Right ventricular dysfunction in left ventricular assist device candidates: is it time to change our prospective?

The use of left ventricular assist devices (LVAD) has significantly increased in the last years, trying to offer a therapeutic alternative to heart transplantation, in light also to the significant heart donor shortage compared to the growing advanced heart failure population. Despite technological improvements in the devices, LVAD-related mortality is still fairly high, with right heart failure being one of the predominant predictors. Therefore, many efforts have been made toward a thorough right ventricular (RV) evaluation prior to LVAD implant, considering clinical, laboratory, echocardiographic, and invasive hemodynamic parameters. However, there is high heterogeneity regarding both which predictor is the strongest as well as the relative cut-off values, and a consensus has not been reached yet, increasing the risk of facing patients in which the distinction between good or poor RV function cannot be surely reached. In parallel, due to technological development and availability of mechanical circulatory support of the RV, LVADs are being considered even in patients with suboptimal RV function. The aim of our review is to analyze the current evidence regarding the role of RV function prior to LVAD and its evaluation, pointing out the extreme variability in parameters that are currently assessed and future prospective regarding new diagnostic tools. Finally, we attempt to gather the available information on the therapeutic strategies to use in the peri-operative phase, in order to reduce the incidence of RV failure, especially in patients in which the preoperative evaluation highlighted some conflicting results with regard to ventricular function.

Left ventricular assist device in cardiac amyloidosis: friend or foe?

The prevalence of cardiac amyloidosis has progressively increased over the last years, being recognized as a significant cause of heart failure. In fact, the management of advanced heart failure is a cornerstone treatment of amyloid cardiomyopathy due to the frequent delay in its diagnosis. Left ventricular assist devices (LVADs) have been gaining importance in the scenario of end-stage heart failure, representing an alternative to heart transplant. However, only few studies have investigated the role of LVAD in restrictive cardiomyopathies such as cardiac amyloidosis, since there are several problems to consider. In fact, both anatomical factors and the restrictive physiology of this condition make LVAD implant a relevant challenge in this subset of patients. Furthermore, due to the systemic involvement of amyloidosis, several factors have to be considered after LVAD implant, such as an increased risk of bleeding and right ventricular failure. This review attempts to summarize the current evidence of LVAD in cardiac amyloidosis, especially focusing on the challenges that this cardiomyopathy imposes both to the implant and to its management thereafter.

Echocardiography for left ventricular assist device implantation and evaluation: an indispensable tool.

Echocardiography is an indispensable tool in the evaluation, placement, management and follow-up of patients with left ventricular assist devices (LVAD). While transoesophageal echocardiography is the ideal tool in guiding the implantation procedure, transthoracic echocardiography is essential during the initial evaluation, patient selection and in the post-operative follow-up. This review attempts to summarize which parameters the echocardiographic assessment should focused on during each step. In particular, during the pre-operative assessment, it is of paramount importance to assess the presence of aortic regurgitation and most importantly to evaluate right ventricular function, since it is one of the strongest predictor of post-implant right ventricular failure. During the procedure, through transoesophageal echocardiography, it is possible to confirm the correct placement of the inflow cannula, to assess right ventricular function and to guide the choice of the right pump speed. Transthoracic echocardiographic is an essential part in the patient's follow-up once the LVAD has been implanted, in order to attest the onset of possible complications.

Cor pulmonale: the role of traditional and advanced echocardiography in the acute and chronic settings.

Cor pulmonale is the condition in which the right ventricle undergoes morphological and/or functional changes due to diseases that affect the lungs, the pulmonary circulation, or the breathing process. Depending on the speed of onset of the pathological condition and subsequent effects on the right ventricle, it is possible to distinguish the acute cor pulmonale from the chronic type of disease. Echocardiography plays a central role in the diagnostic and therapeutic work-up of these patients, because of its non-invasive nature and wide accessibility, providing its greatest usefulness in the acute setting. It also represents a valuable tool for tracking right ventricular function in patients with cor pulmonale, assessing its stability, deterioration, or improvement during follow-up. In fact, not only it provides parameters with prognostic value, but also it can be used to assess the efficacy of treatment. This review attempts to provide the current standards of an echocardiographic evaluation in both acute and chronic cor pulmonale, focusing also on the findings present in the most common pathologies causing this condition.

