Cardiogenic shock (CS) remains a highly lethal condition despite many efforts and new interventions. Patients presenting with a rapid onset of hemodynamic instability and subsequent collapse require prompt and appropriate multimodality treatment. Multiple etiologies can lead to heart failure and subsequent shock. As the case prevalence of heart failure increases worldwide, it is of great importance to explore all manners and protocols of presentation and treatment present. With research primarily focusing on CS due to cardiac left-sided pathology, few assessments of right-sided pathology and the subsequent clinical state and treatment have been conducted. This review aims to present an in-depth assessment of the currently available literature, assessing the pathophysiology, presentation and management of CS patients due to right heart failure. Cardiogenic shock (CS) describes a life-threatening circulatory failure resulting in high rates of mortality, despite a profound advancement in treatments that has been seen in recent years. In fact, with in-hospital mortality reaching up to 50% in some studies  and the A wide array of etiologies could lead to the manifestation of CS, including both mechanical and structural abnormalities starting with acute myocardial infarction (AMI), as well as other causes leading to acute and chronic heart failure (HF). While there is an abundance of scientific literature assessing the association between AMI and CS relating to its pathogenesis, management and prognosis, there is relatively scarce knowledge when it concerns other etiologies. In particular, causes manifesting as right heart failure (RHF) resulting in CS have gained less focus, with fewer in-depth assessments conducted.HF is described as a state of either inadequate cardiac contraction or the impairment of ventricular filling that leads to elevated intracardiac pressure and/or failure of the heart to adequately perfuse organ systems. Some relate to HF and CS as a continuum of the same disease spectrum, even at times approaching CS as an exacerbation of HF. HF could be dissected into subcategories by acuity and by the predominant chamber of the heart that is involved, with each subtype characterized by different symptomatology and prognostic qualities. In fact, this condition is now considered one of the leading causes of morbidity and mortality in the world, with an estimated prevalence of up to 2% in developed countries; this is expected to be on the rise with an aging population globally .Though CS associated with RHF represents only 5% of CS patients, based on recent data, RHF rates are rising. This is thought to be due to the increased life expectancy, the improvement in diagnostic modalities and the increased awareness. Additionally, a substantial quantity of RHF cases are a result of left ventricular (LV) dysfunction, thus further increasing the prevalence ,5. It isIn this report, we sought to summarize the contemporary understanding in the scientific literature regarding the role of predominantly right-sided cardiac disease in CS with respect to clinical manifestation, diagnosis, treatment and prognosis.(1)Hypotension—with a systolic blood pressure <90 mm Hg for at least 30 min or the requirement of supportive measures to maintain the systolic blood pressure at 90 mm Hg.AND(2)2.Cardiac index ≤ 2.2 L/min/mAND(3)Pulmonary capillary wedge pressure greater than or equal to 15 mm Hg.CS is an acute hemodynamic state of hypo-perfusion caused by decreased CO, which results in multi-end-organ damage. CS has been defined in various ways, and one of the most common and practiced definitions arises from the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, which proposes the following criteria :(1)HypotThe SCAI shock classification  defines The further delineation of CS could be by the dominant side of the heart that is involved, or it could also be described as biventricular shock when the simultaneous failure of both the right and the left chambers occurs . Additio [The diagnosis of RVF is based on the extent of ventricular impairment, using the central venous pressures (CVP), pulmonary capillary wedge pressure (PCWP) , pulmonaressure)  and righessure))  as indicessure))   criteria. RHF, defined by INTERMACS, is based on two parameters: the documented elevated central venous pressure (CVP) and manifestations of elevated CVP in patients with symptoms or findings of persistent RVF. Elevated CVP can be documented using direct measurement with a CVP or right atrial pressure >16 mm Hg, a significantly dilated inferior vena cava with the absence of inspiratory variation by echocardiography or elevated jugular venous distension at least half-way up the neck in an upright patient. Elevated CVP can manifest as peripheral edema , ascites or palpable hepatomegaly on physical examination or by diagnostic imaging, or it can manifest as evidence of worsening hepatic  or renal dysfunction .The Academic Research Consortium definition for RHF further divides patients based on the time of onset and duration. These criteria depict the urgency of the implantation of mechanical assist devices .When classifying CS due to RVF, an alternative form of classification is implemented, based on the underlying physiological mechanisms that cause CS. These include contractility failure, pressure overload secondary to LV dysfunction or other causes of pulmonary HTN, volume overload secondary to right-sided valvular insufficiency and volume overload secondary to an increase in the venous return or following LVAD implantation .The high sensitivity of the RV to changes in pressure originates from the nature of the RV, with its high-compliance, low-resistance pulmonary circulation, which makes it suited to adapt to changes in volume rather than pressure . In factAdditionally, the ventricular shapes of the two ventricles differ—the LV has an ellipsoidal shape, while the RV has a more triangular shape when assessed from the anterior frontal view and a crescent shape when viewed in a cross-sectional cut. Other factors influence the reduced strength generated by the RV, such as the different consistency of the ventricle compared to that of the left. The RV consists of circumferential and longitudinal orientations, while the LV obliquely arranges myofibers superficially and longitudinal myofibers in the sub-endocardium, with predominantly circular myofibers in between. This arrangement makes the LV more durable, with reduced points of frailty due to the interchanging fiber arrangement . AnotherIt Is important to note that, with the two ventricles sharing a common septum, this union affects the function of each ventricle, particularly that of the right. With the contraction of the oblique muscle of the LV, with a circular rotation and an LV contractile twist, a longitudinal movement of the heart occurs, with an anchoring source of the septum. This sends force to the RV, meaning that the LV is responsible for a portion of the contractile force of the RV.As mentioned above, hypoperfusion is the landmark of cardiogenic shock, and once it is sensed by carotid baroreceptors and juxtaglomerular cells in the kidney, a reflexive sympathetic and neurohormonal response occurs. An increase in catecholamines leads to vascular endothelial constriction. With low perfusion, the renin–angiotensin–aldosterone axis is activated, consequently promoting salt and water retention. These steps result in an increased myocardial afterload and circulating plasma volume. If treatment is not promptly applied, a cycle of decreasing cardiac output (CO) and progressive volume overload ensues, leading to a reduction in coronary artery perfusion pressure, myocardial ischemia, worsening cardiac function and circulatory collapse .When examining an RV insult and its progression to shock, acute damage and subsequent failure lead to a reduction in the LV preload, reduced CO and shock . This isVolume overload can also contribute to RV failure and subsequent CS in special circumstances involving the use of mechanical support devices. A common instance would be a congested state after LVAD implantation. LVAD unloads the LV and derives an increased venous return to the right side of the heart, which can exacerbate pre-existing RV failure .With the volume expansion and the subsequent rise in pressure, the pressure–volume loop of the right ventricle shifts, causing suboptimal ejection and cardiac function .Right heart involvement in CS could also be approached by dividing the pathophysiology according to the higher afterload the ventricle needs to work against, the declined contractility or the reduced preload of the RV. While, physiologically, the RV has an advantage of pumping blood into a low-compliance pulmonary vasculature, in diseased states such as heart failure, pulmonary hypertension or acute pulmonary embolism, a rise in the RV afterload increases RV pressures and volumes and consequently reduces the RV stroke volume . It is nAdditionally, it is essential to note that acute insults to an already ailing heart, such as chronic heart failure, can lead to CS. With the gradual increase in pressure and the more indolent decline in stability, the RV can become engorged, particularly in cases where the pericardium is intact. This can subsequently lead to the impairment of the LV chamber, impeding LV filling and equalizing biventricular diastolic pressures. RV systolic and biventricular diastolic dysfunction reduces CO, reducing coronary blood flow and worsening peripheral and abdominal volume accumulation. This could potentially lead to biventricular heart failure. This state is a deadly cycle, as, by disturbing the LV, reduced left-sided heart (LH) filling is more likely to cause RV dilation and ventricular interdependence and further hamper the RV output .RV–AMI, which occurs acutely, has strong hemodynamic implications, with approximately 25% to 50% of RV infractions being hemodynamically significant due to reduced contractility . The occHemodynamic instability depends upon the extent of the ischemia and infarcted myocardium. Furthermore, elevated filling pressures of the right side of the heart also cause coronary sinus congestion, which deprives the myocardium from coronary blood flow and can provoke RV ischemia and worsen RV function . SubsequAdditionally, cardiac tamponade, a pericardial emergency with fluid accumulation, is a worrisome form of CS which can impair RV function . The rapInflammation of the myocardium, also known as myocarditis, can potentially damage the integrity of the muscle, leading to a decline in RV contractility. There are several causes that lead to myocarditis, most prominently viral, microbial and autoimmune. Viruses represent a major pathogenic factor, which include enteroviruses such as Coxsackie B virus, erythroviruses , adenoviruses and herpes viruses . In the Other infectious causes of acute functional impairment include systemic infection and sepsis, which have been shown to increase pulmonary vascular pressure and propose both to HF and CS . This isAcute LV failure can cause congestion and, in severe cases, lead to acute RV decompensation and shock . SimilarAdditional causes, though less prevalent, include various cardiac surgeries that can lead to CS. RV failure in these cases is caused by a volume overload through complications of myocardial ischemia and arrhythmias due to surgery . FurtherFor patients suffering from chronic right HF from various causes , even a slight insult can lead to CS, especially among chronic RVD with an elevated pulmonary afterload. A second acute hit due to either an ischemic event, volume overload or intra/post-operative complications could definitely lead to RV-predominant CS .The diagnosis of CS is a moltimodility-dependant process, combining clinical symptomatology, physical findings and hemodynamical and echocardiographic assessement. Using these tools, an acurate portrayal of a clincal state can be achived .The general presentation of CS patients tends to be unpredictable, though undeniably in severe distress. Patients are most commonly described as ‘cold and wet’, referring to cold extremities and pulmonary congestion. This is usually coupled with oliguria (urine output < 30 mL/h), dizziness and mottled skin. Once severe, confusion and alterations in one’s mental status can be present . SymptomNonetheless, in patients with CS due to an RV MI, the presentation varies, with some remaining asymptomatic, while others experience severe hypotension. Patients present with dyspnea less frequently and more commonly have general malaise prior to medical