In this review we have looked at indications for cardiac transplantation in congenital heart disease. An outline of the general principles of the use of transplant as a management strategy both as a first line treatment and following other surgical interventions is discussed. We explore the importance of the timing of patient referral and the evaluations undertaken, and how the results of these may vary between patients with congenital heart disease and patients with other causes of end-stage heart failure. The potential complications associated with patients with congenital heart disease need to be both anticipated and managed appropriately by an experienced team. Timing of transplantation in congenital heart disease is difficult to standardize as the group of patients is heterogeneous. We discuss the role and limitations of investigations such as BNP, 6 minute walk, metabolic exercise testing and self estimated physical functioning. We also discuss the suitability for listing. It is clear that congenital heart patients should not be considered to be at uniform high risk of death at transplant. Morbidity varies greatly in the congenital patient population with the failing Fontan circulation having a far higher risk than a failing Mustard circulation. However the underlying issue of imbalance between donor organ supply and demand needs to be addressed as transplant teams are finding themselves in the increasingly difficult situation of supporting growing numbers of patients with a diverse range of pathologies with declining numbers of donor organs.  The surgical technique of cardiac transplantation was first described in 1960, followed seven years later by the first successful human heart transplant. The procedure has subsequently evolved to provide a hugely important treatment modality to manage cardiac conditions which have either exhausted medical management strategies or would otherwise prove terminal. Although transplant is a valuable treatment, with the benefits of improving quality and duration of life, it is does not offer a cure in the conventional sense as it is currently unable to restore a fully normal life expectancy. The use of transplant is restricted by rigorous selection criteria of the transplant programme, assessment of the presenting condition, underlying pathology and co-morbidities being essential for full evaluation of the patient as to their suitability for transplant. The programme is limited however by the availability of donor organs, resulting in an increasing mismatch between supply and demand within the transplant service. As a result even with stringent assessment of those deemed suitable for transplant, additional consideration must be made to finding the most suitable recipient for the scarce and precious donor organ when it does become available. Conditions for which transplant may be an option are similar in both adult and paediatric populations, however the proportions of each presenting condition understandably are very different. In general heart transplantation is considered in individuals with end stage heart failure, with a life expectancy of less than 18 months, where other medical therapy has been exhausted or ineffective. Heart transplant is generally offered to patients who are under the age of 60 years. There are absolute and relative contraindications to cardiac transplantation, including significant medical, infective and psychiatric co-morbidities in addition to physiological status at the time of assessment, however there are no UK or international guidelines specifically relating to patients with congenital heart disease See Appendix ppendix AApproximately 1 in every 145 births in the UK is affected by congenital heart conditions  some areOf the 4,600 babies born with congenital heart disease every year in the UK  approximIn the UK during the period 2009 to 2010 120 heart transplants were performed, of which 40 were in children (heart-lung transplant data for the same period being 5 in adults and none in children) . In congThe majority of patients with congenital heart disease who receive a heart transplant do so after other surgical interventions have been attempted, either palliative or reparative. Those who receive a transplant as a first line management usually do so in early life, with subsequent peaks of transplants occurring in the 6 month to 6 year age group, adolescents and 20-40 year age group, reflecting the natural course of the underlying pathologies . IncreasHeart transplants used as the first line management option for patients with congenital heart disease are usually performed in infancy. As a treatment modality it is deemed appropriate to offer the opportunity of transplant if the congenital lesion is not suitable for other surgical intervention or if the risk of other management, including surgery, is greater than that of transplant itself. On this basis transplant for patients with hypoplastic left hearts was advocated early in the history of paediatric cardiac transplantation when the outcome of palliative procedures was less successful. The early positive results seen as a result of transplant in these patients demonstrated its possible utilisation in the management of other cardiac conditions requiring intervention in early life and resulted in its wider use in the management of other congenital cardiac lesions, disease and cardiomyopathies of infancy. The outcome of staged palliative surgical procedures for hypoplastic left heart has subsequently improved and as a result the use of transplant as first line management in hypoplastic left heart disease has decreased . The early experience of the newborns with hypoplastic left hearts has resulted in the wider use of transplant in infancy for other pathologies. As a consequence the infant donor pool has remained relatively constant. Congenital lesions that are now considered for heart transplant as a first choice management include hypoplastic left heart with abnormalities which preclude the Norwood operation (eg impaired ventricular function), severe Ebstein’s anomaly, pulmonary atresia with intact ventricular septum associated with abnormal coronary anatomy, severe valve abnormalities and heterotaxy lesions Transplantation in infancy appears to confer an immunological advantage long term, as infants do not produce ABO antibodies for the first few months of life and so their risk of hyper-acute rejection related to ABO incompatibility is reduced . ABO misPost transplant coronary artery disease is also seen less in infants, possibly related to infection exposure of both the donor and recipient. Heart transplantation may be required after previous cardiac surgical procedures, many operations performed for patients with congenital heart disease not being curative, and ultimately resulting in heart failure after variable periods of time. A patient may be referred for transplant acutely if peri-operative complications are encountered, or electively after a longer period of management following a corrective or palliative procedure. Surgery performed on patients with congenital heart conditions may be complicated by associated defects such as abnormal situs, presence of collaterals and atypical vasculature. Unusual anatomy makes accurate transplant assessment of this patient group more difficult. Pulmonary vascular resistance (PVR) needs to be assessed prior to transplant to avoid later post transplant right heart failure in the transplanted heart . PVR meaIn some cases the PVR is elevated post Fontan procedure. The failing Fontan is a difficult situation where collaterals and intracardiac shunts make accurate estimation of the PVR complicated. Fontan circulation deterioration may present as either ventricular failure with a normal PVR or with high venous pressures and relatively preserved cardiac function, the latter is usually related to high PVR. Failing Fontan physiology may be demonstrated clinically by protein losing enteropathy, ascites, plastic bronchitis and pleural effusions . The conEarly transplant assessment of any patient but particularly those with congenital heart disorders is clearly prudent . AssessmThe transplant assessment is a dynamic process involving physiological and psychological determination of parameters regarding the potential recipient which may indicate short and long term, pre, peri and post operative complications for consideration. A full previous medical history must be taken from the patient and allied professionals and medical records providing details of previous surgical interventions or cardiothoracic procedures that may help evaluate the previous anatomy and condition of the recipient. Surgical procedures confer different risks for any subsequent transplant to the individual patient through sensitisation, increased risk of bleeding, infection, wound dehiscence and adhesions. Previous surgery may have implications of later complications at transplant surgery. Repeat sternotomies may increase the risk of re-entry injury however data seems to suggest that this is not associated with increased risk of subsequent morbidity or of peri-operative mortality, it should however remain a factor for the operating team to be aware of , 15. PrePrior surgical intervention indicates the potential previous exposure of the patient to blood products and human tissue homografts, an additional aspect of the patient’s history which must be fully evaluated prior to listing as use of such products increases the problem of immunological sensitisation of the patient, an issue that will be discussed later.Those who have undergone earlier cardiac surgery may also be left with atypical anatomy and communications that necessitate technical modification of the usual transplant procedure. Classically older patients with heart failure that are being considered for heart transplant present with symptoms of cardiogenic shock, shortness of breath, reduced exercise tolerance, anorexia and weight loss. In children signs may be more subtle and difficult to interpret, poor feeding, vomiting and lethargy not being uncommon findings within the paediatric setting, but growth failure generally providing a good warning sign that further investigation is warranted. Cardiopulmonary exercise testing is frequently used to evaluate patients prior to transplant. This assessment tool is mainly used in adult patients and some older paediatric patients, the information obtained contributing to the overall evaluation of the condition of the potential transplant recipient. The data obtained provides an indicator measure of morbidity and mortality relative to age and sex, although definitive statistics are difficult to obtain regarding the implication of exercise testing results as numerous exercise protocols exist. Oxygen consumption during a period of exercise is measured, and also commonly in the UK a six-minute walk test is performed, but increasingly additional parameters are being considered as equal if not more reliable indices of assessment. Reduced autonomic response to exercise as determined by minimal heart rate elevation in response to an exercise challenge is associated with a higher risk of mortality in adult patients with congenital heart disease in general . AdditioEchocardiogram is the most widely used imaging modality in cardiology, and it is a valuable tool in the assessment of potential transplant patients. Increasingly the more refined three dimensional imaging obtained by cardiac magnetic resonance imaging is being utilised to add to pre-operative assessment of patients. This imaging modality provides the clinician with invaluable additional data regarding structure, function, failure, tissue mass and fluid flow of the cardiovascular system. The relationship of any conduits to the sternum and the venous connections should be determined. The pulmonary arteries need to be carefully imaged to allow a planned repair of these at transplant if needed. However, it is well known that pulmonary artery reconstruction is an important risk factor for transplant . Natriuretic peptides (NP) are a group of hormones responsible for the regulation of sodium and fluid