Most available sequences are generally acquired within a breath-hold using a balanced SSFP (bSSFP) imaging readout. However, the signal obtained from a bSSFP imaging readout is T2 dependent, sensitive to magnetization transfer and has increased susceptibility to the B0 field inhomogeneity leading to regional variations in T1 estimates (1). Recently, we developed a novel T1 mapping sequence for free-breathing, multi-slice, myocardial T1 mapping using a slice-interleaved T1 sequence with spoiled gradient echo (GRE) imaging readout. However, the feasibility of this sequence in patient has not yet been studied. In this study, we sought to demonstrate the feasibility of this sequence in patients and its ability to detect abnormal T1 times.Quantitative myocardial T1 mapping was performed using a free-breathing slice interleaved acquisition which enables simultaneous acquisition of 5 slices using multiple inversion recovery (IR) experiments (2). All the 5 slices are acquired once in each IR experiment, which enables the sampling of the undisturbed T1 recovery curve. Each T1-weighted image was acquired using an ECG-triggered acquisition with a GRE imaging readout . Prospective slice tracking was combined with retrospective image registration to correct for respiratory motion. Myocardial native T1 values were evaluated using a 16 myocardial segment model for all healthy subjects and patients.Sixteen patients referred to clinical CMR for assessment of cardiomyopathy  and eleven control healthy adult subjects  were recruited for this study. Subjects were scanned on a 1.5 T Philips scanner. Native T1 times in the healthy subject control group were 1094±24ms. Figure 1 maps obtained in three patients where native T1 times  were in the same range as in the healthy subject control group. Homogeneous and consistent T1 times were obtained over the whole myocardium in these patients and the visual quality of T1 map was excellent. Figure 1 maps obtained in two patients where elevated T1 times can be observed (1197ms and 1158ms). Elevated T1 times were consistent across multiple myocardial segments.Native T1 mapping using magnetization-prepared slice interleaved spoiled gradient echo imaging is feasible in patients and provides excellent T1 map quality which enables the detection of altered native T1 times in the presence of specific cardiomyopathies.Free-breathing myocardial T


To date, no data are available regarding native left ventricular (LV) T1 relaxation time in AF patients referred for pulmonary vein isolation (PVI). The purpose of this study was to compare native myocardial T1 value between AF patients undergoing PVI and control subjects.Native T1 mapping images were acquired using a Modified Look-Locker imaging sequence (MOLLI) in 3 short-axis planes  using an ECG-triggered single-shot acquisition with a balanced SSFP readout . Late gadolinium enhanced (LGE) MRI was acquired to evaluate for myocardial scar.Thirty one AF patients referred for PVI  and 17 control subjects  were retrospectively identified. All patients were in sinus rhythm during the CMR scan. No AF patient had a history of myocardial infarction but 7 of 31 (23%) AF patients had history of hypertension. Non-contrast T1 was significantly elevated in AF patients . Multivariate linear regression analysis selected presence of AF as an independent and significant predictor of elevated native T1 after adjustment for age and gender .LV ejection fraction was similar between groups . No LGE myocardial scar was observed in any AF patient or control subject. Myocardial native T1 between AF patients referred for PVI. These data suggests that T1 mapping may be useful for early detection of subclinical LV myocardial abnormalities in the AF population.Our study suggests that there are subclinical differences  in native myocardial TShingo Kato, MD receives scholarship from Banyu Life Science Foundation International.


Microvascular obstruction (MVO) at the acute phase of myocardial infarction (MI) is associated with poor prognosis. We aimed to evaluate the correlation between plasma cardiac troponin I (cTnI) at the acute phase of MI and extent of no-reflow, as assessed by 3-T cardiac magnetic resonance imaging (MRI). Secondly, we defined a cut-off value for cTnI predictive of no-reflow.51 consecutive patients with no previous history of cardiovascular disease, presenting ST elevation MI within <12 h. Infarct size and extent of no-reflow were evaluated by 3-T MRI at day 5. Extent of no-reflow at 15 minutes (MVO) was correlated with cTnI at admission, 6, 12, 24, 48 and 72 hours. At 6 months, MRI was performed to evaluate the impact of MVO on LV remodeling.MVO was diagnosed in 29 patients (57%). Extent of MVO was significantly correlated to peak troponin, cTnI  and area under the curve. Using Receiver-operating characteristic (ROC) curve analysis, a cut-off cTnI value >89 ng/mL at 12 h seemed to best predict presence of early MVO . At 6 months, MVO was associated with left ventricular (LV) remodeling, resulting in higher LV volumes.There is a relationship between cTnI at the acute phase of AMI and extent of MVO as assessed by 3-T cardiac MRI. A cut-off cTnI value of 89 ng/mL at 12 h seems to best predict presence of MVO, which contributes to LV remodeling. In acute ST-segment-elevation myocardial infarction (STEMI), primary percutaneous coronary intervention is the treatment of choice to restore myocardial revascularization and minimize ischemic damage to the myocardium . SeveralThe aim of our study was to evaluate the relationship between plasma levels of cardiac troponin I (cTnI) and microvascular obstruction (MVO) as assessed by magnetic resonance imaging (MRI) at day 5, and to define a cut-off value for cTnI that predicts MVO.th percentile of the upper reference limit (URL)), together with evidence of myocardial ischemia .This study was a prospective single-center study. Patients < 75 years old referred to our department for a first ST elevation MI (STEMI) and admitted within 12 hours of symptom onset were considered for inclusion. MI was defined by the guidelines of the joint Task Force of the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the World Heart Federation (WHF) . MI was Exclusion criteria were: previous cardiovascular or pulmonary diseases, cardiogenic shock and contraindication for MRI.The study protocol was approved by the local ethics committee  and informed consent was obtained from all enrolled patients.All patients were referred to the catheterization laboratory within the first 24 hours after admission for coronary angiogram, and received medication according to current guidelines .The initial and post-procedural blood flow in the infarct-related artery was graded according to the Thrombolysis in Myocardial Infarction (TIMI) grading system . A succeAll CE-MRI studies were conducted at 3.0 field strength  and performed in the acute phase and repeated at 6 months. Left ventricular function was assessed by ECG-gated cine steady-state free precession (SSFP) breath-hold sequences in the two-chamber and four-chamber views as well as in the short cardiac axis from base to apex .Contrast-enhancement imaging was performed at 3 and 15 min with a breath-hold ECG-gated T1-weighted sequence after the injection of a bolus of gadolinium  at a single dose of 0.1 mmol/kg . The number and position of slices were the same as used for functional imaging.Image analysis was performed in a blind fashion by two operators using an off-line dedicated workstation . Left ventricular (LV) ejection fraction (LVEF), end-diastolic (LVEDVI) and end–systolic volume index (LVESVI) and mass were calculated from SSFP short-axis views. MVO was assessed on the initial CE-MRI performed during in-hospital stay. Infarct size was assessed from the same initial CE-MRI and at 6 months follow-up. Infarct size and MVO (if present) were manually traced from the contrast-enhancement short-axis images . MyocardSerum levels of troponin I (TnI), creatine kinase (CK) and creatine kinase isoenzyme myocardial and brain (CK-MB) were determined on admission, and 6, 12, 24, and 48 hours after onset of MI. cTnI was measured quantitatively using sandwich immunoassay . The lower limit of detection for this assay was 0.04 ng/ml. A value of cTnl > 0.15 ng/ml was considered indicative of myocardial necrosis for the purposes of clinical care. The peak level was determined as the highest value.Quantitative continuous variables are expressed as mean ± standard deviation, and qualitative variables as number and percent. The Student t test and Chi square or Fisher’s exact tests were used for comparisons, as appropriate. We calculated the relative change at 6 months from baseline in LV end-diastolic volume index, LV end-systolic volume index, and LV ejection fraction. The model used to take initial infarct size into account was the calculation of relative change, normalized for baseline infarct size. The correlations between serum enzyme levels and MVO at day 5 were assessed using the Spearman rank test. A receiver-operating characteristic (ROC) curve was used to define the threshold value of troponin levels predictive of MVO at day 5. A p-value <0.05 was considered statistically significant. All analyses were performed using SAS version 9.2 .Between 2006 and 2008, 51 patients were enrolled in the study. Mean age was 54 years; there were 9 women and 42 men. Baseline and angiographic characteristics of the study population are shown in Table pos patients) diagnosed by MRI and 22 (43%) had no MVO (MVOneg patients). MVOpos and MVOneg patients were comparable as regards baseline characteristics.The percentage of patients with TIMI flow grade ≤2 before PCI was significantly higher in the MVO pos group. After PCI, the rate of TIMI flow grade 3 was comparable in both groups  had MVO .MRI was performed at 5.7 ± 2.7 days after symptom onset and at 6 ± 1 months follow-up. MRI was not performed in 6 patients at 6 months due to patient refusal, or intervention (PCI or CABG) during the follow-up period.pos patients versus 12.7 ± 9.4% in MVOneg patients (p = 0.0001). There was a significant correlation between the extent of MVO at day 5 and the infarct size at day 5 . Similarly, we observed a significant correlation between extent of MVO and time to reperfusion .At day 5, the extent of MVO was 7.3 ± 3.7%. Infarct size was 23.5 ± 8.4% in MVOpos patients between MVO at day 5 and infarct size at 6 months  and in LV end-systolic volume index (LVESVI) was significantly greater than in MVOneg patients   Figure . There wpos patients (respectively p = 0.0006 and p = 0.006) (Table Peak troponin and peak CK were significantly higher in MVO6) Table .There was no significant difference in terms of peak troponin values between patients with TIMI flow grade 3 and those with TIMI flow ≤2 after revascularisation .The extent of MVO at day 5 was significantly correlated with peak troponin Figure  and tropPeak troponin and all cTnI levels except cTnI