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Aims To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low–middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients. Methods and results A prospective UK–India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P Conclusion For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

The burden of cardiovascular disease in people living with HIV (PLWH) has tripled over the last 20 years, with cardiac manifestations of disease ranging from coronary disease to heart failure (1). The pathophysiological mechanisms involved in the development of HIV cardiomyopathy remain elusive. Subclinical structural and functional changes have been demonstrated in PLWH, but studies that used advanced imaging techniques focused on patients already treated with antiretroviral therapy (ART), potentially limiting the understanding of cardiac manifestations of HIV...

Cardiac Magnetic Resonance (CMR) is a crucial diagnostic imaging test that redefines diagnosis and enables targeted therapies, but the access to CMR is limited in low-middle Income Countries (LMICs...

Cardio-oncology is the care of cancer patients with cardiovascular disease. The need for a dedicated subspecialty emerged to address heart failure caused by drugs such as anthracyclines and anti-human epidermal growth factor receptor 2 (HER2) therapies, but over time has expanded into an exciting subspecialty with widening horizons. While still dealing with a lot of commonly recognised toxicities, such as heart failure, hypertension and coronary disease, new and revolutionary cancer therapies have been associated with challenging cardiovascular complications, requiring specialist input to manage effectively. Echocardiography is a key investigation, with advanced techniques such as three-dimensional and strain assessment allowing more accurate diagnosis and earlier detection of subtle changes. Cardiac magnetic resonance and biomarkers are useful adjuncts to aid diagnosis and management. With increasing cancer incidence and improved cancer survival rates, it is important that general cardiologists and physicians are aware of cardiac complications associated with cancer and how to manage them.

This article provides a review of how rapid Cardiac Magnetic Resonance (CMR) has been used successfully in different clinical settings, outlining the current role of CMR and the unique, incremental information provided in the care of the patient. The article will provide a review of the abbreviated protocols used, future developments and ways to optimize these protocols. A major emphasis of the application of this technology is in Low and Middle-Income Countries (LMICs) where Cardiovascular disease (CVD) is the major cause of morbidity and mortality, however the principles and protocols can be applied across a broad array of clinical platforms. By using a truncated protocol for CMR, most scans can be performed in under 30 minutes, with an average time of 18 minutes for scans which evaluates function and fibrosis (contrast study). A study can be performed within 8 minutes for the assessment of cardiac iron overload (non-contrast study). Rapid CMR can alter clinical management in up to 56% of patients. Rapid CMR protocols do not need state-of-the-art equipment or software. These protocols can be implemented in many centers around the world with appropriate exposure and training. CMR can be performed rapidly without compromising the diagnostic yield of the technique. Rapid CMR can reduce the costs of performing CMR, increase throughput through the scanner and potentially increase the use of the modality in centers worldwide. This could lead to the improvement of clinical care through superior diagnostics and better targeting of therapy.

Cardio-Oncology is the care of cancer patients with cardiovascular disease, overt or occult, already established or acquired during treatment. Cancer patients can present with a variety of cardiovascular problems not all of which are directly related to cancer therapy (medications or radiotherapy). The cardiovascular problems of oncology patients can range from ischaemia to arrhythmias and can also include valve problems and heart failure. As such, within cardiology, teamwork is required with members of different cardiology subspecialties. The way forward will be to adopt a multidisciplinary approach to produce optimal individual care. Close collaboration between cardiology and oncology specialists in a Cardio-Oncology setting can make this happen.

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient.

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

Thalassemia is the most common monogenetic disorder worldwide, with 60 000 infants with thalassemia major born annually.1 Survival often depends on regular blood transfusions to correct anemia and to reduce ineffective erythropoiesis, but these transfusions can result in iron overload and organ failure unless chelation therapy is undertaken. Serum ferritin levels continue to be used as a guide to chelation but are unreliable, and the availability of cardiovascular magnetic resonance (CMR) T2* imaging has transformed patient management by allowing organ-specific quantification of iron content. Countries with a high prevalence of thalassemia major have CMR, but magnet time is expensive and analytic expertise lacking. The aim of TIC-TOC (Thailand and UK International Collaboration in Thalassaemia Optimising Ultrafast CMR) was to investigate whether ultrafast CMR mapping could provide reliable immediate diagnoses of heart and liver iron content, eliminating the need for complex analysis, thus reducing costs to a level within local resources. The research received approval by the Institutional Review Board of the Faculty of Medicine at Chulalongkorn University. All participants provided written informed consent.

