Recent studies hypothesized left ventricular (LV) twist as a potential biomarker for evaluation of sub clinical myocardial disease, however its relationship with aortic stiffness has yet to be investigated. Chronic kidney disease (CKD) has been identified as a risk factor for both myocardial and arterial disease. As such we sought to explore the relationship between aortic stiffness and LV twist in CKD patients without known cardiovascular disease (CVD).In this prospective, observational study we enrolled 106 CKD patients (Stages 1 to 5) with normal LVEF as assessed by conventional echocardiography. Aortic stiffness was measured using aortic pulse wave velocity (aPWV). We defined increased aPWV as ≥10 m/s. LV Twist was measured using two-dimensional speckle tracking echocardiography.p = 0.002) but similar LVEF (p = 0.486). Aortic PWV correlated crudely with age (p < 0.001), the presence of diabetes (p < 0.001), hypertension (p < 0.001), eGFR (p < 0.001), LVMI (p = 0.01), e/e’ (p < 0.001) and LV twist (p = 0.003). In multivariable analyses after adjusting for age, gender, cardiovascular risk factors and hypertensive medication, aPWV was independently associated with LV twist .Patients with increased aPWV had higher LV twist (Aortic stiffness independently associates with LV Twist in asymptomatic CKD patients. These findings suggest a close interaction between LV twist mechanics and arterial remodeling even before CVD becomes clinically relevant. Recent data suggests that chronic kidney disease (CKD) patients develop both arterial and myocardial dysfunction at an early stage of the disease. Wang and colleagues identified that increased arterial stiffness is evident as early as CKD stage 2 . Even thPanoulas et al identified Left Ventricular (LV) twist as a potential marker of sub clinical LV systolic dysfunction in CKD patients with normal ejection fraction, as measured by conventional 2D echocardiography . AbnormaTo date, no study has explored the relationship between arterial stiffness and LV twist mechanics. As CKD has been identified as a risk factor for both arterial and myocardial disease we aimed to explore this association in this high-risk patient cohort.A total of 123 consecutive patients with CKD stages 1 to 5 were enrolled from Imperial College Healthcare NHS Trust renal outpatient clinics between 2011 and 2014. Chronic kidney disease was defined on the basis of impaired eGFR plus microalbuminuria, present on at least two occasions over three months or more. Patients with: clinical or echocardiographic evidence of LV systolic dysfunction, significant valvular abnormalities (moderate or severe), presence of atrial fibrillation or flutter, pulmonary hypertension, congenital heart disease, cardiomyopathy, pericardial disease or inadequate echocardiographic acoustic windows were excluded from this study. Written informed consent was obtained from all participants. The study was approved by the UK National Research Ethics Committee Service (REC 10/H0704/81).The collection of anthropometric data included height (cm), weight (kg), body mass index  and body surface area . Using a structured questionnaire and medical notes review we collected the following data: systolic and diastolic blood pressure, both measured in the sitting position in mmHg, hypertension (defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or on antihypertensive treatment), diagnosis of diabetes, treated hypercholesterolaemia , family history of ischaemic heart disease, smoking status  and detailed list of current medication. Biochemical results were obtained from the most recent renal clinic review (within 1 month of recruitment) provided that there was no evidence of superimposed acute kidney injury during the time of blood sampling. The value of eGFR was calculated using the four-variable equation in the Modification of Diet in Renal Disease study .Transthoracic echocardiography was performed using a commercially available system  by a single, accredited echocardiographer according to a standardised protocol. All echocardiographic parameters were measured offline in batches by one observer blinded to clinical and outcome data. Interventricular septum thickness, posterior wall thickness, LV mass index (LVMI), tissue Doppler imaging S’ wave (TDI S’), left atrial (LA) dimension and LVEF were measured according to the recommendations of the American Society of Echocardiography .Speckle tracking analysis was performed offline by the customised software for Vivid . Basal and apical parasternal short axis views were recorded for each patient. The basal plane was defined as that allowing visualization of the mitral valve with the cross-section as circular as possible. The apical plane was acquired distally to the papillary muscles . LV twisWhile acquiring two-dimensional images we kept the focus position at intermediate depth and adjusted the sector depth and width to include little but the region of interest. Furthermore, the sampling region of interest was adjusted to ensure that most of the wall thickness was incorporated in the analysis avoiding the pericardium. Frame rate was between 60 frames/s and 80 frames/s.On the same day, around 10 min after performing the echocardiogram, blood pressure was measured with the subjects in supine position. Pressure waveforms were recorded on the radial, carotid and femoral arteries using applanation tonometry . CarotidPrevious studies have demonstrated that a aPWV cut off of 10 m/s has been shown to provide risk stratification and prognostic value in CKD patients . TherefoIn order to test inter and intra-observer variability for both LV Twist and aPWV indices, we reassessed the measurements on a sub-group of 20 randomly selected patients. Shortly after the first assessment a second operator, who was blinded to the results, analysed aPWV and LV twist. Subsequently the first operator re-measured the same indices.t-test for continuous normally distributed data and Wilcoxon rank sum test for continuous non-normally distributed data. Correlations were assessed for normal and non-normal variables using Pearson’s and Spearman’s coefficients respectively. Univariate and multivariate analyses were used to evaluate the relationship between, arterial stiffness and a range of variables including general demographics, cardiovascular risk factors, conventional echocardiographic and speckle tracking parameters including LV Twist. Intraclass correlation coefficients (ICC) and Bland-Altman plots were determined to assess the inter-operator and intra-operator variability of speckle tracking and arterial stiffness measurements. The criterion for statistical significance used was a P-value of ≤0.05 to a 95 % confidence interval.Statistical analysis was performed using SPSS software, version 22 . Variables were tested for normality by the Kolmogorov-Smirnov test. Firstly, analysis was performed by dividing the patients into 2 groups; one with aPWV < 10 m/s and the other with PWV ≥ 10 m/s. Differences between the 2 groups were analyzed using chi-square test for categorical data, n = 20): the ICC for LV twist 0.80, p < 0.001.Inter-operator variability (n = 20): the ICC for LV twist 0.89, p < 0.001.Intra-operator variability , atrial fibrillation (n = 4) valvular abnormalities (n = 1) and regional wall motion abnormalities (n = 1). A total of 106 patients were finally included in the study , followed by vasculitis (N = 18), post-renal causes (N = 10), IgA nephropathy (N = 7), focal glomerulosclerosis (N = 6), membranous glomerulonephritis (N = 5), hypertension (N = 4), adult polycystic kidney disease (N = 3), renovascular disease (N = 3), and minimal change disease (N = 3). In six patients, aetiology was unknown.95 CKD patients (89.6 %) underwent renal biopsy to determine the cause of their CKD. The most common CKD aetiology was diabetes (p < 0.001) and hypertension (p < 0.001) and lower eGFR (p < 0.001). Table p = 0.03), global longitudinal strain (GLS) (p = 0.002), higher LVMI (p = 0.01), E/e’ (p = 0.01), LV Twist (p < 0.001)- Fig. p = 0.482). Table Patients were stratified in two different groups according to aPWV: normal aPWV <10 m/s, increased aPWV ≥ 10 m/s. Table p < 0.001), the presence of diabetes (p < 0.001), hyperlipidemia (p = 0.013), peripheral SBP (p < 0.001), hypertension (p < 0.001), eGFR (p < 0.001), LVMI (p < 0.001), E/e’ (p < 0.001), TDI S’ (p = 0.03), GLS (p = 0.01) and LV twist (p = 0.003). Figure Table p < 0.001), diabetes , hypertension , eGFR , LMVI  and LV twist  Table In the linear regression model, aPWV was independently associated with age .Firstly due to the observational design of the study we cannot determine causality between subclinical 2DSTE abnormalities and aPWV and our results should be viewed as hypothesis generating. Secondly, even though patients recruited in the current study were asymptomatic from the cardiovascular point of view, with no previous history of ischaemic heart disease and a structurally normal heart on transthoracic echocardiogram, the presence of significant coronary artery disease was not ruled out with a functional or invasive test. However, in a subset of 20 pre-dialysis patients who subsequently underwent elective invasive angiography as part of their pre-transplant assessment, the vast majority 19 (95 %), had no significant disease in their epicardial arteries. This fact supports the hypothesis that microvascular ischaemia may be accountable for the LV twist patterns observed in our CKD population.In summary the current study provides for the first time a link between LV twist assessed by STE and early peripheral arterial disease, in asymptomatic CKD patients with preserved LVEF. Future studies of patients with these early subclinical markers of CVD should be undertaken, randomizing their participants to aggressive risk factor management versus watchful waiting. If early risk factor modification in patients with abnormal LV twist and PWV values improves outcomes, these markers could be used for risk stratification purposes in this population.


