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To describe the overlap between structural abnormalities typical of arrhythmogenic right ventricular cardiomyopathy (ARVC) and physiological right ventricular adaptation to exercise and differentiate between pathologic and physiologic findings using CMR. We compared CMR studies of 43 patients (mean age 49 ± 17 years, 49% males, 32 genotyped) with a definitive diagnosis of ARVC with 97 (mean age 45 ± 16 years, 61% males) healthy athletes. CMR was abnormal in 37 (86%) patients with ARVC, but only 23 (53%) fulfilled a major or minor CMR criterion according to the TFC. 7/20 patients who did not fulfil any CMR TFC showed pathological finding (RV RWMA and fibrosis in the LV or LV RWMA). RV was affected in isolation in 17 (39%) patients and 18 (42%) patients showed biventricular involvement. Common RV abnormalities included RWMA (n = 34; 79%), RV dilatation (n = 18; 42%), RV systolic dysfunction (≤ 45%) (n = 17; 40%) and RV LGE (n = 13; 30%). The predominant LV abnormality was LGE (n = 20; 47%). 22/32 (69%) patients exhibited a pathogenic variant: PKP2 (n = 17, 53%), DSP (n = 4, 13%) and DSC2 (n = 1, 3%). Sixteen (16%) athletes exceeded TFC cut-off values for RV volumes. None of the athletes exceeded a RV/LV end-diastolic volume ratio > 1.2, nor fulfilled TFC for impaired RV ejection fraction. The majority (86%) of ARVC patients demonstrate CMR abnormalities suggestive of cardiomyopathy but only 53% fulfil at least one of the CMR TFC. LV involvement is found in 50% cases. In athletes, an RV/LV end-diastolic volume ratio > 1.2 and impaired RV function (RVEF ≤ 45%) are strong predictors of pathology.

Aims\ud CKD‐HF patients suffer excess hospitalization and mortality, often under‐treated with life‐prolonging medications due to fear of worsening renal function and hyperkalaemia. Yet, role of inter‐disciplinary working in improving therapy is unknown, which this study aims to investigate.\ud \ud Methods and results\ud Clinical, biochemical data, and medications at first and last clinic visit were obtained from patient records for 124 patients seen in kidney failure–heart failure clinic (23 March 2017 to 11 April 2019). Medication dose groups (none, low, and high dose), number of RAASi agents, and blood test results were compared between first and last visit in patients with at least two clinic visits (n = 97). Patient characteristics were age 78.5 years (IQR 68.1–84.4 years), male 67.7%, diabetes 51.6%, moderate (45.2%) vs. severe (39.5%) CKD, HF with reduced ejection fraction (HFrEF) (49.2%), follow‐up 234 days (IQR 121–441 days). HFrEF was associated with increased risk of death (adjusted OR 4.49, 95% CI 1.43–14.05; P = 0.01).\ud \ud Distributions of patients according to number of RAASi agents they were on differed between first and last visit (P = 0.03). Dosage was increased in 25.9% for beta‐blockers, 33.0% for ACEi/ARBs, and 17.5% for MRAs. Distributions of patients across MRA dosage groups was different (P = 0.03), with higher proportions on higher dosages at last visit, without significant changes in serum potassium or creatinine. Serum ferritin improved (131.0 vs. 267.5 μg/L; P < 0.001), and fewer patients had iron deficiency (56.7% vs. 26.8%; P = 0.002) at last visit compared to the first.\ud \ud Conclusions\ud This inter‐disciplinary clinic improved guideline‐recommended medication prescription, MRA dosages in CKD‐HF patients without significant biochemical abnormality, and iron status. A prospectively designed study with medication titration protocol and defined patient‐centred outcomes is needed to further assess effectiveness of such clinic.

Aims Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. Methods and results Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff–Parkinson–White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. Conclusion Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

Background CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy. Methods We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants’ RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George’s Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline. Discussion This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded. Trial registration EudraCT number 2020–002946-18. Registered on 08 June 2020. Online record pending.