PubMed ID: 23812939, Accumulation of myocardial iron is the cause of heart failure and early death in most transfused thalassemia major patients. T2* cardiovascular magnetic resonance provides calibrated, reproducible measurements of myocardial iron. However, there are few data regarding myocardial iron loading and its relation to outcome across the world. A survey is reported of 3,095 patients in 27 worldwide centers using T2* cardiovascular magnetic resonance. Data on baseline T2* and numbers of patients with symptoms of heart failure at first scan (defined as symptoms and signs of heart failure with objective evidence of left ventricular dysfunction) were requested together with more detailed information about patients who subsequently developed heart failure or died. At first scan, 20.6% had severe myocardial iron (T2*?10ms), 22.8% had moderate myocardial iron (T2* 10-20ms) and 56.6% of patients had no iron loading (T2*>20ms). There was significant geographical variation in myocardial iron loading (24.8-52.6%; P

Disorders of haemoglobin synthesis, such as thalassaemia, are the most common monogenetic disorders worldwide. When first described, thalassaemia major (TM) was universally fatal in childhood, but after the adoption of regular blood transfusion, survival until early teenage and adulthood was to be expected. Sadly as these individuals aged organ failure followed, due to the accumulated iron secondary to regular blood transfusion. Principal among the tissues affected by iron overload is the heart and even to the present day, heart disease accounts for the overwhelming majority of premature deaths in this population. For nearly four decades the only available treatment was the demanding regime of parenteral chelation therapy, required on a daily basis, to achieve growth, development and survival with limited or no organ damage. Despite the adoption of these treatment strategies the outlook for thalassaemia patients remained poor, with a 30% to 40% mortality occurring between late teenage and 30 years of age, even in well organised health care systems, such as in the UK, where regular transfusion and deferoxamine (DFO) treatment were readily available. This dreadful early mortality, largely as a consequence of myocardial iron overload, is now improving so that in the UK and other developed nations, heart failure in thalassaemia patients has become uncommon and premature death a much rarer tragedy. This editorial reviews, from a personal viewpoint of a cardiologist involved in the care of these patients for the last 25 years, the progress in the management of the cardiovascular complications of TM, which has followed better techniques of identifying those individuals at greatest risk, improved chelation strategies making best use of the three chelating agents that are now available and improved co-ordinated holistic treatment strategies, derived from a better understanding of this complicated disease state. The first clinical descriptions of thalassaemia as a new disease entity were …

Percutaneous coronary intervention (PCI) has become the predominant procedure for coronary revascularization in patients with both stable and unstable coronary artery disease (CAD). Over the past two decades, technical advances in PCI have resulted in a better and safer therapeutic procedure with minimal procedural complications. However, about 30% of patients undergoing elective PCI sustain myocardial injury arising from the procedure itself, the extent of which is significant enough to carry prognostic importance. The peri-procedural injury which accompanies PCI might therefore reduce some of the beneficial effects of coronary revascularization. The availability of more sensitive serum biomarkers of myocardial injury such as creatine phosphokinase MB isoenzyme (CK-MB), Troponin T, and Troponin I has enabled the quantification of previously undetectable myocardial injury. Peri-procedural myocardial injury (PMI) can also be visualized by cardiac magnetic resonance imaging, a technique which allows the detection and quantification of myocardial necrosis following PCI. The identification of CAD patients at greatest risk of sustaining PMI during PCI would allow targeted treatment with novel therapies capable of limiting the extent of PMI or reducing the number of patients experiencing PMI.

Purpose To use cardiovascular magnetic resonance (CMR) techniques to examine possible causes for the left ventricular (LV) dilatation that occurs in sickle cell disease (SCD), including the effects of chronic anemia, iron-induced cardiomyopathy, and regional fibrosis due to sludge infarcts that occur during sickle crises. Materials and Methods A total of 47 patients with sickle cell anemia were assessed for LV function and myocardial iron levels using CMR measurements; 30 of these were also assessed for regional fibrosis using late gadolinium-enhancement CMR. The LV function was compared to both normal controls and transfusion dependent non-iron-loaded (NIL) thalassemia major (TM) patients. Results Only one SCD patient had significant myocardial iron loading, and only two patients had regional fibrosis. There were significant differences in ventricular volumes of the sickle patients compared with both the normal controls and the NIL-TM population (P < 0.01). Conclusion The LV changes seen in SCD are partly the result of a chronic anemia but there appears to be another contributory factor. This extra factor is not myocardial iron loading or regional fibrosis, although a homogenous fibrotic disorder affecting the left ventricle cannot be excluded. J. Magn. Reson. Imaging 2007;26:564–568. © 2007 Wiley-Liss, Inc.

Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long‐term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia‐reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia‐reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC‐ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC‐ONC trial is a single‐center, blinded, randomized, sham‐controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline‐based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5‐minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high‐sensitivity troponin‐T over 6 cycles of chemotherapy and 12 months follow‐up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N‐terminal pro‐brain natriuretic peptide levels at 3 months follow‐up, and changes in mitochondrial DNA, micro‐RNA, and proteomics after chemotherapy. The ERIC‐ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low‐cost cardioprotectant in cancer patients undergoing anthracycline‐based chemotherapy.

Purpose To compare left ventricular (LV) diastolic function with myocardial iron levels in beta thalassemia major (TM) patients, using cardiovascular magnetic resonance (CMR). Materials and Methods We studied 67 regularly transfused patients with TM and 22 controls matched for age, gender, and body surface area. The early peak filling rate (EPFR) and atrial peak filling rate (APFR) were determined from high-temporal-resolution ventricular volume-time curves. Myocardial iron estimation was achieved using myocardial T2* measurements. Results Myocardial iron loading was found in 46 TM patients (69%), in whom the EPFR correlated poorly with T2* (r = −0.20, P = 0.19). The APFR (r = 0.49, P < 0.001) and EPFR/APFR ratio (r = −0.62, P < 0.001) correlated better with T2*. The sensitivity of the diastolic parameters for detecting myocardial iron loading ranged from 4% (EPFR and APFR) to 17% (EPFR/APFR ratio). Conclusion Myocardial iron overload results in diastolic myocardial dysfunction, but low sensitivity limits the use of a single estimation for early detection of iron overload, for which T2* has a superior categorical limit of normality. J. Magn. Reson. Imaging 2005;22:229–233. © 2005 Wiley-Liss, Inc.

Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron-induced cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5.1 +/- 1.9 to 8.1 +/- 2.8 ms, P = 0.003), liver iron (9.6 +/- 4.3 to 2.1 +/- 1.5 mg/g, P = 0.001), LV ejection fraction (52 +/- 7.1% to 63 +/- 6.4%, P = 0.03), LV volumes (end diastolic volume index 115 +/- 17 to 96 +/- 3 ml, P = 0.03; end systolic volume index 55 +/- 16 to 36 +/- 6 ml, P = 0.01) and LV mass index (106 +/- 14 to 95 +/- 13, P = 0.01). Iron cleared more slowly from myocardium than liver (5.0 +/- 3.3% vs. 39 +/- 23% per month, P = 0.02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.\ud \ud METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.\ud \ud RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p

Hemodynamic performance and core temperature were recorded during transurethral prostatectomy in 52 patients who were stratified according to cardiac symptom score and then randomized to undergo standard (31) or isothermic (21) transurethral prostatectomy. During the standard procedure ambient temperature (21C) irrigant was used, while during isothermic prostatectomy warmed irrigant at 38C was used to prevent heat loss from the bladder, and a warming blanket and humidifying filter were used to decrease cutaneous and respiratory heat loss. Core temperature decreased by a mean of 0.8C (95% confidence interval −0.9 to −0.7) during standard transurethral prostatectomy and by 0.27C (−0.4 to −0.15) during the isothermic procedure. The standard prostatectomy group showed a significant hemodynamic response consisting of increased mean arterial pressure (p

Background— Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited. Methods and Results— Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean±SD global myocardial iron causing severe heart failure in 10 patients was 5.98±2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] ( R 2 =0.910, P −1.22 for the clinical calibration equation with [Fe] in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. Conclusions— These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.

