Advances in perinatal management have led to improvements in survival rates for premature infants. It is known that the transitional period soon after birth, and the subsequent weeks, remain periods of rapid circulatory changes. Preterm infants, especially those born at the limits of viability, are susceptible to hemodynamic effects of routine respiratory care practices. In particular, the immature myocardium and cardiovascular system is developmentally vulnerable. Standard of care  respiratory interventions, administered as part of neonatal care, may negatively impact heart function and/or pulmonary or systemic hemodynamics. The available evidence regarding the hemodynamic impact of these respiratory practices is not well elucidated. Enhanced diagnostic precision and therapeutic judiciousness are warranted. In this narrative, we outline (1) the vulnerability of preterm infants to hemodynamic disturbances (2) the hemodynamic effects of common respiratory practices; including positive pressure ventilation and surfactant therapy, and (3) identify tools to assess cardiopulmonary interactions and guide management. Improvements in perinatal care have led to increasing survival amongst premature infants, especially those born at the limits of prematurity . The traThe fetal circulation is characterized by “physiologic pulmonary hypertension” with high pulmonary vascular resistance (PVR), low pulmonary blood flow (PBF), dependence on placental circulation, and minimal lung involvement . OxygenaIn extremely preterm infants, the postnatal transition is influenced by respiratory and cardiovascular immaturity, leading to poor aeration of the lung and suboptimal increase in PBF . The alvThe premature neonatal myocardium is poorly responsive to loading conditions (preload and afterload) primarily secondary to alterations calcium sensitivity, sarcomere arrangement and immaturity, metabolism, and collagen deposition. Lung aeration (spontaneous or assisted) triggers significant cardiovascular changes in the immediate transitional period; specifically, decrease in PVR leads to a decrease in afterload aiding RV adaptation. In contrast, systemic vascular resistance (SVR) and LV afterload increase upon removal of the low resistant placental circulation. Contractility is impacted by cardiac loading conditions (preload and afterload), as demonstrated on the Frank Starling Curve. The ability of the immature myocardium to increase contractility in response to increase preload (Frank Starling Law) is diminished (flattened curve) in comparison to the mature heart. In addition, the contractile potential of the immature ventricle (RV > LV) to increased afterload (stress-velocity relationship) is also limited.ventriculo-ventricular interactions  and ventricular interdependence (shared contractile fibers).The morphology of the ventricles also impacts their adaptation to alterations in loading conditions. The RV is the dominant, and metabolically more active, ventricle during fetal life. After birth, the crescentic and thin walled RV is more sensitive to alterations in afterload than the ellipsoid and thick-walled LV. Myocardial performance is also impacted by The PDA is a dynamic shunt that can persist after the transitional period, allowing for alterations in pulmonary and systemic blood flow . Pretermor under-ventilation may be equally damaging with a U-shaped effect on PVR. For example, exposure to high tidal volumes (over-recruitment) during delivery room resuscitation or failure to wean distending pressure settings in response to rapidly improving lung compliance, may lead to elevated PVR and/or compromise pulmonary and systemic blood flow. In contrast, provision of suboptimal respiratory support (under-recruitment) by non-invasive means may lead to hemodynamic instability, through increasing the risk of pulmonary vascular disease and increased RV loading. While achieving the ideal distending pressure is necessary for optimal alveolar recruitment, the impact of altered mean airway pressure (MAP) on intrathoracic pressure, venous return, PBF, and LV preload and afterload is variable. Figure Mechanical ventilation is an essential component of preterm respiratory care, especially in extremely premature infants. Spontaneous breathing establishes a positive gradient between extrathoracic venous pressure and right atrial pressure that supports systemic venous return. The effects of both non-invasive and invasive forms of mechanical ventilation on intrathoracic and abdominal pressure are likely to be magnified in the most immature infants with potentially negative effects on pulmonary/systemic venous return, heart function, affecting cardiac function and output. The magnitude of the effects of mechanical ventilation on preterm cardiovascular function are likely to vary according to the underlying pathophysiologic disease state. In addition, the hemodynamic effects of both over- First, over-distension of alveoli can lead to an increase in PVR secondary to extrinsic compression of alveolar vessels. Second, collapsed alveoli can have the same effect by way of compression of extra-alveolar vessels [Native PVR is in part driven by the adequacy of oxygenation and ventilation, combined with distension of the alveoli and compression of the alveolar and extra-alveolar vessels. An optimal positive end expiratory pressure (PEEP) may allow for lung recruitment and improvement in oxygenation, decrease in PVR, without hemodynamic compromise . Obtaini vessels  Fig. 3)First, ovThe specific effects of mechanical ventilation on global heart function are also noteworthy. While the RV and LV are both impacted by ventilation induced alterations in intrathoracic pressure, the adaptive response of RV vs LV to altered loading conditions varies.In preterm infants needing positive pressure ventilation (PPV), RV function is impacted by transmural pressure, ventricular compliance, venous return, and PVR  Fig. 2)2). Incre. [LV performance is impacted by the adequacy of RV function, SVR, and PBF. Through ventriculo-ventricular interaction, the pressure loaded RV may lead to paradoxical septal bowing which limits LV filling and alters the ellipsoid shape, thereby negatively impacting contractility and cardiac output . LV prelessure). . Lung reessure). . While tessure). –26. Thisessure). –30. FiguAs previously discussed, the transductal gradient is modified by alterations in PVR and SVR, viscosity, and ductal size. Alterations in PEEP, oxygenation, ventilation, and changes in transmural pressure can impact the ductal gradient in addition to cardiac loading conditions. Studies have investigated the modulator effects of PEEP and ventilation strategies on ductal flow patterns, however with conflicting results , 32.2O), and subsequently, 1 h after being off CPAP. A reduction in superior vena caval flow and RV output were noted, which was accompanied by a simultaneous increase in the inferior vena cava diameter [2O or after sequential increases  in CPAP levels [Non-invasive respiratory support is associated with decreased barotrauma and volutrauma, avoiding the need for mechanical ventilation, and therefore has become the primary means of respiratory support for many preterm infants , 34. In diameter . Hsu et diameter . Other iP levels , 38. TheP levels . WhereasP levels . The autP levels . More reThe cardiovascular effects of modes of conventional mechanical ventilation have been the subject of clinical trials; however, the impact of these respiratory strategies on hemodynamics is poorly delineated. A recent Cochrane review of volume targeted vs pressure limited ventilation demonstrated that the former is associated with a decreased risk for death, chronic lung disease, cerebral injury, and air leak . These oWhile the favourable effects of first-intention HFV on alveolar gas exchange and lung protection, using stable alveolar distending pressures and lower tidal volume, are well established , the hemSRT is an essential treatment for premature infants with developmental lung immaturity. The impact of SRT on transitional hemodynamics and end-organ related effects, however, represents a knowledge gap. Rapid changes in PVR, with systemic to pulmonary circulatory shifts, in the setting of myocardial immaturity and the inherent autonomic dysregulation affecting regulation of vascular smooth muscle tone, may be critical factors influencing end-organ blood flow.There is evidence from both animal experimental models and preterm infants that SRT is followed by early falls in PVR, due to enhanced lung compliance. Kaapa et al. demonstrated a marked decrease in PAP within 15 min of SRT , which hAs PVR is the primary driver of RV afterload, surfactant related effects are important. Due to the preserved effects of ventriculo-arterial coupling, SRT may also affect RV systolic function; specifically, an increase in tissue Doppler peak systolic velocity and tricuspid annular plane systolic excursion , 54. ThiThe influence of SRT on LV output remains poorly defined with echocardiography assessments of LV output showing conflicting results. Evidence from a lamb experimental model revealed an increase in LV output after SRT, possibly due to increased pulmonary venous flow and left heart preload augmentation –57. Studet al. demonstrated changes in trans-ductal diameter, flow direction and shunt magnitude, after SRT in newly born preterm infants [p < 0.01), larger trans-ductal diameter (p = 0.01), and increased rate of therapeutic interventions to close the PDA (p < 0.01) than those not treated with SRT[The SRT impact on PVR can promote a major circulatory shift, favouring the pulmonary circulation (at the expense of systemic circulation) through the PDA , 58, 59. infants . Kumar e with SRT. The com with SRT, 56, 61.or no change in systolic BP [Longitudinal evaluation of the effects of SRT on blood pressure (BP) from animal experimental models has demonstrated either a decrease tolic BP . Informatolic BP . The devtolic BP . Most stIn a meta-analysis of clinical trials, SRT was shown to be associated with pulmonary haemorrhage, although the exact underlying aetiology remained unclear . It is bThe variance in underlying pathophysiologic disease in the setting of a clinical phenotype and the multiplicity of cardiovascular effects of assisted respiratory support provides biological justification for longitudinal echocardiography evaluation. While most clinicians rely on biochemical and clinical parameters such as changes in serum lactate, heart rate or arterial BP, these may occur late, providing little diagnostic insight. In addition, a symptom-based approach to neonatal care is imprecise and is limited by the fact that similar symptoms may be seen in disease states that require a differential approach to treatment. For example, oxygenation failure may be seen in both pulmonary hypertension and a hemodynamically significant PDA. An approach to intervention,  with either inhaled nitric oxide (treatment for pulmonary hypertension) or non-steroidal anti-inflammatory medications (treatment for PDA) may have negative effects.Targeted Neonatal Echocardiography (TnEcho) is a useful tool to monitor rapid circulatory changes in order to determine ‘need’ for therapeutic interventions, the effect of these interventions, thereby a more pathophysiologically precise approach to treatment. Recent studies have demonstrated the impact of TnEcho on changing clinical management , 69, imp2 in the capillary bed and is a marker of tissue perfusion. Cerebral tissue saturation has been used in anaesthesia to guide respiratory management but it remains to be seen whether it could decrease neurologic sequelae [In addition, adjunctive tools such as lung ultrasound and near-infrared spectroscopy (NIRS) are non-invasive, easily accessible, and reproducible tools to assess hemodynamic effects of common non-cardiovascular interventions in preterm infants. The latter non-invasively measures StOsequelae . Lung ulsequelae .Premature infants have unique lung physiology which makes management of hemodynamic disturbances with routine interventions challenging. Considering the biologic nature of hemodynamic disturbances, a potential relationship to ‘non-cardiovascular’ interventions needs better appreciation. Despite the importance of understanding cardiopulmonary interactions, there continues to be a lack of evidence to guide ventilatory strategies and tailor them according to unanticipated hemodynamic effects. One of the challenges with both mechanical ventilation and the use of surfactant in preterm neonates is the inability to determine the therapeutic inflexion point, where these interventions change from a state of enhanced cardiopulmonary interaction (benefit) to causing hemodynamic compromise (harm). Recognition of the hemodynamic impact of routine care practices is an important, yet variably recognized, modulator of organ health and neonatal outcomes. Precision medicine with the utilization of non-invasive modalities to evaluate cardiopulmonary interactions is needed to guide care in this high-risk population. Finally, with increasing evidence of cardiac maldevelopment during the fetal-neonatal course, it is incumbent of researchers to design prospective studies which enable characterization of modulators of these effects .


