Introduction
Heart failure (HF) is a clinical syndrome characterized by typical symptoms (shortness of breath, fatigue, leg swelling) that may be accompanied by clinical signs (elevated venous pressure, inspiratory crackles, peripheral edema). This syndrome is caused by structural and/or functional abnormalities of the heart that result in reduced stroke volume and/or increased intracardiac pressure during exertion or at rest. (1)
Cardiac asthma is not asthma in the usual sense. It is not caused by inflammation or bronchoconstriction. Instead, it occurs as a consequence of HF, predominantly left-sided heart failure. It is caused by pulmonary congestion resulting from the failure of the left side of the heart. Cardiac asthma is a clinical syndrome characterized by paroxysmal dyspnea, as well as pulmonary wheezing and coughing.
The Spanish painter Francisco Goya (1746-1828) painted his Self-Portrait with Dr. Arrieta as early as 1820. He created the painting out of gratitude to his doctor, who had successfully treated him. The artwork faithfully depicts the clinical presentation of cardiac asthma. In the painting, Goya is seated, sweating, pale, slightly cyanotic, and gasping for air with his mouth open, while Dr. Arrieta supports him and administers medication. (2) The term cardiac asthma was first employed by British physician James Hope in 1832. (3) He described various types of asthma as well as the symptoms that differentiate asthma caused by lung diseases from asthma due to heart disease. (4)
According to GINA (Global Initiative for Asthma) guidelines, asthma is a heterogeneous disease characterized by chronic inflammation and airway hyperreactivity. Symptoms such as wheezing, shortness of breath, chest tightness, and coughing vary over time, occurring at different intervals and with varying intensity. One of its key characteristics is variable airway obstruction, which may become persistent over time. (5) Treatment is based on inhaled corticosteroids.
The definition of chronic obstructive pulmonary disease (COPD) also describes a heterogeneous disease characterized by chronic symptoms (shortness of breath, cough, sputum production) resulting from changes in the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema), which cause persistent, often progressive airway obstruction. One of the leading causes of COPD is smoking. Bronchodilators represent the basis for the treatment of the disease. (6)
Heart failure, COPD, and asthma are among the most significant health issues in the modern world. HF as comorbidity is present in 20% of patients with COPD, while at least 50% of them have systolic dysfunction of the left ventricle. Conversely, approximately 35% of patients with HF have COPD as comorbidity. (7)
The current guidelines of the European Society of Cardiology (1,8) no longer mention cardiac asthma in their classification but instead categorize HF as acute or chronic. Chronic HF is further classified into the following types based on left ventricular ejection fraction (EF):
Chronic heart failure with preserved ejection fraction (HFpEF) – LVEF ≥50%
Chronic heart failure with mildly reduced ejection fraction (HFmrEF) – LVEF 41–49%
Chronic heart failure with reduced ejection fraction (HFrEF) – LVEF ≤40%
In addition to classification by ejection fraction, the 2022 American guidelines for HF (9) also describe four stages of HF:
Stage A – At risk for HF: The individual has no symptoms, no structural heart disease, and no elevated biomarkers (e.g., individuals with hypertension, metabolic syndrome, or a family history of heart disease).
Stage B – Pre-heart failure: No symptoms or signs of HF, but with structural heart disease, elevated cardiac filling pressures, or increased levels of natriuretic peptides (NT-proBNP, BNP).
Stage C – Symptomatic HF: Structural heart disease with symptoms and signs of HF.
Stage D – Advanced HF: Severe symptoms that interfere with daily activities and lead to frequent hospitalizations.
The severity of HF symptoms and the functional capacity of the patient are classified according to the NYHA (New York Heart Association) classification, which ranks symptom severity into four grades. Despite its limitations, the NYHA classification remains an independent predictor of patient mortality.
Class 1 – No limitation of physical activity. Ordinary physical activity does not cause shortness of breath, fatigue, or palpitations.
Class 2 – Mild limitation of physical activity. No symptoms at rest, but ordinary activity causes shortness of breath, fatigue, or palpitations.
Class 3 – Significant limitation of physical activity. No symptoms at rest, but even minimal physical activity triggers symptoms.
Class 4 – Unable to perform any physical activity; symptoms may be present even at rest.