intervention . NotablyCS events with a prominent cardiometabolic phenotype  are more likely to have right heart dysfunction and liver injury. This is particularly true for patients suffering from more chronic RHF and subsequent CS. Cardiogenic cirrhosis includes the spectrum of hepatic disorders that occur secondary to hepatic congestion due to cardiac dysfunction, most prominently originating in the RV . The symExaminations can yield several findings. Jugular venous distention with prominent v waves, an evident hepatojugular reflux and peripheral edema can be present. In severe cases, anasarca can develop. Additionally, hepatomegaly and splenomegaly can develop due to systemic congestion. When auscultating, a holosystolic murmur of tricuspid regurgitation might be present. Though the blowing murmur may be absent in patients with acute RVF, a hepatic pulse and signs of concomitant LV dysfunction can be heard. Furthermore, a paradoxical pulse can be felt ,40.Overall, hemodynamic change and instability are prominent characteristics of CS. Hypotension, a common feature of CS, is present in an overwhelming majority of patients, though other hemodynamic alterations can occur as well, such as a narrow pulse pressure . Though The pulmonary artery index pressure (PAPI) is a crucial parameter used to assess RV function, and it is defined as the ratio between pulmonary artery pulse pressure and right atrial pressure. A PAPI of <1.0 is a highly sensitive indicator of RV failure in the setting of an acute myocardial infarction . RV stroNotably, the cause of CS can also lead to different hemodynamic alterations. Heart failure, pulmonary hypertension or acute pulmonary embolism can all result in a rise in RV afterload and increased RV pressures and volumes followed by reduced RV SV . HF patiAlterations in electrical activity are expected due to the potential damage to the atrioventricular and sinoatrial nodes. This is more often followed by supraventricular arrhythmias and sinoatrial or complete atrioventricular blocks . AdditioDue to hypoperfusion and systemic congestion, subsequent sharp increases in circulating transaminases and lactic acidosis are particularly more likely to be present among patients with RV damage and CS due to RV impairment ,11. WithCardiorenal syndrome, a state of acute decompensated heart failure leading to kidney injury, could accompany right-sided CS. An increase in CVP and a consequent rise in renal vein pressure can cause kidney congestion with heightened blood urea nitrogen levels and creatinine ,55.Trans thoracic echocardiography is the most common non-invasive tool used to assess RHF; it is carried out by assessing the motion of the RV and the PA pressure using RV dynamic characteristics. While a RV basal diameter of over 4.2 cm is indicative of RV distension and increased pressure, additional hemodynamic alliteration occurs. An RV fractional area change of under 35%, a tricuspid annular plane systolic excursion of less than 16 mm, a systolic annular velocity of under 10 cm/s and an RV ejection fraction of under 44% are indicative of impaired RV function .Due to the curved shape and structure of the RV, volumes are challenging to evaluate in an objective manner . Some diPulmonary artery catheterization (PAC) or right heart catheterization (RHC) enable comprehensive hemodynamic assessment. RV injury, leading to a reduction in the RV peak systolic pressure, an increase in the RV end-diastolic volume, a reduction in the RV stroke volume (SV) and a subsequent afterload increase, is seen. These pressures can be assessed using PAC .RHC’s benefit has been contested, with the ESCAPE trial not demonstrating a clinical benefit or shorter hospitalization in stable, hospitalized patients, and this is thought to be due to the invasive nature of the procedure. On the contrary, other assessments have shown a reduction in admission mortality and 30-day readmission with the use of RHC-guided therapy in cardiogenic shock patients . This, iThe approach to the management of right-side-predominant CS needs to take into consideration the etiology of shock, with an attempt to directly treat a reversible cause, when possible. In addition, the management will be guided by hemodynamic evaluation and be in accordance with the presumed pathophysiology. The spectrum of interventions includes the volume administration, vasoactive drugs, diuretics, agents that enhance cardiac contractility and invasive intervention with mechanical support devices in cases of refractory shock .Inotropic agents: Generally, over 90% of patients with CS receive some form of vasoconstrictive medication [dication . These cdication .The first group of drugs is inotropic agents with a vasoconstrictive effect, including agents such as epinephrine and norepinephrine alongside dopamine at high doses. The use of vasopressors in patients with RVD and CS is advocated in order to maintain blood pressure and ensure perfusion. This is particularly true in patients with a systolic BP <80–90 mm Hg . GeneralThis second group of agents includes drugs such as dobutamine, levosimendan and phosphodiesterase III inhibitors (milrinone), agents that have both ionotropic and vasodilatory effects. These agents should be used with great caution, as they can precipitate hypotension, though in cases when LV function is intact, they can simultaneously improve contractility and increase CO and are thus indicated in patients with RV-predominant HF causing CS ,19,62.Agents in this group have been shown to have equivocal hemodynamic properties. Levosimendan and milrinone may favorably affect ventricular–arterial coupling by combining RV inotropy and pulmonary vasodilation, and they might be preferentially indicated in patients with pulmonary hypertension caused by left heart disease. For patients with severe pulmonary hypertension, milrinone is usually the preferred agent for reducing pulmonary-artery pressures and improving RV function ,63,64. MThough the superiority of different drugs has been assessed, randomized controlled trials failed to show any superior effects of either drug. Additionally, an overwhelming majority of the research focuses on CS due to LV pathology. A more in-depth assessment of the two drug groups among patients with CS due to RVD is needed in order to find the optimal drug protocol and sequence. Vasopressin: Unlike the previous agents, vasopressin has no inotropic properties and does not improve the cardiac power index and CI [x and CI ,60. Argix and CI . Vasoprex and CI . Cautionx and CI .Volume maintenance: As RV-predominant shocks are preload-dependent, the optimization of CVP and the management of the total body volume status are essential. The goal of reaching an optimal RV preload is a very challenging task and requires close hemodynamic evaluation. As a result, therapy could include either volume expansion or diuretics, at times aiming to maintain CO without worsening venous congestion [ngestion .Adding fluids often depends upon the LV filling pressure, with low parameters increasing the risk of prerenal azotemia. Furthermore, in cases of adequate renal function, the urine output can serve as an indicator of whether fluids are needed. If the risk of renal damage due hypovolemia is feared, fluids could be given, though cautiously . HoweverAs a result, diuretics are frequently used as the first-line agents, reducing volume overload and systemic congestion. The extent of treatment is etiology- and comorbidity-based, with many patients having renal impairment ,16. MostThe elevated renal venous pressure often found in such patients contributes to decreased renal blood flow and reduces the perfusion pressure, which decreases the diuretic efficacy. Monitoring can be carried out by assessing the urinary sodium content ,16. In cPulmonary vasodilator therapies: Pulmonary hypertension is a condition often seen together with HF and can be a cause of RV failure due to primary vascular pathology or secondary to other conditions such as pulmonary embolism or left heart pathology or failure. In any of these cases, RV afterload reduction is important in negating RV distention [stention .Furthermore, it is shown that pulmonary vasodilators may improve RV CO while not increasing the pulmonary arterial pressure and reducing the RV afterload, though more data on this topic are needed ,59,60.Epoprostenol, a vasodilator, has long-term clinical benefits, including an improved survival and functional capacity for patients with pulmonary HTN. It is given either in an inhaled form or intravenously, with the latter being more potent. Nitric oxide is another agent that has potent vasodilatory effects and is regularly used in this subset of patients. Both of these agents have been shown to improve oxygenation and pulmonary vascular resistance. Due to the rapid action of the intravenous modalities, they are used in acute and intensive care settings .Furthermore, administering vasodilators to patients with pulmonary hypertension has to be carried out with great caution, as different subtypes can respond differently. Among patients with features of venous or capillary involvement (veno-occlusive disease and pulmonary capillary hemangiomatosis), vasodilators and prostacyclins have been shown to be dangerous and increase mortality ,67.Caution should be taken when considering the administration of vasodilatory therapy in the context of CS, as a further decrease in systemic blood pressure may occur, with subsequent potential reduction in the RV preload and worsening RV ischemia. This, in turn, can worsen CS due to an RV insult .A novel treatment is the Omecamtiv agent, a selective cardiac myosin activator targeting the myotrope. Though its primary use has been for patients with HF with reduced ejection fraction (HFrEF), it has shown promising trial results aimed at RVD management. With promising results, 20 weeks after the trail initiation, an improvement in RV regarding the RV systolic ejection time, RV outflow tract velocity time integral, RV end-systole area, RV afterload and RV–pulmonary artery coupling was seen among these patients. This can be a potential treatment option for patients with HFrEF who are experiencing an exacerbation of a hemodynamic state . Percutaneous coronary intervention (PCI): This invasive intervention has a role when a reversible cause such as obstructive coronary disease is deemed to be the cause of RV-predominant CS [inant CS . Early ainant CS .Multivessel revascularization or culprit vessel intervention is an additional consideration when assessing a treatment. It is thought that culprit vessel intervention has a significant benefit over multivessel revascularization, though research assessing its efficacy among RVD is needed . As in aInteratrial shunt: Among patients with CS with acute RV failure and PAH that are not responding to medical therapy, a bridge to transplantation  in the form of a surgically created passage in the atrial septum could be employed. A balloon atrial septostomy (BAS) provides a right-to-left shunt to unload the RV. Additionally, though not always implemented, a BAS might be followed by a Potts shunt formation procedure. A distinct approach creates a shunt between the left PA and the descending aorta [ng aorta .2. Furthermore, proper preoperative preparation is of great importance. The optimization of filling pressures and periprocedural inotropic support could be needed [This procedure will most certainly derive a decrease in systemic oxygenation and thus must be outweighed by the increased oxygen delivery mediated by the increased CO. The identification of appropriate patients is needed, and the criteria include: patients with severe RHF or an RAP > 20 mmHg, significant hypoxemia (<90% on room air) or a pulmonary vascular resistance index > 4400 dynes·s·cm−5/me needed .With a similar rationale, it was observed that a natural patent foramen ovale has been associated with more favorable hemodynamics and improved survival, though further research is needed .Thrombolysis and thrombectomy: Among patients with CS due to PE, thrombolysis or thrombectomy could be indicated. Thrombolysis is intended to break down the thrombus using anticlotting agents, primarily the tissue plasminogen activator (tPA). This is in contrast to thrombectomy or surgical embolectomy, which are forms of mechanical thrombus removal [h after the symptom onset, though variations can be considered. If contraindicated, patients can be treated with surgical embolectomy, or percutaneous catheter-directed treatment can be provided [ removal . Systemiprovided ,71.Additional