Adverse cardiac remodelling is the main determinant of patient prognosis in degenerative valvular heart disease (VHD). However, to give an indication for valvular intervention, current guidelines include parameters of cardiac chamber dilatation or function which are subject to variability, do not directly reflect myocardial structural changes, and, more importantly, seem to be not sensitive enough in depicting early signs of myocardial dysfunction before irreversible myocardial damage has occurred. To avoid irreversible myocardial dysfunction, novel biomarkers are advocated to help refining indications for intervention and risk stratification. Advanced echocardiographic modalities, including strain analysis, and magnetic resonance imaging have shown to be promising in providing new tools to depict the important switch from adaptive to maladaptive myocardial changes in response to severe VHD. This review, therefore, summarizes the current available evidence on the role of these new imaging biomarkers in degenerative VHD, aiming at shifting the clinical perspective from a valve-centred to a myocardium-focused approach for patient management and therapeutic decision-making.  However, optimal timing of intervention remains a clinical challenge, balancing the risks of intervening too early, and therefore exposing patients to unnecessary peri-procedural and long-term complications, in contrast to a watchful waiting strategy, with the possible occurrence of sudden cardiac death or heart failure. Current guidelines4 recommend intervention based on VHD severity, presence of symptoms, and/or of left ventricular (LV) remodelling or reduced ejection fraction (EF). Despite the profound clinical implications, assessment of symptoms can be challenging: symptoms can be under-reported by the patient, could be related to concomitant comorbidities  and, most importantly, they often appear at a late stage, when systemic and pulmonary circulation are significantly impaired and possibly irreversible myocardial damage has already occurred. When VHD is significant, cardiac chambers are exposed to either pressure (as in AS) or volume overload (as in MR), which triggers at first a series of adaptive mechanisms to release wall tension and maintain cardiac output . However, these compensatory phenomena are soon followed by maladaptive myocardial changes such as reactive fibrosis, microvascular ischaemia and cell death with replacement fibrosis, which substantially impair LV function, but only later result in a reduced left ventricular ejection fraction (LVEF). An impaired LVEF is therefore a strong prognosticator but, reflecting the complete exhaustion of these compensatory mechanisms, is a late marker of myocardial dysfunction, lacking sensitivity to depict the myocardial damages which already took place. To avoid the occurrence of irreversible myocardial damage, new biomarkers capable of depicting the occurrence of such maladaptive changes are advocated with important potential impact on patient risk stratification and on interventions’ results. To answer this need, advanced imaging may play a crucial role in identifying adverse myocardial remodelling at an early stage. Particularly, echocardiography is the first-line diagnostic modality, and along with strain imaging can provide an advanced assessment of myocardial mechanics; LV global longitudinal strain (LVGLS) has shown to be a sensitive marker of systolic dysfunction in various cardiovascular diseases including degenerative VHD.5 Cardiac magnetic resonance imaging (CMR) has the key strength of myocardial tissue characterization, including fibrosis and inflammation, but also myocardial perfusion and energetics, and therefore offers an in vivo ‘virtual histology’ of great value also in degenerative VHD.Valvular heart disease (VHD) is a major cause of morbidity and mortality worldwide, affecting >2% of the general population.Table 1), and seeks to highlight their potential in shifting the focus of the clinical assessment from the valve to the myocardium, in order to improve patient management and therapeutic decision-making.The current review, therefore, summarizes the evidence on the role of imaging biomarkers of myocardial response in degenerative VHD  and Barlow’s disease.6 Although a clear distinction cannot always be made, patients with Barlow’s disease are usually younger and the mitral valve is characterized by thickened leaflets, with multi-segmental prolapse, chordal elongation, and typical annular abnormalities, such as dilatation, posterior disjunction, and abnormal displacement. In turn, patients with FED are typically older (and therefore with more comorbidities) and show thin or normal leaflets, with single segment prolapse/flail by chordal rupture. Regardless of the aetiology, when severe MR develops, left atrial (LA) and LV dilatation occurs as adaptive mechanisms to accommodate the volume overload and maintain cardiac output. In most cases, during this phase, pulmonary pressures remain within normal limits, LVEF remains falsely normal or supra-normal (considering the reduced afterload) and patients are asymptomatic. However, a chronic increase in LV wall stress leads to non-ischaemic fibrosis and adverse myocardial remodelling, which may progress to overt LV dysfunction. Also, the further upstream effect of a severe MR will eventually lead to elevated pulmonary pressures, which often induce right ventricular (RV) dilatation, secondary tricuspid regurgitation (TR), and ultimately RV dysfunction. However, this pathophysiological cascade is not homogeneous in all patients, and the mechanisms by which the cardiac chamber remodels to hemodynamically adapt to severe MR can vary significantly. Age, mechanism of MR, and associated comorbidities may influence cardiac remodelling response to volume overload. In Barlow’s disease particularly, a specific cardiomyopathy has been suggested as part of the phenotype leading to a LA and LV dilatation disproportionate to the severity of MR.7 Current guidelines, beyond symptoms, consider LVEF and end-systolic diameter as main gatekeepers (Class I) to surgery; additional reasons for intervention (Class II) are also considered atrial fibrillation, LA dilatation and increased pulmonary pressure.4 However, LVEF may remain normal for relative long time without properly reflecting ongoing important damages of the myocardium; also, the cut-off values of the other echocardiographic parameters of chamber remodelling have been derived mainly from symptomatic patients,8 when myocardial structural changes may have already occurred and may not be reversed after intervention. Therefore, there is still a need for new imaging biomarkers able to better understand myocardial involvement in degenerative MR, possibly at an early stage, and to refine indication for intervention.MR is classified as primary when it is due to intrinsic lesions of the mitral valve, rather than to a disease of the LV as in secondary MR. Primary MR can be caused by congenital malformations or endocarditis, but most frequently is degenerative, either due to rheumatic disease or myxomatous infiltration as in mitral valve prolapse (MVP).9 However, also waiting for LV and LA dilatation may increase the risk of incipient myocardial damage that is not detectable by conventional echocardiographic techniques. Strain echocardiography has shown that in patients with severe primary MR and a mean LVEF >60%, LVGLS was significantly impaired as compared to controls, and decreased with increasing LV diameters and regurgitant volume.10 Furthermore, the prognostic value of LVGLS to predict post-operative LV dysfunction and mortality after surgery in patients with severe primary MR has been demonstrated in several studies. Among 593 patients with severe primary MR, those who presented an LVGLS ≥20.6% had better outcomes after surgical mitral valve repair as compared to those patients with an LVGLS <20.6% .11 Similar results were demonstrated also in asymptomatic patients with severe primary MR.13 Of note, the relatively preserved values of LVGLS could be related to the reduced afterload since the LV empties into a low chamber pressure, the LA.Standard echocardiography can provide all the parameters currently used to recommend intervention in degenerative MR, including LV diameter and EF, LA diameter and volume, and pulmonary pressure. Particularly, the presence of pulmonary hypertension and also of RV dysfunction (possibly signs of exhaustion of the LV and LA compensatory mechanisms) has been associated with poor outcomes, and patients presenting with these characteristics should undoubtedly be referred to surgery at an earlier stage.14 also significant mitral valve annular abnormalities were observed, including annular dilatation and disjunction, described in MVP patients as a separation between the LA wall at the level of the mitral valve junction with the LV free wall. These results highlight the presence of a cardiomyopathic process with structural abnormalities that affect myocardial mechanics at an earlier stage than LVEF.Based on strain imaging, the time delay of LV longitudinal strain can be derived as a measure of LV mechanical dispersion which has been associated with the occurrence of ventricular arrhythmias. In 610 patients with MVP, those with symptomatic ventricular arrhythmias had worse LVGLS and more pronounced mechanical dispersion as compared to patients without ventricular arrhythmias, despite having similar LVEF;Figure 1).15Strain measures can also be applied to the LA to assess its reservoir function and by reflecting LA compliance, may therefore identify early signs of LA remodelling. In a recent study, LA reservoir strain was independently associated with all-cause mortality  in patients undergoing mitral valve repair for severe primary MR, and with incremental prognostic value over current clinical and echocardiographic factors .17 Replacement myocardial fibrosis as assessed by late gadolinium enhancement (LGE) has been noted in the setting of primary MR with several key caveats.18 First, LGE is much more prevalent in primary MR due to myxomatous MVP than other non-myxomatous aetiologies, supporting the hypothesis that these specific mitral valve alterations are also associated with myocardial abnormalities and a pro-fibrotic milieu. Second, LGE is commonly located in the segments adjacent to the posteromedial papillary muscle  and to the mitral valve, suggesting also a mechanical trigger (pulling of the elongated chorda and hyperdynamic annular motion and disjunction) to the development of fibrosis.19 Third, the prevalence of LGE increases with the severity of MR, being as high as 50% in patients with severe MR, and confirming the irreversible myocardial damages secondary to the volume overload.Considering the key parameters to trigger MR intervention, CMR is a well-established method for quantifying LV dimension and EF, with high reproducibility and obviating the need for geometric assumptions. However, LV volumes may be a more reliable marker of LV remodelling and in a series of