at admission were significant predictors of MVO Table . The AreWe aimed to find an accessible prognostic marker that could identify patients with microvascular dysfunction after reperfusion at the acute phase of myocardial infarction. Our data demonstrated that troponin levels (except troponin at admission), and particularly peak troponin, were correlated with the extent of MVO on MRI at day 5. A troponin I level > 89 ng/ml at 12 hours was found to be the best cut-off value to predict MVO, with a sensitivity of 63% and a specificity of 88%.The phenomenon of no-reflow ,26 or miThis is strong evidence that both serial and single-point measurements of troponin correlate well with infarct size ,9,20. InOne of the advantages of the present study is the large number of repeat troponin measures, at relatively short time intervals, which allowed more accurate determination of a threshold value that could predict MVO at the acute phase of infarction.It has previously been shown that a longer duration of ischemia is associated with more pronounced impairment of myocardial perfusion and consequently, infarct size . In our Newton et al. previously studied MVO on MRI in the context of non-ST elevation MI, and observed that MVO was correlated with infarct size and troponin levels. Thus, it would appear that the results observed in the context of STEMI are also applicable in NSTEMI .This is a single-center study, with a relatively small population of highly selected patients. Nonetheless, the selection of the population made it possible to independently analyse MVO as evaluated by MRI in the absence of other cardiovascular comorbidities. Secondly, we did not evaluate blush grade, which corresponds to the angiographic evaluation of microcirculation after revascularisation. Our study focused on MVO at 5 days, which is a different phenomenon, and shown to be an independent prognostic factor in acute MI. These results merit further confirmation in a larger, prospective study. Thirdly, reperfusion strategy (primary PCI or thrombolysis) may possibly influence the occurrence of MVO. In particular, it has been shown that rescue PCI is associated with an increased thrombotic risk in this setting. However, in our study, only 6 12%) patients underwent rescue PCI. This likely did not impact on the relation observed between MVO and peak troponin, as there was no significant difference between groups (Table 2% patienOur results suggest a correlation between plasma levels of cardiac troponin I at the acute phase of AMI, and the extent of MVO as assessed by 3-T cardiac magnetic resonance imaging. The extent of MVO at 5 days post-STEMI is correlated with infarct size, and negatively impacts on LV remodeling at 6 months. A cut-off value of 89 ng/mL for cTnI at 12 hours seems to best predict the presence of early MVO with high sensitivity and specificity. Troponin measurement is an easily accessible prognostic marker that could help identify patients with MVO and unfavorable prognosis.The authors declare that they have no competing interests.Study conception and design: KP, MFS, NM. Acquisition of data: KP, RC, MFS, PP, FS, NM. Analysis and interpretation of data: FE, RC, PP, FS, NM. Drafting of the manuscript and critical revision: All. All authors read and approved the final version of the manuscript to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/57/prepub


Cardiac involvement is a major risk factor for sudden death in patients with systemic sarcoidosis. Pathologically, cardiac sarcoid lesions can be classified as early , intermediate (active granulomatous), and late phase (primarily scar). These pathological processes can affect the myocardial extracellular space volume (ECV) in cardiac sarcoid. We hypothesize that quantitative measurement of ECV using a T1 mapping technique with CMR may yield new insights for the assessment of cardiac sarcoid.Nine patients with confirmed sarcoidosis were examined on a 1.5T MR system. First, a short-axis SSFP stack of slices covering the ventricles were acquired, and then a pre-contrast modified Look-Locker sequence was performed with 8 time points in a mid-LV level from which a T1 map and average LV myocardium T1 was derived. Post-contrast LGE-CMRs using IR-FGRE and multi-contrast late-enhancement were performed 10-15 minutes after a double-dose intravenous bolus injection of Gd-DTPA. A repeated T1 mapping sequence with the same localization as pre-contrast T1 measurement was acquired around 20 minutes post-contrast. The average myocardial T1 measurements did not exclude regions corresponding to LGE positive foci. LV function, LGE determination and quantitative T1 calculation used commercial software CMR42. Myocardial ECV was calculated according to the formula of ECV = (1-haematocrit) × (ΔR1myocardium/ΔR1blood).The LV functional parameters in nine subjects were in the normal range . Three of nine subjects (33.3%) had cardiac involvement with LGE positive foci. Figure This pilot study demonstrated increased myocardial ECV in patients with cardiac sarcoid, which may represent the combination of diffuse interstitial fibrosis and replacement scar. Further study is warranted for the clinical utility of T1 mapping and determination of ECV in the management of patients with cardiac sarcoid.NA.


South African Medical Journal just three weeks after the event and is one of the most cited articles in the cardiovascular field. In the lay media as well, this first transplant remains the most publicised event in world medical history.Christiaan (Chris) Barnard was born in 1922 and qualified in medicine at the University of Cape Town in 1946. Following surgical training in South Africa and the USA, Barnard established a successful open-heart surgery programme at Groote Schuur Hospital and the University of Cape Town in 1958. In 1967, he led the team that performed the world’s first human-to-human heart transplant. The article describing this remarkable achievement was published in the Although the first heart transplant patient survived only 18 days, four of Groote Schuur Hospital’s first 10 patients survived for more than one year, two living for 13 and 23 years, respectively. This relative success amid many failures worldwide did much to generate guarded optimism that heart transplantation would eventually become a viable therapeutic option.This first heart transplant and subsequent ongoing research in cardiac transplantation at the University of Cape Town and in a few other dedicated centres over the subsequent 15 years laid the foundation for heart transplantation to become a well-established form of therapy for end-stage cardiac disease. During this period from 1968 to 1983, Chris Barnard and his team continued to make major contributions to organ transplantation, notably the development of the heterotopic (‘piggy-back’) heart transplants; advancing the concept of brain death, organ donation and other related ethical issues; better preservation and protection of the donor heart (including hypothermic perfusion storage of the heart; studies on the haemodynamic and metabolic effects of brain death; and even early attempts at xenotransplantation. Christiaan Barnard with his team, performed the world’s first human-to-human heart transplant operation on 3 December 1967. It was a major historical event and a significant breakthrough for medical science. The article describing this remarkable achievement, titled ‘A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town’ was published just three weeks after the event in a special edition of the South African Medical Journal.Media coverage around the world of this event and subsequent transplants was front page and appeared daily for weeks and months on end, describing all aspects in detail and giving progress reports on the postoperative course of the patients. This degree of public acclaim had not been previously experienced by any other physician or surgeon and nor would it be experienced subsequently. This was in part because the dramatic nature of the operation had captured the public’s imagination, but was equally a response to Chris Barnard’s youthful good looks and charismatic personality On the night of 2/3 December 1967, Barnard performed the world’s first human-to-human orthotopic heart transplant in his patient, Louis Washkansky. Today, when heart transplantation has become a relatively routine and commonplace procedure, one may be inclined to underestimate Barnard’s immense courage in undertaking this first operation. Washkansky, a 53-year-old man with severe coronary insufficiency, was far from an ideal recipient by today’s standards, being a diabetic and a smoker with peripheral vascular disease. Furthermore, his massive dependent oedema had required drainage by needles placed into the subcutaneous tissues of the lower legs, and these puncture sites and accompanying stasis ulcers had become infected.On 2 December, a young white woman, Denise Darvall, sustained a massive head injury after being hit by a car and was certified as having a lethal brain injury without any chance of recovery, by the neurosurgeon who had been called to treat the patient and who eventually referred her as an organ donor. There were no laws relating to brain death and organ transplantation in South Africa at that time, as elsewhere, and Barnard elected to take no chances. He invited the State’s forensic pathologist to the operating room, where ventilation of the donor  was discontinued. The blood pressure steadily fell and the heart arrested. The medical examiner pronounced that death had occurred. Barnard’s assistants then rapidly opened the chest, initiated pump-oxygenator support, cooled the heart to a low temperature and excised it.The recipient had been prepared in the adjacent operating room and Barnard proceeded with the transplant. The enormity of what he was attempting was impressed upon him when, for the first time in his life, he looked into the chest and saw an empty pericardial cavity. The procedure went well and the heart functioned satisfactorily. No photographs were taken during the operation and so there is no visual record of this historic surgical procedure.Within 48 hours the world’s press had descended on Cape Town and Barnard had become a household name. This intense public interest resulted in the appearance of Barnard and his transplant on the front covers of Time, Life, Newsweek and many other major foreign magazines within two to three weeks of the transplant. The world’s most publicised medical event had taken place.Washkansky’s daily progress was followed intensely around the world, with almost every aspect of his care being made public. His early recovery was excellent, and the team was impressed with how rapidly the patient’s peripheral oedema was lost as his new heart functioned strongly. This excellent progress continued for almost two weeks, when Washkansky’s condition began to deteriorate and he developed radiographic infiltrates in the