balance within the body. Of the three major classes of natriuretic peptides, A, B and C, A type natriuretic peptide (ANP) and B type natriuretic peptide (BNP) are released predominantly by the heart, their levels alter measurably in the blood in response to the mechanical stress placed on the myocardium. BNP is a valuable prognostic marker used in the assessment of heart failure. A strong association between BNP levels has been demonstrated with echocardiogram indices, clinical status and prognosis in children with left ventricular failure . The eleIn adults a single BNP measurement in patients with chronic heart failure may similarly identify those patients at highest risk of death, and may be a better predictive indicator than measurement of left ventricular ejection fraction by echocardiogram, peak oxygen uptake on exercise testing or composite scoring systems such as heart failure survival score , 23. HowA matching system using human leucocyte antigens, those proteins on the cell surface that enable the host to differentiate self from non-self, is used in other solid organ transplant protocols. The aim being to have as close a match in these presenting proteins as possible to reduce the likelihood of transplanted organ rejection by the host. Although it is known that as few as three HLA mismatches may result in greater predisposition to rejection, unlike in other organ transplant programmes, full cross matching is not possible prior to transplant because of the limited supply of organs and an ischaemic time that must be kept to a minimum. A pre-transplant screening of the anti-HLA antibodies of potential recipients is however performed using a panel of antibodies sensitised to those most common HLAs. Panel Reactive Antibody (PRA) screening provides the transplant team with an indication of the potential immunological difficulty in finding a suitable donor organ, and some insight as to the extent of immunomodulation therapy that will be required to either empirically prepare a patient for transplant or manage the patient post-operatively. Patients with congenital heart disease are more likely than most other potential heart transplant recipients to be exposed to blood products or human tissue during their previous management. The increasing use of mechanical cardiac support and left ventricular assist devices, requiring frequent blood product transfusion also primes the recipient against HLAs. Such exposure of the patient to foreign HLA proteins greatly magnifies the risk of pre-transplant sensitisation, reducing the probability of finding an immunologically good tissue match at transplant. Special precautions are therefore required to deal with the likelihood of sensitisation in this patient group. Combating this higher risk scenario requires directed immunotherapeutic strategies pre- and post transplant, with a considerable risk of early rejection a consequence if they are not adequately controlled. With a failing circulation cardiac output is inadequate to meet the requirements of other vital organs. Resultant end-organ damage is frequently encountered and may be either reversible if addressed early or irreversible if refractive to therapy and intervention. With patients suffering with congenital heart disease surviving longer into adult life, additional complications and co-morbidities are being increasingly observed as a result of end organ damage. The risk of end organ damage may be age-related, especially in patients with congenital heart disease as increased duration of exposure to a sub-optimal circulation and the risk of additional organ damage is more predictable. With the limited supply of transplantable hearts it is vital the potential host is assessed to establish the severity and reversibility of such damage. Although transplant may be the only treatment modality to extend life in certain patients, it is inappropriate to transplant a new organ into a failing body that will not be able to recover sufficiently its other vital functions. Even if additional organ failure is severe it may be reversible if provided with a restored and appropriate circulation, it is therefore the reversibility of the end organ damage that is most important for transplant teams to assess but difficult to predict. All organ systems will be affected to some extent when in an environment of a failing circulation. Renal dysfunction is commonly seen as a consequence of heart failure. Approximately half the adult patients with congenital heart disease, particularly those with cyanotic conditions, have been observed to have significantly impaired renal function . A threeThe pathophysiology of renal failure seen in patients with congenital heart disease is likely to be similar to that seen in heart failure acquired secondary to other conditions. Low cardiac output causing chronic renal hypoperfusion results in neurohormonal and autonomic upregulation measures in an attempt to restore an appropriate circulatory pressure. This unsustainable situation culminates in renal damage quantifiable in terms of blood analysis and GFR measurement.Persistent hyponatraemia appears to be an indicator of outcome in patients with heart failure, independent of haemodynamic status . Anaemia is seen in adults with congenital heart disease, and may be associated with a three- fold increase in the risk of death . The patLiver disease is also observed in patients with end stage cardiac failure, the hepatic dysfunction seen causing abnormal clotting and fibrosis, later leading to cirrhosis. Liver status clearly being an important factor in pre-transplant assessment. This is a particular problem with the failing Fontan circulation .Both subjective and objective evaluation of the potential transplant patient is important. The use of the Minnesota Living with Heart Failure self assessment questionnaire is frequently used in adult heart failure patients. Other similar self- assessment surveys also exist focusing on additional specific aspects of heart failure, such as the London Chest Activities of Daily Living Scale. The wording and interpretation of the questions by patients in self evaluation does however result in variable reliability in the data that it is intended to assess . Self esThe psychological stability of patients being assessed for transplant is also reviewed. Adults with chronic psychiatric illness or substance dependence may be deemed unsuitable for the transplant process. The wait for transplant once listed is also an extremely difficult time for all patients and their families so ongoing support and assessment should be maintained. Poor quality of life and inability to participate in the normal routines and activities of daily living affect the emotional well being of children and adults alike. Patients with congenital heart disease frequently only rate their physical functioning and general health during assessment, rarely ranking psychosocial aspects of their illness, despite observations that even minor symptoms of depression exert a more significant impact on their quality of life than exercise capacity , 33.The neurological status and development of patients with congenital heart disease is also pertinent. Neurological complications of uncorrected congenital disorders include stroke and brain abscess, as well as the adverse influence on neuro-development. In addition there are complications that arise as a consequence of cardiac surgery especially in the young, the neurological complications of cardiac bypass and hypothermic circulatory arrest being well documented . When the cardiac status fails completely and mechanical support is required to preserve life, the risk of additional complications is magnified both through the severity of the presenting heart failure and the risks associated with its management. Extra-corporeal membrane oxygenation (ECMO) may be more rapidly utilised than left ventricular assist devices and may provide short term support in emergency situations, but carries considerable procedural and consequent risk. It has been more commonly used in paediatrics than in adults. It is clear that ECMO significantly increases the risk of heart transplantation. Left ventricular assist devices however offer the patient the advantages of long term cardiac support without the need for continuous sedation or respiratory support, indeed many patients live relatively normal lives with an LVAD inserted whilst waiting the increasingly long periods for a transplant. Studies have concluded that children requiring LVAD support prior to heart transplant have the same survival outcomes as those who do not . However, there is very little in the literature on VAD support for failing congenital heart disease. It is clearly difficult to balance pulmonary and systemic flow in the failing single ventricle and may be very difficult in the failing Fontan circulation. There are some successful case reports, but the wider US experience with the Berlin Heart which will be published in the near future will give a much clearer idea about the risk of support in complex congenital heart disease. The need for ventilator support prior to cardiac transplant also confers poorer prognostic outcome. Rigorous assessment by the multi-disciplinary team enables the most appropriate candidates to be selected for heart transplantation. Patients may be categorised on the results of the described investigations as being either high or low risk for the procedure and are also classified as either urgent or standard depending on their prevailing clinical condition. Some patients with congenital cardiac defects who do survive childhood and progress to adult cardiac services may not however get listed due to the consequent high risk presentation of end organ damage, raised PVR, previous thoracotomies and associated adhesions, chronic formation of collateral circulations and immune sensitisation. Due to the shortage of donor organs priority is generally given to the sickest patients, with those individuals listed as urgently needing a new organ being considered before others that are more stable when an organ becomes available. The psychological strain on the individual and the family involved whilst waiting for an indeterminate duration on a transplant waiting list is hard to comprehend The clinical status of the patient may fluctuate during this time and due to the supply and demand inequality of the transplant programme, patients die whilst waiting for a new heart. In the United States of all the children listed for heart transplantation between 1999 and 2006 17% died before an organ became available for them . To optimise the effectiveness of a cardiac transplantation programme for patients with congenital heart disease facilities and skills need to be appropriate for the difficulties that may be encountered. The available surgeons and transplant team including nurses, anaesthetists, perfusionists, cardiologists and intensivists need to be skilled in the field of congenital cardiac surgery themselves, so that atypical anatomy, previous reparative surgical techniques and potential hazards may be appreciated and anticipated. Donor organs for patients with congenital defects often require extended structures to remain intact at explantation to permit effective transplantation into the recipient with structurally abnormal anatomy. Extended harvest of systemic and pulmonary vasculature may assist with the implantation into the recipient but may limit the use of other potential donor organs, particularly the lungs. Consideration needs also to be paid to managing the medical risk factors and complications highlighted such as renal dysfunction, clotting aberrations, elevated PVR and sensitisation. At a critical time for the heart transplant service, as donor organs are in such low supply, but demands in all age groups remain high, serious thought must be given as to how we may redress the balance. More rigorous assessment criteria could be imposed restricting the use of the limited organs offered to those with the best potential outcome, but this would limit the service by exclusion of whole patient populations, including those with