Background and Aims The presence of CKD impacts short term survival of heart failure patients however impact on long term survival is not well known. The aim of this study was to investigate the impact of CKD on long term survival. Method Data were collected on long term survival of 845 patients (1029 admissions) admitted with diagnosis with acute heart failure. Data on mortality was collected by electronic patient records. Data were analysed using IBM SPSS 25. Results The baseline characteristics were: age 76 (13) mean (SD); Haemoglobin 11.8 (2), urea 37.2 (26.8), eGFR 63.3 (30.4), potassium 4.34 (0.70) and 36% diabetics, 567 patients (67%) died during follow up of median 916 days (IQR 188-1936 days). Patients who died were older, with higher urea, creatinine, potassium and NT proBNP. In a survival analysis adjusted for diabetes and haemoglobin; age, urea, NT-proBNP baseline eGFR and potassium predicted mortality (see table). CKD patients with eGFR 60 (log rank p=0.000) (see figure 1) Conclusion Long term mortality in patients with CKD was higher which was an independent predictor of survival

Background There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease. Objective The purpose of this study was to characterize patients with Brugada syndrome (BrS) using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Methods BrS was diagnosed according to international guidelines. Twenty-six percent of patients with BrS carried SCN5A mutations. CMR data from 78 patients with BrS were compared with 78 healthy controls (44 ± 15 vs 42 ± 14 years; P = .434; and 64% vs 64% male; P = 1). Results Right ventricular (RV) ejection fraction was slightly lower (61 ± 8% vs 64 ± 5%; P = .004) and RV end-systolic volume slightly greater (31 ± 10 mL/m2 vs 28 ± 6 mL/m2; P = .038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% of patients with BrS (left ventricular midwall LGE in 5%) but not in controls (P = .028). In patients with BrS with midwall LGE there were no other features of cardiomyopathy at the time of CMR, but genetic testing and follow-up revealed a desmoplakin mutation in 1 patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy. Conclusion Some patients with BrS have left ventricular midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

Background The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging and some structural abnormalities typical of the disease may overlap with changes reflective of cardiac adaptation to exercise. Purpose The aim of the study was to assess the performance of the cardiac magnetic resonance (CMR) 2010 Task Force Criteria (TFC) in a cohort of patients with definite diagnosis of ARVC and define the overlap with a cohort of highly trained athletes of similar age and sex. Methods We compared the CMR features of 43 patients (mean age 49±17 years, 49% males, 32 (74%) genotyped) with a definite diagnosis of ARVC according to the revised TFC to 97 (mean age 45±16 years, 61% males) highly-trained athletes of similar age and sex, in whom cardiac disease was excluded after comprehensive work-up. Results The CMR was abnormal in 37 (86%) patients. The right ventricle (RV) was affected in isolation in 17 (39%) patients, with 18 (42%) patients exhibiting biventricular involvement and 2 (5%) patients showing isolated left ventricular (LV) involvement. The most common RV abnormalities were regional wall motion abnormalities (RWMA) (n=34; 79%), RV dilatation fulfilling a major or minor volume TFC (n=18; 42%), impaired systolic function (RV ejection fraction (EF) ≤45%: n=17; 40%) and myocardial fibrosis (n=13; 30%). The predominant LV abnormality was myocardial fibrosis (n=20; 47%), with a small proportion of patients exhibiting RWMA (n=6; 14%) and impaired systolic function (LVEF Conclusions The great majority (86%) of patients with ARVC demonstrates structural abnormalities suggestive of cardiomyopathy on CMR but only 53% fulfills any of the CMR TFC. Only a small proportion (16%) of older athletes demonstrate significant RV dilatation that overlaps with the volume criteria for ARVC, in juxtaposition to younger athletes who exhibit a greater degree of overlap. The emergence of ARVC as a biventricular disease provides an opportunity to re-evaluate the diagnostic criteria and include LV involvement in conjunction with RV involvement to improve diagnostic accuracy. Acknowledgement/Funding CRY (Cardiac Risk in the Young) charity