asymptomatic MR patients, CMR-derived LV end-systolic volume index demonstrated a higher predictive value than echo-derived LV end-systolic diameter for survival free of mitral surgery.19 By using CMR in a US-based series, patients with MVP and evidence of LGE experienced a 7.7% rate of arrhythmic events  as compared to 2.7% for MVP patients without replacement fibrosis, and 0.6% for the group with primary MR due to non-MVP aetiology .18 Similarly, a French study of MVP patients demonstrated a higher likelihood of arrhythmic events in presence of LGE.20 Furthermore, MVP patients with replacement fibrosis experienced a 2.6-fold higher rate of cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, or life-threatening ventricular arrhythmia, supporting the growing evidence that LGE is associated with an increased risk of adverse cardiovascular events in these patients.Several recent studies have also demonstrated a prognostic implication of replacement fibrosis in the setting of MVP. Starting from autopsy studies, analysis of sudden cardiac death victims with MVP revealed the presence of LV replacement fibrosis and with the propensity of segments adjacent to the posteromedial papillary muscles.17 Studies have shown myocardial ECV to be correlated with histologically quantified diffuse interstitial myocardial fibrosis in several medical conditions,21 including VHD. A cross-sectional study of patients with asymptomatic moderate or severe primary MR noted that ECV was correlated with total exercise time, metabolic equivalent, and peak oxygen consumption.22 In a large study of patients with chronic primary MR, ECV was higher in patients with symptomatic MR.23 Furthermore, when followed longitudinally, patients with an ECV ≥30% experienced a higher likelihood of death or need for mitral valve surgery24 and a recent study also showed an association between ECV  and complex ventricular arrhythmias.25 While still an emerging marker, current evidence suggests that ECV may represent a marker of maladaptive remodelling and subclinical decompensation in chronic primary MR.CMR can also quantify myocardial extracellular volume (ECV) by T1 mapping, based on the change in T1 times before and following administration of gadolinium contrast.26 After surgery, a significant reduction in ECV fraction and indexed ECV, proportional to their preoperative expansion was observed, but not in LGE. These findings suggest that interstitial reactive fibrosis is probably reversible while replacement fibrosis is not. Also, preoperative ECV predicted the degree of post-operative remodelling irrespective of symptoms, highlighting that although patients with LGE and interstitial fibrosis still benefit from surgery, they are less likely to demonstrate reverse remodelling after surgery and a deleterious effect on LV function remains.Recently, a prospective multicentre study enrolled 104 patients with primary MR who underwent CMR before and on an average of 8 months after mitral valve repair.de novo even after mitral valve repair.28Finally, CMR tagging and feature-tracking also allow for assessment of myocardial deformation (strain), and initial studies in patients with chronic primary MR have shown namely a decrease in regional circumferential strain, persistent or occurring Further studies are needed to confirm whether these CMR measures can help in timing mitral valve interventions in these patients, and if mitral valve repair is a strategy to lessen the excess risk conferred by replacement and diffuse interstitial fibrosis.29 In parallel to the progressive LV hypertrophy, there is an increase in interstitial fibrosis and myocyte apoptosis, due to oxygen supply-demand mismatch and myocardial ischaemia. If the valve is left untreated, the LV myocardium develops areas of myocyte loss and three distinct patterns of fibrosis have been described: thickened endocardium, development of irreversible microscars particularly in the sub-endocardium with a gradient from the inner to the outer third of the myocardium, and inter-fiber and perivascular fibrosis throughout the myocardium.30 These important structural abnormalities lead at a later stage to LV systolic dysfunction, which when overt has been associated with poor outcome and included as an important criterion to indicate surgery in patients with severe AS with or without symptoms.4 Risk stratification and the best timing for prophylactic intervention, however, remain controversial in asymptomatic patients with preserved LVEF, and is currently being evaluated in several prospective randomized controlled trials. Other prognostic factors should be considered in patients with severe AS, as for example it has been demonstrated for the right heart involvement , shown to be associated with poor prognosis even in asymptomatic patients.32 In addition, transthyretin cardiac amyloidosis (ATTR) has been recognized as an important combined myocardial and aortic valve pathology, which poses diagnostic challenges due to presentation with low-flow, low-gradient AS and, more importantly, is characterized by a more severe phenotype with more frequently heart failure, arrhythmias, and higher mortality.33–37In patients with severe AS, LVEF is often preserved and LV hypertrophy develops gradually to reduce wall stress and maintain cardiac output.Figure 3). In particular, Vollema et al.38 compared 220 asymptomatic patients with severe AS to 220 age- and sex-matched controls without AS; both groups had similar, preserved LVEF, but LVGLS was significantly reduced in the patients with severe AS . Dahl and coworkers39 published a systematic review that confirmed that patients with severe AS are often asymptomatic, present with normal LVEF (≥50%) but have an impaired LVGLS. Subsequent studies showed also the strong prognostic value of LVGLS in patients with severe AS.40 In the aforementioned study by Vollema and colleagues,38 in patients with asymptomatic severe AS and preserved LVEF, LVGLS deteriorated during a median follow-up of 12 months  when treated conservatively. Moreover, patients with reduced LVGLS at baseline were at higher risk of developing symptoms and need for aortic valve replacement (AVR) during follow-up. An individual participant data meta-analysis,41 totalling 1067 asymptomatic patients with severe AS and LVEF >50%, showed that a cut-off value of LVGLS <14.7% was associated with a 2.5-fold increased risk of death. When considering only patients with an LVEF ≥60%, the association between LVGLS and all-cause death remained significant.The functional abnormalities resulting from the above-mentioned structural changes are better detected by advanced echocardiographic parameters such as LVGLS, which are more sensitive than LVEF. Several studies showed that LVGLS is impaired in patients with severe AS even in case of preserved LVEF and absence of symptoms  can be incorporated to construct pressure-strain loops of the LV and obtain myocardial work measures which take into account LV afterload: in a recent study, LV global work index and constructive work showed an independent association with heart failure symptoms in patients with severe AS.44–47 More importantly, CMR allows the visualization of both patchy non-infarct pattern scar by LGE imaging49 as well as the diffuse fibrosis in the mid-myocardium using T1 and ECV . With progressive AS, LGE accumulates over time, slowly in mild AS , but faster in moderate and severe AS with an apparent acceleration trajectory of scar extent.50 Prevalence of LGE in severe AS ranges from 27 to 51%, is associated with more severe valvular stenosis and worse LV systolic and diastolic function; furthermore, it correlates with histology and appears to be irreversible at 9 and 12 months after surgical AVR.51–56 Importantly, LGE independently predicted all-cause and cardiovascular mortality, regardless of type of LGE (infarct pattern vs. non-infarct pattern) or intervention .57 After AVR, de novo LGE may occur in between 5 and 18% of patients but myocardial vulnerability during surgery is not yet well understood.57–61 Whether early intervention guided by LGE improves survival is currently under investigation in the EVOLVED trial (NCT03094143), assessing early intervention in asymptomatic patients with LGE.59CMR is more sensitive than echocardiography to identify altered global LV geometry , and has revealed marked sex dimorphism in the remodelling response to severe AS. Men show higher indexed LV mass, lower LVEF, and increased myocardial stiffness, while women present more concentric remodelling with higher relative wall thickness and LVEF; however, the scale of the differences is being increasingly recognized with apparently more maladaptive myocardial response to AS in men.60 Diffuse fibrosis prior to AVR has been shown to predict symptomatic and LV function improvement.61–63 In a recent multicentre study in 440 patients with severe AS prior to surgery, ECV fraction was independently associated with cardiovascular and all-cause mortality.64 Importantly, reverse remodelling after AVR was associated with early normalization in LV function within the first 6 months, and LV mass regression in the first 6 to 12 months with up 20–30% LV mass reduction at 1 year.65–73 Of note, early mass regression was greater in the presence of more LV hypertrophy, and in absence of scar.74Beyond LGE, T1 mapping and ECV quantification allow assessment of diffuse fibrosis that precedes irreversible focal fibrosis.64 Early ECV data interrogating LV mass regression at 6 months post-AVR noted cellular regression without significant extracellular matrix changes,75 but more recent data demonstrated both cellular and matrix regression at 1 year ; scar by LGE however was irreversible.56 This highlights that myocardial compartments are plastic, providing scar is absent.ECV quantification allows further interrogation of this process by splitting LV mass into a matrix and cell compartment. Prevalence of increased myocardial ECV in severe AS (using the threshold of >28%) ranges from 33% up to 54% depending on the studied population.76LV myocardial strain as measured by CMR was also shown in initial studies on AS, to discriminate between asymptomatic vs. symptomatic patients and to be associated with outcomes after surgical or transcatheter interventions.33–37 In principle, AVR should not be withheld from patients with dual pathology but patients should be considered for amyloid-specific therapies.77Nuclear scintigraphy has not played a significant role in the management of AS until recently, when bone scintigraphy  has been increasingly used to diagnose ATTR amyloidosis. Other imaging modalities, including CMR but also ECV by computed tomography can also help in characterizing myocardial involvement in this disease: the AS-amyloid prevalence in severe AS patients ranges between 8 and 16% depending on the age of the patients but in patients above the age of 75 years appears to affect 1 in 8.78 LV dilatation is considered an important criterion in current guidelines for the management of patients with severe AR by using LV linear