Introduction

Pulmonary hypertension (PH) is a severe and progressive lung condition characterised by elevated pressure in the pulmonary arteries. Patients with PH often experience disabling symptoms such as shortness of breath, fatigue, fainting, and chest pain, placing them at significant risk for right ventricular failure and early mortality.¹ Clinically, when measured by right cardiac catheterisation, PH is defined as a mean pulmonary artery pressure of more than 20 mmHg at rest.² PH can have a serious effect on the heart and lungs. As the illness worsens, the right ventricle has to work harder to pump blood into the lungs due to the pulmonary arteries' increased pressure.³ This increased workload has the potential to cause right ventricular hypertrophy and ultimately right heart failure.¹ Since the right ventricle grows in response to the higher pressure it must resist, there is a well-established correlation between PH and heart enlargement.¹ This article aims to provide a comprehensive overview of pulmonary hypertension, focusing on three key areas:

• Diagnostic approach: This article will outline the steps involved in accurately diagnosing PH, including clinical evaluation, imaging studies, and the gold standard right heart catheterisation.
• Treatment options: This article will address the range of treatment options available for PH, encompassing both specialised therapies for certain PH populations and general supportive interventions.
• Management strategies: We will discuss the value of a multidisciplinary strategy for managing Parkinson's disease, including risk assessment, routine monitoring, and the function of specialised PH centres.

Mechanism and risk factors

PH initiates a cascade of events that ultimately result in increased strain on the heart, particularly the right ventricle. The primary mechanism involves elevated pressure in the pulmonary arteries, which forces the right ventricle to work harder to pump blood through the lungs.⁴ The pulmonary artery walls thicken and stiffen in PH, which limits the artery's capacity to enlarge and accommodate blood flow.⁵ The pulmonary artery pressure rises as a result of this higher resistance, increasing the stress on the right ventricle. The right ventricle experiences structural and functional modifications in order to maintain sufficient cardiac output while it battles to lower this excessive pressure.⁴ Enhanced pulmonary pressures over an extended period trigger the right ventricle’s adaptive mechanisms.⁶ The right ventricle first reacts by growing its muscular walls to produce greater pressure and keep the heart's output normal. The right ventricle may eventually widen, causing tricuspid regurgitation and a reduction in contractility, though, if the pressure overload continues.⁶ 

Primary PH and secondary PH are the two basic categories into which the condition falls. Secondary PH results from underlying illnesses including heart disease, chronic lung disease, or pulmonary embolism, whereas primary PH has no known cause.

Several factors can increase an individual's risk of developing PH such as:

• Obesity: Excess weight can contribute to left heart disease and sleep-disordered breathing, both of which are associated with PH²
• High blood pressure: Systemic hypertension can lead to left ventricular dysfunction and subsequent PH⁶
• Family history: Genetic factors play a role in some forms of pulmonary arterial hypertension, with mutations in certain genes increasing susceptibility²

Other risk factors include connective tissue disorders, HIV infection, and exposure to certain drugs or toxins.

Diagnosing PH in patients with heart enlargement

Clinical symptoms and signs

The initial step in diagnosis of the condition is identifying the distinctive symptoms and indicators of PH. Common symptoms include fatigue, dizziness, chest pain, shortness of breath (dyspnea), especially after activity, and swelling in the legs or belly (edema).⁷ These symptoms frequently appear gradually, and they could be confused with those of other cardiovascular disorders.

A physical examination may identify multiple important indicators:

• A loud sound as the pulmonary valve closes
• Dilated veins in the jaw
• Heave in the right ventricle
• Edema peripheral

Hepatomegaly occurs in more severe situations. It is crucial to remember that these symptoms might not exist in the early stages of the illness, highlighting the necessity of treating at-risk patients with a high degree of suspicion.⁷

Echocardiography

The gold standard for diagnosing PH is transthoracic echocardiography (TTE), which is usually the first imaging modality used. It offers a non-invasive way to measure pulmonary artery pressure and can identify heart enlargement in general and right ventricular hypertrophy and dilatation in particular.⁸ Assessing right ventricular function, a critical prognostic feature in PH, is another important purpose of TTE.

Important echocardiographic discoveries in PH comprise:

• Higher than 2.8 m/s tricuspid regurgitation velocity
• Malfunction and dilatation of the right ventricle
• Interventricular septum flattening
• Dilated right atrium
• Electrocardiogram (ECG)

When it comes to right heart strain, an ECG might provide important information. Typical discoveries in PH consist of:

• Deviation from the right axis
• Hypertrophy of the right ventricle
• Enlargement of the right atrium (P pulmonale)
• Block of the right bundle branch

Even though these ECG alterations are not unique to PH, when paired with additional clinical and imaging abnormalities, they can help confirm the diagnosis.⁹

Chest X-ray

An X-ray of the chest can show pulmonary vascular abnormalities and heart enlargement related to pneumonia. Typical results consist of:

• Expanded pulmonary arteries at the centre
• Cardiomegaly, namely swelling of the right atrium and ventricle
• Peripheral pulmonary artery pruning

However PH is not ruled out by a normal chest X-ray, particularly in the early stages of the illness.⁹

For the diagnosis of PH, right heart catheterisation is still considered the gold standard. It offers accurate measurement of cardiac output, pulmonary vascular resistance, and pulmonary artery pressure. When the mean pulmonary artery pressure is at rest and ≥25 mmHg, PH is clearly diagnosed.⁶ Catheterisation plays a critical role in diagnosis confirmation, PH severity assessment, and treatment planning.

