The aim of this review article is to summarize current knowledge of the pathophysiology underlying right ventricular failure (RVF), focusing, in particular, on right ventricular assessment and prognosis. The right ventricle (RV) can tolerate volume overload well, but is not able to sustain pressure overload. Right ventricular hypertrophy (RVH), as a response to increased afterload, can be adaptive or maladaptive. The easiest and most common way to assess the RV is by two-dimensional (2D) trans-thoracic echocardiography measuring surrogate indexes, such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tissue Doppler velocity of the lateral aspect of the tricuspid valvular plane. However, both volumes and function are better estimated by 3D echocardiography and cardiac magnetic resonance (CMR). The prognostic role of the RV in heart failure (HF), pulmonary hypertension (PH), acute myocardial infarction (AMI), and cardiac surgery has been overlooked for many years. However, several recent studies have placed much greater importance on the RV in prognostic assessments. In conclusion, RV dimensions and function should be routinely assessed in cardiovascular disease, as RVF has a significant impact on disease prognosis. In the presence of RVF, different therapeutic approaches, either pharmacological or surgical, may be beneficial.  In the normal adult, the mass of the RV is also only about one-third that of the left ventricle (LV): 26 ± 5 (17–34) g/m2 for the RV versus 87 ± 12 (64–109) g/m2 for the LV [The RV has a unique crescent shape which influences its physiological properties. The normal range of right ventricular end-diastolic volume (RVESV) is 49–101 mL/m6 ± 5 17–4 g/m2 foThe RV encompasses two myocardial bands: the ventriculo-infundibular band; a muscular fold between the pulmonary valve and the tricuspid valve (TV) that extends to the subpulmonary infundibulum of the RV outlet, and the septomarginal band, extending from the septum to the anterior wall and supporting a papillary muscle. RV contraction is peristaltic, from the sinus to the conus, with a major radius of curvature of roughly 4 cm and a small radius of curvature of 0.8 cm ,6. This The RV propels blood into the pulmonary circulation; a huge territory that has low hydraulic impedance. As a consequence, the thickness of the free wall in the RV is lower than in the LV. In the LV, there is a third layer of fibres  which account for the reduction of ventricular diameter. The RV, lacking this layer, has to rely more on longitudinal shortening than the LV. RV contractions mainly depend on its loading conditions.The pressure-volume relationship of the RV was defined by Redington et al.  as a triKovalova et al.  found thThe ventricles share not only the visceral cavity (pericardium) but also myofibres, particularly in their superficial layers, and the interventricular septum, which contributes to the ejection of both cavities. Damiano et al.  suggesteRVF can result from global or regional ischaemia due to coronary disease, but most commonly it is the result of increased afterload. In fact, even mild increases in afterload can lead to profound decreases in RV stroke volume . In someThe RV pressure-volume pattern (being related to low flow impedance) is a dynamic phenomenon in which a slowly progressive rise in pulmonary arterial impedance causes a progressive change towards a LV-type pressure–volume loop  Figure .Right ventricular hypertrophy (RVH), as a response to increased afterload, can be either adaptive  or maladaptive . In some cases, increased RV mass is sufficient to compensate for increased afterload while maintaining an unchanged RV cardiac output. When insufficient, increased RV mass leads to a maladaptive response and rapid decompensation ,14. The Moreover, coronary perfusion may fail to meet the increased demands for oxygen in RVH, causing ischaemia, and leading to RVF  Right coIn chronically increased afterload, the RV pressure-volume relationship shifts from a trapezoidal shape (reflecting its high efficiency/low impedance) to a square or rectangular shape with well-developed isovolumic contraction and relaxation periods rendering the normal LV pressure-volume loop indistinguishable from that of the RV .Nowadays, it is well-known that the main differences between the two ventricles are not limited to global structure and loading conditions, as early during cardiac development LV cardiomyocyte differentiation begins to diverge from that of the RV .In fact, differences at the cellular and molecular levels form the basis of differential right versus left ventricular responses to pressure overload stress. Both ventricles exhibit similar alterations in the genes regulating the extracellular matrix and cytoskeletal remodeling, but with significant differences in those genes regulating energy production, mitochondrial function, reactive oxygen species (ROS) production, antioxidant protection, and ischaemia ,24,25. FIn patients with PAH, leftward displacement of the interventricular septum hampers LV filling .There are several known causes of RVF, but this condition is generally attributed to PAH, TV disease, left-side heart failure with secondary pulmonary hypertension, chronic pulmonary disease, left ventricular assist device (LVAD) implantation, or congenital heart diseases.PAH is a type of pre-capillary pulmonary hypertension, characterized by normal or low wedge pressure , which cThe decompensated phase of right ventricular systolic failure produces symptoms with minimal activity or at rest. Elevated right atrial pressure and systemic venous hypertension cause hepatic congestion, leading to an enlarged, pulsatile liver and ascites. Renal venous congestion, combined with decreased renal arterial perfusion causes diuretic resistance, reduced urine output, and prerenal azotemia . A low cTricuspid valve regurgitation (TR) is most commonly secondary to left ventricular valve disease, and is mainly consequent to mitral valve disease. More rarely, TR occurs as a result of valve endocarditis, rheumatic valve disease, carcinoid or congenital heart disease. The RV and the tricuspid valve have a bidirectional relationship, as TR can cause RV failure and RV failure can cause TR. Functional tricuspid regurgitation (FTR), , is the result of both annular dilatation and leaflet tethering due to RV enlargement, factors which can themselves also influence leaflet coaptation via different mechanisms.The annular enlargement develops mainlyat the level of the free wall and is accompanied by changes in planar shape. Ton-nu et al.  found thHowever, annular dilatation alone is insufficient to cause TR, even if it can impair proper coaptation of the leaflets. In an interesting study, Sadeghi et al.  reportedRV dilatation causes an inward displacement toward the centrum of the three papillary muscles (PMs), caused by the displacement of the septal wall into the RV as occurs with increased LV volume. Changes in LV geometry are transferred to the RV though the interventricular septum , resultiThe interdependence of RV and LV is the root cause of biventricular failure at end-stage heart failure. In the case of increased RV afterload, RV systole is prolonged, extending into LV diastole, and is worsened by increasing heart rate. Hence, RV filling time is severely shortened , compromThe interaction between the two ventricles is particularly evident when LV is mechanically unloaded. Mau et al.  demonstrMost of the effects of LV contraction on the RV are mediated by the interventricular septum. During systole, the septum twists and shortens, causing a reduction in ventricular volume and forceful ejection of blood out of both ventricular cavities. In the RV, in the absence of septal twisting due to septal damage, ventricular ejection is produced by circumferential constriction caused by the contraction of the basal wall that contains predominantly transverse fibres. Such constriction may not allow for the delivery of enough contractile force to ensure adequate cardiac output when pulmonary vascular resistance is increased. Septal dysfunction may form the basis of RV dysfunction that develops perioperatively, together with new septal akinesia or hypokinesia.When the RV is dilated, the interventricular septum shifts toward the left, altering LV geometry and increasing pericardial constriction. As a consequence, LV preload is decreased and LV end-diastolic pressure is increased, causing low cardiac output states ,40. WhenThe interdependence between right and left ventricles is the basis for the use of an intra-aortic balloon pump (IABP) in cases of RVF. Left diastolic dysfunction related to septal bowing to the left can improve after IABP positioning, and also causes an indirect positive effect on RV performance .According to World Health Organization (WHO), the majority of cases of PH and RVF are those associated with chronic lung diseases; such as chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and sleep disordered breathing (SDB) .The pathophysiological changes underlying RVF in chronic pulmonary disease are increased pulmonary vascular resistance (PVR), resulting in the pulmonary arterial pressure rising roughly 3 mmHg/year and RV pressure overload. Chronic hypoxaemia and the disruption of pulmonary vascular beds through parenchymal loss and fibrosis, are the key mechanisms through which chronic lung disease increases PVR. As for PAH, concentric hypertrophy of the RV is an adaptive mechanism to preserve systolic function , but thi2) in the absence of an elevated left atrial/pulmonary capillary wedge pressure (PCWP) >18 mmHg; tamponade; ventricular arrhythmias or pneumothorax requiring right ventricular assist device (RVAD) implantation or requiring inhaled nitric oxide or inotropic therapy for a duration of more than one week at any time after LVAD implantation; ascites or evidence of moderate-to-severe peripheral oedema; evidence of elevated CVP by echocardiogram (dilated inferior vena cava without collapse); and signs of increased jugular venous pressure during the physical exam. The optimal haemodynamic parameters of preoperative RV function, indicating a low probability of developing RVF, are CVP ≤ 8 mmHg; PCWP ≤ 18 mmHg; CVP/PCWP ≤ 0.66; PVR < 2 wood units; and right ventricular stroke work index (RVSWI) ≥ 400 mmHg mL/m2 [RVF represents a frequent complication following LVAD implantation; with the incidence of RVF ranging from 20% to 50% of LVAD cases. Although, in theory, RVF may benefit from a reduction of left atrium pressure, leftward intraventricular septum (IVS) shift and increased venous return, may lead to RV dysfunction . The detHg mL/m2 .RVF remains an important clinical problem in several congenital heart diseases (CHDs). Pressure-overload RV failure is caused by RV outflow tract obstruction after total correction of tetralogy of Fallot, pulmonary stenosis, atrial switch operation for transposition of the great arteries, congenitally corrected transposition of the great arteries, and systemic RV failure after the Fontan operation. Volume-overload RV failure may be caused by an atrial septal defect, pulmonary regurgitation, or tricuspid regurgitation .Isolated pulmonary stenosis is the most common right ventricular outflow tract (RVOT) obstructive CHD. Although the obstruction may also occur at the subvalvar or supravalvar levels, 80% to 90% of cases have valve-level obstruction . RegardlIn moderate-to-severe pulmonary valve stenosis, patients remain asymptomatic until adulthood. The right ventricle is able to adapt to pulmonary valve stenosis. However, long-lasting untreated severe obstruction may lead to RV failure and tricuspid regurgitation. Congenitally corrected transposition of great vessels (TGA) is associated with moderate-to-severe systemic atrioventricular valve  regurgitation and RVF .2, leading to an atrialized RV and moderate-to-severe tricuspid regurgitation. RVF in the Ebstein anomaly results from volume overload of the RV and from a hypoplastic RV chamber unable to manage the systemic venous blood [The RV adapts better to volume overload than to pressure overload ; howeverus blood .The prognostic role of RVF in LV heart failure (HF), PH, acute myocardial infarction (AMI), and cardiac surgery has been overlooked for many years. However, more recently, several studies have attributed a more prominent role to the RV in prognostic assessments ,72,73,74In a recent study, the roles of PH and right ventricular dysfunction were evaluated in patients with AMI and LV dysfunction. The impact of RV dysfunction without PH on mortality was restricted to the first 30 days after the infarct, without any effect on long-term mortality or the risk of re-admission for HF. Beyond the 30-day timepoint, PH was the dominant risk factor for long-term mortality. In addition, PH , was a strong independent predictor of re-admission for HF, whereas RV dysfunction without PH was not .Right ventricular dysfunction may develop in association with left ventricular dysfunction via a number of different mechanisms listed here. Firstly, left