COVID-19 and the burning issue of drug interaction: never forget the ECG.

The coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), has been rapidly escalating, becoming a relevant threat to global health. Being a recent virus outbreak, there are still no available therapeutic regimens that have been approved in large randomised trials and so patients are currently being treated with multiple drugs. This raises concerns regarding drug interaction and their implication in arrhythmic burden. In fact, two of the actually used drugs against SARS-CoV2, such as chloroquine and the combination lopinavir/ritonavir, might determine a QT (the time from the start of the Q wave to the end of the T wave) interval prolongation and they show several interactions with antiarrhythmic drugs and antipsychotic medications, making them prone to an increased risk of developing arrhythmias. This brief review focuses the attention on the most relevant drug interactions involving the currently used COVID-19 medications and their possible association with cardiac rhythm disorders, taking into account also pre-existing condition and precipitating factors that might additionally increase this risk. Furthermore, based on the available evidence and based on the knowledge of drug interaction, we propose a quick and simple algorithm that might help both cardiologists and non-cardiologists in the management of the arrhythmic risk before and during the treatment with the specific drugs used against SARS-CoV2.

COVID-19 in patients with heart failure: the new and the old epidemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread in nearly 200 countries in less than 4 months since its first identification; accordingly, the coronavirus disease 2019 (COVID 2019) has affirmed itself as a clinical challenge. The prevalence of pre-existing cardiovascular diseases in patients with COVID19 is high and this dreadful combination dictates poor prognosis along with the higher risk of intensive care mortality. In the setting of chronic heart failure, SARS-CoV-2 can be responsible for myocardial injury and acute decompensation through various mechanisms. Given the clinical and epidemiological complexity of COVID-19, patiens with heart failure may require particular care since the viral infection has been identified, considering an adequate re-evaluation of medical therapy and a careful monitoring during ventilation.

The acute impact of an ultramarathon on right heart: A 12-lead ECG study.

BACKGROUND: Some concerns exist about possible detrimental effects on cardiac function of ultra-endurance competitions. The aim of this study was to evaluate the acute effects of an ultramarathon by comparing pre- and post-race 12-lead ECG features. METHODS: A total of 301 competitive athletes (mean age: 48 ± 9 years) running a 50-km ultramarathon were analyzed. Twelve-lead ECG was collected the day before the race and immediately at the finish line. According to the Italian law, athletes could have participated only after undergoing pre-participation screening that ruled out the presence of an underlying heart disease. RESULTS: After the race a significant increase in P-wave voltage (P < .001) and P-wave duration (P < .001) was found as compared to pre-race data with a higher percentage of athletes fulfilling the ECG criteria for right atrial enlargement (RAE; from 3% to 17%, P < .001). The presence of RAE post-race significantly correlated with age, hours of training/week, and years of training and inversely with time at the finish line and the final position in the ranking. T-wave and R-wave amplitude (P < .001) and QTc-interval duration (P < .001) significantly increased after the race. No significant differences in terms of supraventricular or ventricular arrhythmias were found. CONCLUSIONS: A sizeable proportion of athletes running a 50-km ultramarathon demonstrated post-race ECG signs of right heart overload but no arrhythmias. This finding supports the hypothesis that ultra-endurance races may induce transient right heart overload.

More than 10 years of speckle tracking echocardiography: Still a novel technique or a definite tool for clinical practice?

Speckle tracking echocardiography (STE) cannot be considered a recent technique anymore. Its application has gained growing importance over the last decade in several clinical settings, and the deformation analysis has fully entered in diagnostic algorithms and guidelines of various pathologies. STE allows to track the displacement of "speckles" in two-dimensional (2D) echocardiographic images in an angle-independent way and to assess their movement (strain) during the cardiac cycle. Its high feasibility, reproducibility, and accuracy have been widely demonstrated. In this review, we describe how STE has been applied to different aspects of the daily clinical practice, including ischemic heart diseases, heart valve disease, heart failure, and prognostication, highlighting the possible added value that strain parameters have shown over the years.