Background Structural cardiac adaptations due to hypertension (HTN) present a diagnostic challenge when differentiating from hypertrophic cardiomyopathy (HCM), using traditional imaging techniques such as echocardiography (echo). Cardiac magnetic resonance imaging (CMR) offers reproducible anatomical, functional quantification and myocardial tissue characterisation which discriminates between hypertension and HCM. Purpose To identify hypertensive individuals with undiagnosed HCM using CMR imaging. Methods 100 consecutive hypertensive patients underwent CMR at a tertiary centre dedicated blood pressure clinic (55% male, mean age 51 years). In keeping with ESC guidelines, end diastolic wall thickness (EDWT) ≥15mm identified individuals within the “grey zone” between hypertension and with a potential HCM diagnosis. 19 individuals were referred on to the dedicated inherited cardiac conditions clinic for further evaluation. Four patients expressed a definitive LV phenotype and were diagnosed with HCM. CMR parameters were compared in three groups: Hypertensive (HTN), “grey zone” Hypertensive (GZH) and HCM. Results CMR demonstrated end diastolic wall thickness (EDWT) >11 mm in 50% of hypertensives. 73% of the referred patients were Afro-Caribbean (AC) and all 4 HCM patients were AC. All referrals demonstrated EDWTs ≥14mm, 9 (47%) demonstrated late gadolinium enhancement of which 3 (16%) had HCM. Three had asymmetrical septal hypertrophy – 2 were in the HCM cohort and one underwent endomyocardial biopsy confirming HTN. Left ventricular mass index (LVMI) was significantly higher in GZH compared to HTN (p Table 1. P-values for CMR data in hypertensive (HTN), gray zone hypertensive (GZH) and hypertrophic cardiomyopathy (HCM) cohorts CMR Parameter HCM vs. HTN GZH vs. HTN GZH vs. HCM EDVI NS p=0.025 NS EDWT p=0.0002 p Conclusion This study reports a 4% prevalence of HCM among hypertensive patients - 20 x greater than in the general population - which would be left undiagnosed using echo alone. Screening hypertensive individuals with CMR is not routine but we advocate its use in these individuals especially in Afro Caribbeans and in those in the “grey zone”, to identify undiagnosed HCM, which has significant implications for lifestyle modification and family screening. Acknowledgement/Funding Cardiac Risk in the Young

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) has recently published a review of the care received by patients who died in UK hospitals following an admission with acute heart failure (HF).1 A sample of up to six adults who died during an admission to each hospital in the UK in 2016 was selected, with a total of 603 deaths being examined in detail by a multidisciplinary group of case reviewers. Various aspects of care, both organisational and clinical, were reviewed and graded as either good practice, room for improvement or less than satisfactory. There were six principal recommendations, shown in the box 1.Box 1 ### Principal recommendations of the NCEPOD review of HF deaths in UK hospitals1 1. An acute HF clinical guideline should be available in all hospitals. Care should be in a specialist unit, with HF team review within 24 hours, a standard protocol for diagnosis including natriuretic peptide (NP) testing and echocardiography, and medication guidance for immediate treatment prior to specialist review. 2. All HF patients should have access to a HF multidisciplinary team, including a cardiologist, specialist HF nurse, pharmacist, palliative care specialist and a member of the primary care team, with other services (including elderly care, clinical psychology, physio- or occupational therapists, cardiac rehabilitation) as appropriate. 3. Serum NP should be included in the first set of blood tests in all patients with acute breathlessness who do not have a past diagnosis of HF. 4. An echocardiogram should be performed for all patients with suspected AHF …

Background Non-ischaemic cardiomyopathy has been associated with better left ventricular (LV) remodelling and outcomes post-cardiac resynchronisation therapy (CRT) but has separately been linked to poorer outcomes when associated with mid-wall fibrosis (MWF) on cardiac magnetic resonance. Therefore, we aimed to confirm the impact of MWF in patients with non-ischaemic cardiomyopathy and CRT. Methods We retrospectively evaluated data from 164 consecutive patients with a diagnosis of non-ischaemic cardiomyopathy and CRT implants. Non-eligible patients were excluded (eg. ischaemic, amyloid or sarcoid cardiomyopathy, missing data). Patients with or without mid wall fibrosis (MWF+, n=69 vs MWF-, n=99), were compared and evaluated for major cardiovascular event (including all-cause mortality or hospitalizations for ventricular arrthythmias, heart failure or myocardial infarction) from time of CRT implant. Results were reported as mean ± SD. p≤0.05 was deemed statistically significant. Results Mean age of patient cohort was 66 ± 14 years with total follow-up duration of 1140 ± 1018 days. Between the groups, no significant difference in baseline demographics was observed in terms of age, gender, comorbidities (hypertension/diabetes), medication profiles, electrocardiographic measures (intrinsic rhythm and QRS duration). MWF+ demonstrated lower LV ejection fraction (28 ± 10 vs 31 ± 13%, p=0.02) and higher LV end-systolic volume (211 ± 90 vs. 181 ± 96 ml, p=0.05) when compared to MWF-. However, there were no significant differences between MWF+ vs MWF- in terms of all-cause mortality (34% vs 24%, see Figure 1), or hospitalisations for ventricular arrhythmia (5% vs 2%) or heart failure (18% vs 22%), respectively. Conclusion This retrospective study demonstrated that MWF+ was associated with lower LV ejection fraction and higher LV end-systolic volumes compared to MWF-. However, we observed no significant between-group diferrence in major adverse cardiovascular events. Further evaluation of this patient cohort in larger studies is warranted. Conflict of Interest Nil