Pulmonary function and blood work

Spirometry and diffusion capacity for carbon monoxide (DLCO), two tests of pulmonary function, are crucial for determining the presence of underlying lung disease and distinguishing between different types of PH. Tests on blood, such as NT-proBNP levels, can offer more diagnostic and prognostic data.⁶ 

MRI or CT scan

CT pulmonary angiography and cardiac MRI are examples of advanced imaging technologies that provide a thorough assessment of the anatomy of the heart and lungs. These techniques are especially beneficial for:¹

• Examining the structure and function of the right ventricle
• Recognising congenital cardiac abnormalities
• Assessing the lung parenchyma and pulmonary vasculature
• Recognising chronic thromboembolic disorders

Accurate evaluation of right ventricular mass, function, and volumes is possible using cardiac MRI; these parameters are critical prognostic markers in PH.

Treatment of PH in patients with heart enlargement

For patients with PH and heart enlargement, early detection and treatment are essential for improved outcomes. For optimal care, a multidisciplinary care team of cardiologists, pulmonologists, and specialised PH nurses is necessary.¹ Lowering pulmonary pressure, alleviating symptoms, quality of life improvement, and avoiding consequences related to illness development are the main objectives of treatment.

The underlying cause of PH, the degree of symptoms, and the existence of comorbidities such as heart enlargement should all be taken into consideration while developing treatment plans. To provide the best possible care for the patient, regular check-ups and plan modifications are required.

Endothelin receptor antagonist (ERA)

Endothelin is a strong vasoconstrictor and ERAs like bosentan prevent its effects. For patients with PH, these drugs can lower pulmonary vascular resistance and increase exercise capacity.¹ Enzymatic replacement therapies may also improve cardiac remodelling in patients with enlarged hearts.

Inhibitors of phosphodiesterase-5 (PDE-5)

PDE-5 inhibitors raise cyclic guanosine monophosphate (cGMP) levels in vascular smooth muscle cells, which improves vasodilation and lowers pulmonary pressure.¹ Patients with PH, particularly those with left heart disease, have demonstrated improved exercise capacity and hemodynamics when using these drugs.

Prostacyclin analogues

Prostacyclin analogues, such as epoprostenol, promote vasodilation and inhibit platelet aggregation. These medications are particularly effective in severe cases of PH and can be administered through various routes, including intravenous, subcutaneous, and inhaled formulations.¹ In patients with heart enlargement, prostacyclin analogues may help improve right ventricular function and reduce pulmonary vascular resistance.

Diuretics

Diuretics play a crucial role in managing fluid overload and symptoms of heart failure often associated with PH and heart enlargement. They help reduce congestion, improve breathlessness, and decrease right ventricular preload [10]. Careful monitoring of electrolytes and renal function is essential when using diuretics.

Anticoagulants

Patients with PH may benefit from anticoagulant medication, particularly if they have a history of chronic thromboembolic pulmonary hypertension (CTEPH) or thromboembolic events.¹ However, because of the possible increased risk of bleeding, anticoagulant usage in individuals with left heart disease should be carefully considered.

Lifestyle modifications

For patients with heart enlargement, lifestyle changes are just as important in controlling PH as medication interventions:

• Weight control: Retaining a healthy weight helps enhance general cardiovascular health and lessen the strain on the heart
• Low-sodium diet: Cutting back on sodium eases the load on the heart and helps control fluid retention
• Physical activity: Under medical supervision, a customised exercise program can enhance exercise capacity and quality of life⁴
• Stop smoking: Giving up smoking is essential for reducing cardiovascular risk and improving lung function

Diagnostic challenges

Overlapping symptoms

One of the primary challenges in diagnosing PH in patients with heart enlargement is the similarity of symptoms to other cardiac and pulmonary conditions.¹¹ Common symptoms such as shortness of breath, fatigue, and chest pain can be attributed to various heart or lung diseases, making it difficult to pinpoint PH as the underlying cause. This overlap often leads to delays in diagnosis and appropriate treatment initiation.

Late presentation and misdiagnosis

PH is frequently diagnosed at an advanced stage due to the non-specific nature of its early symptoms.¹² Patients with heart enlargement may have their symptoms initially attributed solely to their cardiac condition, overlooking the possibility of concurrent PH. This delay in recognition can result in disease progression and poorer outcomes.