The role of the left atrial function in the surgical management of aortic and mitral valve disease.

The right management of both mitral and aortic disease can be challenging, especially in asymptomatic patients. The current guidelines recommend valve repair or replacement when symptoms arise or when there is an evident left ventricular dysfunction. However, deciding the optimal surgical timing can be very difficult, since the line between the absence of symptoms and being minimally symptomatic, especially in the elderly, is blurred. Another relevant issue regards the second surgical criterion: operating on a patient with a reduced left ventricular ejection fraction or with a dilated left ventricle might jeopardize the possibility of a fully reverse remodeling of the heart after surgery. In this scenario, the left atrium might play an important role. In particular, left atrial deformation might be a very useful tool to detect early ultrastructural alterations, and help or support guiding a patient-tailored treatment at an early stage, optimizing the outcome in the long term.

Effects of levosimendan in heart failure: The role of echocardiography.

Heart failure (HF) represents a deadly epidemic that nowadays affects more than 2% of the general population, representing a major public health concern that implies a high economic burden for the health system. Levosimendan in HF patients is usually used for its inotropic and vasodilator effects that act without myocardial oxygen consumption, differently from other inotropic drugs. The symptoms and hemodynamic profile improve together with the myocardial function, and this can be demonstrated by an echocardiographic examination. Currently, the available data about the effects of levosimendan assessed by echocardiography are still lacking. This review discusses the role of echocardiography in the evaluation of therapeutic effects of levosimendan in HF.

Multimodality Imaging for Selecting Candidates for CRT: Do We Have a Single Alley to Increase Responders?

Cardiac resynchronization therapy has evolved in recent years to provide a reduction of morbidity and mortality for many patients with heart failure. Its application and optimization is an evolving field and its use requires a multidisciplinary approach for patient and device selection, technical preprocedural planning, and optimization. While echocardiography has always been considered the first line for the evaluation of patients, additional imaging techniques have gained increasing evidence in recent years. Today different details about heart anatomy, function, dissynchrony can be investigated by magnetic resonance, cardiac computed tomography, nuclear imaging, and more, with the aim of obtaining clues to reach a maximal response from the electrical therapy. The purpose of this review is to provide a practical analysis of the single and combined use of different imaging techniques in the preoperative and perioperative phases of cardiac resynchronization therapy, underlining their main advantages, limitations, and information provided.

Right ventricular myocardial work for the prediction of early right heart failure and long-term mortality after left ventricular assist device implant.

AIMS: Right heart failure (RHF) after left ventricular assist device (LVAD) implant is burdened by high morbidity and mortality rates and should be prevented by appropriate patient selection. Adequate right ventricular function is of paramount importance but its assessment is complex and cannot disregard afterload. Myocardial work (MW) is a non-invasive Speckle Tracking Echocardiography-derived method to estimate pressure-volume loops. The aim of this study was to evaluate the performance of right ventricular myocardial work to predict RHF and long-term mortality after LVAD implant. METHODS AND RESULTS: Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam prior to LVAD implant were excluded. MW analysis was performed. The primary endpoints were early RHF (<30 days from LVAD implant) and death at latest available follow-up. We included 23 patients (mean age 64 ± 8 years, 91% men). Median follow-up was 339 days (IQR: 30-1143). Early RHF occurred in six patients (26%). A lower right ventricular global work efficiency [RVGWE, OR 0.86, 95% confidence intervals (CI) 0.76-0.97, P = 0.014] was associated with the occurrence of early RHF. Among MW indices, the performance for early RHF prediction was greatest for RVGWE [area under the curve (AUC) 0.92] and a cut-off of 77% had a 100% sensitivity and 82% specificity. At long-term follow-up, death occurred in 4 of 14 patients (28.6%) in the RVGWE > 77% group and in 6 of 9 patients (66.7%) in the RVGWE < 77% group (HR 0.25, 95% CI 0.07-0.90, P = 0.033). CONCLUSION: RVGWE was a predictor of early RHF after LVAD implant and brought prognostic value in terms of long-term mortality.