ventricular failure increases afterload by increasing pulmonary venous and ultimately pulmonary arterial pressure; the same cardiomyopathy may simultaneously affect both ventricles; myocardial ischaemia may involve both ventricles; left ventricular dysfunction may lead to decreased right ventricular coronary perfusion, which may be an important factor influencing onright ventricular function; and lastly, ventricular interdependence due to septal dysfunction may occur so that left ventricular dilatation in a limited pericardial compartment may restrict right ventricular diastolic function. In patients with advanced congestive heart failure due to cardiomyopathy or ischaemia, right ventricle shortening is the only significant independent factor found by multivariate analysis to be associated with survival . Patients with right ventricular shortening <1.25 cm have a significantly worse actuarial survival over two years (16% versus 68% for >1.25 cm) . PreservRV dysfunction has been found to be an independent risk factor for both overall and cardiovascular mortality in HFpEF with eight years of follow-up .In cardiac surgery, although there is sufficient evidence in favour of a routine pre-operative assessment of the RV ,66,67,68In contrast, PH is considered to be a strong predictor for mortality after cardiac surgery. However, as has been already demonstrated in patients with HF, PH does not always mirror RV dysfunction, which has an independent and additive prognostic value . In addiFollowing cardiac surgery with cardiopulmonary bypass and pericardial incision, patients show a marked change in the RV contractile pattern, with a relative loss of longitudinal shortening and a gain in transverse shortening. This can occur as a result of a poor myocardial protection or intra-operative myocardial infarction due to early graft failure, a prolonged donor ischaemic time, and a donor RV not adapted to elevated pulmonary vascular resistance in the recipient, as a consequence of end-stage HF.The most common way to assess the RV is through two-dimensional trans-thoracic echocardiography (2D TTE). Although, it should be noted that the assessment of RV morphology and function is very difficult with this method due to the position of the RV immediately below the sternum.However, the systematic assessment of the right side of the heart is still not routinely performed. This is due to the greater consideration given to left side of the heart during patient evaluation, a lack of familiarity with ultrasound techniques that can be employed in imaging the right side of the heart, and the rarity of studies reporting normal reference values for RV dimensions and function. Consequently, a recent review was published by the American Society of Echocardiography, and endorsed by the European Association of Echocardiography and the Canadian Society of Echocardiography, with the aim of proposing guidelines and standards for the assessment of the right side of the heart in adults .The right ventricular chamber size can be assessed at end-diastole from the apical four-chamber view (A4CV) with the focus on the RV. Three different widths can be assessed: basal, mid-cavity, and longitudinal diameter. Another parameter to assess is the RV free wall thickness, measured at end-diastole in subcostal view, at the level of the tip of the anterior tricuspid leaflet; usually an RV free wall thickness >5 mm is considered abnormal.The estimation of right ventricular systolic function by means of ejection fraction (RVEF), derived from RV volumes in 2D echocardiography, shows several limitations mainly due to the particular shape of the RV ,76,77. I2.The evaluation of systolic pulmonary artery pressure with an estimation of peak tricuspid regurgitation (TRV) velocity and right atrial pressure derived from inferior vena cava size and collapse, should be routinely performed to complete the right ventricular heart echocardiographic assessment . However3D real-time transesophageal echocardiography is a very accurate way to assess RV volumes and RVEF, even if minimal data are available in either normal or dilated RV states. Moreover, both volumes and function are underestimated with 3D echocardiography with respect to cardiac magnetic resonance imaging (CMR). Although CMR is nowadays considered to be the most accurate imaging technique for the study of morphology, volumes, function, and tissue determination of the RV, it is still costly and not widely used.RVF can be treated either medically or surgically. First, preload should be optimized and afterload must be reduced. Finally, myocardial contractility should be improved.The most common conditions leading to RVF are characterized by high RV afterload. Hence, reducing excessive RV preload with diuretics or haemofiltration is necessary to reduce RV dilatation and free wall tension, minimizing RV ischaemia and optimizing contractility. Diuretics are recommended in patients with PAH or secondary PH . ConversAcidosis, hypoxia, and hypercapnia have to be corrected in order to reduce PVR as well as RV afterload. Pulmonary vasodilators include several classes of drugs that are approved for use in PAH. However, vasodilators have the potential to cause systemic hypotension. Only a small number of patients do well with calcium-channel blockers (CCBs). The most commonly used CCBs are nifedipine, diltiazem, and amlodipine, with nifedipine and diltiazem deemed most important ,80. The In the acute decomposed phase, improving right ventricular contractility, can be achieved using low-dose dobutamine (5–10 µg/kg/min), which has been shown to restore cardiac output better than norepinephrine . DopaminLevosimendan, a calcium sensitizer, has been shown to improve RV function in left heart disease . HoweverWhen RVF is caused by left ventricular failure, congenital heart disease, or tricuspid regurgitation, the identification and management of treatable causes of RVF is an important aspect of any management strategy. Thus, surgery can be an option to correct coronary artery disease and valve heart disease. In this review, we limited the discussion to the surgical correction of functional tricuspid regurgitation.Surgical strategies to correct FTR are directed mainly to the annulus, using an incomplete ring or a band , or to tIn patients undergoing TV surgery, RV dilatation and severe tethering are frequently observed. In these circumstances, TV annuloplasty leads to increased tethering of the anterior and posterior leaflets, as the annulus is displaced towards the septum. As a consequence, in the presence of RV dilatation, surgical tethering will result in the worsening of post-operative FTR rather than better leaflet coaptation. The recurrence rate of moderate or greater FTR ranges from 2.5% to 5.5% at one-year follow-up .® RP System , and TandemLife  using the PROTEK Duo™ cannula. Surgically cannulated pumps such as the Levitronix® CentriMag® left ventricular assist system  can also offer RV support, when employed in a right atrial and pulmonary artery configuration. Although none of the durable ventricular assist devices are currently approved for RV support, their use has been reported. In recent years, the need for RVAD during LVAD implantation has decreased significantly, as demonstrated in the INTERMACS report of 2001 the implantation rate has decreased from 24.7% in 2006 to 5% in 2011 and 2.9% in 2012, attributed to better patient selection for LVAD. Selected patients with refractory RHF may be candidates for transplantation or total artificial heart implants.In cases refractory to medical therapy or surgery, the timely deployment of mechanical circulatory support may offer a bridge to recovery or to definitive management of the underlying cause. Percutaneous support options include extracorporeal membrane oxygenation (ECMO), which offers right- and left-sided circulatory support. Currently available options for percutaneous right ventricular assist devices include the ImpellaWhen the right ventricle fails, it does so mostly in the presence of pressure overload, as occurs in several cardiovascular diseases. RV failure has a significant impact on disease prognosis, therefore, RV dimensions and RV function should be routinely assessed during patient evaluation. In the presence of RV failure, different approaches, either pharmacological or surgical, may help improve patient outcomes.


The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death.Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan–Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay.P = 0.043, OR 9.207 [2.036–41.643], P = 0.004, separately). Further Kaplan–Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years .A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037–9.500], Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP. Cardiovascular disease comprises all cardiac and vascular disorders, including coronary arterial disease and peripheral vascular disease, among which coronary atherosclerotic heart disease (CAD) is responsible for a large portion . With imIn a previous cross-sectional study , we founThe study subjects, as reported previously, comprised 253 patients at baseline . We revi3 − LVDd3] + 0.6. The LV mass index was calculated as the LV mass divided by the body surface area. The LVEF was measured via Simpson’s method in the apical 4-chamber view. The left ventricular shortening fraction was calculated by (LVDd–LVSd)/LVDd.Echocardiography was performed by a trained specialist with a Philips IE33 ultrasonic device. The left ventricular end-diastolic diameter (LVDd), the interventricular septum dimension (IVST) and the left ventricular posterior wall thickness (PWT) were measured in the parasternal long axis view at the end of the diastolic period. The left atrial diameter (LAD) and the left ventricular end-systolic diameter (LVSd) were measured in the parasternal long axis view at the end of the systolic period. The left ventricular mass (LV mass) was calculated by a formula from Devereux et al.  as LV maGraded left ventricular dysfunction was defined according to the recommendations for cardiac chamber quantification by echocardiography in adults published by the American Society of Echocardiography and the European Association of Cardiovascular Imaging as in the normal range , in the mildly abnormal range , in the moderately abnormal range (30–40%) and in the severely abnormal range (<30%)  were significantly correlated with left ventricular systolic dysfunction at baseline. After multivariate analysis of both variables included in the regression (model 2), we found that a significant independent correlation between the variables and left ventricular systolic dysfunction at baseline still existed  and NT-pro-BNP  remained significant in identifying future risk of cardiac death.Finally, we did a Cox multivariate analysis to adjust survival for confounding factors Table . The resWe determined the relationship between left ventricular systolic dysfunction and FGF21, as well as the traditional indicator NT-pro-BNP, and the identification of these two variables in cases of cardiac death in both cross-sectional and follow-up analysis. We found that FGF21 and NT-pro-BNP were both correlated with left ventricular systolic dysfunction at baseline. Both higher FGF21 and higher NT-pro-BNP levels could predict cardiac death within five years. We therefore concluded that FGF21 was non-inferior to NT-pro-BNP at identifying both left ventricular systolic dysfunction at baseline and cardiac death within five years.FGF21 is involved in the pathogenesis of cardiovascular diseases and metabolic disorders . FGF21 iFew studies have reported the relationship between FGF21 and cardiac function as evaluated by echocardiography. Chou et al.  reportedVentricular remodeling is an adaptive response caused by the hypertrophy of myocardial cells during stress. Mature myocardial cells are differentiated cells that cannot regenerate. Myocardial cells tend to be hypertrophic rather than differentiated during stress, resulting from increased amounts of extracellular matrix and fibroblasts in the heart . FGF21, There are some limitations to this study. First, the sample size of this study is small and we did not calculate the sample size at baseline. Our preliminary results should be validated in further studies with a larger sample size, which can provide sufficient statistical power. Second, the subjects enrolled in our study at baseline are all from the department of cardiology, and tend to be elderly. We also intend to recruit subjects from different age ranges to generalize our results. Finally, no relationship between FGF21 and age is observed at baseline, which is not consistent with another study . PatientIn conclusion, we may consider serum FGF21 levels to be correlated with left ventricular systolic dysfunction at baseline. Patients with higher FGF21 levels at baseline are at greater risk of CVD mortality. The role of FGF21 in both left ventricular systolic dysfunction and cardiac death is not inferior to that of NT-pro-BNP.