Diagnostic accuracy of non-invasive tests

Echocardiography has limits in patients with heart enlargement, despite being a useful screening tool for premature cardiac hypertrophy. Studies have shown that there is only roughly 50% agreement between echocardiographic estimations and right heart catheterisation measurements, indicating that the accuracy of predicting pulmonary artery systolic pressure (PASP) using echocardiography may be reduced in these patients.¹³ This disparity may cause PH to be diagnosed incorrectly or too frequently.

Treatment challenges

PH management in patients with heart enlargement necessitates a careful drug regimen to treat both issues without making any worse. Vasodilators, for example, are used to treat PH, but they may exacerbate the symptoms of left heart failure by increasing pulmonary edema. On the other hand, patients with severe PH may not tolerate all heart failure drugs.

Adherence and adverse reactions

Long-term PH-specific medication usage can have serious adverse effects that affect a patient's quality of life and ability to stick to their treatment plan. Prostacyclin analogues, for example, can result in headaches, jaw pain, and systemic hypotension even though they are successful in treating PH.¹² Patients who are already experiencing signs of heart enlargement may find these side effects especially difficult to manage.

Complexity of treatment plans

Individuals who have cardiac enlargement in addition to PH may need complicated drug regimens. Adherence problems may arise from this complexity, particularly with older or cognitively impaired patients. The burden of therapy increases for patients and healthcare professionals when regular monitoring and dose modifications are required.

Prognosis and follow up care

Effects of early diagnosis and timely intervention

For patients with heart enlargement from PH, timely detection and therapy initiation are critical factors in determining the outcome. Delays in diagnosis have been linked to worse results and higher death rates, according to studies. According to one study, echocardiography-defined PH was discovered in 12.7% of newly diagnosed multiple myeloma patients and was associated with unfavourable outcomes, demonstrating the critical role echocardiography plays in early diagnosis.¹⁴

Regular echocardiographic evaluation

A vital component of follow-up care for PH patients with cardiac enlargement is echocardiography. To evaluate the effectiveness of treatment and the course of the disease, routine echocardiograms are crucial. Important variables to monitor are:

• Right ventricular size and function
• Estimated pulmonary artery systolic pressure (PASP) 
• Left ventricular diastolic function
• Presence and severity of tricuspid regurgitation

It's crucial to remember that right ventricular systolic pressure estimated by echocardiography might be off by more than 10 mm Hg from right heart catheterisation readings in around 50% of cases.¹ Thus, in certain situations, clinical correlation and even a second right cardiac catheterisation may be required.

Ongoing management of comorbidities

PH patients with heart enlargement must have their comorbidities effectively managed in order to maximise their outcomes. Important areas of attention consist of:^1,7,15

High blood pressure: Systemic hypertension can exacerbate PH and contribute to left ventricular dysfunction, therefore careful blood pressure management is crucial.

• Diabetes: Since diabetes can worsen cardiovascular problems and affect prognosis overall, glucose management is crucial
• Obesity: Maintaining a healthy weight is essential since obesity can exacerbate left heart disease and is linked to poorer results for people with PH
• Sleep-disordered breathing: As disorders like obstructive sleep apnea can exacerbate PH, it's critical to screen for and treat them
• Functional assessment and quality of life: Monitoring patients with PH who have cardiac enlargements requires routine evaluations of their functional capacity and quality of life. Usually, this includes:
  • Six-minute walk test: This easy test can be used to monitor the course of a condition and the effectiveness of treatment. It also gives important information about one's ability to exercise 
  • Cardiopulmonary exercise testing (CPET): Research has demonstrated that CPET is helpful in identifying aberrant exercise responses unique to PH and can yield comprehensive information regarding cardiopulmonary function
  • Quality of life questionnaires: Monitoring patient-reported outcomes on a regular basis can aid in making management decisions and assessing the treatment's overall impact

Conclusion

Improved outcomes for people with PH and heart enlargement require prompt diagnosis and individualised treatment. Prompt diagnosis enables therapy to be started, which may delay the progression of the illness and enhance quality of life. It is impossible to overestimate the significance of a multidisciplinary approach since it allows for holistic care that addresses underlying cardiac problems as well as PH.

In these patients, right ventricular function has come to light as a crucial prognostic marker. Frequent echocardiographic evaluation of parameters provides important information on the course of the disease and the effectiveness of treatment.¹⁴ Treatment options have increased due to recent developments in PH-specific treatments. There is hope for better results with the approval of new drugs like Winrevair (sotatercept-csrk), which targets a novel biological route.¹⁶

Patient outcomes can be greatly impacted by early detection and referral to specialised PH facilities. To give their patients the best care possible, medical professionals should participate in continuing medical education programs and stay up to date on the most recent advancements in PH therapy.

In summary, even though the treatment of PH in patients with heart enlargement has advanced significantly, more research and clinical attention are required to enhance results. By maintaining a proactive approach to diagnosis, embracing new treatment options, and participating in ongoing research, healthcare professionals can contribute to a better quality of life and improved long-term outcomes for patients with this challenging condition.