Several exogenous or endogenous factors can lead to inflammatory heart disease. Beside infectious myocarditis, other systemic inflammatory disorders such as sarcoidosis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Churg-Strauss syndrome, and rheumatoid arthritis can affect the myocardium. Myocardial inflammation may have a major impact on the outcome of these patients, resulting in sudden cardiac death, severe arrhythmias, or end-stage heart failure. The current gold standard for definite confirmation of inflammatory heart disease is endomyocardial biopsy (EMB), but is invasive and suffers low sensitivity and specificity due to sampling errors. Thus, non-invasive methods for detecting the extent and changes over time of the inflammatory myocardial disease are needed. Cardiac magnetic resonance (CMR) is such a non-invasive method. We will describe and discuss different approaches for CMR assessment of inflammatory myocardial disease including early gadolinium enhancement (EGE), T2-weighted imaging, late gadolinium enhancement (LGE), the newer mapping proton relaxation techniques , and the hybrid PET/MRI technique. Several exogenous or endogenous factors can lead to acute or chronic inflammatory heart disease. Beside infectious myocarditis, which is mostly viral in origin, other systemic inflammatory disorders such as sarcoidosis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Churg-Strauss syndrome, and rheumatoid arthritis can affect the myocardium.Myocardial inflammation may have major impact on the outcome of these patients, resulting in sudden cardiac death, severe arrhythmias, or end-stage heart failure ••. CurreCardiac magnetic resonance (CMR) is such a new non-invasive method, which has high spatial resolution, allows evaluation of morphology, function, and tissue characterization as a one stop shop, and works without any radiation. In this manuscript, we will describe and discuss different approaches for CMR assessment of inflammatory myocardial disease  after application of gadolinium. At that time, contrast is washed out in normal myocardium (which is nulled), but in regions with enlarged extracellular/interstitial space due to acute necrosis, chronic scar, or fibrotic tissue, the contrast agent exhibit delayed washout, appearing hyperintense on the images . Hence, 5–25 min There is an ongoing debate about the best diagnostic approach to inflammatory heart disease using different CMR sequences. In 2009, some experts formulated an approach to detect myocardial inflammation using EGE, T2-weighted, and LGE imaging. Based on collective evidence available at that time, albeit small number studies, the diagnostic accuracy of acute myocarditis may be improved when two out of the three imaging techniques were positive, also known as the “Lake Louise criteria” . This isRecently developed pre-contrast T1 quantitative mapping techniques represent a fundamental step forward in the non-invasive assessment of myocardial inflammation . DespitePost-contrast T1 mapping techniques are also available; these are currently being used to assess for expansion of interstitial space/fibrosis  and distinguish it from replacement fibrosis (such as scarred myocardium) , 22. UsiThe diagnostic accuracy of T1 mapping techniques can be hampered by motion artifacts due to inconsistent breath-holding or patient movements. To overcome these limitations, technical developments allowing for motion correction and co-registration are now available .Spin echo-based T2 mapping techniques are known to be prone to effects of cardiac motion and stimulated echoes . T2 mappMyocardial inflammation and edema are characterized by an increase in free water content, which prolongs both T2 and T1 relaxation times. Myocardial T1 and T2 mapping have been validated against microspheres to detect myocardial edema in experimental animal models •• and al18F-FDG PET cumulates in inflammatory regions due to the glycolytic activity of cells, which participate in inflammatory processes . Disadvantages of PET are radiation exposure and reduced spatial resolution, so small areas of inflammation might be missed. Hence, a combination with MRI  seems reasonable [PET/MRI combines the strengths of both techniques. PET is a non-invasive imaging technique, which can detect metabolic active processes with high sensitivity: asonable .Viral myocarditis is the most common inflammatory heart disorder. Symptoms and clinical presentation may vary, making the diagnosis a challenge. Furthermore, the clinical course comprises a wide spectrum ranging from complete recovery to terminal heart disease or sudden cardiac death. Autopsy studies revealed that myocarditis is responsible for 5 to 20 % of sudden deaths in young adults , so gettCMR and its unique ability of non-invasive tissue characterization are extremely helpful in the work-up of suspected myocarditis. There are three stages of myocardial alterations in these patients: firstly, myocardial damage due to the trigger; secondly, myocardial inflammation by the host immune system; and thirdly, chronic myocardial inflammation, which may result in myocardial fibrosis, leading to remodeling, consequent ventricular dysfunction  and arrhThese alterations lead to acute myocardial necrosis and/or chronic scarring/fibrosis reflected by subepicardial or intramural regions of LGE, often patchy, and preferentially located in the posterolateral wall , see FigIn the setting of viral myocarditis, CMR studies with LGE are being performed for more than 10 years, first looking at the diagnostic performance of the technique, followed by prognostic data. To date, there is clear evidence that positive LGE is associated with an adverse outcome: patients with LGE are at increased risk of suffering adverse cardiac events. Grün et al. demonstrated in more than 220 patients with biopsy-proven viral myocarditis that the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality •. NevertDespite the limitations of EGE and T2-weighted imaging, these techniques may be useful in supporting the acute nature of the inflammatory process when images are diagnostic. Friedrich et al. recently published data on 35 patients with suspected acute myocarditis, in whom the overall diagnostic accuracy of “T2 and/or LGE” was significantly better than LGE alone. For patients in whom a high positive likelihood ratio is needed, the full Lake Louise criteria may be useful [Recently, mapping techniques have been shown to have great utility in this disease owing to its sensitivity to detecting myocardial water and pixel-wise quantification. Ferreira and Piechnik et al. •• first Compared to the diagnostic performance of some of the Lake Louise criteria, native T1 mapping, as a method for imaging edema, may replace dark-blood T2-weighted imaging either as a single criterion or in combination with LGE. ShMOLLI T1 mapping offers a number of advantages to conventional dark-blood T2-weighted imaging such as for cases in which tachyarrhythmia, patient inability to perform long breath-hold or skeletal muscle inflammation lead to non-diagnostic or false-negative images. The added ability of T1 mapping to demonstrate non-ischemic patterns of myocardial injury using incremental thresholds means that T1 mapping can effectively act as a method for both edema and LGE pattern imaging. In the future, it may be possible to perform a gadolinium-free CMR protocol using cine and T1 mapping, with T1 mapping as a single criterion demonstrating around 90 % in sensitivity, specificity, accuracy, PPV, and NPV .Luetkens et al.  comparedECV quantification has utility in acute to subacute, severe myocarditis, as shown by Radunski et al. , who assT2 mapping techniques have been shown to allow detection of myocardial edema beyond standard techniques such as wall motion abnormalities, T2-weighted, or LGE in a variety of cardiac pathologies including myocarditis. As shown by Thavendiranathan et al. , T2 mappOverall, while quantitative mapping techniques hold promise to diagnose myocarditis, establishing which method has the best diagnostic accuracy is still challenging and requires further evidence, such as larger studies and multicenter trials.Sarcoidosis is a systemic granulomatous inflammatory disease with unknown etiology that can affect the heart additionally, or isolated. In case of cardiac involvement, typical manifestations include arrhythmias, heart failure and/or sudden cardiac death, which is a frequent cause of death in these patients. Prevalence of cardiac involvement ranges from 20 to 30 % , dependiPET/MRI is a promising approach in patients with known or suspected cardiac sarcoidosis to detect inflammation with high sensitivity (active cardiac sarcoidosis), as well as fibrosis by LGE (chronic cardiac sarcoidosis), which may have implications for diagnosis and clinical follow-up , 43. FirThe group of collagenosis consists of a heterogenous group of systemic diseases affecting connective tissue and is characterized by necrosis or vasculitis.This disease affects predominantly females, with cardiac involvement reported in 60–70 % of the patients. These patients are exposed to an increased risk of coronary atherosclerosis, which may result in myocardial infarction. Beside of atherosclerosis, myocarditis and pericardial effusion could be observed, justifying the use of non-invasive imaging techniques. The prevalence of LGE in these patients ranges from low to high in the literature. This might be due to the fact that there is a wide spectrum of disease activity in these patients. Nevertheless, a study from Mavrogeni et al. , which cNative T1 mapping and ECV quantification were able to detect subclinical myocardial involvement in patients with SLE who were asymptomatic and had normal LV indices •. ComparIn contrast to SLE, the role of SSc in the pathogenesis of coronary atherosclerosis is not as well defined: data range from elevated risk to risk equal to the general population. There is consensus about potential cardiac involvement, which can manifest as myocardial damage, disturbances of the conduction system, pericardial disease, or alterations of the valves. Aside from that, secondary cardiac complications may occur due to extracardiac manifestations of SSc: e.g., secondary pulmonary hypertension due to sclerotic pulmonary alterations.A recent study  revealedThree groups of investigators have been able to detect early subclinical myocardial involvement in systemic sclerosis using T1 mapping and ECV quantification when there is no apparent cardiac disease. Ntusi et al.  found thThe vasculitides encompass a wide spectrum of diseases with different entities. Aside from large-vessel vasculitis , vasculitis of the small vessels  has gained attention, showing some impressive cardiac manifestation leading to impaired left ventricular function. Interestingly, LGE images show a subendocardial and also intramural pattern, sometimes resembling ischemic heart disease, but typically not related to a coronary territory, representing destructed coronary capillaries due to the inflammation process. More recent advances in characterizing inflammation by mapping sequences seem promising, but there is no published data yet.Patients with rheumatoid arthritis (RA) suffer accelerated atherosclerosis. The prevalence of myocardial tissue involvement is very variable in the literature, due to different inclusion criteria and patient population.Ntusi et al.  comparedFurther, the utility of T1 mapping and ECV has been shown in patients with RA but no prior history of cardiovascular disease and normal LV indices . CompareIn summary, CMR techniques are able to provide detailed information about myocardial inflammation. LGE is the most validated tool for diagnosis and prognosis, but has limitations in detecting acute inflammatory processes without scar or fibrosis. EGE and T2-weighted imaging may be useful in increasing the diagnostic accuracy of acute inflammatory myocardial processes in selected cases but can be challenging to apply in the practical clinical setting due to recognized technical and methodological limitations. Novel quantitative mapping techniques seem very promising, as they can detect edema as well as fibrosis while circumventing some of the challenges of conventional CMR techniques, allowing a more holistic approach to the different stages of inflammation. Prospective multicenter studies are warranted to clarify the future role of their clinical utility.