dimensions.4 However, it is well known that LV linear dimensions have limitations and volumetric measurements by echocardiography, especially when with three-dimensional imaging,79 can more precisely and accurately identify the complex LV remodelling which occurs in chronic AR.81 Echocardiographic LV volume assessment has been shown to have good reproducibility in patients with moderate-severe and severe AR and a LV end-systolic volume ≥45 mL/m² was independently associated with all-cause mortality as well as cardiac symptoms.80Acute aortic regurgitation (AR) most often results from endocarditis, aortic dissection, chest trauma, or iatrogenic injury. When severe, acute LV volume overload generally leads to a low output state and pulmonary oedema. Thus, early surgical intervention occurs prior to the hemodynamic myocardial consequences which are expected in chronic AR. In contrast, in chronic severe AR, the LV faces a prolonged volume overload and relative pressure overload, with adaptive eccentric hypertrophy with cardiomyocyte growth by addition of new sarcomeres in series, and therefore increase in LV volumes and mass .78 In a population of 41 patients with ≥ moderate-severe chronic AR, advanced diastolic dysfunction including pseudo-normalization or restrictive filling was present in 25% and has been associated with worse outcome after AVR.82The chronic volume (and pressure) overload which characterizes AR leads also to the development of myocardial fibrosis, diastolic dysfunction and ultimately impairment of contractile function.83–85 In this regard, the functional consequences of the maladaptive processes to volume overload might be better reflected by myocardial strain measurements. Patients with severe AR and LVEF >50% have shown impaired values of LV longitudinal, circumferential and radial strain by echocardiography as compared to controls.86 When dividing patients according to the presence of symptoms, symptomatic patients had also more impaired LV longitudinal , circumferential , and radial  strains as compared to asymptomatic patients. Furthermore, LVGLS has been associated with all-cause death in 865 patients with severe AR who were asymptomatic or mildly symptomatic and had an LVEF ≥50%. Alashi et al.87 showed, that patients with an LVGLS <19.5% had higher mortality rates at 6 years follow-up as compared to patients with an LVGLS ≥19.5% . Each 1% absolute worsening in LVGLS was independently associated with all-cause death with a hazard ratio of 1.11.Finally, mortality in chronic AR increases by reduced LVEF, which however occurs at a late stage in the natural history of this VHD, and several studies have suggested that valve intervention should be considered at an earlier stage of ventricular remodelling than recommended by guidelines.et al.88 showed in 57 patients with moderate and severe chronic AR and preserved LVEF who were referred for surgical AVR, that the majority of the patients had normal or increased myocardial work. However, after aortic valve surgery, 28% of patients presented impaired LV myocardial work. The post-operative impairment of LV global myocardial work was associated with a lesser degree of LV reverse remodelling suggesting that there was prior to surgery a more advanced LV myocardial remodelling.To integrate the loading conditions in the assessment of LV systolic function, the calculation of pressure-strain loops and myocardial work has been proposed also in patients with chronic severe AR. Meucci 89 namely by a better characterization of LV remodelling, precise quantification of AR severity, but more importantly identifying the development of myocardial fibrosis (6). Presence of either ischaemic or non-ischaemic myocardial fibrosis identified by CMR was seen in up to a third of patients chronic AR.90 Importantly, it was associated with 2.5-fold increase in mortality and mitigated by AVR. Particularly, ECV fraction was shown to have a strong correlation with AR severity measured by aortic regurgitant fraction, and both were associated with worse outcomes in chronic AR patients.91CMR evaluation may provide incremental value over echocardiography,92When feature-tracking CMR was used to measure strain, LVGLS showed to be impaired early in the course of the disease and a marker of AR severity, while circumferential and radial strain worsened later and were associated with outcome, namely the need for aortic valve surgery.In summary, given the current widespread use of volumetric measurements and improved standardization, future guidelines should support the use of volumetric rather than linear measurements of the LV, either obtained by echocardiography or by CMR. Assessment of myocardial strain and fibrosis appears very promising for further risk stratification in severe chronic AR.93 The type and extent of RA and RV remodelling induced by TR is crucial for the management of these patients, and has been included as last topic of current review to create further awareness on the importance of standard and new imaging biomarkers to assess myocardial involvement of the right heart.93 The myocardial structural changes, including accumulation of collagen in the extracellular matrix, may differ significantly across the spectrum of TR aetiologies and severity.94 The RV histological changes are more pronounced in pressure overload conditions as compared to volume overload circumstances, and increased myocardial fibrosis has been described in experimental and clinical models particularly as results of pulmonary hypertension.95–97 However, combined pressure and volume overload is common in these patients whose overall myocardial remodelling and insult are amplified.97 Pressure-volume overload may lead also to RV ischaemia which further enhances myocardial fibrosis development. These structural changes all lead ultimately to impaired RV functional parameters which underlies the poor outcomes of these patients. It is therefore important to identify sensitive functional and anatomical imaging biomarkers to better risk stratify patients with TR. However, most of current functional parameters are influenced by the loading conditions (preload and afterload), presence of ischaemia, pericardial constraint and the interventricular dependence. Therefore, any RV functional imaging is an imperfect indirect marker of RV structural remodelling .The aetiology of TR can be quite heterogeneous due to the interplay between the right atrium (RA), the RV, tricuspid annulus and pulmonary pressures, but also to leaflet morphology and other contributors such as atrial fibrillation and presence of intracardiac devices.P = 0.003).98 To account for the afterload, especially important among patients with pulmonary hypertension and secondary severe TR, Fortuni and coworkers99 showed that the ratio between TAPSE and systolic pulmonary artery pressure reflected the RV to pulmonary arterial (RV-PA) coupling and had important prognostic implications. Patients with RV-PA uncoupling  had 46% increased risk of all-cause death as compared to patients with preserved RV-PA coupling.Bearing in mind those limitations, echocardiography is the imaging technique most frequently used in the evaluation of the patients with severe TR. Among the various parameters of RV function, longitudinal strain has demonstrated incremental prognostic value over RV fractional area change and tricuspid annulus plane systolic excursion (TAPSE). Among 896 patients with moderate and severe TR, RV longitudinal strain detected more frequently RV dysfunction as compared to RV fractional area change or TAPSE, and each 1% impairment in RV longitudinal strain was independently associated with increased all-cause death .Difficulties for CMR performance in this population are related to common presence of atrial fibrillation and intracardiac devices which can create artefacts. Nonetheless, the growing use of CMR in TR patients has led to a better understanding of its importance for this patient population for the following two main reasons: (i) being the gold standard for quantification of RV remodelling and RV function, uncovering the shortcomings of 2D echocardiography, and (ii) it evaluates using LGE the extent and pattern of myocardial fibrosis leading to the diagnosis of the underlying cardiomyopathy101Ongoing transcatheter tricuspid replacement trials use cardiac computed tomography for anatomical screening and procedural planning but have not yet leveraged the full analytical capabilities of this imaging modality such as its functional assessment, quantification of TR severity (via measurement of effective regurgitant orifice area), myocardial strain or myocardial ECV fraction, a surrogate of diffuse myocardial fibrosis.Graphical Abstract). Cumulative evidence is already available on the use of advanced echocardiographic techniques and CMR unique capabilities to predict adverse myocardial remodelling and therefore refine timing for intervention. However, these imaging biomarkers are still largely underused, possibly because of lack of availability, standardization  and prospective validation. The application in clinical practice particularly of novel CMR imaging biomarkers such as native T1 mapping, ECV, but also strain measures, will need to follow a careful implementation roadmap which has been outlined in a specific SCMR document.17 The access continues to improve as all CMR vendors already have T1 mapping sequences available and many commercial solutions for post-processing the data analysis. Nevertheless, the clinical implementation and expertise for the interpretation and reporting needs to be coupled with important review of the data acquisition, imaging quality, variability of the measures102 and attention to potential confounders (including loading conditions) or artefacts.17 Of note, since ECV calculation is derived from a ratio of myocardial/blood pool T1 value changes, ECV values are typically not influenced by the pulse sequence and/or magnetic field strength . As a consequence, native or post-contrast T1 mapping values have greater variability limiting their clinical applicability in multicentre studies.In degenerative VHD, although valve stenosis or regurgitation are the primary insult, is the myocardial response that determines how the insult is tolerated and the prognosis of the patients, and should therefore drive the decision on in whom and when to intervene. Novel imaging biomarkers are therefore advocated to better understand myocardial changes secondary to volume or pressure overload or possibly concomitant to the valvular abnormalities, and, most importantly, to depict the crucial switch from adaptive (and reversible) to maladaptive (possibly irreversible) myocardial remodelling (Finally, the results of ongoing randomized trials including these novel imaging biomarkers as inclusion criteria, and future research, possibly applying new diagnostic algorithms from machine learning on big data, are highly awaited to help changing our perspective from a valve-centred to a myocardium-focused approach in managing patients with degenerative VHD.