Heart transplantation and anti-HLA antibodY: myocardial dysfunction and prognosis - HeartLAy study.

AIMS: The presence of anti-human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non-invasive parameters early signs of myocardial dysfunction in the presence of anti-HLA antibodies but without evidence of antibody-mediated rejection (AMR) and its possible prognostic impact. METHODS AND RESULTS: A total of 113 heart-transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA-' (63 patients)], based on the presence of anti-HLA antibodies. Each patient was followed for 2 years after the enrolment, recording episodes of AMR, ACR, CAV, and mortality. Clinical characteristics were similar between the two groups. Among laboratory data, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin values were significantly higher in the presence of anti-HLA antibodies (P < 0.001 and P = 0.003, respectively). The echocardiographic parameters that showed a statistically significant difference between the two groups were deceleration time of E wave (DecT E, P < 0.001), left ventricular global longitudinal strain (P < 0.001), tricuspid annular plane systolic excursion (P = 0.011), tricuspid S' wave (P = 0.002), and free wall right ventricular longitudinal strain (fwRVLS, P = 0.027), whereas left atrial strain did not differ significantly (P = 0.408). Univariate analysis showed that anti-HLA antibodies were associated with the development of CAV at both 1 and 2 year follow-up [odds ratio (OR) 11.90, 95% confidence interval (CI) 1.43-90.79, P = 0.022 and OR 3.37, 95% CI 1.78-9.67, P = 0.024, respectively]. Bivariate analysis demonstrated that both fwRVLS and DecT E were predictors of CAV development independently from HLA status. CONCLUSIONS: The presence of circulating anti-HLA antibodies is correlated with a mild cardiac dysfunction, even in the absence of AMR, and CAV development. Interestingly, reduced values of DecT E and fwRVLS were predictors of future development of CAV, independently from anti-HLA antibody.

Tricuspid Regurgitation Velocity and Mean Pressure Gradient for the Prediction of Pulmonary Hypertension According to the New Hemodynamic Definition.

BACKGROUND: The hemodynamic definition of PH has recently been revised with unchanged threshold of peak tricuspid regurgitation velocity (TRV). The aim of this study was to evaluate the predictive accuracy of peak TRV for PH based on the new (>20 mmHg) and the old (>25 mmHg) cut-off value for mean pulmonary artery pressure (mPAP) and to compare it with the mean right ventricular-right atrial (RV-RA) pressure gradient. METHODS: Patients with advanced heart failure were screened from 2016 to 2021. The exclusion criteria were absent right heart catheterization (RHC) results, chronic obstructive pulmonary disease, any septal defect, inadequate acoustic window or undetectable TR. The mean RV-RA gradient was calculated from the velocity-time integral of TR. RESULTS: The study included 41 patients; 34 (82.9%) had mPAP > 20 mmHg and 24 (58.5%) had mPAP > 25 mmHg. The AUC for the prediction of PH with mPAP > 20 mmHg was 0.855 for peak TRV and mean RV-RA gradient was 0.811. AUC for the prediction of PH defined as mPAP > 25 mmHg for peak TRV was 0.860 and for mean RV-RA gradient was 0.830. A cutoff value of 2.4 m/s for peak TRV had 65% sensitivity and 100% positive predictive value for predicting PH according to the new definition. CONCLUSIONS: Peak TRV performed better than mean RV-RA pressure gradient in predicting PH irrespective of hemodynamic definitions. Peak TRV performed similarly with the two definitions of PH, but a lower cutoff value had higher sensitivity and equal positive predictive value for PH.

ADONHERS (Aged DONor HEart Rescue by Stress Echo) National Protocol: Recipient's Survival after 10-Year Follow-Up.