Tissue Doppler imaging is used routinely to quantify both left and right ventricular function. However, normal reference values of echocardiography parameters of the right ventricle in Iranian population are still unknown.Accordingly, we conducted a study to determine the normal values of echocardiography parameters of right ventricular function in a healthy Iranian population.One hundred and eighty seven healthy volunteer subjects enrolled. Normal subjects were chosen by taking into account history, physical examination, ECG and echocardiography.Reference ranges  for tricuspid E velocity, A velocity, E/A ratio, deceleration time, annular Sa velocity, Ea velocity, and E/Ea ratio were derived for the whole individuals and for each of the three age groups . The deceleration time, E/ Ea ratio and acceleration time of the iso-volumetric contraction time (IVA) were greater in male than in female. All measured parameters were bigger but not statistically significant in the 40-49 year-old group in comparison with the < 30 year-old group. Comparison of data between different groups showed no significant differences between the majority of data when they have been adjusted to body surface area, age and sex.The reference ranges presented for the echocardiography parameters of right ventricular function, albeit not conducted in a sizable sample of normal cases, will help to standardize the assessment of RV functions, particularly by tissue Doppler imaging. Importance of the right ventricular (RV) function has been partly underestimated. The main role of the RV is contribution into the normal cardiac pump function so as to maintain adequate pulmonary perfusion pressure and low systemic venous pressure in order to prevent tissue and organ congestion.The RV fAccordingly, we designed and conducted a study, to determine the normal values for echocardiographic measurements of the right side of the heart. The present study evaluated 187 healthy volunteer subjects between 18 and 49 years of age. These healthy subjects were chosen by taking into account history, physical examination, ECG and comprehensive transthoracic echocardiography. The study was approved by the ethics committee of Rajaie Cardiovascular Medical and Research Center, and informed consent was obtained from all subjects.All subjects were studied using M-mode and two-dimensional echocardiography and conventional Doppler and TDI in accordance with the American society of echocardiography guidelines .Tissue Doppler Imaging: Myocardial velocities were measured on-line using a standard pulsewave Doppler echocardiography. Color-coded images were acquired during a breath hold over three consecutive cycles using tissue Doppler imaging at a frame rate of 150 MHz. The imaging angle was adjusted parallel with the myocardial segment of interest. The sample volume was placed at the junction of the RV free wall with the tricuspid annulus in the apical 4-chamber view. All the echocardiography measurements were performed using a General Electric Vivid 7 phased-array system . Velocities were measured on-line at a sweep speed of 50-100 mm/s as if needed. All the parameters were calculated as the mean of three consecutive cycles. Following indices were determined by comprehensive Doppler inflow studies of both mitral and tricuspid valves: E wave deceleration time , E/A ratio , annular tissue Doppler velocities and the ratio of the early diastolic inflow velocity to the early tissue Doppler diastolic velocity (E/Ea).The following measures of right ventricle were obtained additionally by TDI: iso-volumetric contraction time (IVCT); systolic annular velocity; early diastolic annular velocity; late diastolic annular velocity; and iso-volumetric relaxation time (IVRT). We measured different right-sided time intervals as following: acceleration time of the iso-volumetric contraction time (IVA); duration of S wave; time interval from the beginning of the QRS complex to the beginning of the early tissue Doppler diastolic velocity; duration of IVRT; time interval from the beginning of the IVCT to the beginning of the early tissue Doppler diastolic velocity. Mean TR velocity and IVC diameter and respiratory variation were measured to calculate pulmonary artery systolic pressure.Statistical analysis was performed using SPSS 15 for Windows , and the variables were expressed as mean ± SD. The Kolmogorov-Smirnov test was employed to check normal distribution of the continuous variables; standard statistical techniques was used to test the differences between patient subgroups with and without major cardiovascular events; Student t-test was used for the normally distributed continuous variables; and Mann-Whitney test for the non-normally distributed continuous and ordinal categorical variables. For all methods, a P value < 0.05 was considered statistically significant.Study subjects consisting of 136 (85%) female and 51 (15%) male. r EDT, r E/ Ea , IVA, time interval from the beginning of the QRS complex to the beginning of Ea velocity, and IVC dimension . All measurements were classified based on body surface area in the three groups . CompariDiastole is the period of ventricular relaxation and encompasses periods of iso-volumetric relaxation and early and late diastolic filling. Impaired diastolic function with relative preservation of the systolic function is an early feature of either the right and or left ventricular impairment . The RV


Cardiogenic shock and myocardial rupture can complicate an acute myocardial infarction (AMI). A case is reported in which a 58-year-old male with an acute inferior myocardial infarction required placement of biventricular assist device for hemodynamic support eight days after the onset of his AMI; eleven days after his AMI, the patient developed abrupt onset of hemodynamic instability with massive bleeding from his chest tube due to delayed free wall myocardial rupture that was discovered when he was taking emergently to the operating room. Myocardial rupture in patients with a ventricular assist device should be considered in the differential diagnosis in the event of acute hemodynamic compromise. A high level of suspicion for such a complication should prompt aggressive and emergent actions including surgery. We present a case of delayed free wall myocardial rupture following an acute inferior wall myocardial infarction in a patient with biventricular mechanical circulatory support. Ventricular free wall rupture is a fatal complication after myocardial infarction. With an increase in the management of cardiogenic shock with mechanical circulatory support devices, there should be a high level of suspicion for mechanical complications after myocardial infarction. The possibility that the VAD may contribute to the rupture also needs to be explored.A 58-year-old male with a history of coronary artery disease presented to an outside hospital with an acute inferior wall myocardial infarction and cardiogenic shock. An emergent cardiac catheterization was performed and a bare metal stent was placed to the right coronary artery. An intra-aortic balloon pump (IABP) was inserted due to hemodynamic instability. Further, an Impella 2.5  cardiac assist device was also placed via a percutaneous approach from the femoral artery. A transthoracic echocardiogram performed demonstrated severely dilated ventricles with severe biventricular systolic dysfunction. The patient at that time was transferred to our facility, a large tertiary medical center, for further management. Due to continued cardiac decompensation upon arrival, the IABP and Impella 2.5 were removed, and the patient was placed on venoarterial extracorporeal membrane oxygenation (ECMO) using the femoral vessels.The patient continued to require hemodynamic support with ECMO eight days after his myocardial infarction; thus, a decision was made to provide biventricular mechanical support as a bridge to heart transplantation. In the operating room, the ECMO circuit was explanted and biventricular assist devices (BIVADs)  were plaEleven days following his initial presentation and three days after the BIVAD placement, the patient developed acute hypotension with massive (approximately 2 liters) bleeding from his chest tubes. The patient was emergently taken to the operating room with a provisional diagnosis of cannula dislodgement. In the operating room, the patient was placed on emergent cardiopulmonary bypass. On entering the pericardial cavity, copious bleeding was observed from the diaphragmatic surface of the heart. Aggressive suctioning of the blood demonstrated a 5 cm × 5 cm necrotic area with myocardial rupture on the inferior myocardial wall of the left ventricle corresponding to the distribution of the right coronary artery and away from the cannulas. The myocardial rupture was repaired successfully using Teflon strips and large caliber sutures. The patient was weaned-off cardiopulmonary bypass, and the BIVAD support was reinstituted. Unfortunately, a computed tomography scan of the brain that was obtained after surgery demonstrated diffuse cerebral edema with global ischemia. After discussing with family members, supportive comfort care measures were instituted, and the patient expired three days after his operation for his myocardial rupture repair.The complications of acute myocardial infarction may include cardiac arrhythmias, ventricular dysfunction with varying degrees of heart failure, mechanical complications including papillary muscle rupture leading to acute mitral regurgitation, free wall myocardial rupture, and ventricular sepal defect in the zone of infarct . MyocardCardiogenic shock after an acute myocardial infarction secondary to severe left or right ventricular systolic dysfunction is associated with a mortality of approximately 59% and 55%, respectively . With inMyocardial rupture complicated by an acute myocardial infarction may be delayed in patients with ventricular assist devices. Myocardial rupture in patients with a ventricular assist device should be considered in the differential diagnosis in the event of acute hemodynamic compromise. A high level of suspicion for such a complication should prompt aggressive and emergent actions including surgery.