Despite myocardial perfusion imaging (MPI) by cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera is largely used in the diagnosis and risk stratification of patients with suspected or known coronary artery disease (CAD), no data are available on the prognostic value of a regional MPI evaluation. We evaluated the prognostic value of regional MPI by the CZT camera in predicting clinical outcomes at the vessel level in patients with available angiographic data.P < 0.001). The receiver operating characteristics area under the curve for regional ITPD for the identification of vessel-related events was 0.81 . An ITPD value of 2.0% provided the best trade-off for identifying the vessel-related event. At multivariable analysis, both CAD ≥ 50% and ITPD ≥ 2.0% resulted in independent predictors of events.Five hundred and forty-one subjects with suspected or known CAD referred to 99mTc-sestamibi gated CZT-SPECT cardiac imaging and with available angiographic data were studied. Both regional total perfusion deficit (TPD) and ischemic TPD (ITPD) were calculated separately for each vascular territory . The outcome end points were cardiac death, target vessel-related myocardial infarction, or late coronary revascularization. The prevalence of CAD ≥ 50%, regional stress TPD, and regional ITPD was significantly higher in vessels with events as compared to those without (both Regional myocardial perfusion assessed by the CZT camera demonstrated good reliability in predicting vessel-related events in patients with suspected or known CAD. Myocardial perfusion imaging (MPI) by cadmium-zinc-telluride (CZT) camera has been largely validated in the diagnosis and risk stratification of patients with suspected or known coronary artery disease (CAD) –5. Noninn = 132) with previous coronary bypass surgery were excluded. Of the remaining 2074 patients, 620 had available coronary angiography. Patients (n = 30) referred to early revascularization (within 3 months) after MPI were not included, leaving 590 patients for the final analysis. Demographic information, as well as clinical history, cardiovascular risk factors, such as diabetes, hypertension, dyslipidemia, smoking history, family history of CAD, chest pain symptoms, electrocardiographic abnormalities, previous history of myocardial infarction or coronary revascularization, were collected. Patients were considered diabetic in the case of a previous diagnosis of diabetes mellitus or treatment with oral hypoglycemic drugs or insulin. Hypertension was defined as a known history of systolic blood pressure > 140 mm Hg or treatment with antihypertensive medication. Dyslipidemia was defined as a known history of dyslipidemia or the use of cholesterol-lowering medication. A positive family history of CAD was defined as the presence of CAD in first-degree relatives. All the data were verified and complemented with demographic and clinical information collected from medical records. The review committee of our institution approved this study, and all patients gave informed consent .A total of 2206 consecutive patients with suspected or known CAD, were referred to stress CZT-SPECT cardiac imaging between February 2016 and June 2020. For the present investigation, patients (−1 × minute−1 intravenous over 4 min). All patients were instructed to withhold beta-blocking medications, calcium antagonists for 48 h, and nitrates for 12 h before examination. For patients undergoing a pharmacological stress test, consuming caffeine was not allowed for 24 h before testing. Rest and peak stress heart rate and blood pressure were recorded; monitoring of heart rate, rhythm, and ECG were performed all along the stress protocol. Physical test endpoints were achievement of 85% maximal predicted heart rate, horizontal or down-sloping ST-segment depression > 2 mm, ST-segment elevation > 1 mm, moderate to severe angina, systolic blood pressure decrease > 20 mm Hg, blood pressure > 230/120 mm Hg, dizziness, or clinically important cardiac arrhythmia. At peak exercise or 4 min after dipyridamole infusion, a bolus of 99mTc-sestamibi was intravenously injected. In case of chest pain or other symptoms, as well as significant ST depression, 100 mg of aminophylline was administered intravenously.All patients underwent gated stress/rest MPI after intravenous injection of 99mTc-sestamibi (185 MBq for stress and 370 MBq for rest images) using a cardio-dedicated SPECT camera . Stress testing was performed using physical exercise by treadmill or dipyridamole , incorporating the extent and severity of perfusion defects and expressed as a percentage of the left ventricular (LV) myocardium, was calculated by an automated software program , using standardized segmentation of 17 myocardial regions; moreover, LV ejection fraction (EF) was automatically computed. The ITPD was defined as stress TPD—rest TPD. Both regional TPD and ITPD were calculated separately for each vascular territory: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) [The decision to refer patients to coronary angiography after MPI was made by the referring physicians. Coronary angiography was performed within 90 days before MPI in 242 patients and within 90 days after in 348 patients, using the standard Judkins method. No patients studied in the 3 months before MPI received treatment during coronary angiography. Results of coronary angiography were visually interpreted by experienced cardiologists, and significant CAD was considered in the presence of luminal diameter stenosis ≥ 50% in at least one of the three major vascular territories , 19.Patient follow-up was prospectively obtained by a questionnaire assessed during a phone call to all patients and general practitioners or cardiologists and by review of the hospital or physicians’ records by individuals blinded to the patient’s test results. The outcome was a composite end point of cardiac death, target vessel-related myocardial infarction, or late coronary revascularization (> 6 months after MPI), whichever occurred first. The cause of death was confirmed by a review of the death certificate, hospital chart, or physician’s records. Death was considered of cardiac origin if caused by acute myocardial infarction, congestive heart failure, valvular heart disease, sudden cardiac death, and cardiac interventional/surgical procedure related. Myocardial infarction was defined when more than 2 of the following 3 criteria were met: chest pain or equivalent symptom complex, positive cardiac biomarkers, or typical electrocardiographic changes . To defit-test and chi-square test were used to compare the differences in continuous and categorical variables, as appropriate. A P value < 0.05 (two-sided) was considered statistically significant. The receiver operating characteristics (ROC) area under the curve (AUC) was applied to evaluate the diagnostic ability of regional ITPD in identifying the vessel-related event and to establish the best trade-off between sensitivity and specificity for different cutoff points of regional ITPD. The optimal cutoff point was determined by the ROC curve based on the Youden index. Hazard ratios with a 95% confidence interval (CI) were calculated by univariable and multivariable Cox regression analysis. Variables showing a P value < 0.05 at univariable analysis were considered for multivariable analysis. Annualized event rate (AER), expressed as % person-years or as % vessel-years, was calculated as the cumulative number of events divided by person-time or vessel-time. Event-free survival curves were obtained by the Kaplan–Meier method and compared with the log-rank test. Statistical analysis was performed using STATA software .Continuous data are expressed as mean ± standard deviation and categorical data as a percentage. A Student two-sample Follow-up was 92% complete, leaving 541 subjects for the analysis. During a median follow-up of 27 months (range 7–56 months), 31 cardiac events occurred . The events were cardiac deaths in 4 (13%) patients, nonfatal myocardial infarctions in 7 (23%), and late coronary revascularizations in 20 (64%) subjects. Clinical characteristics and imaging findings of patients with and without events are summed in Table P < 0.001). The AUC for regional ITPD for the identification of vessel-related events was 0.81 . An ITPD value of 2.0% provided the best trade-offs for identifying vessel-related events  showed CAD ≥ 50% on coronary angiography, while 1193 (73%) did not. The vessel-related events were observed in 39 (2%) vessels. In particular, 6 patients experienced events on multiple vessels: 2 patients underwent PCI on 2 vessels during follow-up, and among 4 cardiac deaths, the event was assigned to all the stenotic vessels of each patient (3 vessels for 2 patients and 2 vessels for 2 patients). Regional imaging findings according to vessel-related events are reported in Table P < 0.05). Finally, event-free survival analysis by the Kaplan–Meier method was performed according to CAD and ITPD as shown in Fig. P < 0.001).The results of Cox regression univariable and multivariable analysis are depicted in Table To our knowledge, this is the first study analyzing the prognostic value of regional perfusion assessed by the CZT camera in predicting vessel-related events, in patients with suspected or known CAD and angiographic correlation. Our data highlight that regional ITPD is a significant predictor of vessel-related events. The prognostic significance of stress perfusion abnormalities assessed by the CZT camera in the prediction of adverse cardiac events has been extensively addressed. All published data confirmed that the presence of a normal scan is associated with a good outcome, whereas the degree of myocardial perfusion defect is a good predictor of cardiovascular events –13. EngbRegional myocardial perfusion assessed by the CZT camera demonstrated good reliability in predicting vessel-related events in patients with suspected or known CAD. In particular, an ITPD ≥ 2.0% resulted in an independent predictor in identifying high-risk vessels. These findings suggest that using a regional evaluation of myocardial perfusion may help in refining risk stratification and in identifying high-risk coronary stenosis at higher risk of events, in which a change in a patient management could be hypothesized.