considerations include worsening respiratory insufficiency, severe RVD or major myocardial necrosis, all along with low risk of bleeding complications . SurgicaPericardiocentesis: In cases such as extensive pericardial effusion or tamponade, an echo-guided pericardiocentesis might be indicated. This is dependent upon the etiology, the size and the effect on hemodynamic stability. Though the size of the effusion is not always indicative, the presence of tachycardia, tachypnea, pulsus paradoxus and echo-Doppler features including cardiac chamber collapse and the increased respiratory variation of transvalvular flow velocities could indicate a life-threatening state [ng state .Oxygenation: Proper oxygenation is critical in trying to prevent intubation for as long as possible. Supplemental oxygen is recommended in patients in order to maintain oxygen saturations greater than 92%. This is to avoid hypoxic pulmonary vasoconstriction and increases in the RV afterload. Additionally, metabolic and respiratory acidosis should be monitored and corrected in order to prevent an increase in pulmonary vascular resistance [sistance . Proper sistance .Mechanical ventilation: For CS patients who are hemodynamically unstable or have difficulty breathing, mechanical ventilation could be indicated, though this has to be employed with caution in patients with RHF. Mechanical ventilation may negatively impact both the RV preload and afterload, worsening shock. This is due to the difference between spontaneous and mechanical respiration physiology. Spontaneous inspiration leads to negative intrathoracic pressure transmitted to the right atrium and enhances the venous return. This is in contrast to positive pressure ventilation and positive end-expiratory pressure (PEEP), which have the opposite effect. Though no specific ventilation strategy among CS patients with RHF is recommended by guidelines, the damaging effects of mechanical ventilation on RV function can be diminished by the precise use of PEEP and by limiting the tidal volume to avoid lung over-distension [stension .In cases where non-invasive modalities are not sufficient, early mechanical circulatory support (MCS) should be considered as a measure for preventing multi-organ or BiV failure . This isA spectrum of devices is available, each with a different specialty structure and mechanism. As the heart hemodynamics differ between sides, machines are adjusted to properly fit each side and guarantee optimal hemodynamic aid. They can be divided into direct RV bypass and indirect RV bypass systems. Direct systems, such as Impella RP and TandemHeart RVAD, move blood from the RA to the PA, thus directly bypassing the RV. This is in contrast to systems such as VA-ECMO, which moves and oxygenates the blood from the RA to the femoral artery, thus indirectly bypassing the RV by skipping the PA and the respiratory system and dispersing throughout the body . SeveralIntra-aortic balloon pump (IABP): This computer-controlled device is mainly used in acute conditions once CO is severely impaired [impaired . IABP isimpaired . Nonetheimpaired . This isimpaired . Generalimpaired . In caseimpaired .Impella: This intracorporeal micro-axial MCS device is primarily used for patients with CS, it being placed across the aortic valve into the LV. Blood is actively pumped from the LV into the aorta, thereby unloading the heart and increasing CO. The active unloading of the LV reduces the myocardial load and oxygen demand, improving coronary perfusion and increasing peripheral tissue perfusion [erfusion .2 (p < 0.001)) and reduced CVPs (from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001)) [Several types of Impella are currently offered, including the Impella RP, which is exclusively used for right heart support. The device inflow portion is located in the IVC or close to the junction with the right atrium and the flexible nitinol pump is advanced into the outlet portion at the pulmonary artery, thus significantly increasing RV CO and reducing the central venous pressure following the placement and increasing MAP. It has been seen to have a more beneficial effect in improving hemodynamics compared to IABP . Even on 0.001)) . Additio 0.001)) .Common serious complications of using the Impella are the risk of bleeding, which is four times higher than that in control groups, and peripheral vascular complications, which are twice more prevalent . CautionThese types of devices are intended for use for a longer period of time and work by blood withdrawal from the right atrium or by ventricle pumping it to the main PA, based on an extracorporeal energy source. Its use is indicated when cardiac function is not predicted to improve to allow for a bridge for further interventions and to promote functional improvement. It has been used in a wide array of cases from severe RV MI to severe pulmonary hypertension, severe mitral regurgitation, allograft failure following heart transplantation as well as post-LVAD implantation . SeveralTandemHeart: The Tandem Heart (TH)  is an extracorporeal centrifugal pump and a continuous flow percutaneous mechanical assist device that can be used to treat extreme, refractory CS due to acute RVF. Two venous cannulas are introduced: an inflow for drainage of the right atrium and an outflow cannula that is placed in the pulmonary artery. The cannulation of these cannulas is usually executed through the left femoral and the right femoral veins, respectively [ectively . Accordiectively ,16. The However, complications were evident in clinical trials and included cannula migration causing acute hemodynamic collapse, RV arrhythmia, perforation as well as persistent bleeding around the cannulation site and in the GI tract and hemolysis. Further, an increased risk of stroke and cardiac tamponade was seen among these patients ,80.ProtekdDuo: This device is very similar to the previous one but has a unique dual lumen cannula that can enable single venous access via the right internal jugular vein for use with the TandemHeart-RVAD [art-RVAD . The useart-RVAD . A flow art-RVAD .CentriMag: Similar to the previous devices, the CentriMag  is an extracorporeal RVAD with a centrifugal pump and a motor, but it is implanted surgically. Its unique design is thought to reduce blood trauma and mechanical failure such as clotting and hemolysis [emolysis . Compareemolysis . Obviousemolysis .When compared retrospectively, percutaneous RVAD use was associated with reduced morbidity, including a decreased blood transfusion requirement and a shorter time spent being mechanically ventilated. This would support the use of pRVAD among patients who are expected to need a more intensive treatment to support their RV and CS management. Ventricular assist devices enable patients to stay mobile during treatment and many times reinstitute daily activity. Nonetheless, currently, no FDA-approved long-term implantable devices designed to maintain RV support are available ,83.It is not uncommon that RVADs are used as part of biventricular assist devices in cases where both ventricles are incompetent. This is particularly common among patients with RV MCS as a consequence of durable LVAD placement. These patients tend to have very poor outcomes, with less than half of patients remaining stable after the removal of temporary RVAD support. For these patients, the HeartWare  was available; a ventricular assist device was developed which was mostly used for patients awaiting a heart transplant, though it was discontinued in 2021 due to high thromboembolic events. Additionally, HeartMate 3  from Abbott can be adjusted to function as a biventricular assist device, even in the highly trabeculated RV. Nonetheless, treatment places the patients under a significant risk of thrombosis development .Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO): This system is composed of a circuit oxygenating blood, bypassing the heart and the lungs with a venous inflow cannula, a centrifugal flow pump, an oxygenator, a heat exchanger and an outflow arterial cannula with either central or peripheral employment methods [ methods . Providi methods , irrespe methods . VA-ECMO methods . In acut methods . VA-ECMO methods ,30,71. I methods . When as methods ,74.Treatment with VA–ECMO comes with its risks, some of them being life-threatening. Some of the most dreadful ones are thrombosis, with estimates reaching a rate of 21.5%, and lower extremity ischemia, with estimates being as high as 24% . The firAn alternative to VA ECMO is the veno-veno ECMO (VV ECMO), which is thought to be the preferred system in cases of isolated RV failure secondary to acute hypoxemic respiratory failure. It takes deoxygenated blood and returns oxygenated blood to the venous system. VV ECMO is known to reduce PA pressures, improve CI and reduce the central venous pressure (CVP). Furthermore, its further benefit is by mediating a decrease in hypoxia-mediated pulmonary vasoconstriction, along with improvements in PaCO2 and pH, resulting in increased cardiac contractility (CC) .Anticoagulation and MCS devices: Meticulous anticoagulant therapy is needed throughout the treatment duration to maintain a thrombus free circuit, required in all RVAD systems. The first-line option is heparin, monitored with the activated clotting time (ACT) or partial thromboplastin time (PTT), with a target of about 1.5 to 1.9 times the laboratory normal levels. Second-line agents include bivalrudin or argatroban, with a potential consideration of warfarin treatment. With excessive treatment, bleeding can occur, which is usually quickly corrected with blood products such as platelets and cryoprecipitate. If weaning attempts are carried out, protamine can be used to reverse effects [ effects .® RV pulsatile right ventricular support device augments the efficacy of the IABP device, with a pump chamber connected to an outlet tube and a pulmonary trunk, bypassing the right heart. Though showing a promising efficacy, tests have been limited to animal models, showing an increased cardiac output by 59% in sheep suffering from acute RHF [Currently there are several new treatment modalities aimed at improving treatment efficacy and patients’ outcomes. The PERKATcute RHF ,87.Another focus point of novel treatment is venous decongestion. The Doraya Catheter is a temporary intravenous flow regulator installed in the inferior vena cava. This is thought to improve hemodynamic parameters and renal function outcomes. With the first human study showing promising results and safety approval, further research and advances are bound to occur in this field .An additional venture is the Circulite device (HeartWare Inc.), a fully implantable hybrid axial-centrifugal–flow pump moving blood from the RA to the PA. Testing among patients with RV failure and pulmonary hypertension is currently in progress. With potential positive results, the further improvement in hepatic and renal congestion may evolve .Generally, CS, being the most extensive form of heart impairment, naturally has a very poor prognosis, with an in-hospital mortality rate of up to 50% . Aside fIt is clear that the prognosis of patients is dependent on the disease severity. As a result, several score modalities were designed in order to assess patients’ potential for clinical instability and 30-day mortality probability. One of these is the CLIP score, which assesses cystatin C, lactate, interleukin-6 and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels at admission. Though its specific benefit among patients with RV failure CS has not been established, it has shown great efficacy generally among patients with CS . An addiOn the bright side, a profound improvement in RV function in survivors of CS caused mainly by RVD is often seen, particularly following the RV infarct. A better prognosis and clinical progression are seen among patients who are recognized to have RVD early, along with treatment aimed at the quick relief of RV ischemia . Recent CS caused by right heart dysfunction is a cause of cardiovascular morbidity and mortality that has gained less scientific focus compared with CS due to LV dysfunction. Various etiologies can cause RVD and the subsequent deterioration to CS, with the treatment being greatly dependent upon the pathological source. With RHF rates increasing and expected to rise in the upcoming years, this topic needs further research assessing the current protocols, treatment management modalities and mechanisms while simultaneously developing new methods of reducing morbidity and mortality that are more phenotype-specific for RV failure.


