Heart transplantation and biomarkers: a review about their usefulness in clinical practice.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Speckle tracking echocardiography in plasma cell disorders: The role of advanced imaging in the early diagnosis of AL systemic cardiac amyloidosis.

INTRODUCTION: Amyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments. MATERIALS AND METHODS: 108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score. RESULTS: At ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1). CONCLUSION: Multi-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.

How to deal with low-flow low-gradient aortic stenosis and reduced left ventricle ejection fraction: from literature review to tips for clinical practice.

Low-flow low-gradient aortic stenosis (LFLG AS) with reduced left ventricle ejection fraction (LVEF) is still a diagnostic and therapeutic challenge. The aim of this paper is to review the latest evidences about the assessment of the valvular disease, usually difficult because of the low-flow status, and the therapeutic options. Special emphasis is given to the available diagnostic tools for the characterization of LFLG AS without functional reserve at stress echocardiography and to the factors that clinicians should evaluate to choose between surgical aortic valve repair, transcatheter aortic valve implantation, or medical therapy.

The role of non-invasive imaging modalities in cardiac allograft vasculopathy: an updated focus on current evidences.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy affecting almost 50% of patients after 10 years from heart transplant and represents the most common cause of long-term cardiovascular mortality among heart transplant recipients. The gold standard diagnostic technique is still invasive coronary angiography, which however holds potential for complications, especially contrast-related kidney injury and procedure-related vascular lesions. Non-invasive and contrast-sparing imaging techniques have been advocated and investigated over the past decades, in order to identify those that could replace coronary angiography or at least reach comparable accuracy in CAV detection. In addition, they could help the clinician in defining optimal timing for invasive testing. This review attempts to examine the currently available non-invasive imaging techniques that may be used in the follow-up of heart transplant patients, spanning from echocardiography to nuclear imaging, cardiac magnetic resonance and cardiac computed tomography angiography, weighting their advantages and disadvantages.

Clinical, echocardiographic and hemodynamic predictors of right heart failure after LVAD placement.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implant is associated with increasing morbidity and mortality. The aim of this study was to identify the best predictors of RVF post LVAD-implant among biochemical, haemodynamic and echocardiographic parameters. From 2009 to 2019, 38 patients who underwent LVAD implantation at our centre were prospectively enrolled. Preoperative clinical, laboratory, echocardiographic and haemodynamic parameters were reported. Overall, eight patients (21%) developed RVF over time, which revealed to be strongly related to overall mortality. Pulmonary artery pulsatility index (PAPi) resulted to be the most significant right heart catheterization index in discriminating RVF vs no RVF patients [(1.32 ± 0.26 vs. 3.95 ± 3.39 respectively) p = 0.0036]. Regarding transthoracic echocardiography, RVF was associated with reduced free wall right ventricular longitudinal strain (fw-RVLS) (- 7.9 ± 1.29 vs. - 16.14 ± 5.83) (p < 0.009), which was superior to other echocardiographic determinants of RVF. Among laboratory values, N-terminal pro-brain natriuretic peptide (NT-proBNP) was strongly increased in RVF patients [(10,496.13 pg/ml ± 5272.96 pg/ml vs. 2865, 5 pg/ml ± 2595.61 pg/ml) p = 0.006]. PAPi, NT-proBNP and fwRVLS were the best pre-operative predictors of RVF, a post-LVAD implant complication which was confirmed to have a great impact on survival. In particular, fwRVLS has been proven to be the strongest independent predictor.

Risk stratification in cardiogenic shock: a focus on the available evidence.

Cardiogenic shock is a clinical syndrome which is defined as the presence of primary cardiac disorder that results in hypotension together with signs of organ hypoperfusion in the state of normovolaemia or hypervolaemia. It represents a complex life-threatening condition, characterized by a high mortality rate, that requires urgent diagnostic assessment as well as treatment; therefore, it is of paramount important to advocate for a thorough risk stratification. In fact, the early identification of patients that could benefit the most from more aggressive and invasive approaches could facilitate a more efficient resource allocation. This review attempts to critically analyse the current evidence on prognosis in cardiogenic shock, focusing in particular on clinical, laboratoristic and echocardiographic prognostic parameters. Furthermore, it focuses also on the available prognostic scores, highlighting the strengths and the possible pitfalls. Finally, it provides insights into future direction that could be followed in order to ameliorate risk stratification in this delicate subset of patients.