Heart failure (HF) with preserved ejection fraction (HFpEF) is thought to be driven by increased cardiac afterload, which consequentially leads to left ventricular (LV) diastolic dysfunction. The ratio of LV diastolic elastance (Ed) to arterial elastance (Ea) significantly increases in older hypertensive women without HF and is coincident with cardiac structural alterations. Ed/Ea is reported to be a prognostic factor for all-cause mortality in patients admitted with HFpEF. In this short article, I provide a possible view of this novel index as having diagnostic potential for HFpEF in clinics and playing a prognostic role in HF with reduced ejection fraction (HFrEF). Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with increased hospitalizations, especially within the older population. After an older patient admitted with HFpEF is discharged, medical therapy aims to reduce the likelihood of their re-admission for HF and to ease the socioeconomic burden on healthcare. However, considering that Japan is expecting an increase in healthy life expectancy stemming from its super-aging society and declining population, it is important to reduce both re-admission for HF and all-cause mortality in ordinary people.Historically, HFpEF was thought to be driven by increased cardiac afterload, which consequentially was taken to lead to left ventricular (LV) diastolic dysfunction. There were no pharmacological agents that could reduce all-cause mortality in patients with HFpEF; sodium-glucose co-transporter 2 inhibitors showed no advantage in reducing all-cause mortality ,2, even To determine the prognostic factors in patients with HFpEF, important clinical variables including laboratory data such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and evidence of comorbidities must be adjusted in addition to age and sex during multivariable model analysis. Under these conditions, Ed/Ea is a prognostic factor for all-cause mortality in addition to re-admission for HF in patients with HFpEF . This isIt is unknown whether Ed/Ea level directly results in a poor prognosis in patients with HF with reduced ejection fraction (HFrEF). Reduced LV ejection fraction could improve to the normal range in cases of reversible ischemia or diabetic origin. Under these conditions, the Ed/Ea levels would change in accordance with changes in pathophysiological status on a moment-to-moment basis. By serially examining changes in Ed/Ea levels, one may reveal that the patients with reversible HFrEF could have a better prognosis. For example, the reversal of myocardial ischemia would cause the elevation of LV systolic function, leading to improved systolic blood pressure. Furthermore, this would recover LV diastolic function, which in turn could change depending on the severity of myocardial ischemia. When recovering from myocardial ischemia, the improvement of diastolic function requires a longer duration than that of systolic function;  thus, thIn conclusion, Ed/Ea, a prognostic factor for all-cause mortality in HFpEF, has a possible role to play in diagnosing HFpEF in clinics and may have an alternative significance in manipulating the patients with HFrEF.


In contrast to the advanced development of the left ventricular assist device (LVAD) therapy for advanced heart failure, the mechanical circulatory support (MCS) with biventricular assist device (BVAD) and total artificial heart (TAH) options remain challenging. The treatment strategy of BVAD and TAH therapy largely depends on the support duration. For example, an extracorporeal centrifugal pump, typically referred to as a temporary surgical extracorporeal right ventricular assist device, is implanted for the short term with acute right ventricular failure following LVAD implantation. Meanwhile, off-label use of a durable implantable LVAD is a strategy for long-term right ventricular support. Hence, this review focuses on the current treatment strategies and clinical outcomes based on each ventricle support duration. In addition, the issue of heart failure post-heart transplantation (post-HT) is explored. We will discuss MCS therapy options for post-HT recipients. The clinical data of mechanical circulatory support (MCS) for biventricular heart failure (BHF) is limited due to the low prevalence of treating severe right heart failure (RHF). The complexity of the BHF treatment strategy also makes the situation challenging. The reason for the complexity is that the BHF treatment strategy will be determined with the consideration of support duration for both ventricles. Furthermore, the clinical scenario will be important to determine the device; for example, the device selection may differ with the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles and baseline patient characteristics, including the diagnosis , 2.BHF support conditions have combinations of chronic/temporary support duration and left/right ventricle, which is as follows: (1) Chronic left ventricular (LV) support with chronic right ventricular (RV) support; (2) Chronic LV support with temporary RV support; 3) Temporary LV support with chronic RV support; and (4) Temporary LV support with temporary RV support. In this review, we will focus on 1, 2, and 4, because the temporary LV support with chronic RV support situation is quite rare due to RHF pathogenesis  patients . Since tThere are two options for chronic LV support with chronic RV support: using a continuous-flow (CF) left ventricular assist device (LVAD) and using one more LVAD as a right ventricular assist device (RVAD); or a total artificial heart (TAH). Patients requiring RVAD after LVAD implantation, or lower INTERMACS patient profile patients with biventricular failure diagnosis, are the most frequent example for this clinical situation.® (HM3)  pivotal and post-pivotal trial study, 4.1 and 7.4% of patients, respectively required BVAD , according to the Twelfth INTERMACS Report, approximately 2,700–3,000 patients in the United States (US) receive an LVAD implant each year; and, in 2020, CF LVADs have accounted for the most , which is mainly used in pediatric patients. Due to anatomical and physiological limitations  described that survival outcomes among the BVAD patients (BVAD was defined as LVAD and RVAD implanted in the same operation) were 68% at 6 months and 62% at 12 months  showed that survival at 1 year was 53.2% and 33.9% at 2 years    –39, and  Sweden) –42.via the femoral vein) into the right atrium (RA), and the outflow cannula is placed directly, or (via a sutured prosthesis graft) into the pulmonary artery (PA) . The advantage of this system is that it is easy to place, so if RV failure presents during the HM3 implantation procedure, the sRVAD can be placed through a sternotomy. Also, this system is able to provide much larger flows than a veno-arterial extracorporeal membrane oxygenation system. The disadvantage of this system is that it may require a re-sternotomy to explant the sRVAD, which increases the risk of infection.For chronic LV support with short to intermediate RV support duration (0–30 days), an extracorporeal centrifugal pump has been widely used. Customarily, this configuration is called a surgical extracorporeal RVAD (sRVAD). In sRVAD, the inflow cannula is placed directly, or (ery (PA) , 43. BotThe RVAD implantation following LVAD implantation occurs within 0–2 days , and a s® , described that 77.4% of patients reached the primary end-point which was survival at 30 days, or discharge after device explant, or induction of anesthesia for a long-term therapy , has been increasingly used as temporary LV support, and sometimes it is used in combination with a p-RVAD. In a retrospective study among 5 U.S. hospitals (n = 20),with a combination of left side Impella and Impella RP, called BiPella , such as Impella BiPella , it was  BiPella . The adv BiPella , 50–52.de facto goals of current end-stage HF treatment, which has an overall median survival of 12.5 years, and a conditional survival curve of 14.8 years for those who survived the first year (n = 26) reported that 42% of patients with late graft failure were treated with BVAD and TAH   (50 mL); this size difference influences device location inside the patient’s chest. HM3 is likely to be implanted into the free wall of the RA. The pump is wrapped in Gore-Tex® , or a polytetrafluoroethylene sheet, and is placed as it protrudes into the right thoracic cavity through a slit in the pericardium (p = 0.02), and did not show significant differences in postoperative complications, such as pump thrombosis. Therefore, a small, durable pump implanted into the RA appears to be a viable option for RVAD used in chronic BVAD.Regarding chronic BVAD, dual HM3 is the most commonly used configuration. The adverse event most noted is RVAD pump thrombosis, which has been consistently reported with occurrence of 36–37% , 57, 58.icardium , 29. Alticardium . RA-implIn conclusion, the percutaneous temporary RVAD may increase its prevalence in temporary biventricular support. As for long-term biventricular support, the development of a durable, specifically designed RVAD, with a wide operation range and suitable inflow cannulas, is expected. Furthermore, the development of a durable BVAD, including TAH, may provide a valid solution for the management of heart failure among post-HT patients.TK: manuscript preparation. CM: critical manuscript review. KF: critical revision of article. JK: critical revision and approval of article. All authors contributed to the article and approved the submitted version.