congenital lesions. But not all congenital heart disease is the same. For example transplant following the Senning and Mustard procedures is possible with low risk, while transplant for the failing Fontan patients has an 8.6 times increased relative risk of death . CarefulWith the advantages of heart transplant in infancy observed, perhaps more transplants should be aimed at this age group, even if organs are not best matched immunologically and may even be marginal in other characteristrics such as size, good outcomes are still observed. Heart transplantation in infancy may be advantageous in many ways but may also enforce the life- limiting implications of transplant onto the extremely young before the natural course of the disorder can be fully determined. Ethical debate persists as to how donors may be most appropriately selected and creates another topic for crucial negotiation . As heart failure management progresses, particularly with the increasing use of mechanical support in all age groups, perhaps clinicians will be focusing on alternative and novel treatment modalities to reduce the need of transplant, especially for conditions where a structurally normal heart exists, but where dysfunction has occurred via disease processes such as muscle damage. Reducing the demand for organs by medical or surgical means would begin to modify such an unbalanced situation.The field of cardiac transplantation is clearly complicated with additional early risk factors for morbidity and mortality attached than are encountered in many other transplant situations, but with careful planning these may be addressed and minimised. If patients survive the early operative complications of their transplant, late survival rates appear to be comparable to survival of transplant for other cardiac indications such as cardiomyopathy . This trMany factors contribute to the decision to transplant patients with congenital heart disease. Consideration should be paid to the optimal timing of referral to a transplant team for assessment. Assessment of paediatric and adult patients varies considerably in ease of assessment and reliability of results. Certain clinical presentations and underlying diagnoses as well as co-morbidities are recognised as stratifying patients to high risk and low risk categories for outcome of transplant, indeed certain pathologies are deemed to be contraindications to transplant. The ISHLT has brought together experts in the field of heart transplantation from around the world to develop consensus guidelines for the management of transplantation. Their guidelines offer advice regarding suitability of donor organs and peri-and post operative management. via consultation and database registries to permit effective management of the individual patient. Difficulty arises however when attempting to provide a unified management strategy when clearly the field of congenital heart disease is such a heterogeneous topic, with variability in risk factors, co-morbidities and outcomes [With increasingly short supplies of organs available for transplantation, and those being donated often crossing international boundaries, it is more important than ever that transplant teams, clinicians and co-ordinators maintain communication to produce and update structured guidelines and international standards on which informed and rational decisions can be made as to how these organs can be most effectively utilised. The complex and continually evolving field of transplantation, particularly for congenital heart disease, deserves international collaboration outcomes  yet it i


Progressive left ventricular (LV) diastolic dysfunction due to hypertension (HTN) alters left atrial (LA) contractile function in a predictable manner. While increased LA size is a marker of LV diastolic dysfunction and has been shown to be predictive of adverse cardiovascular outcomes, the prognostic significance of altered LA contractile function is unknown.A consecutive group of patients with chronic hypertension but without significant valvular disease or prior MI underwent clinically-indicated CMR for assessment of left ventricular (LV) function, myocardial ischemia, or viability. Calculation of LA volumes used in determining LA emptying functions was performed using the biplane area-length method.Contractile) demonstrated strong unadjusted associations with patient mortality, non-fatal events, and all MACE. For every 10% reduction of LAEFContractile, unadjusted hazards to MACE, all-cause mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds, respectively. In addition, preservation of the proportional contribution from LA contraction to total diastolic filling  was strongly associated with lower MACE and patient mortality. By multivariable analyses, LAEFContractile was the strongest predictor in each of the best overall models of MACE, all-cause mortality, and non-fatal events. Even after adjustment for age, gender, left atrial volume, and LVEF, LAEFContractile maintained strong independent associations with MACE (p < 0.0004), all-cause mortality (p < 0.0004), and non-fatal events (p < 0.0004).Two-hundred and ten patients were included in this study. During a median follow-up of 19 months, 48 patients experienced major adverse cardiac events (MACE), including 24 deaths. Decreased LA contractile function (LAEFIn hypertensive patients at risk for left ventricular diastolic dysfunction, a decreased contribution of LA contractile function to ventricular filling during diastole is strongly predictive of adverse cardiac events and death. Left Ventricular (LV) diastolic dysfunction as a consequence of chronic hypertension is a prevalent condition associated with significant morbidity and mortality. Current strong prognostic markers that reflect diastolic dysfunction remain limited, but their identification may improve treatment planning and monitoring of patients with chronic hypertension. LA size reflects the duration and severity of exposure to increased diastolic filling pressures in the LV and is relatively load-independent. As LV diastolic impairment progresses, effective diastolic filling becomes increasingly dependent on LA contractile function until the LA contractile reserve can no longer meet the demand of elevated diastolic ventricular pressure-3. WhileWe studied a consecutive series of patients with history of chronic hypertension medically treated for at least 6 months who were referred to undergo cardiac magnetic resonance imaging (CMR) for clinical purposes. Patients were referred either for a) evaluation for myocardial ischemia with stress CMR or b) assessment of regional and global left ventricular function and myocardial mass. Patients with any of the following were excluded: a) any evidence of myocardial infarction by history, medical record, or abnormal cardiac enzymes, b) any significant aortic or mitral valvular dysfunction , and c) confirmed (by biopsy) myocarditis, infiltrative cardiomyopathy , or pericardial disease. Other exclusion criteria included concurrent unstable angina, NYHA class IV heart failure, hemodynamic instability, claustrophobia precluding CMR, and metallic hazards. Patients with patterns of late gadolinium enhancement consistent with infiltrative cardiomyopathy or myocarditis were also excluded. The institutional ethics committee of the Brigham and Women's Hospital  approved the clinical follow-up activities of the study.All patients underwent a detailed history immediately before the CMR. Hypertension, hypercholesterolemia, diabetes, and family history of premature CAD were defined by published criteria-7. Signi® CV/i, GE Healthcare, USA) with a 4-element or 8-element phased-array surface coil. CMR study consisted of cine SSFP imaging  of LV function and late gadolinium enhancement imaging  for myocardial scar. All images were acquired using retrospective ECG gating and breath-holding. Cine and late enhancement imaging were obtained in 8-14 matching short-axis (8 mm thick with 0 mm spacing) and 3 radial long-axis planes. The 3 radial long-axis planes were prescribed at 60 degrees apart. Typical view per segment during a cine SSFP acquisition was 12 yielding a temporal resolution of approximately 45 ms and maintaining a breath-hold of approximately 10-12 seconds for each slice location. A previously described segmented inversion-recovery pulse sequence for late enhancement imaging was used[All patients were studied supine in a 1.5T CMR system  and minimum LA volumes (LAVmin). Total LA emptying volume was divided into LA passive emptying volume (VPassive) and LA contractile volume (VContractile), in which VPassive was calculated as the difference between LAVmax and the LA volume preceding atrial contraction (LAVac) and VContractile was calculated as the difference between LAVac and LAVmin. LA total, passive, and active emptying functions  were calculated according to the following formulas:Quantitative Analysis of the left atrium is illustrated in Figure s Figure . ConsistIn additon, we calculate the proportional contribution of LA contraction during diastole by calculating the following parameters:While left atrial dimension (in millimeters) was made available to the attending physicians on the day of the CMR, all other quantitative measurements of the left atrium were not reported as part of the routine clinical care.All images were analyzed with specialized software . We graded segmental systolic wall motion as normal or abnormal in each study and also graded segmental wall motion using a 4-point scale  according to the standard 17-segment ACC/AHA nomenclature. We inteResting 12-lead ECGs were obtained at a median of 1 day (interquartile range: 0-7 days) from CMR. We confirmed that no cardiac event or revascularization occurred between the collection of ECG and the CMR study. ECG interpretation was first performed by computer analysis followed by visual over-reading by a single reader blinded to the CMR results and the clinical outcome. ECG left atrial enlargement was defined by a terminal negative P-wave duration of > 40 ms and depth ≥ 1 mm measured on lead V1. We used the Sokolow-Lyon index to indicate LV hypertrophy on ECG.At least 6 months following the CMR, clinical information was obtained from patient telephone interviews, contacting patients' physicians, and hospital records. A standard questionnaire was used during telephone interview. Survival was obtained from the National Social Security Death Index in patients lost on first contact. Major aContractile, were compared by Student's t-test or Fisher's exact test. Kaplan-Meier distributions for MACE, all-cause mortality, and nonfatal events were stratified by the median value of LAEFContractile and were compared by log-rank tests. We fitted Cox proportional-hazards models to estimate the likelihood ratio chi-square (LRχ2) and the unadjusted hazard ratios (HR) of all the variables. We also assessed the univariable association of the proportional contribution of LA contraction during diastole  with MACE and other other events. To determine the set of variables that were most strongly associated with LAEFContractile, we performed linear regression using LAEFContractile as a continuous dependent variable, with all variables in Table Contractile by Spearman correlation.Baseline demographic differences, classified by the median LAEFContractile after adjustment to well-known risk predictors. Therefore, we sought to determine if LAEFContractile remained a significant predictor after adjustment to patient age, gender, minimal left atrial volume, and left ventricular ejection fraction. The validity of the proportional-hazards assumptions of this final model for MACE was again tested and was valid for all the variables in this model. All analyses were performed with SAS 9.1  for Windows.We performed 2 separate multivariable approaches to analyze the predictive value of CMR variables for MACE and all-cause mortality. In the first approach, we sought to determine the strongest set of variables that were associated with MACE, all-cause mortality, and non-fatal events, respectively, in this study cohort. We used a stepwise forward selection