Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated.

Pulmonary arterial hypertension (PAH) is a rare condition characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. It primarily affects the pre-capillary pulmonary vascular system. The exact pathophysiological mechanisms underlying PAH are not entirely known. Environmental factors; genetic predisposition; mitochondrial and microRNA dysfunction; and inflammatory, metabolic, and hormonal mechanisms may be involved. A central role is played by the dysfunction of the pulmonary vascular endothelium. This alteration is characterized by a reduction in vasodilatory and antiproliferative factors such as prostacyclin and nitric oxide and an increase in vasoconstrictive and mitogenic substances such as endothelin and thromboxane A2. Such imbalance leads to a progressive increase in pulmonary vascular resistance. The aim of the present review is to focus on the vascular endothelium and its role as a potential therapeutic target in PAH.

Cardiopulmonary Exercise Testing (CPET) is the gold standard for the functional assessment in patients with heart failure (HF), providing objective parameters that reflect the integrated response of the cardiovascular, respiratory, and muscular systems, in addition several CPET-derived variables have shown independent prognostic value in patients with both reduced (HFrEF) and preserved ejection fraction (HFpEF) HF. This review aims to critically analyze the main CPET prognostic variables in heart failure, highlighting their underlying pathophysiological mechanisms, their predictive capacity for mortality and hospitalizations, and their integration into clinical decision-making models. Parameters such as peak oxygen uptake (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, periodic breathing (or exercise oscillatory ventilation—EOV), anaerobic threshold (AT), oxygen pulse, and VO₂/work slope provide complementary insights into clinical risk; moreover, the combination of multiple CPET variables allows for more accurate risk stratification compared to the isolated use of each parameter. Multiparametric prognostic models such as the Metabolic Exercise Cardiac Kidney Index (MECKI) score, the Seattle Heart Failure Model, and the Heart Failure Survival Score (HFSS) incorporate these variables alongside clinical and laboratory data to guide advanced management and therapeutic decisions, including heart transplantation or left ventricular assistant device (LVAD) implantation. For these reasons, CPET-derived variables are essential prognostic tools in heart failure. Beyond improving risk stratification, their integration into multiparametric models supports a more personalized therapeutic approach, including tailored pharmacological management.

Acute myocarditis (AM) is an inflammatory cardiac condition resulting from infections, toxic exposures, or immune-mediated mechanisms, with clinical presentations ranging from mild symptoms to heart failure (HF) or cardiogenic shock. Although viral infections remain the predominant cause, both the absolute prevalence and the relative distribution of different etiologies may change over time and across regions depending on endemic diseases. Immune checkpoint inhibitor (ICI)-associated myocarditis has emerged as a newly recognized entity, with diagnostic rates increasing in parallel with growing awareness and the expanding population of cancer patients eligible for ICI therapy. Additionally, genetic predisposition—particularly mutations linked to arrhythmogenic cardiomyopathy—is also being increasingly acknowledged as a susceptibility factor. Recent advances have markedly improved the diagnostic approach to AM. The availability of high-sensitivity cardiac troponins and the widespread use of cardiac magnetic resonance imaging (CMRI) have enhanced early detection and tissue characterization. CMRI, especially following the updated Lake Louise Criteria (2018), which incorporate T1 and T2 mapping, enables accurate assessment of myocardial inflammation and fibrosis. Endomyocardial biopsy (EMB) remains essential in complicated cases, particularly to identify histologic subtypes that may benefit from immunosuppressive therapy. Early EMB (within 48 h) has been associated with better outcomes in fulminant presentations. The use of immunohistochemistry with leukocyte-specific markers has further increased the sensitivity of EMB. Therapeutic strategies now integrate etiology-specific approaches. Immunosuppressive therapy is indicated for distinct histological forms such as eosinophilic (EM) and giant cell myocarditis (GCM) or cases associated with systemic autoimmune disease. Conversely, in most patients with acute myocarditis complicated by acute HF or cardiogenic shock, no specific treatment is currently recommended beyond evidence-based management of acute HF and general supportive therapy.

Major surgery imposes physiological stress requiring coordinated adaptation of the cardiovascular, respiratory, hematological, and musculoskeletal systems. Conventional preoperative assessment remains essential but may underestimate heterogeneity in physiological reserve because resting measurements incompletely capture the response to increasing metabolic demand. Cardiopulmonary exercise testing (CPET) provides an integrated assessment of oxygen transport and utilization, linking pulmonary ventilation and gas exchange to cardiovascular performance and peripheral oxygen extraction. This narrative review examines the role of CPET in preoperative assessment, from prognostic testing to physiological phenotyping and personalized perioperative care. We summarize the physiological basis of key variables, including peak oxygen uptake, anaerobic threshold, oxygen pulse, ventilatory efficiency, end-tidal carbon dioxide, breathing reserve, and exercise kinetics, and discuss how integrated interpretation can identify patterns suggestive of haemodynamic, ventilatory, pulmonary vascular, or peripheral limitations. Evidence across major surgical populations is critically appraised, with attention to isolated thresholds and the distinction between prognostic association and clinical effectiveness. The current data support selective rather than universal use of CPET, particularly when functional capacity is uncertain or physiological information may alter management. We propose a phenotype-oriented framework in which CPET findings identify potentially modifiable impairments and inform cardiovascular optimization, respiratory treatment, nutritional support, exercise training, and prehabilitation. Emerging approaches combining complex CPET, non-invasive haemodynamic assessment, wearable technologies, and artificial intelligence may enable personalized profiling, although prospective validation remains necessary. CPET should therefore be considered not simply a risk-prediction tool, but an in vivo interrogation of physiological reserve that can contribute to mechanism-oriented perioperative assessment.