Obesity is a prominent public health problem that has increased cardiovascular mortality risks. However, the specific effects of obesity, independent of comorbidities, on cardiac structure and function have not been well clarified, especially those effects on the right ventricle (RV). Cardiovascular magnetic resonance (CMR) tissue tracking can assess detailed RV mechanical features. This study aimed to evaluate RV strain using CMR in uncomplicated obese adults and assess its association with fat distributions.A total of 49 obese patients and 30 healthy controls were included. The RV global systolic function and strain parameters based on CMR were assessed. Body fat distributions were measured with dual X-ray absorptiometry. RV function indices of obese patients were compared with those of healthy controls. Correlations among related body fat distribution parameters and RV function indices were conducted with multivariable linear regression.P < 0.05), while LV and RV ejection fractions were not significantly different between the two groups (P > 0.05). Multivariable linear regression analysis demonstrated that android fat% was independently associated with longitudinal PS , longitudinal PDSR , and circumferential PSSR . Trunk fat% was independently associated with longitudinal PSSR . In addition, the strongest correlations of circumferential PDSR were BMI and gynoid fat% .Compared with healthy controls, the obese group had impaired RV strain with lower global longitudinal peak strain (PS), longitudinal peak systolic strain rate (PSSR), circumferential and longitudinal peak diastolic strain rates (PDSR)  has a negative effect on subclinical RV function, while peripheral obesity (gynoid fat distribution) may have a positive effect on it.Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476). Overweight and obesity have rapidly increased global disease burden over the last decades. To date, no country has successfully reversed this obesity epidemic , 2. SincRV function assessment has been known to provide a prognostic role in several cardiac diseases . PreviouBody mass index (BMI) is the most widely used index of general obesity and is associated with other cardiovascular disease risks. Previous studies have found that different regions of fat deposition have various effects on the heart. For example, one study showed that visceral fat rather than subcutaneous fat was significantly associated with decreased RV strain . Dual X-2 (ranging from 27.5 to 34.9 kg/m2) and 30 healthy volunteers (18.5 ≤ BMI ≤ 23.0 kg/m2) between 18 and 60 years old from September 2019 to September 2021. Subjects were excluded if they had any of the following conditions: hypertension or diabetes measured by oral glucose tolerance; history of cardiovascular diseases or history of any cardiovascular procedures; major systemic diseases that could affect the myocardium, such as connective tissue diseases and sarcoidosis; endocrine disease, such as hyperthyroidism and hypothyroidism; metabolic diseases, such as a history of alcohol abuse or amyloidosis; obstructive sleep apnea; any contraindication to CMR imaging. The study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of the West China Hospital in Sichuan University. Written informed consent was obtained from all study participants.We prospectively recruited 49 obese subjects defined by a BMI ≥ 27.5 kg/mBaseline data of the participants were collected, including medical history, anthropometric measurements (weight and height), heart rate, and blood pressure. Fasting blood glucose and serum lipid profiles, including triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), were also measured.2) was calculated as weight (kg) divided by height squared (m2). According to the Chinese criteria, BMI was categorized into the following three groups: healthy weight (18.5-23.0 kg/m2), overweight (23.0-27.5kg/m2), and obese (≥27.5kg/m2) (Waist circumference (WC) was measured at the midway between the last rib and the iliac crest, and hip circumference (HC) was measured at the largest diameter of the hip. WC and HC were measured to the nearest 0.5 cm. The waist-to-hip ratio and waist-to-height ratio were calculated. Body mass index (BMI) (kg/m.5kg/m2) . Total f.5kg/m2) . Percent2, matrix size = 208 × 166, and a temporal resolution = 39.34 ms.CMR examinations were performed using a 3 Tesla whole-body scanner  with an 18-channel phased-array body coil on patients in a supine position. With a standard ECG-triggering device, data was acquired during the end-expiratory breath-hold period. A segmented breath-hold balanced steady-state free precession (bSSFP) sequence was used to obtain 8–14 contiguous cine images from the base to the apex in the short-axis view and the two- and four-chamber cine images in the long-axis view. The bSSFP parameters are as follows TR/TE = 3.3/1.22 ms, flip angle = 41°, slice thickness = 8 mm, field of view = 360 × 320 mmAll CMR data was imported to commercially available software . Two radiologists with more than 3 years of CMR experience analyzed the measurements and were blinded to the subject status (obesity vs. control).Epicardial adipose tissue (EAT) represents high-signal intensity region between the myoepicardium and parietal pericardium. The EAT volume was measured on the short-axis cine slices during the end-diastolic phase. The myoepicardial and parietal pericardial contours were manually delineated per slice, extending from the mitral valve hinge down to the ventricular apex. High-signal intensity regions between the myoepicardium and parietal pericardium were semi-automatically traced and calculated, excluding blood vessels.The endocardial and epicardial contours of the right ventricle (RV) and left ventricle (LV) myocardium on the short-axis cine images were manually traced during the end-diastolic and end-systolic phases of the CVI42 short-3D module software. The global conventional functional parameters, namely EF, end-diastolic volume (EDV), end-systolic volume (ESV), and LV mass at end-diastole, were automatically computed. In addition, the average LV regional values for 16 myocardial segment thicknesses (American Heart Association standard segmentation model) were also automatically computed. Finally, the LV thickness and interventricular septal (IVS) thickness averages were calculated.L0, in end-diastole) to its maximum length : myocardial strain = (L − L0)/L0. Strain rate represents the rate of length shortening  and IVS thickness were assessed in obese patients. Pearson's correlation coefficient was used to determine the correlations between regional fat, blood lipids, and RV functional parameters  in whole population. Stepwise multivariable linear regression was used to estimate the associations between regional fat distributions and RV functional parameters in whole population. Related fat distribution, including android fat%, gynoid fat%, trunk fat%, peripheral fat%, visceral fat%, EAT were entered in univariable analyses. Variables with statistical significance in the univariable analyses were then included in a stepwise multivariable analysis. In order to determine the association between obesity and RV function independent of growth differences, age and sex were added in multivariable analyses. The intraclass correlation coefficient (ICC) was used to evaluate both inter-and intra-observer variabilities. A P < 0.05 indicated statistical significance.All statistical analyses were performed using SPSS software . Continuous data with normal distributions were compared between the obese and healthy groups with the student's 2) and 30 healthy controls (19.7 ± 1.1 kg/m2), and the baseline characteristics of the patients are shown in This study included 49 obese subjects  compared with the controls. Compared with the healthy controls, obese patients exhibited greater RV sizes , LV sizes , LV geometric parameters (LV mass and LV average thickness), and IVS average thickness. For RV strain, the obese group showed lower global longitudinal PS, PSSR and PDSR, circumferential PDSR, and preserved circumferential PS and PSSR compared with the control group  for all obese patients and neither were statistically different between the two groups ; whereas RV size (RVEDV and RVESV), LV size (LVEDV and LVESV), LV mass, LV average thickness, and ISV average thickness showed weak-moderate negative correlations with RV strain indices (r = −0.3 to −0.5). Among them, LV average thickness was strongest for the longitudinal PS (r = −0.504). In addition, LVEF was positively correlated with RV longitudinal PS, PSSR, and PDSR (r = 0.3 to 0.4); LV longitudinal, circumferential, and radial PS had positive correlations with the RV strain parameters (r = 0.3 to 0.4) .BMI, EAT, android fat%, and trunk fat% were positively correlated with fasting blood glucose, triglycerides, total cholesterol, and LDL (r = 0.3 to 0.6), while were negatively correlated with HDL (r = −0.4 to −0.6). In contrast, gynoid fat% had negative associations with triglycerides, total cholesterol, and LDL (−0.2 to −0.5), while had a positive association with HDL (r = 0.484); peripheral fat% was negatively associated with fasting blood glucose and total cholesterol  .Univariable analysis showed that BMI, android fat% and trunk fat% were negatively associated with longitudinal PS, longitudinal and circumferential strain rate (PSSR and PDSR) (r = −0.3 to −0.5). Visceral fat% and EAT were negatively associated with circumferential PDSR and longitudinal PS, PSSR and PDSR (r = −0.3 to −0.4). In contrast, gynoid fat% and peripheral fat% were positively associated with circumferential PDSR, and longitudinal PS, PSSR and PDSR (r = 0.4 to 0.5); gynoid fat% was positively associated with RVEF (r = 0.264) .P < 0.001, model R2 = 0.219), longitudinal PDSR , and circumferential PSSR . Trunk fat% was independently associated with longitudinal PSSR . In addition, the strongest correlates of circumferential PDSR were BMI and gynoid fat%   .The intra- and inter-observer variability for EAT quantifications and strain parameters are summarized in In this study, we compared RV functional parameters in adults with uncomplicated obesity with those in normal controls using CMR and assessed associations between fat distributions and RV function in whole population. The main findings were as follows: (1) although the RVEF was within the normal range in both groups, the subjects with obesity had impaired RV myocardial contractility manifestied by lower longitudinal PS, longitudinal PSSR, and circumferential and longitudinal PDSR; (2) Decreased LV longitudinal and circumferential PS and preserved LVEF in obese group compared with healthy group. (3) the individuals with obesity had cardiac remodeling with greater RV size, LV size, LV myocardial mass, and LV wall thickness compared with controls; (4) the impaired subclinical RV function was associated with cardiac remodeling; (5) BMI, as an index of overall obesity, was independently associated with subclinical RV dysfunction. In addition, central fat distribution indicators (android fat% and trunk fat%) were negatively correlated with subclinical RV function, whereas peripheral fat distribution indicator (gynoid fat%) was positively correlated with it. Until now, no studies have documented RV strain changes in obese adults with no clinical signs or comorbidities using CMR tissue tracking and the associations between DXA-related fat distributions and RV function.Our study revealed no statistical differences for RVEFs between the two groups, indicating a lack of global right ventricular systolic functional impairment. This result is consistent with that of previous echocardiographic studies of obese adults without known cardiovascular diseases , 7. Neve2), but not in mild-to-moderate obesity  compared with those of the normal subjects in our study. A echocardiographic study demonstrated that RV volumes significantly increased only in the severely obese group  in obese adults. LV myocardial remodeling was negatively associated with the RV strain parameters, which indicated that RV function could be impacted by LV myocardial remodeling through ventricular-ventricular interactions. Similar results were also reported in a CMR study with uncomplicated obese children . In an eOur study described the linear relationships between regional fat distributions and RV functional assessments, and the results showed that central fat distribution indicators (android fat% and trunk fat%) had deleterious effects on subclinical RV function, whereas peripheral fat distribution indicator (gynoid fat%) had a positive effect on it. Notably, our result showed that visceral fat and EAT volume were negatively associated with RV strain in univariate analysis, while no linear relationship with RV strain parameter