Platypnea-orthodeoxia syndrome: a diagnostic challenge.

Platypnea-orthodeoxia (P-O) syndrome is an underdiagnosed condition characterized by dyspnea and deoxygenation accompanying a change from a recumbent to an upright position. It is caused by increased right-to-left shunting of blood on assuming an upright position. The diagnosis of this shunt is often challenging. A case where a diagnosis was missed despite performing a tilt transesophageal echocardiogram with bubble study and a technetium labeled macroaggregated albumin scan is presented. However, a large patent foramen ovale (PFO) was found on autopsy. A brief overview of the diagnostic workup and management of this condition along with methods to increase the sensitivity of diagnostic tests is discussed.

Treatment of pulmonary hypertension with left heart disease: a concise review.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥ 25 mmHg, as determined by right heart catheterization. Pulmonary arterial hypertension (PAH) can no longer be considered an orphan disease given the increase in awareness and availability of new drugs. PH carries with it a dismal prognosis and leads to significant morbidity and mortality. Symptoms can range from dyspnea, fatigue and chest pain to right ventricular failure and death. PH is divided into five groups by the World Health Organization (WHO), based on etiology. The most common cause of PH in developed countries is left heart disease (group 2), owing to the epidemic of heart failure (HF). The data regarding prevalence, diagnosis and treatment of patients with group 2 PH is unclear as large, prospective, randomized controlled trials and standardized protocols do not exist. Current guidelines do not support the use of PAH-specific therapy in patients with group 2 PH. Prostacyclins, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and guanylate cyclase stimulators have been tried in treatment of patients with HF and/or group 2 PH with mixed results. This review summarizes and critically appraises the evidence for diagnosis and treatment of patients with group 2 PH/HF and suggests directions for future research.

The safety and effectiveness of riociguat to treat chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an insidious, progressive disease with a poor prognosis. The treatment of choice is pulmonary thromboendarterectomy, although not all patients benefit from surgery at a specialized center. Riociguat, an oral soluble guanylate cyclase (sGC) stimulator is the first pharmacotherapeutic agent that has been shown to improve exercise capacity and hemodynamics in a large multicenter, double-blind, randomized placebo-controlled trial for the treatment of patients with inoperable or persistent CTEPH. Riociguat stimulates sGC directly in a nitric oxide (NO)-independent manner, thereby increasing the sensitivity of sGC to NO, and also in synergy with NO, leading to increased production of cyclic guanosine monophosphate, an intracellular messenger involved in regulating vascular tone, smooth muscle cell proliferation, fibrosis and inflammation. This review will summarize the pharmacodynamics, pharmacokinetics as well as safety and efficacy data of riociguat in inoperable or persistent CTEPH.

A comparison of the pathological, clinical and radiographical, features of cryptogenic organising pneumonia, acute fibrinous and organising pneumonia and granulomatous organising pneumonia.

AIMS: Cryptogenic organising pneumonia (COP) and acute fibrinous and organising pneumonia (AFOP) are recognised patterns of organising pneumonia (OP), a condition that resembles pneumonia but is not caused by infection. We have recognised granulomatous organising pneumonia (GOP) to be a similar histopathological entity where non-necrotising granulomata are intimately associated with the organising connective tissue. To what degree COP, AFOP and GOP represent distinct clinical and pathological disorders is unknown. This cross-sectional study sought to compare the pathological, clinical, and radiographical features of these OP patterns. METHODS: Surgical lung biopsy specimens were reviewed for consecutive patients referred with OP to a metropolitan cancer centre. Clinical information and CT images were acquired from the hospital electronic medical record to determine the clinical and CT characteristics of each OP pattern. RESULTS: Sixty-one patients (35 men, 26 women), mean age 61.5 years (range 8-85 years), were available for analysis. Of these, 43 patients (70%) had at least one prior cancer; 27 (44%) had received chemotherapy and 18 (30%) had received radiation. Approximately, half (32 patients) had respiratory symptoms, most commonly cough, dyspnoea and/or wheezing. While symptoms and mortality rates were not different among OP groups, AFOP patients more commonly had fever (p=0.04). GOP patients less commonly had received chemotherapy (p=0.03) and were more likely to present as masses/nodules (p=0.04). CONCLUSIONS: AFOP and GOP, a newly described OP form, possess clinical and pathological findings that set it apart from a COP, suggesting an emerging spectrum of OP.

Comparison of acute hemodynamic effects of inhaled nitric oxide and inhaled epoprostenol in patients with pulmonary hypertension.

Inhaled nitric oxide (iNO) is used for acute vasoreactivity testing in pulmonary arterial hypertension (PAH) patients. Inhaled epoprostenol (iPGI2) has pulmonary selectivity and is less costly. We sought to compare acute hemodynamic effects of iNO (20 ppm) and iPGI2 (50 ng/kg/min) and determine whether their combination has additive effects. We conducted a prospective, single center, randomized, cross-over study in 12 patients with PAH and seven with heart failure with preserved ejection fraction (HFpEF). In PAH patients, iNO lowered mean pulmonary artery pressure (mPAP) by 9 ± 12% and pulmonary vascular resistance (PVR) by 14 ± 32% (mean ± SD). iPGI2 decreased mPAP by 10 ± 12% and PVR by 12 ± 36%. Responses to iNO and iPGI2 in mPAP and PVR were directly correlated (r(2) = 0.68, 0.70, respectively, P < 0.001). In HFpEF patients, mPAP dropped by 4 ± 7% with each agent, and PVR dropped by 33 ± 23% with iNO, and by 25 ± 29% with iPGI2 (P = NS). Pulmonary artery wedge pressure (PAWP) increased significantly with iPGI2 versus baseline (20 ± 3 vs. 17 ± 2 mmHg, P = 0.02) and trended toward an increase with iNO and the combination (20 ± 2, 19 ± 4 mmHg, respectively). There were no additive effects in either group. In PAH patients, the vasodilator effects of iNO and iPGI2 correlated at the doses used, making iPGI2 a possible alternative for testing acute vasoreactivity, but their combination lacks additive effect. Exposure of HFpEF patients to inhaled vasodilators worsens the PAWP without hemodynamic benefit.