strategy and considered all clinical, ECG, or left ventricular variables as listed in Table Contractile (33%). Baseline average left ventricular ejection fraction at rest was low normal at 58 ± 13%. During the study period, 53 patients were referred to undergo coronary angiography at a median 34 days (interquartile range 1-12 days) from CMR study. Among them 38 patients (72%) were found to have significant (>70%) luminal stenosis. LAEFContractile dichotomized by its median level did not show correlation to the presence of angiographic coronary stenosis, history of percutaneous coronary intervention, or history of cardiac bypass surgery. Patients with LAEFContractile below median value demonstrated a larger LA antero-posterior dimension , lower left ventricular ejection fraction , and higher left ventricular end-systolic volume index . There was high inter-observer correlation in quantifying LA volume (kappa statistic 0.83) across the three time phases of the cardiac cycle.From a consecutive series of 225 patients with a history of chronic hypertension, 3 1%) had unsuccessful CMR due to large body habitus or technical problem. Seven patients (3%) had moderate or severe aortic or mitral valvular dysfunction and were excluded from the study. Five patients were lost to follow-up but were reported alive. The remaining 210  formed the study cohort and were followed for a median 19 months (range 6-50 months). Patients were referred to undergo stress CMR for evaluation of ischemia (n = 106) or for assessment of left ventricular function (n = 104). Table % had unsAt a median follow-up of 19 months (range 6 to 47 months), 48 MACE occurred. Among them were 21 cases of death, 3 acute myocardial infarction, 12 cases of hospitalization for unstable angina, and 12 cases of congestive heart failure requiring hospitalization.min (P = 0.045) and did not demonstrate significant correlation with above median LAVmax. Left atrial enlargement by ECG demonstrated poor sensitivity (16%) but excellent specificity (93%) in identifying patients with above median LAVmin. Left atrial enlargement by ECG could not differentiate above or below median level of LAEFContractile. While LV mass (g) is slightly higher in patients with above median LAVmin , it was not significantly different among patients with above or below median level of LAEFContractile. Left ventricular ejection fraction was negatively correlated with LAVmin  and positively correlated with LAEFContractile . By multivariable linear regression, a history of atrial fibrillation on ECG, LAVmin, and left ventricular ejection fraction were most strongly predictive of LAEFContractile.Twenty patients (10%) demonstrated left atrial enlargement on ECG. The presence of left atrial enlargement by ECG was only weakly associated with a higher than median LAVmin or LAVmax, and presence of late gadolinium myocardial enhancement were all associated with non-fatal events but did not achieved significant association with MACE or mortality. LAVmin (in ml/m2), LAEFContractile, and LAEFTotal demonstrated strong association with patient mortality, non-fatal events, and all MACE. Figure Contractile , with a preserved Contractile/Total ratio portended to lower likelihood to mortality . On the contrary, LA antero-posterior dimension only demonstrated a weak unadjusted prognostic association with non-fatal events but not with all-cause mortality , all-cause mortality , and non-fatal events .In the first multivariable approach, stepwise forward selection strategy demonstrated that LAEFy Figure . In the Contractile was not significantly different between patients with or without myocardial ischemia . In the subgroup of patients who underwent CMR ischemia evaluation, presence of ischemia did not demonstrate any significant association with MACE, all-cause mortality, and non-fatal events . When presence of myocardial ischemia was entered into a model that contains LAEFContractile, the significant associations of LAEFContractile with MACE and all-cause mortality, respectively, were not altered .One hundred and six patients (50%) of the cohort underwent CMR for evaluation of myocardial ischemia. Among them 52 (49%) underwent dobutamine stress cine and 54 (51%) underwent adenosine stress perfusion imaging. Nineteen (17%) of the 106 patients were found to have myocardial ischemia during stress CMR. Twenty-six (25%) of the 106 patients experienced MACE during study follow-up, among them 11 died. Mean LAEFIn this present study of hypertensive patients without significant valvular disease or myocardial infarction, a decreased contribution of LA contractile function to ventricular filling during diastole was strongly predictive of MACE, mortality, and non-fatal events. We found that in these patients, proportional contribution of the LA contraction as measured by the LA Contractile/Total ratio are strongly associated with MACE and patient mortality. These observations were true even after adjustment for age, gender, LA volume and left ventricular ejection fraction. This postulates that altered LA mechanical contractile function by CMR in patients with or at risk for diastolic dysfunction from hypertension provides unique and independent prognostic value to adverse cardiovascular outcomes. To our knowledge, this is the first study which demonstrates a relationship between altered LA contractile function and CV outcomes, including mortality, in hypertensive patients.In normal humans, passive emptying of the LA (a combination of the reservoir and conduit functions of the LA) during ventricular diastole contributes 75-80% of LV filling. LA contractile function normally contributes approximately < 25% of the total LV filling volume, but becContractile utilizing CMR as in the current study. Conformed to the existing body of echocardiographic literature, we used planar images of the LA acquired along its long axis and then used two dimensional measurements and standardized formulas to calculate LA volumes by the biplane area length method. It is therefore conceivable that the CMR findings of our study can be applied to similar patients undergoing echocardiographic assessment.In this study, CMR is able to quantify LA contractile function at high spatial resolution for border delineation and adequate temporal resolution to capture LA motion throughout the cardiac cycle. We demonstrated such LA quantitative results are highly reproducible. While echocardiographic studies have assessed the relationship between LA volume and clinical outcomes, the prognostic relationship between the different components of LA mechanical function and clinical outcomes has not been well studied. We postulate that exposure of the LA myocardium to elevated left ventricular diastolic pressure can result in LA myopathy which can be quantified by LAEFLA size has long been reported to be a sensitive and load-independent marker of both the severity and duration of LV diastolic dysfunction-24. TherThere are a number of study limitations. This study was a retrospective referral-based cohort study at a single center. All of the subjects studied had been referred for CMR examination, while the clinical indications of such were appropriate, the generalizability to other populations with hypertension may be limited. Only 50% of the current study cohort underwent stress CMR evaluation for myocardial ischemia. While we found that presence of myocardial ischemia did not seem to alter the prognostic significance of LA contractile function with the clinical outcomes, the current report does not have the study design or power to properly address whether myocardial ischemia could have been a confounding variable. The method of LA volume quantitation in this study can only provide estimates of LA volumes since it has not been validated against the axial stacked volumetric imaging. The study is also limited by its sample size and the small number of patients who experienced MACE, therefore some degree of model overfitting in the multivariable analyses may have occurred. For this reason, confirmation of the current study findings and exploration of potential therapeutic implications that can alter LA mechanics are necessary in a larger prospective study. Finally, concurrent load-independent measures of LV diastolic function such as tissue Doppler velocity are not available in the current study, thus prohibiting probing in the mechanism of the significant prognostic findings being reported in the current study. Such association of LA contractile function with imaging markers of diastolic dysfunction and serum markers such as naturetic peptide levels, will neIn patients with a history of chronic hypertension, a decreased contribution of LA contractile function to ventricular filling during diastole appears to be a novel predictor of adverse cardiac events and death.The authors declare that they have no competing interests.MK performed and MJH helped in post-processing and off-line analyses of the CMR images. MK, and KS collected clinical follow-up data in all of the patients. ST and TH participated in the design of the study, assisted in data entry, and performed the statistical analysis. RK conceived of the study, participated in its design, oversaw data acquisition at all levels, and helped to draft and revise the manuscript. All authors read and approved the final manuscript.


Increased left ventricular (LV) torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM), and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness.Seventeen carriers with an LV wall thickness <10 mm, and seventeen age and gender matched controls had cardiovascular magnetic resonance (CMR) cine imaging and tissue tagging. LV volumes and mass were calculated from the cine images. LV torsion, torsion rate, endocardial circumferential strain and torsion-to-endocardial-circumferential-shortening (TECS) ratio, which reflects the transmural distribution in contractile function, were determined using tissue tagging.LV volumes, mass and circumferential strain were comparable between groups, whereas LV ejection fraction, torsion and TECS-ratio were increased in carriers compared to controls .Carriers with normal wall thickness display increased LV torsion and TECS-ratio with respect to controls, which might be due to subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy. Hypertrophic cardiomyopathy (HCM) is characterized by asymmetrical  hypertrophy in the absence of increased external load and is caused by mutations in mainly sarcomeric genes that have an autosomal-dominant pattern of inheritance ,2. SeverIn the healthy heart, myocardial deformation is predominantly based on contraction of helically oriented bundles of myofibers in the endo- and epicardium . A paramAltered torsion is found to be a sensitive marker for both systolic and diastolic dysfunction -18. ElevHistological studies -25 reveaSeventeen HCM mutation carriers and seventeen age and gender matched controls without medical history (e.g. no evidence of other systemic or cardiac disease associated with LV hypertrophy) were included in the study. Families of control patients were deprived of sudden cardiac death and cardiomyopathies. Carriers were first-degree relatives of HCM index patients and recruited after genetic testing at the cardiogenetic outpatients' clinic. They had either a 2373insG mutation in the gene encoding for cardiac myosin binding protein C (MYBPC3) , or a GlAll subjects were imaged on a 1.5 T whole body scanner , using a six-channel phased-array body coil. All cine studies were performed in a single breath hold during mild expiration.Retro-triggered, balanced steady-state free precession (SSFP) short-axis cine imaging with full coverage of the LV was acquired for quantification of LV volumes, mass and ejection fraction (EF) Figure . Image pA high temporal resolution (14 ms) 3-chamber cine image was performed to determine the opening and closing time of the valves.