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Background Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular (RV) failure. The failing RV, through interventricular uncoupling, deleteriously impacts the left ventricle and overall cardiac efficiency. We hypothesised that the ratio of the pulmonary artery pulse pressure to the systemic pulse pressure (“pulmonary-systemic pulse pressure ratio”, or PS-PPR) would be associated with mortality in PAH. Methods We conducted a retrospective analysis of 262 patients in the National Institute of Health Primary Pulmonary Hypertension Registry (NIH-PPH). We evaluated the association between the PS-PPR and mortality after adjustment for the Pulmonary Hypertension Connection (PHC) risk equation. Results Among 262 patients (mean age 37.5 ± 15.8 years, 62.2% female), median PS-PPR was 1.04 (IQR 0.79–1.30). In the Cox proportional hazards regression model, each one unit increase in the PS-PPR was associated with more than a two-fold increase in mortality during follow-up (HR 2.06, 95% CI 1.40–3.02, p = 0.0002), and this association of PS-PPR with mortality remained significant in the multivariable Cox model adjusted for the PHC risk equation, mean pulmonary artery pressure, and body mass index (BMI) (adjusted HR 1.81, 95% CI 1.13–2.88, p = 0.01). Furthermore, PS-PPR in the upper quartile (>1.30) versus quartiles 1–3 was associated with a 68% increase in mortality after adjustment for these same covariates (adjusted HR 1.68, 95% CI 1.13–2.50, p = 0.01). Conclusions Pulmonary-systemic pulse pressure ratio, a marker of biventricular efficiency, is associated with survival in PAH even after adjustment for the PHC risk equation. Further studies are needed on the wider applications of PS-PPR in PAH patients.

Second-order Moller-Plesset theory (MP2) has been used to calculate the equilibrium geometries and relative energies of the chair, 1,4-twist, 2,5-twist, 1,4-boat, and 2,5-boat conformations of thiacyclohexane 1-oxide (tetrahydro-2H-thiopyran 1-oxide), 4-silathiacyclohexane 1-oxide, cis- and trans-4-fluoro-4-silathiacyclohexane 1-oxide, and 4,4-difluoro-4-silathiacyclohexane 1-oxide. At the MP2/6-311+G(d,p) level of theory, the chair conformer of axial thiacyclohexane 1-oxide is 0.99, 5.61, 5.91, 8.57, and 7.43 kcal/mol more stable (ΔE) than its respective equatorial chair, 1,4-twist, and 2,5-twist conformers and 1,4-boat and 2,5-boat transition states. The chair conformer of equatorial thiacyclohexane 1-oxide is 4.62, 6.31, 7.56, and 7.26 kcal/mol more stable (ΔE) than its respective 1,4-twist and 2,5-twist conformers and 1,4-boat and 2,5-boat transition states. The chair conformer of axial 4-silathiacyclohexane 1-oxide is 1.79, 4.26, 3.85, and 5.71 kcal/mol more stable (ΔE) than its respective equatorial chair, 1,4-twist, and 2,5-twist conformers and 2,5-boat transition state. The 2,5-twist conformer of axial 4-silathiacyclohexane 1-oxide is stabilized by a transannular interaction between the sulfinyl oxygen and silicon, to give trigonal bipyramidal geometry at silicon. The chair conformer of equatorial 4-silathiacyclohexane 1-oxide is 2.47, 7.90, and 8.09 kcal/mol more stable (ΔE) than its respective 1,4-twist, and 2,5-twist conformers and 2,5-boat transition state. The chair conformer of axial cis-4-fluoro-4-silathiacyclohexane 1-oxide is 4.18 and 5.70 kcal/mol more stable than its 1,4-twist conformer and 2,5-boat transition state and 1.51 kcal/mol more stable than the chair conformer of equatorial cis-4-fluoro-4-silathiacyclohexane 1-oxide. The chair conformer of axial trans-4-fluoro-4-silathiacyclohexane 1-oxide is 5.02 and 6.11 kcal/mol more stable than its respective 1,4-twist conformer and 2,5-boat transition state, but is less stable than its 2,5-twist conformer (ΔE = −1.77 kcal/mol) and 1,4-boat transition state (ΔE = −1.65 kcal/mol). The 2,5-twist conformer and 1,4-boat conformer of axial trans-4-fluoro-4-silathiacyclohexane 1-oxide are stabilized by intramolecular coordination of the sulfinyl oxygen with silicon that results in trigonal bipyramidal geometry at silicon. The chair conformer of axial 4,4-difluoro-4-silathiacyclohexane 1-oxide is 3.02, 5.16, 0.90, and 6.21 kcal/mol more stable (ΔE) than its respective equatorial chair, 1,4-twist, and 1,4-boat conformers and 2,5-boat transition state. The 1,4-boat conformer of axial 4,4-difluoro-4-silathiacyclohexane 1-oxide is stabilized by a transannular coordination of the sulfinyl oxygen with silicon that results in a trigonal bipyramidal geometry at silicon. The relative energies of the conformers and transition states are discussed in terms of hyperconjugation, orbital interactions, nonbonded interactions, and intramolecular sulfinyl oxygen–silicon coordination. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

