Michael Dandel

Right ventricular pressure overloading [RVPO] with secondary maladaptive RV remodeling and progressive myocardial dysfunction in patients with pulmonary hypertension associated with left-sided heart diseases [PH-LHDs] and in those with pulmonary arterial hypertension [PAH] still remains one of the most complex challenges in cardio-pulmonary medicine. Despite the advances in the optimization of diagnostic tools and the expansion of treatment options, there is still a great need for further research to gain a better understanding of the major pathophysiological mechanisms involved in both the RV responses to PO and to find new possibilities to stop the progression of the alterations inside the pulmonary arterial circulation [PAC]. This article summarizes current knowledge about the particularities of the RV structural and functional responses to abnormal PO and also provides an overview of the benefits and limitations of the currently available tools for clinical evaluations of the RV adaptability to high afterload. A major focus of this review relates to the possibilities for obtaining evidence about the existence of a still remaining adaptability to a normal afterload in an over-burdened RV, in case of abolition of the pathological PO and, in this regard, to also evaluate the clinical usefulness of the RV adaptability estimation for certain critical therapeutic decisions. Among the most important conclusions of this updated overview are: 1. Whereas single parameters are insufficiently reliable for the evaluation of RV dysfunction and for predictions of its prognostic relevance across the whole spectrum of RVPO, properly selected and integrated multiparametric approaches had meanwhile unequivocally proved that they can usually become sufficiently reliable. 2. Multiparametric approaches can substantially improve the prediction of a preserved RV responsiveness to the abolition of its steady PO by reversal of RV maladaptive remodeling and by the normalization of RV pump function. Such a prediction, which can be decisive for therapeutic decision-making especially in candidates for ventricular assist device [LVAD] implantation or thoracic organ transplantation, can have a crucial impact on patient survival. 3. The complex and temporally highly variable interactions between certain structural and functional changes in both the PAC and in the hemodynamic overloaded right-sided heart, as well as between the two ventricles, can often hamper the interpretation of certain changes in the measured parameters and even relevantly alter their reliability. Additionally, the progressive aggravation of a secondary tricuspid regurgitation [TR] has a particularly high negative (often also misleading) impact on the diagnostic and prognostic relevance of RVPO evaluations.

Cardiac structural and functional damage induced and/or increasingly aggravated by aortic valve stenosis

There is increasing evidence that β1-adrenoreceptor autoantibody (β1AR-AAb) elimination can break the vicious circle induced by certain pathological conditions associated with alteration of the physiological self-tolerance, followed by generation of such AAbs and activation of cell-mediated immune processes directed against the myocardium. Concerning this, the present narrative review article provides an updated overview of the state of knowledge about the role of auto-immunity in the etiopathogenesis of cardiomyopathies, with a particular focus on immunoadsorption (IA) therapy for β1AR-AAb-positive adult patients with a dilated cardiomyopathy (DCM)-associated refractory heart failure (HF). Among many relevant findings, the increasing prevalence (up to 97%) of β1AR-AAb-positive patients related to the aggravation of HF, the high prevalence (between 84% and 91%) of HF patients in which IA can reduce to a minimum any increased β1AR-AAb level, as well as the high prevalence (about 80%) of responders to the IA-induced normalization of β1AR-AAb levels by long-term improvement in LV ejection fraction with increase in LV stroke volume and cardiac output, are of particular relevance. Given that after the elimination of β1AR-AAbs in potential candidates for heart transplantation (HTx), the post-IA 3- and 5-year HTx-/mechanical support-free survival probability reached 80% and 63-69%, respectively, the good tolerability of IA and the possibility to repeat that therapy also in elderly persons strongly suggest that in appropriately selected patients, this therapy deserves much more attention in the future.

Ventricular pump function, which is determined by myocyte contractility, preload and afterload, and, additionally, also significantly influenced by heart rhythm, synchrony of intraventricular contraction and ventricular interdependence, explains the difficulties in establishing the contribution of myocardial contractile dysfunction to the development and progression of heart failure. Estimating myocardial contractility is one of the most difficult challenges because the most commonly used clinical measurements of cardiac performance cannot differentiate contractility changes from alterations in ventricular loading conditions. Under both physiological and pathological conditions, there is also a permanent complex interaction between myocardial contractility, ventricular anatomy and hemodynamic loading conditions. All this explains why no single parameter can alone reveal the real picture of ventricular dysfunction. Over time there has been increasing recognition that a load-independent contractility parameter cannot truly exist, because loading itself changes the myofilament force-generating capacity. Because the use of a single parameter is inadequate, it is necessary to perform multiparametric evaluations and also apply integrative approaches using parameter combinations which include details about ventricular loading conditions. This is particularly important for evaluating the highly afterload-sensitive right ventricular function. In this regard, the existence of certain reluctance particularly to the implementation of non-invasively obtainable parameter combinations in the routine clinical praxis should be reconsidered in the future. Among the non-invasive approaches used to evaluate ventricular function in connection with its current loading conditions, assessment of the relationship between ventricular contraction (e.g., myocardial displacement or deformation) and pressure overload, or the relationship between ejection volume (or ejection velocity) and pressure overload, as well as the relationship between ventricular dilation and pressure overload, were found useful for therapeutic decision-making. In the future, it will be unavoidable to take the load dependency of ventricular function much more into consideration. A solid basis for achieving this goal will be obtainable by intensifying the clinical research necessary to provide more evidence for the practical importance of this largely unsolved problem.