A 14-year-old boy after balloon valvuloplasty of severe aortic valve stenosis in the neonatal period was referred for heart-lung transplantation because of high grade pulmonary hypertension and left heart dysfunction due to endocardial fibroelastosis with severe mitral insufficiency. After heart catheterization, hemodynamic parameters were invasively monitored: a course of levosimendan and initiation of diuretics led to a decrease of pulmonary capillary wedge pressure (from maximum 35 to 24 mmHg). Instead of an expected decrease, mean pulmonary artery pressures (mPAP) increased up to 80 mmHg with increasing transpulmonary pressure gradient (TPG) up to 55 mmHg. Oral bosentan and intravenous epoprostenol then led to a ~50% decrease of mPAP (TPG between 16 and 22 mmHg). The boy was listed solely for heart transplantation which was successfully accomplished 1 month later. A 14-year-old boy presented with the history of severe aortic valve stenosis; he had undergone successful balloon valvuloplasty at the age of 3 days. He was on followup elsewhere and was reportedly in stable clinical condition for 13 years, performing alpine skiing, cross country running, and mountain biking. He reportedly had normal systolic left heart function in the presence of left ventricular endocardial fibroelastosis (EFE) without signs of elevated right ventricular pressure on echocardiography. Neither heart catheterization nor cardiopulmonary exercise testing was performed. At the age of 14 years, he complained of fatigue during cycling and hiking for the first time. On echocardiography at that time severe mitral valve regurgitation and a markedly enlarged left atrium were seen besides the well-known mild aortic valve stenosis/regurgitation and endocardial fibroelastosis. Tricuspid valve regurgitation was demonstrated with a maximum velocity of 5.28 m/sec presuming a systolic pulmonary artery pressure of 111 mmHg . 2) was 97%. He had a 3/6 systolic heart murmur with punctum maximum over the third intercostal space at the left and the right parasternal border and a pronounced 2nd heart sound. The boy was scheduled for heart catheterization. On admission, he was physically still active but had stopped sports. On physical examination, he was eupneic with a heart rate of 79 beats per minute at rest, blood pressure was 100/60 mmHg, and transcutaneous oxygen saturation  11 WU × m2; there was no pressure gradient across the aortic valve. On pulmonary vasoreactivity testing (100% oxygen + nitric oxide 20 ppm), mPAP increased to 67 mmHg, PCWP increased to 35 mmHg, TPG increased to 31 mmHg, and CI increased to 3.1 l/min/m2, while PVRI basically remained unchanged with 10 WU × m2. A Swan Ganz catheter was inserted, the patient was put on diuretics , and a course of levosimendan (0.1 µg/kg/min for 24 hours) was administered. After levosimendan, PCWP constantly decreased to values around 25 mmHg but mPAP increased up to 80 mmHg while cardiac index remained stable  58 mmHg, pulmonary capillary wedge pressure (PCWP) 30 mmHg, transpulmonary pressure gradient (TPG) 28 mmHg, cardiac index (CI) 2.6 l/min/md stable . 2) and PCWP . TPG thus decreased to values of 16 to 22 mmHg. Calculated PVRI was between 4 and 5 WU × m2 , mPAP (19 mmHg), PVRI (3.5 WU × m2), and TPG (13 mmHg)  . Four weGross examination of the explanted heart showed globular enlargement and an extensive endocardial fibroelastosis of the left ventricle with involvement of the aortic and mitral valves, the papillary muscles, and chordae tendineae .Pulmonary hypertension (PH), secondary to structural or functional left heart disease in children, represents a delicate clinical condition where treatment options are often limited. The presence of endocardial fibroelastosis  in congeMedical treatment of pulmonary hypertension by advanced therapies without treating the underlying left heart disease can lead to severe pulmonary congestion . TherefoWhat is remarkable in this case is the substantial and somewhat unexpected increase of pulmonary artery pressure after improvement of left ventricular restrictive kinetics by diuretics and levosimendan. At that point, we felt safe enough to initiate pulmonary vasodilative therapy in order to lower PVR.The positive inotropic action of levosimendan is due to its binding to troponin C which facilitates the interaction between actin and myosin filaments without changes in intracellular Ca++ ion concentrations , 11. BecAfter consultation of several centers with superb expertise, surgical options like resection of EFE and mitral valve plasty as well as extra corporal mechanical support by means of left ventricular assist device were omitted in our patient and heart transplantation was considered as the therapeutic strategy with most favorable prognostic outcome for this young boy. Diuretics and levosimendan led to a substantial improvement of diastolic left heart function. Our own experience of beneficial effects of pulmonary vascular dilative medical therapy with bosentan in patients with heart failure with a normal ejection fraction with PVH and right ventricular failure  led us tThe pursued stepwise increase of epoprostenol from the initial dose of 2 ng/kg/min could not be carried out due to systemic hypotension (RR < 100/60 mmHg), most probably because of synergistic vasodilative effects of both drugs on the systemic vasculature. Therefore we consider bosentan as the main acting drug on the pulmonary vascular bed in this case. Invasive monitoring of therapeutic effects on left heart function and pulmonary vasoreactivity is mandatory before deciding on heart or heart lung transplantation in patients with pulmonary hypertension owing to left heart disease.


Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function.31P MR spectroscopy, respectively.Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion  and oxygenation  during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and AS patients had reduced MPRI  and BOLD SI change during stress , as well as reduced PCr/ATP  and LV strain . Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (−19.4 ± 2.5%) improved significantly.Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand–supply balance to preserve myocardial energetics and LV function are promising future therapies. Aortic valve stenosis (AS) is characterized by pressure overload left ventricular hypertrophy (LVH) and impaired myocardial perfusion reserve . This haand oxygenation in the same setting during vasodilator stress ) and %LV mass (17.9 ± 6.8%) were also similar to the CMR indices of the patients with follow-up scan, all p > 0.05.We further explored the data by comparing the baseline characteristics, severity of AS and CMR findings of the AS patients with (n = 14) and without follow-up (n = 11). Patients who did not have follow-up CMR were older than those who had follow-up CMR after AVR (73 vs. 65 years), in which the 3 patients who had perioperative complications (2 deaths and 1 pacemaker implantation) were among the oldest in that group. The rest of the baseline characteristics and severity of AS were similar in both groups (results not shown). The CMR indices of patients without follow-up CMR scan, in particular BOLD SI change (5.0 ± 11.2%), MPRI (0.9 ± 0.2), circumferential strain (−16.0 ± 3.3%), PCr/ATP ratio (1.43 ± 0.25), LVMI (90 ± 27 g/mand oxygenation response to vasodilator stress in severe AS patients and normal epicardial coronaries, which correlate with the degree of impairment in myocardial energetics and contractility. Second, following AVR, alterations in myocardial perfusion and oxygenation are reversible along with improvements in energetics and circumferential strain.There are two main findings of this study. First, we demonstrated that significant impairment in myocardial perfusion Microvascular dysfunction is a well-established phenomenon in pressure-overload LVH . This caIn the absence of obstructive CAD, the hypertrophied ventricle is vulnerable to ischemia especially under stress . This isOur results confirm the previous finding of reduced PCr/ATP ratio in patients with severe AS ,12. We nWe showed that improvement in oxygenation 8 months after AVR occurred in parallel with improvements in stress perfusion , energetOur findings suggest that substantial microvascular dysfunction leading to myocardial tissue ischaemia during vasodilator stress is present in severe AS without epicardial CAD. A reduced capacity to augment myocardial oxygenation during stress may contribute to poor clinical outcome, as prognosis rapidly deteriorates after development of symptoms such as angina and the onset of LV dysfunction. Oxygenation-sensitive CMR together with MR-spectroscopy provide a comprehensive insight into the pathophysiology of ischaemia and metabolic derangements in AS patients. Importantly, our findings suggest a potential new avenue for therapy targeted at improving microcirculation and reducing oxygen demand, e.g. nitrates , calciumWe included a small number of AS patients with diabetes, hypertension and dyslipidaemia, which may contribute to myocardial perfusion abnormalities. However, only patients with well-controlled diabetes and BP were included and the few patients who had dyslipidaemia were well treated by statin. It would be challenging to recruit patients with severe AS without any of these conditions which are very common in the elderly population. However, the reversibility of our findings after AVR strongly suggests that our findings were not due to concomitant diseases. Although the present BOLD technique only acquired a single mid-ventricular slice, this should not affect the result as left ventricular hypertrophy in AS is general. Our study demonstrates proof of concept, and confirmation of our findings in larger scale studies is warranted.In severe AS without epicardial CAD, there is blunted oxygenation response to adenosine stress suggestive of microvascular impairment, which correlates with impaired energetics and subclinical LV dysfunction. Myocardial perfusion, oxygenation, energetics and contractility are restored following AVR. Oxygenation-sensitive CMR provides pathophysiologic insight, may become a helpful diagnostic tool, and suggests novel strategies for therapy in AS aimed at improving the oxygen demand/supply balance.AS: Aortic stenosis; AVR: Aortic valve replacement; BOLD: Blood-oxygen level dependent; CMR: Cardiovascular magnetic resonance; FWHM: Full width half maximum; LGE: Late gadolinium enhancement; LVEF: Left ventricular ejection fraction; LVH: Left ventricular hypertrophy; LVMI: Left ventricular mass index; MPRI: Myocardial perfusion reserve index; PCr/ATP ratio: Phosphocreatine to adenosine triphosphate ratio; SI: Signal intensity.The authors declare that they have no competing interests.MM: contributed to the conception, design and coordination of the study, substantially acquired and analyzed the data, performed statistical analysis and drafted the manuscript; JMF and NP contributed to data acquisition and critical revision of the manuscript; AL contributed to data analysis and critical revision of the manuscript; SD, RDS, MP, RS, SW, MDR, HA have critically revised the manuscript; SN and TDK participated in the conception and design of the study and critically revised the manuscript. All authors read and approved the final manuscript.