-1 [In addition, in 15 of the control subjects and in 13 of the HCM mutation carriers, velocity encoded cine CMR was applied for quantification of mitral valve inflow velocities in order to obtain E/A ratios as reflection of diastolic function. Flow measurements were performed in a retrospective fast low angle shot (FLASH) phase-contrast technique with a velocity sensitivity set at 100 cm s-1 .2, flip-angle: 20°, repetition time: 3.6 ms, echo time: 1.8 ms, receiver bandwidth: 850 Hz/pixel, matrix size: 256 × 78, slice thickness: 6 mm, tag-line distance: 7 mm. Acquisition time per slice was approximately 3-4 minutes. After tagging images were derived, we administered 0.2 mmol/kg Gadolinium-DTPA  solely to the HCM mutation carriers, in order to obtain Late Gadolinium Enhancement (LGE) images for the detection of intramyocardial fibrosis.Myocardial tissue tagging Figure  was perfLV and LA volumes, mass and blood-flow velocities were analyzed offline, using dedicated software packages . From these, volumes, ejection fraction (EF), stroke volume (SV) and E/A ratio were derived.From the tagging images, LV torsion was calculated as the circumferential-longitudinal shear angle using Harmonic Phase displacement tracking as described before ,33. For From the torsion curves, peak torsion was derived. Peak rate of systolic and diastolic torsion was determined by calculating the time derivative of the torsion curves, with a temporal resolution of three phases (45 ms). The peak rates of systolic and diastolic torsion were corrected for peak torsion, since this parameter has been shown to increase in proportion to the value of peak torsion during exercise .Furthermore, Lagrangian circumferential strain was calculated from the tagging images using the Harmonic Phase method as described previously . StrainsBesides, the ratio of peak LV torsion to peak endocardial circumferential shortening (TECS-ratio) was calculated as an alternative to TSR. We must note that TECS and TSR are not comparable in absolute terms, since the calculation of subendocardial circumferential strain is based upon different definitions TSR see -12,17).,17.12,17All data are presented as mean ± SD. LA and LV volumes, LV mass, function, torsion, torsion rates and circumferential strain were compared between the carrier and the control group using Student's T-test or Mann-Whitney U test, when appropriate. Torsion was calculated on different longitudinal levels  and compared within patients using paired Student's T-test. Interobserver variability in peak LV torsion was assessed by redrawing of myocardial contours in 5 randomly selected healthy subjects and carriers and recalculating peak torsion by two independent observers (WPB and IKR). Bland-Altman analysis and intraclass correlation (ICC) were assessed to determine agreement. Two-sided p-values < 0.05 were considered as statistically significant.Subject characteristics are presented in Table In Table A significant increase in peak base-apex torsion was found in HCM mutation carriers with respect to controls (p = 0.001) Table , while pNo significant differences could be detected in peak systolic and diastolic torsion rate, after correction for peak torsion. This is also shown in Figure A total of 4 mutation carriers showed small areas of focal intramyocardial contrast enhancement. In order to rule out a potential influence of fibrosis on torsional behaviour and TECS measurements, we compared the values between LGE positive and LGE negative HCM mutation carriers. Results showed non-significant differences between both groups: 9.3 ± 1.85° vs 10.4 ± 2.63°, p = ns for torsion, and 0.54 ± 0.08°/% vs 0.51 ± 0.16°/%, p = ns for TECS respectively.Inter-observer agreement for peak torsion was high, with an ICC of 0.94 , and limits of agreement are -0.1 ± 16.4%  hypertrophy, like hypertension or aortic valve stenosis ,13,17,20Remarkably, non-hypertrophied HCM carriers show similar contraction patterns including a relative increase in LV torsion with respect to subendocardial circumferential contraction (e.g. increased TECS-ratio). It was expected that, due to the elevated ejection fraction in carriers, torsion and subendocardial circumferential strain (which is related to ejection volume) values would show parallel increments, resulting in unaltered TECS-ratio. Apparently, impairment of subendocardial contraction of myofibers changed the balance between torsion and ejection in mutation carriers irrespective of LV wall thickness.A variety of disease-related morphological and functional alterations could have attributed to this finding. Although currently unknown, changes in transmural distribution and/or angulation of subendocardial myofibers might have influenced regional contraction patterns in carriers. Besides, perturbations of myocardial perfusion cannot be ruled out, since studies in HCM hearts revealed abnormalities in small intramural coronary arteries and subendocardial arterioles ,23. A siExcept for myocardial disarray and/or disturbed regional myocardial perfusion as potential explanations for the relatively impaired subendocardial fiber shortening, other factors might be affecting LV torsion in HCM mutation carriers. Interestingly, mutation carriers showed a (slightly) increased ejection fraction , which This seems in line with the detected rises in systolic and diastolic torsional rates ,39,40 unThe number of patients enrolled in the study is limited, and therefore, results should be interpreted with care. Nevertheless, the data indicate that significant changes in LV torsion are present in HCM mutation carriers. Besides, not all control subjects were genetically screened for HCM mutations, which theoretically might have biased results, although prevalence is rather low for the general population. In addition, since HCM is associated with an abundance of defects in sarcomeric genes, findings in carriers with only two types of mutations might not be entirely representative for the general HCM population.Finally, we did not perform LGE imaging in healthy individuals and cannot rule out the presence of fibrosis in these patients. Nevertheless, the probability to encounter areas of focal fibrosis in healthy subjects is very low, and moreover, we demonstrated that the presence of LGE has little significance on torsional behaviour and TECS-values in mutation carriers.To clarify the meaning and potential clinical implications of increased torsional values in HCM carriers, we compared our findings with a group of 10 aged matched patients (44 ± 8 years) with manifest HCM. As Figure This study demonstrates that increased torsional deformation already exists in healthy mutation carriers, even in the absence of hypertrophy. Although the exact underlying mechanisms are currently unknown, we speculate that disease related subendocardial dysfunction might be responsible for alterations in torsion.The authors declare that they have no competing interests.IKR and WB: Study design, writing the manuscript, data analysis and interpretation; TG: Study design, revising the manuscript, patient inclusion, acquiring CMR data, coordination of genetic screening; PK: Study design, data interpretation, revising the manuscript; JTM: CMR protocol design, data interpretation, revising the manuscript; JvdV: Study design, data interpretation, revising the manuscript; MJWG: Study design, data interpretation, revising the manuscript; ACvR: CMR protocol design, revising the manuscript.


Recently two parturients with Eisenmenger's syndrome underwent caesarean section at our hospital. They were managed by a multidisciplinary team during their perioperative period. The caesarean sections were uneventfully performed, one under general anaesthesia and one with epidural anaesthesia, with delivery of two newborns with satisfactory Apgar scores. One patient died in the post-partum period, and the other did well. We discuss the anaesthetic considerations in managing these high-risk patients. During a normal pregnancy, parturients undergo dramatic physiological changes in multiple organ systems. Changes in the cardiovascular system include decreased systemic vascular resistance (SVR), increased blood volume, and increased cardiac output (CO) secondary to increased heart rate (HR) and stroke volume (SV). Cardiac disease is a major cause of maternal death, and approximately 25% of maternal cardiac deaths in the last 30 years have been due to congenital heart disease . EisenmeEisenmenger's syndrome is characterized by right-to-left or bidirectional shunting from severe pulmonary hypertension. Despite advances in medicine, the perioperative maternal mortality remains unacceptably high (estimated at 30%–50%) [−1, respiratory rate (RR) 24 breaths·min−1, blood pressure (BP) 140/95 mmHg, and oxygen saturation by pulse oximetry (SpO2) 74% on 6 L·min−1 of oxygen by facemask. Auscultation revealed a loud P2 and a grade 4/6 systolic murmur at the pulmonary area. There were jugular venous distention and mild lower extremity edema. Arterial blood gas analysis on room air demonstrated pH 7.41, PaO2 38 mmHg, PaCO2 33 mmHg, and SaO2 72%. Laboratory tests included hemoglobin (Hb) 13 g·dL−1, hematocrit (Hct) 43%, platelets 15 × 109·L−1, alanine aminotransferase (ALT) 267 U·L−1, aspartate aminotransferase (AST) 230 U·L−1, albumin 2.96 g·dL−1, D-dimer 1585 ng·mL−1, and fibrin degradation products (FDPs) 11.4 μg·mL−1. aPTT, PT, electrolytes, and serum creatinine levels were normal. Transthoracic echocardiography showed a 13 mm VSD with prominent right-to-left shunt, dilated right atrium (55 mm) and right ventricle (48 mm), right ventricular hypertrophy (12 mm), moderate-to-severe tricuspid regurgitation, estimated systolic pulmonary artery pressure of 107 mmHg, and an estimated left ventricular ejection fraction (EF) of 74%. Uterine ultrasonography showed IUGR.A 19-year-old primigravida  at 33-week gestation was referred to our hospital for VSD with Eisenmenger's syndrome. A cardiac murmur was noted in childhood, but no diagnosis or treatment was performed. She had no symptoms until she developed frequent and severe nausea and vomiting during her pregnancy. Nine days prior to admission, she developed severe fatigue, progressive cough, and shortness of breath. Past medical history was significant only for penicillin allergy. Physical examination revealed cyanosis and clubbing of her fingers. Vital signs were temperature 36.8°C, heart rate (HR) 84 beats·min−1, HR 99 beats·min−1, BP 120/53 mmHg, and SpO2 77% on 100% oxygen. General anaesthesia was chosen due to thrombocytopenia. The patient was monitored with electrocardiography, pulse oximetry, and end-tidal capnography, and noninvasive BP and left uterine displacement was applied by a 15° left-tilt of the operation table. As rapid sequence induction (RSI) with predetermined dose of anesthetics may be either excessive or inadequate, RSI was not performed after we weighed the risks of aspiration against hemodynamic instability. Slow induction of general anesthesia with titrate-to-effect etomidate 10 mg was used to avoid dramatic hemodynamic fluctuations. Intubation was facilitated with atracurium 30 mg. Atracurium was chosen to avoid further exacerbation of the compromised liver function. Anaesthesia was maintained with sevoflurane  in oxygen and remifentanil infusion at the rate of 0.08–0.10 μg·kg−1 min−1. BP and heart rate were stable  during the 45-minute operation, and SpO2 remained 67%–76% throughout the uneventful procedure. A female baby was delivered with Apgar scores of 8 at 1 min, 9 at 5 min, and 10 at 10 min. Estimated blood loss was 100 mL, and fluid administration was 550 mL Lactated Ringer's solution. Urine output was 200 mL. The patient was extubated in the operating room, and vital signs in the ICU showed BP 138/88 mmHg, HR 100 beats·min−1, RR 26 breaths·min−1, and SpO2 66%. Blood gas analysis demonstrated PaCO2 36 mmHg, PaO2 41 mmHg, and SaO2 72%. She received transfusion of fresh frozen plasma and platelets in the ICU. Intravenous morphine 3–5 mg was administered by nurse when necessary . The patient was reintubated due to severe hypoxemia 2 hours following extubation. On the 1st and 2nd postoperative days (PODs), her BP and HR were stable with administration of 0.2–0.5 μg·kg−1·min−1 nitroglycerin, while SpO2 remained in the range of 62%–74%. On the 3rd POD, her SpO2 acutely decreased