Heart-lung interactions in COVID-19: prognostic impact and usefulness of bedside echocardiography for monitoring of the right ventricle involvement.

Due to the SARS-CoV-2 infection-related severe pulmonary tissue damages associated with a relative specific widespread thrombotic microangiopathy, the pathophysiologic role of heart-lung interactions becomes crucial for the development and progression of right ventricular (RV) dysfunction. The high resistance in the pulmonary circulation, as a result of small vessel thrombosis and hypoxemia, is the major cause of right heart failure associated with a particularly high mortality in severe COVID-19. Timely identification of patients at high risk for RV failure, optimization of mechanical ventilation to limit its adverse effects on RV preload and afterload, avoidance of medication-related increase in the pulmonary vascular resistance, and the use of extracorporeal membrane oxygenation in refractory respiratory failure with hemodynamic instability, before RV failure develops, can improve patient survival. Since it was confirmed that the right-sided heart is particularly involved in the clinical deterioration of patients with COVID-19 and pressure overload-induced RV dysfunction plays a key role for patient outcome, transthoracic echocardiography (TTE) received increasing attention. Limited TTE focused on the right heart appears highly useful in hospitalized COVID-19 patients and particularly beneficial for monitoring of critically ill patients. In addition to detection of right-sided heart dilation and RV dysfunction, it enables assessment of RV-pulmonary arterial coupling and evaluation of RV adaptability to pressure loading which facilitate useful prognostic statements to be made. The increased use of bedside TTE focused on the right heart could facilitate more personalized management and treatment of hospitalized patients and can contribute towards reducing the high mortality associated with SARS-CoV-2 infection.

Severe low-gradient aortic stenosis: impact of inadequate left ventricular responses to high afterload on diagnosis and therapeutic decision-making.

The fact that nearly 50% of patients with an aortic valve (AV) area < 1.0 cm2, consistent with severe aortic stenosis (AS), can have mean trans-AV pressure gradients < 40 mmHg, consistent with non-severe AS, indicates that "low-gradient" (LG) severe AS, which is often associated with poor prognosis, deserves particular consideration. Inadequate left ventricular (LV) adaptation to severe AV stenosis resulting from preexistent intrinsic myocardial damages and/or maladaptive LV responses to increased afterload are typical features of severe LG-AS. The diagnosis and management of patients with severe LG-AS are particularly challenging because the discrepancy between the AV area and the trans-AV pressure gradient raises doubts concerning the actual severity of AS and therefore also about the necessity of AV replacement (AVR). LG-AS diagnosis requires integrative multimodality evaluation of both the AV and the LV and therapeutic decision-making necessitates careful individual benefit-risk estimation. Although patients with severe LG-AS associated with low trans-AV flow (i.e., stroke volume ≤ 35 ml/m2) have worse outcomes after AVR than those with high-gradient severe AS, even those with reduced LV ejection fraction (LVEF) can have a significant survival benefit particularly by transcatheter AVR. Dobutamine stress echocardiography facilitates distinction between true-severe and pseudo-severe low-flow LG-AS with reduced LVEF. The review aimed to provide an updated theoretical and practical basis for those engaged in this demanding and still current topic due to the new aspects which have emerged in conjunction with both the evolving scientific knowledge about the various LV responses to the increased afterload and the increasing use of the less invasive transcatheter AVR.

Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure.

Allograft rejection-related acute and chronic heart failure (HF) is a major cause of death in heart transplant recipients. Given the deleterious impact of late recognized acute rejection (AR) or non-recognized asymptomatic antibody-mediated rejection on short- and long-term allograft function improvement of AR surveillance and optimization of action strategies for confirmed AR can prevent AR-related allograft failure and delay the development of cardiac allograft vasculopathy, which is the major cause for HF after the first posttransplant year. Routine non-invasive monitoring of cardiac function can improve both detection and functional severity grading of AR. It can also be helpful in guiding the anti-AR therapy and timing of routine surveillance endomyocardial biopsies (EMBs). The combined use of EMBs with non-invasive technologies and methods, which allow detection of subclinical alterations in myocardial function (e.g., tissue Doppler imaging and speckle-tracking echocardiography), reveal alloimmune activation (e.g., screening of complement-activating donor-specific antibodies and circulating donor-derived cell-free DNA) and help in predicting the imminent risk of immune-mediated injury (e.g., gene expression profiling, screening of non-HLA antibodies, and circulating donor-derived cell-free DNA), can ensure the best possible surveillance and management of AR. This article gives an overview of the current knowledge about the reliability and clinical value of non-invasive cardiac allograft AR surveillance. Particular attention is focused on the potential usefulness of non-invasive tools and techniques for detection and functional grading of early and late ARs in asymptomatic patients. Overall, the review aimed to provide a theoretical and practical basis for those engaged in this particularly demanding up-to-date topic.

