Myocardial infarction (MI) leads to heart failure in a substantial number of patients. Investigation of temporal dynamics of perfusion in the infarct-adjacent segments can offer better insights into left ventricular remodeling. It is the aim of this study to compare myocardial blood flow (MBF) with cardiac magnetic resonance (CMR) in the infarct borderzones (BZ) and the remote myocardium (RM) in a large patient population 4 months after MI.In this substudy of the NOMI-trial  using the placebo arm, 64 patients underwent a CMR with rest and adenosine stress perfusion 4 months after acutely revascularized ST-elevation MI, in a 1.5 tesla MR scanner . TIMI 2-3 flow was achieved in all patients after PCI. MBF was quantified using Fermi deconvolution with a dual bolus analysis technique ) in basal and midventricular short axis perfusion slices. For stress imaging, 140 µg/kg/min of adenosine was administered intravenously for approximately 4 minutes. Stress and rest imaging were separated by at least 10 minutes. A segmental model was applied on corresponding images of perfusion and late gadolinium enhancement (LGE). The MBF of the infarct zone (IZ) was calculated as the mean perfusion of segments with LGE. The mean perfusion of the adjacent 30 degree segments was defined as MBF of the BZ. The mean perfusion of the remaining segments determined the MBF of the RM. Apical slices seldomly included more than one myocardial zone and were excluded from analysis.One hundred twenty eight slices were analyzed for rest and stress perfusion. Rest perfusion 4 months after MI was not significantly different in BZ and RM  . Stress perfusion however, was significantly lower in BZ than in RM . (cf. Table)Myocardial stress perfusion in infarct-adjacent segments is significantly impaired 4 months after revascularized MI. Persistend regional perfusion deficit may offer new opportunities for targeted angiogenic therapies.No disclosures.


The interest in beating heart surgery is growing since better results can be obtained with this procedure compared to conventional myocardial protection techniques using cardioplegic solutions. This led us to consider mitral valve replacement with beating heart.This study aimed to determine the safety and efficacy of beating heart mitral valve replacement without cross clamp.This prospective study was conducted on the patients with isolated mitral valve disease requiring mitral valve replacement according to ACC / AHA guidelines. In this study, 15 patients underwent mitral valve replacement using beating heart technique (Group A) and 15 ones underwent mitral valve replacement using arrested heart technique (Group B). The patients were randomized using block randomization. The data were analyzed using the SPSS statistical software.Preoperative parameters were comparable in the two groups. Most of the patients in both study groups were in NYHA class III or IV. Postoperatively, however, most of the patients in the two groups were either in NYHA class I or II. No mortality occurred in the beating heart group, while one mortality occurred in the arrested heart group. The results showed a significant difference between the two groups regarding the mean bypass time, mean operating time, mean ICU stay, and mean length of hospital stay.Beating heart mitral valve replacement is equally safe as the arrested heart technique. Thus, it is recommended as an appropriate alternative to the arrested heart technique for mitral valve replacement. The main concern of surgical teams after cardiopulmonary bypass invention has been the deleterious effects of myocardial ischemia. Therefore, ways and means of preventing the harmful effects of myocardial ischemia were taken into account . A varieInterest in beating heart cardiac surgery without aortic cross clamping and, whenever possible, without Cardiopulmonary Bypass (CPB) has increased in the recent years as a means of avoiding the adverse effects of CPB and cross-clamp. Coronary artery bypass surgery has been one of the major beneficiaries of this technique -6. OveraIn Kashmir valley, minimally invasive cardiac surgery along with off-pump beating heart CABG, beating heart ASD repair has been performed for over a decade now, resulting in significant reduction in ischemic damage to myocardium and fewer postoperative complications . Given tWe decided to conduct a study to assess the safety and efficacy of beating heart mitral valve surgery compared to arrested heart mitral valve surgery.The present study was conducted on 30 patients who had isolated mitral valve disease and were subjected to mitral valve replacement. In this study, 15 patients underwent mitral valve replacement using beating heart technique (Group A) and 15 ones underwent mitral valve replacement using arrested heart technique (Group B). The patients were randomized into two groups by computer generated numbers. The same general anesthetic technique with routine arterial and venous monitoring was utilized for both groups. Additionally, mitral valve replacement was performed by the same surgical team. In each patient, the diseased mitral valve was replaced with the mechanical / bioprosthetic valve. The same CPB machine was used in both study groups. Mitral valve was replaced through either sternotomy or right anterolateral thoracotomy.2). The mean systemic pressure was maintained above 60 - 80 mmHg. The heart was perfused through the aortic root. No cardioplegia was used. During the procedure, the patients were placed in Trendelenburg position to prevent air embolism. Then, the left atrium was opened and the mitral valve was examined and excised. Chordae sparing technique was used whenever possible. Afterwards, the valve was replaced using prosthesis  through continuous suture technique. After valve replacement, the left atrium was closed in two layers by non-absorbable sutures. We also used aortic and pulmonary vents for removal of air and maintained them until the patients were weaned off bypass. Simultaneously, the lung was briefly inflated to help air removal. Myocardial function was monitored intra-operatively using five-lead electrocardiography (ECG). Arterial blood pressure, central venous pressure, and urine output were also monitored continuously. Arterial blood gas was done every 30 minutes. The patients were weaned off bypass slowly and decannulated as usual after heparin reversal.In Group A, the valve replacement procedure was carried out on beating heart under normothermic conditions. After heparinisation, CPB was established using ascending aorta and bi-caval cannulation. A vent was placed through the right superior pulmonary vein into the left atrium. No vascular cross clamp was placed on the ascending aorta between the arterial perfusion cannula and the cardioplegic cannula. Body temperature was kept at 36°C - 37°C. The maximum flow rate was calculated as per body surface area , version 22. The two groups were compared regarding the NYHA class and its effect on the outcome. Mann-Whitney U test was used to compare the two groups concerning the mean bypass time, mean operation time, mean ICU stay, mean length of hospital stay, and mean postoperative ventilation time.Rheumatic heart disease was responsible for 93.3% of cardiac valvular lesion in both study groups. The mean age of the patients in the beating heart group was 42.66 ± 7.1 years, whereas the mean age of those who underwent mitral valve replacement on arrested heart was 43.13 ± 8.5 years (P = 0.723). All the patients were in either NYHA class III or IV