to 42%, and she became unarousable. Despite aggressive resuscitative efforts, she died two hours later. Postmortem examination was denied.The patient was transferred to the intensive care unit (ICU) and treated by a multidisciplinary team of obstetricians, cardiologists, and anaesthesiologists. She received oxygen by facemask with bed rest in the left lateral decubitus position. Dexamethasone 6 mg was given to accelerate fetal lung maturity. In view of her hypoxemic condition and IUGR, a caesarean section was scheduled and metoclopramide and ranitidine were used as aspiration prophylaxis. Upon arrival in the operating room, RR was 21 breaths·min2P1, weight 62 kg, height 162 cm) with a 33-week gestation had dizziness, fatigue, dyspnea, and lower extremity edema for 1 week. She was diagnosed with congenital heart disease 10 years ago but remained asymptomatic without therapy until this time. She delivered a female baby by caesarean section without incident at another hospital 6 years ago. There was no other significant past medical history. Vital signs were HR 84 beats·min−1, RR 20 breaths·min−1, BP 125/80 mmHg, and SpO2 58% on room air and 75%–88% on oxygen at 6 L·min−1 by facemask. She had marked cyanosis and clubbing of her fingers. Auscultation revealed a loud P2 and a grade 5/6 systolic murmur in the pulmonary area. There was moderate lower extremity edema. Laboratory test results included Hb 14.5 g·dL−1, Hct 45%, platelets 173 × 109·L−1, ALT 271 g·L−1, AST 184 g·L−1, albumin 3.52 g·dL−1, and normal PT and aPTT. Blood gases showed pH 7.35, PaO2 61 mmHg, PaCO2 34 mmHg, HCO3− 18.1 mmol·L−1, base excess (BE) −6.6, and SaO2 90.1%. Transthoracic echocardiography revealed a 20 mm VSD with bidirectional blood flow at rest, enlarged left ventricle (54 mm), mild dilation of the right atrium, hypertrophy of the right ventricle, mild tricuspid regurgitation, estimated systolic pulmonary artery pressure of 166 mmHg, mild pericardial effusion, and an estimated left ventricular EF of 61%.A 30-year-old woman  10 cm HPregnancy-induced systemic vasodilation is detrimental in parturients with Eisenmenger's syndrome. Reduced SVR may increase right-to-left shunting and decrease pulmonary blood flow, leading to further hypoxemia with significant risks for both mother and fetus. Anaesthetic management of caesarean section in parturients with Eisenmenger's syndrome requires balancing SVR and pulmonary vascular resistance (PVR).General anaesthesia is often used for emergency caesarean section. However, positive pressure ventilation may decrease venous return and systemic blood pressure, which can increase the right-to-left shunting. In our hospital, general anaesthesia is used when there are contraindications to neuraxial anaesthesia or in cases of life-threatening emergency with inadequate time for neuraxial anaesthesia. The parturient in our first case had thrombocytopenia. Intravenous etomidate was used for induction to minimize the risks of decreased SVR and cardiac depression. For maintenance of anaesthesia, nitrous oxide was avoided because it is a potent pulmonary vasoconstrictor. Remifentanil can be used to produce stable hemodynamics without subsequent neonatal depression . Materna6 block without significant circulatory changes. Epinephrine should be avoided because it can produce tachycardia and arrhythmias, which will increase myocardial oxygen demand and be poorly tolerated in Eisenmenger's syndrome [6, and we think may be it is better than the traditional T4 level which can cause dangerous bradycardia with blockade of sympathetic cardioaccelerator fibres in these high-risk patients. A review of 57 articles involving 103 patients showed the safety of regional anaesthesia and recommended its use in Eisenmenger's syndrome [Neuraxial anaesthesia has the advantage of avoiding myocardial depression, but the risk of excessively decreased SVR due to the existence of sympathetic blockade, especially with single-shot spinal anaesthesia. In our second case, small boluses of 2% lidocaine were used to produce a Tsyndrome . The choVigilant intraoperative monitoring is essential for these patients. Pulse oximetry is the simplest way to assess the degree of right-to-left shunt. Invasive arterial blood pressure and CVP monitoring are recommended. Because blood pressure is often a poor indication of tissue perfusion, monitoring of cardiac output may be needed. The usefulness of a pulmonary artery catheter is controversial in patients with Eisenmenger's syndrome. Transesophageal echocardiography can provide information about cardiac function and intracardiac shunting, but it may not be tolerated in conscious patients. In our second case, continuous arterial and CVP monitoring were valuable in guiding fluid therapy and infusion of vasopressors during operation. Titrated perioperative fluid therapy is critical in patients with Eisenmenger's syndrome. Efforts should be made to avoid intravascular hypovolemia from prolonged fasting with consequent dehydration. Sympathectomy-mediated vasodilatation with neuraxial anaesthesia can produce hypotension, so volume expansion and vasopressors should be provided immediately. The use of uterine displacement promotes venous return to the heart. However, excessive fluid administration can overwhelm the compromised right heart. CVP monitoring was indicated in our case to maintain constant filling pressures in the perioperative period.Management of patients with Eisenmenger's syndrome may include the use of supplemental oxygen, digitalis, diuretics, vasodilators, and anticoagulants. Supplementary oxygen for elective and emergency caesarean section is controversial for healthy patients . In patiThe role of anticoagulation in Eisenmenger's syndrome is controversial. Pregnancy represents a hypercoagulable state, and evidence suggests pulmonary thromboembolism as a cause for maternal demise. However, adverse outcome has been associated with prophylactic heparin therapy in parturients with Eisenmenger's syndrome. Judicious use of antithrombotic drugs and early ambulation may increase survival in patients with Eisenmenger's syndrome. We did not use anticoagulation in the first case because of the high risk of hemorrhage with thrombocytopenia and coagulopathy. The cause of death was discussed by the multidisciplinary team, and pulmonary embolism was a suspected cause of death. Autopsy was suggested to get the definite cause of death, however, it was denied by the family of the patient. In summary, patients with Eisenmenger's syndrome undergoing caesarean section present many anaesthetic challenges, but an understanding of the underlying physiology and the use of a multidisciplinary team can guide anaesthetic management.


There is an epidemic of obesity and Type-2 Diabetes Mellitus (T2DM) in the developed world. Subclinical diastolic dysfunction in diabetes is associated with the development of overt heart failure. Although diabetic cardiomyopathy is well documented in older adults with T2DM there are scarce data on younger adults and no published CMR data. We aimed to assess the prevalence and potential mechanisms of subclinical left ventricular (LV) dysfunction in young T2DM adults compared to healthy lean (LC) and obese controls (OC).40 subjects  underwent CMR assessment on a Siemens Avanto 1.5T system. LV function and volumes were assessed using SSFP. Circumferential strain was assessed using a high temporal-resolution CSPAMM tagging sequence at 3 slices . Rest and stress perfusion was assessed quantitatively for perfusion defects and by calculating myocardial perfusion reserve (MPR) using model independent deconvolution at 3 slices. In a subset of the cohort  T1 mapping with heart-rate correction in a single short-axis slice was performed using a Modified Look-Locker Inversion Recovery (MOLLI) sequence before and 16 minutes post administration of 0.2mmol/kg of Gadovist. Aortic distensibility was assessed on high temporal-resolution gradient echo images.Subjects were well matched for age, height, blood pressure and time of T1 assessment post contrast. Global peak early diastolic strain rate (PEDSR) was significantly lower in T2DM, compared with LC and OC .


Left ventricular geometry is associated with cardiovascular events and prognosis. The Tei index of myocardial performance is a combined index of systolic and diastolic dysfunction and has been shown to be a predictor of cardiovascular outcome in heart diseases. The relationship between the Tei index and left ventricular geometry has not been well studied. This study examined the association between the Tei index and left ventricular geometry among hypertensive Nigerian subjects.We performed echocardiography on 164 hypertensives and 64 control subjects. They were grouped into four geometric patterns based on left ventricular mass and relative wall thickness. The Tei index was obtained from the summation of the isovolumic relaxation time and the isovolumic contraction time, divided by the ejection time. Statistical analysis was done using SPSS 16.0.Among the hypertensive subjects, 68 (41.4%) had concentric hypertrophy, 43 (26.2%) had concentric remodelling, 24 (14.6%) had eccentric hypertrophy, and 29 (17.7%) had normal geometry. The Tei index was significantly higher among the hypertensives with concentric hypertrophy (CH), concentric remodelling (CR) and eccentric hypertrophy (EH) compared to the hypertensives with normal geometry . The Tei index was higher among hypertensives with CH and EH than those with CR. Stepwise regression analysis showed that the Tei index was related to ejection fraction, fractional shortening and mitral E/A ratio.Among Nigerian hypertensives, LV systolic and diastolic functions (using the Tei index) were impaired in all subgroups of hypertensive patients according to their left ventricle geometry compared to the control group. This impairment was more advanced in patients with concentric and eccentric hypertrophy. Hypertension remains the commonest cardiovascular risk factor in Nigeria.Hypertension can lead to both systolic and diastolic abnormalities. There are several conventional indices for evaluating systolic function, such as ejection fraction, cardiac output, cardiac index and fractional shortening, while diastolic index can be assessed among others by transmitral Doppler wave pattern, isovolumic relaxation time, tissue Doppler and deceleration time. These indices are specific for systolic or diastolic function and each is associated with significant limitations with regard to their interpretation/relevance to clinical status and haemodynamic state.The myocardial performance index, otherwise called the Tei index, is a combined index of systolic and diastolic dysfunction and has been shown to correlate significantly with other conventional indices.Patients and controls were consecutively recruited from the echocardiographic laboratory of our hospital. This study was cross-sectional and comprised 164 hypertensive subjects seen at the cardiology clinic of our hospital. They had had complete echocardiography done on them, including two-dimensional, Doppler and M-mode echocardiography. Adult hypertensive subjects who were at least 18 years old and who were willing to participate in the study were included.Blood pressure was measured in the clinic with an Accosson’s sphygmomanometer and hypertension was diagnosed when blood pressure was persistently ≥ 140 and/or ≥ 90 mmHg and/or the use of antihypertensive therapy according to standardised procedures and guidelines.Sixty-four normotensives were used as controls. They were randomly recruited from patients’ relatives and hospital staff who were willing to participate. They were well matched in age and gender distribution with the hypertensive subjects. Patients with diabetes mellitus or a history of heart or renal failure were excluded from the study. Determinations of the Tei indices were done differently without access to the clinical data of the subjects.All the subjects had transthoracic echocardiography done according to the recommendation of the American Society of Echocardiography.LVM (g) = 0.81 [1.04 3 – 3] + 0.6.152.7. Correcting LVM for height 2.7 has been shown to minimise the effect of gender, race, age and obesity on the validity of various parameters for the diagnosis of left ventricular hypertrophy (LVH), for which many parameters exist.2.7.LVM index (LVMI) was calculated as LVM/height (m)LV geometry was determined after calculation of the relative wall thickness (RWT) using the formula:2 × posterior wall thickness LV end-diastolic internal dimension. 