This case report is an extremely rare case of a traumatic left ventricular aneurysm in a 3-year-old child who also had tricuspid valve avulsion due to blunt trauma. The diagnostic findings and treatment protocols are discussed to provide a clinical reference. The left ventricular aneurysm can be categorized as congenital or acquired. The congenital left ventricular aneurysm is a dysplastic heart malformation thataffects approximately 0.04% of the population . The mosA 3-year-old child was admitted to our department with blunt injuries from a road traffic accident. Following the crash, he remained conscious while crying and was taken to our the emergency department of our hospital. The child felt considerable pain when pressure was applied to his right thigh during the physical examination without revealing any further abnormalities. Radiographs of his extremities showed a fractured right femur, and chest X-rays showed that the lungs were normal. An electrocardiogram (ECG) revealed low and flat T waves in leads III, aVF, and V1. Laboratory examination indicateda slight elevation in troponin to 21 ng/mL. Using transthoracic echocardiography (TTE), anterior tricuspid leaflet prolapse was observed because it is the first-line diagnostic tool for evaluating the tricuspid valve . This trAfter 6 months, ECG revealed continuous abnormal Q waves in leads III and aVF during normal myocardial enzymes. TTE revealed avulsion of anterior tricuspid leaflet resulting in moderate tricuspid regurgitation, a 23 × 38 mm giant aneurysm with a 19-mm diameter of the neck in the left ventricular posterior wall (LVPW) , and visDuring surgery, after sternotomy and the pericardium being incised, we found that the aneurysmal portion of the left ventricle was thinned and was greatly expanded , and theThe case reported here has the following two notable features. Initially, the patient presented with only an anterior tricuspid leaflet avulsion on an ECG following blunt chest injury, but 6 months later he developed a massive ventricular aneurysm. A second observation was that the posterior left ventricle branch was well protected in the process of ventricular aneurysmectomy and aneurysmorrhaphy in a “sandwich” structure. In addition, the third strip of the felt pad was added to reinforce the “sandwich” structure.The left ventricular aneurysm can be congenital or acquired, while both types present as a nodular structure protruding out of the cardiac chamber with regional ventricular wall expansion and thinning. A congenital ventricular aneurysm is a highly rare dysplastic heart malformation reported in around 0.04% of the population and is characterized by aberrant wall motion abnormality and large variations in size. Acongenital ventricular aneurysm is mainly presented in the neonatal period, and is generally accompanied by other congenital malformations, such as ventricular septal defect, atrial septal defect, tricuspid atresia, and tetralogy of Fallot . The acqEarly findings in the present case included low T waves in leads III, aVF, V1, elevation in troponin, moderate tricuspid regurgitation, and no evidence of ventricular aneurysms. After 6 months of injury, continuous abnormal Q waves in leads III and aVF were demonstrated on ECG while myocardial enzymes were normal. Furthermore, TTE identified a massive aneurysm located in the left ventricle. This suggests that in pediatric cases suffering from a blunt chest injury, especially those experiencing cardiac injury such as complex valvular injury, the possibility of ventricular aneurysm should be considered.An untreated large ventricular aneurysm carries a high risk of rupture and embolization. Due to the childbeing young and having a poor prognosis, conservative treatment arrangements were made to address the initial finding of tricuspid regurgitation. Surgery was performed after 6 months for the diagnosed sizeable ventricular aneurysm. The timing of surgery for traumatic ventricular aneurysms remains undetermined because of its rarity and lack of evidence regarding its management. In the present case, the ventricular aneurysm boundary and the scar wereformed after 6 months of injury, which may facilitatethe surgical procedure.Traumatic tricuspid insufficiency is an uncommon complication of blunt cardiac injury . In avoiSurgery for ventricular aneurysms requires protection for the major coronary branches, as the deformation and tamponade of the coronary postoperatively can cause malignant arrhythmia and death . As obseWe reported an extremely rare case of traumatic left ventricular aneurysm combining tricuspid valve avulsion following blunt injury. We present confirmed diagnosis, ventricular aneurysmorrhaphy, and tricuspid valvuloplasty with a successful clinical outcome. It suggests that in pediatric cases suffering from a blunt chest injury, especially experiencing a cardiac injury, a ventricular aneurysm may be considered and coronary arterial branches should be well protected in ventricular aneurysmectomy in a “sandwich.”The original contributions presented in the study are included in the article/Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the minor(s)' legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.DZ and SW performed the data analyses and wrote the manuscript. WT contributed to provided and analyzed intraoperative and postoperative cardiac ultrasound images required for the study. RX and YL contributed significantly to analysis and manuscript preparation. DL helped perform the analysis with constructive discussions. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (Grant No. 82160060) and Guizhou Provincial Science and Technology Projects ZK [2022] YB669 and ZK [2022] YB652.The 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.


Amyloid transthyretin (ATTR) amyloidosis is a clinically heterogeneous and fatal disease that results from deposition of insoluble amyloid fibrils in various organs and tissues, causing progressive loss of function. The objective of this review is to increase awareness and diagnosis of ATTR amyloidosis by improving recognition of its overlapping conditions, misdiagnosis, and multiorgan presentation. Cardiac manifestations include heart failure, atrial fibrillation, intolerance to previously prescribed antihypertensives, sinus node dysfunction, and atrioventricular block, resulting in the need for permanent pacing. Neurologic manifestations include progressive sensorimotor neuropathy  and autonomic dysfunction . Non-cardiac red flags often precede the diagnosis of ATTR amyloidosis and include musculoskeletal manifestations . Awareness and recognition of the constellation of symptoms, including cardiac, neurologic, and musculoskeletal manifestations, will help with early diagnosis of ATTR amyloidosis and faster access to therapies, thereby slowing the progression of this debilitating disease. Amyloid transthyretin (ATTR) amyloidosis is a progressively debilitating, clinically heterogeneous, and fatal disease caused by the buildup of transthyretin (TTR) amyloid fibrils in various organs and tissues, resulting in multisystem dysfunction particularly in the heart, along with the peripheral and autonomic nervous systems –3. The dTTR gene. More than 130 mutations have been identified to date, with some mutations more often associated with either predominant polyneuropathy or cardiomyopathy; however, most patients experience a mixed phenotype with both neuropathic and cardiac symptoms [There are two forms of ATTR amyloidosis: wild type (ATTRwt) and hereditary (ATTRv [variant]). In ATTRwt amyloidosis, which was previously termed senile cardiac amyloidosis, a native non-mutated TTR protein misfolds into amyloid fibrils, primarily resulting in dysfunction of the heart that is characterized by restrictive cardiomyopathy; this is predominantly seen in males aged > 60 years –16. Althsymptoms , 17–19. symptoms , 21. In symptoms .ATTR amyloidosis is often overlooked or misdiagnosed in patients, at least early in its course, due to the non-specific, heterogeneous, multisystem presentation of the disease . As the The signs and symptoms that should raise suspicion of ATTR amyloidosis with cardiomyopathy (ATTR-CM) often overlap with other more commonly recognized cardiovascular diseases, such as heart failure with preserved ejection fraction, hypertensive cardiomyopathy, aortic stenosis, hypertrophic cardiomyopathy, and light chain amyloidosis Table  25, 27––27–29. GEarly suspicion and recognition of ATTR amyloidosis can lead to an earlier diagnosis and treatment; there is evidence to suggest that a delay in treatment leads to irretrievable loss of quality of life and progression of the polyneuropathic and cardiac manifestations for most patients , 9–13. RATTR-CM is characterized by increased ventricular wall thickness, increased valve thickness, and interatrial and interventricular septum thickness that present as restrictive cardiomyopathy and progress to heart failure—initially in the setting of preserved ejection fraction, conduction system disturbances, and arrhythmias—with resulting impaired functional capacity, syncope, or palpitations , 32–34. Patients with amyloid polyneuropathy, such as ATTR amyloidosis, are frequently misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) , 25, 40.TTR mutation in the case of ATTRv amyloidosis, distal and occasionally proximal limb weakness may be prominent [ATTR-PN is characterized by symmetrical length-dependent peripheral neuropathy; depending on the rominent , 19. As rominent –43. Earlrominent . Examinarominent . As ATTRrominent , 43–45.In addition to signs and symptoms of sensorimotor neuropathy, autonomic dysfunction is observed early in the course of ATTR amyloidosis and can precede motor impairment, but it often goes unrecognized , 46, 47.Patients with ATTR amyloidosis may develop musculoskeletal manifestations 5 to 15 years prior to other symptoms Fig.  4, 7, 5, 51. NumOrthopedic surgery is significantly more common in patients with ATTR-CM compared with the general population . ArthropCardiologists should screen for ATTR amyloidosis in patients with clinical signs and symptoms suggestive of multisystem involvement, particularly those with the constellation of cardiac, neurologic, and musculoskeletal manifestations described in this review. Given the multisystemic nature of ATTR amyloidosis, a multidisciplinary approach to assessment, diagnosis, and management of patients is recommended by the guidelines , 28. TheIt can be challenging to identify ATTR amyloidosis given the diversity of diagnostic clues that can manifest in a patient over time (across many years). As cardiac amyloidosis is present in 10% to 15% of patients with heart failure with preserved ejection fraction , 58, 60,Awareness of the non-cardiac symptoms that cluster with cardiac and neurologic symptoms can unmask a diagnosis of ATTR amyloidosis and prompt referral to a center with expertise in this disease Fig.  3, 24, , 24, 28.