preoperatively. However, two months after the operation, a statistically significant improvement was observed in the NYHA class. All the patients were in either class I or II two months after the surgery . Most ofChronic rheumatic disease is endemic in the developing world in contrast to the West and remains the most common cause of both mitral stenosis and regurgitation . CalcifiIn order to perform a precise and complete surgical procedure on the heart, it is optimum to have mechanically quiescent heart with bloodless field. These optimal conditions are provided at the cost of global myocardial ischemia (due to cross clamp) and necessitate appropriate myocardial management to limit the damage that would otherwise result from the period of global myocardial ischemia. Damage from a period of ischemia may result in a variable and sometimes prolonged period of both systolic and diastolic dysfunction without muscle necrosis. This condition is now termed as myocardial stunning. The period of ischemia may also result in irreversible damage . Some investigators have obtained information indicating that this can develop after as little as 20 minutes of normothermic ischemia , 15. NayAll these effects of global myocardial ischemia are absent without a cross clamp. Therefore, operating a patient on beating heart without cross clamp nullifies all the harmful effects of global myocardial ischemia. By nullifying the effects of global myocardial ischemia, these patients have better outcomes compared to those operated on arrested heart with cross clamp. In the present study, 15 patients with mitral valve disease were operated on beating heart without cross clamp. The chief criticism in the literature regarding this approach is the risk of air embolism. According to the literature, the major cerebrovascular events after open heart surgery varied from 1% to 4% . In thisIn the present study, the mean bypass time was 108.33 ± 9.9 minutes in the patients who underwent mitral valve replacement on beating heart and 127.93 ± 15.4 minutes in those of the arrested heart group and the difference was statistically significant (P = 0.000). Ghosh S et al.  reportedAccording to the present study findings, the mean operating time was 163.20 ± 9.4 and 186.66 ± 19.56 minutes in the beating heart group and arrested heart group, respectively and the difference was statistically significant (P = 0.000). Similar results were also obtained by Ghosh S , and GerIn the current study, most of the patients in the beating heart group were extubated within 6 hours of surgery, while it took more than six hours for most of the patients in the arrested heart group to get extubated. However, the difference was not statistically significant (P = 0.244). In the same line, Morfa GM et al.  showed nIn this study, the patients in both groups were electively ventilated after the surgery and were extubated in the surgical ICU. Afterwards, the patients were shifted to the main cardiac ward. The patients who underwent mitral valve replacement on beating heart stayed in ICU for a mean duration of 15.66 ± 6.97 hours, whereas those in the arrested heart group had a mean ICU stay of 22.40 ± 11.12 hours. The results revealed a statistically significant difference between the two groups concerning the mean ICU stay (P = 0.013). These findings were consistent with those of the studies by Ghosh S , Morfa GBeating heart mitral valve replacement is a safe myocardial protection technique compared to the arrested heart technique. The chief criticism in the literature regarding this approach is the risk of air embolism. However, none of our patients developed the features of air embolism. Another criticism put forward regarding beating-heart mitral valve surgery is the presence of blood at the surgical site which can impair visualization. However, we did not experience problems concerning the visualization of the surgical site because of our venting technique. The advantages of on-pump, beating-heart mitral valve surgery are based on the fact that the heart is operating under a more physiological condition compared to the cardioplegic arrested state, thus eliminating the adverse effects of global myocardial ischemia occurring due to the reperfusion injury. However, the efficacy of this procedure needs to be determined in a larger prospective randomized control trial to compare it with conventional techniques.


Antibody-mediated rejection (AMR) is characterized by histopathological and immunophenotypic findings such as activated endothelial cells, intravascular macrophages and evidence of capillary C4d deposition. This inflammatory reaction could be followed by diffuse fibrosis. Cardiac magnetic resonance (CMR) with recently T1 mapping is a promising technique to identify diffuse myocardial fibrosis. The purpose of this study was to assess T1 mapping in patients with AMR.Two patients with clinical AMR  performed a CMR study one week (for the first patient) and 3 weeks (for the second patient) after the treatment of AMR . Images were acquired on a 1.5 Tesla scanner (Siemens) including T1 mapping using a shortened modified look-locker inversion-recovery sequence and T2 mapping in a matched mid-ventricular short axis slice using a black- blood single shot fast spin echo pulse sequence. Segmental and global T1 values were measured before and 15 minutes after administration of 0.2 mmol/kg of Gadoteric acid and compared to our cohort of 17 controls.Mean non contrast T1 values were significantly higher in heart transplants patients compared to controls . Segmental T1 values were significantly higher in the 6 regions of interest compared to controls . Mean post contrast T1 values were not significantly different in patients and controls. Mean T2 value was higher in patients compared to controls (73 ± 13 vs 50 ± 4 ms), suggesting the presence of global edema.Heart transplant patients with clinical antibody-mediated rejection show a significant increased global and segmental non contrast T1 values suggesting the presence of diffuse myocardial fibrosis. Further studies are required to confirm these data.No funding.


T1 mapping is increasingly employed for evaluation of diffuse fibrosis within the left ventricular (LV) myocardium. Physiological confounders require correction of raw data prior to analysis. T1 values have been inversely correlated with LV systolic and diastolic function. We sought to evaluate the feasibility of right ventricular (RV) T1 mapping and to assess its relationship with RV function.Post-contrast, T1 mapping was performed with a Look-Locker technique using inversion recovery imaging in 102 consecutive subjects with non-ischemic cardiomyopathy. Regional T1 values of the RV free wall, RV septum and lateral LV were calculated using prototype analysis software. CMR volumetric data was measured offline using a cine short axis stack to establish RV end-diastolic-volume (RVEDV), end-systolic-volume (RVESV) and ejection fraction (RVEF). Simultaneous subject biochemical and anthropometric data were recorded.Subjects demonstrated mild to moderately impaired global RV systolic function . LV function was moderately reduced (LVEF 31 ± 17%). Good correlation was observed between mean LV and RV T1 values [Table Right ventricular T1 mapping appears technically feasible with good agreement between regional RV and LV T1 values. RV T1 values appear proportionally related to RV ejection fraction, suggestive that RV dysfunction in this population may be mediated by fibrotic factors.No funding disclosures.