Background: The gold-standard treatment for end-stage heart failure is heart transplantation, but the lack of organ donors remains an important limitation in this field. An accurate selection of marginal hearts is fundamental to increase organ availability. Purpose: In our study we analyzed if recipients receiving marginal donor (MD) hearts, selected by dipyridamole stress echocardiography according to the ADOHERS national protocol, had different outcomes compared to recipients with acceptable donor (AD) hearts. Methods: Data were collected and retrospectively analyzed from patients who received an orthotopic heart transplant at our institution between 2006 and 2014. Dipyridamole stress echo was performed on identified marginal donors and selected hearts were eventually transplanted. Clinical, laboratory and instrumental features of the recipients were evaluated and patients with homogenous baseline characteristics were selected. Results: Eleven recipients transplanted with a selected marginal heart and eleven recipients transplanted with an acceptable heart were included. Mean donor age was 41 ± 23. The median follow-up was 113 months (IQR 86-146 months). Age, cardiovascular risk and morpho-functional characteristics of the left ventricle were comparable between the two populations (p > 0.05). Left atrial size was significantly higher in patients with marginal hearts (acceptable atrial volume: 23 ± 5 mL; marginal atrial volume: 38 ± 5 mL; p = 0.003). Acceptable donor recipients showed a higher impact of Cardiac Allograph Vasculopathy (p = 0.019). No rejection differences were found between the two groups. Four patients deceased, three were standard donor recipients and one was from the marginal donor group. Conclusions: Our study shows how cardiac transplant (Htx) from selected marginal donor hearts through a non-invasive bedside technique can alleviate the shortage of organs without a difference in survival compared to acceptable donor hearts.

Pressure-strain loops unveil haemodynamics behind mechanical circulatory support systems.

AIMS: Mechanical circulatory support (MCS) systems are increasingly employed in cardiogenic shock and advanced heart failure. A thorough understanding of the complex interactions occurring among heart, vasculature, and device is essential to optimize patient's management. The aim of this study is to explore non-invasive haemodynamic profiling of patients undergoing MCS based on pressure-strain (PS) analysis. METHODS: Clinical and echocardiographic data from consecutive patients undergoing different MCS systems positioning/implantation admitted to the third level cardiological intensive care unit of Siena Hospital from August 2021 to November 2021 were retrospectively reviewed. Patients without a useful echocardiographic exam or without arterial blood pressure recording at the time of echocardiography were excluded. Myocardial work analysis was performed in the included patients. RESULTS: We reviewed 18 patients, of which nine were excluded. Included patients were three patients with intra-aortic balloon pump (IABP), two patients with durable left ventricular assist device (dLVAD), two patients with Impella®, one patient with extracorporeal membrane oxygenation (ECMO), and one patient with ECMO and IABP. Myocardial work analysis was feasible in each included patient. The use of IABP shifted the PS curve rightward and downward. Global work index (GWI) and global wasted work (GWW) decreased after IABP positioning, whereas global work efficiency (GWE) increased. The use of continuous-flow pumps, whether temporaneous (Impella®) or long term (dLVAD), induced a change in the PS loop morphology, with a shift towards a triangular shape. ECMO positioning alone resulted in a narrowing of the PS loop, with a decrease in GWI and GWE and an increase in GWW and mean arterial pressure. The combined used of IABP with ECMO widened the PS loop and improved GWI and GWE. CONCLUSIONS: PS loops analysis in patients undergoing MCS seems to be feasible and may unveil MCS-induced haemodynamic variations. Myocardial work could be used to monitor ventricular-arterial-device coupling and guide tailored MCS management.

Biomarkers in Patients with Left Ventricular Assist Device: An Insight on Current Evidence.

Left ventricular assist devices (LVADs) have been representing a cornerstone therapy for patients with end-stage heart failure during the last decades. However, their use induces several pathophysiological modifications which are partially responsible for the complications that typically characterize these patients, such as right ventricular failure, thromboembolic events, as well as bleedings. During the last years, biomarkers involved in the pathways of neurohormonal activation, myocardial injury, adverse remodeling, oxidative stress and systemic inflammation have raised attention. The search and analysis of potential biomarkers in LVAD patients could lead to the identification of a subset of patients with an increased risk of developing these adverse events. This could then promote a closer follow-up as well as therapeutic modifications. Furthermore, it might highlight some new therapeutic pharmacological targets that could lead to improved long-term survival. The aim of this review is to provide current evidence on the role of different biomarkers in patients with LVAD, in particular highlighting their possible implications in clinical practice.