Objective: To present a case of a serious manifestation of scorpion sting, which was not reported before in Qatar, review the literature, and compare with previously reported similar cases.Case presentation and intervention: A young male patient was admitted to CCU with a clinical picture of acute toxic myocarditis and cardiogenic shock with abnormal ECG and elevated cardiac markers after a scorpion sting to his right big toe. Thorough investigations, including echocardiography, cardiac MRI and right heart catheterization, supported the diagnosis. Coronary angiography was normal. Patient was managed conservatively with supportive measures, mechanical ventilation, IV fluids, inotropic agents, steroids, antibiotics and Prazocin. Over 9 days of hospital course, patient gradually improved, was successfully extubated, and was discharged in a stable condition.Conclusion: Toxic myocarditis , pulmonary edema and cardiogenic shock are reported manifestations of scorpion venom intoxication. Creatures that are capable of producing a poison in a gland and then delivering that toxin by stinging or biting are called venomous animals. Arthropods  are examples.3. Several clinical syndromes with variable hemodynamic patterns may dominate the clinical presentation3.Scorpion envenomation is potentially fatal in many regions worldwide. Children form the majority of victims. The sting effect depends on the size of the victim, the season, the age of the offender and the delivery dose of the scorpionLeiurus Quinquestriatus , IV hydrocortisone 200 mg, and 2000 ml of normal saline over 4 hrs. The IV fluids were stopped when the patient developed signs of pulmonary edema.ECG showed sinus tachycardia with diffuse ST segment depression . Cardiac2 , systemic vascular resistence of 3150 d s/cm5 , and pulmonary capillary wedge pressure of 32 mmHg  . Right heart catheterization suggested a picture of cardiogenic shock with cardiac output of 1.88 l/min , cardiac index of 1.34 l/min/m12 mmHg) .Next day, the patient was febrile with a temprature of 39°C. He developed short runs of ventricular tachycardia  which sp2, with clear lung fields. He was then successfully extubated.After one week of CCU course, patient was off-sedation, fully conscious, afebrile wih stable hemodynamics. He was maintaining good oxygen saturation on 40% FiOTwo days later, echocardiography revealed significant improvement with normal LV systolic function (EF: 55%). Coronary angiography was normal for both left and right coronary arteries  and 10. Leiurus Quinquestriatus envenomation), this can be associated with hypertensive encephalopathy. Occasionally hypotension with or without bradycardia is the dominating hemodynamic picture2.Clinical manifestation of scorpion envenomation varies from a localized pain in the site of the sting to a severe generalized intoxication. Cardiovascular involvement include hemodynamic disturbances with hypertensive phase and tachycardia dominating the majority of cases , and elevated plasma and urine chatecolamines. In one review of 32 children following Leiurus Quinquestriatus envenomation, 13 out of 32 patients (40.6%) had evidence of myocardial damage manifested by elevated cardiac enzymes  and CK-MB/CK ratio > 6%, while only 6 out of these 13 patients had ECG changes suggestive of myocardial injury5.Sinus tachycardia, variable ST-T changes and prolonged QTc are the most common ECG changes reported in scorpion envenomation. Other changes include bradycardia, myocardial infarction-like changes, conduction abnormalities and rhythm disturbances1. In a 16 patient review in Venzuella, this echocardiographic finding of diffuse hypokinesia was associated with higher plasma levels of noradrenaline. With gradual clinical improvement, both noradrenaline levels and LV contractility with systolic function were normalized simultaneously6. A cohort study of nine patients with scorpion  envenomation in Tunisia found a correlation between the depressed LV systolic function, which was reported in all 9 patients (EF: 26 +∕ − 12%), and the hemodynamic profile which was in all patients suggestive of acute congestive heart failure (PCWP: 24 +∕ − 2 mmHg). Other echocardiographic findings included transient mitral regurgitation and LV diastolic function. One mortality case was reported, otherwise the other 8 patients improved gradually over 5-7 days untill complete recovery7.Both echocardiography and nuclear scintigraphy show global hypokinesia with LV systolic and diastolic dysfunction in the majority of cases, most of which were found to improve gradually till complete resolutionIn our case, which is the first to reported in Qatar, the initial presentation was hypotention, tachycardia and heart failure. However there were a few hours prior to the patient’s presentation during which his hemodynamic picture was unknown.The invasive hemodynamic study completed immediately after admission confirmed the cardiogenic rather than anaphylactic or septic etiology of his shock status. Laboratory, electrocardiographic, and echocardiograhic findings were compatible with the commonly reported findings in previous similar cases.Cardiac MRI, which was not one of the routine investigations for previously reported cases, was done for our case and revealed global LV hypokinesia and impaired systolic function with diffuse myocardial edema suggestive of acute myocarditis  and 7. TThe markedly elevated cardiac markers as well as the significant ST segment changes in the ECG made ischemic etiology (acute coronary syndrome) a possibility, however the echocardiographic and cardiac MRI findings, i.e. the absence of both segmental wall motion abnormalities and myocardial scarring were against this possibility, putting the inflammatory (toxic) etiology on top of deferrential diagnosis list. The normal coronary angiography proved this result later on.As in the majority of reported cases, the gradual and full improvement and resolution of the clinical, hemodynamic, electrocardiographic and echocardiographic abnormalities was observed in our case.8.Management of scorpion envenomation consists of supportive measures and close monitoring, anti-venom adminstration, and Prazocin. Supportive measures include admission to intensive care unit, close monitoring, good hydration and fluid balance, mechanical ventilation and respiratory support, cautious use of inotropic agents if needed, steroids and antibiotics as needed. Inotropic agents role is questionable since their effect of hemodynamic support has no proved mortality benefit6. In a review of the Saudi Arabian experience with antivenom (serotherapy) which involved more than 3,800 cases of scorpion stings, it was established that the incidence of severe venom toxicity was almost negligible in the patients who received early antivenom with reduced hospital stay duration. No significant side effect or serious reactions were reported from the serotherapy in this Saudi experience9.Early administration of anti-venom has been associated with both less cardiovascular manifestations and lower plasme noradrenalin levels10. Similar encouraging results were reported in Saudi Arabia for patients who received prazocin after sub-optimal outcomes with antivenom therapy11.Prazocin, an alpha adrenergic blocker, was found to add a significant benifit to the outcomes of scorpion sting management. In a review from west India, the mortality rates in the pre-prazocin era (1961-1983) were ranging from 25% to 30%. Later on with prazocin therapy the mortality rate was reduced significantly to less than 1%. Prazocin was then considered as an antidote to scorpion venomMyocaritis, pulmonary edema, and cardiologic shock are reported complications of scorpion envenomation. Supportive measures, early anti-venom administration and Prazocin therapy are the main management lines. Cardiac MRI is recommended, when available, as one of the main diagnostic tests in such cases.