Recently two novels indicators of left ventricular (LV) performance assessed by Cardiovascular Magnetic Resonance (CMR) have been introduced: the LV global function index (LVGFI) and the LV mass/volume ratio (LVMVR). The LVGFI combines LV stroke volume, end-systolic and end diastolic volumes, as well as LV mass, integrating structural as well as mechanical behaviour. Elevated LVMVR is indicative of concentric remodelling. A LVGFI <37% and a LVMVR>1 were shown to be associated with the occurrence of cardiovascular events in no-thalassemic populations.This retrospective cohort study aimed to systematically evaluate in a large historical cohort of thalassemia major (TM) in the CMR era whether the LVGFI and the LVMVR were associated with a higher risk of heart failure.We considered 812 TM patients , consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. LVGFI and LVMRI were quantitatively evaluated by SSFP cine images. The T2* value in all the 16 cardiac segments was evaluated and a global heart T2* value <20 ms was considered indicative of myocardial iron overload (MIO).Eighty (9.9%) patients had a LVGFI<37% and, compared to the patients with a normal LVGFI, they showed a significant higher frequency of heart failure . Patients with a LVGFI<37% had a significant higher risk of heart failure . The risk remained significant also adjusting for the presence of MIO .Thirty (3.7%) patients had a LVMVR≥1% and, compared to the patients with a normal LVMRI, they showed a significant higher frequency of heart failure . Patients with a LVMVR≥1% had a significant higher risk of heart failure . The risk remained significant also adjusting for the presence of MIO .In a multivariate model including LVGFI, LVMVR and heart iron, the significant predictors of heart failure were a LVGFI<37%  and a global heart T2*<20 ms .In TM patients a LVGFI<37% was associated with an higher risk of heart failure, independent by the presence of MIO. A widespread program using CMR exploiting its multi-parametric potential can have considerable power for the early identification and treatment of patients at risk for heart failure.The MIOT project receives "no-profit support" from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.).


There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral  and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics ; the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach. Approximately 5.1 million people > 20 years old in the USA live with chronic Heart Failure (HF). An estimated 670,000 new cases are diagnosed annually among USA adults > 45 years old, and HF causes or contributes to almost 300,000 deaths each year. Various demographic trends, including the aging of the population and greater likelihood of survival after acute myocardial infarction, suggest that the prevalence of HF will likely continue to increase; indeed, the American Heart Association (AHA) estimates that by 2030, HF prevalence will increase by 25% over 2013 estimates[Although there have been significant advances in the treatment of HF, morbidity and mortality remain high. Pharmacologic regimens have become increasingly complex, and standard therapy now often consists of multiple drugs . The economic impact is significant as well and costs of HF hospitalizations amount to $29 billion/year in the USA alone. Given these epidemiologic and economic pressures, there is increasing interest in using cardiovascular biomarkers for a personalized medicine approach to more effectively guide diagnosis, risk stratification, and therapy[In many disease states, drug selection and dosage are strictly dependent from biomarkers. ClassicRecognizing the heterogeneity of HF and dissecting it into different therapeutic groups would improve the targeting of interventions, which in turn could improve response rates and avoid adverse effects in patients unlikely to benefit. Studies have demonstrated the need to target specific phenotypes based on this heterogeneity. MoreoveCirculating levels of NP are normally very low in healthy individuals. In response to increased myocardial wall stress due to volume- or pressure-overload states (such as in HF), the Brain Natriuretic Peptide (BNP) gene is activated in cardiomyocytes. This results in the production of an intracellular precursor propeptide (proBNP108); further processing of this propeptide results in release of the biologically inert aminoterminal fragment called N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)and the biologically active BNP. In addiBNP and NT-proBNP levels are increased in HF, and correlate well with ventricular wall stress and severity of HF. The Breathing Not Properly Multinational Study and the Pro-BNP Investigation of Dyspnea in the Emergency Department showed that NP levels were more accurate for diagnosis or exclusion of Acute Decompensated Heart Failure (ADHF) than clinical judgment, particularly in the context of diagnostic uncertainty. When added to comprehensive clinical assessment, BNP and NT-proBNP are both incrementally useful for diagnosis of ADHF, and both are endorsed in current practice guidelines for HF evaluation (particularly when diagnostic indecision is present). Elevated BNP (above approximately 125 pg/mL) or NT-proBNP (above approximately 1000 pg/mL) values are prognostically meaningful in chronic HF, and a rising pattern is predictive of impending adverse outcome, irrespective of other subjective and objective prognostic metrics. Furthermore, therapies that are favorable for chronic HF  tend to lower concentrations of BNP or NT-proBNP.Thus, there is increasing interest in guiding HF therapy with BNP or NT-proBNP, with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and AHA/American College of Cardiology (ACC) guidelines,7 did noLimitations of NP-based approach include major limitations  and minor weaknesses - such as cost and venipuncture.The term "biological variability" refers to the extent of changes of a biomarker in a stable physiological state. In practice, biological variability indicates the change in measurement that have a biological significance. Both BNP and NT-proBNP are limited in their clinical use by an excess variability that reaches 40% for BNP and 25% for NT-proBNP. Given aIdeally, a biomarker should reflect as quickly as possible improvement or worsening of patients’ conditions, either spontaneous or therapy-induced. A fast response is even more essential in critical conditions such as decompensated HF. Unfortunately, data from studies of serial BNP measurements suggest that concentrations of NT-proBNP require from 2 to 4 weeks after a therapy change to stabilize. ObviousMost cardiologists believe that BNP and NT-proBNP directly reflects variations in volume of cardiac chambers. This is certainly true, but by no means a specific finding. In fact, BNP and NT-proBNP levels change also in response to arrhythmias, myocardial ischemia, valvular heart disease, changes of filling pressures, diastolic function, only to mention cardiac factors. Also non-cardiac factors, including age, sex, body mass index and genetic factors are important confounders, as are pulmonary hypertension, pulmonary embolism and chronic kidney disease. NP leve.In the era of evidence based medicine, no guideline can be proposed if not supported by sound data. More than 9 trials have been completed and published since when NP levels have been proposed to guide HF therapy. The natriuretic peptide guided- strategy is associated with reduction in all-couse mortality and HF- related hospitalization as well as with the risk of readmission for HF worsening, as shown by recent meta-analyses. However further evidence is still needed to support a more general use of NP, since the results of this trial are inconclusive as regards cardiac death,23.The results of these trials are inconsistent and inconclusive. The clear demonstration of this statement is that an additional trial is being conducted and eagerly waited by both supporters and skeptics . The mixed results are after all not so surprising in the light of previous limitations. NP increase is determined by a spectrum of different pathophysiological conditions  and triggers a monotonous therapeutic response, of questionable benefit in the individual patient, and typically associated with a relative increase in the use of angiotensin-enzyme inhibitors, beta-blockers, angiotensin receptor blockers, and spironolactone over standard, symptom-guided care. If the physician relies on NP levels to assess volume status, the choice of dose escalation of loop diuretics in patients without pulmonary congestion may increase the rate of hypotension, renal dysfunction and adverse outcome.HF poses a heavy economic burden on western economies, being one of the largest contributors to health cost. NP measurements, though not very expensive add to the overall cost of HF