BACKGROUND: Right ventriculo-arterial coupling (RV-PA) can be estimated by echocardiography using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) and it has prognostic value in the general heart failure (HF) population. We aimed to study the clinical correlates and prognostic value of RV-PA in HF patients undergoing cardiac resynchronization therapy (CRT). METHODS: We retrospectively studied 70 HF patients undergoing CRT implantation. RESULTS: RV-PA coupling was estimated by TAPSE/PASP ratio using baseline echocardiography. Non-response to CRT was defined as improvement of left ventricular ejection fraction < 5% in a follow-up echo 6-12 months after CRT. Those with lower TAPSE/ PASP ratios (worse RV-PA coupling) had higher NT-proBNP concentrations and increased E/e′ ratio. TAPSE/PASP ratio and PASP, but not TAPSE, predicted nonresponse to CRT with TAPSE/ PASP ratio showing the best discriminative ability with a sensitivity of 76% and specificity of 71%. Among these parameters, PASP independently predicted all-cause mortality. CONCLUSIONS: RV-PA coupling estimated by TAPSE/PASP ratio was associated with established prognostic markers in HF. It numerically outperformed PASP and TAPSE in predicting the response to CRT. Our data suggest that this simple and widely available echocardiographic parameter conveys significant pathophysiological and prognostic meaning in HF patients undergoing CRT.
Adenosine triphosphate (ATP) is a primordial versatile autacoid that changes its role from an intracellular energy saver to a signaling molecule once released to the extracellular milieu. Extracellular ATP and its adenosine metabolite are the main activators of the P2 and P1 purinoceptor families, respectively. Mounting evidence suggests that the ionotropic P2X4 receptor (P2X4R) plays pivotal roles in the regulation of the cardiovascular system, yet further therapeutic advances have been hampered by the lack of selective P2X4R agonists. In this review, we provide the state of the art of the P2X4R activity in the cardiovascular system. We also discuss the role of P2X4R activation in kidney and lungs vis a vis their interplay to control cardiovascular functions and dysfunctions, including putative adverse effects emerging from P2X4R activation. Gathering this information may prompt further development of selective P2X4R agonists and its translation to the clinical practice.
Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such difference suggests that other ion currents may contribute to adenosine chronoselectivity. In isolated spontaneously beating rat atria, blockade of KCa2/SK channels with apamin and Cav1 (L-type) channels with nifedipine or verapamil, sensitized atria to the negative inotropic action of the A1 agonist, R-PIA, without affecting the nucleoside negative chronotropy. Patch-clamp experiments in the whole-cell configuration mode demonstrate that adenosine, via A1 receptors, activates the inwardly-rectifying GIRK/KIR3.1/KIR3.4 current resulting in hyperpolarization of atrial cardiomyocytes, which may slow down heart rate. Conversely, the nucleoside inactivates a small conductance Ca2+-activated KCa2/SK outward current, which eventually reduces the repolarizing force and thereby prolong action potentials duration and Ca2+ influx into cardiomyocytes. Immunolocalization studies showed that differences in A1 receptors distribution between the sinoatrial node and surrounding cardiomyocytes do not afford a rationale for adenosine chronoselectivity. Immunolabelling of KIR3.1, KCa2.2, KCa2.3, and Cav1 was also observed throughout the right atrium. Functional data indicate that while both A1 and M2 receptors favor the opening of GIRK/KIR3.1/3.4 channels modulating atrial chronotropy, A1 receptors may additionally restrain KCa2/SK activation thereby compensating atrial inotropic depression by increasing the time available for Ca2+ influx through Cav1 (L-type) channels.
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