Conclusions: TR was not associated with outcome in AHF using guideline measures. A new assessment of “Disproportionate” TR carries a higher risk than proportionate TR but was not related to outcome based on multivariate analysis. Further research is needed to quantify TR more effectively to identify cut-offs for future guidelines and disproportionate TR may be an important part of Heart Failure 2.0.Background: The prognostic impact of tricuspid regurgitation (TR) in acute heart failure (AHF) remains uncertain. Methods: We retrospectively assessed 418 consecutive AHF patients who underwent comprehensive echocardiographic assessment within 24 h of study recruitment. TR was quantitatively assessed with 3 guideline-directed measures: regurgitant volumes (RgVol), effective regurgitant orifice area (ERO) and vena contracta (VC) diameter. Disproportionate TR was assessed by the ratio of the VC diameter to the tricuspid annulus diameter (VC/TA) ≥ 0.24. Results: The prevalence of significant  TR differed when various standard assessment parameters were applied to quantification: RgVol 50.3% (173/344), ERO 75.6% (260/344) and VC diameter 94.6% (335/354). None were able to delineate those at excess risk of all-cause 2-year mortality using guideline-directed cut-offs of mild, moderate and severe TR. Using a cut-off of VC/TA ≥ 0.24, we identified that 36.9% (130/352) had “disproportionate” TR. Disproportionate TR was associated with an excess risk of mortality at 2 years compared to proportionate TR; HR 1.48 (95% CI 1.06–2.06 [ Acute heart failure (AHF) remains a substantial cause of morbidity and mortality. It accounts for a quarter of European in-hospital deaths or discharges ,2 and inTricuspid regurgitation (TR) is present in 60% of hospitalized AHF patients ,2, the vThis uncertainty is a consequence of a diverse array of comorbid conditions straining the right heart alongside the technical challenges of precise quantitative assessment of the tricuspid valve apparatus and the right ventricle (RV) .Unlike left heart geometry, there is substantial difficulty obtaining orthogonal views of the RV and the tricuspid valve. Significant variation in RV/right atrial/tricuspid annular remodelling makes linear assessments  diameters and PISA radii) highly variable between individuals and between imaging planes within the same individual ,12.International guidelines rely on a mixture of qualitative, semi-quantitative and quantitative assessments ,14 but tacute heart failure.A novel concept of disproportionality has been developed in the context of MR in chronic HF ,16,17, wThis was a retrospective analysis to assess for the impact of TR in AHF using the Mitral Regurgitation in Acute Heart Failure (MRAHF) study results. MRAHF study details are published previously . In summTM  for patient records, including death certificates, used at our centre.Participants were followed up for 2 years and assessed for all-cause mortality through the UK summary care record system used nationally by general practices  in the United Kingdom and by the online software EvolveTrial oversight was by the Ashford & St Peter’s NHS Trust Research and Development team and was approved by the institutional review board and ethics committee. All patients gave written informed consent prior to enrolment in the study. All authors had access to data and this manuscript for review. The experimental design and decision for publication was by AB. Most statistical analysis was carried out at an independent company with established expertise in medical trials with input from MB.Echocardiography was carried out with G.E. Vivid S70  and analysed and stored using EchoPac v202.5 . Most exams were performed by a single accredited operator with a dedicated protocol . OfflineAssessment of left and right atrial and ventricular geometry, systolic and diastolic function were obtained using a standard TTE minimum dataset approach advocated by the British Society of Echocardiography . The LV Traditional TR assessment was performed by qualitative, semi-quantitative and quantitative parameters to gauge lesion severity according to the 2017 guidelines of the American Society of Echocardiography Society and society for Cardiovascular Magnetic Resonance . QuantitTricuspid annulus and VC diameter used in the disproportionate assessment of TR were obtained from the RV-focussed apical four chamber view. The vena contracta was selected visually from the best image in mid-systole. The TA diameter measurement was made from the frame closest to end-systole where the leading-edge to leading-edge diameter was at its widest by visual assessment. In the interest of image quality and optimal frame rate for accurate and precise measurement, a different image from the same acoustic window and probe position was used for vena contracta. Disproportionate TR was defined by the ratio of the VC diameter to the tricuspid annulus diameter, with a binary threshold of ≥0.24 used to identify disproportionate TR. This cut-off was previously identified by Fortuni et al. .RV GLS free wall analysis was performed using an optimized RV apical 4 chamber view. One cardiac cycle was isolated where optimal visualisation of the free wall myocardium was obtained. A region of interest (ROI) was defined segmentally from free wall base to the apex. This was performed as a ‘single wall’ analysis excluding the interventricular septum to minimize the impact of LV myocardial deformation. GE EchoPAC LV 2D strain package was repurposed for this retrospective analysis of RV strain.RV peak GLS was defined as the maximal strain value obtained at any point during systole. RV end-systolic GLS was defined by the strain value at the time of pulmonary valve closure (PVC). The timing of PVC was identified in the parasternal short axis view with Doppler spike of PVC on Doppler contour when the sample volume is placed immediately proximal to the pulmonary valve. GE EchoPac then automatically applies the corresponding timepoint on the ECG to identify PVC in the apical view used to analyse the RV strain outlined above. Demographic and clinical cardiac characteristics were summarized for all participants at the point of study inclusion. Patients were divided into two groups according to the VC/TA cut-off ratio of 0.24. Between groups comparisons were carried out using non-parametric Mann–Whitney U test for continuous data (represented as median (inter-quartile range)), as normality testing (via Shapiro–Wilk) indicates data were not normally distributed, and chi-square test for categorical data (represented as %). Kaplan–Meier overall survival estimates were generated for four metrics of interest  with groupings being categorized as mild, moderate, and severe based on pre-determined guideline-directed thresholds for each variable. Univariate analyses were initially undertaken to identify potential associations with 2-year all-cause mortality. Significance was assessed using the log-rank method and Cox’s proportional hazards model. Individual associations with outcome were then included in a multivariate model. Statistical significance was accepted at a two-tailed α-value of 0.05 throughout.Variables to be included in multivariate analysis were selected by MB & AB and included: age, gender, BMI, the presence of coronary artery disease, hypertension, diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disorder (COPD), previous cerebrovascular accident (CVA), right atrial size, left atrial size, moderate or greater MR, systolic pulmonary artery pressure, tricuspid annular plane systolic excursion (TAPSE), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), blood urea nitrogen, plasma sodium, brain-natriuretic peptide (BNP), haemoglobin (Hb), estimated glomerular filtration rate (eGFR), RV end-diastolic area indexed to body surface area (RVA diastole index) and the presence or absence of disproportionate TR.616 patients presenting with signs of AHF were assessed for eligibility and 72.6% (447) of participants were recruited. 418 individuals were included in final analysis after excluding rehospitalisation . Every pAmong those with 2-year outcome data: quantification of RgVol was available in 83.1% (344/414); 49.7% (171/344) displayed volumetrically defined mild TR, 12.5% (43/344) displayed moderate TR and 37.7% (130/344) severe TR. ERO assessment was available in 83.1% (344/414), with 24.4% (84/344) displaying mild ERO-defined TR, 26.4% (91/344) moderate and 49.1% (169/344) severe TR. VC diameters were available in 85.5% (354/414) of jets, 5.4% (19/354) displayed VC diameter-defined mild TR, 43.5% (154/354) moderate TR and 51.1% (181/354) severe TR. Disproportionate TR was identified in 36.9% (130/352) of patients with both VC and TA diameters available and proportionate TR in 63.1% (222/352).p = 0.034]), with lower eGFR (48.5 mL/m2 vs. 54 mL/m2). 