Heat stress limits the injury associated with myocardial ischaemia and reperfusion, an effect previously attributed to enhanced endogenous anti-oxidant activity. We examined the influence of heat stress on the calcium paradox, an injury in which oxidant stress is not thought to play a major role. Twenty-four hours following sham or true heat stress, rabbits were re-anaesthetized and hearts either removed for stress protein analysis (n = 8), or Langendorff-perfused (n = 20) and subjected to a calcium paradox. Ten minutes following calcium repletion (Ca2+ = 1.3 mM), left ventricular developed pressure was better preserved in heat stress vs control hearts (38.3 +/- 5.0 vs 18.8 +/- 4.1 mmHg, respectively, P = 0.003) whilst contracture, measured by left ventricular end-diastolic pressure, was diminished (21.6 +/- 4.7 vs 39.9 +/- 5.2 mmHg, respectively, P = 0.02). Creatine phosphokinase release at 1 min was less in heat stress vs control hearts (10.6 +/- 8.6 vs 86.4 +/- 33.7 U/min/g, respectively, P = 0.01). The myocardial content of the 72 kDa stress protein was elevated eight-fold in heat stress vs control hearts (2.8 +/- 0.2 vs 0.4 +/- 0.1 U, respectively, P = 0.01). This study suggests that some portion of the stress protein response represents a form of cardiac adaptation capable of limiting myocyte injury independent of antioxidant mechanisms.

Aims Myocardial T2* cardiovascular magnetic resonance (CMR) provides a rapid and reproducible measure of cardiac iron loading and is being increasingly used worldwide for monitoring of transfusion-dependent thalassaemia patients. Although myocardial siderosis (T2* 20 ms), the RV ejection fraction (EF) was within the normal range in 98% of patients. When myocardial T2* was

Introduction Beta-thalassemia major (TM) patients have a severe anemia requiring lifelong transfusion to allow normal development and prolong survival. Left ventricular volumes and ejection fraction in these patients differ from the normal population because of chronically increased cardiac output, and this can affect the interpretation of scan results. However, normal ranges for RV parameters and function are unknown.

Background and Purpose —Cerebral embolism with clinical sequelae may rarely complicate cardioversion and cardiac catheterization. Transcranial Doppler sonography has recently been introduced to monitor microemboli entering the middle cerebral artery in cardiac and carotid surgery. We therefore used this technique to evaluate the risk of asymptomatic embolism during common cardiac procedures. Methods —Patients were monitored by transcranial Doppler while undergoing direct current cardioversion (n=15) and cardiac catheterization (n=17). Results —Microemboli were detected in all patients having cardiac catheterization but in only 1 patient after cardioversion. Conclusions —Microembolism occurred frequently during cardiac catheterization and rarely during cardioversion. It is not yet known whether this has clinical relevance.

Background In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis. Methods T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up. Results At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006). Conclusion In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans. Trial registration This trial is registered as NCT00103753

It is believed that myocardial iron deposition and the resultant cardiomyopathy only occur in the presence of severe liver iron overload. Using cardiovascular magnetic resonance, it is now possible to assess myocardial and liver iron levels as well as cardiac function in the same scan, allowing this supposition to be examined. We describe a patient with progressive myocardial iron deposition and the development of early iron overload cardiomyopathy despite excellent compliance to standard subcutaneous desferrioxamine, minimal liver iron and well-controlled serum ferritin levels. These indirect markers remained far below the thresholds conventionally believed to be associated with increased cardiac risk.

Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron-induced cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5.1 +/- 1.9 to 8.1 +/- 2.8 ms, P = 0.003), liver iron (9.6 +/- 4.3 to 2.1 +/- 1.5 mg/g, P = 0.001), LV ejection fraction (52 +/- 7.1% to 63 +/- 6.4%, P = 0.03), LV volumes (end diastolic volume index 115 +/- 17 to 96 +/- 3 ml, P = 0.03; end systolic volume index 55 +/- 16 to 36 +/- 6 ml, P = 0.01) and LV mass index (106 +/- 14 to 95 +/- 13, P = 0.01). Iron cleared more slowly from myocardium than liver (5.0 +/- 3.3% vs. 39 +/- 23% per month, P = 0.02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver.