Case Report: Two Case Reports of Acute Myopericarditis After mRNA COVID-19 Vaccine.

Background: Cases of myocarditis and myopericarditis after mRNA COVID-19 vaccines have been reported, especially after the second dose and in young males. Their course is generally benign, with symptoms onset after 24-72 h from the dose. Case Summary: We report two cases of myopericarditis after the second dose of the mRNA-1273 COVID-19 vaccine in two young males. Both the patients were administered the mRNA-1273 COVID-19 vaccine from the same batch on the same day and experienced fever on the same day of the vaccine, and symptoms consisted of myopericarditis 3 days after the dose. Discussion: Myopericarditis is usually considered an uncommon adverse reaction after various vaccinations, reported also after the mRNA COVID-19 vaccine. Several explanations have been proposed, including an abnormal activation of the immune system leading to a pro-inflammatory cascade responsible for myocarditis development. Both patients experienced the same temporal onset as well as the same symptoms, it is also useful to underscore that both vaccines belonged to the same batch of vaccines. However, despite these cases, vaccination against COVID-19 far outweighs the risk linked to COVID-19 infection and remains the best option to overcome this disease.

Diastolic function in heart transplant: From physiology to echocardiographic assessment and prognosis.

Heart transplant (HTx) still represents the most effective therapy for end-stage heart failure, with a median survival time of 10 years. The transplanted heart shows peculiar physiology due to the profound alterations induced by the operation, which inevitably influences several echocardiographic parameters assessed during these patients' follow-ups. With these premises, the diastolic function is one of the main aspects to take into consideration. The left atrium (LA) plays a key role in this matter, and that same chamber is significantly impaired with the transplant, with different degrees of altered function based on the surgical technique. Therefore, the traditional echocardiographic evaluation of diastolic function applied to the general population might not properly reflect the physiology of the graft. This review attempts to provide current evidence on diastolic function in HTx starting from defining its different physiology and how the standard echocardiographic parameters might be affected to its prognostic role. Furthermore, based on the experience of our center and the available evidence, we proposed an algorithm that might help clinicians distinguish from actual diastolic dysfunction from a normal diastolic pattern in HTx population.

Left Ventricular Mass with Delayed Enhancement as a Predictor of Major Events in Patients with Myocarditis with Preserved Ejection Fraction.

Background: Cardiac Magnetic Resonance (CMR) has a key role in subjects presenting with acute myocarditis, independent from left ventricular ejection fraction; it is widely used as a non-invasive imaging test for both diagnostic and prognostic purposes. However, poor data is available about the CMR-derived prognostic parameters of acute myocarditis with preserved ejection fraction (AMpEF). The aim of this study was to investigate the role of CMR in predicting outcomes in patients followed up for AMpEF, using a composite endpoint of all-cause mortality and hospitalization for heart failure (HF). Methods: We retrospectively enrolled 61 patients with diagnosed AMpEF. All patients underwent biohumoral, echocardiographic and CMR evaluation in the acute phase. Myocarditis was confirmed by Lake-Louis criteria assessed on CMR images. Mean follow-up was 4.8 ± 0.6 years during which a composite endpoint of all-cause mortality and hospitalization for HF was investigated. Results: The population was fairly homogeneous regarding baseline clinical features. In particular, no significant differences in age and main cardiovascular risk factors were found between patients with and without events at follow-up. Seven patients met the endpoint. They had significantly higher levels of circulating neutrophils in the acute phase (76 ± 7% vs. 61 ± 11%, p = 0.014) and a higher amount of left ventricular mass with delayed enhancement (DE-LVM, 18 (14-29.5) vs. 12 (8-16) g, p = 0.028). At Cox univariate analysis, DE-LVM was the only significant predictor of endpoint, regardless of the site of inflammation. Conclusions: DE-LVM can predict the composite endpoint of all-cause mortality and hospitalization for HF in a population of patients with AMpEF, representing a new added tool for prognostic stratification.