The medication treatment for HF is based on the following medications: renin-angiotensin-aldosterone system inhibitors (ACE inhibitors and angiotensin receptor blockers (ARBs), with or without angiotensin receptor-neprilysin inhibitors – ARNI), beta-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRA) and diuretics, most commonly loop diuretics, used to relieve symptoms. Other medications and the management of other comorbidities also play a crucial role in HF treatment. In advanced HF management, implantable devices such as cardioverter defibrillators, cardiac resynchronization therapy devices and long-term mechanical circulatory support devices may be used, with heart transplantation as the final treatment option. (1)
Case report
Herein we present the case of a male patient with dilated cardiomyopathy of unknown etiology and reduced systolic function of the left ventricle, whose first manifestation of heart failure (HF) was in the form of cardiac asthma (NYHA Class 4).
A 64-year-old long-term smoker with a history of previous stroke was initially treated at the County Hospital for the exacerbation of a psychiatric condition related to post-traumatic stress disorder. During hospitalization, the patient began complaining of exertional dyspnea. His prior treatment included a short-acting beta-agonist (salbutamol) prescribed by his primary care physician, but it was no longer effective. The patient had never been evaluated by a pulmonologist and did not have a clear diagnosis of asthma or COPD.
At the first examination by an internal medicine specialist, the patient was tachypneic at rest and using accessory respiratory muscles. Physical examination revealed prolonged expiration with wheezing bilaterally, but with no signs of peripheral congestion. The chest X-ray showed increased transparency of both lung fields without fresh infiltrates, with discreet pathological interstitial changes in the mid-lung periphery. There was no pleural effusion, mediastinal shadow width was normal, and with no hilar pathological changes. Heart size was normal, with rounded contours of the left ventricle. The initial 12-lead ECG recorded a normal electrical axis and atrial tachycardia with a ventricular rate of 131 bpm, with occasional ventricular extrasystoles. The initial working diagnosis established at the ward was COPD or asthma exacerbation, and treatment was started with IV methylprednisolone and short-acting bronchodilator inhalations. No significant clinical improvement occurred on this therapy. Laboratory findings showed acute kidney injury, elevated liver enzymes, and mildly elevated C-reactive protein (CRP), with markedly elevated NT-proBNP, exceeding the measurement range in the laboratory. HF treatment was initiated based on these findings, comprising treatment with diuretics along with an empirical broad-spectrum antibiotic (ceftriaxone), nebivolol, and dapagliflozin. In addition to the above, treatment with corticosteroids and bronchodilators was continued as well. ACEi/ARB were not initially introduced due to low arterial blood pressure. After five days of treatment, the patient showed significant clinical improvement and a significant decrease in NT-proBNP levels (now 5386 pg/mL), but with further worsening of kidney function. Additional diagnostics were performed as well. Spirometry findings confirmed COPD. Echocardiography showed dilation of all four cardiac chambers (LVIDd 60 mm, LA 52 mm, RV 35 mm, RA 52×34 mm), global akinesia with hypokinesis of the lateral wall and septum (functionally belonging to the right ventricle), along with inferior and inferolateral wall thinning with an aneurysm of the basal third of the inferior wall. Left ventricular ejection fraction was severely reduced (EF 15%). Doppler findings indicated severe secondary mitral and tricuspid regurgitation with indirect markers of pulmonary hypertension and grade III diastolic dysfunction. Based on these findings, eplerenone, a mineralocorticoid receptor antagonist, was added to the therapy. An angiotensin receptor-neprilysin inhibitor was not introduced due to symptomatic hypotension preventing valsartan titration above 40 mg. A 24-hour Holter ECG recorded asymptomatic, non-sustained ventricular tachycardias.
Medication dosages were optimized during further treatment, and recovery of kidney function was observed; consequently, the patient was discharged with the following therapy: nebivolol 10 mg, empagliflozin 10 mg, eplerenone 50 mg, valsartan 40 mg, furosemide 80 mg, acetylsalicylic acid 100 mg, atorvastatin 40 mg, umeclidinium bromide/vilanterol 55/22 mcg (1 inhalation daily).