In normal ageing, both vascular and ventricular properties change, and how these affect left ventricular function is not clear.96 subjects (ages 20–79) without cardiovascular disease underwent cardiac magnetic resonance (MR) imaging for measurement of global function, diastolic function (E/A ratio), MR tagging for measurement of torsion to shortening ratio , and phase contrast MR imaging measurement of central aortic pulse wave velocity (PWV). The Vicorder device was used to measure carotid to femoral PWV.Univariate correlations established that the 4 principal age-related changes in the left ventricular function were: 1) diastolic function: E/A ratio ; 2) global systolic function: cardiac output , 3) structure: end-diastolic volume index , and 4) systolic strains: TSR . Multiple linear regression analysis showed that age was the dominant factor in predicting changes in cardiac output and E/A ratio (both p < 0.01). Increased TSR was significantly related to reduced cardiac output and end-diastolic volume index (p < 0.05 and p < 0.01 respectively). Measures of vascular stiffness were not significantly related to any of these variables, but increased effective arterial elastance (afterload) was significantly related to reduced E/A ratio (p < 0.05).In this group of normal ageing subjects, afterload but not vascular stiffness is significantly related to diastolic dysfunction. Increased TSR, suggesting relative subendocardial dysfunction, has a significant role in reductions of cardiac output and end-diastolic volume index. Vascular stiffening increases from the 3rd decade or earlier in normal subjects Magnetic resonance imaging can accurately assess changes in left ventricular blood pool volumes with age Torsion, and the ratio of torsion to endocardial circumferential shortening (TSR) are also known to increase with normal ageing 22.1NCT01504828). All subjects had measurements of pulse wave velocity by the Vicorder device and the MRI on the same day within 2 h.Ninety-six subjects  aged between 20 and 79 years were recruited into six discrete age bands, with 16 subjects in each decade 20–29, 30–39, 40–49, 50–59, 60–69 and 70–79 years. The subjects were screened with a 12-lead electrocardiogram, fasting lipid profile, and blood pressure measurements. Subjects with hypertension (systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mm Hg), were excluded from the study, as well as any other cardiovascular diagnosis, diabetes mellitus or dialysis-dependent renal failure, or any treatment with antihypertensive therapy. There were 9 patients that were deemed not suitable for the study after attending for a screening visit. These were 2 patients aged 40–49, 1 50–59, 4 60–69 and 2 70–79. The reasons for failing the screening visit: were 7 had BP > 150 systolic or 90 diastolic, 1 patient was on a thiazide diuretic, and 1 patient had musculoskeletal problems making MR imaging problematic. Informed written consent was obtained for all patients, and this study was approved by a UK National Health Service Research Ethics Committee  is an inflatable cuff-based device that simultaneously measures the upstroke of carotid and femoral pulsations to calculate pulse wave velocity, and has been evaluated extensively by comparing with invasive measurements and other tonometric devices 2.32, velocity encoding (Venc) = 150 cm/s, 44 phases, breath hold duration ~ 19 s) A Philips Achieva 3T scanner and a 6 channel receiver array coil were employed to acquire cardiac MRI data as previously described, and validated against the Vicorder measures of PWV 2.4Details of cardiac cine imaging have been previously reported in detail 2.5Tagged short axis images were obtained at the same session. A turbo-field echo sequence with acceleration factor 9 was employed  2.6The strategy was to determine how measures of vascular function and afterload  changed with age, and identify which parameters of systolic, diastolic function and strains were most strongly related to age by the Pearson correlation method. We then used the Bonferroni correction procedure for multiple comparisons when comparing measures of vascular stiffness with left ventricular function. Those variables that were significantly related with this univariate analysis were then used in the multiple linear regression analysis to determine independent predictors of the measures of age-related measures of left ventricular function, while additionally accounting for the effects of gender. Comparisons of means between groups were tested using ANOVA. Where appropriate, data were normalised to body surface area. Statistical testing was performed using Matlab, Mathworks, Cambridge, UK, and SPSS version 22. Statistical significance level was taken to be p < 0.05.3Key subject characteristics are reported in 3.1PWV increased significantly with age with both techniques , as shown in 3.2Cardiac output  and TSR , while late filling rate increased , there was marked decrease in the early filling percentage  and early to late ventricular filling ratio (E/A ratio)  and systolic strains (TSR), and one measure of the left ventricular structure (end-diastolic volume index)  were comBased on the outcomes of the analysis in 4We have demonstrated that in a group of normal subjects without cardiovascular diagnoses of a wide range of ages using state of the art MR imaging that a) with normal ageing there is development of abnormalities of left ventricular function characterised by abnormal diastolic function and reduced cardiac output, b) these parameters of normal ageing are not significantly related to 3 measures of vascular stiffness, though diastolic function is related to afterload and also reduced end-diastolic volume index, c) females have greater reduction in cardiac output with ageing, and d) reductions in cardiac output and end-diastolic volume index are significantly related to increased TSR.4.1In animal experiments it is well recognized that afterload affects relaxation of left ventricular myocardium, with higher afterload resulting in impaired relaxation 4.2o to the fibre direction (cross fibre shortening) Torsion is the result of obliquely orientated subepicardial fibres exerting a mechanical advantage over the inner layers by virtue of their greater radius . SubendoIncreases in torsion and TSR are a significant abnormality of left ventricular ageing detected in this study. TSR is significantly related to both reduced cardiac output and end-diastolic volume index, though is not related to measures of vascular stiffening or afterload. This last point appears to agree with previous studies looking at load sensitivity of torsion. Studies in human transplant recipients who had radio opaque markers implanted at the time of transplant to quantify strains radiologically show that torsion is quite insensitive to increased afterload Several studies recently have highlighted the significance of reduced end-diastolic volume in older age. Cheng and colleagues 4.3This is a cross-sectional study, and longitudinal studies will be more powerful at detecting mechanisms of age-related left ventricular dysfunction. We cannot rule out that in a larger study population that measures of vascular stiffness would be significantly related to left ventricular function, even though we have comprehensively examined the role of vascular stiffness with 3 different methods. Likewise we cannot rule out whether another imaging method of measuring diastolic function would have produced a significant relationship. Those limitations must be balanced against our ability to comprehensively and accurately assess multiple aspects of the left ventricular systolic and diastolic function, left ventricular structure and vascular stiffness, which are not possible with other imaging techniques. None of the subjects in this study had a diagnosis of hypertension, and indeed there is a relatively small age-related increase in systolic blood pressure in this study. Recently and after the completion of this study, it has been suggested that the thresholds to diagnose hypertension should be lowered 4.4Ageing in this cohort of normal subjects without cardiovascular diagnoses is characterised by 2 principal effects on the left ventricular function — impaired diastolic function and reduced cardiac output. Impaired diastolic function is not related to measures of vascular stiffening, but is related to increased afterload and also reduced end-diastolic volume. Increased TSR, suggesting relative subendocardial dysfunction, is significantly related to reduced cardiac output and reductions in end-diastolic volume. These data provide important information about normal ageing, and will help determine how ageing contributes to heart failure in later life.British Heart Foundation Clinical Leave Research Fellowship to GMacG (FS/11/89/29162). No other conflicts of interest.This study was supported by the


Panel A) and sagittal (Panel B) views. This CT abnormality raised the suspicion of left atrial thrombus or tumour, prompting further cardiac imaging.A 52-year-old woman with atopic asthma and a long smoking habit underwent CT pulmonary angiography (CTPA) for investigation of atypical, pleuritic chest pain. There was no history of heart disease or cardiovascular risk factors. As per usual practice for non-cardiac imaging, CTPA was performed without ECG gating. While there was no pulmonary embolism, CT showed an apparent large left atrial filling defect (arrows), demonstrated in axial  and four-chamber  views, showed the left atria to be of normal size and devoid of any visible mass. There was, however, an atrial septum aneurysm, which exhibited 2 cm shift from midline (arrows). Bi-ventricular size and function were normal, and there was no intra-atrial shunt seen on colour Doppler. No medical or surgical intervention was required for this incidental radiographic finding.Transoesophageal echocardiography, shown in short-axis .J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). J.H.F.R. is part supported by HEFCE. M.R.B. and J.H.F.R are supported by the NIHR Cambridge Biomedical Research Centre and the British Heart Foundation.European Heart Journal— Cardiovascular Imaging online.Supplementary data are available at


Symptoms of breathlessness, fatigue, and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging.To evaluate the performance of a clinical decision rule (CDR), with or without N-Terminal pro-B type natriuretic peptide (NT-proBNP) assay, for identifying heart failure.Prospective, observational, diagnostic validation study of patients aged >55 years, presenting with shortness of breath, lethargy, or ankle oedema, from 28 general practices in England.The outcome was test performance of the CDR and natriuretic peptide test in determining a diagnosis of heart failure. The reference standard was an expert consensus panel of three cardiologists.Three hundred and four participants were recruited, with 104  having a confirmed diagnosis of heart failure. The CDR+NT-proBNP had a sensitivity of 90.4% (95% CI = 83.0 to 95.3) and specificity 45.5% (95% CI = 38.5 to 52.7). NT-proBNP level alone with a cut-off <400 pg/ml had sensitivity 76.9% (95% CI = 67.6 to 84.6) and specificity 91.5% (95% CI = 86.7 to 95.0). At the lower cut-off of NT-proBNP <125 pg/ml, sensitivity was 94.2% (95% CI = 87.9 to 97.9) and specificity 49.0% (95% CI = 41.9 to 56.1).At the low threshold of NT-proBNP <125 pg/ml, natriuretic peptide testing alone was better than a validated CDR+NT-proBNP in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The higher NT-proBNP threshold of 400 pg/ml may mean more than one in five patients with heart failure are not appropriately referred. Guideline natriuretic peptide thresholds may need to be revised. The diagnosis requires objective evidence of cardiac dysfunction, usually found using echocardiography, but deciding which patients to refer for further testing is challenging. This study found a validated clinical decision rule (CDR) added little to diagnostic accuracy and that N-Terminal pro-B type natriuretic peptide levels (NT-proBNP) testing alone should be carried out in symptomatic patients with suspected heart failure. The cut-off needs to be low enough to ensure cases are not missed.The REFER study was a prospective, observational, diagnostic validation design to assess the performance of the Male, Infarction, Crepitations, Edema (MICE) rule and NT-proBNP level in identifying patients with heart failure. The study population was primary care patients aged >55 years presenting with recent new-onset shortness of breath, lethargy, or peripheral ankle oedema of >48 hours’ duration for which there was no other obvious cause. Patients were excluded if they were unable to give consent, had a previous confirmed diagnosis  of heart failure, an obvious alternative diagnosis, severe symptoms requiring immediate management, or recent (within 60 days) acute coronary syndrome.The original study protocol stated a recruitment target of 500 participants from 20 practices  over an 18-month period. Due to difficulties in prospectively recruiting patients within GP appointments at a time of unprecedented demand on the service, the length of the recruitment period was extended and the number of practices increased.The recruitment phase of the REFER study started on 1 May 2011 