The accurate identification of patients at increased risk for future cardiovascular events is challenging. Commonly utilized risk prediction tools, such as the Framingham risk score, rely on a small number of well-­validated standard cardiovascular risk factors. Although this easily applied and widely-available approach has been shown to have reasonably good risk predictive value, it may fail to recognize a significant proportion of patients at increased risk for future cardiovascular events. In addition, the risk prediction provided is of a relatively limited time horizon (10 years). Numerous novel biomarkers, such as highly sensitive C-reactive protein (hsCRP), oxidized low-density lipoprotein (ox-LDL), LDL particle sizes, myeloperoxidase and matrix metalloproteinase, have been evaluated in an effort to improve cardiovascular risk prediction and ultimately guide the application of preventative therapies. Among these, highly-sensitive hsCRP has been the most extensively studied and has been shown to modestly improve risk prediction beyond the use of standard cardiovascular risk factors among low-intermediate risk screening patients. However, limitations to the use of hsCRP include its modest incremental improvement on the FRS, known genetic polymorphisms which increase hsCRP levels unrelated to cardiovascular events, and its inferior risk prediction as compared to coronary artery calcium scanning. Current American College of Cardiology/American Heart Association guidelines on screening and prevention endorse the use of hsCRP in adults without diabetes, chronic kidney disease and known cardiovascular disease, with LDL < 130 and not already on a statin (IIa recommendation). The oxidation of LDL results in foam cell production and subsequent atherosclerosis progression. However, the measurement of the LDL oxidation process using serum markers is currently not widely available and well-validated. Similarly, despite evidence demonstrating that LDL particle sizes, myeloperoxidase, and matrix metalloproteinases are associated with atherosclerosis progression, plaque instability, and future cardiovascular events, their independent, incremental value beyond standard cardiovascular risk factors has not been validated and requires further study.

To test whether cardioprotection induced by ischemic preconditioning depends on the opening of mitochondrial ATP-sensitive K+(KATP) channels, the effect of channel blockade was studied in barbital-anesthetized open-chest pigs subjected to 30 min of complete occlusion of the left anterior descending coronary artery and 3 h of reflow. Preconditioning was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. 5-Hydroxydecanoate (5 mg/kg iv) was injected 15 min before preconditioning or pharmacological preconditioning induced by diazoxide (3.5 mg/kg, 1 ml/min iv). Infarct size (percentage of the area at risk) after 30 min of ischemia was 35.1 ± 9.9% ( n = 7). Preconditioning markedly limited myocardial infarct size (2.7 ± 1.6%, n = 7), and 5-hydroxydecanoate did not abolish protection (2.4 ± 0.9%, n = 8). Diazoxide infusion also significantly limited infarct size (14.6 ± 7.4%, n = 7), and 5-hydroxydecanoate blocked this effect (30.8 ± 8.0%, n = 7). Thus the opening of mitochondrial KATP channels is cardioprotective in pigs, but these data do not support the hypothesis that opening of mitochondrial KATP channels is required for the endogenous protection afforded by preconditioning.

Fulminant (peri)myocarditis is a very infrequent EIM of IBD and oft en presents with sudden-onset severe congestive heart failure (4,5) . Clinical presentation is variable, but in the 2 – 4 weeks before presentation, patients oft en have fl u-like (e.g., fevers, arthalgias and malaise) and gastrointestinal symptoms. Laboratory fi ndings may include leukocytosis, eosinophilia, and elevated levels of ESR, cardiac troponin, and C-reactive protein. Myocarditis in these patients appears not to correlate with disease activity (2,3) . Early recognition of myo(peri)carditis is crucial and needs prompt treatment. Treatment of fulminant disease includes aggressive inotropic support possibly accompanied by the placement of an intra-aortic balloon pump and / or a ventricular assist device. In conclusion, this case report demonstrates the occurrence of lymphocytic myocarditis in a patient with previously undiagnosed Crohn ’ s disease. It cannot be fully excluded that the myocarditis found in this patient was unrelated to his Crohn ’ s disease. However, the reported occurrence of perimyocarditis in Crohn ’ s disease in the absence of another explanation for the myocarditis strongly suggests that the two are related. Awareness of the possibility of this rare and potentially life-threatening EIM of IBD is therefore important.