Recovery of failing hearts by mechanical unloading: Pathophysiologic insights and clinical relevance.

By reduction of ventricular wall-tension and improving the blood supply to vital organs, ventricular assist devices (VADs) can eliminate the major pathophysiological stimuli for cardiac remodeling and even induce reverse remodeling occasionally accompanied by clinically relevant reversal of cardiac structural and functional alterations allowing VAD explantation, even if the underlying cause for the heart failure (HF) was dilated cardiomyopathy. Accordingly, a tempting potential indication for VADs in the future might be their elective implantation as a therapeutic strategy to promote cardiac recovery in earlier stages of HF, when the reversibility of morphological and functional alterations is higher. However, the low probability of clinically relevant cardiac improvement after VAD implantation and the lack of criteria which can predict recovery already before VAD implantation do not allow so far VAD implantations primarily designed as a bridge to cardiac recovery. The few investigations regarding myocardial reverse remodeling at cellular and sub-cellular level in recovered patients who underwent VAD explantation, the differences in HF etiology and pre-implant duration of HF in recovered patients and also the differences in medical therapy used by different institutions during VAD support make it currently impossible to understand sufficiently all the biological processes and mechanisms involved in cardiac improvement which allows even VAD explantation in some patients. This article aims to provide an overview of the existing knowledge about VAD-promoted cardiac improvement focusing on the importance of bench-to-bedside research which is mandatory for attaining the future goal to use long-term VADs also as therapy-devices for reversal of chronic HF.

Temporary assist device support for the right ventricle: pre-implant and post-implant challenges.

Severe right ventricular (RV) failure is more likely reversible than similar magnitudes of left ventricular (LV) failure and, because reversal of both adaptive remodeling and impaired contractility require most often only short periods of support, the use of temporary RV assist devices (t-RVADs) can be a life-saving therapy option for many patients. Although increased experience with t-RVADs and progresses made in the development of safer devices with lower risk for complications has improved both recovery rate of RV function and patient survival, the mortality of t-RVAD recipients can still be high but it depends mainly on the primary cause of RV failure (RVF), the severity of end-organ dysfunction, and the timing of RVAD implantation, and much less on adverse events and complications related to RVAD implantation, support, or removal. Reduced survival of RVAD recipients should therefore not discourage appropriate application of RVADs because their underuse further reduces the chances for RV recovery and patient survival. The article reviews and discusses the challenges related to the pre-implant and post-implant decision-making processes aiming to get best possible therapeutic results. Special attention is focused on pre-implant RV assessment and prediction of RV improvement during mechanical unloading, patient selection for t-RVAD therapy, assessment of unloading-promoted RV recovery, and prediction of its stability after RVAD removal. Particular consideration is also given to prediction of RVF after LVAD implantation which is usually hampered by the complex interactions between the different risk factors related indirectly or directly to the RV potential for reverse remodeling and functional recovery.

Deleterious effects of catecholamine administration in acute heart failure caused by unrecognized Takotsubo cardiomyopathy.

The potential life-threatening consequences of catecholamine use for emergency circulatory support in Takotsubo cardiomyopathy-related acute heart failure is a major challenge in cardiovascular emergences. In their recent work in BMC Cardiovascular Disorders Ansari U. et al. demonstrated the harmful effects of catecholamines on the outcome of patients with Takotsubo cardiomyopathy. Concerning this matter we emphasize the usefulness of speckle-tracking-derived echocardiography for early recognition of an acute phase of a Takotsubo syndrome in order to avoid the deleterious effects of a catecholamine therapy in patients with Takotsubo-associated acute heart failure.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

AIMS: Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS: Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION: Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION: This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

Load dependency of right ventricular performance is a major factor to be considered in decision making before ventricular assist device implantation.