and completed on 31 August 2013. Participants were recruited from a random sample of 28 general practices in central England, stratified by practice list size and deprivation quartile.Assessments were carried out within 7 days of recruitment by trained research nurses and an echocardiographer accredited by the British Society of Echocardiography (BSE). Informed consent was obtained, and then detailed clinical history and examination, blood testing, electrocardiograph (ECG), and echocardiogram were carried out. Two attempts at blood taking were allowed. The NT-proBNP level was determined using a point-of-care device .The reference standard was an expert consensus panel of three cardiology specialists, who reviewed each case blinded to the assessments by other panel members. The ESC 2012 guideline was used to define heart failure.A sample of 500 symptomatic patients attending their GP with breathlessness, lethargy, or ankle swelling was proposed. This sample size was sufficient to estimate the sensitivity of the CDR to within 4% and specificity to within 6% at the 95% confidence level. Calculations were based on a sensitivity of 94% and specificity of 48% obtained from the previous individual patient data meta-analysist-tests or Wilcoxon ranked sum tests for continuous measures and χ2 tests for categorical variables. The main outcome measures were test performance of the CDR and natriuretic peptide test — alone and in combination — in estimating a diagnosis of heart failure. The findings of the expert consensus panel determined if heart failure — the Observed Disease — was present or absent. The CDR and NT-proBNP results were also used to determine whether heart failure was likely to be present — the Test Disease — and referral for echocardiography would have been indicated. Observed versus Test Disease status was then cross-tabulated to determine the sensitivity and specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CDR, NT-proBNP, and their combination; and also by NT-proBNP cut-offs of 125 pg/ ml and 400 pg/ml suggested by the ESC and NICE guidelines respectively.4,8Participants with and without a diagnosis of heart failure at Step 3 were compared using independent The binomial exact method was used to calculate 95% confidence intervals (CIs). Receiver operating characteristics (ROC) curves were generated to determine the overall discriminatory ability of each test in predicting a diagnosis of heart failure. Comparisons were made between performance characteristics of the current cohort and those observed in the original derivation dataset.The clinical and demographic characteristics of the study population are shown in The REFER cohort, although similar in age and sex to the derivation dataset,The expert panel reviewed the data for each participant and determined whether or not a heart failure diagnosis was present; 104 participants had heart failure, which represented 34.2% (95% CI = 28.9 to 39.8) of the cohort. The objective abnormalities found on ECG and echo are shown in The characteristics of participants with and without heart failure are shown in The median NT-proBNP level was significantly higher in the heart failure group. At the lower 125 pg/ml cut-off, over half of patients without heart failure had an NT-proBNP above the threshold for referral to echocardiography.The diagnostic accuracy of the CDR, NT-proBNP level, and their combination is shown in P<0.0001) were observed between the areas under the receiver operating curves (AUROCs) shown in These performance characteristics were mostly lower in magnitude than the corresponding values observed in the derivation dataset. However, comparison of the CIs suggests that the differences were not statistically different at the 5% level. P<0.05).The performance characteristics for the CDR+NT-proBNP or NT-proBNP alone at Steps 1 to 3 are shown in The CDR was not clinically helpful in isolation; NT-proBNP testing alone performed as well as the validated CDR in determining which patients presenting with possible heart failure symptoms went on to have a diagnosis of heart failure. At a NT-proBNP threshold of 125 pg/ml, as advised in ESC guidance, 94% of patients who went on to have heart failure were identified. However, at an NT-proBNP threshold of 400 pg/ml, the current level recommended by NICE in England, only 77% of heart failure patients were appropriately referred. More than one in five patients in this study would have been misdiagnosed.4This study included patients presenting prospectively to their GP. A large proportion of health care in England is provided through general practice, and testing the CDR in a real-life clinical setting where most patients are managed allows accurate validation of the rule.The number of participants with heart failure due to reduced ejection fraction was unexpectedly low in the cohort. This may reflect the nature of heart failure presentation where those with left ventricular systolic dysfunction may be more likely to present acutely direct to secondary care, or may already be under the care of a cardiologist for a known cardiovascular comorbidity such as coronary artery disease.26The increase in performance across the stepped diagnosis suggests that the sensitivity of the index tests may have been overestimated due to incorporation bias. However, evaluation of the results at Step 2  confirms that the diagnostic accuracy of the NT-proBNP test alone at the lower cut-off is similar to that of the CDR+NT-proBNP.–31Heart failure can be a difficult diagnosis to make and the idea of a CDR to help primary care clinicians with the decision of who to refer for objective testing is justifiable.28The reason the CDR performed no better than NT-proBNP alone may be due to the diagnosis of heart failure in the cohort being largely heart failure with preserved ejection fraction. This spectrum of patients was different from previous studies of heart failure where the prevalence of a low ejection fraction (<40%) was more common. The derivation and initial validation of the CDR relied predominantly on epidemiological studies, which included heart failure with reduced ejection fraction, so may not directly apply to the REFER population.32,The threshold for NT-proBNP below which heart failure can be reasonably excluded is also an area of ongoing research.4


In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) successfully restores normal antegrade flow in the infarct-related artery in nearly 99% of patients. However, approximately half of all STEMI patients have failed microcirculatory reperfusion, as reflected by microvascular obstruction (MVO), and one-third have myocardial haemorrhage, reflecting severe, ‘downstream’, potentially irreversible, microvascular injury.MVO is the ‘Achilles Heel’ of primary PCI, yet clinicians are generally unaware of the occurrence of MVO and myocardial haemorrhage in their patients, unless cardiac magnetic resonance (CMR) is performed. However, CMR is not done routinely. Other established investigations for detecting failure of myocardial reperfusion, such as angiographic, or electrocardiographic parameters, lack sensitivity and reproducibility in clinical practice.Immediate invasive measurement of microvascular resistance at the time of PCI has the potential to optimise the approach to therapeutic interventions by: (1) acutely identifying patients at high risk of MVO who are most likely to benefit from adjunct therapy, for example, with glycoprotein IIb/IIIa inhibitors, (2) targeting novel therapies in clinical trials to patients with evidence of microvascular dysfunction and (3) allowing immediate evaluation of the efficacy of reperfusion therapy. However, invasive tests of the efficacy of myocardial reperfusion in STEMI patients have been hampered by a number of methodological and technical shortcomings. The ideal acute invasive test of microvascular perfusion and dysfunction should be reliable and reproducible, operator independent and easy to perform with standard PCI equipment.Currently, the index of microvascular resistance (IMR) has the most extensive evidence base to support its use as a reference test of culprit artery microvascular function in patients with acute STEMI. IMR is a thermodilution-derived index, measured using a guide wire that combines a pressure and temperature sensor. Specifically, IMR is defined as distal coronary pressure multiplied by the mean transit time of a 3 mL bolus of saline at room temperature during maximal coronary hyperaemia. IMR measured at the end of primary PCI reproducibly reflects the extent of MVO, observed on CMR. Moreover, an IMR >40 (postprimary PCI) reliably predicts mortality and heart failure (independent of infarct size) at 1 year.et al showed that IMR >40 and CFR ≤2 combined did not confer incremental prognostic value in STEMI patients.CFR reflects epicardial and microvascular vasodilator capacity ; however, CFR does not allow discrimination between the two components. In a previous study, Carrick Heart manuscript, de Waard et alIn their IMR also has drawbacks. A potential limitation of using IMR to assess MVO is that (unlike HMR) the location of the sensor influences transit time so should be constant during repeated measurements and in general standardised to 6–9 cm from the guide catheter. IMR has a weak association with LV mass (unlike CFR).et al-1-s was more strongly predictive for the composite endpoint, HR: 7.0, 95% CI 1.5 to 33.7, was an independent predictor for its individual components and remained independently associated with the composite outcome after adjustment for baseline and procedural characteristics. Furthermore, compared with CFR, HMR was a superior predictor of MVO (defined by CMR). The authors therefore concluded that HMR is superior to CFR, for identifying MI patients with MVO who are at high risk of adverse clinical outcome.De Waard et alLike IMR, HMR represents an emerging approach for the immediate assessment for MVO in the catheter laboratory, but given the considerations around its use, it may be most useful for research purposes rather than unselected real-world practice. Alternatively, IMR would seem better disposed for use in real-world practice. The findings of de Waard The limitations of the current studyFurther work in this area is warranted. In particular, the findings of the current studyIMR and HMR have potential as novel indices for patient selection and as biomarkers of the efficacy of therapy; however, more research is needed to assess whether IMR and HMR are modifiable. Further research is also warranted to validate IMR and HMR as novel tests of the efficacy of intracoronary therapies; should this be the case, the results would support the use of IMR and HMR as a biomarker of the efficacy of therapeutic interventions designed to improve myocardial reperfusion, as assessed in future trials.et alet alIn conclusion, the study by de Waard


A myocardial contusion refers to a bruise of the cardiac muscle, the severity of which can vary depending on the severity of the injury and when the injury occurs. It is a major cause of rapid death which happens after blunt chest trauma and should be suspected at triage in the emergency department. We demonstrated that suspected myocardial contusion patients who have normal electrocardiograms (ECGs) and biomarker tests can be safely discharged. However, if the test results are abnormal, the next steps should be echocardiography and more advanced measures. Diagnosing myocardial contusion is very difficult because of its nonspecific symptoms. If a myocardial contusion happens, cardiogenic shock or arrhythmia must be anticipated, and the patient must be carefully monitored. Several methods are available for its detection, such as Electrocardiography (ECG), echocardiography, nuclear cardiac imaging, and heart biomarkers, none of which have 100% sensitivity.2, 3 Phase approach to patients with suspected myocardial contusion will lead to a significant reduction in the number of trauma patients admitted to the hospital and a reduction in the number of unnecessary diagnostic procedures.4 It has been documented that implementing ECG in the first stage of treating a person with a traumatic contusion (significant thoracic trauma) on the chest shows if the probability of contusion is high; thus, it is a class I recommended diagnostic test.5 Significant thoracic trauma could include multiple rib fractures, simultaneous pulmonary contusion, and hemothorax.Myocardial contusion is an uncommon complication of blunt chest trauma; it is more likely to occur from injuries resulting from accidents related to a sudden decrease in vehicle speed.5, 6 If the results of tests in steps 1 and 2 are abnormal, or if the patient is in shock and cardiac causes are being considered, an echo or long-term monitoring (24–48 hours) is recommended.7-10 The most recent studies have minimized the necessity of echocardiography in sternal fractures.1 Therefore, a recommendation for routine echocardiography is of limited value.In these conditions, one is strongly recommended against adding biomarkers to the ECG. In cases of an abnormal ECG, however, measuring biomarkers at the beginning of hospitalization and again 4-6 hours later will increase the negative predictive value of this method alone. Measuring biomarkers is part