Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial.

AIMS: The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. METHODS AND RESULTS: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control -0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. CONCLUSION: Low-dose exercise training at 4-7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.

Pulmonary hypertension due to left heart disease: updated Recommendations of the Cologne Consensus Conference 2011.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH including PH owing to left heart disease. The guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) have not been sufficiently investigated in other forms of PH. However, despite the lack of respective efficacy data an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary describes in detail the results and recommendations of the working group which were last updated in October 2011.

Decision for aggressive therapy in acute pulmonary embolism: implication of elevated troponin T.

BACKGROUND: Elevated cardiac troponin T (cTnT) has been described in the setting of acute pulmonary embolism (PE) earlier, though currently it has no implication on the therapy in this setting. The protocol established in our institution recommends the use of fibrinolytic therapy as first-line therapy in these patients only when cTnT is elevated. This analysis was performed to evaluate the safety of this regimen in regard to 30-day mortality, morbidity and complications. METHODS AND RESULTS: A total of 192 consecutive patients with confirmed PE, presenting at our institution during 2000-2005, were recruited. Right ventricular function was determined echocardiographically. CTnT was determined in all patients on admission. Patients without elevated cTnT were treated with anticoagulation alone, while patients with a TnT level above 0.1 ng/mL PE could be treated with thrombolysis on the discretion of the physician in charge. On day 30, cTnT elevation was associated with a higher mortality (P = 0.009). Moreover, in patients with intermediate-risk PE that were cTnT negative anticoagulation alone was safe showing a 30-day mortality of 1.8%, similar to low-risk PE (2.0%). In contrast to this patients with intermediate-risk PE with cTnT elevation showed a mortality rate of 20.8%, which was significantly higher (P < 0.001). CONCLUSIONS: In patients with intermediate-risk PE without elevated cTnT, anticoagulation alone seems to be a safe regimen. The midterm prognosis of these patients is as good as the prognosis of patients with low-risk PE. In this cohort of patients with PE, beginning with a more conservative treatment strategy per se did not lead to an unfavourable outcome.

Automated phase correction via maximization of the real signal.

Due to improved quantification capabilities and enhanced signal-to-noise ratio (SNR), phase-corrected real reconstruction in magnetic resonance imaging is superior to the common magnitude reconstruction, especially at low SNR. This requires the development of an automated phase-correction algorithm. Existing methods are not well suited for multiple unconnected regions of very low SNR. For this situation, a method based on the real-signal maximization is implemented, in which the experimental image phase is approximated by a three-dimensional polynomial of up to third order. The presented implementation was successfully applied to data originating from different samples and pulse sequences.

13C NMR relaxation rates in the ionic liquid 1-methyl-3-nonylimidazolium hexafluorophosphate.

A new method of obtaining molecular reorientational dynamics from 13C spin-lattice relaxation data of aromatic carbons in viscous solutions is applied to 13C relaxation data of the ionic liquid, 1-methyl-3-nonylimidazolium hexafluorophosphate ([MNIM]PF6). Spin-lattice relaxation times (13C) are used to determine pseudorotational correlation times for the [MNIM]PF6 ionic liquid. Pseudorotational correlation times are used to calculate corrected maximum NOE factors from a combined isotropic dipolar and nuclear Overhauser effect (NOE) equation. These corrected maximum NOE factors are then used to determine the dipolar relaxation rate part of the total relaxation rate for each aromatic 13C nucleus in the imidazolium ring. Rotational correlation times are compared with viscosity data and indicate several [MNIM]PF6 phase changes over the temperature range from 282 to 362 K. Modifications of the Stokes-Einstein-Debye (SED) model are used to determine molecular radii for the 1-methyl-3-nonylimidazolium cation. The Hu-Zwanzig correction yields a cationic radius that compares favorably with a DFT gas-phase calculation, B3LYP/(6-311+G(2d,p)). Chemical shift anisotropy values, delta sigma, are obtained for the ring and immediately adjacent methylene and methyl carbons in the imidazolium cation. The average delta sigma values for the imidazolium ring carbons are similar to those of pyrimidine in liquid crystal solutions.

Molecular reorientational dynamics of the neat ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate by measurement of 13C nuclear magnetic relaxation data.

The reorientational dynamics of the ionic liquid 1-butyl-3-methylimidzolium hexafluorophosphate ([BMIM]PF6) were studied over a wide range of temperatures by measurement of 13C spin-lattice relaxation rates and NOE factors. The reorientational dynamics were evaluated by performing fits to the experimental relaxation data. Thus, the overall reorientational motion was described by a Cole-Davidson spectral density with a Vogel-Fulcher-Tammann temperature dependence of the correlation times. The reorientational motion of the butyl chain was modelled by a combination of the latter model for the overall motion with a Bloembergen-Pur-cell-Pound spectral density and an Arrhenius temperature dependence for the internal motion. Except for C2 in the aromatic ring, an additional reduction of the spectral density by the Lipari-Szabo model had to be employed. This reduction is a consequence of fast molecular motions before the rotational diffusion process becomes effective. The C2 atom did not exhibit this reduction, because the librational motion of the corresponding C2-H vector is severely hindered due to hydrogen bonding with the hexafluorophosphate anion. The observed dynamic features of the [BMIM]+ cation confirm quantum-chemical structures obtained in a former study.