17RWT was considered abnormal if it was ≥ 0.45.17Four left ventricular geometric patterns were described based on RWT and left ventricular mass index (LVMI): normal geometry, concentric remodelling, eccentric hypertrophy and concentric hypertrophy. LV geometry was defined as concentric hypertrophy (elevated LVMI and RWT), concentric remodelling , eccentric hypertrophy  and normal geometry .The Tei index reflects both systolic and diastolic function. It was defined as the sum of the isovolumic relaxation time and isovolumic contraction time divided by the ejection time obtained from the left ventricular inflow and outflow.t-test and chi-squares were used as appropriate for intergroup comparisons. Correlation analysis was used for univariate associations between numerical variables. Values with p < 0.05 were taken as statistically significant. Ethical approval was obtained for the study.The Statistical Package for Social Sciences, SPSS 16.0 (Chicago Ill.) was used for the study. Quantitative data were summarised using means ± standard deviation (SD) while qualitative data were summarised using percentages and proportions. The Student’s The clinical characteristics of the study population are shown in r = –0.142) and mitral E/A ratio (r = –0.280) Univariate correlation coefficients of the echocardiographic parameters with Tei index  are shown in This study revealed some important findings. Firstly, the Tei index was significantly different between hypertensive subjects with normal and those with abnormal left ventricular geometry. Secondly, concentric hypertrophy was the commonest abnormal pattern of left ventricular geometric pattern in this study, followed by concentric remodelling and then eccentric hypertrophy. Only 17.7% of the hypertensive subjects had normal left ventricular geometry. Thirdly, the Tei index was highest among hypertensive subjects with concentric hypertrophy, closely followed by those with eccentric hypertrophy, with no significant difference between the two groups. Fourthly, multiple regression analysis suggests that there was no significant association between left ventricular geometric pattern and Tei index.The pattern of Tei index in this study therefore indicated the pattern/severity of combined systolic and diastolic function associated with each type of left ventricular geometry among these hypertensive subjects and was not a function of the left ventricular geometry itself. Earlier studies have found concentric and eccentric hypertrophy to be associated with a higher degree of cardiovascular events, and systolic and diastolic dysfunction.Ejection fraction, fractional shortening and mitral E/A ratio were the main echocardiographic parameters associated with Tei index among hypertensive Nigerian subjects. This study therefore demonstrates the potential clinical usefulness of the Tei index in stratifying left ventricular systolic and diastolic dysfunction across all age strata and patient groups, notwithstanding the body mass index and left ventricular mass.Use of the Tei index for assessing cardiac performance has a potential clinical advantage over the use of other classical echocardiographic indices for estimating left ventricular diastolic and systolic function. Ejection fraction and left ventricular volumes, which are measures of systolic function, are prone to large errors when the ellipsoid shape of the heart is altered. Age, rhythm, preload and afterload changes affect the transmitral Doppler signal, which is a measure of diastolic function. Therefore the use of these conventional indices when left ventricular geometry is altered may be further error-prone.Left ventricular geometric pattern has been shown to be related to diastolic and systolic function.21Several geometric variations are cardiac adaptations to pressure and volume changes in hypertension, with the aim of maintaining normal function. The early phases of altered geometry are associated with compensated left ventricular function to a near-normal level. This study revealed that the Tei index was significantly higher among hypertensive subjects with concentric hypertrophy compared to those with concentric remodelling. Concentric hypertrophy has been associated with an increase in cardiovascular events associated with systolic and diastolic dysfunction in various studies.23et al. reported in 2004 that the systolic and diastolic LV functions  were impaired in all subgroups of hypertensive patients according to their left ventricle geometry compared to the control group. This impairment was more advanced in patients with concentric hypertrophy than in those with other LV geometric patterns.Other studies have reported the relationship between left ventricular geometry and systolic function in other populations. In terms of the limitations of this study, it does not provide any information on the prognostic potential of the Tei index among hypertensive subjects. Therefore, a prospective study to determine the prognostic potential of the Tei index among black hypertensive subjects would be relevant. Also, the impact of antihypertensive therapy on the Tei index was not studied. It has been shown that the Tei index is able to detect improvement in systolic function in heart failure patients using carvedilol, and improvement in systolic function in subjects with acute myocardial infarction.27


Serological markers of cardiac injury are elevated following intense exertion. Whether myocardial tissue is actually injured remains unresolved, although we have found evidence for systolic and diastolic dysfunction following exertion. Furthermore, we have also observed that a significant proportion of well-trained elite endurance athletes present with evidence of myocardial fibrosis at rest.Myocardial edema reflects an acute reversible injury that may be associated with reduced ventricular compliance. Accordingly, the purpose of the current investigation was to determine whether myocardial edema develops acutely in active men challenged with an incremental test to exhaustion and a high-intensity interval exercise training session, as visualized by T2-weighted imaging.16 physically active men (age 33±11 years) were recruited for a 2-day study. LV function and T2-weighted imaging were performed on a 1.5T MRI system, prior to and within an hour of exertion. During study day 1, participants completed an incremental test to exhaustion on a braked cycle ergometer, where load was increased by 15-25 Watts every 2 minutes until physical exhaustion. The point of exhaustion was considered to be the maximal power output. During study day 2, a high-intensity interval training session was performed where athletes completed 15 repetitions of cycling at maximal power output for 1 minute followed by 2 minutes of light recovery.The extent of myocardial edema was assessed quantitatively using semi-automated detection, where myocardial regions that had signal intensity (SI) above a threshold of twice the mean SI of skeletal muscle were considered to be edematous. Global edema was measured by normalizing myocardial SI to skeletal muscle SI, generating a T2-ratio.The ratio of global myocardial edema increased following both incremental exertion to exhaustion  and intense interval training .The spatial extent of myocardial edema also increased following both incremental exhaustion challenge  and high-intensity interval training  (Figure We provide first evidence for the development of myocardial edema following an acute incremental challenge to exhaustion and high-intensity interval exertion in healthy men. The extent of edema may be related to diastolic dysfunction. These findings have implications for the safety of sport for athletic and non-athletic populations.


Due to possible induction of hypotonic blood circulation, intravenous vasodilators  should be administered with the greatest care. A method of treating elevations in pulmonary pressure with selective pulmonary vasodilation by inhalation should be available intraoperatively  in addition to invasive hemodynamic monitoring. During the postoperative phase, patients must be monitored continuously and receive sufficient analgesic therapy over an adequate period of time. All in all, perioperative management of patients with pulmonary hypertension presents an interdisciplinary challenge that requires the adequate involvement of anesthetists, surgeons, pulmonologists, and cardiologists alike.Pulmonary hypertension is a major reason for elevated perioperative morbidity and mortality, even in noncardiac surgical procedures. Patients should be thoroughly prepared for the intervention and allowed plenty of time for consideration. All specialty units involved in treatment should play a role in these preparations. After selecting each of the suitable individual anesthetic and surgical procedures, intraoperative management should focus on avoiding all circumstances that could contribute to exacerbating pulmonary hypertension (hypoxemia, hypercapnia, acidosis, hypothermia, hypervolemia, and insufficient  Pulmonary hypertension represents an important risk factor for increased perioperative morbidity and mortality. Stress, pain, ventilation, and surgery-related inflammation can further increase pressure and resistance within the pulmonary arteries and cause right-sided heart failure. Ramakrishna et al. have described a number of independent factors leading to an increased perioperative risk for patients with pulmonary hypertension. Conditions that caused one or more perioperative complications in 42% of all patients were heart failure of NYHA class II or higher, a history of pulmonary embolism, high-risk surgery , and an anesthesia duration of more than 3 hours . The litIn a recently published study, Kaw et al. examined the clinical progression of 96 patients with pulmonary hypertension who underwent a noncardiac surgical procedure. The PH patients had a significantly increased risk for hemodynamic instability, heart failure, postoperative sepsis, and respiratory failure. In addition, they required significantly prolonged postoperative ventilation and a longer intensive care stay and had to be readmitted for inpatient treatment much more frequently within the first 30 days following surgery ..28].Characteristic findings for pulmonary hypertension include right-ventricular hypertrophy, dilation of the central pulmonary arteries, and vascular rarefaction in the peripheral pulmonary parenchyma .In the ECG, characteristic changes are also more pronounced if major right-ventricular load already prevails . TypicalIt is recommended, in particular for patients with chronic lung disease as a cause of pulmonary hypertension, that an examination of pulmonary function and an arterial blood gas analysis be conducted prior to the surgical intervention .2), the ventilatory equivalent ratio for CO2 (VE/VCO2), and the partial pressure of end-tidal carbon dioxide (PETCO2).Important information for estimating the severity and progression of the disease can be obtained using spiroergometry . The mosEchocardiography is currently the noninvasive method with the highest sensitivity and specificity for diagnosing PH . FurtherRight-heart catheterization is a direct means of measuring the hemodynamic parameters in pulmonary circulation and obtaining important information about the severity of pulmonary hypertension and right-ventricular functionality . For patnitric oxide (NO) or iloprost is assured, as both substances can be administered for the selective therapy of an acute increase in pulmonary artery pressure  [For intra- and postoperative treatment options, it is important to know if responsiveness to inhaled vasodilators such as agement) .Before surgical