Background Structural cardiac adaptations caused by hypertension present a diagnostic challenge when differentiating from hypertrophic cardiomyopathy (HCM), using traditional imaging techniques such as echocardiography (echo). Cardiac magnetic resonance imaging (CMR) offers reproducible anatomical, functional quantification as well as myocardial tissue characterisation which discriminates between hypertension and HCM. Purpose To identify hypertensive individuals with undiagnosed HCM using CMR imaging. Methods 100 consecutive African Caribbean (AC) and Caucasian hypertensive patients underwent CMR at a tertiary centre dedicated blood pressure clinic (55% male, mean age 51 years). In keeping with ESC guidelines, end diastolic wall thickness (EDWT) ≥ 15mm identified individuals within the “grey zone” between hypertension and with a potential HCM diagnosis.19 individuals were referred on to the dedicated inherited cardiac conditions clinic for further evaluation. Four patients expressed a definitive LV phenotype and were diagnosed with HCM. CMR parameters were compared in three groups: Hypertensive (HTN), grey zone Hypertensive (GZH) and HCM. See figure 1 and table 1. Results CMR demonstrated end diastolic wall thickness (EDWT) >11 mm in 50% of hypertensives. 73% of the referred patients were AC and all 4 HCM patients were also AC. All referrals demonstrated EDWTs ≥14mm, 9 (47%) demonstrated late gadolinium enhancement of which 3 (16%) had HCM. Three had asymmetrical septal hypertrophy – 2 were in the HCM cohort and one underwent endomyocardial biopsy confirming HTN. Left ventricular mass index (LVMI) was significantly higher in GZH compared to HTN (p Conclusion This study reports a 4% prevalence of HCM among hypertensive patients - 20 × greater than in the general population - which would not be diagnosed using echo alone. Screening hypertensive individuals with CMR is not yet routine but we advocate its use in these individuals especially in those of AC ethncitiy and in those in the “grey zone”, to identify undiagnosed HCM, which has significant implications for lifestyle modification and family screening. Conflict of Interest none

Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non-specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point-of-care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short-term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre- and post-discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure.

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

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson–Fabry disease is emerging.

BACKGROUND: There is a need for improved worldwide access to tissue iron quantification using T2* cardiovascular magnetic resonance (CMR). One route to facilitate this would be simple in-line T2* analysis widely available on MR scanners. We therefore compared our clinically validated and established T2* method at Royal Brompton Hospital (RBH T2*) against a novel work-in-progress (WIP) sequence with in-line T2* measurement from Siemens (WIP T2*). METHODS: Healthy volunteers (n = 22) and patients with iron overload (n = 78) were recruited (53 males, median age 34 years). A 1.5 T study (Magnetom Avanto, Siemens) was performed on all subjects. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used to acquire both RBH T2* images and WIP T2* maps for each participant. Cardiac white blood (WB) and black blood (BB) sequences were acquired. Intraobserver, interobserver and interstudy reproducibility were measured on the same data from a subset of 20 participants. RESULTS: Liver T2* values ranged from 0.8 to 35.7 ms (median 5.1 ms) and cardiac T2* values from 6.0 to 52.3 ms (median 31 ms). The coefficient of variance (CoV) values for direct comparison of T2* values by RBH and WIP were 6.1-7.8 % across techniques. Accurate delineation of the septum was difficult on some WIP T2* maps due to artefacts. The inability to manually correct for noise by truncation of erroneous later echo times led to some overestimation of T2* using WIP T2* compared with the RBH T2*. Reproducibility CoV results for RBH T2* ranged from 1.5 to 5.7 % which were better than the reproducibility of WIP T2* values of 4.1-16.6 %. CONCLUSIONS: Iron estimation using the T2* CMR sequence in combination with Siemens' in-line data processing is generally satisfactory and may help facilitate global access to tissue iron assessment. The current automated T2* map technique is less good for tissue iron assessment with noisy data at low T2* values.