therapy. The additional cost for each BNP measurement varies largely from hospital to hospital, and averages 30 €. NT-proBNP measurement is generally more expensive. Given the need for serial measurements and the number of the HF populations, it is easy to estimate how much a systematic NP based approach would impact on health cost. That is why a generalized use of NP based therapy is not justified until conclusive evidence is provided of its cost-effectiveness.This may appear as a minor nuisance for doctor and patients, but sometimes the blood sampling may be a challenging task in elderly, fragile, obese patients.Based on the concepts expressed in preceding paragraphs, therapy of HF might be reconsidered. An effort should be made to identify the agents and the dosages to be prescribed to patients according to the etiology of the HF and to the severity of symptoms, abandoning the current strategy of giving all agents, at the highest tested dose, to all patients. It is conceivable that in this context, patients can be identified in whom NP dosage may provide a good guidance to therapy, and patients that do not have benefit from such approach. This hypothesis would become even more appealing if biomarkers with less biological variability, greater specificity and faster time response can become available..Echocardiography-derived parameters can fulfill the definition of biomarkers since in 2001, a working group of the National Institutes of Health standardized the definition of a biomarker as a "characteristic that is objectively measured and established as an indicator of normal biological pathologic processes, pathogenetic processes, or pharmacologic responses to a therapeutic intervention". A biomarker may be measured on a biosample  or it may be an imaging test .The ideal candidate biomarker should fulfill some basic pre-requisites: 1) easily defined, safe, and reproducible in each patient; 2) appropriate therapeutic counter measures should be available to reset the abnormal biomarker values towards normal range; 3) the biomarker-triggered therapy change should improve outcome; 4) the biomarker-driven approach should provide an improved benefit and cost-benefit over standard approach.A classical example of a powerful risk marker unsuitable as a therapeutic target is serum sodium concentration. The lower the sodium concentration, the higher the degree of neuro-hormonal activation and the poorer the prognosis, but treatment aimed at normalizing sodium levels will not improve clinical outcomes.Echo biomarkers in HF show several prerequisites for being useful. According to the recent ESC guidelines on HF, echocardiography is the imaging method of choice for reasons of accuracy, availability (including portability), safety and cost. The more frequently used echo parameters are reported in Table .In spite of the unsurpassed appeal in terms of low cost, widespread access, versatility of the information provided, there are limitations of echo-based approach, including dependence on patient’s acoustic window, operator’s expertise and lack of sufficient evidence based-data in echo-driven management of HF patients.Although last generation echocardiographic instruments allow satisfactory to excellent imaging in > 90% of patients referred to echocardiography lab, poor acoustic windows exist in a significant portion of subjects, for instance with morbid obesity or lung disease. The use of intravenous contrast agents for endocardial border enhancement and better left ventricular cavity recognition is indicated whenever ≥2 contiguous segments are not adequately visualized and consThe echocardiographic examination is highly dependent on the quality of image acquisition and analysis. Therefore, strict criteria of image acquisition, storage and analysis are required when echocardiographic data are used in a clinical trial. The American Society of Echocardiography issued some recommendations on these aspects, suggesting that only certified and trained sonographers are involved in data acquisition, and in multicenter trials core lab reading by experinced operators blinded to patient identity and study condition is recommended. In addi.Although a large number of observational studies support the use and prognostic values of several echocardiographic markers of HF, we still miss prospective randomized trials based on echo parameters as a guide to treatment. When this has been done in other fields, results have not been always in line with the expectation and conventional wisdom. For instance PROSPECT study did not confirm that mechanical dyssynchrony with echo is associated to better outcome with CRT therapy; COURAGEIt is obvious at this point that we need stronger evidence from prospective randomized outcome data before we can use echocardiography to guide our therapy choices in heart failure.An integrated ultrasound assessment with echocardiographic and lung ultrasound, in resting conditions and even better during stress, can proThe concept of the application of biomarkers as a guide to therapy is certainly an interesting one, which has stood the test of time. Not all HF patients with the same clinical picture were created equal, and NP assessment identifies higher and lower risk subgroups, which may help in guiding a different level of treatment intensity. We have learned in the past 15 years that the good clinician needs little help in starting an appropriate therapy of HF patient, but even the best clinician needs help in tailoring the best therapy in the HF patient to prevent acute decompensation or catastrophic complications. Many attempts in these directions including the simple NP-guided therapy met only limited success with uncertain impact on mortality. On the light of the evidences presented, this cannot be considered surprising since the increase in NP is a monotonous response to a variety of different patho-physiological input conditions and, furthermore, it evokes a rather monotone output response with intensification of drug treatment. This simple and straightforward diagnostic and therapeutic algorithm can be beneficial in some patients, neutral in others, and detrimental in a subset. For instance, an increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral  and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics ; the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or CRT therapy-35. To eADHF: Acute decompensated heart failure; AHA/ACC: American heart association/American College of Cardiology; BNP: Brain natriuretic peptide; CRT: Cardiac resynchronization therapy; ESC: European Society of Cardiology; EF: Ejection fraction; HF: Heart failure; LV: Left ventricular; NP: Natriuretic peptides; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; RCT: Randomized Clinical Trials.The author(s) declare that they have no competing interests.MCS conceived the study and drafted the manuscript which was critically reviewed by AS, FLL and MM. All authors read and approved the final manuscript.


Peripheral vascular disease is commonly associated with concomitant coronary heart disease and congestive heart failure.We aim to perform a cohort study to evaluate if revascularization of lower limb is sufficient for wound healing in patients with impaired cardiac function.We performed a retrospective study in a tertiary vascular surgical centre on patients with elective lower limb angioplasty for critical limb ischaemia from June 2011 to June 2012. 190 patients were included in this study. Pre-operative demographics, comorbidities, post-operative 30-day mortality, amputation and re-intervention data were collected. The cardiac function was defined as poor (≥40%), moderate (40-54%), and good (≤55%). Univariate and multivariate analyses were done to identify the pre-operative morbidities and whether cardiac function affects the outcomes for these groups of patients. The outcomes measured were re-intervention, limb amputation, wound re-debridement, 30-day post-operative mortality.Our patient population consisted of 190 patients with 97 males and 93 females. The most common pre-operative morbidity is diabetes (85%). Overall 30-day mortality rate is 5.2%. Poor cardiac function (p = 0.013) and ischaemic heart disease (0.032) were significantly associated with post-operative mortality in univariate analysis. In multivariate analysis, poor cardiac function showed significant association with post-op mortality (p = 0.045). Below knee angioplasty was significantly associated with the need in amputation in univariate (p = 0.014) and multivariate analyses (0.02).Poor EF is associated with post-angioplasty 30-day mortality. Below knee angioplasty appears to be associated with higher amputation risk. This is the first evidence in the literature that show the association between impaired heart function and adverse outcome after lower limb angioplasty for critical limb ischemia.


