failure, hypotension, or hyperkalemia.

Among HFrEF patients with NYHA functional class II symptoms or higher, sinus rhythm, and heart rate >70/min despite maximum doses of evidence-based β-blockers , the pre-discharge period during hospitalized HF provides the opportunity to introduce ivabradine given its ability to reduce HF hospitalizations and morbidity.

Future editions of the HF guidelines will likely reflect the role of sodium-glucose cotransporter-2 inhibitors in decreasing HF mortality and hospitalizations for all those arriving with cardiac problems, regardless of hemoglobin A1c, given the recent results of the DAPA-HF trial. This strategy will make the optimal GDMT for HFrEF include at least 3 drug classes (ACEI/ARB or NRI, ß blockers and AA) to at least 4 drug classes that could also be started in the hospital.

Although not essential to the management of hospitalized patients, discussions regarding the use of implantable cardioverter defibrillators, cardiac synchronization therapy, and percutaneous mitral regurgitation repair can be initiated before discharge. The electrophysiology service may be consulted to consider the use of an implantable cardiac defibrillator for patients with HFrEF with an ejection fraction <35%, to prevent sudden cardiac death, or to implement cardiac resynchronization therapy for individuals with an ejection fraction <35%, left bundle branch block and QRS >150 ms, and residual HF symptoms despite taking HF medications that have been maximally tolerated for at least 3 months.

Patients with HFrEF and residual severe functional mitral regurgitation with persistent HF symptoms or hospitalizations despite being at maximum tolerated GDMT, and with adequate decongestion and potential use of cardiac resynchronization therapy, should be referred to the cardiology team. , including an expert HF cardiologist, structural cardiologist, and cardiothoracic surgeon, to consider percutaneous edge-to-edge mitral valve repair.

The COAPT trial found a 38% relative decrease in overall mortality and a 47% decrease in hospitalizations after 2 years of transcatheter mitral valve repair, following optimization using GDMT.

Other considerations by a cardiology team in this setting may include advanced therapies, such as the use of a left ventricular assist device or heart transplant , particularly for patients with a poor prognosis despite optimized medical treatment and devices. used. The phenotypic management of HFpEF contained in the 2013 guidelines defines it as an ejection fraction >50%.

The increasing burden of HFpEF (preserved ejection fraction), especially in the elderly, requires proper categorization of the disease phenotype to administer appropriate therapy. To date, HFpEF clinical trials have failed to produce a medical therapy that has demonstrated a mortality benefit. However, given that 50% of hospitalized HF are now attributed to HFpEF, it is important to implement treatment to reduce HF hospitalization and morbidity, given the significant financial burden and deterioration in quality of life.

In the absence of infiltrative cardiomyopathy leading to HFpEF syndrome, guidelines from major American medical societies emphasize the management of cardiovascular comorbidities , conditions that contribute to HFpEF syndrome, which can be addressed during hospitalization. due to acute decompensation.

These factors include recommendations for decongestion with diuretics and adequate blood pressure control according to clinical practice guidelines and recommendations for possible coronary revascularization in the setting of myocardial ischemia and rate and rhythm control in atrial fibrillation. .

Furthermore, data from the TOPCAT trial support the recommendation to administer spironolactone (aldosterone antagonists) to reduce cardiac hospitalizations in individuals with HF, an ejection fraction >45%, and an estimated glomerular filtration rate >30 mL/min. , a serum creatinine <2.5 mg/dl and a potassium <5.0 mEq/l.

Not all HFpEF syndromes can be managed with a single therapy, reflecting the heterogeneous nature of a syndrome that often includes comorbid myocardial disease, chronic kidney disease, obesity, altered lung mechanics, and reduced muscle reserve. skeletal.

After decongestion, an examination of clinical features, advanced echocardiographic studies to evaluate myocardial mechanics, and stress/strain imaging can clarify various phenotypic groups of the overall diagnosis of HFpEF. The identification of a cardiometabolic alteration of myocardial relaxation, and cardiorenal syndrome, with poor right ventricular mechanics, can guide possible treatments. Shah et al. have proposed an iterative framework for the management of various HFpEF syndromes that reflects clinical features and non-cardiac comorbidities, and cardiac diagnoses that may help optimize treatment.

Recent results from the PARAGON-HF trial, which compared sacubitril/valsartan with valsartan in HF patients with an ejection fraction ≥45%, did not show a statistical decrease in mortality and HF hospitalizations. However, the trial does not distinguish possible differences in response to therapy based on gender and ejection fraction ranges. Women and those with an ejection fraction of 45% to 57% (less than the median in the study) appeared to gain the most benefit.

It is increasingly recognized that older men with HFpEF have cardiac transthyretin amyloidosis , which may explain the lack of benefit of an NRI in the trial. On the other hand, patients with lower ejection fraction in the trial may reflect the group of patients transitioning to HFrEF and have more neurohormonal activation, for whom NRIs may provide more physiological and structural benefit.

The possibility of including many patients with transthyretin amyloidosis in HFpEF trials, which the PARAGON-HF trial recently did, further emphasizes the need for in-depth HFpEF phenotyping during acute decompensated HF hospitalizations. , so the use of precision medicine, advanced imaging and genotypic information can clarify the phenotypic manifestations of the disease. For example, a contemporary series predicts that almost 15% of hospitalized patients with HFpEF and left ventricular hypertrophy have wild-type transthyretin cardiac amyloidosis .

Advanced cardiac imaging using stress echocardiography, cardiac MRI, and technetium pyrophosphate scintigraphy during hospitalization for acute decompensated HF may help diagnose cardiac transthyretin amyloidosis in these cases. This strategy is critical, given the results of the ATTR-ACT study of patients with transthyretin cardiac amyloidosis, which demonstrated lower overall mortality and cardiovascular hospitalizations in these patients compared to placebo.

After decongestion, in-depth phenotyping, and optimization of HF therapies for both HFrEF and HFpEF, patients are vulnerable and at high risk for further hospitalization soon after discharge. Some estimates are 25% within 30 days. Implementing robust transitions in care programs may be effective in reducing failed repeat hospitalizations.

Before discharge, best care practices include assessment of cardiac biomarkers and potential lung water content, ensuring drug treatment reflects GDMT, explanation of how medications are used, and nutritional counseling.

After discharge, expert consensus recommends telephone follow-up within 48-72 hours of discharge to assess any gaps in care and ensure follow-up by a specialist within 7-14 days of discharge.

During hospital follow-up, the focus should be on providing quality care to improve survival and not simply prevent readmission. The authors express the need to establish quality metrics given the potential harm associated with the approach of emphasizing the reduction of hospitalizations. Continued work is needed, they say, to balance decongestion, optimize GDMT, and make safe transitions to decrease readmissions and, ultimately, mortality.