For heart failure with reduced pump function (HFrEF), the ESC guidelines updated last year recommend a new treatment algorithm. In addition, current data show that SGLT-2 inhibitors may benefit not only patients with reduced ejection fraction but also those with HFmrEF or HFpEF. Especially with regard to the treatment of heart failure with preserved pump function, an ‘unmet need‘ is thus covered. There are also interesting new findings regarding diagnosis of HFpEF.
Dyspnea, fatigue or fluid retention are typical symptoms of chronic heart failure, but can also be caused by many other conditions. Crucial for a reliable diagnosis of heart failure is confirmation of systolic or diastolic dysfunction of the left ventricle or other structural heart disease, for example, mitral ventricle [1]. Diagnostically, heart failure is classified based on left ventricular ejection fraction (LVEF) as follows: HFpEF=preserved LVEF (≥50%), HFmrEF=slightly reduced LVEF (41-49%), HFrEF=reduced LVEF (≤40%). Treatment options have expanded compared to the past. “Today, we have a very good armamentarium to treat patients with heart failure,” said Prof. Otmar Pfister, MD, Head of Outpatient Cardiology at the University Hospital Basel [2]. In patients with reduced pump function (HFrEF), the ‘fantastic four’ i.e. ARNI or ACE inhibitor, beta-blocker, aldosterone antagonist and SGLT-2 inhibitor are considered the new therapeutic standard (Box). “Use them early, even in low doses, as you go along they will be titrated up,” explains the expert [2]. Even in patients with mildly reduced pump function (HFmrEF), the drugs used in HFrEF have prognostic efficacy. The results of the EMPEROR-PRESERVED study published last year represent a major advance [3]. This showed that empagliflozin significantly reduced rehospitalization rates in both HFmrEF and HFpEF.
Detecting and treating HFpEF: What’s New?
In addition to dyspnea and LVEF ≥50%, evidence of elevated filling pressures is critical for the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF). It is also important to consider predisposing factors: if it is older, obese, female patients with atrial fibrillation, the likelihood that heart failure is present is very high, Prof. Pfister said [2]. Also common in HFpEF patients is arterial hypertension and/or diabetes. If additionally elevated NT-proBNP values are present, this is a further indication. However, peptide determination alone is not suitable for confirming the diagnosis because elevated natriuretic peptides have a high negative predictive value but only a moderate positive predictive value [1]. If NT-proBNP is elevated, patients should be referred for echocardiography, the speaker advises.
Until recently, treatment options for patients with HFpEF were limited to therapy of comorbidities (e.g., hypertension, obesity) and lifestyle measures (e.g., regarding exercise and diet). This has changed, and there are now two drugs for which there is good evidence: firstly, spironolactone – this can benefit obese patients in particular (BMI>30), and studies have shown a reduction in the risk of rehospitalization. Second, with respect to the SGLT-2 inhibitor (SGLT-2-i) empagliflozin, the EMPEROR-Preserved study demonstrated that the risk of heart failure-related hospitalization could also be effectively reduced in HFpEF in a placebo comparison (HR 0.73; 95% CI, 0.61-0.88; p<0.001). (Fig. 1). Inthe EU, empagliflozin received a marketing authorization extension for this indication a few months ago; in Switzerland, the SGLT-2-i can only be used off-label for this indication so far. Beta-blockers often need to be reduced to reduce any chronotropic incompetence present, according to Prof. Pfister [2].
HFrEF: Taking advantage of a quad combination
The SGLT-2 inhibitors dapagliflozin and empagliflozin, approved in Switzerland for heart failure with reduced left ventricular ejection fraction (HFrEF), are available at a fixed dose of 10 mg. They are very effective drugs (NNT=21), reducing mortality by about 18% and heart failure-related hospitalization by 30%. “The new credo in heart failure therapy is ‘establish first, titrate second'”. It is attempted to start with this already in the inpatient setting, and the up-dosage is then carried out in the special outpatient clinic or by the general practitioner [2]. “The special thing is that the effect comes early, you see a benefit in studies already in the first 30 days compared to placebo,” said Prof. Pfister [2]. The safety of SGLT-2-is good, blood pressure is only slightly lowered, and they are drugs that can be used in severe renal insufficiency (up to eGFR 20 ml/min).
As first-line therapy for HFrEF, the fixed combination of sacubitril and valsartan can be used as an alternative to an ACE inhibitor in HFrEF. In long-term therapy , sacubitril/valsartan is preferable, and studies have shown benefit in terms of reduction in mortality rates and heart failure-related hospitalization rates [4]. In normotensive patients, sacubitril/valsartan can be used initially; in hypertensive patients, ACE inhibitors should be used first.
Check iron status regularly
According to empirical studies, one in two patients with chronic heart failure is affected by iron deficiency. The incidence increases with the severity of heart failure and is prognostically unfavorable regardless of the presence of anemia [5]. The current ESC guidelines recommend that iron status be checked regularly in all patients with suspected chronic heart failure [6]. The iron content in the blood is essential for oxygen transport and energy production by the body’s cells. In the case of iron deficiency, the mitochondria can produce less energy, but the heart muscle in particular depends on a high energy supply for its pumping function. Studies have shown that in patients with chronic heart failure and iron deficiency, intravenous administration of ferric carboxymaltose can improve symptoms and quality of life and reduce the risk of hospitalization [7].
Congress: medArt
Literature:
- National Care Guideline: Chronic Heart Failure, 3rd edition, 3rd version, www.awmf.org/uploads/tx_szleitlinien/nvl-006l_S3_Chronische_Herzinsuffizienz_2021-09_01.pdf, (last accessed Aug. 26, 2022).
- “Heart Failure,” Prof. Otmar Pfister, MD, medArt June 20-24, 2022.
- Anker SD, et al; EMPEROR-Preserved Trial Investigators: N Engl J Med. 2021; 385(16): 1451-1461.
- McMurray JJ,; PARADIGM-HF Investigators and Committees. N Engl J Med 2014; 371(11): 993-1004.
- Klip et al. Am Heart J 2013;165(4): 575-582.
- McDonagh TA, et al: ESC Scientific Document Group: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42(36): 3599-3726.
- Ponikowski P, et al: Lancet 2020; 396, 10266: 1895-1904.
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HAUSARZT PRAXIS 2022; 17(9): 18-19