Background— It has been reported that subjects of African descent present with heart failure at a younger age and because of different causes than whites. We present contemporary data from UK Afro-Caribbean patients in London. Methods and Results— All patients with heart failure presenting to St George’s Hospital Heart Failure clinic between 2005 and 2012 were included (n=1392). Patients were predominantly white (71%) and male (67%), and median age at presentation was 73 years (range, 18–100 years). In 211 Afro-Caribbean patients, the most common cause of heart failure was nonischemic dilated cardiomyopathy in 27.5% (whites, 19.9%; P P Conclusions— In London, the cause of heart failure varies depending on ethnicity and affects age of presentation and outcomes. In Afro-Caribbean patients, ATTR V122I is an underappreciated cause of heart failure, and cardiomyopathy is often misattributed to hypertension. As promising TTR therapies are in development, increased awareness and proactive detection are needed.

Aims To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. Methods and Results We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Conclusions Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality.

About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date.Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size.We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen (P.05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing.Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.

A 59-year-old woman presented with a sudden onset of breathlessness and chest pain. An echocardiography and CT scan showed pulmonary embolism and infarction with a paradoxical thrombus visualised in both atria. For haemodynamically stable patients, the optimal management strategy is poorly defined. Three main strategies were considered: surgical thrombectomy, thrombolysis and anticoagulation. Surgery with reversal of anticoagulation may lead to further coagulation and increased risk of bleeding complications. The significant pulmonary hypertension and right ventricular infarction raised the prospect of difficult weaning from cardiopulmonary bypass following thrombectomy. Thrombolysis, which has significant mortality rate, and systemic embolisation including pulmonary infarction with haemorrhagic transformation were also contraindications. A multidisciplinary approach was adopted and anticoagulation was therefore believed to be the safest and effective approach. Here, the use of anticoagulation alone was fortunately successful but could as easily end in disaster. This approach should be considered the ideal paradigm to yield optimum outcomes.

Echocardiography has a leading role in the routine assessment and diagnosis of hypertrophic ventricles. However, the use of M-mode echocardiography and measurement of global left ventricular function may be misleading. Traditionally, systolic function was thought to be preserved in patients with hypertrophic myopathies until the late stages of the disease, and hypertrophic myopathies were thought to affect the myocardium more diffusely than ischemic heart disease. Ultrasound deformation imaging, either by Doppler myocardial imaging or speckle tracking, provides more-sensitive detection of regional myocardial motion and deformation than standard echocardiography. Basic and clinical studies that apply these techniques have revealed early, often subclinical impairment in systolic function. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance. Physiological hypertrophic remodeling seen in athletes differs from pathological myocardial hypertrophy, which can be caused by compensatory reactive hypertrophy owing to pressure overload in patients with aortic stenosis or hypertension, as well as amyloidosis, Fabry disease or Friedreich ataxia. Each of the etiologies associated with hypertrophy demonstrate distinct regional changes in myocardial deformation, which allows identification of the underlying processes, and will improve the assessment and follow-up of patients with hypertrophic myopathies.

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.

Purpose To develop a reproducible fast spin-echo (FSE) technique for accurate myocardial T2 measurement with application to iron overload assessment in thalassemia. Materials and Methods An FSE sequence was developed to permit acquisition of multiple TE images in one breathhold (BH-FSE). A dynamic black-blood scheme was introduced to better cancel blood signal. A nonselective refocusing train was also adopted to suppress stimulated echoes. The optimized technique was tested on phantoms and then applied to 10 normal volunteers and 10 thalassemia patients. Interstudy reproducibility was measured on all the 20 subjects. Results The mean difference in T2 values was 1.7% from phantom experiments between BH-FSE and the conventional spin-echo (SE) technique. High contrast BH-FSE images were acquired from human subjects, with minimal stimulated echoes and effective blood suppression (P = 0.0005). The coefficient of variation for interstudy reproducibility was 4.3%. T2 values from thalassemia patients were substantially lower than those from the normal subjects (45.2 ± 26.1 msec vs. 56.9 ± 8.4ms, P = 0.02). Conclusion The dynamic black-blood T2 sequence is a fast reproducible acquisition that compares favorably with conventional techniques, is robust to motion artifacts, and yields high blood-myocardium contrast. This technique may provide a useful tool in thalassemia and other scenarios requiring myocardial T2 quantification. J. Magn. Reson. Imaging 2006. © 2006 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.