We assessed the effects of a 6-week exercise programme on the thallium-201 myocardial perfusion characteristics of patients following myocardial infarction.Twenty-five patients presenting with a first acute myocardial infarction were randomised into two groups: (i) those undergoing a supervised exercise training programme over 6 weeks (n=15) and (ii) a control group who did not attend the exercise programme (n=10). All underwent three sequential stress thallium myocardial perfusion scans at 10 days, 6 weeks and 3 months after infarction. The stress conditions were identical on each occasion. The images were analysed using a polar plot with a computer assisted algorithm comparing stress and redistribution data. Values for extent, severity and percentage redistribution of the thallium images were generated.A total of 29 perfusion defects were identified, 18 in the exercise group and 11 in the control group. Over 3 months in the exercise group the mean extent of the stress image defect fell from 109+/-64 to 95+/-51 pixels (P0.05) while in the control group there was an increase from 133+/-57 to 144+/-57 pixels (P=ns). Stress defect severity fell in the exercise group from 581+/-417 to 494+/-346 S.D. (P0.05) but increased in the control group from 765+/-494 to 877+/-543 S.D. (P=ns). On redistribution imaging in the exercise group a significant decrease was observed in both extent (94+/-56 to 76+/-43 pixels (P0.05)) and severity (541+/-387 to 438+/-291 S.D. (P0.05)) of the defects. However in the control group no significant change was observed for extent (125+/-54 to 125+/-52 pixels) or severity (745+/-485 to 820+/-503 S.D.) of the redistribution defects (P=ns). Reversibility of the defects increased slightly in both the exercise group (from 14.6+/-17 to 17.5+/-20%) and the control group (5.2+/-5 to 9.6+10%) (P=ns).Following myocardial infarction a 6-week exercise programme improves myocardial perfusion characteristics. An exercise programme should be integrated into cardiac rehabilitation protocols for patients after infarction.

The aim of this study was to test the hypothesis that acute myocardial ischaemia increases QT dispersion measured from the 12-lead electrocardiogram.Incremental atrial pacing was used to induce myocardial ischaemia in 18 patients with coronary artery disease and QT dispersion was measured. Six patients with normal coronary arteries served as the control group.All the patients with coronary artery disease developed angina and/or ST depression accompanied by marked increases in QT dispersion (mean increase 38 ms, 95% CI 30 to 45 ms, p0.001). In contrast, in the six patients with normal coronary arteries who remained without symptoms and without ST changes, there was no significant change in QT dispersion in response to pacing. Baseline QT dispersion did not distinguish those patients with coronary artery disease from those with normal coronary arteries (44 ms [95% Cl 39-49 ms] vs 40 ms [25-55 ms]), respectively.These results demonstrate that myocardial ischaemia induced by incremental atrial pacing in patients with coronary artery disease causes an acute increase in QT dispersion. Such "inducible" QT dispersion may prove more useful than resting QT dispersion in assessing the individual risk of arrhythmic events in patients with coronary artery disease.