2-year mortality was significantly higher in disproportionate TR (47.7% vs. 36.5% [p = 0.02]).Comparison of demographics, clinical background, presenting features and mortality are displayed of patients with and without disproportionate TR in p < 0.001]), ERO (1.10 cm2 vs. 0.50 cm2 [p < 0.001]) and VC diameter (0.6 cm vs. 0.2 cm [p < 0.001]) (p < 0.003). Both disproportionate and proportionate TR displayed similarly impaired (or borderline-impaired) longitudinal and radial systolic function measured by TAPSE (1.4 cm vs. 1.5 cm [p = 0.16] and RV FAC (37.9 vs. 33.7 [p = 0.16] (p = 0.0023]) (p < 0.001]) (In disproportionate TR there were higher RgVol (61.0 mL vs. 17.0 [ 0.001]) . Both th = 0.16] . Despite0.0023]) . Systoli 0.001]) . RV stra2 vs. 27.5 cm2 [p = 0.015]) but LV volumes were similar and within the normal range (p = 0.63]) as were all other parameters of systolic function including LV strain and strain rate. Patients with disproportionate TR had a greater prevalence of more than mild MR  with mild TR, there were also no differences in outcome  (p = 0.95). Independent prognostic indicators associated with increased risk of mortality were age, the presence of COPD, LVEDV, blood urea and BNP  [ 0.020]) . Other v and BNP . p = 0.10]) . Within this group, disproportionate TR was not significantly associated with worse outcome; HR 2.03 (95% CI 0.87–4.75 [= 0.10]) . The resData were analysed using a cox-proportional hazards model to generate survival estimates between subgroups of each variable and with respect to the covariates selected. The covariates listed were selected for post hoc, multivariate analysis if demonstrating statistical significance in the univariate analysis reported in When undergoing early echocardiography, TR was a highly prevalent feature of those admitted with AHF with more than 85% displaying quantifiable regurgitation. The prevalence of TR severity varied depending on the quantitative feature used as a cut-off. TR severity defined by RgVol, ERO or VC diameter was unable to identify those at risk of poor outcome at 2 years, based on unadjusted Kaplan–Meier estimates. A novel assessment of disproportionate TR was not significantly associated with outcome on multivariate assessment.). These challenges are driven by several well-characterized limitations to the assessment of TR.These findings highlight the inconsistencies and challenges facing objective and quantitative assessment of TR. The guideline indicated assessments  in this study described very different proportions of >mild TR   despite In this study a novel assessment of TR in which the VC diameter is indexed TA diameter, identified an excess risk of mortality (HR 1.48) in the 129/358 (36.0%) of patients with disproportionate TR, compared to proportionate TR. This, however, was not significant on multivariate assessment in our AHF cohort. Instead, drivers of outcome were confounders with known associations with outcome . may reflect a more diverse comorbid profile than the original derivation study in Fortuni et al. Our entire MRAHF study cohort differed to Fortuni as they were older (78 yr vs. 70 yr), had a higher burden of cardiovascular risk factors and higher proportions of “haemodynamically significant”  MR 39% vs. 18%) [% [18]. U2/m2) and disproportionate TR (12.2 cm2/m2) groups were within the normal range (<12.6 cm2/m2) ) but did not reach significance. Nevertheless, the presence of ‘Fortuni’ cohort in our study reflects on general applicability of the original Fortuni assessment to a “real-world” AHF setting given that original cohort data collection occurred over 21 years and was focused on stable patients with normal LV function. It will be interesting to collate the data from other AHF studies as it appears to show some utility when applied to the much broader AHF “all-comers” in this investigation.It is interesting that a proportion (14.1%) of the total number of patients in our study met similar echo criteria to Fortuni (n = 59) study. In this subgroup there was a trend towards worse outcome  [This disproportionality framework continues to be debated, with doubt as to the relevance of indexing markers of mitral, or tricuspid, regurgitation to ventricular parameters . This noc shock) .There are also limitations to PISA-derived quantification of regurgitant pathology in general, with many assumptions on single, central or symmetrical jets which are captured on only one cardiac cycle, which is independent of the CW interrogated cardiac cycle for velocity time integral assessment. However, when these techniques are applied consistently by observers this should limit the inherent physiological shortcomings of Doppler assessment of regurgitant lesions.For future work on disproportionate TR, there is an obvious discrepancy between the evaluation of disproportionate TR and MR because LV volumetric assessment is readily available in MR due to orthogonal views of left heart geometry. Attempts of RV volumetric assessments by echocardiography  have beeThere are several limitations of this study. This was a single-centre study which limits the generalisability of its findings. A further limitation is that this is a retrospective analysis of a study designed to evaluate the impact of MR in AHF. Prospective studies to assess for TR, for example with prespecified to further investigate the prognostic impact of disproportionate TR are warranted.In summary, this study highlights the variation in the quantitative evaluation of TR and inadequate discriminatory capacity to identify those at risk of long-term poor outcomes following hospitalisation for acute heart failure. It also highlights a role for more novel assessments of TR, including the evaluation of disproportionate TR, which warrant further study.In summary, this study highlights the variation in the quantitative evaluation of TR and inadequate discriminatory capacity to identify those at risk of long-term poor outcomes following hospitalisation for acute heart failure. It also highlights a role for more novel diagnostic assessments of TR, including the evaluation of disproportionate TR, which warrant further study.


Conclusions: In patients treated for acute STEMI, acute %SAS is associated with post-infarct LVR. Therefore, we suggest performing such evaluations on a routine basis to identify, as early as possible, STEMI patients at higher risk.Background: Measures of global left ventricular (LV) systolic function have limitations for the prediction of post-infarct LV remodeling (LVR). Therefore, we tested the association between a new measure of regional LV systolic function—the percentage of severely altered strain (%SAS)- and LVR after acute ST-elevation myocardial infarction (STEMI). As a secondary objective, we also evaluated the association between %SAS and clinical events during follow-up. Methods: Of 177 patients undergoing echocardiography within 24 h from primary percutaneous coronary angioplasty, 172 were studied for 3 months, 167 for 12 months, and 10 died. The %SAS was calculated by dividing the number of LV myocardial segments with ≥−5% peak systolic longitudinal strain by the total number of segments. LVR was defined as the increase in end-diastolic volume >20% at its first occurrence compared to baseline. Results: LVR percentage was 10.2% and 15.8% at 3 and 12 months, respectively. Based on univariable analysis, a number of clinical, laboratory, electrocardiographic and echocardiographic variables were associated with LVR. Based on multivariable analysis, %SAS and TnI peak remained associated with LVR (for %SAS 5% increase, OR 1.226, 95% CI 1.098–1.369,  Left ventricular remodeling (LVR) is a complication of acute myocardial infarction (MI). It has a negative prognostic value and is the main cause of heart failure in acute MI survivors ,2. SeverIn this study, we sought to verify whether a new measure of regional longitudinal strain—the percentage of severely altered strain (%SAS)—evaluated by STE during the acute phase of ST-elevation MI (STEMI) is associated with subsequent development of LVR and is better than the other echocardiographic predictors. The rationale underlying the use of %SAS is that it represents the amount of acute severely injured myocardium, without including mildly injured, normal or hypercontractile LV areas, thus avoiding a fundamental limitation of global LV function indices.Patients were referred to the catheterization laboratory of the Cardiac Unit of the University Hospital of Ferrara for primary PCI for suspected STEMI between September 2015 and 2017. The diagnosis of STEMI was made according to standard clinical and electrocardiographic criteria  and confThis was a single-center observational study. According to the follow-up program for STEMI patients treated at the Ferrara Cardiac Unit, all patients were scheduled for echocardiography 3 months (T1 time) and 12 months (T2 time) after discharge.The primary objective of the study was to verify whether acute %SAS (at T0) is associated with the development of LVR. Because LVR is a progressive phenomenon detected echocardiographically up to 1 year from the acute event , the 12-To provide information about the clinical value of acute %SAS, we also verified whether this measure was associated with clinical events during follow-up (secondary objective). For this purpose, death from any cause and re-hospitalization for heart failure or acute coronary syndrome were chosen as clinical events and grouped into a composite endpoint. Outcome status was assessed by review of the medical records through the hospital medical informatic platform. If a patient had more than one clinical event, the first one that occurred temporally was considered. The median duration of follow-up from STEMI occurrence was 43 months (interquartile range: 36–51 months).(A) Image acquisition. The 2D echocardiographic examination was performed using commercial echo scanners  equipped with a 3.5 MHz phased-array transducer. All Doppler and echocardiographic acquisitions were obtained at held end-expiration. Sector width was optimized to allow visualization of the whole LV myocardium in the 3 standard apical views  and to maximize frame rate (which varied between 60 and 100 fps). (B) Image analysis. Analysis of the echocardiographic images was performed off-line using a commercially available software . LV end-diastolic volume (EDV), ESV, EF and left atrial volume index (LAVI) were calculated using the biplane Simpson’s method . WMSI waAfter testing for normal distribution with the Kolmogorov–Smirnov test, continuous variables were expressed as median values with 25th and 75th percentiles. Categorical variables were expressed as percentages. Variables of patients with and without LVR or with and without clinical events were compared using the Mann–Whitney U test or the chi-square test, when appropriate. Values of continuous variables at T0, T1 and T2 were compared using the Friedman test, and pairwise comparisons were performed with a Bonferroni correction.For the primary objective, a univariable logistic regression, including the clinical and echocardiographic variables, was performed to evaluate the association with LVR. For the multivariable analysis, the following variables were selected a priori: time from symptoms’ onset to STEMI diagnosis ≥ 3 h, peak of TnI, ST-resolution, use of MRAs at discharge, LV ESV, EF, GLS, WMSI, %WMA, and %SAS. Except for %SAS, all of these variables are known to be associated with LVR from previous studies ,17,18,19For the secondary objective, we performed a univariable and a multivariable Cox analysis. The hazard ratio (HR) for each statistically significant variable was calculated together with the 95% CI. For the multivariable Cox analysis, it was