lungs. The surgical team was uncertain whether these were due to pulmonary oedema associated with cardiac failure from rejection, or with infection. Mistakenly, they initially elected to treat for rejection, intensifying the immunosuppressive therapy. This step was a lethal error as the patient had developed bilateral pneumonia, which was aggravated by the enhanced immunosuppression, and he unfortunately succumbed from severe pneumonia and septicaemia on the 18th day post-operatively.Not daunted by this failure, Barnard immediately selected his second patient, a 59-year-old local dental surgeon named Philip Blaiberg. The operation was performed on 2 January 1968. On this occasion, the surgical technique was slightly modified from the approach developed in dogs by Shumway and the Stanford group.Blaiberg did well and was the first heart transplant patient to leave hospital. Media attention was enormous and his return to a relatively normal life was followed intensely over many months. It was Blaiberg’s success, perhaps more than any other single factor, that led to guarded optimism that heart transplantation would eventually prove a valuable treatment option. Blaiberg was the shining beacon, whereas the majority of other attempts at heart transplantation worldwide in the late 1960s and early 1970s seemed doomed to early failure. Blaiberg eventually died 19 months after his transplant. His autopsy demonstrated severe and widespread coronary artery disease. This was the first example of transplant coronary artery disease that now dominates as the major cause of graft failure after the first post-transplant year.4The persistence of media coverage of heart transplantation at Groote Schuur gave Chris Barnard immense public and professional recognition on one hand, but on the other also evoked mixed and even heated reaction at times, regarding the question of ethics in organ transplantation. There were those critics who believed that this form of therapy was an unjustifiable and unethical form of palliation. Others responded with tremendous enthusiasm, as reflected by the fact that over one hundred heart transplants were performed in various centres all over world within the next year (1968).However, the rather poor results following this experience, with a two-year survival of only 11%, had a negative effect on the initial enthusiasm over heart transplantation During the 1970s, Barnard’s programme, together with those at Stanford (under Norman Shumway), the Medical College of Virginia, and Hôpital La Pitie in Paris, were the only major centres continuously performing heart transplantation, and therefore the only centres where advances in heart transplantation were pioneered.Between December 1967 and November 1974, exclusively orthotopic heart transplantation was performed. Ten such heart transplants were performed at Groote Schuur Hospital. The results, although poor by today’s standards, were exceptional when one considers the primitive nature of the immunosuppressive therapy available at the time , and the team’s lack of experience in diagnosing and treating rejection episodes.Of the 10 orthotopic heart transplants, four lived for more than 18 months, two of whom became long-term survivors. Dorothy Fisher lived for over 13 years and Dirk van Zyl lived for over 23 years.This early experience established sound criteria for the selection of recipients who would derive maximum benefit from heart transplantation. Experience was also obtained in methods of diagnosis and treatment of the acute rejection.In 1973, Barnard performed a heart transplant and the donor heart failed to function satisfactorily, so the patient died in the operating theatre. When Barnard came out to break the sad news, he was asked why he could not put the old heart back, as at least it had kept the patient alive. This struck Barnard as a distinct possibility. If the patient’s own heart had been left in place, and the transplant was inserted as an auxiliary pump, failure of the donor heart may not have caused the patient’s demise. Furthermore, during severe rejection episodes, which were common in those early days and a major cause of the poor results at the time, the native heart might be able to maintain the circulation while rejection was reversed by increased therapy.Barnard set Jacques Losman, a junior surgeon on his team, to develop the surgical technique of heterotopic heart transplantation in the animal laboratory. The concept was for a second heart to be placed in the right chest and for the two hearts to function in parallel.in situ, even if it were no longer functioning. This prevented the necessity of dissecting the donor heart from the right lung, to which it might be tightly adherent.Forty-nine consecutive heterotopic heart transplants were performed in Cape Town between 1974 and 1983, with moderately good results for that era.Two 14-year-old boys, both of whom initially received heterotopic transplants, underwent a second (orthotopic) heart transplant for graft atherosclerosis, and were therefore the first patients in the world to have two donor hearts in their chest at the same time. The first of these remains well, 29 and 26 years after the hetero- and orthotopic transplants, respectively. In the other, the second transplant also eventually failed and he underwent a third transplant, again in the orthotopic site, and thus became one of the few humans to have had four hearts in his lifetime.With the introduction of cyclosporine and the greatly reduced incidence of severe life-threatening rejection episodes, Barnard’s group resumed orthotopic heart transplantation. Heterotopic heart transplantation now has only a very small role, in, for example, the treatment of patients with fixed increased pulmonary vascular resistance, or when there is donor–recipient heart size mismatch.8The ability of the heterotopic heart to provide temporary circulatory support to a failing native heart, in the hope that the native heart would recover, was extended into the realm of xenotransplantation. On two occasions in 1977, when a patient’s left ventricle failed acutely after routine open-heart surgery and when no human donor organ was available, Barnard transplanted an animal heart heterotopically. On the first occasion, a baboon heart was transplanted, but this failed to support the circulation sufficiently, the patient dying some six hours after transplantation. In the second patient, a chimpanzee heart successfully maintained life until irreversible rejection occurred four days later, the recipient’s native heart having failed to recover during this period.ex vivo for up to 48 hours was developed. A baboon’s heart could be stored by hypothermic perfusion and then replaced in the original baboon, which had been kept alive during this period by an orthotopic cardiac allograft. Some baboons were followed for up to two years after these procedures and showed normal cardiac function and myocardial histology throughout this period.10Largely through the work of a young biochemist working in Barnard’s department, Winston Wicomb, a hypothermic perfusion system for storing hearts With the success of this storage system in the laboratory, Barnard encouraged his team to use it in the clinical transplant programme. This would enable the transportation of hearts from distant centres in South Africa, which had hitherto been impossible, all donor hearts being procured locally in Cape Town. The device was used successfully on several occasions.This alerted the team to the fact that brain death must have a detrimental effect on myocardial function, and led to extensive investigations into the haemodynamic and metabolic changes during and after brain death, and the implications of these changes. This work was the first comprehensive study investigating the effects of brain death.It was documented that these could have a detrimental effect on subsequent myocardial function and were sometimes associated with histopathological features of myocardial injury. Previously unrecognised major endocrine changes that occur following brain death were documented. These include a massive catecholamine surge and a depletion of thyroid hormones and insulin, and other neuro-hormonal effects. These were associated with a loss of myocardial energy stores and other detrimental effects on cardiac function. Experimental studies in baboons indicated that aerobic metabolism soon ceases after brain death, and life is sustained by anaerobic metabolism.15The concept of hormone-replacement therapy was proposed, particularly with regard to thyroid hormone replacement, which experimentally was reported to be beneficial to the maintenance and improvement of myocardial function. Subsequently, this therapy was administered to a number of human heart donors, with documented improvement in haemodynamic function.17As previously mentioned, there were no laws relating to brain death at the time of the first transplant. This undoubtedly helped to accelerate the growth of bioethics and to wrestle from the medical profession the monopoly over medical ethics, which they previously held. In February 1968, three months after the first heart transplant, a bill was introduced in the US Congress to ‘establish a commission to assess and report on the ethical, legal, social and political implications of medical advances’. It was evident that transplantation had raised serious ethical and legal questions for society.Doctors were still very much committed to the view that the profession should make the decisions about contentious issues such as the moment of death and when to stop certain treatment. Most of the medical witnesses who appeared before the congressional hearings were opposed to the bill. Many did not resent input from philosophers or theologians but most felt that doctors ought to retain control and have the final say. None was more outspoken than Christiaan Barnard whose opposition to the proposal was ‘unqualified, almost nasty, perhaps reflecting the fact that in South Africa a doctor’s authority was still unchallenged or that he was not dependant on Congress or the National Institute of Health (NIH) for funding’.The debates surrounding brain death and related ethical issues continued for many years and in 1981 the President’s commission in the United States declared that individual death depended on either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all functions of the entire brain. In 1976 the UK Conference of Royal Medical Colleges accepted the view that damage to the brainstem was the crucial factor causing profound irreversible coma, and this became the definition of brain death.18Barnard was also a champion of the disadvantaged and the poor, and an opponent of racism and apartheid, who welcomed its demise. He did his best to not allow racial segregation of patients within his department, in defiance of Government policy to segregate patients in hospitals according to race, as elsewhere in South