the impact of delayed treatment on 6 minute walk distance test in patients with pulmonary arterial hypertension a meta analysis

Abstract Background The impact of treatment delay in stable patients with pulmonary arterial hypertension (PAH) remains unaddressed. Methods This meta-analysis included six datasets of PAH therapies with randomized-controlled trials (RCT) and corresponding open-label extension (OLE) studies. We evaluated the change in 6MWD at 1year in the OLE studies by active treatment versus ex-placebo group. The ex-placebo group (i.e., the patients randomized to placebo in the RCT and ultimately treated with active therapy in the OLE) represented the "delay-in-treatment" population. Results Patients with a treatment delay of 12–16weeks in PAH targeted therapy had an improvement in 6-minute walk distance (6MWD) test at 1year, but this improvement did not amount to the same degree of improvement as their initially treated counterparts. The difference in 6MWD was 15m to 20m at 1year. Conclusion A short-term delay in PAH targeted therapy may adversely affect functional capacity in patients with PAH. This meta-analysis provides some insight as to whether earlier treatment would benefit stable patients with PAH

Role of endogenous opioids on nociceptive threshold in patients with exercise-induced myocardial ischemia.

To evaluate whether endogenous opioids (EO) play a role in the perception of anginal pain, a randomized double blind clinical trial, using naloxone (N) and placebo (P) and measuring beta-endorphin (beta-ep) plasma levels, was performed. We studied 10 patients with angiographically assessed coronary artery disease (CAD) and stable exercise-induced myocardial ischemia (established by 2 preliminary bicycle ergometric tests) of whom 5 symptomatic (SYM) and 5 asymptomatic (ASYM) and 5 subjects without CAD as a control group (CON). On a third exercise test the beta-ep plasma level (fmol/ml) was measured at rest (SYM 5.4 +/- 2.3 vs ASYM 7.2 +/- 2.3 vs CON 6.8 +/- 2.6, NS), at peak exercise (SYM 4.4 +/- 1.8 vs ASYM 8.0 +/- 4.2 and vs CON 6.2 +/- 2.7, NS) and during recovery (SYM 7.5 +/- 4.2 vs ASYM 7.2 +/- 3.0 vs CON 6.7 +/- 2.5, NS). On 2 subsequent tests patients received N (0.2 mg/kg) or P intravenously and chest pain was evaluated on an analogue scale (score from 1 to 10). After N compared to P we observed: an increased perception of chest pain in SYM (6.8 +/- 1.5 vs 4.2 +/- 1.0; p less than 0.01) without significant changes of the ischemic threshold (total work, heart rate-blood pressure product, ST segment changes, 2D-echocardiographic wall motion abnormalities); no modifications in ASYM and CON.(ABSTRACT TRUNCATED AT 250 WORDS

Transesophageal dipyridamole echocardiography for diagnosis of coronary artery disease.

The value of transthoracic dipyridamole echocardiography has been extensively documented. However, in some patients, because of a poor acoustic window, the rest transthoracic examination is not always feasible and the transesophageal approach is more convenient. Therefore, transesophageal echocardiography with high dose dipyridamole (up to 0.84 mg/kg body weight over 10 min) was performed in 32 patients in whom the transthoracic dipyridamole test either was not feasible (n = 29) or yielded ambiguous results (n = 3). The transesophageal echocardiographic test results were considered abnormal when new dipyridamole-induced regional wall motion abnormalities were observed. All 32 patients underwent coronary angiography; significant coronary artery disease was defined as greater than or equal to 70% lumen diameter narrowing in at least one major vessel. All patients also performed a bicycle exercise test 1 day before transesophageal dipyridamole echocardiography. Transesophageal stress studies were completed in all patients, with a maximal imaging time (in tests with a negative result) of 20 min. No side effects or intolerance to drug or transducer was observed. The left ventricle was always visualized in the four-chamber and transgastric short-axis views. High quality two-dimensional echocardiographic images were obtained in all patients both at rest and at peak dipyridamole infusion and were digitally analyzed in a quad-screen format. Coronary angiography showed coronary artery obstruction in 24 patients: 6 had single-, 9 double- and 9 triple-vessel disease. The transesophageal dipyridamole test showed a specificity of 100% and an overall sensitivity of 92%. The sensitivity of this test for single-, double- and triple-vessel disease was 67%, 100% and 100%, respectivel

Treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass: a randomized, prospective, double-blind study.