BACKGROUND: Left ventricular assist devices (LVADs) provide better outcome than biventricular devices, but it is a challenge to predict the impact of LV mechanical unloading on postoperative right ventricular (RV) function preoperatively. We assessed the load dependency in RV performance before and after LVAD implantation aiming to improve preoperative decision making. METHODS AND RESULTS: Laboratory, echocardiography, and right heart catheterization data collected from 205 patients before LVAD implantation were tested for relationship with postoperative RV function. Comparing patients with different time-course of RV function after LVAD implantation, we found significant differences (P<0.01) in preoperative RV end-diastolic short-/long-axis and long-axis/length-area ratios, tricuspid annulus peak systolic velocity, RV peak longitudinal global systolic strain rate, systolic pressure gradient between RV and right atrium (ΔPRV-RA), tricuspid regurgitation velocity-time integral, and pulmonary arterial pressure between patients with and without postoperative RV failure. High predictive values for postoperative RV failure were found for end-diastolic short-/long-axis ratio ≥ 0.6, tricuspid annulus peak systolic velocity <8 cm/s, and peak systolic longitudinal strain rate <0.6/s in patients with maximum ΔPRV-RA <35 mm Hg. These parameters also seemed predictive for RV failure in patients with tricuspid regurgitation grade >2 and pulmonary arterial pressure <50 mm Hg. End-diastolic short-/long-axis ratio <0.6, tricuspid annulus peak systolic velocity ≥ 8 cm/s, and peak systolic longitudinal strain rate ≥ 0.6 in patients with maximum ΔPRV-RA ≥ 35 mm Hg showed high predictive values for postoperative freedom from RV failure. The RV load adaptation index seemed particularly predictive for RV function after LVAD implantation. CONCLUSIONS: RV geometry and velocity of contraction before LVAD implantation become more predictive for postoperative RV function and can improve decision making before VAD implantation if preoperative RV pressure load and tricuspid regurgitation are also considered.

Monitoring of the right ventricular responses to pressure overload: prognostic value and usefulness of echocardiography for clinical decision-making.

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.

Pre-explant stability of unloading-promoted cardiac improvement predicts outcome after weaning from ventricular assist devices.

BACKGROUND: Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation. METHODS AND RESULTS: Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively. CONCLUSIONS: Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.

Temporary right ventricular mechanical support in high-risk left ventricular assist device recipients versus permanent biventricular or total artificial heart support.

Early planned institution of temporary right ventricular assist device (RVAD) support with the CentriMag (Levitronix LLC, Waltham, MA, USA) in left ventricular assist device (LVAD) recipients was compared with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Between 2007 and 2011, 77 patients (age range: 25-70 years) with preoperative evidence of biventricular dysfunction (University of Pennsylvania score >50; University of Michigan score >5) were included. Forty-six patients (38 men; median age 54.5 years, range: 25-70 years) underwent LVAD placement combined with temporary RVAD support (group A); in 31 patients (25 men; median age 56.7 years, range: 28-68 years), a permanent BVAD or TAH implantation (group B) was performed. Within 30 days, 12 patients from group A (26.08%) and 14 patients from group B (45.1%) died on mechanical support (P = 0.02). Thirty patients (65.2%) in group A were weaned from temporary RVAD support and three (6.5%) underwent permanent RVAD (HeartWare, Inc., Framingham, MA, USA) placement. A total of 26 patients (56.5%) were discharged home in group A versus 17 (54.8%) in group B (P = 0.56). Three patients (8.5%) received heart transplantation in group A and six (19.3%) in group B (P = 0.04). In group A, 90-day and 6-month survival was 54.3% (n = 25) versus 51.6% (n = 16) in group B (P = 0.66). In group A, 1-year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B (P = 0.81). The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results if compared with those of a similar permanent BVAD/TAH population. Weaning from and removal of the temporary RVAD support may allow patients to be on LVAD support only despite preoperative biventricular dysfunction.

Cardiological Challenges Related to Long-Term Mechanical Circulatory Support for Advanced Heart Failure in Patients with Chronic Non-Ischemic Cardiomyopathy.

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.