Africa. Nevertheless nationalist politicians undoubtedly exploited him in the years following the first transplant, in order to improve the image of South Africa around the world, a time when repression was at its fiercest within the country and the worldwide condemnation of the apartheid regime was on the increase.Raymond Hoffenberg, a colleague of Barnard’s and an exceptional academic doctor did not allow himself to be exploited by the Government and took a firm stand against the injustices which were perpetrated on its citizens in order to maintain apartheid; he was served with a banning order which forced him into voluntary exile a few weeks after Barnard’s surgical triumph. He went on to be a leading physician in Britain, eventually becoming president of the Royal College of Physicians and being knighted by the Queen.By the early 1980s, Barnard was tiring of the stresses and strains of clinical heart surgery and was losing interest in running a busy department. Furthermore, rheumatoid arthritis in several joints was causing him constant pain and making it increasingly difficult to operate to his satisfaction. In 1983, at the age of 61, he took early retirement from Groote Schuur Hospital and the University of Cape Town.One Life, which sold widely throughout the world.Barnard took the opportunity to pen an autobiography, Soon after announcing his retirement, Barnard was invited to act as a consultant at Baptist Medical Center in Oklahoma City, where a new heart transplant programme was being planned. He spent six months a year for a number of years in Oklahoma, advising on the establishment of this programme, although not participating in the actual surgery. He finally retired from medicine in 1988 and settled back in Cape Town. He remained active as an international speaker on medical matters of general interest and continued to travel widely. He died during one of his travels on the island of Cyprus on 2 September 2001.Chris Barnard’s department at Groote Schuur Hospital and the University of Cape Town has subsequently taken his name and has maintained an active heart transplant programme despite financial constraints imposed by the present Government’s reprioritisation of health expenditure on primary and preventative healthcare in a new post-apartheid South Africa, and the negative impact of HIV and AIDS on the healthcare sytem.While no longer actively involved in basic laboratory transplant research, the Chris Barnard Division of Cardiothoracic Surgery at the University of Cape Town still has an internationally renowned cardiovascular research laboratory, directing its current research into methods of improving the surgical management of cardiac valvular and coronary diseases, which are more relevant to the cardiovascular diseases common in the African population. The most recent advance from this research unit has been the development of an external support for venous conduits used for coronary artery bypass grafting, which promises to increase the long-term patency of these grafts, and an international clinical trial using this mesh is currently underway.21


Introduction:Preterm infants are at increased risk of having a patent arterial duct (PAD). PADs may cause congestive heart failure, respiratory distress, necrotizing enterocolitis, and renal impairment. Consequently, in some infants, it becomes necessary to attempt closure of the PAD. Surgical closure can be difficult in small infants and is not without its risks; thus, medical closure offers advantages. Cyclooxygenase inhibitors have been used for medical closure of the PAD with both ibuprofen and indomethacin having been used clinically.Methods:We performed a systematic review of the literature to identify all studies comparing ibuprofen and indomethacin. Studies comparing ibuprofen and indomethacin for closure of the PAD in premature infants were included in the meta-analysis. A subanalysis was performed to compare the route of administration. Efficacy endpoints studied were PAD closure and surgical ligation while adverse effects studied were death in the first month of life, necrotizing enterocolitis, gastrointestinal bleeding, intestinal perforation, bronchopulmonary dysplasia in the first month of life, Grade 3 or 4 intraventricular hemorrhage, and change in the serum creatinine after treatment.Results:Ibuprofen and indomethacin were equally effective in closing the PAD in premature infants and demonstrated no difference in the incidence of adverse events. In respect to the route of administration, oral ibuprofen was as effective as intravenous indomethacin. When comparing both drugs via the intravenous route, the only difference noted between the ibuprofen and indomethacin was that ibuprofen was associated with a lesser increase in serum creatinine after treatment.Conclusion:Ibuprofen and indomethacin are equally effective in PAD closure without any difference in the incidence of adverse events. Importantly, oral ibuprofen was as effective as intravenous indomethacin. The arterial duct (AD) is a vascular structure that is necessary for fetal life, allowing for much of the right ventricular output to be shunted from the pulmonary artery to the descending aorta, thereby allowing for the developing lungs to receive enough blood to sustain development. Oxygenation, however, occurs at the level of the placenta during fetal life, and thus, blood does not need to pass through the pulmonary vasculature itself. The AD closes shortly after birth. In infants born at 30 to 40 weeks gestational age, the AD closes by 72 hours in 90%, and in infants born at greater than 40 weeks gestational age, the AD closes in 100% by 72 hours .-31.10-31A total of 1,583 patients were included in this pooled analysis. Of the 22 studies, 14 compared IV ibuprofen to IV indomethacin with 552 patients in the ibuprofen group and 516 in the indomethacin group; six studies compared oral ibuprofen to IV indomethacin with 193 patients in the ibuprofen group and 219 in the indomethacin group; and two studies compared oral ibuprofen to oral indomethacin with 58 patients in the ibuprofen group and 45 in the indomethacin group. Additional data regarding patient characteristics can be found in Table 2=0%) so a fixed-effects model was used. There was no statistically significant difference in PAD closure with IV ibuprofen when compared to IV indomethacin  . There was no statistically significant difference in PAD closure with oral ibuprofen when compared to IV indomethacin   so a fixed-effects model was used. There was no statistically significant difference between oral ibuprofen and oral indomethacin in respect to PAD closure  . No statistically significant difference was noted in the need for surgical ligation between IV ibuprofen and IV indomethacin .Data regarding the need for surgical ligation comparing IV ibuprofen and IV indomethacin was available from nine studies with 418 patients having received ibuprofen and 417 having received indomethacin. A fixed-effects model was used as there was no significant heterogeneity . The need for surgical ligation did not statistically significantly differ between oral ibuprofen and IV indomethacin .Four studies compared need for surgical ligation in 159 patients having received oral ibuprofen and 183 having received IV indomethacin. A fixed-effects model was used as there was not significant heterogeneity . There was no statistically significant difference between those having received IV indomethacin and those having received IV ibuprofen .A total of nine studies compared death in the first 30 days of life between 485 patients having received IV ibuprofen and 459 having received IV indomethacin. Significant heterogeneity was not present . No statistically significant difference in necrotizing enterocolitis was noted between IV ibuprofen and IV indomethacin .Eight studies compared the occurrence of necrotizing enterocolitis between IV ibuprofen and IV indomethacin with 412 and 413 patients in the two groups, respectively. No significant heterogeneity was present so a fixed-effects model was used . No statistically significant difference was noted in necrotizing enterocolitis between oral ibuprofen and IV indomethacin .Data regarding necrotizing enterocolitis comparing oral ibuprofen and IV indomethacin was available from five studies with 181 patients having received ibuprofen and 210 having received indomethacin. A fixed effects model was used as there was no significant heterogeneity .2=27%). A statistically significant difference in gastrointestinal bleeding was not found between oral ibuprofen and IV indomethacin .A total of three studies compared gastrointestinal bleeding between oral ibuprofen and IV indomethacin with 144 and 169 patients in each group, respectively. A fixed-effects model was used as significant heterogeneity was not present . A statistically significant difference in intestinal perforation was not noted between IV ibuprofen and IV indomethacin .Seven studies compared intestinal perforation in 380 patients having received IV ibuprofen and 382 patients having received IV indomethacin. Significant heterogeneity was not present so a fixed-effects model was used . No statistically significant difference was noted in bronchopulmonary dysplasia in the first month of life between IV ibuprofen and IV indomethacin .Data regarding the frequency of bronchopulmonary dysplasia in the first month of life was pooled from six studies with 323 patients having received IV ibuprofen and 317 having received IV indomethacin. A fixed-effects model was used as there was no significant heterogeneity noted . No statistically significant difference in the frequency of bronchopulmonary dysplasia in the first month of life was noted between oral ibuprofen and IV indomethacin .A total of four studies were pooled to compare the frequency of bronchopulmonary dysplasia in the first month of life between 120 patients having received oral ibuprofen and 122 having received IV indomethacin. Significant heterogeneity was not present so a fixed-effects model was used . No significant difference was noted in Grade 3 or 4 intraventricular hemorrhage between IV ibuprofen and IV indomethacin .Seven studies were pooled to compare the frequency of Grade 3 or 4 intraventricular hemorrhage between 392 patients having received IV ibuprofen and 393 patients having received IV indomethacin. A fixed-effects model was used as no significant heterogeneity was noted . A statistically significant difference in change in creatinine was present and favored ibuprofen  . No significant difference was noted between oral ibuprofen and IV indomethacin in regards to change in creatinine   Figure .2=0%). A statistically significant difference in change in creatinine was present, favoring oral ibuprofen  (Figure Data regarding change in creatinine between oral ibuprofen and oral indomethacin was available from two studies with 58 and 45 patients in the groups, respectively. A fixed-effects