Ventricular assist devices have been routinely used in patients with end stage heart failure as a bridge to transplantation. We present a case of using a Bi-Ventricular Assist Device (BiVAD) in a patient with fulminant heart failure as a bridge to recovery.A 36 year old lady with a history of Grave's Disease and three months post-partum presented with fulminant myocarditis.She presented to her local hospital on 2nd January with episodes of ventricular tachycardia (VT) and syncope. She was transferred to a tertiary level cardiology centre as she failed to cardiovert. Echocardiography demonstrated significant left ventricular (LV) thickening and LV stasis. She continued to have VT storms and was referred to our advanced heart failure service.On arrival she rapidly deteriorated with recurrent VT and ventricular fibrillation (VF) episodes causing severe haemodynamic compromise. A decision was made to institute mechanical circulatory support with veno-arterial Extra-Corporeal Membrane Oxygenation (VA- ECMO). During cardiopulmonary resuscitation she was placed onto VA-ECMO and stabilised. That same evening she underwent conversion to BiVAD support for offloading of both ventricles.She was extubated on the first post-operative day. Myocardial biopsy performed during BiVAD implantation confirmed florid myocarditis.Over the ensuing days, she was mobilised and rehabilitated on the ITU and there was a gradual recovery of myocardial function. On the 25th post-operative day her BIVAD circuit was explanted following a successful wean.After further rehabilitation she was discharged home, 39 days after admission. MRI prior to discharge demonstrated satisfactory biventricular function with a small right atrial thrombus.Ventricular assist device therapy can be utilised as an effective primary treatment modality for patients in fulminant heart failure within the spectrum of post-partum cardiomyopathy. We suggest early discussions with regional advanced heart failure centres to facilitate prompt intervention leading to full recovery.


Left ventricular cavity dimensions and volumes are useful parameters to diagnose and monitor cardiac pathologies which lead to LV volume overload. 2-D echo/Doppler is the most commonly used imaging modality to assess LV volume overload in patients with valvular regurgitant disease. However, 2-D echo suffers from inherent limitations related to adequacy of the intercostal echo window, anatomic positioning for cavity dimensions and volumes and incomplete visualization of the entire left ventricular cavity. This study was designed to compare assessment of LV cavity dimensions and volumes by 2-D echo and cardiac magnetic resonance (CMR) techniques in patients with LV volume overload due to valvular regurgitationAn institutional cardiac imaging database was queried to identify patients with at least moderate (2+ or greater) mitral regurgitation or aortic regurgitation who had 2-D and CMR studies within 6 months of each other. LV end-diastolic(LVIDd) and end-systolic(LVIDs) dimensions were tabulated, along with LV end-diastolic(LVEDV) and end-systolic(LVESV) volumes and severity of valvular regurgitation  for both 2-D and CMR. 2-D regurgitation was estimated by Doppler analysis and CMR regurgitation was estimated by calculation of the regurgitant fraction using phase velocity mapping. The mean values for LVIDd, LVIDs, LVEDV and LVESV by 2-D and CMR were computed and statistically compared using a paired-sample t-test. Each parameter was also analyzed as a function of severity of regurgitation.Of 1,817 patients in the CMR database, 102 patients met study inclusion criteria, 52 with AR and 63 with MR. The mean LVIDd by CMR was 5.87 cm and 5.09 cm by 2-D (p < 0.001). The mean LVIDs by CMR was 4.03 cm and 3.46 cm by 2-D (p < 0.001). The mean LVEDV by CMR was 166.16 ml and 129.48 ml by 2-D (p < 0.001). The mean LVESV by CMR was 77.71 cm and 56.06 ml by 2-D (p < 0.001). Parameter analysis as a function of severity of regurgitation is shown in the Figure In patients with LV volume overload due to valvular regurgitation, 2-D echo significantly underestimates LVIDd, LVIDs, LVEDV and LVESV, resulting in over-estimation of global LV ejection fraction. In patients with mitral regurgitation, increases in LV end-diastolic dimension and LV end-diastolic volume on CMR are indicative of worsening regurgitation. A similar relationship to severity of mitral regurgitation could not be demonstrated for these parameters when assessed by 2-D echo techniques.None.


Amyloidotic cardiomyopathy (AC) in Hereditary Transthyretin Amyloidosis (ATTR) determines prognosis and treatment options. Cardiac Magnetic Resonance (CMR) has shown its utility in the diagnosis and characterization of AC. Moreover, CMR T1 mapping techniques are useful to assess myocardial extracellular volume (ECV) fraction in AC.We hypothesized that ECV allows identification of AC in ATTR patients and that there is a correlation between cardiac ECV and the degree of neurological impairment caused by TTR amyloid extracardiac deposits.31 genetic proven ATTR patients at different stages of the disease  underwent a T1 mapping CMR study and a neurological evaluation with NIS-LL score , Norfolk-QOL questionnaire  and Karnofsky index . AC was defined by positive 99mTc-DPD scintigraphy (uptake grade>2) or left ventricular hypertrophy >12mm. with typical gadolinium kinetics/enhancement of amyloidosis at CMR in the absence of DPD-scan (9 patients).5 patients had AC . Mean ECV was increased in patients with AC . ECV correlated with age , NTproBNP , maximum wall thickness , left ventricular mass index , left ventricular ejection fraction , NIS-LL , Norfolk-QOL  and Karnofsky . A cut-off value of ECV=0.357 calculated by ROC curve, was diagnostic of AC with 100% sensibility and specificity (P<0.001). ECV and NTproBNP values were the only cardiac parameters that significantly correlated with neurological scores.ECV quantification by CMR allows identification of AC in ATTR and correlates with the degree of neurological impairment. This non-invasive technique could be a useful tool for early diagnosis and to track cardiac and extracardiac amyloid disease.


