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Vol 18, No 4 (2023)
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HFpEF mimics: hypertrophic cardiomyopathy in light of the 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure with Preserved Ejection Fraction

Kacper Maj1, Katarzyna Major1, Małgorzata Lelonek1
Folia Cardiologica 2023;18(4):182-186.

Abstract

Hypertrophic cardiomyopathy is a genetic condition which leads to myocardial hypertrophy. Main cause of death in a group of patients with this disease is sudden cardiac death. In this article we present a diagnostic path which is consistent with the American College of Cardiology Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction diagnostic path. This led to diagnosis of hypertrophic cardiomyopathy and classifying it to the newly established amongst heart failure with preserved ejection fraction group — HFpEF mimics.

HEART FAILURE

Folia Cardiologica 2023

vol. 18, no. 4, pages 182–186

DOI: 10.5603/fc.96348

Copyright © 2023 Via Medica

ISSN 2353–7752

e-ISSN 2353–7760

HFpEF mimics: hypertrophic cardiomyopathy in light of the 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure with Preserved Ejection Fraction

Kacper MajKatarzyna MajorMałgorzata Lelonek
Department of Noninvasive Cardiology, Medical University of Lodz, Łódź, Poland

Address for correspondence: Kacper Maj MD, Zakład Kardiologii Nieinwazyjnej, Uniwersytet Medyczny w Łodzi, ul. Żeromskiego 113, 90–549 Łódź, Poland, phone: +48 784 573 181, e-mail: kacper.a.b.maj@gmail.com

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

Abstract
Hypertrophic cardiomyopathy is a genetic condition which leads to myocardial hypertrophy. Main cause of death in a group of patients with this disease is sudden cardiac death. In this article we present a diagnostic path which is consistent with the American College of Cardiology Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction diagnostic path. This led to diagnosis of hypertrophic cardiomyopathy and classifying it to the newly established amongst heart failure with preserved ejection fraction group — HFpEF mimics.
Key words: hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, heart failure, sudden cardiac death
Folia Cardiologica 2023; 18, 4: 182–186

Introduction

Hypertrophic cardiomyopathy (HCM) is a disease with a prevalence of 0.02% to 0.23% in adults, and it has a genetic background. The European Society of Cardiology guidelines define HCM as a thickening of the left ventricular wall ≥ 15 mm detected using any imaging method, which cannot be solely explained by its increased load [1]. The pathophysiology of HCM includes not only myocardial hypertrophy but also diastolic dysfunction, mitral regurgitation, myocardial ischemia, and in some patients, left ventricular outflow tract obstruction (LVOTO). The clinical presentation of the disease can take various forms, depending on the predominant pathophysiological factor or as a result of their mutual interactions [2].

According to this year’s expert statement from the American College of Cardiology regarding heart failure with preserved ejection fraction (HFpEF), HCM belongs to the newly distinguished group of HFpEF mimics. HFpEF mimics refer to patients with clinical symptoms of heart failure (HF), a left ventricular ejection fraction (LVEF) ≥ 50%, and a primary cardiac cause of HF (infiltrative cardiomyopathy, HCM, valvular heart diseases, diseases of pericardium) or non-cardiac causes of HF (kidney or liver diseases) [3].

The presented case is described in the context of the most current knowledge.

Case report

A 68-year-old female patient was admitted to the hospital due to palpitations, exertional dyspnea, and worsening exercise tolerance. According to the patient, the symptoms had been present for several months and worsened over the last few weeks. The patient also complained of presyncopal and syncopal episodes without any preceding warning signs.

Moreover, the patient had a history of thyroidectomy and partial resection of the left kidney due to tuberculosis.

Upon admission, the patient was classified as New York Heart Association class II patient. Physical examination revealed crackles that were audible at the lung bases during chest auscultation, and mild edema of the lower extremities up to the ankles. No other abnormalities were observed.

Chest X-ray showed an enlarged cardiac silhouette. Resting electrocardiogram (ECG) showed sinus rhythm with a heart rate of 65/min and signs of left ventricular hypertrophy (S in V3 + R in aVL > 20 mm).

Transthoracic echocardiography revealed significant asymmetric hypertrophy of the left ventricular myocardium, especially in the parabasal segments of the posterior wall and lateral wall, where thickness of the myocardium reached 18 mm in diastole. There was no increased intraventricular gradient recorded, which in the LVOT was max. 10 mm Hg, nor abnormal anterior mitral valve leaflet motion. The LVEF was preserved, however, elevated filling pressures indicative of diastolic dysfunction were observed.

Selected laboratory test results are shown in Table 1.