Introduction. Left ventricular outflow obstruction might be part of the pathophysiological mechanism of Tako-tsubo cardiomyopathy. This obstruction can be masked by Tako-tsubo cardiomyopathy and diagnosed only by followup. Case Presentation. A 70-year-old female presented with Tako-tsubo cardiomyopathy and masked obstructive hypertrophic cardiomyopathy at presentation. Conclusion. Tako-tsubo cardiomyopathy typically presents like an acute MI and is characterized by severe, but transient, regional left ventricular systolic dysfunction. Prompt evaluation of the coronary status is, therefore, mandatory. The prognosis under medical treatment of heart failure symptoms and watchful waiting is favourable. Previous studies showed that LVOT obstruction might be part of the pathophysiological mechanism of TCM. This paper supports this theory. However, TCM may also mask any preexisting LVOT obstruction.  Tako-tsubo cardiomyopathy (TCM) is an acute cardiac syndrome of unknown etiology characterized by severe but transient systolic dysfunction of the apical and/or mid segments of the LV mimicking myocardial infarction in the absence of obstructive coronary artery disease , 2. ThisSeveral studies showed that left ventricular outflow tract obstruction (LVOTO) might be present in up to 25% of patients with TCM. It remains unclear if LVOTO is the cause or result of TCM. There are a few case reports in the literature reporting an association between TCM and hypertrophic obstructive cardiomyopathy (HOCM). In these patients, there was a pressure gradient below the level of the aortic valve between the aorta and the left ventricle. A 70-year-old female patient presented to the emergency room complaining of sudden onset shortness of breath. Past medical history was noncontributory except for hypertension. Patient's vital signs included: blood pressure 160/80 mmHg, resting heart rate 84 beats/min, respiratory rate 18 breaths/min, oxygen saturation 95%, and temperature 37.0°C. Cardiac auscultation revealed normal first and second heart sounds and no murmurs. Jugular venous pressure was normal. Neither lower limb edema nor signs of pulmonary congestion were noticed. The initial ECG showed ST-elevation in the precordial leads from V2 to V4 . The iniμmol/s/L to 3.1 μmol/s/L , and troponin I from 2.04 ng/mL to 5.89 ng/mL  during the first 6 hours after admission. The patient was transferred to ICU and stabilized by standard medical heart failure management including beta blockers, diuretics, and ACE-inhibitors.The patient's complete blood count, basic metabolic panel, and liver function tests were all within normal range. Two sets of myocardial enzyme assays showed a progressive increase in creatine phosphokinase from 2.1 After 3 days, echocardiography revealed normal LV systolic function, no resting wall motion abnormalities, LV septal wall thickness of 24 mm, and systolic anterior motion (SAM) of the anterior mitral valve leaflet. There was a peak systolic pressure gradient below the level of aortic valve of 20 mmHg at rest, increasing to 70 mmHg after Valsalva maneuver.On day four, a second invasive hemodynamic evaluation was performed, confirming a simultaneous pressure gradient between the LV and aorta of 45 mmHg at rest that increased to 70 mmHg after Valsalva maneuver . PressurThe patient was discharged on medical treatment including beta blocker, statins, and low dose aspirin. Upon followup after 3 months, the patient was asymptomatic whereas transthoracic echocardiography continued to show the same gradient of 50 mmHg across the LVOT.Tako-tsubo cardiomyopathy, also known as stress cardiomyopathy, transient apical ballooning, or broken heart syndrome, has raised interest since it was first described by Dote et al., who named it Tako-tsubo since the shape of the LV resembles a Japanese octopus trap, with a round bottom and narrow neck .The prevalence of TCM among patients with symptoms suggestive of acute MI is 0.7–2.5% , 7, 8. IThere are no controlled data to define the optimal medical regimen of the disease. It appears reasonable to treat these patients with standard medications for LV systolic dysfunction including ACE-inhibitors, beta blockers, diuretics, inotropes, and intra-aortic balloon counterpulsation if needed , 16, 17.The exact etiology of TCM is still unknown, but several theories have been proposed. These include multivessel coronary artery spasm, obstruction of the LVOT, impaired cardiac microvascular function, impaired myocardial fatty acid metabolism, acute coronary syndrome with reperfusion injury, and endogenous catecholamine-induced myocardial stunning and microinfarction , 18–21.Exposure to endogenous  or exogenous  stress and increased sympathetic activity have been reported in most cases of TCM. This association suggests that the mechanism of disease might be sympathetically mediated . Plasma Early studies showed that LVOT obstruction might be present in 25% of patients with TCM. Echocardiography reveals a typical septal bulge associated with systolic anterior motion of the mitral valve and mitral regurgitation similar to the findings associated with HOCM . It remaThere are very few case reports about TCM in patients with hypertrophic obstructive cardiomyopathy . They alTako-tsubo cardiomyopathy typically presents like an acute MI and is characterized by severe, but transient, regional left ventricular systolic dysfunction. Prompt evaluation of the coronary status is, therefore, mandatory. The prognosis under medical treatment of heart failure symptoms and watchful waiting is favourable.Previous studies showed that LVOT obstruction might be part of the pathophysiological mechanism of TCM. This paper supports this theory. However, TCM may also mask any preexisting LVOT obstruction.