This case displays limited utility of left ventricular ejection fraction to detect acute graft failure due to microvascular vasculopathy and suspected humoral rejection. Despite severe and progressive graft failure, clinically and by right heart catheterizations, left ventricular ejection fraction remained unchanged, indicating need of more reliable noninvasive methods for graft function surveillance. Global longitudinal strain relates to clinical heart failure, filling pressure, and cardiac index during suspected humoral rejection and microvascular dysfunction in this HTX patient. We suggest routine monitoring of graft function by global longitudinal strain as supplement to routine left ventricular ejection fraction and diastolic Doppler measurements. Heart transplant recipients are at increased risk to develop myocardial dysfunction due to rejections, fibroses, and vasculopathy. Standard surveillance of graft function after heart transplantation (HTX) includes measurement of left ventricular (LV) ejection fraction (EF) and diastolic function by mitral valve Doppler flow. Our clinical experience shows that left LV-EF often presents itself within normal range during acute rejection, despite severe vasculopathy, suggesting that LV-EF is an inappropriate parameter for detecting impaired myocardial function. Global longitudinal strain (GLS) by 2-dimensional speckle tracking (2D-STE) represents a new angle-independent echocardiographic tool for global assessment of LV systolic function. GLS is a direct measurement of myocardial longitudinal deformation, less dependent on heart rate and loading conditions than LV-EF and diastolic Doppler measurements . This caμg/L. CRP was slightly elevated, 20.3 mg/L, and Nt-Pro-BNP was moderately elevated, 2018 ng/L. Chest X-ray was without acute pathology.A 49-year-old female heart-transplanted (HTX) patient was hospitalized on December 3, 2010, due to one week with dyspnea (NYHA IIb) and dizziness. Blood pressure was 143/100, heart rate 125 (sinus rhythm (SR)), and saturation 97%. Electrocardiogram showed 1-2 mm ST-depression in V2–V6. Blood samples revealed myocardial necrosis, TNT 148 ng/L, and CKMB 6 The patient was priorly transplanted in March 2008 due to terminal ischemic heart failure. Donor was an 18-year-old male; both donor and patient were blood type A. Transplantation was completed with 4 HLA mismatches . No prospective cytotoxic crossmatch was performed. Cold ischemic time was three hours; the heart started spontaneously in SR. Echocardiography showed normal biventricular systolic function. First endomyocardial biopsy (EMB) showed signs of ischemic transport damage, afterwards no treatment demanding rejections. Coronary angiographies showed normal coronary arteries within the first two years after HTX.Echocardiography at hospitalization (December 2010) revealed significant restrictive filling with preserved LV-EF but decreased longitudinal biventricular function  −8.9%, TAPSE 1 cm, and right ventricular (RV)-GLS −6.4%). Intravenous methylprednisolone of 1 g daily for three days was immediately initiated, due to severe suspected acute cellular rejection. EMB and coronary angiography on December 6 showed 1R cellular rejection, significant myocytolysis, and angiographically normal coronary arteries. Intravascular ultrasound examination of all three major branches on December 13 confirmed normal coronary arteries, and repeated EMB showed 1R cellular rejection with significant myocytolysis. C4d was only positive in necrotic areas; no significant histological signs of humoral rejection were described. A DDD-pacemaker was implanted due to symptomatic episodes with sinus bradycardia and nodal rhythm. On December 16 a flow cytometric crossmatch performed on donor T- and B-cells was found negative, not supporting the diagnosis of humoral rejection. Luminex analysis showed three donor-specific HLA antibodies, anti-DR12 (5.200 MFI), anti-DR7 (2.500 MFI), and anti-DR52 (3.500 MFI) indicating some donor reactivity. Serological markers of myocardial necrosis remained elevated. The clinical condition declined with decreasing diuresis, increasing s-creatinine, and dyspnea (NYHA IV). Right heart catheterization on December 28 showed severely elevated biventricular filling pressure and heart failure (right atrium (RA) 23/14 mmHg (20), pulmonary artery (PA) 32/20 mmHg (24), pulmonary capillary wedge pressure (PCWP) 27/10 mmHg (18), and cardiac index (CI) 1.7 L/min, SvO2 53% SaO2 92%). At this point Nt-Pro-BNP was increased to 5034 ng/L. Former EMBs were reevaluated revealing occlusion of several minor arterial branches. Overall, humoral rejection was most likely the cause of microvascular dysfunction. On December 29, plasmaferese, intravenous methylprednisolone, immunoglobulin, and rituximab were initiated. Echocardiography showed unchanged preserved LV-EF and severely reduced biventricular longitudinal function  . A new LAutopsy findings of the explanted heart revealed histological signs of humoral rejection with severe graft vasculopathy in the microvascular system by means of occlusive intima fibrosis involving myofibroblast proliferation, macrophages, and lymphocytes. In the myocardium, severe diffuse myocytolysis and bleeding were seen . No signThe diagnostics of humoral rejection and microvascular dysfunction are challenging in the clinical setting. Despite relevant examinations, treatment for humoral rejection in this present case was initiated 26 days after hospitalizing. Microvascular dysfunction and humoral rejection should be suspected in HTX patients with clinical heart failure, without evidence of cellular rejection or epicardial vasculopathy. The combination of preserved LV-EF and severely reduced GLS indicates impaired subendocardial perfusion. Longitudinal myocardial function predominantly represents function of the subendocardial longitudinally oriented fibers. These fibers are the most sensitive for impaired myocardial perfusion, edema, and fibrosis . PreviouIn this case, progressive heart failure was confirmed by elevated filling pressures, decreased CI, and long-axis analysis of both ventricles, whereas LV-EF was only slightly affected and unchanged during the clinical course. When evaluating myocardial function in HTX patients, LV-EF is often within normal range despite significant cardiac rejection or vasculopathy, indicating that LV-EF is unreliable in graft function surveillance.In contrast to LV-EF, GLS relates to clinical heart failure, filling pressure, and CI during microvascular dysfunction and suspected humoral rejection in HTX patients. We suggest routine monitoring of graft function by GLS as supplement to routine LV-EF and diastolic Doppler measurements.


