Frantz, Robert P.

Background Patients with heart failure (HF) often develop pulmonary system abnormalities. Specifically, an abnormal ventilation relative to metabolic demand (V E /VCO 2 , ventilatory efficiency) during exercise has been shown to be an important marker of disease severity and prognosis. The purpose of this investigation was to focus on the factors that underlie the abnormal breathing efficiency in this population. Methods 14 controls (10 male) and 40 (36 male) mod‐severe HF patients, age 52±12 and 56±8 yrs, respectively, performed graded exercise on a cycle ergometer. Gas exchange and blood gas measurements were made during submaximal exercise (~65% peak VO 2 ) and used to quantify the influence of hyperventilation (PaCO 2 ) and dead space ventilation (V D ) on V E /VCO 2 . Results The V E /VCO 2 ratio was lower in controls (30±4) than in HF (45±9, p<0.001) due to a lower PaCO 2 and higher V D /V T that contributed an estimated 29% and 71%, respectively, to the increased V E /VCO 2 (p<0.05). The elevated V D /V T in HF was in turn the result of a tachypneic breathing pattern (lower V T , 877±306 vs 2003±504ml, p<0.01) in the presence of a relatively normal V D (9.6±3.8 vs 11.9±5.7 L/min, p=0.094). Conclusion The abnormal ventilation in relation to metabolic demand in HF during exercise is predominantly due to alterations in breathing pattern, rather than hyperventilation or changes in ventilation/perfusion relationships. HL71478

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health‐care utilization. We performed a cross‐sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6‐min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow‐up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow‐up, and have increased health‐care utilization.

Longitudinal trends demonstrate an increase in the prevalence of cardiovascular (CV) risk factors in the general population; however, the burden of CV risk factors or established disease in patients across WSPH groups remains unknown. Accordingly, we examined the prevalence of CV risk factors and established disease in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) cohort. PVDOMICS enrolled 1,097 subjects with pulmonary hypertension (PH) (mPA ≥ 25 mmHg) and at-risk disease comparators (mPa < 25 mmHg) from six US centers. Compared to participants with PH attributable to left heart disease (LHD-PH; WSPH Group 2, n=145) who are expected to have a high burden of CV risk factors and disease, patients with WSPH Groups 1,3,4,and 5 (non-LHD-PH)(n=618) were younger (56.2 ± 14.5 vs 67.7 ± 11.7 yrs, p<0.02) with no difference in %female or race. Non-LHD-PH had a lower prevalence of the CV disease risk factors hypertension (38.6% vs. 66.7%, p<0.02), diabetes mellitus (21.4 vs. 41.0%, p<0.02), and metabolic syndrome (30.8 vs. 48.4%, p<0.02) compared to LHD-PH, while smoking, hypercholesterolemia, and family history of CV disease were similar between groups. The prevalence of established CV disease, including myocardial infarction, CABG or stent, stroke, arrhythmia, or peripheral arterial disease was significantly lower in non-LHD-PH than in LHD-PH. At right heart catheterization, although mPA pressures were similar between the groups, PVR (5.5[3.3, 8.7] vs. 3.7[7.2, 5.7] WU, p<0.02), and cardiac output were higher (5.4 ± 1.9 vs. 4.9 ± 1.6 L/min, p<0.02) in non-LHD-PH compared to LHD-PH. This corresponded to a higher left ventricular ejection fraction by echo (62.2 ± 8.2 vs. 54.0 ± 14.0 %, p<0.02) and greater 6-minute walk distance (361.8 ± 134.7 vs. 294.7 ± 118.7 m, p<0.02). Non-LHD-PH also had better cardiovascular health compared to LHD-PH with higher modified American Heart Association Life’s Simple 7 scores (6.7 ± 1.6 vs. 5.8 ± 1.5, P<0.02). Taken together, these data demonstrate that CV disease risk factors and CV disease are frequent comorbidities that occur in patients with non-LHD-PH, although CV health is not as impaired as in patients with LHD-PH. How this affects PH-related outcomes remains to be determined.

Abstract The diagnosis and management of pulmonary arterial hypertension (PAH) includes several advances, such as a broader recognition of extrapulmonary vascular organ system involvement, validated point-of-care clinical assessment tools, and focus on the early initiation of multiple pharmacotherapeutics in appropriate patients. Indeed, a principal goal in PAH today is an early diagnosis for prompt initiation of treatment to achieve a minimal symptom burden; optimize the patient’s biochemical, hemodynamic, and functional profile; and limit adverse events. To accomplish this end, clinicians must be familiar with novel risk factors and the revised hemodynamic definition for PAH. Fresh insights into the role of developmental biology (i.e., perinatal health) may also be useful for predicting incident PAH in early adulthood. Emergent or underused approaches to PAH management include a novel TGF-β ligand trap pharmacotherapy, remote pulmonary arterial pressure monitoring, next-generation imaging using inert gas–based magnetic resonance and other technologies, right atrial pacing, and pulmonary arterial denervation. These and other PAH state of the art advances are summarized here for the wider pulmonary medicine community.