of the predictive negative value of class II.Diagnosing myocardial contusion in trauma patients in the emergency department is still challenging, and the most advanced diagnostic tests are expensive and unavailable under the current dire conditions in Iran. This study attempted to provide the appropriate diagnostic algorithm and the steps to eliminating many of the uncertainties in dealing with such patients. Statement of ProblemBased on the prevalence of trauma in urban communities and the lack of specific tests for the diagnosis of contusion and myocardial contusion, we decided to suggest a step-by-step diagnostic logic as a guideline which would reduce unnecessary diagnostic costs and long-term hospitalizations for trauma patients. We should devise a safe protocol that is appropriate for managing patients with suspected myocardial contusions referring to centers with different levels of facilities particularly in areas with limited resources.ProcessMyocardial Contusion) AND (Blunt Chest Trauma). Articles were selected from joint research centers of cardiology and cardiovascular surgery. The related articles of PubMed were also selected and used to identify the articles similar to primary strategy. Out of 104 articles recognized by these 2 methods, 33 were confirmed for myocardial contusion after blunt chest trauma. Each article was reviewed by 2 of our authors of the work group. Data were collected, and a consensus was achieved for the final opinion and recommendations vis-à-vis this guideline.There is no unique approach for diagnosing myocardial contusion, with the only conclusive test being autopsy. Therefore, we propose a suitable approach from the analysis of a number of papers, and we offer a reasonable and affordable guideline based on available statistical data and scientific evidence. A computerized search of MEDLINE was undertaken using PubMed interface. English language citations were enquired for myocardial contusion from 1977 through 2012 using the primary search strategy:  after blunt thoracic trauma (BTT)?MCI is an uncommon side effect of BTT and usually results from a motor vehicle accident or an accident caused by sudden loss of speed, which is called a deceleration injury. It can also result from a direct blow to the chest.11 A definite diagnosis can be achieved only by direct viewing at autopsy. Strong suspicion is required to diagnose MCI. Patients who sustain significant thoracic trauma are susceptible to MCI. In these situations, significant trauma includes multiple rib fractures, hemothorax, pulmonary contusion, and intrathoracic vascular injury. Patients with these injuries have a 13% chance of blunt myocardial contusion. They may also experience pain such as angina and infarct that is not reduced with analgesics. Patients may have shortness of breath; therefore, the examination should be nonspecific. They may have flail chest, chest wall tenderness, dysrhythmias or ectopic beat, or sinus tachycardia. Sometimes they have no common symptoms. It should be noted that a sternum fracture does not necessarily indicate significant damage. Therefore, the patient’s symptoms and a physical examination are not specific for diagnosing MCI. Based on the mechanism of trauma severity, appropriate diagnostic measures should be undertaken. The exact incidence of MCI after BTT is unknown, but a study has reported it to be between 8% and 71%.2. What is a reasonable and appropriate diagnostic measure for a patient suspected of having MCI? 12, 13Based on trials made on such patients, the class I recommendation is 12-lead ECG. Notably, a right ECG (V4R) adapted on the right ventricle (RV) and an ECG with limited leads are not helpful; consequently, the 12-lead ECG is the first step for a patient suspected of having MCI.ECG is a sensitive method and the best single predictor of MCI. Indeed, between 40% and 83% of MCI patients will have an abnormal ECG. Maximum abnormality which will be visible in an ECG is arrhythmia, which is generally seen within the first 24–48 hours. Ventricular fibrillation is the most common cause of death. Left ventricle (LV) contusion will be present as an abnormality of ST-T and pathologic Q waves. Atrial fibrillation is correlated with poor outcomes. A right bundle branch block is common. First-degree atrioventricular (AV) block, left bundle branch block, hemi-blocks, and third-degree AV block are also seen. 6, 14Unfortunately, there is no relation between the severity of contusion and arrhythmia, and the ECG changes associated with the effects of trauma are weak.15-18 In a patient who is suspected of having MCI, one will be able to decide by evaluating troponin levels and an ECG:Some studies have shown that measuring troponin levels is useful as screening before an ECG.1. If the ECG is normal and the troponin test is negative, MCI is almost ruled out, and, if stable, the patient can be discharged.2. If the initial ECG is abnormal, 24–48 hours of monitoring is recommended. To increase sensitivity, it is better to compare a second ECG with the previous one.5, 63. If the first ECG is abnormal and the troponin test is positive, the next diagnostic step is required. The most appropriate and cost-effective step is echocardiography (class II recommendations).Transesophageal echocardiography (TEE) is more sensitive than is transthoracic echocardiography (TTE) because it is not necessary to maintain the proper position (unlike TTE) but the thoracic aorta is not seen, and 90% of aortic ruptures occur in the isthmus which illustrates the rupture well. The RV outflow tract cannot be seen with TTE, but it can be detected with TEE. TTE does not have a good correlation with ECG and enzyme testing. Echocardiography is reasonable and necessary under the following conditions:1. When the initial ECG is abnormal and the troponin test is positive.2. When a trauma patient is in shock and noncardiac causes are rejected.5, 6, 19-223. When hemodynamic instability or arrhythmia is seen in the ECG. If TTE is not helpful and there is a suspicion of cardiac causes, TEE is recommended.It is noteworthy that sternum fracture does not mean MCI, and monitoring is not required in the presence of a normal ECG and negative troponin test. If the chest X-ray, ECG, and troponin level are normal, the patient can be discharged. 23 Therefore, echocardiography is not recommended in isolated sternum fracture.23In a retrospective study, 67 out of 100 patients had isolated sternum fractures, and based on abnormal ECG results, MCI was reported at 4%.The probability of these disorders can be seen in echocardiography. Accordingly, subsequent treatment steps can be determined based on the following observable impairments in MCI patients: 1. Angiography is needed when a wall motion abnormality and reduced ejection fraction is seen in an echocardiogram with an ECG abnormality.2. When there is significant effusion and tamponade, requiring intervention and surgery.3. Significant valvular heart disease and LV dysfunction requiring immediate surgery are seen in the echocardiogram 4. In cases of acute deterioration of cardiac function following trauma, normal angiography treatment with positive inotrope and intra-aortic balloon pump is essential.65. Ruptured structure will be decided based on the severity of visible abnormalities like ventricular septum, ventricular aneurysm, and aortic fistula to heart chambers.A small percentage of MCI patients with myocardial infarction symptoms will refer to hospital. Most of them are not actual coronary stenosis and will show ST changes 5–7 days after trauma. These patients definitely require angiography but often have normal coronary activity. The reason for these patients having a myocardial infarction could be in-situ thrombosis or dissection. If they are not barred from taking anticoagulants, percutaneous coronary intervention can be performed.3. Under what conditions is a nuclear study reasonable?99 is capable of demonstrating a reduction in myocardial perfusion, but it is not recommended for the diagnosis of MCI and is not reasonable for routine use. Myocardial perfusion using TC24-27 Some studies have shown that scanning is not useful for examining MCI.24-27Myocardial perfusion with thallium is useful for left ventricular (LV) evaluation, but because of the right ventricular (RV) position, right ventricular (RV) contusion has doubled the LV.28, 294. Is the study of myocardial metabolism with positron emission tomography (PET) valuable in trauma?29Metabolism can be evaluated with PET and single-photon emission computerized tomography (SPECT) perfusion, if echocardiography and ECG results are abnormal and coronary angiography is normal. If perfusion and metabolic defects are matched, an infarct diagnosis will be established. The first report of using PET metabolic in a 45-year-old who was suspected of having myocardial infarction was discussed in a study by Pai M. et al.18F-FDG), although it is not recommended for routine use. Today, the best method to assess myocardial viability is PET with fluorine-18 In a patient with normal echocardiography, CT scan or heart magnetic resonance imaging, angiography or drug therapy is not useful.30 (Swan Ganz) in elderly patients with heart disease and unstable conditions associated with an abnormal ECG.Surgery is reasonable with monitoring and use of a pulmonary artery catheterIn short, a new algorithm for the detection of MCI in trauma patients admitted to the trauma emergency ward is shown in Cardiac EnzymesCardiac enzymes are small molecules released in blood circulation for whatever reason following damage to the myocardial cell membrane. There are several types of cardiac enzymes and the most specific are troponin I and troponin T. Other enzymes such as keratin phosphokinase and myoglobin have a great deal of false positive with increases of CPK MB in terms of muscle mass trauma and are not recommended for trauma patients.Sternal FracturesToday, sternal fracture does not reflect the severity of trauma and has no additional diagnostic value with echocardiography and indication of normal troponin enzyme. Therefore, we will be able to safely discharge these trauma patients. Surgical RepairIn trauma patients, surgical repair is needed in significant and serious valvular damage. If valve damage is leading to heart failure and shock, surgical repair and/or valve replacement is inevitable. In the case of myocardial rupture leading to cardiac tamponade or coronary artery laceration or aorta, surgical repair is reasonable and necessary.Other Miscellaneous Diagnostic Tests31 The results of a study by Elie et al.32 showed that utilizing a combination of echocardiography, ECG, and troponin tests for suitable patients might advance the diagnosis and risk stratification of blunt trauma injury patients.The indication of routine, time-efficient, and cost-effective tests in conditions of suspected contusion injury has been described in the text. Tests such as nuclear cardiology scans and myocardial perfusion scans are too costly. In some patients who experience rib and lung injuries associated with the accident leading to heart contusion, other tools may be used to determine if there are significant injuries to the heart, ribs, or arteries or if there are fractures. These tools include computed tomography (CT) scan of the heart, chest X-ray, and ECG to monitor heart activity, and echocardiogram to visualize the flow of blood through the heart.Future and Controversy33The future pathway to improving management and diagnosis of blunt chest trauma involves diagnostic tests, endovascular techniques, and patient selection. The use of thoracoscopy for the management and diagnosis of thoracic injuries will increase. The use of ultrasounds for diagnosis in cases such as hemothorax and cardiac tamponade will become more widespread. Finally, CT scanning techniques will be used more frequently to diagnose major injuries to the thoracic aorta and its branches. Endovascular techniques will be developed further, and they will be used more frequently to repair great vessel injuries. Nonsurgical techniques and patient selection will be redefined for delayed operative management of thoracic aortic rupture.RecommendationsThe first step in the diagnostic and class I recommendations is ECG in all trauma patients with suspected myocardial contusion based on trauma mechanism. Control of the cardiac enzyme is not recommended by class I, but control of simultaneous cardiac enzymes together with ECG in patients strongly suspected of having a contusion is a class II recommendation.Echocardiography is not the first line of diagnosis. If the echocardiogram is abnormal, cardiac enzymes and shock are unjustified based on surgical causes, and therefore echocardiography is logical and recommended as a component of class II.A myocardial contusion refers to a bruise of the cardiac muscle secondary to trauma, the severity of which can vary depending on the severity of the transferred energy to the heart and preexisting heart’s conditions. Diagnosing myocardial contusion is difficult due to the patient’s nonspecific symptoms and the lack of an ideal diagnostic test. It is necessary to have an algorithm about how to approach to the patient when there is a possibility of myocardial contusion with respect to local facilities.