Abstract 1011 Background. CMR was introduced in London to assess myocardial iron loading in 1999 and some of these patients now have 10 years of follow-up, most with contemporary CMR determinations. The impact of long-term monitoring of myocardial iron loading in thalassemia major (TM) on the proportion of patients with increased myocardial iron (cT2* Patients and Methods. All patients regularly attending two London thalassemia centres, who received their first CMR Jan 1999 - Dec 2000 were analyzed as a cohort. Patients underwent initial CMR at the Royal Brompton Hospital and received CMR follow up (FU) either there or at the Heart Hospital (UCLH). 132 patients were identified as having received a CMR in 1999–2000. A minimum 7 years CMR FU was required for inclusion in the long-term CMR analysis. 109 patients had at least 7 years of CMR follow up (range 7.0–10.6 years, median 9.2). The median age at 1st CMR was 27.9 years (range 7.7 – 49.5 years). At baseline, patients were receiving chelation with deferoxamine (DFO) monotherapy (70%), deferiprone (DFP) monotherapy (21%), or a combination of these agents (9%). At latest FU, patients were receiving DFO (32%), deferasirox (DFX) (28%), DFP (22%), or combined DFP and DFO therapy (18%). Results: Improvement in cardiac iron: In 1999–2000, 60% of TM patients had cT2* values ≤20ms and 17% had cT2* values Changes to chelation therapy: 31% of patients stayed on the same chelator; 33% had 1 chelator switch, 26% 2 switches and 11% 3 or more switches. 18 switches in chelation therapy were due to side-effects (12 DFP, 5 DFX, 1 DFO). There were 9 breaks in chelation therapy during pregnancy in 8 different women. The proportions of patients with T2* < 20ms fell significantly for those who remained on DFO or DFP monotherapies throughout, or who changed chelation modalities on only one (p=0.002) or two (p=0.02) occasions. Patients who received had 3 or more switches did not show a improvement in this respect. The latter group was also the only subset that showed significant deterioration in myocardial iron (p Mortality rates: the overall mortality rate for the initial cohort was 1.65 per 1000 patient years (95% CI 0.71 – 3.24); median age at death 35.6 years (range 27.3–48.4). This is a substantial improvement in the mortality index compared with the UK thalassemia registry data, of 4.3 per 1000 patient years during the period 2000–2003 (Modell et al, JCMR, 2008). The incidence rate ratio is 0.387 (95% CI 0.11–0.961), p Causes of death: there were 8 deaths during the FU period: 3 with complications of hepatitis C (all with cT2* > 20ms), 3 with sepsis (2 with cT2* 20ms). Thus in only 2 patients could excessive cardiac iron loading be considered a causal/contributory factor. There was no significant difference in the baseline cT2* between those who died and those currently still alive (p= 0.2), meaning that death as a drop-out cause does not explain iron loading trends over FU. Chelators at death: DFO (4), DFP (2), DFX (1), combination (1). Conclusions: Over a decade we have seen an almost 3 fold fall in the proportion of patients with myocardial iron overload. Mortality has become substantially lower and cardiac iron overload is no longer the leading cause of mortality. In addition to CMR, this decade has seen the advent of two new oral iron chelators and many patients switched chelation regimen, sometimes several times, during the follow up period. Whilst the contribution of the individual components of this practice to the improved outcome cannot be concluded without randomized studies, it is clear that this modern management of TM is associated with reduced TM mortality. Disclosures: Off Label Use: Deferiprone is off label in the USA but licensed in Europe. Shah:Novartis: Honoraria, Speakers Bureau; Apotex/ Swedish Orphan: Honoraria. Pennell:Siemens: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Apotex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cardiovascular Imaging Solutions: Director of CVIS, Equity Ownership. Porter:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Cine magnetic resonance imaging (MRI) provides a tomographic method of assessing regional ventricular function in any desired plane. It has not been possible to obtain adequate images during dynamic exercise, and this has limited its value in patients with coronary artery disease (CAD). Therefore, an infusion of dobutamine was used to study 25 patients with exertional chest pain and abnormal exercise electrocardiograms. Areas of abnormal wall motion were compared with areas of abnormal myocardial perfusion imaged by dobutamine thallium emission tomography and with coronary arteriography. Twenty-two patients had significant CAD. Twenty-one (96%) of these patients had reversible myocardial ischemia shown by dobutamine thallium tomography, and 20 (91%) had reversible wall motion abnormalities shown by dobutamine MRI. Comparison of abnormal segments of perfusion and wall motion showed 96% agreement at rest, 90% agreement during stress, and 91% agreement for the assessment of functional reversibility. The normalized magnetic resonance signal intensity of the ischemic segments showed a small but significant reduction when compared with that of normal segments (-67 units [9.2%]; p less than 0.05). Dobutamine infusion was well-tolerated, despite causing chest discomfort in 24 patients (96%). Nine patients (36%) developed a minor dysrhythmia that was usually ventricular premature complexes, but this did not limit infusion, and other side effects were mild. The short plasma half-life of dobutamine makes it ideal as a stress agent for imaging techniques (such as MRI), and these results suggest that it is more effective in the provocation of wall motion abnormalities than is dipyridamole in patients with CAD.