OBJECTIVE: Pulmonary hypertension can already be present in patients undergoing cardiac surgery or can be exacerbated by cardiopulmonary bypass. Postoperative treatment is still a challenge for physicians. The aim of this study was to evaluate the effects of inhaled prostacyclin (iPGI2) and nitric oxide (iNO) compared with those of intravenous vasodilators. METHODS: This prospective, randomized, double-blind study included 58 patients affected by severe mitral valve stenosis and pulmonary hypertension with high pulmonary vascular resistance (> 250 dynes x s x cm(-5)) and a mean pulmonary artery pressure > 25 mmHg. All patients were monitored by central venous, radial arterial and Swan-Ganz catheters. Data were recorded at six different time points, before induction of anaesthesia, during and after surgery. Prostacyclin and nitric oxide were administered by inhalation 5 min before weaning from cardiopulmonary bypass and continued in the intensive care unit. Right ventricular function was evaluated by transoesophageal echocardiography. RESULTS: Hospital mortality was 3.4%. After drug administration, the mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased in the iNO and iPGI2 groups with respect to the baseline values (P < 0.05) and such a decrease was maintained throughout the study; this was not observed in the control group. In the iNO and iPGI2 groups we demonstrated a significant increase in cardiac indices and right ventricular ejection fraction after drug administration with respect to baseline. Furthermore, patients in the inhaled drug groups were weaned easily from cardiopulmonary bypass (P = 0.04) and had a shorter intubation time (P = 0.03) and intensive care unit stay (P = 0.02) than the control group. CONCLUSIONS: Our data suggest that both iNO and iPGI2 are effective in the treatment of pulmonary hypertension. iPGI2 has a number of advantages over iNO, including its easy administration and lower cost. Intravenous vasodilator treatment, on the other hand, is effective in terms of mortality but has a higher morbidity rate

Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension

Background: Right ventricular (RV) diastolic dysfunction may be prognostic in pulmonary hypertension (PH). However, its assessment is complex and relies on conductance catheterisation. We aimed to evaluate echocardiography-based parameters as surrogates of RV diastolic function, provide validation against the gold standard, end-diastolic elastance (Eed), and define the prognostic impact of echocardiography-derived RV diastolic dysfunction. Methods: Patients with suspected PH who underwent right heart catheterisation including conductance catheterisation were prospectively recruited. In this study population, an echocardiography-based RV diastolic function surrogate was derived. Survival analyses were performed in patients with precapillary PH in the Giessen PH Registry, with external validation in patients with pulmonary arterial hypertension at Sapienza University (Rome). Results: In the derivation cohort (n=61), the early/late diastolic tricuspid inflow velocity ratio (E/A) and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (E/e') did not correlate with Eed (p&gt;0.05). Receiver operating characteristic analysis revealed a large area under the curve (AUC) for the peak lateral tricuspid annulus systolic velocity/right atrial area index ratio (S'/RAAi) to detect elevated Eed (AUC 0.913, 95% confidence interval (CI) 0.839-0.986) and elevated end-diastolic pressure (AUC 0.848, 95% CI 0.699-0.998) with an optimal threshold of 0.81 m2·s-1·cm-1. Subgroup analyses demonstrated a large AUC in patients with preserved RV systolic function (AUC 0.963, 95% CI 0.882-1.000). Survival analyses confirmed the prognostic relevance of S'/RAAi in the Giessen PH Registry (n=225) and the external validation cohort (n=106). Conclusions: Our study demonstrates the usefulness of echocardiography-derived S'/RAAi for noninvasive assessment of RV diastolic function and prognosis in PH

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Anatomico-functional changes in the right ventricle of the athlete

The aim of this study was to compare the morpho-functional modifications of the right cardiac sections of the athlete's heart, with those of sedentary healthy control subjects. We studied 24 endurance athletes (mean age 28.17 +/- 7.28 years), 21 power athletes (mean age 25.86 +/- 4.96 years), and 20 sedentary healthy control subjects (mean age 33.22 +/- 6.67 years). We examined the right cavities by standard echocardiographic projections and the following parameters were evaluated: right ventricular longitudinal diameter; under tricuspid valve and medium ventricular transversal diameter immediately under the tricuspid plane and at medium ventricular level; right atrial transversal and longitudinal diameters. All parameters were corrected for body surface area. Our data showed that the right ventricle presents morphological adaptations to endurance exercise; modification is represented mainly by an increase in the mean transversal ventricular diameter with a consequent reduction in the transversal/longitudinal diameter ratio accompanied by modification of the ventricular geometry. In addition the data showed an increase in longitudinal and transversal diameters of the right atrium. On the contrary, the power athletes did not show statistical modification of the right ventricle and atrium. The different modifications of the right heart side diameter are probably due to the different hemodynamic loading, which is involved in the endurance and power training respectively