Table 1. Results of selected laboratory tests

Total cholesterol

mmol/L

6.16

High-density lipoprotein

mmol/L

1.34

Non-high-density lipoprotein

mmol/L

4.82

Low-density lipoprotein

mmol/L

4.28

Triglycerides

mmol/L

1.21

Na

mmol/L

139.2

K

mmol/L

4.66

Cl

mmol/L

104.3

Glomerular filtration rate

mL/min/1.72 m2

55.2

Creatinine

µmol/L

94.7

Urea

mmol/L

5.8

N-terminal pro-B-type natriuretic peptide

pg/mL

1778

CA125

U/mL

13

Ferritin

µg/L

18.6

Uric acid

µmol/L

417.8

It was decided to prolong the Holter ECG monitoring of cardiac function. The 48-hour recording revealed sinus rhythm with an average rate of 63/min, 13 episodes of non-sustained ventricular tachycardia with a maximum rate of 145/min (Figure 1), as well as episodes of ventricular trigeminy lasting a few seconds.

Figure 1. Ventricular tachycardia episode recorded on Holter electrocardiogram recording

A computed tomography scan of the coronary arteries performed during hospitalisation revealed mural atherosclerotic lesions.

Based on the diagnostic process, HF was diagnosed, and further imaging studies were planned. The patient was prescribed a beta-blocker titrated to heart rate, a statin, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor. Treatment for reducing uric acid levels was intensified, and intravenous iron infusion was administered due to concurrent iron deficiency. Single-photon emission computed tomography with 3,3-diphosphono-1,2-propanodicarboxylic acid was performed to rule out amyloidosis, yielding a negative result.

Cardiac magnetic resonance (CMR) imaging was ordered to verify the findings of transthoracic echocardiography and exclude potential storage diseases that may cause myocardial hypertrophy. Myocardial thickening was observed in the basal segments of the anterior wall up to 17 mm, lateral wall up to 20 mm, and inferior wall up to 15 mm, while in the middle segments of the anterior wall, inferior wall and interventricular septum up to 13 mm. Focal and linear intramural areas of increased contrast accumulation indicative of fibrosis were present in the thickened LV segments. The assessed LVEF was 70%. Right ventricular outflow tract subvalvular obstruction resulting from concentric wall thickening was described, without RV enlargement or RV systolic dysfunction. Late gadolinium enhancement (LGE) assessed during CMR reflects the degree of myocardial fibrosis associated with life-threatening arrhythmias and sudden cardiac death (SCD). If LGE is ≥ 15% of LV mass, the patient is at high risk of SCD and implantation of a cardioverter-defibrillator is recommended [4]. How­ever, this parameter was not evaluated in the CMR of this patient due to the lack of appropriate software.

According to the recommended diagnostic process for HFpEF by the ACC, non-cardiac causes such as kidney and liver diseases, and chronic venous insufficiency were excluded in this patient. Then, in accordance with the proposed algorithm, cardiac causes of HF belonging to the newly distinguished group of HFpEF mimics were considered, including secondary cardiomyopathies, HCM, diseases of pericardium, and valvular heart diseases. HCM without LVOTO was diagnosed based on echocardiography and CMR findings. The entire diagnostic process ultimately led to the diagnosis of HFpEF mimics (Figure 2).

Figure 2. Diagnostic pathway for the diagnosis of HFpEF mimics — based on the 2023 ACC Expert Consensus Decision pathway on management of heart failure with preserved ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee

The patient’s family history did not indicate a history of SCD, and the patient’s children were informed about the need for diagnostic evaluation for HCM. Genetic testing was not performed in this patient due to the limited availability of tests for detecting the mutations responsible for the disease.

Based on the patient’s symptoms, family history, and additional test results, a 5-year risk of SCD was calculated using the European Society of Cardiology recommended SCD SCORE calculator, resulting in a score of > 6% (Table 2) (https://doc2do.com/hcm/webHCM.html). Consequently, the patient was referred to a reference center for the implantation of a cardioverter-defibrillator as primary prevention of SCD. The patient was also informed that there is no need to restrict physical activity.

Table 2. Data used for calculating the sudden cardiac death (SCD) score using the recommended European Society of Cardiology (ESC) calculator

Age

68 years

Max. left ventricular wall thickness

18 mm

Left atrial dimension

46 mm

Max. gradient in the left ventricular outflow tract

10 mm Hg

Family history of SCD

No

Non-sustained ventricular tachycardia

Yes

Unexplained syncope

Yes

5-year risk of SCD

6.24%

ESC recommendation

Implantable cardioverter- defibrillator should be considered

Lampert et al. [5] in the observational study LIVE-HCM (Lifestyle and Exercise in Hypertrophic Cardiomyopathy) involving a group of 1660 patients with HCM or genetically predisposed to it did not observe a higher risk of death or life-threatening arrhythmias among patients engaging in intense physical activity compared to the group of patients with moderate physical activity or a sedentary lifestyle.