Heart failure (HF) is expected to be highly prevalent in nursing home residents, but precise figures are scarce. The aim of this study was to determine the prevalence of HF in nursing home residents and to get insight in the clinical characteristics of residents with HF.The study followed a multi-centre cross-sectional design.n = 501) in the southern part of the Netherlands aged over 65 years and receiving long-term somatic or psychogeriatric care were included in the study. The diagnosis of HF and related characteristics were based on data collected from actual clinical examinations , patient records and questionnaires. A panel of two cardiologists and a geriatrician ultimately judged the data to diagnose HF.Nursing home residents  were also more prevalent in those with HF. Residents with HF had a higher score on the Mini Mental State Examination. 54 % of those with HF where not known before, and in 31 % with a history of HF, this diagnosis was not confirmed by the expert panel.This study shows that HF is highly prevalent in nursing home residents with many unknown or falsely diagnosed with HF. Equal number of HF patients had reduced and preserved left-ventricular ejection fraction.NTR2663 (27-12-2010)The Netherlands National Trial Register  In Western countries, heart failure (HF) is common in older people. The prevalence of HF increases up to 17.4 % at the age of 85 years and more . In addiEarly diagnosis and treatment of HF may prevent progression and lead to improvement of symptoms and quality of life , 7, whicThis study followed a multi-centre cross-sectional design as previously published . The stuIn the southern parts of the Netherlands, long-term care is covered by five organizations providing nursing home care, with an overall number of approximately 4.500 nursing home residents. Nursing home care in the Netherlands is provided by teams of registered nurses, nurse assistants, paramedical professionals and nursing home physicians, who are employed by the nursing homes themselves . The typn = 1 920). To complete the study within the specified time period (January 2011 to June 2013) and for practical and logistical reasons, nursing home residents living in the facilities with the highest number of residents were first recruited within each care home organization. The number of locations involved per organization differed from 3 to 8. Residents were eligible if they received chronic somatic care or psychogeriatric care and were over 65 years of age. Residents who received palliative care or were admitted for short-term rehabilitation (staying less than 2 months) were excluded. Informed written consent was obtained from the residents themselves or from their legal representatives in the case of psychogeriatric disorder, or residents with aphasia.Nursing home residents at 28 locations allocated to these five long-term care organizations were asked to participate in the study  to 983 residents (if p = 0.20) [Based on our systematic review, the expected prevalence of HF was 20 % with a range of 15–45 % . For theData regarding general and clinical characteristics were gathered for all participating residents. These included age, gender and symptoms and signs of HF , fatigue, increased weight, pulse rate, blood pressure, increased jugular venous pressure, hepatojugular reflux, right ventricular pulsations, hepatic pulsations, hepatomegaly, oedema, palpable apex, displacement of the apex, third heart sound, murmur, pulmonary rales, pleural effusion). Moreover, information regarding cardiac history , co-morbidity, cardiovascular risk factors (Body Mass Index (BMI), hypercholesterolemia, DM and smoking) and medication (cardiac and non-cardiac medication) were collected. Patients underwent a Mini Mental State Examination (MMSE), blood sampling, a standard 12-lead electrocardiogram (ECG) and an echocardiogram. Doppler-echocardiography was performed according to current standards from parasternal, apical and epigastric views .First, a nursing home physician (NHP) assessed medical history and performed physical examination. Before the start of the study, this NHP (3–4 per organization) had received a refresher course on diagnosing HF and performing a structured physical examination. The training included a review of signs and symptoms of HF followed by bedside teaching (3 h), a lecture on ECG findings in relation to HF (2 h) and a visit to the outpatient HF clinic of the Maastricht University Medical Centre (3 h). Two research nurses and an NHP/researcher were responsible for recording the ECGs, collecting the blood samples, gathering data from the medical records and filling in the questionnaires. Qualified (fellow) cardiologists recorded an echocardiogram on site. The entire assessment was carried out on site in the participating nursing homes with a mean time span of four weeks to complete data collection per resident.The actual history and physical examination were recorded on a client record file developed for this study. Somatic residents answered the history-related questions and for psychogeriatric residents, these questions were answered by the nurses responsible for their daily care or the main family caregiver of the resident. N-terminal of the prohormone brain natriuretic peptide (NT-pro BNP), haemoglobin and serum creatinine concentrations were analysed at the clinical chemistry laboratory of the Maastricht University Medical Centre on an Elecsys 2010 . A standard 12-lead ECG was made using the Cardiovit AT-10 plus . The following (possibly HF-related) ECG findings were recorded: sinus tachycardia (heart rate > 100 beats/min), sinus bradycardia (heart rate < 60 beats/min), pathological Q-waves, atrial fibrillation, ventricular arrhythmia, different degrees of AV-block, low voltage of the QRS complexes , QRS widening (>0.12 ms) due to right bundle branch block, left bundle branch block or non-specific widening and left (LV) and/or right ventricular (RV) hypertrophy . The echSigns and symptoms of HFPresence of structural or functional cardiac abnormalities.An expert team of two cardiologists and a geriatrician were responsible for the final diagnosis of HF using all data collected by the NHP, research nurse and (fellow) cardiologist, based on the current ESC guidelines .Signs anThe members of the expert team judged all files independently. First the data were judged on the presence of signs and symptoms. Subsequently, the measurements of the echocardiography and the ECG were used to assess functional and/or structural cardiac abnormalities, compatible with the diagnosis of HF. In the absence of current signs and symptoms, medical history and medication provided important information to make the diagnosis of HF. In residents without an echocardiogram or in the case of uncertainty regarding the diagnosis, the NT-pro BNP value, ECG findings, medical history and medication (in that order) were considered for the final diagnosis.When there was mutual agreement on the diagnosis, the file was closed. All files with disagreement were discussed in the presence of all three members of the expert team to reach a consensus on the final diagnosis.t-tests or analysis of variance (ANOVA) for continuous variables and Chi-square test  and multivariable logistic regression analysis for discrete variables, respectively, with a level of significance of p < 0.05 for all variables. The selection of variables included in the multivariable logistic regression analysis was based on the literature and expert opinion. These variables were gender, CAD, BMI, DM, chronic obstructive pulmonary disease (COPD), haemoglobin, creatinine, heart rate, systolic blood pressure, pre-existing HF, arrhythmia, valvular heart disease, [Statistical analyses were performed using IBM SPSS statistics software version 20 and included descriptive frequency distributions for all variables. Differences between groups were tested using Student’s disease, , 22. To n = 3) and extreme tremor in the limbs (n = 2). Missing outcomes of echocardiography were mainly caused by poor image quality due to e.g. obesity and in case of COPD. In a minority of cases (n = 10) psychogeriatric residents resisted against the echocardiography.Of the residents fulfilling the inclusion criteria, 27 % of those or their legal representatives agreed to participate. Main reasons for not participating included that residents considered themselves too old or believed that the investigations were too burdensome. The expert team eventually assessed 501 client record files and decided on the diagnosis of HF. HF assessment  was completed for 87 % of the participating residents  were removed stepwise using the backward procedure. The final model showed that the variables, CAD, arrhythmia, age, creatinine and HF in history being significant in univariate analysis were independent factors associated with the presence of HF.The independent predictors of prevalent HF entered in the multivariable logistic regression model are presented in Table In this study, the prevalence of HF was 33 % for all participating nursing home residents, of which more than half were previously undiagnosed and a previous diagnosis of HF was rejected in almost one third. HFpEF and HFrEF were equally prevalent. Therefore, the hypothesis that HF is highly prevalent in nursing home residents is confirmed, and the prevalence was clearly higher than among older persons in the general population .The prevalence of 45 % found in a study by Butler et al. in whichResidents with HF had less cognitive disorders; a result which is not in line with studies in the literature where patients with HF suffer more often from cognitive disorders , 25. ThiIn the study by Hanock et al. , more paMultivariable analysis showed that factors such as arrhythmia, CAD, age, a history of pre-existing HF were associated with the presence of HF. Interestingly, there was no association found with gender, which may be a risk factor for the development of HF in the general population . There wFurthermore, the diagnosis HF was not known in more than half of those having HF and a previous diagnosis of HF was not confirmed by the expert team in one third of all cases. These findings indicate an important problem as a significant number of residents obviously might not be treated correctly. This could be of significant impact to residents of nursing homes as it can be expected that symptoms are not adequately recognised and treated in a substantial number of patients. Although not prospectively investigated by randomised treatment trials in this population, this may have important impact on well-being and quality of life. Moreover, it implies a challenge to improve the diagnostic process of HF in nursing homes residents. The implementation of the structured procedure used by the expert team may improve the diagnostic process significantly. This includes echocardiography using mobile devices in residents suspected to suffer from HF. The clinical features identified in this study to be accompanied with increased risk of prevalent HF may help to detect such patients that should undergo such structured work-up.The strength of the present study is the thorough method of data collection using an on-site integral examination of each resident. On the other hand, the participation rate was not as high as anticipated (27 %). A consideration here is that legal representatives often do not want to decide for participation on behalf of the residents, which explains the lower participation rate of psychogeriatric patients. Our findings are in line with a study conducted by Barnes  on HF inMoreover, we did not investigate to what extent treatment would have changed based on more accurate diagnosis and the impact on the patients’ well-being is unknown. This is particularly true since the large treatment trials that are the basis for the treatment recommendations did not include the population of our study. Still, guideline recommendations are independent of patient’s age. Therefore, the diagnostic approach we used would at least result in treatment which is better following current guidelines. Finally, we included residents in one region only and results might be different in other countries and may depend on the structure of health care in each country. Therefore, it is important to conduct such studies in different countries as results in this regard are still very limited.HF is highly prevalent in nursing home residents with many unknown or falsely diagnosed with HF. Equal number of HF patients had reduced and preserved left-ventricular ejection fraction.