Introduction Current intervention criteria for the thoracic aorta concentrate on size. However, the complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are reached. Computational fluid dynamics (CFD) is a non-invasive approach to quantify haemodynamics in assessment of aneurysms and rupture risk. Wall shear stress (WSS) measuring viscous shearing forces on the endothelium, and oscillatory shear index (OSI) measuring disturbed flow, are a pathophysiological stimulus to gene expression, extracellular-matrix remodelling, and aortic wall thinning. We aimed to evaluate the efficacy of a new patient-specific approach to CFD of the thoracic aorta, and its functional and haemodynamic indices in assessment of aortic pathology. Methods 45 subjects were divided into 5 groups: Volunteers, AR-TAV, AS-TAV, AS-BAV(RL), AS-BAV(RN), where AR=aortic regurgitation, AS=aortic stenosis, TAV=tricuspid aortic valve, BAV=bicuspid aortic valve, RL=right-left cusp fusion, RN=right-non cusp fusion. Subjects underwent magnetic resonance angiography, with phase-contrast MRI at the sino-tubular junction to define patient-specific inflow velocity profiles. Three-dimensional aorta models were constructed from MRA data and discretized to form a finite element mesh. The 3D velocity profile from PC-MRI was mapped onto the inflow mesh, allowing prescription of patient-specific inflow boundary conditions. Blood pressure, cardiac output, and cross-sectional area of each vessel were processed to assign outflow boundary conditions to arch vessels and descending aorta. Results CFD enabled measurement of WSS throughout the thoracic aorta. WSS was significantly elevated in aortic stenosis, highest in AS-BAV(RN) (mean WSS=37.1 ± 4.0 dyn/cm2, compared to 19.9 ± 1.9 dyn/cm2 for AS-BAV(RL), 25.7 ± 1.2 dyn/cm2 in AS-TAV, 12.3 ± 3.4 dyn/cm2 in AR-TAV, and 9.9 ± 5.4 dyn/cm2 in healthy volunteers, p Eccentricity of flow was higher in bicuspid patients (Flowasymmetry= 84.1 ± 5.4%, compared to 28.1 ± 21.5 for tricuspids, p Conclusions BAV displays eccentric flow with high helicity. Presence of AS, particularly in BAV-RN led to higher WSS and lower OSI in the greater curvature of the ascending aorta. Patient-specific CFD provides non-invasive functional assessment of the thoracic aorta, and enables development of a personalized approach to diagnosis and management of aortic disease beyond traditional guidelines.

Purpose To assess interscanner reproducibility of tissue iron measurements in patients with thalassemia using gradient echo T2* measurements on two different MRI scanners. Materials and Methods Twenty-five patients with thalassemia major had liver and myocardial T2* assessment using a Picker Edge 1.5T Scanner and a Siemens Sonata 1.5T scanner, with similar gradient echo sequences. In a subset of 13 patients, two scans on the Siemens scanner were performed to assess interstudy reproducibility. Results There was a highly significant, linear correlation between T2* values obtained for both the heart (r = 0.95) and the liver (r = 0.99) between scanners. The mean difference, coefficient of variability, and 95% confidence intervals between scanners were 0.8 msec, 9.4% and –5.0 to 6.7 msec for the heart; and 0.9 msec, 7.9% and –2.0 to 3.9 msec for the liver. The interstudy mean difference and coefficient of variability on the Siemens scanner was 0.3 msec and 4.8% (r = 0.99) for the heart, and 0.04 msec and 1.9% (r = 0.99) for the liver. Conclusion The T2* technique for measuring tissue iron is reproducible between the two manufacturers' scanners. This suggests that the widespread implementation of the technique is possible for clinical assessment of myocardial iron loading in thalassemia. J. Magn. Reson. Imaging 2003;18:616–620. © 2003 Wiley-Liss, Inc.