intervention, medication should be critically examined from a pulmonological and cardiological perspective and under consideration of recent hemodynamic findings, with a view to possible optimization. This applies, in particular, to the specific therapy of pulmonary hypertension. At the time of surgery, the patient should ideally have been in a stable condition for an extended period of time , 30.and/or right-heart catheter.If the pulmonary hypertension was discovered immediately prior to urgent surgery that could not be postponed, Fox et al. recommended starting treatment with sildenafil (50–100 mg/day) and L-arginine (15 g/day) as early as possible . We do nGiven that patients with pulmonary hypertension suffer significantly increased perioperative morbidity and mortality, a perioperative assessment of risks and possible benefits of surgical intervention plays a critical role. For this reason, patients should, whenever possible, be thoroughly informed about possible risks long before surgery in order to give them sufficient time for consideration. Close family members should also be involved if possible.Risk disclosure involves explaining necessary preoperative tests, presenting intra- and postoperative monitoring methods , a thorough description of surgical and anesthetic procedures and their respective risks, recovery (intensive and/or intermediate care unit stay), as well as possibilities of postoperative analgesic therapy. Depending on the initial condition of each patient, they may also need to be explicitly informed about the possibility of severe complications that can lead to extended hospitalization or even death.For patients with pulmonary hypertension, intraoperative monitoring should be adapted to the severity of the disease and the invasiveness of the surgical procedure, although, to date, there is no evidence to suggest that any specific type of monitoring has an influence on patient morbidity and mortality. However, the authors believe that early recording of deviations from the initial condition (in particular in relation to right-heart function) can make a decisive contribution to recognizing and avoiding severe complications from the outset.2 and end-expiratory CO2). Intermittent blood gas analysis should also be carried out using an arterial catheter. Fox et al. recommend measuring the central venous pressure (CVP) for intraoperative volume control [Whereas basic monitoring can be considered sufficient for minor and medium procedures in functional state II, all major interventions and those in functional state III should be carried out under an extended monitoring . Invasiv control . However control .For all patients in the late stages of the disease and with existing right-sided heart failure, pulmonary artery catheterization and transesophageal echocardiography (TEE) are the methods for an adequate intraoperative monitoring of right-heart function and visualization of the required therapy effects if necessary . TEE offThe intraoperative use of pulmonary artery catheters is subject to controversial discussions in the current literature. Whereas Rinne and Zwissler rarely found it necessary , Fox et 2) is a surrogate of the mixed venous saturation (SvO2), it reliably can be used as a marker of global tissue perfusion and may represent an alternative way of intraoperative monitoring. Studies from cardiac surgery have shown that there is a predictive power of intermittently measured ScvO2 for adverse events [2 values intraoperatively and therefore limit the validity for intraoperative decision making. A decrease in ScvO2 may be caused by (a) a decrease in SaO2, (b) a decrease in cardiac output, (c) a decrease in hemoglobin level, and (d) an increase of oxygen consumption [As the central venous saturation , as they have no influence on pulmonary vascular resistance and oxygenation [For these reasons, a “gentle” introduction phase that avoids arterial hypotension is vital, in particular for patients with pulmonary hypertension. All standard induction agents  can, in principle, be used in combination with opioids  for isoflurane, desflurane, and enflurane, but not for sevoflurane , 54. SomThe particularities of the introduction and maintenance of anesthesia have already been described previously. The most important requirement for intraoperative management and maintenance of anesthesia is to avoid anything that could increase right-ventricular afterload or decrease contractility of the right ventricle, as both factors will ultimately lead to ischemia and right-sided heart failure . Perfusi2 0.6–1.0) to minimize the risk of hypoxic phases. This treatment can be supported by carefully performed recruitment maneuvers to largely eliminate inadequate ventilation-perfusion ratios [2 of 30–35 mmHg) should be carried out under continuous blood gas analysis, but without allowing the pH value to fall below 7.4 [As one of the strongest inducers of pulmonary vasoconstriction is hypoxia, inspiratory oxygen administration should be set to a sufficiently high degree  inhibitor milrinone has successfully been used in patients with pulmonary hypertension and cardiac surgery, and growing experience has been gathered to date in its administration [The phosphodiesterasestration , 62, 64.stration . Bolus astration . The intIn 2010, sildenafil was approved for intravenous therapy of pulmonary arterial hypertension (PAH) and may be, for example, an attractive option for the perioperative management of patients who are treated with oral sildenafil.therefore may lead to a decrease of the pulmonary shunt and improved oxygenation [Selective pulmonary vasodilator therapy by inhalation offers several advantages over intravenous vasodilation. As alveoli and pulmonary capillaries are located in close proximity, the effect on the pulmonary vascular bed is limited, which avoids systemic vasodilation. Vasodilation therapy by inhalation can therefore also be administered to patients who already show limited right-ventricular function and for whom a further decrease of myocardial perfusion must be avoided. In addition, substances that are administered by inhalation only have an effect on ventilated lung areas, and the consecutive vasodilation in the ventilated areas genation .milliseconds [Several substances are currently available for vasodilator therapy by inhalation in patients with pulmonary hypertension . Nitric iseconds . Howeveriseconds . In a reiseconds . In mostiseconds .Similar points can be made in relation to the equally short-acting prostacyclin which triggers vasodilation by elevating cAMP in the vascular muscle cells. Its half-life is only 2-3 minutes, and so the inhalation of prostacyclin also demands controlled ventilation . The effDue to its longer half-life of 20–30 minutes, the stable prostacyclin analog iloprost can be administered intermittently to ventilated and spontaneously breathing patients and therefore offers significant advantages over short-acting inhaled vasodilators Figures  and 6 6. It is aAnother option for vasodilator therapy by inhalation, which, to date, has not been thoroughly described, is the inhalation of milrinone. In 2001, the working group headed by Haraldsson first described the inhaled administration of milrinone in combination with prostacyclin for cardiac surgical patients . Dosage A new option as inhalative therapy of pulmonary hypertension is inhaled treprostinil, a chemically stable tricyclic benzindene prostanoid which was initially studied as a continuous subcutaneous infusion , 90. DueIt has been shown by the study of Loh and colleagues that inhalation of nitric oxide in patients with reactive pulmonary hypertension secondary to left-ventricular failure, inhalation of NO, causes reciprocal changes in the PVR (decrease) and left-ventricular filling pressure (increase) . This rePatients with pulmonary hypertension are at risk of developing elevated pulmonary pressure and right-sided heart failure not only during the perioperative phase itself, but also in the postoperative course. These patients should therefore be placed under intense postoperative monitoring for a period appropriate to the degree of surgical trauma; the target monitoring time should be between 24 hours for small interventions and several days for major procedures . Depending on the patient's initial condition , hemodynamic monitoring may need to be continued postoperatively until pulmonary pressures, and right-sided heart functions have stabilized at the preoperative level .In this phase, sufficient analgesic therapy can make a decisive contribution to the avoidance of elevated pulmonary pressures. In the ideal case, analgesic therapy in the form of continuous regional anesthesia can be designed in a way that avoids higher doses of opioid-based analgesics. The basic treatment of patients with pulmonary hypertension therefore includes daily visits by pain management nurses. The specific therapy for pulmonary hypertension should be resumed at the preoperative dosage as soon as possible. In the postoperative course, it is also advisable to treat pressure elevations with iloprost inhalation, which can also be administered intermittently due to its long half-life.Pulmonary hypertension is a major reason for elevated perioperative morbidity and mortality, even in noncardiac surgical procedures. Patients should be thoroughly prepared for the intervention and allowed plenty of time for consideration. All specialty units involved in treatment should play a role in these preparations. After selecting each of the suitable individual anesthetic and surgical procedures, intraoperative management should focus on avoiding all circumstances that could contribute to exacerbating pulmonary hypertension . A method of treating elevations in pulmonary pressure with selective pulmonary vasodilation by inhalation should be available intraoperatively, in addition to invasive hemodynamic monitoring. During the postoperative phase, patients must be monitored continuously and receive sufficient analgesic therapy over an adequate period of time. All in all, perioperative management of patients with pulmonary hypertension presents an interdisciplinary challenge that requires the adequate involvement of anesthetists, surgeons, pulmonologists, and cardiologists alike.


Accurate non-invasive risk stratification may management and impact survival of CAD patients. Stress perfusion CMR reliably assesses ventricular function, viability and myocardial ischemia in a single examination. While prognostic information may be derived from individual components of a comprehensive CMR exam, evidence that they provide complementary prognostic information is still limited. We sought to determine whether the presence of myocardial ischemia by stress perfusion CMR provides incremental prognostic information for major adverse cardiovascular events (MACE) beyond ventricular function, the presence of myocardial scar and traditional risk factors in a large cohort of patients referred for non-invasive assessment of CAD.χ2, 51.62 and 17.02, both P<0.0001, tableχ2 26.1, HR 7.4, P<0.0001). By stepwise forward selection  referred to assess myocardial ischemia with an intermediate pre-test likelihood of CAD (mean pre-test likelihood of CAD 22±18%). Rest and vasodilator stress perfusion CMR were performed each using a 0.1mmol/Kg bolus infusion of gadolinium, followed by cine function imaging and late gadolinium enhancement (LGE) 10 minutes after a cumulative dose of 0.2mmol/Kg of gadolinium. The presence of myocardial ischemia was defined by a segmental stress-induced perfusion defect without matching segmental LGE. At a median follow-up of 21.4 months (range 2.5 months to 8.2 years), 52 MACE (8%) had occurred . By univariable analysis, the presence of ischemia and LGE portended to > 11-fold and > 3-fold increases in MACE (LRThe presence of ischemia by stress perfusion CMR provides robust prognostic information for MACE beyond the presence of scar, LVEF, and classical clinical and ECG markers of cardiac prognosis.. The combined absence of ischemia by myocardial perfusion imaging and scar by LGE imaging identifies a very low risk population.