Multimodality imaging of the ischemic right ventricle: an overview and proposal of a diagnostic algorithm.

Right ventricular (RV) involvement is frequently detected in patients presenting with acute left ventricular myocardial infarction. The ischemic right ventricle carries a dismal outcome by predisposing the heart to arrhythmic events and mechanical or hemodynamic complications. A comprehensive RV evaluation by multimodality imaging could guide clinical practice but has always been a conundrum for the imagers. Two-dimensional echocardiography is the best first-line tool due to its availability of bedside capabilities. More advanced imaging techniques provide a more comprehensive evaluation of the complex RV geometry but are mostly reserved for the post-acute setting. Three-dimensional echocardiography has improved the evaluation of RV volumes and function. The recent application of speckle-tracking echocardiography to the right ventricle appears promising, allowing the earlier detection of subtle RV dysfunction. Cardiac magnetic resonance imaging is considered the gold standard for the RV assessment. Cardiac multidetector computed tomography could be a reliable alternative. The aim of this review is to focus on the growing importance of multimodality imaging of the ischemic right ventricle and to propose a diagnostic algorithm, in order to reach a comprehensive assessment of this too frequently neglected chamber.

Detection of cardiac allograft vasculopathy by multi-layer left ventricular longitudinal strain in heart transplant recipients.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse type of coronaropathy that develops in the transplanted human heart, representing a major cause of graft failure and mortality. Nowadays the gold standard for the diagnosis of CAV is coronary angiography (CA). Non-invasive CAV detection, especially in the early stages of the disease, is still challenging. Our study aimed to investigate the role of speckle tracking echocardiography (STE), in particular three-layer STE, in predicting CAV at early stages, and if other traditional echocardiographic, clinical or biochemical parameters could relate to CAV. The study population was composed of a total of 33 heart transplanted patients, divided accordingly to the presence or absence of CAV (12 CAV+ , 22 CAV-). All subjects underwent a complete transthoracic echocardiographic examination on the same day of the CA, and all conventional parameters of myocardial function were obtained, including strain values assessed by STE. Strain values were significantly reduced in presence of CAV, at each myocardial layer but in particular the endocardial-epicardial gradient (- 4.15 ± 1.6 vs - 1.7 ± 0.4% < .0001) that was also highly predictive of CAV (AUC at ROC curve 0.97). Among diastolic parameters, the E wave deceleration time (DT) and the mean E/e' ratio were strongly positively associated with CAV. In our population, left ventricular global longitudinal strain (GLS), layer-specific GLS and the endocardial-epicardial LS gradient, E wave DT and E/e' ratio were the best independent non-invasive predictors of CAV.

Cardiogenic shock and acute kidney injury: the rule rather than the exception.

Cardiogenic shock (CS) is a life-threatening condition of poor end-organ perfusion, caused by any cardiovascular disease resulting in a severe depression of cardiac output. Despite recent advances in replacement therapies, the outcome of CS is still poor, and its management depends more on empirical decisions rather than on evidence-based strategies. By its side, acute kidney injury (AKI) is a frequent complication of CS, resulting in the onset of a cardiorenal syndrome. The combination of CS with AKI depicts a worse clinical scenario and holds a worse prognosis. Many factors can lead to acute renal impairment in the setting of CS, either for natural disease progression or for iatrogenic causes. This review aims at collecting the current evidence-based acknowledgments in epidemiology, pathophysiology, clinical features, diagnosis, and management of CS with AKI. We also attempted to highlight the major gaps in evidence as well as to point out possible strategies to improve the outcome.

Right cardiac involvement in lung diseases: a multimodality approach from diagnosis to prognostication.