We invented novel mitral valve repair technique; rough-zone trimming procedure (RZT) for anterior mitral valve prolapse. Prolapse site was resected in obtuse triangle shape and sutured edges to creates deep coaptation and improves regurgitation. Though it is simple and reproducible technique, functional mitral stenosis is a risk. Valve function and hemodynamics were investigated using dobutamine stress echocardiography (DSE) in patients after mitral valve repair using RZT.Patients underwent RZT for the anterior mitral valve , quadrangular resection (QR) of the posterior mitral valve , RZT + QR of bileaflet valves  and healthy individuals  and were assessed by DSE (doses up to 20 μg/Kg/min). Echocardiographic data including mitral valve area (MVA), mitral valve mean pressure gradient (MVmeanPG), and systolic pulmonary artery pressure (sPAP) were measured at rest and at peak stress.2), MVmeanPG (mmHg) and sPAP (mmHg) were 2.8 ± 0.4 and 3.4 ± 0.3, 3.3 ± 1.1 and 7.4 ± 4.1, and 25.7 ± 4.7and 49.1 ± 4.1, respectively, in the AML group. Dobutamine stress increased all parameters but not to pathological levels. The results were similar to those of the other groups after mitral valve repair, whereas MVA was larger and MVmeanPG was lower in the control than in the AML group.Rest/stress MVA (cmValve repair using RZT does not pathologically obstruct the mitral valve, either at baseline or during dobutamine stress, and does not affect valve hemodynamics and reserve. Mitral valve repair rather than replacement has become the first choice of surgical treatment for mitral valve regurgitation because unnecessary of anticoagulant therapy and restoration of left ventricular function. Several techniques to repair the mitral valve have been presented and we invented a novel mitral valve repair technique (rough-zone trimming: RZT) to treat anterior mitral valve prolapse. The prolapse site is resected in RZT within a small obtuse triangle shape limited to the rough zone and re-sutured edges. This creates deep coaptation and prevents regurgitation. Among repaired mitral valves in 96 patients between February 2007 and January 2013, 49 of them were repaired using RZT . The early and midterm (>12 months) outcomes of RZT for the repair of the anterior mitral leaflet were satisfactory  to assess the hemodynamics of mitral valves that were repaired using RZT.All patients underwent mitral valve repair of anterior leaflets between February 2007 and January 2013. Patients who underwent mitral valve repair for posterior leaflets, bileaflets and healthy controls were also included. The elimination criteria comprised serious disorders such as angina pectoris, severe hypertension, arrhythmia, cerebral bleeding, aortic aneurysm, aortic dissection, < 6 months after mitral valve repair and withholding written consent to participate. Our institutional review board and medical ethics committee approved the present study .Cardiopulmonary bypass was established via a full median sternotomy, the ascending aorta, and the superior and inferior vena cava were directly cannulated, the ascending aorta was cross-clamped, and then antegrade and retrograde cardioplegic solution was injected. The mitral valve was exposed via a conventional left atriotomy.The mitral valve configuration and the prolapse site were checked using saline injection. Anterior and posterior mitral commissures were compressed using horizontal mattress sutures (3–0 polyester with pleget). We ensured that the stitch was bigger on the posterior annular side, which led to not only deeper leaflet coaptation, but also the ability to draw the posterior leaflet upwards to the same plane as the anterior leaflet. Thus, the prolapse site became obvious. The technique is similar to Kay sutures , but theWe used the RZT to repair prolapse sites that were located in the anterior leaflet. Prolapsed sites were resected in the shape of an obtuse triangle and confined to the rough zone. The resected height of the triangle is confined to the rough-zone (not cut into the clear zone). The resected base length of the triangle is only the degenerated and thickened area. Resected edges were then brought together with interrupted 6–0 monofilament sutures. The repaired site of the valve leaflet was brought down into the left ventricular side to acquire deeper coaptation, which improved mitral valve regurgitation.  . The posWe repaired prolapse sites in the anterior and posterior leaflets (bileaflet) using both RZT and QR techniques.After repairing mitral valve leaflets, annuloplasty proceeded using a suitable flexible band to prevent future annular dilation. Since the annular size was adjusted by ESS, we did not apply annular plication with the flexible band. After completing a series of valve repairs procedures, we performed retrograde cardioprotective beating test (RC-beating test) to check for residual regurgitation . Under aOne investigator evaluated all patients using a Phillips iE33 ultrasound device . Left ventricular diameters , volumes , ejection fraction (EF) derived from the Teichholz and Simpson rule. Cardiac output was calculated as stroke volume (LVEDV - LVESV) × heart rate (HR). The mitral valve area (MVA) was calculated using the pressure half-time (PHT) method. Mean and peak transmitral pressure gradients  were determined using continuous wave Doppler echography. Systolic pulmonary pressure (sPAP) was derived from the maximal velocity of the tricuspid Doppler tracing at a fixed right atrial pressure of 10 mmHg. The degree of mitral regurgitation (MR) was estimated from the maximum regurgitant jet area (MRA) in color flow Doppler echocardiograms.2, or MVmeanPG under stress of > 15 mmHg, or sPAP under stress of > 60 mmHg were defined as severe mitral stenosis requiring surgery.The protocol for dobutamine stress echocardiography is described below. All patients were placed in the left decubitus position for echocardiographic assessment at rest. Thereafter, the DSE study was started by intravenously infusing dobutamine (5 μg/Kg/min) using a syringe driver. Blood concentration were allowed to stabilize for five minutes and then the first stage of the echocardiographic study started by increasing the dobutamine dose in 5 μg/Kg/min increments every three minutes to a maximum of 10, 15 and 20 μg/Kg/min. Echocardiographic data were collected at each stage. Blood pressure, oxygen saturation and electrocardiographic findings were continuously monitored throughout the study, which was stopped when either of the following end-points was achieved: target heart rate of > 85% of maximum predicted (220 - age) or the dobutamine dose was maximal (20 μg/Kg/min). The study was discontinued if any of the following events occurred: intolerable symptoms (chest pain or progressive dyspnea), limiting asymptomatic side effects such as systolic or diastolic blood pressure of > 220 and/or > 120 mmHg, hypotension defined as a relative or absolute > 30 mmHg decrease blood pressure, supraventricular tachycardia or atrial fibrillation, ventricular tachycardia or frequent, polymorphous premature ventricular beats. Acquired data were verified according to the American College of Cardiology/American Heart guidelines for the management of patients with valvular heart disease (2008)  in which2; grade 0), mild , moderate , moderately severe  and severe  [The severity of MR was classified as none or trivial (MRA ≤ 2.0 cmgrade 4) .t-test. Between-group comparisons were analyzed using Welch’s t-test. P < 0.05 was considered statistically significant.All values are expressed as means ± standard deviation. Rest and stress data were compared using a paired Nineteen patients with repaired mitral valves and 11 healthy control individuals participated in the DSE study. Paroxysmal supraventricular tachycardia developed in one patient after mitral valve repair for the anterior leaflet and accelerated ideo-ventricular rhythm developed in one healthy control. Both opted out of the study and their data were excluded. Therefore, the DSE study was completed in 10 patients in the AML group, four each in the PML and bileaflet groups and in 10 healthy controls (Table 2) in the AML, PML, bileaflet and control groups were 2.8 ± 0.4/3.4 ± 0.3, (p = 0.0005), 2.8 ± 0.3/3.2 ± 0.3, (p = 0.001), 2.5 ± 0.1/2.9 ± 0.1, (p = 0.022) and 4.1 ± 0.4/5.1 ± 0.5, (p = 0.0001), respectively  also did not appeared at rest and with stress in all patients. Hemodynamic data such as heart rate, systolic blood pressure and cardiac output were significantly increased in all groups. The rest/stress values for MVA , though the posterior leaflet and posterior annuals are drawn to the anterior leaflet, the posterior leaflet is compressed and the posterior leaflet height is also slightly reduced. RZT can also reduce excessed degenerated rough-zone of anterior leaflet by resection. These factors may contribute to prevention of occurrence of SAM. The outcomes of this procedure for 25 and 24 diseased anterior mitral and diseased bileaflets, respectively, between February 2007 and January 2013 were favorable. There is no case of suture dehiscence and SAM.In RZT, resected area of the anterior leaflet was small. We have data for sizes of resected obtuse triangle segments (n = 35). Mean height of the triangles was 4.7 ± 1.9 mm and mean base length of the triangles was 12.8 ± 6.7 mm. However, the resection and suture components of the technique confer risk of creating functional mitral stenosis. It was the only concern about RZT and we had to research about it.Stress (exercise or drug) echocardiography is useful for evaluating mitral valve stenosis  and the 2, respectively), which might have affected the MVmeanPG. However, the MVA was 3.0 cm2 in the other patient (a7) in the AML group and in one patient (p2) in the PML group, and their MVmeanPG was relatively high. The echocardiographic findings of patient a7 in the AML group indicated sclerotic changes at the anterior leaflet and curved transmitral blood flow due to surging against sclerotic AML tissue  [2, 2.7/6.3 and 33.5/41.6 mmHg, respectively. Agricola et al. repaired mitral valves using the edge-to-edge procedure and investigated outcomes using exercise echocardiography [2, 2.8/4.6 and 22.8/28.2 mmHg, respectively. Our findings after RZT for AML prolapse for MVA (rest), MVmeanPG (rest/stress) and sPAP (rest/stress) were 2.8 ± 0.4 cm2, 3.3 ± 1.1/7.4 ± 4.1,and 25.7 ± 4.7/49.1 ± 4.1 mmHg, respectively. Although our sPAP values were relatively high, they were similar to those of healthy controls. Thus, we considered that our values were equivalent to those reported, and that the RZT procedure is an appropriate and feasible technique.We compared our results with those of other echocardiographic findings after mitral valve repair. Zucca et al. repaired mitral valve anterior leaflet prolapse by implanting artificial chordae. Their value for the mean MVA was 2.7 cm2 – 3.0) . Giovann2 – 3.0) . Their viography . Their vAll prescribed drugs were continued during the study to consider the safety of the patients. The study cohort was small, because many patients had a history of serious diseases. Because of the nature of echocardiography, not all relevant parameters were measured and some were impossible to measure.The Dobutamine stress echocardiography study for RZT revealed mitral valvular function reserve and no pathological obstruction. Novel mitral valve repair technique; RZT is simple, safe and reliable procedure.


Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease.82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block.We sought to investigate rubidium-82 (82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII).Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease  and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001).Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by  Noninvasive diagnosis of coronary artery disease (CAD) in left bundle branch block (LBBB) patients is a clinical and methodological dilemma because septal perfusion abnormalities have been demonstrated by myocardial perfusion scintigraphy (gated-SPECT) even in the absence of CAD 82Rb) positron emission tomography (PET) stress myocardial perfusion has emerged in the clinical setting as a noninvasive imaging method for diagnosis and risk-stratification that has several advantages compared to Single Photon Emission Computed Tomography (SPECT). In addition to assessing myocardial perfusion, wall motion and left ventricular function, 82Rb-PET can quantify global and regional myocardial blood flow (MBF) during both rest and stress, and can also measure CFR, which is important for the clinical management of patients with CAD Rubidium-82 , 38 were selected (Group I - GI) who met the inclusion criteria: LBBB and sinus rhythm. The median age was 63.5 years, range 58-68 years and 22 were women (58%). Patients with unstable angina, recent myocardial infarction, pacemaker rhythm and atrial fibrillation or flutter were excluded from GI. In addition, we selected 30 patients without LBBB (Group II - GII), who were free from known CAD and had normal 82Rb-PET studies , and matched them based on the same clinical risk factors that are associated with reduced absolute quantitative flow measurements From February to October 2013, 665 consecutive patients, who were referred for dipyridamole-stress gated-SPECT for the evaluation of known or suspected CAD, underwent 82Rb-PET perfusion study, patients were categorized into a subgroup with LBBB and no CAD .In a subset of patients, a request to perform a coronary anatomy assessment was made by the patient's doctor. Therefore, a cardiac catheterization or coronary computed tomography angiography (CTA) The patients were instructed to fast for 4 h, abstain from caffeine and cigarettes for 24 h and theophyllines for 36 h, and discontinue beta-blocker or calcium-channel blocker medications for 3 days and long-acting nitrates for 6 hours before the study.82Rb  over a 60-second interval.Cardiac PET was performed using a Gemini-TOF 64-slice system . Resting images were acquired using a 3-D list mode acquisition over 8 min, after a square wave intravenous injection of 82Rb activity was administered four minutes later. Stress images were acquired and processed for the resting scan. The symptoms were treated with intravenous aminophylline after the end of image acquisition.Dipyridamole was infused intravenously (0.56 mg/kg) over four minutes and the same 82Rb-PET image acquisitions with two low-dose CT-based attenuation corrections for PET transmission scans were performed , after a normal end-expiration. The estimated effective radiation dose from the complete PET study (rest/dipyridamole 82Rb and 2 CT attenuation corrections) was 3.0 mSv Before rest and after stress, Fused CT and emission images were visually evaluated for alignment by an experienced technologist and, if necessary, corrected by manual 3-D translation. The images were reconstructed using a 3-dimensional row-action maximum likelihood algorithm (3-D-RAMLA), with 3 iterations/33 subsets and a medium filter. The entire 8 min of emission data was binned to form a dynamic image sequence  for MBF quantification and the last 6 min to form myocardial uptake and ECG-gated images. The images were semi-automatically reoriented to generate short-axis and vertical long-axis slices. The left ventricle ejection fraction (LVEF) was calculated from the rest and stress images using 4D QGS The studies were processed in batch mode using QPET  to quantify MBF and CFR. In brief, left ventricle (LV) contours were positioned automatically with an algorithm that determines the LV contours from the summed dynamic images data. The 3-D cylindrical region  for the LV input function was automatically placed in the middle of the valve plane and oriented along the long axis of the heart. Dynamic myocardial samples were obtained from the polar map by analyzing all of the time frames within the fixed LV contour boundaries 1K [mL/min/g of myocardial tissue] and 2k [min−1]), blood-to-myocardial spillover fraction and myocardial partial-volume corrections. A previously calibrated 82Rb extraction fraction was used to estimate MBF from 1KA standard 1-tissue compartment model was used to quantify MBF, which includes regional uptake and clearance parameters , according to the standard 17 segments of the American Heart Association model Rest and stress uptake images were visually analyzed using a 5-point score  for relative myocardial perfusion in 17 segments t or Mann-Whitney tests conditioned by the normality distribution assumption, which was checked using the Anderson-Darling test and the assumption of homogeneity of variances, which was established by the Levene test. In turn, discrepancies among GI-A, GI-B and GII were verified by ANOVA or Kruskal-Wallis tests, supported by the assumptions of normality and homogeneity of variances. Next, multiple comparisons relative to GI-A vs. GI-B and GI-B vs. GII were performed using the parametric or nonparametric Dunnett test Quantitative variables were expressed in medians (25%-75% quartile), while qualitative variables were expressed in percentages. Differences in the quantitative variables between GI and GII were verified by R package, version 3.1.1. Comparisons of the anterior or septal wall with the other walls were evaluated using the paired nonparametric Dunnett test All of the procedures that were performed in studies that involved human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.82Rb-PET perfusion. The median ages were not significantly different . The female gender was predominant in all groups. Furthermore, the main clinical risk factors, such as hypertension, dyslipidemia and diabetes, were also not significantly different between the groups.The patient demographics are summarized in p<0.001), whereas the rest flow was lower only in the septal and apical walls . A comparison of the anterior or septal walls with the other walls in GI revealed that the rest flow, stress flow and CFR were significantly lower in the anterior wall and less so in the septal wall. However, the rest and stress flows were also significantly lower in the septal than in the inferior wall (p=0.05) and could identify CAD in LBBB . We found statistically significant differences between the groups when we considered perfusion abnormalities in the anterior and/or septal walls (p=0.04) as well as in the inferior and/or lateral walls (p=0.003) (Twenty-four patients in GI (63%) had no significant perfusion abnormalities and all patients in GII had normal perfusion. Moreover, the perfusion abnormalities (SSS ≥4 and/or SDS ≥2) tended to be more prevalent in the presence of CAD (GI-A p=0.003) .p<0.001), but no significant differences between GI-A and GI-B (p=ns). However, GI-A had a high prevalence of LVEF dysfunction (<45%) only during stress (p=0.02).LVEF values and LV cavity volumes are summarized in 82Rb-PET, beyond relative myocardial perfusion image interpretation, has already been established. Worse patient outcomes and a higher incidence of cardiac events  have been demonstrated in cases with global CFR <2 mL/min/g in patients with normal and abnormal relative myocardial perfusion An evolution in cardiovascular imaging with PET-CT systems being incorporated into the clinical setting has been occurring since the early 2000s. This trend is partially driven by the fact that cardiac PET-CT offers a noninvasive method to assess relative myocardial perfusion, LV function, MBF and calcium score (15). The importance and independent prognostic values of MBF and CFR using 15O-water PET and the study results showed that the septal/lateral MBF ratio was 19% lower than that in the controls, as a result of functional alterations. Our study assessed LBBB patients and showed that stress MBF as well as CFR were significantly lower in all of the walls in a larger LBBB population compared to the controls. We were careful to compare 2 homogeneous populations that were matched for the presence of primary clinical risk factors, which are associated with reduced stress flow and CFR 82Rb-PET that could aid in the identification of CAD and risk-stratification of LBBB patients.Despite the low prevalence of LBBB in the general population Our results suggest that resting MBF in the inferior wall may not be influenced by the presence of LBBB . In GI-B patients, stress and rest flow were also lower in the anterior than in the septal and inferior walls. It appears that LBBB did not interfere with the evaluation of MBF and CFR in the inferior wall or the abnormal activation of the LV because LBBB is more proximal (anterior and high septum areas), sparing the inferior or even lateral walls, which are opposite and more distal. In the presence of LBBB (both with and without CAD), stress MBF was also lower in the anterior than in the septal wall. The septal wall showed a smaller MBF impairment than that in the anterior wall, which could be explained by the fact that the septum is a less extensive area compared to others and thus, MBF may have a lower expression or be underestimated in a quantitative evaluation.82Rb-PET relative myocardial perfusion could discriminate between LBBB patients with and without CAD, even when considering the LAD territory alone. Perfusion abnormalities were more prevalent in the presence of CAD. Although anterior and septal abnormalities have been described in most similar studies in the absence of CAD, perfusion abnormalities may also result from technical imaging issues , functional ischemia, CFR alterations caused by the LV dynamic asynchrony, or because of subclinical myocardial disease Our study also suggests that Rest and stress LVEFs in LBBB patients were also lower than those in GII. As expected, GI-B had less LV dysfunction than GI-A at stress and it was associated with CAD. Furthermore, GI-A on average had a lower LVEF response to stress compared to GI-B. Nevertheless, even in the absence of established CAD, patients with LBBB demonstrated a decreased LV reserve and might not respond appropriately to stress The mechanisms that underlie the reduced MBF and CFR in nonischemic cardiomyopathy can include endothelial dysfunction, macro- and microvascular obstruction, vascular remodeling and extravascular compressive forces 82Rb-PET is that it could provide additional information for