model was used as there was no significant heterogeneity present (chi-squared=0.22, p=0.64, IThis pooled analysis of 22 studies with 1,582 patients demonstrates that both ibuprofen and indomethacin are effective for PAD closure. Route of administration does not seem to affect efficacy and even oral ibuprofen seems to be equally effective as IV indomethacin. There was no difference in the incidence of surgical ligation between those given indomethacin and those given ibuprofen.In regards to safety, there was no difference in the incidence of adverse outcomes, such as death in the first month of life, necrotizing enterocolitis, gastrointestinal bleeding, intestinal perforation, bronchopulmonary dysplasia in the first month of life, and Grade 3 or 4 intraventricular hemorrhage. There was a smaller increase in serum creatinine after attempted treatment associated with IV ibuprofen when compared to IV indomethacin and when oral ibuprofen was compared to IV indomethacin.Previous studies have demonstrated a similar difference between ibuprofen and indomethacin in regards to change in creatinine , 18, 22.The AD consists of an outer medial layer that consists of circumferential smooth muscle fibers supplied by thin-walled vasa vasorum while the inner medial layer is avascular and consists of longitudinal smooth muscle fibers. The internal elastic lamina separates this medial layer from the intima which is thin until the final end of gestation at which point it thickens. This is in contrast to the main pulmonary artery and the aorta which are comprised of circumferential elastic fibers .The AD facilitates the passage of approximately 30% to 45% of the combined ventricular output in the human fetus, allowing for much of the blood to bypass the fetal lungs, which are immature and fluid filled, thus allowing them to complete development without the burden of a large amount of blood flow -35. SincWhile the specific mechanisms that mediate fetal patency of the AD are not entirely elucidated, several have been proposed, which include low partial pressure of oxygen, maternal prostaglandins, adenosine, and nitric oxide production -46. SincThickening of the intimal layer and the resulting decrease in luminal diameter facilitates closure of the AD. While this thickening occurs throughout gestation, it is particularly marked after birth. The internal elastic lamina also begins to fragment and allow smooth muscle and endothelial cell proliferation. Eventually, the AD constricts to a point where hypoxia develops. The vasa vasorum provides blood to the adventitia while the intima and the media receive blood directly from the lumen. Thus, hypoxia ensues as the AD constricts decreases flow to the media. With this hypoxia comes apoptosis and eventual fibrous tissue deposition, which completes the AD closure. In the former phases of this process where smooth muscle constriction and intimal thickening is occurring, the process may be reversible. Once the fibrous deposition has occurred, however, the process is no longer reversible .Oxygen clearly plays a role in AD closure. Studies have demonstrated that increased partial pressure of oxygen resulted in AD closure -50. ThisNitric oxide, a potent vasodilator, is produced by endothelial cells utilizing the nitric oxide synthase. Nitric oxide synthase has been found in the AD and its surrounding endothelial tissue. Specific nitric oxide synthase inhibitors have also been demonstrated to be ineffective in antagonism of this system in the AD at low partial pressures of oxygen, which may also explain the mechanism by which oxygen affects AD constriction. Additionally, this system thus facilitates AD closure at a later gestational age .Other vasoactive agents, such as adenosine, acetylcholine, bradykinin, and norepinephrine, have also been demonstrated to lead to AD constriction and have synergistic effects to the AD’s response to oxygen. The absence of any of these agents, however, does not impair oxygen-mediated AD constriction. The precise role of these agents is not clearly defined , 55.2 and prostaglandin I2. While prostaglandin I2 is more abundant, prostaglandin E2 is more potent with the AD being nearly 1,000 times more sensitive to prostaglandin E2, which is believed to play a vital role in maintaining the AD during fetal life [2 levels are higher in the fetus than in the mother with levels falling rapidly after birth, such that adult levels are reached by three hours of life [2 levels since the lungs are the site of its metabolism. The partial pressure of oxygen does not impact the effect of prostaglandin E2 on AD constriction. Premature infants have both continued production of prostaglandin E2 but also an increased response to it [Of particular importance is the effect of prostaglandins on AD closure as both ibuprofen and indomethacin target the prostaglandin pathway. Cyclooxygenase is the enzyme responsible for synthesizing prostaglandins from arachidonic acid . There atal life . In fact of life . What isse to it .2. Thus, understanding of the previously mentioned characteristics of the AD make the use of cyclooxygenase inhibitors intuitive in the setting of premature infants with PAD [These findings regarding the effect of prostaglandins on AD closure have important clinical implications. Both ibuprofen and indomethacin are nonselective cyclooxygenase inhibitors and also inhibit the synthesis of prostaglandin Ewith PAD .This study demonstrates that ibuprofen and indomethacin are equally effective in closing the PAD with ibuprofen having a renoprotective effect with some dosage routes. This current manuscript also reviews the embryology and physiology of the AD. This analysis, however, is not without its limitations. Pooled data is study-level rather than patient-level, thus limiting the opportunity for specific meta-regression. Additionally, some endpoints had significant heterogeneity. Even those endpoints without quantitative endpoints may have qualitative heterogeneity. Additionally, no cost analysis could be conducted. There was a small number of studies available to pool in regards to the comparison of the oral ibuprofen and oral indomethacin as well.Ibuprofen and indomethacin are both equally effective in closure of the PAD in preterm infants. Adverse effects associated were not found to differ between the two, although ibuprofen was associated with a lower increase in creatinine.


Cardiac MRI for congenital heart disease (CHD) is an operator dependent and time-intensive examination requiring real-time decision making regarding choice of sequences, planes, and acquisition parameters to adapt to unique morphological and functional variables in a given patient.To evaluate technical feasibility, image quality and quantitative integrity of a free-breathing (FB) protocol following administration of blood pool contrast agent, utilizing 3-dimensional (3D) imaging of morphology, function, and flow without physician supervision in a cohort of patients with CHD.Five patients with CHD were included in this pilot study  and had better inter-slice alignment (1.4 ± 0.5 vs 1 ± 0). Average percentage difference between 2D and 3D cine SSFP volumetric data is shown in table 3, and Figure The free breathing first pass MRA, equilibrium MRA, 3D cine SSFP, and 3D single-phase SSFP exhibit significant clinical utility. We demonstrate the feasibility of performing an observer independent comprehensive CMR in CHD utilizing FB 3D acquisitions for morphology, function and flow within 30 minutes using a 5-channel phased-array coil. Better acquisition hardware  will lead to superior image quality.None.


The aims of the current study were to evaluate native RV T1 values in AFD, with a goal of better understanding the pathophysiology of RV involvement.Anderson-Fabry disease (AFD) is characterized by progressive multiorgan accumulation of intracellular sphingolipids due to α-galactosidase A enzyme deficiency, resulting in progressive ventricular hypertrophy, heart failure, arrhythmias, and death. Decreased native (non-contrast) left ventricular (LV) T1 values were measured in the inferior RV wall (RVI), interventricular septum (IVS), and inferior LV (LVI) in patients with AFD, patients with pulmonary hypertension, who provided an alternative RV pathological process for comparison, and healthy controls. A minimum wall thickness of 4 mm was selected to minimize partial volume errors in tissue T1 analysis. T1 analysis was performed in 6 subjects with AFD, 6 subjects with PH, and 21 controls. Native T1 values were shorter , independent of location, in subjects with AFD  compared to both PH  and HC . RVI measurements were not possible in controls due to insufficient wall thickness.Native TNative T1 values appear similarly reduced in the left and right ventricles of individuals with AFD and RV wall thickening, suggesting a common pathology. In contrast, individuals with PH and thickened RVs showed increased native T1 values in both ventricles, suggestive of fibrosis. Short- and long-axis ventricular cines were performed using balanced steady-state free procession (bSSFP) imaging. Typical scan parameters were 1.24 ms echo time, 2.48 ms repetition time, 51° flip angle, 8 mm slice thickness, 2 mm gap, 400×275 mm field of view, 256×132 acquisition matrix, 75% phase resolution, 14 views per segment, rate 2 parallel imaging (GRAPPA), and 30 reconstructed cardiac phases. Tdescribed, 24. TypManual endocardial tracing of both ventricles was performed for quantification of ventricular end-systolic volume and end-diastolic volume. Ejection fraction was calculated as (end-diastolic volume—end-systolic volume)/ end-diastolic volume. Manual epicardial tracing of the left ventricle, excluding papillary muscles, was performed for quantification of ventricular mass, calculated as the ventricular muscle volume corrected for specific gravity of the tissue (1.05 g/mL). Masses and volumes were indexed to body surface area.1-mapping images. Additional LGE short and long axis slices were used to corroborate the presence or absence of positive enhancement in these locations of interest. Nine subjects with Anderson-Fabry disease did not receive gadolinium contrast, either due to research protocol (n = 8) or renal dysfunction (n = 1).Late gadolinium enhancement images were assessed for the presence of positive enhancement, with specific assessment of the interventricular septum, inferior RV wall, inferior LV wall, and the inferior RV insertion point at the slice location nearest to the corresponding T1-mapping slice location. In subjects with AFD or PH, a minimum RVI of 4 mm was selected as an inclusion criterion for further analysis. This RVI thickness was selected for the T1-mapping data to mitigate potential partial volume contamination of myocardial tissue T1 values from neighbouring epicardial fat and/or blood pool pixels, based on a typical non-interpolated in plane resolution of approximately 1.9 mm. As healthy individuals were