decided a priori to include in the model LVR those variables significantly associated with LVR in the multivariable analysis for the primary objective.p value < 0.05 was considered statistically significant.Intra and interobserver variability for %SAS measurement were assessed in 20 randomly selected patients at T0 using the interclass correlation coefficient (ICC) and the Bland–Altman analysis, calculating bias and limits of agreement (LOAs). The statistical analysis was performed using the IBM SPSS Statistics software, v. 25 . A n = 303) or died before hospital discharge (n = 11). Of the 234 remaining patients, another 57 were excluded: 8 had atrial fibrillation at T0 echocardiography, 22 had inadequate echocardiographic image quality, and 27 were lost to follow-up. Therefore, 177 patients constituted the final study cohort. Five of these patients died before echocardiography at T1 and 5 before echocardiography at T2.Five-hundred forty-eight patients referred to the catheterization laboratory with STEMI diagnosis confirmed by coronary angiography were initially considered. Then, 314 patients were excluded because they were transferred to other hospitals of the Ferrara STEMI network after PCI  patients had LVR; 18 (60%) of them had first evidence of LVR at T1 and 12 (40%) at T2. One patient with LVR at T1 died before T2, and another one showed reversed LVR at T2. The percentage of LVR was 10.2% (18/177) at T1 and 15.8% (28/177) at T2. Of the 28 patients with LVR at T2, 12 (43%) did not show LVR at T1.The main clinical characteristics of patients are reported in No significant differences were observed between patients with and without LVR in terms of age, gender, body surface area, body mass index, cardiovascular risk factors, systolic blood pressure, heart rate, site of infarction, culprit coronary artery, final TIMI flow, time from first medical contact to PCI and staged PCI during hospitalization . LVR patBaseline, T1 and T2 echocardiographic characteristics are reported in In patients without LVR, EDV did not change and ESV progressively decreased over time. Global and regional measures of LV systolic function improved. %SAS reduced markedly. LAVI had a modest, although significant, increase. MR severity decreased at T1 and was maintained at T2. E/e’ ratio decreased progressively. Compared to non-LVR patients, at baseline patients with LVR did not differ in terms of EDV but had lower EF and GLS , and higher ESV, WMSI, %WMA and %SAS. LAVI, MR severity and diastolic measures did not differ. In patients with LVR, EDV and ESV progressively increased over time, and LV-EF improved only mildly. GLS improved, and WMSI did not vary. Regional measures of LV systolic function, such as %WMA and %SAS, declined during follow-up, especially at T2. LAVI increased at T2. MR severity remained similar over time and worse than that in patients without LVR at T1 and T2.In the univariable analysis, time from symptoms’ onset to STEMI diagnosis ≥ 3 h, time from first medical contact to PCI, infarct site, ST-resolution, peak of TnI, peak of CK-MB, glycated hemoglobin, use of MRAs at discharge, LV ESV, EF, GLS, WMSI, %WMA, and %SAS were associated with LVR . A multip < 0.0005) while for peak of TnI, the OR was 1.025 . The ROC curve analysis of this multivariable model showed an AUC of 0.82  (p = 0.483 vs. %SAS), respectively. Optimal baseline cut-off values were 44% for %SAS  and 49 ng/mL for peak of TnI  (p < 0.0005). Model 1 excluded WMSI and %WMA . In this 0.0005) A; AUC ofity 61%) B,C. CorrModel 2 and 3 excluded %SAS and included WMSI and %WMA separately . NeitherDuring the median follow-up period of 43 months, 11 patients died, 15 were re-hospitalized for heart failure, and 15 for acute coronary syndrome as first clinical event, for a total of 41 first events in 41 patients (23% of the entire patient cohort). Because 11 patients had more than one clinical event, the overall clinical events were 55. Survival probability free of clinical events is shown in p = 0.003), TnI at T0 was not different between patients with and without clinical events.Clinical and echocardiographic characteristics of patients with and without clinical events are reported in p = 0.015). In addition to LVR, multivariable Cox analysis included %SAS and peak of TnI  and LVR  were associated with occurrence of clinical events during follow-up, while peak of TnI was not .Baseline variables associated with clinical events in univariable Cox analysis are reported in nsidered , model 1As regards the intraobserver variability of %SAS calculation, the ICC was 0.993, bias −0.2%, and LOAs 5.4 and −5.9%; as regards the interobserver variability, the ICC was 0.975, bias −0.1%, and LOAs 8.7 and −9.9%.This study explored, in patients treated for STEMI, the association between acute echocardiographic measures of LV systolic function and LVR (primary endpoint) and clinical events during follow-up (secondary endpoint). The main findings were: (1) in patients treated for STEMI, acute %SAS was associated with LVR; (2) this association was not observed for conventional echocardiographic measures of global LV function in the multivariable analysis, while it was observed for peak of TnI; (3) acute %SAS was also associated with an unfavorable clinical outcome, while peak of TnI was not; (4) a significant proportion (43%) of patients with LVR at 12 months did not have LVR at 3 months; (5) LVR at its first occurrence was associated with clinical outcome. All of these findings have implications for the acute evaluation and follow-up strategy of patients who experience a STEMI.Investigations performed in the decade between 1996 and 2006 reported a rate of LVR of 16–31% between 6 and 12 months after revascularized acute STEMI ,9,10. MoWe observed a percentage of LVR of 10.2% at 3 months and 15.8% at 1 year. In our opinion, this lower LVR prevalence compared to previous studies could be related to the effectiveness of contemporary STEMI treatments . On the other hand, the persistence of a significant number of patients with LVR also evidences that development of post-infarct LVR is still affected by determinants not fully controlled by current therapeutic strategies .In our patients, LVR was significantly associated with an unfavorable clinical outcome in univariable and multivariable analysis. This confirms previous observations ,14 and uVarious echocardiographic measures of LV global systolic function, including LV-EF, ESV, WMSI and GLS, have been proposed over the years to predict, during the early phase of STEMI, subsequent development of LVR or outcome ,6,15,16.In our study, LV-EF, ESV, and WMSI were not associated with LVR. GLS was significantly associated with LVR only when %SAS was not included in the multivariable analysis . A possiA different approach to prediction of LVR is the evaluation of regional LV systolic function. This approach has been shown to predict LVR in previous investigations based on conventional  and STE Of note, in LVR patients, the baseline %SAS was high (54% on average). This could be related to the very early evaluation of %SAS in the acute phase of STEMI, when infarct size is still far from stabilization. Additionally, because a larger acute infarct size is associated with the presence of microvascular obstruction , the higp = 0.483; In our patient cohort, peak of TnI was also significantly and independently associated with LVR. This finding agrees with that of other authors, showing that patients with LVR after STEMI were characterized by higher levels of peak TnI . The assFirst, multiple Tn assays are needed after the STEMI diagnosis to identify the peak value of Tn, whereas %SAS is a single evaluation, and this may facilitate very early prediction of LVR. Second, the correlation between serum Tn after STEMI and infarct size is impaired in case of slow or incomplete reperfusion and renal insufficiency, which delay peak of Tn , while kIn our patient cohort, %SAS progressively decreased over time after the acute STEMI, with a parallel increase in GLS . This isIn our investigation, the %SAS decrease occurred both in patients with and without LVR, but in those with LVR, the magnitude of reduction was much less . This caFinally, in LVR patients, the median %SAS at 12 months was 12%. This represents the residual infarct size, that is, the non-viable myocardium with transmural scar tissue .The %SAS is an objective measure of regional LV systolic function. This is an advantage compared to other parameters, such as WMSI and %WMA, based on visual interpretation of myocardial contraction. Further, calculation of %SAS is simple and relatively fast with current echocardiographic technology. In fact, the number of segments with severe alteration of strain can be easily obtained just by looking at the LV polar plot automatically provided by the echo scanner .This study was a single-center investigation. This implies a limited number of STEMI patients but had the advantage of a homogeneous approach to treatment and follow-up strategy. In general, patients transferred rapidly after primary PCI to the other hospitals of the STEMI network were clinically more stable or had less residual coronary disease needing deferred PCI. This may have introduced a bias at baseline selection of the patient cohort, but it could not be avoided in a STEMI network organization. Although patients with previous MI were not excluded, they were not significantly different in the LVR and non-LVR subgroups. Because our study did not include cardiac magnetic resonance, we were unable to determine the direct influence of microvascular obstruction and presence of myocardial hemorrhage on LVR. Myocardial strain evaluation was performed using echo scanners of a single vendor; because inter-vendor strain calibration is still lacking ,32, studIn patients treated for STEMI, acute %SAS is significantly and independently associated with development of LVR within 1 year and is better than other echocardiographic LVR predictors; acute %SAS is also associated with unfavorable clinical outcome. Thus, assessment of %SAS after primary PCI could be a helpful routine evaluation to identify very early those STEMI patients at higher risk. Prospective multicenter studies on a wider cohort of STEMI patients are needed to confirm our observations.