ObjectivesThe complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific computational fluid dynamics (CFD) was used to assess effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS) and oscillatory shear index (OSI) in the thoracic aorta.Methods45 subjects were divided into 5 groups: Volunteers, AR-TAV, AS-TAV, AS-BAV(RL), AS-BAV(RN), where AR=aortic regurgitation, AS=aortic stenosis, TAV=tricuspid aortic valve, BAV=bicuspid aortic valve, RL=right-left cusp fusion, RN=right-non cusp fusion. Subjects underwent magnetic resonance angiography, with phase-contrast MRI at the sino-tubular junction to define patient-specific inflow velocity profiles. Hemodynamic recordings were used alongside MRI angiographic data to run patient-specific CFD.ResultsBAV groups had larger mid-ascending aorta diameters (pasymmetry=78.9±6.5% for AS-BAV(RN), compared to 4.7±2.1% for Volunteers, p2, compared to 9.8±5.4 for Volunteers, pConclusionsBAV displays eccentric flow with high helicity. Presence of AS, particularly in BAV-RN led to higher WSS and lower OSI in the greater curvature of the ascending aorta. Patient-specific CFD provides non-invasive functional assessment of the thoracic aorta, and may enable development of a personalized approach to diagnosis and management of aortic disease beyond traditional guidelines.

We thank Barison et al. for their interest in our paper [(1)][1]. Cardiac amyloidosis is gaining significant exposure in the cardiac magnetic resonance (CMR) community because of the characteristic and near pathognomonic findings with the technique. We reported the first study that specifically

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

This report describes proarrhythmia, a rare but in this case fatal complication of ICD therapy due to lead failure.

Aims Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. Methods and results We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [–1407 pg/mL, interquartile range (IQR) –3042 to –346 pg/mL] compared with those requiring

A 53-year-old woman with a history of ventricular ectopic ablation was admitted with weight loss, sweats and low grade fever and was found to have severe aortic incompetence and a dilated left ventricular cavity (6.1 cm) on transthoracic echocardiography (figure 1). No vegetations were seen on transoesophageal echocardiography and sequential blood cultures were negative. Despite extensive investigation she continued to deteriorate clinically and had a persistently elevated C reactive protein and erythrocyte sedimentation rate at 300 mg/l and 108 mm/h respectively. A positron emission tomography (PET)-CT scan with 18F-fluorodeoxyglucose (FDG) …

Cardiac amyloidosis of transthyretin fibril protein (ATTR) type is an infiltrative cardiomyopathy characterised by ventricular wall thickening and diastolic heart failure. Increased access to cardiovascular magnetic resonance imaging has led to a marked increase in referrals to our centre of Caucasian patients with wild-type ATTR (senile systemic) amyloidosis and Afro-Caribbean patients with the hereditary ATTR V122I type. Both subtypes present predominantly as isolated cardiomyopathy. The differential diagnosis includes cardiac amyloid light-chain (AL) amyloidosis, which has a poorer prognosis and can be amenable to chemotherapy. We review here the clinical features of cardiac ATTR amyloidosis and describe the diagnostic tests to determine ATTR type. Correct diagnosis is ever more crucial given that several novel therapies for ATTR amyloidosis are on the near horizon.

T2* is a magnetic relaxation property of any tissue and is inversely related to intracellular iron stores. Measurement is simple, quick, and robust and has high reproducibility. The ability to measure ventricular function plus T2* in the heart and liver during the same scan has revolutionized the understanding of iron storage disease and the management of the iron-loaded patient. The early findings using T2* challenged conventional teachings, and both the technique and the findings were initially viewed with scepticism. However, after a decade of work in validating, calibrating, and expanding access to this method, it is now accepted as the method of choice for tissue iron assessment. In the UK, where T2* measurement was first used in the clinical care of patients with thalassemia major, a large and significant fall in mortality has been seen in this patient group.

To the Editor: We read with great interest the recent article by Ellenbogen et al,1 who compare atrioventricular optimization (AVOpt) in cardiac resynchronization therapy (CRT) with a fixed atrioventricular (AV) delay. Using improvement in left ventricular end-systolic volume (LVESV) at 6 months as the primary end point, the authors conclude that the routine use of AV optimization is no longer warranted. We believe that the study was underpowered to detect the additional response to AVOpt. In the sample size calculation the authors assumed a standard deviation of 60 mL and an expected response to CRT of a 30-mL reduction in LVESV. They then assumed a …

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.