At discharge, the patient was advised to follow up with a pulmonologist and a cardiologist/electrophysiologist for further advanced treatment. A coronary angiography would be required in order to determine the etiology of dilated cardiomyopathy, with cardiac MRI and genetic testing to be considered depending on the findings. Since these tests could not be performed during hospitalization, the patient was referred for further evaluation in his place of residence.
Discussion
Differentiating heart failure (HF) from asthma and COPD is usually straightforward, except in cases where both conditions are present. In such cases, a definitive diagnosis requires an ECG, complete pulmonary function tests, echocardiography, and determining natriuretic peptide levels. However, in clinical practice, the diagnosis is often established based on symptoms alone. In younger patients, the presence of coughing and wheezing has high sensitivity and specificity for asthma, but the risk of misdiagnosis increases in older adults. (10) A misdiagnosis poses a significant risk to patients, as they not only receive incorrect treatment, thus being denied appropriate care, but they also face a higher risk of developing cardiovascular side effects. Medications used to treat asthma (corticosteroids, bronchodilators) are not effective in managing cardiac asthma. In fact, some of these medications can worsen HF. For example, theophylline, a second-line bronchodilator, is contraindicated in patients with HF. (11) When administered orally, corticosteroids cause sodium retention and thus also fluid retention, resulting in HF exacerbation. (12) Beta-2 agonists can affect beta-1 receptors in the heart, thus causing tachycardia that leads to an increased risk of ischemic events. This effect of beta-2 agonists is present regardless of whether they are administered orally or via inhalation. However, some evidence suggests that the beta-2 agonist vilanterol, either alone or in combination with inhaled corticosteroid fluticasone, does not increase cardiovascular mortality risk. (13) Additionally, inhaled anticholinergics are considered a safe alternative for patients with HF and coexisting COPD. (14)
In older individuals presenting with paroxysmal dyspnea and cough for the first time, it is always necessary to consider the possibility of HF. Diagnostic clues that can facilitate this process include electrocardiography, medical history of diuretic use, the presence of arterial hypertension and ischemic heart disease, etc. Diagnosing cardiac asthma is not straightforward and simple, as shares symptoms with various other clinical entities, requiring sharp clinical judgment to establish an accurate diagnosis.
Habaruiga et al. (15) described the case of a 52-year-old patient who was misdiagnosed and unsuccessfully treated for asthma for two years before finally being accurately diagnosed with HFrEF. Other clinical syndromes can also present as cardiac asthma. For example, ischemic heart disease, acute myocardial infarction, unstable angina, myocarditis, postpartum cardiomyopathy, mitral valve diseases, and other diseases can present as cardiac asthma. (16) Veeraraghavan et al. described a case of a giant left atrial myxoma in a 32-year-old woman who was misdiagnosed and treated for recurrent asthma attacks for a year. (17)
One of the reasons why these diagnoses are difficult to differentiate lies in the masking effect on pulmonary function tests. Episodes of heart failure exacerbation can affect pulmonary function test results not only during the exacerbation itself but for up to three months afterwards. Obstructive lung diseases cause lung hyperinflation and an obstructive pattern (Tiffeneau index FEV1/FVC <0.7 and a decrease in forced expiratory volume in the first second (FEV1)), whereas HF causes a restrictive pattern (proportional reduction in FEV1 and forced vital capacity (FVC)). In patients with chronic HF, findings of increased residual volume (RV) and functional residual capacity (FRC) can quickly guide us toward a COPD diagnosis. However, in patients who have COPD along with coexisting HF, the situation is more complex. Congestion, low cardiac output, and reduced pulmonary compliance contribute to restriction. Restriction, if severe enough, will mask lung hyperinflation and lead to a false “normalization” of pulmonary function test results. (18,19)
Conclusion
Instead of a formal conclusion, we would like to emphasize the importance of taking the patient’s medical history, performing a thorough clinical examination, and careful clinical reasoning. It is crucial not to jump to conclusions, as not every wheeze is caused by asthma or COPD exacerbation. Wheezing can also be caused by HF exacerbation or so-called cardiac asthma. Although the term cardiac asthma is less frequently used today, it is still worth bearing in mind in order to avoid hasty conclusions that could lead us astray in diagnosis and treatment.