the assessment of CAD in LBBB patients.Thus, the presence of CAD had a profound effect on CFR and also on traditional relative myocardial perfusion and LV function measures, with a higher prevalence of perfusion and LVEF abnormalities in GI-A. There was a detrimental influence of LBBB over ventricular dynamics, independent of the presence of CAD. These functional abnormalities may be associated with abnormal MBF, perfusion, and function. According to our data, an advantage of using 82Rb-PET has several advantages compared with SPECT studies, one disadvantage is the inability to perform 82Rb-PET in association with exercise stress tests, due to the short half-life of the tracer. However, in LBBB, pharmacological stress is preferable to exercise perfusion imaging for both diagnosis and risk stratification Our study has some limitations. Despite the fact that 82Rb-PET in these patients were expected even in the absence of CAD This was a single-center observational study that was performed with a select population of LBBB patients. Thus, its results may not be applicable to all such patients because the great diversity of clinical situations in which LBBB can be present may yield different results. Moreover, cardiac catheterization or CTA were not available in all LBBB patients. Usually, the absence of relative perfusion defects in PET-CT studies is associated with non-significant CAD 82Rb-PET have decreased MBF and CFR in all LV territories. Moreover, these measures are important diagnostic tools for patients with LBBB and suspected CAD, which might be identified with a CFR evaluation.In the present study, we showed that LBBB patients who were assessed by


Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short-axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age  and ECV  were positively associated with Tmv. The results remained robust in certain subgroups. In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is closely related to LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it’s underlying mechanisms leading to poor prognosis. Non-uniform contraction of left ventricular (LV) myocardial walls due to declining electromechanical synchronicity (LV dyssynchrony) may result in myocardial inefficiency236et al. showed that CMR contrast-enhanced T1 time is associated with outcome in patients with HF and preserved ejection fractionPreviously, the only methodology available to assess myocardial diffuse interstitial fibrosis was the histopathology assessment of endomyocardial tissue biopsy specimen. Recently, diffuse myocardial interstitial fibrosis has been proved to be able to be quantitatively defined by CMR contrast-enhanced T1 mapping technique89In the current study, we planned to investigate the relationship between myocardium regional interstitial fibrosis and dyssynchrony both in HF patients with impaired or preserved systolic function as well as in age-matched controls. We hypothesized that regional difference in myocardial interstitial fibrosis might be closely associated with LV dyssynchrony.Sequential 42 patients with SHF, 76 patients with HFpEF, and 20 patients without HF were enrolled in the study. The demographics of the study population were summarized in The MRI parameters of the three groups were shown in The results of mixed model analyses were shown in To our knowledge, this is the first clinical study to investigate the association between regional interstitial fibrosis and LV intra-ventricular dyssynchrony. Our result demonstrates that regional interstitial fibrosis is positively associated with LV intra-ventricular dyssynchrony irrespective of the LV global function.In physiological condition, the fibrillary collagen network is in intimate contact with myocardial cells and plays a critical role in the maintenance of ventricular shape and functionThe recent advancement in acquisition sequences enables us to quantify diffuse myocardial interstitial fibrosis by T1 mapping with high spatial resolution. Several studies have used post-contrast myocardial T1 time to quantify diffuse myocardial interstitial fibrosis in patients with various cardiac diseases89The association between LV dyssynchrony and fibrosis has been reported before. In one study, a higher global fibrosis index, defined as more LV segments with LGE, is associated with a higher degree of LV dyssynchrony in patients with NICMPMyocardium interstitial fibrosis and dyssynchrony have been shown to coexist in early stage of many disease entities such as DM, hypertension and in aging process18192021222348910Our findings might have some important clinical implications. For example, previous study has demonstrated that patients receiving cardiac resynchronization therapy (CRT) have worse prognosis if there are scars in the regions where the LV pacing leads are placed toFinally, in order to investigate the relationship between regional ECV and dyssynchrony index, the image modality used to measure LV dyssynchrony should be interrogated with T1 mapping. Thus, we used cine MRI instead of cardiac ultrasonography to quantify LV dyssynchrony. In general, myocardial velocity timing could be evaluated by ultrasound tissue Doppler imaging (TDI) and myocardial strain timing could be evaluated by MRI tagging and 2D-strain echocardiography (2DSE)27In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is a major determinant of LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it’s underlying mechanisms leading to poor prognosis.There are several limitations of the study. First, this study design was cross-sectional, we could not clarify the causal relationship between regional interstitial fibrosis and dyssynchrony. Second, our study has no histological evidence to validate the results regarding the changes of myocardial ECV because all subjects have no indication for endomyocaridal biopsy. Third, the temporal resolution of cine MRI is inferior to echocardiography. This results in lower sensitivity of the MRI-derived LV dyssynchrony index, only subjects with higher degree of dyssynchrony could be identified.The research was approved by the institutional review board of the National Taiwan University Hospital Ethics Committee. The study was conducted in accordance with the approved guidelines. All study participants provided written informed consent.One hundred and eighteen patients who met the following criteria were enrolled as the HF group: 1) they had HF symptoms of New York Heart Association (NYHA) classification functional Class II to III or a history of HF symptoms/signs by Framingham criteriaCMRI was performed on a 3 T MRI system  with an 8-channel cardiovascular phased array torso coil. Myocardial T1 mapping was performed with an ECG-triggered Modified Look Locker Inversion recovery (MOLLI) sequence before and 10 minutes after a 0.15 mmole/kg intravenous administration of the gadolinium-based contrast agent . The MOLLI protocol used two Look-Locker cycles to acquire 7 images over 11 heart beats, the scanning parameters were TR/TE, 1.9 ms/1.0 ms; flip angle, 35°; minimum inversion time, 110 ms; inversion time increment, 80 ms; matrix size, 256 × 192; slice thickness, 6 mm; spatial resolution, 1.28 mm; GRAPPA acceleration factor, 2; number of inversions, 2; images acquired after first inversion, 5; pause 4 heart beats and images acquired after second inversion, 2. Five evenly-spaced short-axis slices were acquired sequentially from the LV base to apex. After post-contrast T1 acquisition, LGE images were acquired using an ECG-triggered phase-sensitive inversion recovery (PSIR) prepared segmented fast gradient echo pulse sequenceCine MRI was performed using a segmented balanced steady-state gradient echo pulse sequence with a retrospective ECG R-wave trigger. The scanning parameters were TR/TE, 3.0 ms/1.5 ms; flip angle, 46°; matrix size, 256 × 208 and spatial resolution, 1.21 mm. Multiple short-axis slices were prescribed from the mitral orifice to LV apex with slice thickness of 8 mm and gap of 2 mm. The true temporal resolution was 63 ms and thirty cardiac phases were reconstructed retrospectively for each slice level.Three slices of short-axis LV images at the basal, papillary muscle and apical levels were chosen for further analyses. The cine and T1 MRI were interrogated by choosing the nearest locations at the z axis. At each level, the LV myocardium was divided into 6 segments and in each segment, the mean ECV value and the wall motion were calculated as followings. For T1 MRI, the regions of interest (ROIs) in the blood of central cavity and each segment of LV myocardium were drawn for each slice. The averaged T1 values of the segmented ROIs were then computed. After subtracting the pre-contrast values from the post-contrast values, the changes of the relaxation rate (1/T1) in the blood and in the myocardium were obtained. Myocardial ECV values were calculated using the ratio of the change in relaxation rate in the myocardium to that in the blood and multiplied by (1- hematocrit)For LV function and mass analysis, endocardial and epicardial contours of the LV were determined at each slice level on cine MRI and the area enclosed by each contour was computedSince Shapiro-Wilk test showed that some of the variables were not normally distributed, variables among groups were compared by non-parametric methods. Continuous variables were expressed as medians and interquartile ranges (IQR) and categorical variables were expressed as percentages. Categorical variables were compared among different groups of patients by using Chi-square tests. Continuous variables were tested by the nonparametric Kruskal-Wallis test and the Mann-Whitney U test was used for post-hoc analysis for comparison of the medians between different groups. To test the association between LV dysynchrony and myocardial interstitial fibrosis in all subjects, a linear mixed model using repeated-measures analysis was constructed to analyze the relationship between Tmv and ECV in each LV segment since we collected 18 segments of Tmv and ECV in one patient. Since age, ECV and Tmv were normally distributed, the model was adjusted for age, gender, presence of LGE, QRS over 120 ms, history of diabetes mellitus (DM), hypertension, coronary artery disease (CAD), LV mass index and grouping. Also, an interaction term LGE x ECV was added to test whether the presence of LGE modifies the effect of ECV on Tmv. BIC was used to determine whether the random effects of intercept and ECV should be considered in the model or not. A value of p < 0.05 was considered significant. Statistical analyses were performed using the SPSS software package, version 19 .How to cite this article: Lin, L.-Y. et al. Myocardial Regional Interstitial Fibrosis is Associated With Left Intra-Ventricular Dyssynchrony in Patients With Heart Failure: A Cardiovascular Magnetic Resonance Study. Sci. Rep.6, 20711; doi: 10.1038/srep20711 (2016).