Purpose: To examine the reproducibility of the single breathhold T2* technique fromdifferent scanners, after installation of standardmethodology in five international centers. Materials and Methods: Up to 10 patients from each center were scanned twice locally for local interstudy reproducibility of heart and liver T2*, and then flown to a central MR facility to be rescanned on a reference scanner for intercenter reproducibility. Interobserver reproducibility for all scans was also assessed. Results: Of the 49 patients scanned, the intercenter reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver. Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the liver. Conclusion: These data indicate that T2* MR may be developed into a widespread test for tissue siderosis providing that well-defined and approved imaging and analysis techniques are used. © 2010 Wiley-Liss, Inc., link_to_subscribed_fulltext

International audience; AIM: To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS: A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION: CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Heart failure secondary to myocardial siderosis remains a major problem for patients with transfusional iron overload. Direct measurement of myocardial iron concentration by biopsy is not only highly invasive but unreliable due to uneven myocardial iron deposition. T2*cardiovascular magnetic resonance (CMR) is the only non-invasive technique which is able to assess tissue iron levels. This is a rapid, robust technique with proven reproducibility and inter-site transferability which has been accepted as part of clinical practice worldwide [1]. However, little data is available on the calibration of T2* values against tissue concentration of iron [2].

Appropriate cardiac resynchronization therapy (CRT) enhances quality of life and improves survival in patients with refractory heart failure due to systolic dysfunction and mechanical dyssynchrony. On the assumption that the main therapeutic mechanism of CRT is the correction of dyssynchronous myocardial contraction, imaging-based measures of dyssynchrony have been intensely investigated with the aim of predicting response to therapy. Numerous echocardiographic dyssynchrony parameters have been proposed, but no large prospective trial have been published to prove the clinical utility of any of these indexes. Moreover, the methodology to derive the proposed dyssynchrony indexes has not been standardized. Therefore, the purpose of this article is to critically review the current status of proposed dyssynchrony indexes by echocardiography for patient selection and to recommend future investigations in this area. The adverse effects of dyssychronous activation1 and the ability to correct these abnormalities with biventricular stimulation2 were described long ago, but the potential therapeutic application was not realized until an unprecedented study in 1990 reported recovery from intractable heart failure in 16 patients implanted with conventional dual-chamber pacemakers programmed to a short atrioventricular (AV) delay.3 Although these results could not be reproduced in prospective studies4,5 and improvements could only be demonstrated short-term in highly selected patients,6 the race to find a pacing therapy for heart failure had begun. On the hypothesis that the disappointing results of dual-chamber pacing in prospective studies were due to cancelling or overcoming the beneficial effects of AV synchronisation by the adverse effect of RV pacing-induced dyssynchrony,7,8 Cazeau and colleagues proposed a 4-chamber pacing mode and reported the first successful permanent implant in 1994.9 Early randomized controlled trials confirmed short-term improvements in functional capacity and quality of life for patients.10–13 However it was the Comparison of Medical Therapy, Pacing, and Defibrillation in …

Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine.A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made.Myocardial iron loading (T2*20 ms) was present in 108 (65%) patients, which was severe (T2*8 ms) in 22 (13%). Impaired (56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p0.001), weakly related to serum ferritin (Rs = -0.34, p0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = -0.35, p0.001) and was abnormal in only 5 patients.Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis.

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.

Purpose To assess tissue iron concentrations by the use of a gradient echo T2* multiecho technique. Materials and Methods We compared the results of measurements of heart T2* from 32 patients using the established multiple breath-hold variable TR technique with a new multiecho sequence that acquires all images within a single breath-hold with constant TR. Results There was good agreement of myocardial T2* values between both methods in the abnormal range of T2* < 20 msec (mean difference 0.2msec, 95% CI −1.3 to 0.9 msec, r = 0.97, P < 0.0001). The coefficient of variability between the methods was 3.5%. The interstudy reproducibility using the multiecho sequence had a variability coefficient of 2.3% in the abnormal T2* range and 5.8% over all T2* values. There was good agreement between the techniques for the liver T2* values. Conclusions The use of the single breath-hold, multiecho acquisition allowed reliable quantification of myocardial T2*. The good reproducibility, speed, and T1 independence of this technique allows greater accuracy, faster patient throughput, and, therefore, reduced costs (which is important in developing countries where thalassemia is most prevalent). J. Magn. Reson. Imaging 2003;18:33–39. © 2003 Wiley-Liss, Inc.