In cardiotoxicity from the use ofchemotherapeutics, we may find alterations in cardiac mechanics with no modificationof the left ventricle ejection fraction (LVEF). Thus, the analysis of myocardialdeformation brings relevant information in the analysis of regional ventricularsystolic dysfunction in subclinical conditions.2Myocardial deformation (strain) analysis may be done through echocardiography fromdata obtained by tissue doppler technique or two-dimensional images from speckletracking, allowing the calculation of longitudinal, circumferential and radialdeformations of myocardial fibers.4 This phenomenon isdue to a significant decrease in myocardial deformation in three different spatialplanes, triggering deformation modifications in the longitudinal, circumferentialand radial axes.5 In patients whopresent reduced longitudinal myocardial deformation, we can observe radialdeformation that is superior to normality parameters, which may result in preservedventricular function, when estimated by LVEF. Other applications of myocardialdeformation include amyloidosis, hypertrophic cardiomyopathy, right ventriculardysfunction, athlete's heart, cardiac dyssynchrony and valve diseases .2Similarly, previous investigations have shown that the study of myocardialdeformation is able to detect sudden and early alterations in systolic function ofvalve disease patients, even before they present LVEF modifications.6 The use of myocardial deformationwith echocardiography in the immediate evaluation of aortic stenosis patientsundergoing TAVE is underexplored.Transcatheter aortic valve implantation (TAVI) appeared as a new option for thetreatment of inoperable aortic stenosis or high surgical risk patients.2, and LVEF (Simpson's method) of 60%.Pre-TAVI strain analysis was -14% and after implantation of aortic prosthesisSapien XT of 23 mm  immediate improvement of themyocardial deformation to -20% was observed.Patient, female, 79 years old, with atrial fibrillation and pulmonaryhypertension, and decreased functional capacity in the last year.Three-dimensional transesophageal echocardiography showed presence of aorticvalve stenosis with maximum transvalvular gradient of 67 mmHg and mean of 39mmHg, valve area of 0.5 cmPatient, male, 81 years old, with cirrhosis from hepatitis B and hypothyroidism,symptomatic, functional class II (NYHA) from aortic valve stenosis. Implantationof aortic valve Sapien XT of 26 mm, with immediate improvement of the strainfrom -15% to -22%. Myocardial dyssynchrony evaluation with analysis through preTAVI systolic time-to-peak calculation method went from 132 ms to 65 ms afterthe procedure.2 andLVEF of 57%. Implantation of aortic valve Sapien XT, 23 mm, with immediatenormalization of the pre-procedure myocardial strain from -12% to -20% after theprocedure . Echocardiogram showed maximum transvalvular gradient of 65 mmHgand mean of 38 mmHg, valve area of 0.6 cmt to 34% . 4Aortic valve stenosis evolution results in pressure overload in the myocardial wall,leading to increased cardiac thickness. Ventricular hypertrophy progresses as aorticstenosis becomes more significant, an adaptation mechanism for ventricular functionmaintenance. However, this compensatory mechanism is finite, triggers an increase inleft ventricular volume (positive remodeling) and a decrease in ejection fractionover time.5 in studiesusing echocardiography, observed the following alterations in patients with aorticstenosis:Lancellotti et al.,asymptomatic patient with significant aortic stenosis presents expressiveincrease in global left ventricular afterload;Ventricular afterload increase negatively affects myocardial function,especially in the axial deformation, despite the normal ejectionfraction;Elevated afterload in low-flow aortic stenosis patients, when systemicarterial compliance is reduced;The state of low-flow is related to a compromised diastolic function andreduction of myocardial deformation. Longitudinal, radial andcircumferential myocardial deformations are significantly compromised inpatients with elevated afterload. In an initial stage of aortic valvestenosis, however, there is only a reduction in the longitudinalmyocardial deformation, mainly related to alterations in subendocardialcardiac fibers. Radial and circumferential deformations may be,paradoxically, vicarious in this period. Subsequently, with theprogression of aortic stenosis severity, we now have a reduction of theradial and circumferential deformation due to modifications of thefibers of the mid-myocardial layer which present circumferential spatialalignment.7 When compared to patients with preserved systolic function,those with reduced ejection fraction present less favorable clinical evolution aftervalve repair.4 In patients withpreserved ventricular function, myocardial deformation analysis allows earlydetection of subclinical alterations of myocardial mechanics, which could, after theprocedure, positively result in longer survival and better quality of life. Current guidelines recommend aortic valve replacement in symptomatic or asymptomaticaortic valve stenosis patients with reduction of the ejection fraction.4aortic valve replacement surgery improved the analysed parameters through speckletracking, even though the ejection fraction remained unaltered. Additionally, theseauthors report an improvement in myocardial deformation after valve replacement.That solidifies the ability of myocardial deformation analysis to detect suddenalterations in systolic function in patients with severe aortic stenosis. In a study by Delgado et al.,3 whoassessed 8 patients submitted to TAVI, showed improvement in global and regionalsystolic function of the left ventricle, even in patients with reduced ejectionfraction.In another study, Bauer et al.,6observed an improvement of myocardial mechanics in patients submitted to TAVI 12months after the procedure. Becker et al.7 showed a positive response in myocardial deformation 7 daysand 6 months after TAVI. Specifically, there was an improvement in the ejectionfraction of 51±6% pre-TAVI to 54±4% and 57±3%, 7 days and 6months after the procedure. For circumferential myocardial deformation analysis,there was an improvement of -14.9±1 pre-TAVI to -16.1±1.2 and-17.3±1.5 in 7 days and 6 months after TAVI, respectively. Similarly, Sebastian et al.In a similar way, in the present 4-case report, we observed significant improvementof myocardial deformation analysis immediately after TAVI. Three patients presentedpreserved LVEF, and one (Case 4), presented significant ventricular dysfunction,with improvements observed in LVEF and longitudinal myocardial deformation,immediately after the procedure. These data confirm that left ventricular functionin valvulopathies directly depends on the afterload, and immediate relief of thisvariable may positively influence clinical outcomes. The causal relation betweenimmediate recovery of myocardial deformation after TAVI - even in patients withpreserved left ventricular function - and the benefits in symptoms and morbidity andmortality should be explored in future studies.


To quantify mitral regurgitation (MR) with CMR, the regurgitant volume can be calculated as the difference between the left ventricular (LV) stroke volume (SV) measured with the Simpson’s method and the reference SV, i.e. the right ventricular SV (RVSV) in patients without tricuspid regurgitation. However, for patients with prominent mitral valve prolapse (MVP), the Simpson’s method may underestimate the LV end-systolic volume (LVESV) as it only considers the volume located between the apex and the mitral annulus, and neglects the ventricular volume that is displaced into the left atrium but contained within the prolapsed mitral leaflets at end systole. This may lead to an underestimation of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of mitral regurgitation. The aim of the present study was to assess the impact of prominent MVP on MR quantification by CMR.uncorr was calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected LVESVcorr was calculated as the LVESV plus the prolapsed volume, i.e. the volume between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were compared with respect to the MR grading. MR grades were defined as absent or trace, mild (5–29% regurgitant fraction (RF)), moderate (30–49% RF), or severe (≥50% RF).In patients with MVP (and no more than trace tricuspid regurgitation) MR was quantified by calculating the regurgitant volume as the difference between LVSV and RVSV. LVSVp < 0.001). In the subgroup without MR, LVSVcorr was not significantly different from RVSV  while a systematic overestimation was observed with LVSVuncorr . Also, RVSV was highly correlated with aortic forward flow .In 35 patients  the prolapsed volume was 16.5 ± 8.7 ml. The 2 methods were concordant in only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR severity in 23 (66%) patients. For the uncorrected/corrected method, the distribution of the MR grades as absent-trace , mild , moderate , and severe  was significantly different (For patients with severe bileaflet prolapse, the correction of the LVSV for the prolapse volume is suggested as it modified the assessment of MR severity by one grade in a large portion of patients. Mitral regurgitation (MR) is one of the most common valve diseases with an estimated prevalence of 1.7% in the general population, increasing to 9.3% after age 75. Moderate to severe MR represents an important public health issue as it is associated with poor clinical outcome  and it aVol) and regurgitant fraction (RF), two parameters that may be able to identify patients suitable for early surgery [Vol calculation, which are based on the difference between the LV stroke volume (SV) measured with the Simpson’s method and a reference SV either measured as the aortic forward flow (Aoforward) by phase-contrast cine CMR at the level of the ascending aorta or as the right ventricular (RV) SV by the Simpson’s method  [In general, for the quantification of MR severity echocardiography is the method of choice, although some limitations exist. For example, the most frequently used technique, the proximal isovelocity surface area (PISA) method , may be  surgery . Severalitation) –18.With the method of disks, the end-diastolic and end-systolic volumes are measured by tracing the endocardial border of consecutive short-axis cine slices covering the LV from the apex to the mitral annulus. For patients with prominent MVP, this strategy may be inaccurate in systole as the part of the LV volume contained within the prolapsing mitral leaflets  at end-systole is simply neglected and excluded from the total LV end-systolic volume . Thus, the currently accepted approaches –18 do noAccordingly, in this study, we proposed a simple strategy to correct the LVESV for the severity of the prolapse, i.e. for the “prolapsed volume”, and we assessed its impact on the quantification of MR severity in patients with significant MVP.A retrospective search was conducted in our CMR centre between January 2011 and January 2017 to identify the patients, for which the presence of bileaflet MVP could be suspected. The keywords “prolapse”, “billowing”, “Barlow”, and “Marfan” were used to screen the CMR reports and 105 patients were identified. The images were individually reviewed to only include patients presenting with bileaflet