This study aimed to evaluate whether quantification of myocardial susceptibility by cardiac magnetic resonance imaging (CMR) can be an imaging biomarker for cardiac amyloidosis (CA).Twenty-six patients with CA underwent CMR, including magnetic phase imaging with a 3.0-T magnetic resonance imaging scanner. Myocardial susceptibility was quantified as a phase shift slope value by magnetic phase analysis. Those values from patients with CA were compared with corresponding values from 18 controls and 15 healthy volunteers. A univariate logistic regression analysis was conducted to identify significant parameters related to CA.p < 0.01). From a total of 17 tested variables, 6 were considered to be significant predictors of CA (p ≤ 0.05) during the univariate analysis. The phase shift slope yielded the best AUC of 0.89 (95% CI = 0.79–0.98) for the prediction of CA (p < 0.01). The phase shift slope was significantly correlated with the end-diastolic thickness of the interventricular septum  and posterior wall of the left ventricle .The phase shift slope, a quantitative parameter of myocardial susceptibility, was significantly lower in the CA group compared with the control group and compared with healthy volunteers (Myocardial susceptibility analysis by CMR helps in the diagnosis of patients with CA and can be a new quantitative imaging biomarker for CA. Cardiac amyloidosis (CA) is caused by an accumulation of amyloid fibrils in myocardial interstitium, which induces a characteristic progressive and restrictive infiltrative cardiomyopathy. Cardiac involvement is the most significant predictor of poor prognosis in patients with systemic amyloidosis . AmyloidCardiac magnetic resonance imaging  using late gadolinium enhancement (LGE) imaging helps in the diagnosis of cardiac involvement in patients with systemic amyloidosis . The assRecently, attention has been focused on performing more specific diagnosis by multiparametric analysis using a number of the nonspecific quantitative imaging biomarkers, including T1 mapping. Some previous studies have reported the potential value of multiparametric CMR analysis in identifying cardiac damage . In the Magnetic susceptibility describes the extent to which a substance becomes magnetized when placed in an external magnetic field. Many biological tissues exhibit either positive or negative susceptibility and are termed paramagnetic or diamagnetic, respectively. Moreover, some of these tissues also have susceptibilities that are dependent on tissue orientation. Particularly, striated muscle tissue is known to exhibit anisotropic magnetic susceptibility. Although susceptibility-weighted imaging successfully demonstrated that field inhomogeneity induced by susceptibility could be used to infer the tissue property, the missing link between the observed phenomenon and underlying cause was not connected, and it does not provide quantitative measures of magnetic susceptibility. Local susceptibility directly or indirectly affects phase differences in magnetic resonance phase images. Therefore, it is possible to quantify local susceptibility based on phase differences. Quantitative susceptibility imaging (mapping) is a new MRI technique that aims to extract the spatial susceptibility distribution of tissues from the measured MRI phase or local field data . To the This study aimed to evaluate whether the quantification of myocardial susceptibility by CMR can be an imaging biomarker for CA.This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The retrospective study was approved by our institutional review board, and patient informed consent was waived. Between July 2015 and July 2016, 26 patients with CA ; range, 28–86 years) and no contraindications for CMR were enrolled in this study. Eighteen patients had hereditary (variant) transthyretin amyloidosis, six had wild-type transthyretin amyloidosis, and two had immunoglobulin light-chain amyloidosis. CA was diagnosed based on clinical findings, amyloid deposition, and genetic testing. It was histologically confirmed by Congo red and immunohistochemical staining of bone marrow, soft tissue, fat, upper gastrointestinal tract, rectal, and liver specimens. Eighteen patients  clinically referred for CMR had normal heart structure and function and were age- and sex matched to the CA group as control (control group). Clinical indication of CMR in patients assigned as controls was abnormal electrocardiogram or history of syncope. Fifteen healthy volunteers  with no prior cardiac history or symptoms of cardiovascular disease or known cardiac risk factors, who had normal electrocardiographic findings, and who did not take any cardiovascular medications were also enrolled in this study. Informed consent was obtained from healthy volunteers before their participation in this study. Three patients with CA were excluded from the study because of the poor image quality.E velocity), deceleration time of the mitral inflow, and mitral annular velocity at the septal annulus (eʹ velocity), we used the standard apical four-chamber view.All patients underwent standard echocardiographic studies on a commercial ultrasound machine  equipped with a 3.5-MHz transducer. The examinations were performed by experienced investigators. All measurements were performed in accordance with the current American Society of Echocardiography and European Association of Echocardiography guidelines , 9. We mAll CMR studies were performed on a 3.0-T MRI scanner . The patients were scanned in the supine position using a 16-channel phased-array coil. Images were acquired using T2-weighted black blood with the short tau inversion recovery. Cine imaging was obtained with a segmented steady-state free-precession sequence. LGE imaging was performed in short- and three long-axis views  with a mid-diastolic inversion-prepared two-dimensional (2D) gradient echo (GRE) sequence and three-dimensional (3D) phase-sensitive inversion recovery sequence. Data acquisition started 8 min after injection of 0.2 mmol/kg of a gadobutrol .r = 2.0, acquisition matrix size = 1.25 × 1.56 mm, reconstruction matrix size = 0.63 × 0.63 mm, slice thickness = 7.0 mm, bandwidth = 289.4 Hz per pixel, scan duration = 14.8 s and black-blood pulse. Cardiac triggering was set for mid-diastole to reduce motion artifact. Both magnitude and phase images were generated from each echo. All phase data were processed using an integrated phase unwrapping algorithm that created phase maps . The imaging parameters included: repetition time = 18 ms, echo time = 3.8–15.2 ms (four echoes), flip angle = 20°, field of view = 200 × 200 mm, SENSE factoFor the quantification of myocardial susceptibility, regions of interest (ROIs) were manually drawn on the septal midventricular wall on each phase map by two cardiovascular radiologists with 10 and 13 years of experience in CMR. The ROI on the magnitude image was copied and pasted onto the phase map Fig. . Myocardt-test and Mann–Whitney U-test, respectively. The χ2 test was also used for comparisons between the two groups. One-way analysis of variance was used in multiple comparisons of the mean phase shift slope of patients with CA, controls, and healthy volunteers. If a significant difference was observed, then pairwise comparisons were performed with the Tukey’s test. The intraclass correlation coefficient (ICC) was calculated in order to determine the level of interobserver agreement for quantification of myocardial susceptibility. To identify significant parameters related to CA, univariate logistic regression analyses were performed, and the area under the receiver operating characteristic curve (AUC) of each parameter was calculated to assess the diagnostic accuracy. Results are presented in the form of odds ratio (ORs) with 95% confidence intervals (CIs) and p-values. Correlations were assessed with the Pearson correlation or Spearman coefficient. Differences of p < 0.05 were considered statistically significant. All statistical analyses were performed with the Bell Curve for Excel .All numeric values were reported as mean ± standard deviation. Differences of the mean values between the CA and control groups with normally and non-normally distributed data were determined with the two-tailed independent p < 0.01). There was no significant difference in the end-systolic dimension and left ventricular ejection fraction between the groups. The ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (E/eʹ) was significantly greater in the CA group (p < 0.01). High-sensitivity cardiac troponin T (hs-cTnT) levels were significantly higher in patients with CA (p = 0.02).The baseline characteristics of our patients are presented in Table p < 0.01) .The phase shift slope, a quantitative parameter of myocardial susceptibility, was significantly lower in the CA group compared with that in the control group and healthy volunteers (01) Fig. . There wRepresentative cases are shown in Fig. p < 0.05) during the univariate analysis, including IVSTd, PWTd, E/eʹ, plasma B-type natriuretic peptide level, hs-cTnT level, and phase shift slope. The phase shift slope yielded the best AUC of 0.89 (95% CI = 0.79–0.98) for the prediction of CA (p < 0.01)  and PWTd  in all patients (controls and CA). No significant correlation between all clinical parameters and the phase shift slope was found in CA.As shown in Table We demonstrated that the phase shift slope that serves as a quantitative parameter of myocardial susceptibility was significantly lower in the CA group than in the control group and healthy volunteers and identified it as a predictor of CA. The predictive ability of the myocardial susceptibility was high, with an AUC of 0.89. The myocardial susceptibility was significantly correlated with the IVSTd and PWTd in all patients. This observation may be of practical importance and identifies myocardial susceptibility analysis by unenhanced CMR as a noninvasive technique for quantitative marker of patients with CA. Although the underlying etiology for the change in myocardial susceptibility in CA has been unknown, possible causes include the iron distribution, metabolic oxygen consumption, blood degradation, calcification, myocardial anisotropy, and other pathophysiological conditions.Verifying the myocardial susceptibility and its underlying mechanisms using CMR may lead to improved techniques for the examination of microstructure of the heart. Myocardial fiber organization and structure are important determinants of myocardial stress and strain. These are altered by cardiac hypertrophy, fibrosis, infarction, and material deposition. They also seemed to play an important role in arrhythmogenesis. In CA, extracellular ß-pleated amyloid deposits cause disruption in myocardial architecture . Hence, Changes in myocardial susceptibility do not appear to be disease specific, but this needs further validation. According to our results, myocardial susceptibility analysis can be used in the assessment of cardiac involvement in patients with systemic amyloidosis or in cases wherein CA is highly suspected. Moreover, myocardial susceptibility analysis by CMR has the potential to serve as a noninvasive imaging marker for disease surveillance, possibly contributing to the management of patients with CA.T2*-weighted GRE CMR has shown potential as a method for the assessment of myocardial susceptibility . The GREMyocardial anisotropy is assessed with diffusion tensor imaging and histology –15. EvenMyocardial T1 mapping that is typically used to evaluate the myocardial T1 relaxation time facilitates noninvasive detection and quantification of biologically important processes associated with myocardial edema, fibrosis, and material deposition. Unenhanced T1 mapping or native T1 mapping reflects myocardial diseases, involving the myocyte and interstitium, without use of gadolinium-based contrast agents. Furthermore, contrast-enhanced T1 mapping enables the calculation of the extracellular volume (ECV) fraction. CA is associated with significantly elevated native T1 and ECV values relative to those documented in other cardiac diseases, demonstrating the high-diagnostic precision of T1 mapping in CA detection , 17. BasRecently, Wen et al. investigated the feasibility of quantification of myocardial susceptibility using CMR, and reported that mixed-venous oxygen saturation which is an important indicator of cardiac function can be measured non-invasively . DeoxyheThis study had several limitations. First, the number of patients was small, and the study was performed at a single center. Validation with a similar cohort would be useful to support our results, but this cohort was unavailable. This is the first cohort study in which patients with CA underwent CMR myocardial susceptibility analysis that constitutes the novel and creative features of our study. Large-scale prospective clinical studies are required for rigorous evaluation of the feasibility of our methods. Second, we did not examine the relationship between histological findings and myocardial susceptibility results. Third, we did not evaluate the myocardial susceptibility for cardiac diseases other than CA, such as hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive heart disease, etc. The applicability of CMR myocardial susceptibility analysis for the characterization of these cardiac diseases should be explored. Lastly, we did not compare the myocardial susceptibility findings in CA subtypes because the sample size was too small for meaningful comparative analyses. Large-scale comparative studies are needed to define the myocardial susceptibility features of each type of CA.In conclusion, myocardial susceptibility analysis by unenhanced CMR helps the diagnosis of patients with CA. The quantification of myocardial susceptibility by CMR may offer new insights for cardiac diseases and can be a new quantitative imaging biomarker for CA. Additional pathological studies are needed to explain the relationship between the observed phenomenon and underlying causes.