not expected to have increased RV wall thickness, their LV T1-mapping data was included if the septal or inferior LV wall thickness was at least 4 mm.Inferior RV wall thickness (RVI thickness), interventricular septal wall thickness (IVS thickness), and inferior LV wall thickness (LVI thickness) was measured in all subjects at a diastasis cardiac phase on short-axis cine images , for a s1-mapping acquisition were registered to correct for in-plane motion occurring during the breath hold[1)), where k denotes a scaling constant, η represents the saturation efficiency, TS represents the saturation recovery time, and T1 represents the longitudinal relaxation time. For the assessment of reproducibility, analysis was performed on each subject twice, independently by two observers (JP and RBT). Subjects’ images were loaded randomly, with blinding between repeated observations and observers. T1 analysis was performed offline using custom software .In all healthy controls, along with subjects with AFD or PH who met the criteria for minimum inferior RV wall thickness of 4 mm, the 10 images in the Teath hold, 25. Regeath hold. Manual 1 values are presented as mean±standard deviation. Group differences, except with respect to gender, were compared using Kruskal-Wallis One-Way ANOVA, with multiple pair-wise comparisons performed using the Mann-Whitney U Test. Gender differences between groups were compared using Chi-squared analysis. Ventricular T1 values within subjects were compared using the Friedman test, with multiple pair-wise comparisons performed using the Wilcoxon signed rank test. Reliability was measured using Coefficient of Variation (CoV), defined as the standard deviation of the differences between repeated measurements divided by the measurement mean. Significance was set at p<0.05, with a Bonferroni correction where applicable. Statistical analysis was performed using STATA statistical software .Subject characteristics and CMR variables, including wall thickness and ventricular T1-mapping analysis. One subject with PH had unanalyzable T1 datasets due to significant image artifact and was excluded and two HC subjects LVI T1 values were excluded due to LVI thickness < 4 mm. The characteristics of those included in T1 analysis are included in Of the subjects included initially in the study, 6 subjects with AFD, 7 subjects with PH, and 0 healthy controls had inferior RVI thickness ≥ 4 mm and were therefore included for further T1 is shorter in subjects with AFD  compared to those with PH  and HC  . Subjects with PH had longer LVI-T1 than HC (adjusted p = 0.02), but the IVS-T1 was not statistically different (adjusted p = 0.24), with a wide range of values (1140 to 1477 ms). T1 values for all groups are shown in As shown in 1 values were not statistically different between the two LV and RV locations (p = 0.31). Similarly, subjects with PH also showed non-significant differences between regional ventricular T1 values (p = 0.51).Comparing regions in subjects with AFD, TOf the subjects with AFD who received contrast agents (n = 3), none were positive for LGE in the inferior RV, septal, or inferior LV regions. One subject showed positive enhancement at the inferior RV insertion point. One subject with PH showed inferior RV wall enhancement, 2 showed septal enhancement, and 1 showed enhancement at the inferior LV. All subjects with PH showed enhancement at the inferior RV insertion point.Coefficient of Variability (CoV) for the repeated analyses by observer 1 was 1.4%, 0.9%, and 1.5% for the RVI, IVS, and LVI, respectively. For observer 2, the CoV was 1.2%, 0.6%, and 2.7% for the RVI, IVS, and LVI, respectively. For interobserver agreement, the CoV was 1.7%, 1.5%, and 1.8% for the RVI, IVS, and LVI, respectively.1 values in the right and left ventricle of patients with AFD and thickened right ventricles, both of which are reduced in comparison to LV T1 values in the healthy heart and as compared to patients with pulmonary hypertension. Reduced LV native T1 values were reported previously in patients with AFD[1 values in the current study likely reflect the same pathology and mechanisms as within the LV.The primary finding of the current study is the similar native T with AFD–13, but  with AFD–20, typi with AFD, thus th1 in AFD values still requires further elucidation. Reduced LV T1 values have also been seen in individuals with iron overload[1-mapping in general has not been systematically characterized, with one report of normal LV lipid content in AFD patients using 1H NMR spectroscopy[1 differences noted in this study between AFD and PH suggests different origins of RV thickening between the conditions, indicating that RV thickening in AFD is not primarily related to increased RV afterload. Larger, and ideally longitudinal, studies including T1-mapping in the LV and RV would be useful in further elucidating the nature of RV involvement in subjects with AFD. Certainly, there is excitement in the community of the promise of T1-mapping, in either the LV or RV, to offer a potential biomarker to follow patients with AFD, particularly with respect to responses to enzyme replacement therapy.The exact cause and mechanism of the reduced native T overload, howeverctroscopy. Interesctroscopy, 20. In ctroscopy. This su1 values in PH (1239±41 ms versus 1096±49 ms in AFD) likely reflect fibrosis, or more specifically the increased water mobility associated with increased extracellular volume fraction, related to long standing pressure overload. In this study we also show that LV and RV native T1 values appear to be increased in those with PH and thickened RVs as compared to healthy control LV T1 values. There is limited existing literature to corroborate this finding, however a recent publication also showed increased native T1, along with extracellular volume fraction, in the RV of subjects with PH versus healthy controls[1 values have been demonstrated at the RV insertion points in an animal model of chronic pulmonary hypertension[1 values were increased, though not statistically, likely reflecting pathological remodelling including a degree of interstitial and replacement fibrosis, evident by cases with positive late enhancement and reduced RV ejection fraction.In contrast, the increased native RV T controls. Elevateertension, though 1-mapping, using native T1 values, has been used for non-invasive tissue characterization in a variety of disease conditions[1-mapping sequences typically have an in-plane spatial resolution of approximately 2 mm, thus making it difficult to apply in the right ventricle, where, in normal hearts the mean diastolic wall thickness of the RV is ≤ 4–5 mm[1 estimation (ANGIE) technique[1-mapping was performed at end-systole, the authors found healthy control RV T1 and extracellular volume fraction values are similar to those found in the LV. Unfortunately, the high-resolution ANGIE sequence takes much longer than standard T1-mapping sequences (~3 minutes vs. 9–17 heart beats), may still be subject to partial volume contamination effects, and more practically is not yet widely available.Quantitative Tonditions–16; howe ≤ 4–5 mm, 31, comtechnique, 32. Usi1 values in the LV and RV, while those with Anderson-Fabry disease have T1 values that are reduced in both ventricles. The primary technical concern with RV tissue characterization is systematic artifactual bias of these values from partial volume errors with epicardial fat or blood pool . The consistently increased native T1 values in the PH group and reduced values in the AFD group, as compared to controls, and the excellent reproducibility of T1 values by two observers in the blinded analysis suggest that partial volume errors did not confound the major findings of the current study. Nonetheless, in the absence of robust techniques to remove the signal from blood and fat, the potential for signal contamination remains.In the present study, the effects of partial volume contamination by either blood or epicardial fat was mitigated by selecting individuals with an increased RVI thickness, which is a cardinal feature of patients with Anderson-Fabry disease and pulmonary hypertension . Importantly, both patient groups’ RVI thickness were similar to the inferior LV thickness of healthy controls (6±1 mm), suggesting a similar small risk of partial volume contamination for parts of the LV. Subjects with PH were shown to have elevated T1 values for comparison. However, Mehta et al., showed similar normal LV and RV native T1 values using a high spatial resolution fat-supressed method[1-mapping methods, we limited our investigation to patients with thickened RV walls and therefore were unable to study the RV of healthy volunteers. This fact also limits the generalizability of our findings to other patients with Anderson-Fabry disease or pulmonary hypertension without a thickened RV. Also, while the inferior RV wall was consistently the most clearly discernible location with least amount of trabeculation and epicardial fat content (as observed on bSSFP cines), leading to our decision to perform analysis in that location, performing analysis on a small region at a single slice location may not accurately represent the entire ventricle. There is currently no data to suggest that there are intrinsic differences in native T1 values regionally within the RV.Our study is primarily limited by its small numbers and lack of normal RV Ted method, 32, sug1 values, could not be ruled out. Previous reports typically describe elevated native T1 values in areas of positive LGE[1 analysis was not performed. Due to the lack of contrast administration, we are also not able to provide extracellular volume fraction estimates, which require native and post-contrast T1 measurement in the blood and tissue for calculation.Unfortunately, LGE imaging was not performed in all of the subjects with Anderson-Fabry disease so replacement fibrosis, and its potential to alter our reported Titive LGE–13 whereitive LGE–35. Thus1 measurements, however without significant improvements to T1-mapping techniques, larger scale RV imaging studies are not feasible.Further study, including clinical and function correlates, would add important diagnostic and prognostic significance to T1 in the RV are still unknown, native T1 values appear similarly reduced in the left and right ventricles of individuals with AFD and right ventricular wall thickening, likely driven by the same pathological processes. In contrast, individuals with pulmonary hypertension and right ventricular wall thickening show increased native T1 values in both the LV and RV, suggestive of fibrosis. While T1-mapping is emerging as a useful marker in the diagnosis and monitoring of numerous cardiac conditions, its use in the right ventricle remains a challenge given this ventricles relative thinness and potential for blood pool or epicardial fat contamination.Though normal values for native TS1 File(XLSX)Click here for additional data file.


