Session 2

Increased Wedge Pressure Facilitates Decreased Lung Vascular Resistance during Upright Exercise

In heart failure with preserved ejection fraction (HFpEF), the prognostic value of pulmonary vascular dysfunction (PV-dysfunction), identified by elevated pulmonary vascular resistance (PVR) at peak exercise, is not completely understood. We evaluated the long-term prognostic implications of PV-dysfunction in HFpEF during exercise in consecutive patients undergoing invasive cardiopulmonary exercise testing for unexplained dyspnea.

Patients with HFpEF were classified into 2 main groups: resting HFpEF (n = 104, 62% female, age 61 years) with a pulmonary arterial wedge pressure (PAWP) >15 mmHg at rest; and exercise HFpEF (eHFpEF; n = 81) with a PAWP <15 mmHg at rest, but >20 mmHg during exercise. The eHFpEF group was further subdivided into eHFpEF + PV-dysfunction (peak PVR ≥80 dynes/s/cm⁻⁵; n = 55, 60% female, age 64) group and eHFpEF – PV-dysfunction (peak PVR <80 dynes/s/cm⁻⁵; n = 26, 42% female, age 54 years) group. Outcomes were analyzed for the first 9 years of follow-up and included any cause mortality and heart failure (HF)-related hospitalizations. The mean follow-up time was 6.7 ± 2.6 years (0.5–9.0).

Mortality rate did not differ among the groups. However, survival free of HF-related hospitalization was lower for the eHFpEF + PV-dysfunction group compared with eHFpEF – PV-dysfunction (P = .01). These findings were similar between eHFpEF + PV-dysfunction and the resting HFpEF group (P = .774). By Cox analysis, peak PVR ≥80 dynes/s/cm⁻⁵ was a predictor of HF-related hospitalization for eHFpEF (hazard ratio 5.73, 95% confidence interval 1.05–31.22, P = .01). In conclusion, the present study provides insight into the impact of PV-dysfunction on outcomes of patients with exercise-induced HFpEF. An elevated peak PVR is associated with a high risk of HF-related hospitalization.

Awareness has grown in recent years that right ventricular (RV) function is equally important as left ventricular (LV) function in the setting of left-sided heart disease. RV dysfunction can be the consequence of an increased afterload imposed by the failing LV. The concept of “afterload” is physically most correctly described by vascular input impedance. However, for clinical purposes, afterload is most often modeled to consist of 3 components; pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), and characteristic impedance. Whereas PVR is historically most described, PAC (which represents the distensibility of the vasculature) has rapidly gained recognition for its prognostic ability in both pulmonary arterial hypertension and left-sided heart disease. Owing to the specific anatomy of the pulmonary circulation, PVR and PAC have an inverse hyperbolic relationship, which position can be shifted by varying wedge pressures. Knowledge of the afterload components helps one to understand how elevated left-sided filling pressures increase pulsatile load on the RV. An increase in resistive load (known as “reactive” or “out-of-proportion” pulmonary hypertension) ultimately complements the increase in pulsatile load. Perturbations in nitric oxide metabolism are thought to be crucial in this evolution and have therefore been sought as a major therapeutic target.

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.

To determine whether intense, prolonged activity can induce transient pulmonary edema, eight highly trained male cyclists (mean ± S.D.: age, 26.9 ± 3.0 years; height, 179.9 ± 5.7 cm; weight, 76.1 ± 6.5 kg) performed a 45-min endurance cycle test (ECT). ${\dot{V}}_{{\text{O}}_2\text{,max}}$ was determined (4.84 ± 0.4 L min⁻¹, 63.7 ± 2.6  ml min⁻¹ g⁻¹) and the intensity of exercise for the ECT was set at 10% below ventilatory threshold (∼76% ${\dot{V}}_{{\text{O}}_2\text{,max}}$ 300 ± 25 W). Pre- and post-exercise pulmonary diffusion (DL_CO) measurements and magnetic resonance imaging of the lung were made. DL_CO and pulmonary capillary blood volume (VC) decreased 1 h post-exercise by 12% (P = 0.004) and 21% (P = 0.017), respectively, but no significant change in membrane diffusing capacity (DM) was found. The magnetic resonance scans demonstrated a 9.4% increase (P = 0.043) in pulmonary extravascular water 90 min post-exercise. These data support the theory that high intensity, sustained exercise in well-trained athletes can result in transient pulmonary edema.

Over the past 15 years evaluation of the patient with exertional complaints has changed from a simple qualitative estimate of overall fitness to a detailed assessment of cardiovascular and pulmonary pathophysiology. By quantifying exercise impairment and identifying the physiological limit to exercise, CPEx can help direct and evaluate the efficacy of medical and surgical interventions. Although no clear consensus has emerged, an objective determination of the etiology of exercise intolerance may also help identify the patient at increased risk for postthoracotomy complications.