in multivariate analysis. Previous CMR studies on obesity with no complications have reported that visceral fat, EAT volume or area had linear relationships with LV subclinical dysfunction in multivariate analysis , 27. HowOne explanation for the different effects of regional fat distributions on RV function was dyslipidemia. Our study revealed that central obesity parameters (android fat and trunk fat) were positively correlated with triglycerides, total cholesterol, and LDL, while were negatively correlated with HDL. The result is consistent with previous researches which demonstrated that central obesity parameters (android fat or trunk fat distributions) had positive associations with triglycerides and LDL levels, while they had negative associations with HDL levels –30. In cIn addition, android fat was correlated with higher blood pressure , 41, whiThere are several limitations in this study. First, this was a cross-sectional study, and we could not determine whether subtle RV contractile impairments cause heart failure with obesity progression and whether these changes can be reversed. Therefore, longitudinal studies are needed to examine dynamic cardiac changes and explore the underlying factors that reverse these changes. Second, past studies have indicated that multiple key inflammatory mediators and insulin resistance are consistently associated with obesity and obesity-related comorbidities. However, we did not examine inflammatory markers and insulin resistence in this study. These laboratory data should be measured and discussed in subsequent studies to clarify the mechanisms of myocardial damage in obese patients.Extensive subclinical RV dysfunction is found in uncomplicated obese adults. BMI, as an index of overall obesity, is independently associated with subclinical RV dysfunction. In addition, central obesity (android fat and trunk fat distributions) has a negative effect on subclinical RV function, while peripheral obesity (gynoid fat distribution) may have a positive effect on it.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of the West China Hospital in Sichuan University. The patients/participants provided their written informed consent to participate in this study.JLiu, JLi, LP, and NT: conception and design and provision of study materials or patients. LP and NT: administrative support and final approval of manuscript. JLiu, JLi, LP, HP, WH, XL, and XZ: collection and assembly of data. JLiu, JLi, and LP: manuscript writing. All authors: data analysis and interpretation.This work was supported by the National Natural Science Foundation of China (Grant Number 81601462), the Key Research & Development Project of Science and Technology of Sichuan Province (Grant Number 2021YFS0142), and 1.3.5. project for disciplines of excellence, West China Hospital, Sichuan University (Grant Number ZYGD18017).XZ was employed by Siemens Healthineers Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Clinical factors, morphology of bridge by quantitative coronary analysis and ten-year long mortality data were collected. The LAD-MBneg group was associated with younger age and decreased incidence of diabetes mellitus, as well as with increased minimal diameter to reference diameter ratio (LAD-MBneg 54.5 (13.1)% vs. LAD-MBpos 46.5 (16.4)%, p = 0.016), while there was a tendency towards longer lesions and higher vessel diameter values compared to the LAD-MBpos group. The LAD-MBpos group was associated with increased mortality compared to the LAD-MBneg group. The analysis of our data showed that morphological parameters of LAD bridge did not influence long-term mortality, either in the overall population or in the LAD-MBneg patients. Morphological parameters of LAD bridge did not influence long-term mortality outcomes; therefore, it suggests that anatomical differences might not predict long-term outcomes and should not influence therapy.Although myocardial bridging (MB) has been intensively investigated using different methods, the effect of bridge morphology on long-term outcome is still doubtful. We aimed at describing the anatomical differences in coronary angiography between symptomatic and non-symptomatic LAD myocardial bridges and to investigate the influence of clinical and morphological factors on long-term mortality. In our retrospective, long-term, single center study we found relevant MB on the left anterior descendent (LAD) coronary artery in 146 cases during a two-year period, when 11,385 patients underwent coronary angiography due to angina pectoris. Patients were divided into two groups: those with myocardial bridge only (LAD-MB Myocardial bridging (MB) is a relatively common congenital coronary anomaly, in which a segment of coronary artery takes an intramuscular course that causes vessel compression during systole . The preWhile myocardial bridging is generally considered as a benign phenomenon and related serious events are uncommon, many cases have been reported where MB was considered responsible for a wide variety of cardiovascular symptoms and complications, including angina, acute coronary syndrome, left ventricular dysfunction, arrhythmias and even sudden cardiac death ,7,8,9,10Despite these data, the prognostic factors and the clinical evaluation of MB has remained limited. Moreover, the relationship between anatomy and potentially dangerous MBs has not yet been clarified. In this retrospective, high-number population-based clinical study we aimed at describing the anatomical differences between symptomatic and non-symptomatic LAD myocardial bridges found on coronary angiography and to investigate the influence of clinical and bridge morphological factors on long-term mortality.A total of 11,385 diagnostic coronary angiographies were performed (indications according to the current European guidelines) in our cardiology center, at the Heart and Vascular Center of the Semmelweis University of Budapest between 25 March 2009 and 12 March 2011. Ethical approval (of enrolled patients) was obtained from the Central Ethics Committee of Hungary, with all of the participants completing informed consent forms, which were in conformity with the WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects.n = 57), see n = 146) were divided into two groups according to accompanying coronary artery disease. Seventy-eight patients were referred for angiography because of typical angina pectoris, and, except for LAD MB, no other underlying, epicardial coronary disease was found (LAD-MBneg group). Sixty-eight patients were also referred for angiography because of angina pectoris, but in this group significant coronary artery disease was also revealed in addition to the LAD MB (LAD-MBpos group). In the LAD-MBpos group coronary plaque was considered significant if lumen narrowing (>50% in diameter) of significant epicardial coronary arteries (>1.5 mm diameter) was observed, and we provided therapy according to current guidelines. Ad-hoc percutaneous coronary intervention was performed in 23 (34%) of these patients, with indications according to current guidelines.We enrolled a total of 203 patients (1.78%) with a clear presence of MBs . To obtain a more consistent study group, we excluded patients with MBs affecting arteries other than the LAD and where any other obvious cause of angina pectoris was presented . Measurements were obtained with digital calipers. All of the MBs were measured in lateral view  in end-systole and end-diastole by an expert interventionist . Three mIn addition to these data, we also recorded height, weight, sex of patients and presence of main cardiovascular risk factors, such as diabetes mellitus, hypertension, and dyslipidemia.We collected information about the patients’ mortality by phone visit and we also checked data on survival status  on 1 April 2020.GraphPad Prism  and SPSS  were used for the statistical analysis.neg and LAD-MBpos groups directly. In the case of normal distribution of continuous data, the unpaired t-test was used. In the case of non-normal distribution, the Mann–Whitney U-test was utilized. To compare parameters with binomial outcomes , the Chi-square test was performed.We compared the LAD-MBMortality rate was summarized by constructing Kaplan–Meier curves, and the distributions of the groups were compared by a log-rank test. For this analysis, median values were used to dichotomize continuous variables .p value < 0.15 by single variable analysis were entered into the multiple variable Cox regression analysis with the parameters of myocardial bridge . Hazard ratio was given with 95% CI interval and p value was provided for the significance of different parameters on clinical outcomes.Single variable Cox regression analysis was used for the search of predictors of death from the data of the patients . All variables associated with a Continuous data are expressed as means with standard deviation.p value < 0.05 was considered significant for all tests.A pos and LAD-MBneg groups regarding sex. The LAD-MBpos patients were characterized by older age and increased presence of type 2 diabetes mellitus, while there was no statistical difference between the presence of hypertension or hyperlipidemia and BMI.Demographic and clinical data and LAD-MB morphological data are summarized in neg group was characterized with more severe morphological features. The shortening of MB  significantly decreased, while the length and reference diameter showed a strong tendency towards the decreased value in the LAD-MBneg group compared to the LAD-MBpos group. The minimal diameter showed no differences between our groups.MB morphological data are also presented in neg group; thus, the all-cause mortality rate in this population with isolated LAD-MB was 10.3% for this follow-up period. We searched for differences between the two prespecified subgroups: the Kaplan–Meier analysis revealed significant disparity in mortality between the LAD-MBneg and LAD-MBpos groups (Long term follow-up: The average follow-up period of this patient population was 3115 (249) days, almost ten years. When we checked survival status, we found that mortality was 16.4% in the overall LAD-MB population. Eight people died in the LAD-MBs groups .neg group. As a first step, we determined factors from the demographic and clinical data using single variable Cox regression  and influencing factors from single variable analysis. Our results show that none of the morphological parameters influence mortality  than by angiography (0.4–15.8%) ,17,18. AThe morphological parameters of these bridges, measured by quantitative coronary analysis , are also comparable with the data from literature  1,19,20,2019,20.Clinical adjudication of myocardial bridges is often difficult. On the one hand, there is an essential discrepancy between the high prevalence of the phenomenon accompanied with excellent prognosis  ,23,24,25pos patients were older and could be characterized by an increased prevalence of type 2 diabetes mellitus and were associated with higher mortality compared to the LAD-MBneg group  was also present, to examine whether in this population–where myocardial bridge might be only an accidental finding–there are different clinical factors and bridge features compared to patients with isolated LAD MB . The cuteg group . From aneg group –despite  studies . Symptom studies .neg group is comparable with 1.1% average yearly mortality in 45–59 years old men and women in Hungary . Therefore, we investigated in the LAD-MBneg group whether the anatomical parameters measured by QCA might influence long-term mortality (Isolated myocardial bridging is generally considered as a benign condition. Beside appealing, unique clinical cases ,7,8,9, sortality . We founortality , Table 2The main limitations of the study were the retrospective design of the study and the lack of non-invasive assessment of MB anatomy with MDCT and invasive imaging techniques, such as IVUS or OCT. Although these measurements, which are not routinely used, would be more precise to describe bridge morphology, they require more financial and medical effort and are associated with increased radiation time. We also emphasize that no healthy control group was investigated to compare mortality directly to these individuals.Here we provided a retrospective, single-center study using long-term follow-up. Morphological parameters of angina-associated, isolated LAD bridges were more severe compared to bridges that were accidentally found in patients with obstructive coronary disease. Our ten-year long follow-up period showed that morphological parameters measured with QCA did not influence long-term mortality outcomes; therefore, it suggests that anatomical differences might not predict long-term outcomes. Our data underline the benign nature of myocardial bridge.