Abstract 2012 Poster Board I-1034 Background: Cardiovascular magnetic resonance (CMR) is being increasingly used worldwide for monitoring chelation therapy in transfusion-dependent β-thalassemia patients. The assessment of cardiac iron loading using myocardial T2 star (T2*) is a reliable, quick and non-invasive method which can be combined with highly accurate and reproducible cardiac volume and function measurements. It has previously been noted that myocardial siderosis (T2* Methods: A retrospective analysis was performed of 323 consecutive β-thalassemia patients referred for their first CMR scan from 21 UK hematology centers. Only patients on a single chelating agent (deferoxamine) were included. All had received chelation from the mid-to-late 1970s or from an early age if born since then. Patients were excluded if there was significant cardiac, vascular or lung pathology (such as aortic stenosis, pulmonary artery stenosis, tetralogy of Fallot or pulmonary hypertension). All scans were performed using a 1.5T Sonata (Siemens Medical Systems, Germany). A single breath-hold multi-echo sequence with 8 different echo times (TE = 2.54-17.9ms) was used to measure T2* from a full-thickness region of interest in the septum of a mid-ventricular short axis slice. Myocardial T2* was calculated from the exponential signal intensity decay curve using a truncation method to account for background noise. RV and LV volumes and ejection fraction (EF) were calculated from a series of short axis ventricular slices (7mm thickness with 3mm gap). Results: In patients with normal T2* (>20ms), RV EF was within normal limits in 98% of cases (RV EF [mean ±SD] = 65.0 ±6.1%). In patients with myocardial siderosis (T2*20ms (LV EF = 69.5 ±5.2%). Once again, where T2* fell below 20ms, there was a progressive decline in LV EF (r=0.40, p Conclusions: There is a strong association between increasing myocardial iron loading and RV dysfunction which mirrors the decrease in LV ejection fraction seen with worsening myocardial siderosis. RV impairment may be a significant contributor to the syndrome of heart failure associated with severe myocardial siderosis. Disclosures: Carpenter: Swedish Orphan: Honoraria; Apotex: Honoraria. Porter:Novartis: Consultancy, Research Funding. He:Novartis: Consultancy. Smith:Novartis: Consultancy. Pennell:Siemens: Consultancy; Novartis: Consultancy; Apotex: Honoraria; Cardiovascular Imaging Solutions, London: Equity Ownership.

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 μg/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion.Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p < 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p < 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p < 0.001), but a wide range of exercise times was achieved in the 15- and 20-μg/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.Dobutamine thallium myocardial perfusion tomography is a useful technique for the detection, localization and assessment of myocardial ischemia, particularly when exercise potential is limited. Both the safety of dobutamine in asthmatic patients and the relation between achieved dose and exercise time represent advantages over the use of adenosine or dipyridamole.

We report the case of a 20-year-old man born with transposition of the great arteries who underwent emergency balloon septostomy and subsequently a Mustard procedure. When aged 20 years, he had several syncopal attacks due to sinoatrial disease for which he was simply and successfully paced transvenously in VVI mode.

Background: In β-thalassemia major (TM) myocardial iron toxicity is the dominant cause of ventricular dysfunction, with heart failure responsible for the majority of deaths. Abnormal endothelial function has also been described in these patients and could further contribute to cardiovascular complications. Endothelial function can be determined by measurement of flow mediated dilatation of the brachial artery (FMD). This can be assessed reproducibly by cardiovascular magnetic resonance (CMR). Aims: To report the changes in endothelial function, LV ejection fraction and ferritin from a randomized placebo controlled trial comparing combined chelation therapy (deferiprone and deferoxamine) with deferoxamine monotherapy. Methods: 65 patients (male 27, female 38, age 28.7+/−4.8years) with mild-moderate myocardial iron loading (heart T2* 8–20ms) were randomized to receive either deferoxamine with placebo (placebo group), or deferoxamine with deferiprone (combined group). FMD was assessed at baseline and after 12 months. Results: There were significant improvements in endothelial function in the combined treatment group compared with the placebo group (+8.8% vs 3.1% p=0.013). This was in accord with improvements in the combined group in left ventricular ejection fraction (+2.4% vs +0.6%, p=0.02), and serum ferritin (−870 vs −194 μg/L; p Conclusion: In patients with mild-moderate cardiac iron loading, the combined therapy of deferiprone and deferoxamine is superior to deferoxamine alone in improving endothelial function, cardiac function and ferritin, as well as reducing myocardial iron.

A model of the formation of faculty attitudes toward collective bargaining is developed which reflects recent developments in theory and research in organizational behavior. The model is an alternative to those grounded in need-satisfaction theories and takes into account interaction effects among variables. Hypotheses are formulated which explore how faculty members develop: (1) beliefs about, and effective responses toward, their work environment; and (2) propensities to wish to change that environment by implementating collective bargaining. Empirical data are analyzed to assess the main effects of, and interactions among, organizational commitment, perceived personal efficacy, and expectations with respect to the impact of bargaining.

Using a panel study approach, this paper builds upon the Getman, Goldberg, and Herman investigation of the impact of campaign activity on voting preferences in union representation elections. The c...