In patients with myocardial infarction (MI), an important factor in determining the long-term prognosis is the degree of regional contractile dysfunction. DENSE (Displacement ENcoding with Stimulated Echoes) is a technique which allows quantification of myocardial strain, and whi50 male patients (age 56 ± 10 years) within 7 days of MI and 30 healthy male controls (age 45 ± 18 years) underwent CMR on a 1.5T Siemens Avanto. The protocol included DENSE and LGE (patients only) obtained from a single mid-ventricular short-axis slice, which was divided into 6 segments for analysis. The percentage of each segment which contained LGE was calculated using a threshold of mean+5SD of remote myocardium intensity. DENSE images were analysed to obtain a value for peak circumferential strain (Ecc). The following analyses were performed: (i) intra- and inter-operator and inter-scan repeatability, (ii) sensitivity and specificity for the detection of LGE, using a reference range established from control data, and ROC analysis and (iii) the ability to distinguish between non-infarcted, <50% and >50% infarction, and between remote, adjacent and infarcted segments.The results of (i) repeatability and (ii) sensitivity, specificity and area under curve (AUC) are summarised in Table DENSE can be successfully applied in a clinical setting, and provides repeatable results. The sensitivity and specificity of the technique for detecting the presence of LGE are good, and the number of segments with LGE correctly identified increases as the extent of LGE increases. Peak Ecc can be used to distinguish between non-infarcted, <50% and >50% infarcted segments, but cannot identify segments which are adjacent to infarction.N/A.


CALM) is sensitive to cardiovascular health status, little is known about the determinants of CALM. The purpose of this integrative study was to evaluate the contribution of left ventricular (LV) cardiac motion and local blood velocity to CALM. Simultaneous ultrasound measurements of CALM, common carotid artery mean blood velocity (MBV), and left ventricular motion were performed in ten young, healthy individuals . Peak anterograde CALM occurred at a similar time as peak MBV . The timing of maximum retrograde CALM displacement was different, but related, to both peak apical  and basal rotation  with peak cardiac displacements preceding peak CALM displacements in both cases. The association between basal rotation and retrograde CALM was further supported by strong correlations between their peak magnitudes , whereas the magnitude of septal longitudinal displacement was not associated with peak CALM . These results suggest that the rotational mechanical movement of the LV base may be closely associated with longitudinal mechanics in the carotid artery. This finding may have important implications for interpreting the complex relationship between ventricular and vascular function.Recent studies have identified a predictable movement pattern of the common carotid artery wall in the longitudinal direction. While there is evidence that the magnitude of this carotid artery longitudinal wall motion ( Recent investigations have revealed a predictable and stable carotid artery longitudinal wall motion (CALM) pattern in healthy individuals, which retains both its pattern and magnitude over time  as well as in the direction opposing blood flow (retrograde), at different time points throughout the cardiac cycle  were recruited for this study. All participants were between the ages of 18–35 years, and free of known cardiovascular disease. Informed consent in writing was obtained prior to participation in the study. The study protocol was submitted to, and approved by, the Hamilton Integrated Research Ethics Board and conforms to the All participants arrived at the lab between the hours of 0800–1000 in the fasted state, after refraining from exercise, alcohol and caffeine for >8 h. Participants then rested in the supine position for 10 min prior to any data collection. For data collection, participants were positioned in the left lateral decubitus position and equipped with three sets of single‐lead ECG to provide heart rate signals to two ultrasound units and a data collection system used to align the simultaneous measures during analysis.2) was manually placed over the media‐adventitia interface of the far wall. To improve resolution, a surrounding region of interest was interpolated to increase the number of pixels by a factor of four. For each successive frame, a normalized cross correlation function identified the peak correlation value for all possible kernel matches, and a shift in pixel position was taken to represent tissue displacement. A value above a lower boundary of 0.7 was considered acceptable for tracking  was 7.8%, which indicates a good reproducibility between measurements, and compares well to other reports . A single focal point was positioned at the far wall and scanning depth was standardized at 2.5 cm to maintain a consistent sampling rate of 102.5 fps. Immediately prior to image acquisition, participants were asked to briefly hold their breath, as breathing artifact has been demonstrated to superimpose movement over longitudinal motion measures  = (8*Blood Velocity at the CCA)/(CCA End Diastolic Lumen Diameter)  was recorded simultaneous to vascular and cardiac imaging using a nonimaging 4 MHz pulsed wave probe at an insonation angle of 40° placed immediately proximal to the vascular probe on the CCA. This nonimaging probe was directly attached to an external spectral analysis system  to determine intensity weighted mean blood velocity traces through a fast‐Fourier transform and these signals were subsequently sampled at 1000 Hz using commercially available hardware . To examine the relationship between the magnitude of carotid and cardiac events, MBV was also measured independent of other outcomes using a linear‐array probe in Duplex mode at 4 MHz  at an insonation angle of 60° at 2–3 cm proximal to the carotid bifurcation, and processed as above. CCA shear rate was estimated using the equation, shear rate  and retrograde (point D–point C) phases, both reported in absolute terms. An average of 3–5 cardiac cycles were used to compare simultaneous data.In addition to apical and basal rotation, we investigated longitudinal displacement of the LV to assess the relationship of CALM events to cardiac motion in the longitudinal plane. Owing to its anatomical proximity to the CCA, the basal septal segment of the 2D strain analysis package was isolated using the custom‐made 2DStrainAnalysis Tool  and processed as above.t‐tests were used to assess differences in the timing between events at the same anatomical level , expressed as a percentage of the cardiac cycle. For comparisons of local events at the CCA, where a time delay between events was not expected, nonsignificant P‐values from the t‐test and significant results from intraclass correlation coefficients (ICC) were interpreted as evidence for associations. Conversely, for comparisons between cardiac and CALM events, where a time delay between events was expected, only significant P‐values from the t‐test and significant results from intraclass correlation coefficients (ICC) were interpreted as evidence for associations. Because of the aforementioned expectation of a time delay between events at the heart and the carotid artery, relationships between the timing of CALM parameters with cardiac motion were determined from Consistency‐type ICCs with a two‐way random model.Statistical analyses were performed on the Statistical Package for the Social Sciences . Data were checked for normality using the Shapiro–Wilk test. Dependent Student's α = 0.05.To further explore associations revealed by the initial analyses, Pearson's correlations were applied to select variables that suggested associations between cardiac and CALM events. Analysis of data was performed on simultaneously collected heart cycles when possible, otherwise using an average of all available data for correlations. Statistical significance was set at n = 10; 6 males, 4 females; 22 ± 1 years) are presented in Table P < 0.01), and the total CALM displacement across one cardiac cycle was 0.50 ± 0.21 mm , with the MBV wave consistently reaching peak velocity before peak anterograde displacement of the wall . The time at peak retrograde displacement (CALM point D) was different from the time of both peak apical (t‐test P < 0.01) and basal (t‐test P < 0.01) rotation, with peak cardiac displacements preceding peak retrograde wall displacements in both cases . This relationship was not found for peak basal septal displacement . Although we also investigated the relationship between early CALM events (points A and B) with local blood velocity and LV motion, these associations did not meet both a priori statistical criteria and were therefore not evaluated further.Figure r = −0.48; P < 0.01), with taller individuals exhibiting less motion. There was no correlation between the magnitudes of anterograde CALM and carotid shear rate . Retrograde CALM had a strong correlation with peak basal rotation  and shear rate , but no statistical correlation with basal septal longitudinal movement  or apical rotation .Those variables that appeared to be temporally associated were further examined for associations between their magnitudes in order to gain greater insight into the strongest correlates between cardiac and CALM mechanics Table . There wIn this study, we show that longitudinal motion of the CCA (CALM) is associated with both local blood velocity and rotation of the LV base, but not with longitudinal septal displacement, thereby suggesting a physiological basis for the different phases of CALM previously observed. We propose that a complex relationship exists between the influences of local blood velocity and left ventricular rotation within the context of a structural ventricular‐vascular coupling theory, as discussed in detail below.The role of cardiac contraction in CALM has been previously theorized in the literature but has never been reported  that superimpose upon each other to create the observed summated function Fig. . We hypoWhile our observations on the association between the timing of events yields insight into the factors associated with the pattern of CALM events during the systolic period, assessing the associations between the magnitude of events may offer further insight. In this regard, we observed no association between the magnitudes of the anterograde CALM component and the local shear rate stimulus, similar to previous reports in a well‐controlled model of the porcine carotid artery  effect on CALM than longitudinal LV displacement.The consistency in which peak basal and apical rotation precede peak retrograde CALM displacement supports a direct relationship between LV rotation and arterial wall motion. Although the relationship between the LV base and CALM is supported by previous work suggesting that the kinetic energy of LV contraction appears to be greater at the LV base than the LV apex  compared with other groups (Yli‐Ollila et al. In summary, we observed a temporal relationship between the blood velocity wave and anterograde CALM, while retrograde CALM was associated in both timing and magnitude with left ventricular rotation, but not longitudinal septal displacement, as originally hypothesized. This relationship between carotid artery movement and left ventricular rotation may have important implications for the regulation of local vascular stiffness properties, and the complex interaction between left ventricular and vascular function.None declared.