MVP, defined as the billowing of both, the anterior and posterior mitral leaflets, with displacement of the leaflets >2 mm into the LA on a 3 chamber long-axis view in systole . The cliImage acquisition was performed on a 1.5 T (Magnetom AERA or Magnetom Symphony) or a 3.0 T (Magnetom Verio or Magnetom Skyra) scanner  using a 32-channels phased-array coil. A balanced steady-state free precession cine sequence was used for ventricular volume assessment . A stack of short axis slices (slice thickness 8 mm and 2 mm gap) from the base to the apex, as well as 3 long-axis slices of the LV, were acquired in all patients. When clinically indicated, a phase-contrast acquisition of the ascending aorta was additionally performed during breath-hold ; the imaging plane for aortic forward flow measurement was defined from two orthogonal long axis cine acquisitions of the ascending aorta and was placed at the level of the right pulmonary artery.uncorr) LV volumes, the basal slice was defined as the slice with LV myocardium detected at least 50% of its circumference [corr) was additionally measured as the standard LVESV (=LVESVuncorr) plus the prolapsed volume. The prolapsed volume was calculated as the area of the basal end-systolic slice multiplied by the mean prolapsed height. The mean prolapsed height was the average of the three individual prolapsed heights of the three standard LV long-axis views of the LV , calculated as the prolapsed area divided by the annulus diameter  was calculated as the LVEDV minus the LVESVuncorr. The prolapse-corrected stroke volume (LVSVcorr) was calculated as the LVEDV minus LVESVcorr.The ventricular volumes were measured according to the Simpson’s method of disks by tracing the endocardial LV border from the basal to the apical slice using a semi-automated border detection software . Muscular trabeculae were included in the blood pool. For end-diastolic (LVEDV) and uncorrected end-systolic  corrected for background phase was measured on phase-contrast cine images of the ascending aorta by manually tracing the aortic surface frame-by-frame using the Argus workstation .The RV volumes were measured from the same set of short-axis cine images in all patients according to the Simpson’s method of disks by tracing the endocardial RV border from the basal to the apical slice using the same semi-automated border detection software. Cross-referencing with a long axis four-chamber cine acquisition was performed in all patients to accurately identify the basal RV slice. The RVSV was calculated as the difference between the end-diastolic and end-systolic RV volume and was considered the reference stroke volume in view of the fact that tricuspid insufficiency was a study exclusion criteria. When available, the aortic forward flow (Aouncorr and the RVSV (= standard or uncorrected method) and between the LVSVcorr and the RVSV (= corrected method). For both methods, the RF was calculated as the ratio between the respective regurgitant volume and the respective LVSV. A RF <5% defined absent or trace MR, 5–29% mild MR, 30–49% moderate MR, and ≥50% severe MR [For the assessment of MR severity, the regurgitant volume was calculated as the difference between the LVSVevere MR .t-tests. Direct comparison between LVSV and the reference stroke volume were performed with Wilcoxon matched-pairs signed ranks test. The comparison of the MR grade distribution was performed with Chi-square test. All calculations were performed with Stata 14 software . A p-value <0.05 was considered as significant.Continuous variables were expressed as mean ± standard deviation and categorical variables as percentages. The correlations and agreements between uncorrected and corrected LVSV were analyzed by linear regression and Bland-Altman statistics . Direct Forty-two patients were identified with bileaflet MVP. One patient was excluded due to the presence of an atrial septal defect with significant left-to-right shunt and six patient had mild or moderate tricuspid regurgitation. Thirty-five patients were therefore included in the analysis. Mean age was 44.0 ± 23.0 years and 14 (40%) were male. Fifteen patients (42.9%) with MVP had no or only trace MR detected on echocardiography, or no MR jet detected on the 3 long axis or basal short-axis cine CMR acquisitions. Additional baseline characteristics are summarized in Table forward measured by phase-contrast cine CMR was available in 24 patients (68.6%) and was highly correlated with RVSV . Agreement between the two methods was also excellent . All analyses were performed using RVSV (n = 35) as the reference stroke volume. The same analyses were repeated in the subset of patients (n = 24) with AOforward as the reference stroke volume, and the corresponding results were indicated for comparison.RVSV was measured in all patients with a mean value of 71.5 ± 24.9 ml. AOn = 35) indicated a good agreement: mean difference: −0.4 ml . The inter-observer analysis indicated a mean difference of −2.6 ml . In the subgroup of patients assessed with a 1.5 T scanner (n = 26), the mean differences were 0.1 ml  and −2.3 ml (−8.7 to 4.1 ml) for intra- and inter-observer analysis, respectively. In the subgroup of patients assessed with a 3.0 T scanner (n = 9), the mean differences were −1.8 ml  and −3.6 ml (−9.2 to 2.0 ml) for intra- and inter-observer analysis, respectively.Intra-observer analysis of prolapsed volume measurement . In the patients with no MR, the LVSVuncorr exceeded the true reference RVSV by 16.9 ± 9.1 ml (p = 0.0007 vs 0), while a non-significant 2.5 ± 4.7 ml overestimation was observed with the LVSVcorr  but not with LVSVcorr .Fifteen patients (42.9%) had no or only trace MR and their reference RVSV was 83.6 ± 28.6 ml. The mean prolapsed height was 7.6 ± 2.1 mm and the prolapsed volume was 14.4 ± 7.0 ml. The LVSVn = 35), the prolapsed height correlated linearly with the difference between uncorrected, and the corrected stroke volume . The uncorrected and corrected method provided significantly different results for LVSV , LVEF , regurgitant volume  and regurgitant fraction  . Overall, the grade of MR severity was concordant for the two methods in only 12 patients (34%), as the uncorrected method overestimated MR severity by 1 grade in 23 (66%) patients , CMR suggested the presence of a mild MR in all patients when the uncorrected method was used (with a mean regurgitant volume of 16.9 ± 9.1 ml and a mean regurgitant fraction of 16.3 ± 5.9%). With the corrected method, 11 out of the 15 patients were correctly classified as having no significant MR. In 4 patients, MR grade was still overestimated by one grade despite low regurgitant volumes .Over the whole cohort n = 3, the proforward was available (n = 24), the uncorrected method resulted in a similar overestimation of the LVSV , the LVEF , the regurgitant volume  and the regurgitant fraction . MR grade severity was concordant between the corrected and the uncorrected methods in only 10 (41.7%) patients, and an overestimation by one grade was observed in 14 (58.3%) patients.Among the subset of patients where AOcorr and the reference RVSV with this correction for the prolapsed volume. Over the whole cohort of patients with MVP, this correction resulted in a difference in MR severity quantification by 1 grade in almost two thirds of the patients. In addition, with this correction, LV ejection fraction was also significantly lower, reflecting the ineffective pump function caused by the systolic displacement of the mitral valve plane into the LA.In the MVP population, the present study suggests a correction of the LVSV by the prolapsed volume, i.e. by the volume “contained” within the prolapsing mitral valve leaflets, impacts on the quantification of MR. This correction reduced the MR severity by one grade in 66% of patients. In the case of a prominent MVP, the mitral annulus is not an adequate landmark to separate the LV from the LA volume in systole, as the systolic billowing of the mitral valve into the LA creates a space in the LA that is occupied by the LV blood pool. This part of the LV blood pool (i.e. the prolapsed volume) is not crossing through the incompetent mitral valve in systole. i.e. this volume does not contribute to the regurgitant volume of the prolapsing mitral valve, and should therefore be corrected for. Accordingly, in the situation of MVP, the proximal border of the LV blood pool is the plane of the mitral valve leaflets, not the mitral annulus. As the mitral valve is a thin structure, it is difficult to recognize on short-axis cine slices of the LV and we propose a method using the 3 long-axis orientations to correct the standard LVESV for the prolapsed volume. In the patients known for having no or only trace MR, a better agreement was found between the LVSVVol and RF with CMR [forward by phase-contrast cine imaging [forward [With regard to the need to undergo MV surgery, one single recent study proposed a validated cut-off value for Regwith CMR , and no with CMR , LVSV wi imaging , 17, tra[forward , 23, or [forward . However[forward , 26. In [forward . Not surp = 0.002) when using the proposed correction method, which considers the prolapsed volume, i.e. the severity of the valve prolapse.From a clinical perspective, mitral valve surgery is indicated in patients with severe MR, who present with symptoms or evidence of LV dilatation or dysfunction , but theThe limitations of this study include the relatively small number of participating patients and the specific mechanism of valve disease investigated, which is not representative for other types of MR. The retrospective design of this study may have selected patients with a more severe degree of MVP (mean prolapsed height was 8.1 mm) and the risk of MR misclassification may be less important for patients with milder degrees of MVP. We are therefore not able to recommend a cut-off value of prolapsed height above which a LVSV correction might be warranted. In this study, the prolapsed volume has been estimated and not directly measured. The geometric assumptions associated with our correction strategy might have induced some variability in the measurements. However, the proposed correction method can be easily applied to conventional CMR protocols which typically include a LV short-axis stack and 3 long-axis cine acquisitions. In this regard, the development of a time-efficient truly three-dimensional technique to accurately measure the prolapsed volume might be of value. Finally no direct comparison with echocardiographic MR quantification was performed in this cohort, as the aim of this study was not to compare the performance of two different imaging methods, but to highlight a potential methodological bias induced by MVP when the quantification of MR severity is performed with a generally accepted standard CMR method.When applying the standard method of discs to measure LV volumes in patients with MVP, the blood volume contained within the valve prolapse is not considered to be part of the LV volume in systole. Consequently, in a severe form of bileaflet prolapse, this may lead to a significant underestimation of the true end-systolic volume and thus, overestimation of MR severity. For these patients, we suggest to correct the LVSV for the prolapsed volume, as it allowed a reclassification of MR severity to a milder grade in two thirds of the MVP patients.