Speckle-tracking echocardiography (STE) parameters are an integral part of the assessment of left ventricular (LV) function. We aimed to evaluate established and novel STE parameters of LV diastolic function and their prognostic role in patients with LV anteroapical aneurysm undergoing surgical ventricular repair (SVR). We retrospectively examined the data of 137 patients with anteroapical LV aneurysm who underwent SVR. In 27 patients, the correlation of STE parameters with invasive hemodynamic parameters was evaluated. Preoperative echocardiographic parameters were assessed for their association with outcome, defined as all-cause mortality, LV assist device implantation, or heart transplantation. The late diastolic strain rate (GLSRa) showed a stronger correlation with mean pulmonary artery pressure (r = − 0.75, p < 0.001) than all other parameters. GLSRa was also significantly correlated with mean pulmonary capillary wedge pressure and LV end-diastolic pressure. In the multivariate model, GLSRa and the ratio of early diastolic filling velocity to GLSRa demonstrated incremental prognostic value in addition to clinical and echocardiographic parameters. Patients with GLSRa < 0.59 s⁻¹ had significantly shorter event-free survival than those with GLSRa > 0.59 s⁻¹ (6.7 vs. 10.9 years, p < 0.001). Peak reservoir left atrial strain showed a weaker association with hemodynamic parameters and outcome compared to GLSRa. In patients with LV aneurysm, late diastolic strain rate and left atrial strain can be used for the assessment of LV diastolic function and have a predictive value for the outcome after surgical ventricular restoration. Graphical

Regardless of whether pulmonary hypertension (PH) results from increased pulmonary venous pressure in left-sided heart diseases or from vascular remodeling and/or obstructions in pre-capillary pulmonary vessels, overload-induced right ventricular (RV) dysfunction and its final transition into right-sided heart failure is a major cause of death in PH patients. Being particularly suited for non-invasive monitoring of the right-sided heart, echocardiography has become a useful tool for optimizing the therapeutic decision-making and evaluation of therapy results in PH. The review provides an updated overview on the pathophysiological insights of heart-lung interactions in PH of different etiology, as well as on the diagnostic and prognostic value of echocardiography for monitoring RV responses to pressure overload. The article focuses particularly on the usefulness of echocardiography for predicting life-threatening aggravation of RV dysfunction in transplant candidates with precapillary PH, as well as for preoperative prediction of post-operative RV failure in patients with primary end-stage left ventricular (LV) failure necessitating heart transplantation or a LV assist device implantation. In transplant candidates with refractory pulmonary arterial hypertension, a timely prediction of impending RV decompensation can contribute to reduce both the mortality risk on the transplant list and the early post-transplant complications caused by severe RV dysfunction, and also to avoid combined heart-lung transplantation. The review also focuses on the usefulness of echocardiography for monitoring the right-sided heart in patients with acute respiratory distress syndrome, particularly in those with refractory respiratory failure requiring extracorporeal membrane oxygenation support. Given the pathophysiologic particularity of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection to be associated with a high incidence of thrombotic microangiopathy-induced increase in the pulmonary resistance, echocardiography can improve the selection of temporary mechanical cardio-respiratory support strategies and can therefore contribute to the reduction of mortality rates. On the whole, the review aims to provide a theoretical and practical basis for those who are or intend in the future to be engaged in this highly demanding field.

Long-term mechanical circulatory support by a left ventricular assist device (LVAD), with or without an additional temporary or long-term right ventricular (RV) support, is a life-saving therapy for advanced heart failure (HF) refractory to pharmacological treatment, as well as for both device and surgical optimization therapies. In patients with chronic non-ischemic cardiomyopathy (NICM), timely prediction of HF’s transition into its end stage, necessitating life-saving heart transplantation or long-term VAD support (as a bridge-to-transplantation or destination therapy), remains particularly challenging, given the wide range of possible etiologies, pathophysiological features, and clinical presentations of NICM. Decision-making between the necessity of an LVAD or a biventricular assist device (BVAD) is crucial because both unnecessary use of a BVAD and irreversible right ventricular (RV) failure after LVAD implantation can seriously impair patient outcomes. The pre-operative or, at the latest, intraoperative prediction of RV function after LVAD implantation is reliably possible, but necessitates integrative evaluations of many different echocardiographic, hemodynamic, clinical, and laboratory parameters. VADs create favorable conditions for the reversal of structural and functional cardiac alterations not only in acute forms of HF, but also in chronic HF. Although full cardiac recovery is rather unusual in VAD recipients with pre-implant chronic HF, the search for myocardial reverse remodelling and functional improvement is worthwhile because, for sufficiently recovered patients, weaning from VADs has proved to be feasible and capable of providing survival benefits and better quality of life even if recovery remains incomplete. This review article aimed to provide an updated theoretical and practical background for those engaged in this highly demanding and still current topic due to the continuous technical progress in the optimization of long-term VADs, as well as due to the new challenges which have emerged in conjunction with the proof of a possible myocardial recovery during long-term ventricular support up to levels which allow successful device explantation.