Discussion

The clinical picture of HCM is diverse. The key in the diag­nostic process is highly specialised imaging to determine the causes of myocardial hypertrophy and the analysis of numerous variables, such as family history, patient-reported symptoms, the presence of LVOTO, or rhythm disorders. Each of these factors will modify the therapeutic approach. The treatment of HCM is focused on reducing symptoms in patients and preventing SCD. In the case of HCM with concomitant LVOTO, pharmacotherapy will involve beta-blockers without vasodilator effect at the highest doses tolerated by the patient. In cases of intolerance to beta-blockers, verapamil or diltiazem can be considered. Additionally, disopyramide may be added to the treatment, as it contributes to reducing the pressure gradient in the LVOT through its antiarrhythmic and negative inotropic effects.

In situations where the pressure gradient in the LVOT exceeds 50 mm Hg, procedural treatment should be considered, such as Morrow procedure (ventricular septal myectomy) or alcohol (septal) ablation.

Great hopes are associated with mavacamten, a selective cardiac myosin inhibitor, which was first approved for the treatment of this form of HCM in the USA in 2022 [6].

The EXPLORER-HCM trial (mavacamten for treatment of symptomatic obstructive HCM) demonstrated improvements in exercise capacity, reduction of HF symptoms, and LVOTO in the group of patients using mavacamten compared to the placebo group [7].

On the other hand, for patients with HCM without LVOTO who are clinically symptomatic, the medications to be considered include beta-blockers, verapamil or diltiazem, and low doses of loop or thiazide diuretics. There are initial reports on the positive effects of SGLT2 inhibitors in this patient group. In a prospective study involving HCM patients taking these medications for 6 months, there was a significant improvement in LV diastolic function parameters, an increase in the 6-minute walking test distance, and a reduction in N-terminal pro-B-type natriuretic peptide levels compared to the placebo group [8].

In conclusion, the ACC consensus highlights the challenge of diagnosing HFpEF and proposes a new diagnostic algorithm enabling the diagnosis of both cardiac and non-cardiac conditions mimicking HFpEF. It identifies a new group called HFpEF mimics. Diagnosing diseases within this group, which have a different pathophysiological mechanism, allows the application of appropriate targeted therapy.

Article information

Acknowledgments

Author contributions

KM and KM — writing; ML — writing and supervision with expertise

Conflict of interest

KM and KM declared no conflict of interest. ML — received lecture and consulting fees from AstraZeneca and Boehringer Ingelheim and were involved in clinical trials from Boehringer Ingelheim.

Ethics statement

Funding

Supplementary material

References

  1. Elliott P, Anastasakis A, Borger M, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. Kardiologia Polska. 2014; 72(11): 1054–1126, doi: 10.5603/kp.2014.0212.
  2. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020; 142(25): e558–e631, doi: 10.1161/CIR.0000000000000937, indexed in Pubmed: 33215931.
  3. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023; 81(18): 1835–1878, doi: 10.1016/j.jacc.2023.03.393, indexed in Pubmed: 37137593.
  4. Morawiec R, Cichocka-Radwan A, Maciejewski M, et al. Kardiomiopatia przerostowa u bezobjawowej 24-letniej kobiety w ciąży — postępowanie według wytycznych ESC. Folia Cardiologica. 2018; 13(1): 55–58, doi: 10.5603/fc.2018.0010.
  5. Lampert R, Ackerman MJ, Marino BS, et al. LIVE Consortium. Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy. JAMA Cardiol. 2023; 8(6): 595–605, doi: 10.1001/jamacardio.2023.1042, indexed in Pubmed: 37195701.
  6. Keam SJ. Mavacamten: First Approval. Drugs. 2022; 82(10): 1127–1135, doi: 10.1007/s40265-022-01739-7, indexed in Pubmed: 35802255.
  7. Olivotto I, Oreziak A, Barriales-Villa R, et al. EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020; 396(10253): 759–769, doi: 10.1016/S0140-6736(20)31792-X, indexed in Pubmed: 32871100.
  8. Subramanian M, Sravani V, Krishna SP, et al. Efficacy of SGLT2 Inhibitors in Patients With Diabetes and Nonobstructive Hypertrophic Cardiomyopathy. Am J Cardiol. 2023; 188: 80–86, doi: 10.1016/j.amjcard.2022.10.054, indexed in Pubmed: 36473308.