Pradhab Kirupaharan

Sotatercept, a first‐in‐class activin signaling inhibitor, improves pulmonary vascular hemodynamics and clinical outcomes in pulmonary arterial hypertension (PAH). However, despite reductions in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), cardiac output (CO) does not generally increase, and some patients experience a decline in CO, a finding of unclear clinical significance. We sought to characterize the heterogeneity of CO responses to sotatercept in PAH and to determine whether incorporating oxygen delivery (DO ₂ ) provides additional insight into the physiological significance of these changes. We retrospectively analyzed PAH patients who underwent right heart catheterization before and during sotatercept therapy (median 7.3 months, IQR 4.8, 9.3). Hemodynamic, echocardiographic, hematologic, and clinical parameters were collected, including functional class, 6‐min walk distance (6MWD) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Patients were dichotomized by CO response (decreased vs. maintained), and DO ₂ was calculated at each catheterization. A total of 56 patients were included. While most demonstrated reductions in PVR and mPAP, 63% experienced decreased CO. Improvements in 6MWD and NT‐proBNP were similar between groups, and hemoglobin increased comparably. However, among patients with decreased CO, 63% had a concomitant decline in DO ₂ accompanied by worsening 6MWD and a reduced NT‐proBNP response. In this real‐world cohort, over half of sotatercept‐treated PAH patients experienced reduced CO despite overall hemodynamic and clinical improvement. Concomitant reductions in DO ₂ identify a subgroup with worse functional outcomes. These findings suggest that DO ₂ adds additional information beyond CO alone when assessing the physiological response to sotatercept.

Patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (PH) frequently experience dyspnea which is not explained by stationary assessment and therefore requires cardiopulmonary exercise testing for further diagnostic insight. Ventilatory inefficiency in CTEPD is commonly identified; however, consensus definitions are lacking. Upright iCPET and careful definition of ventilatory inefficiency (i.e., lack of reduction in VD/VT with exercise) may allow optimal characterization of patients with chronic thromboembolic disease and specifically helps correctly identify patients with preload insufficiency who may otherwise be misclassified or undiagnosed.

The addition of exercise testing during right heart catheterization (RHC) is often required to accurately diagnose causes of exercise intolerance like early pulmonary vascular disease, occult left heart disease, and preload insufficiency. We tested the influence of body position (supine vs. seated) on hemodynamic classification both at rest and during exercise. We enrolled patients with exercise intolerance due to dyspnea who were referred for exercise RHC at the Cleveland Clinic. Patients were randomized (1:1) to exercise in seated or supine position to a goal of 60 W followed by maximal exercise in the alternate position. We analyzed 17 patients aged 60.3 ± 10.9 years, including 13 females. At rest in the sitting position, patients had significantly lower right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP) and cardiac index (CI). In every stage of exercise (20, 40, and 60 W), the RAP, mPAP, and PAWP were lower in the sitting position. Exercise in the sitting position allowed the identification of preload insufficiency in nine patients. Exercise in either position increased the identification of postcapillary pulmonary hypertension (PH). Body position significantly influences hemodynamics at rest and with exercise; however, mPAP/CO and PAWP/CO were not positionally affected. Hemodynamic measurements in the seated position allowed the detection of preload insufficiency, a condition that was predominantly identified as no PH during supine exercise.

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy. Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to our hospital, he was found to have elevated muscle specific enzymes, prompting evaluation for neuromuscular causes of respiratory failure. He was also found to have elevated HMG-CoA Reductase (HMGCR) antibodies. Ultimately, a right quadriceps muscle biopsy was performed and electron microscopy identified nemaline bodies within skeletal myofibers. Given the clinical course and other histopathologic findings, he was diagnosed with Sporadic late-onset nemaline myopathy (SLONM). Conclusion: The diagnosis of neuromuscular disease in patients with ventilator dependent respiratory failure is challenging. A detailed history of a patient’s clinical course prior to hospitalization is key and may raise suspicion for underlying neuromuscular pathology. Further evaluation in non-critically ill patients may include pulmonary function, electromyography and confirmatory muscle biopsy. Sporadic late onset nemaline myopathy remains a rare disease entity which rarely presents with respiratory failure and lacks effective treatment.