Lung diseases are amongst the main healthcare issues in the general population, having a high burden of morbidity and mortality. The cardiovascular system has a key role in patients affected by respiratory disorders. More specifically, the right ventricle (RV) enables the impaired lung function to be overcome in an initial stage of disease process, reducing the severity of dyspnoea. In addition, two of the main causes of death in this setting are RV failure and sudden cardiac death (SCD). Echocardiography is regarded as a useful and easily available tool in assessing RV function. Several noninvasive echocardiographic parameters of elevated pulmonary pressures and RV function have been proposed. The combination of different parameters and imaging methods is paramount and researches regarding RV impairment using these indices has been specifically addressed in relation to the chronic obstructive and restrictive lung disease in order to guide the clinicians in the management of these patients. Cardiac involvement in lung diseases is often observed, and RV changes are reported also in early stages of pulmonary diseases. The role of right ventricle in chronic respiratory disease patients has to be evaluated in detail to describe the response to therapy and the degree of disease progression through multimodality and advanced imaging techniques. The aim of this review is to describe the different pathophysiological mechanisms of cardiac impairment in primary lung disease (such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and sarcoidosis) and to summarize the role of cardiac multimodality imaging in the diagnosis and the prognosis of these diseases.

Traditional and Novel Imaging of Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction.

PURPOSE OF REVIEW: This review attempts to summarize the role of standard and advanced echocardiographic techniques together with CMR in the evaluation of the RV in HF, providing an outlook on the recent evidence. RECENT FINDINGS: In the last decade, there has been growing interest in the study of the RV, and it is now widely established that RV function is a strong predictor of mortality, in several cardiovascular diseases, in particular in the setting of heart failure (HF). The evaluation of RV function might be particularly challenging, which justifies the necessity of multi-modality imaging. The echocardiographic assessment remains the mainstay technique even though it might be complex, due to RV crescent shape and its position in the chest, requiring both qualitative and quantitative parameters. Cardiac magnetic resonance (CMR) represents a complementary exam which is particularly useful when precise structural and functional assessment are needed, considering the most recently developed sequences. Despite the technological improvement attested over the last years, there is still no universally accepted parameter that univocally defines RV function, hence the necessity to evaluate several parameters, combining different imaging techniques.

Effects of Aortic Valve Replacement on Left Ventricular Diastolic Function in Patients With Aortic Valve Stenosis.

The afterload increase imposed by severe aortic valve stenosis (AS) creates concentric left ventricular (LV) remodeling and diastolic dysfunction (DD), which are both markers of poor clinical outcome. Ideally, a correctly timed surgery for isolated AS can reverse the LV remodeling. However, data on LV DD after aortic valve replacement (AVR) are sparse and contrasting. Aims of the study are to define the markers of a favorable evolution of the DD at follow-up. Patients with severe isolated AS, scheduled for AVR were prospectively enrolled. Transthoracic echocardiography with DD assessment was performed before surgery, and at 12 months after surgery. Global LV longitudinal and circumferential strain, peak atrial longitudinal and contraction strain (PALS, PACS) were obtained at baseline. LV septal biopsy to assess fibrosis was performed at the time of AVR. Sixty-seven patients were enrolled, age 72 ± 8 years, 66% female, ejection fraction 61 ± 8%, E/e' 13 ± 6, PALS 23 ± 7%. Normal estimated left atrial pressure was detected in 19/67 (28%) versus 43/67 (64%) at follow-up (p <0.0001). In the 37 patients with biopsy available, fibrosis was 24 ± 12%. PALS and AS severity were correlated with LV fibrosis (R2 = 0.19; p = 0.006, and R2 = 0.15; p = 0.02, respectively). PALS (odds ratio: 1.19 [1.05 to 1.41], p = 0.02) and PACS (odds ratio: 1.24 [1.06 to 1.50], p = 0.006) were the only baseline noninvasive parameters independently associated with normal left atrial pressure at follow-up. Mean follow-up time was 791 ± 245 days, and 8 (12%) patients had cardiovascular events (death, hospital admission due to heart failure or ischemic disease, and onset of atrial fibrillation). Myocardial fibrosis (p = 0.05), baseline PALS (p = 0.004), and PACS (p = 0.03) were associated with cardiovascular events. In conclusion, LV diastolic function generally improves after AVR for severe AS. Baseline PALS, PACS, and LV fibrosis were related to the DD and clinical outcome at follow-up; these parameters might cue a better diastolic response to the afterload correction.