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• Higher pump speed is associated with higher cerebral blood flow. • Cerebral hemodynamic monitoring is feasible during pump-speed optimization. • Cerebral blood flow may provide a novel treatment target in LVAD care. [ABSTRACT FROM AUTHOR]

Background: Invasive hemodynamics are fundamental in assessing patients with advanced heart failure (HF). Several novel hemodynamic parameters have been studied; however, the relative prognostic potential remains ill‐defined. Hypothesis: Advanced hemodynamic parameters provide additional prognostication beyond the standard hemodynamic assessment. Methods: Patients from the PRognostic Evaluation During Invasive CaTheterization for Heart Failure (PREDICT‐HF) registry who underwent right heart catheterization (RHC) were included in the analysis. The primary endpoint was survival to orthotopic heart transplant (OHT) or durable left ventricular assist device (LVAD), or death within 6 months of RHC. Results: Of 846 patients included, 176 (21%) met the primary endpoint. In a multivariate model that included traditional hemodynamic variables, pulmonary capillary wedge pressure (PCWP) (OR: 1.10, 1.04−1.15, p <.001), and cardiac index (CI) (OR: 0.86, 0.81−0.92, p <.001) were shown to be predictive of adverse outcomes. In a separate multivariate model that incorporated advanced hemodynamic parameters, cardiac power output (CPO) (OR: 0.76, 0.71−0.83, p <.001), aortic pulsatility index (API) (OR: 0.94, 0.91−0.96, p <.001), and pulmonary artery pulsatility index (OR: 1.02, 1.00−1.03, p.027) were all significantly associated with the primary outcome. Positively concordant API and CPO afforded the best freedom from the endpoint (94.7%), whilst negatively concordant API and CPO had the worst freedom from the endpoint (61.5%, p <.001). Those with discordant API and CPO had similar freedom from the endpoint. Conclusion: The advanced hemodynamic parameters API and CPO are independently associated with death or the need for OHT or LVAD within 6 months. Further prospective studies are needed to validate these parameters and elucidate their role in patients with advanced HF. [ABSTRACT FROM AUTHOR]

The development of pulmonary hypertension (PH) in patients with heart failure is associated with increased morbidity and mortality. In this article, the authors examine recent changes to the definition of PH in the setting of left heart disease (PH-LHD), and discuss its epidemiology, pathophysiology and prognosis. They also explore the complexities of diagnosing PH-LHD and the current evidence for the use of medical therapies, promising clinical trials and the role of left ventricular assist device and transplantation.

Rajappan Revathi,1 Ramachandran Venkatesha Perumal,2 Karkala Sreedhara Ranganath Pai,3 Govindakarnavar Arunkumar,4 Dharmarajan Sriram,5 Suvarna Ganesh Kini1 1Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 2Bharathi College of Pharmacy, Bharathi Nagara, 3Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 4Manipal Centre of Virus Research, Manipal University, Manipal, Karnataka, India; 5Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Hyderabad, India Abstract: Tuberculosis remains one of the major grievous diseases worldwide. The emergence of resistance to antituberculosis drugs emphasize the necessity to discover new therapeutic agents for preferential tuberculosis therapy. In this study, various novel 1-(1H-benzimidazol-2-ylmethyl)piperidin-4-imine derivatives were developed and checked for favorable pharmacokinetic parameters based on drug-likeness explained by Lipinski’s rule of five. All 20 of the novel chemical entities were found to possess a favorable pharmacokinetic profile since they were not violating Lipinski’s rule of five. The title compounds were also synthesized, characterized, and tested for ex vivo antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC27294). The results revealed that four compounds (2-[1-(1H-benzimidazol-2-ylmethyl)piperidin-4-ylidene]hydrazinecarbothioamide, 2-[1-(1H-benzimidazol-2-ylmethyl)piperidin-4-ylidene]-N-hydroxyhydrazinecarbo-thioamide, 1-[1-(1H-benzimidazol-2-ylmethyl)piperidin-4-ylidene]guanidine, and 2-[1-(1H-benzimidazol-2-ylmethyl)piperidin-4-ylidene]hydrazinecarboxamide) were the most potent (minimum inhibitory concentration 6.25 µg/mL) antitubercular agents, with less toxicity (selectivity index more than 10). The molecules were also subjected to three-dimensional molecular docking on the crystal structure of enoyl-acyl carrier protein (EACP) reductase enzyme (code 1ZID, Protein Data Bank), which represents a good prediction of the interactions between the molecules and EACP reductase with minimum binding energy. Keywords: enoyl-acyl carrier protein reductase, Schiff’s reaction, benzimidazole, Mycobacterium tuberculosis