Diffuse myocardial fibrosis is associated with heart failure and ventricular dysfunction in many diseases. The aim of this study was to relate cardiac magnetic resonance (CMR) measures of diffuse myocardial fibrosis to cardiomechanics and exercise tolerance.In 25 patients  after surgical repair of Tetralogy of Fallot (ToF), T1 measurements were performed at a mid and basal ventricular level in short axis before and 15 minutes after the application of 0.1 mmol/kg gadobenate dimeglumine in the interventricular septum (IVS), left ventricular (LV) lateral wall, complete LV myocardium and diaphragmatic portion of the right ventricle (RV). The extracellular volume (ECV) was calculated from native and post-contrast T1 times of myocardium and blood and the hematocrit.Peak circumferential (LV), longitudinal (RV) and radial (RV) strain as well as the standard deviation of the time to peak strain of different segments (SDpeak) were measured using CMR feature tracking. The correlation of native T1 times and ECV with strain parameters was tested using Pearson's coefficient. Native T1 times and ECV were correlated to exercise test results.2) with near-normal ejection fraction (RV-EF 47±8%). LV measures were unremarkable.  and between males and females, but were higher in the RV as compared to the LV (RV native T1 times 1021±69ms (vs. entire LV p<0.05), ECV 29±6% (vs. entire LV p<0.005)). There was no correlation of LV or RV native T1 times and ECV with peak segmental and global strain  nor with SDpeak . Exercise test results, available in 11 patients, correlated negatively with ECV of the entire LV .The mean pulmonary regurgitation fraction was 36±16% and RV enddiastolic volumes were enlarged (EV-EDV 155±52 ml/mIn patients after ToF repair, CMR measures of diffuse myocardial fibrosis are associated with exercise intolerance but not with LV or RV dysfunction.This study was partly funded by the Labatt Family Heart Centre, Witchell Fellowship, and by Siemens.


Myotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant.The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography.We selected 30 unrelated patients with DM1: 18 patients  with, and 12 patients  without abnormal findings on ECG and Holter-monitoring.Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR.2 (43–83) vs. 46 g/m2 (36–64), p = 0.02), increased left atrial volume (median (range) 52 ml/m2 (36–87) vs. 46 ml/m2 (35–69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38–71) vs. 66% (60–80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18).Myocardial fibrosis was found in 12/30 . The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/mPatients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1. Myotonic dystrophy type 1 (DM1) is an autosomal dominantly inherited neuromuscular disorder caused by an unstable expansion of a tri-nucleotide (CTG) repeat on chromosome 19 in the 3’ untranslated region of the myotonic dystrophy protein kinase gene . Add. Add4]. Myocardial fibrosis has been identified in myocardial autopsies from patients with DM1 together with fat infiltration and myocyte hypertrophy and degeneration -7]. The. The7]. Cardiovascular magnetic resonance (CMR) is a well-established, non-invasive method to quantify heterogeneous myocardial fibrosis and assess left ventricular function and mass . ScreeniWe investigated 30 unrelated and genetically verified DM1 patients with CMR and routine clinical screening to evaluate whether CMR add additional information about subclinical myocardial changes. In addition, our aim was to describe the prevalence and localization of myocardial fibrosis on CMR and to assess whether myocardial fibrosis was associated with abnormal findings on ECG, Holter-monitoring and echocardiography.The study was conducted at the Departments of Cardiology and Neurology, Rigshospitalet, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. We included a subgroup of patients (n = 30) from our cross-sectional study consisting of 129 genetically verified DM1 patients . Except In brief, patients were evaluated with medical history, physical examination, 12-lead electrocardiogram (ECG), trans-thoracic echocardiography , 48-hour ECG-monitoring (Holter-monitoring) and CMR with late gadolinium enhancement (LGE). Blood samples were analyzed for plasma levels of NT-proBNP, myoglobin and creatine kinase (CK).The study was approved by the regional scientific ethics committee (reference number H-d-2008-077) and all participating patients provided written informed consent.A total of 30 patients were included for CMR; 18 patients  with, and 12 patients  without abnormal findings on ECG and Holter-monitoring. Patients matched the main cohort in regard to age, gender and cardiac involvement and none of the patients were related. Patients with contraindications for CMR e.g. respiratory assist devices and claustrophobia were excluded, and few patients declined participation due to severe muscular impairment.The diagnosis of DM1 (based on CTG-repeat length) was confirmed either by Southern blot analysis and/or by TP-PCR .42 . All analyses were performed by an experienced CMR physician (KA). Furthermore, all LGE images were concomitantly analyzed and results agreed upon by two experienced CMR physicians (KA and NV); both blinded for other findings. The inter-observer variation of LGE measurements has previously been described . LV. LV15]. 2 and GLS > −15.9%. Additionally, echocardiography was used to assess valve disease and to estimate LV mass . Ad. Ad26]. So far, no homogeneous LGE pattern has been described in DM1, which is in accordance with our findings ,20]. Ho. Ho20]. Taken together, myocardial fibrosis may play a central role in the pathogenic process in DM1. Our findings emphasize that CMR add additional information to current screening procedures with a potential major impact on future risk stratification for SCD. Assuming that myocardial fibrosis is a predictor of cardiac outcome, CMR may be a unique tool for identifying high-risk DM1 patients in order to optimize early treatment and prevent SCD.Longitudinal studies are needed to investigate the prognostic value of myocardial fibrosis and to assess whether improved periodic cardiac assessment, based on the presence, progression and degree of myocardial fibrosis, can prevent life-threatening brady- and tachyarrhythmias through optimized medical treatment and implantation of PMs and ICDs.Contrast enhanced CMR is a well-established technique to assess focal myocardial fibrosis. We did not assess the degree of diffuse myocardial fibrosis, hence, we may underestimate and even oversee the fibrotic burden in some patients.Some patients were not eligible for CMR due to ventilatory assist devices or claustrophobia and few patients refused to participate due to severe muscular impairment. The exclusion of patients with the most severe muscular and respiratory impairment represents selection bias. However, we believe this would be a common bias for all CMR studies in this field. Furthermore, if these patients would have more cardiac involvement than the remaining patients, it would probably skew our results towards substantiating our conclusion that myocardial fibrosis is a frequent finding in patients with DM1.Several studies have assessed the correlation between CTG repeat length and cardiac involvement with ambiguous results ,45]. A . A 45]. Due to the relatively small number of patients in our study, the impact of our findings on the clinical management of patients with DM1 is limited and needs to be assessed in larger studies.CMR documented a high prevalence of myocardial fibrosis in patients with DM1. Overall, myocardial fibrosis was mainly observed in patients with concomitant abnormal findings on ECG, Holter-monitoring and/or echocardio-graphy. Nevertheless, myocardial fibrosis was also present in 33% of the patients with normal findings on routine cardiac screening. These findings emphasize that a normal ECG, Holter-monitoring and echocardiography cannot exclude myocardial fibrosis.CMR adds additional information to the current standard cardiac assessment and might be a valuable tool for risk stratification in DM1. The progression and the prognostic value of myocardial fibrosis needs to be further investigated in longitudinal studies.The authors declare that they have no competing interests.HP, HB and LK were responsible for the study design. HP and KAA collected data. HP, JV, HB, KAA and LK contributed to data analysis. All authors contributed to data interpretation and preparation of the manuscript. HP and HB are responsible for the overall content of the manuscript. All authors read and approved the final manuscript.


Myocardial inflammation has been described as a global finding in the acute phase of Kawasaki Disease. Despite normal LV systolic function by routine functional measurements, reduced longitudinal strain (S) and strain rate (SR) have been detected by echocardiography in the acute phase, which may potentially predict late onset heart failure.We aimed to determine whether left ventricular (LV) myocardial deformation indices can detect subclinical myocardial abnormalities in Kawasaki Disease (KD) convalescence. We hypothesized that subclinical myocardial abnormalities due to inflammation represent an early manifestation of the disease that persist in convalescence.Peak systolic LV myocardial longitudinal, radial and circumferential S and SR Figure  were exaComparisons were made between normal controls and (i) the entire KD group, (ii) KD group subdivided by coronary artery involvement. Table  ComparedIn this CMR-FT study in KD convalescent patients with preserved conventional functional indices, we observed a trend for lower circumferential and longitudinal strain in KD patients compared to normal controls, irrespective of their coronary artery status.The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The Division of Imaging Sciences receives also support as the Centre of Excellence in Medical Engineering  as well as the BHF Centre of Excellence (British Heart Foundation award RE/08/03).