However, this association has been poorly addressed in senescent rats. Therefore, this study aimed to analyze the influence of streptozotocin-induced DM on ventricular remodeling and oxidative stress in aged spontaneously hypertensive rats (SHR)t test or Mann-Whitney test, p < 0.05.Fifty 18 month old male SHR were divided into two groups: control  and diabetic . DM was induced by streptozotocin . After nine weeks, the rats underwent echocardiography and myocardial functional study in left ventricular (LV) isolated papillary muscle preparations. LV samples were obtained to measure myocyte diameters, interstitial collagen fraction, and hydroxyproline concentration. Gene expression of atrial natriuretic peptide (ANP) and α- and β-myosin heavy chain (MyHC) isoforms was evaluated by RT-PCR. Serum oxidative stress was assessed by measuring lipid hydroperoxide concentration and superoxide dismutase and glutathione peroxidase activities. Statistics: Student’s SHR-DM presented higher blood glucose (487 ± 29 vs. 89.1 ± 21.1 mg/dL) and lower body weight (277 ± 26 vs. 339 ± 38 g). Systolic blood pressure did not differ between groups. Echocardiography showed LV and left atrial dilation, LV diastolic and relative wall thickness decrease, and LV systolic and diastolic function impairment in SHR-DM. Papillary muscle study showed decreased myocardial contractility and contractile reserve in SHR-DM. Myocyte diameters and myocardial interstitial collagen fraction and hydroxyproline concentration did not differ between groups. Increased serum pro-oxidant activity and gene expression of ANP and β/α-MyHC ratio were observed in DM.Diabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats. Heart failure represents a major public health issue reaching epidemic proportions especially in elderly populations . The preDiabetes mellitus is a major risk factor for the development of coronary atherosclerosis and diabetic cardiomyopathy, a non-atherogenic myocardial disease. Diabetic cardiomyopathy results from complex relationships between metabolic abnormalities that accompany diabetes and their cellular consequences leading to alterations in myocardial structure and function -5. Diabe. Although the prevalence of risk factors for cardiovascular disease increases with age, the combined effects of diabetes and hypertension on cardiac remodeling during senescence have been poorly addressed.Diabetes in humans is often associated with systemic arterial hypertension. The combination of DM and hypertension induces greater structural and functional cardiac damage than either condition alone . This coOne widely used experimental model for studying hypertension and heart failure is the spontaneously hypertensive rat (SHR) -19. It pad libitum. All experiments and procedures were approved by the Ethics Committee of Botucatu Medical School, UNESP, Botucatu, SP, Brazil.Male SHR were obtained from the Central Animal House at Botucatu Medical School, UNESP. All animals were housed in a room under temperature control at 23°C and kept on a 12-hour light/dark cycle. Food and water were supplied Eighteen-month-old SHR were assigned into two groups: control  and diabetic . Diabetes was induced by intraperitoneal injection of streptozotocin  at 40 mg/kg body weight diluted in 0.01 M citrate buffer pH 4.5 . The conNarco Bio-System®, International Biomedical Inc., USA).Systolic arterial pressure was measured before streptozotocin injection and at the end of experiment by tail-cuff method using a model 709-0610 electro-sphygmomanometer (3 – (LVDD)3] × 1.04  × 1.04 . Left ve2 and 5% CO2 (pH 7.38). The composition of the Krebs-Henseleit solution in mM was as follows: 118.5 NaCl, 4.69 KCl, 1.25 CaCl2, 1.16 MgSO4, 1.18 KH2PO4, 5.50 glucose, and 25.88 NaHCO3. The spring clips were attached to a Kyowa model 120 T-20B force transducer and a lever system, which allowed for muscle length adjustment. Preparations were stimulated 12 times/min at a voltage 10% above threshold.At the end of the experimental period, myocardial contractile performance was evaluated in all rats using isolated LV papillary muscle preparation as previously described ,29. Ratsmax) was determined. A 15 minute period of stable isometric contraction was imposed prior to the experimental period. One isometric contraction was then recorded for later analysis.After a 60-min period, during which the preparations were permitted to shorten while carrying light loads, muscles were loaded to contract isometrically and stretched to the apices of their length-tension curves. After a 5-min period, during which preparations performed isotonic contractions, muscles were again placed under isometric conditions, and the apex of the length-tension curve (L2), resting tension , time to peak tension , maximum tension development rate , and maximum tension decline rate . To evaluate contractile reserve, the mechanical performance of papillary muscles was evaluated at basal condition and after the following inotropic stimulation: post-rest contractions, extracellular Ca2+ concentration increase, and beta-adrenergic agonist isoproterenol added to the nutrient solution.The following parameters were measured from the isometric contraction: peak developed tension  was calculated from muscle weight and length by assuming cylindrical uniformity and a specific gravity of 1.0. All force data were normalized for muscle CSA. Papillary muscles with CSA >1.7 mmTransverse LV sections were fixed in 10% buffered formalin and embedded in paraffin. Sections (5 μm thick) were stained with hematoxylin–eosin and collagen-specific stain picrosirius red (Sirius red F3BA in aqueous saturated picric acid) . In at lMyocardial hydroxyproline concentration was measured to estimate myocardial collagen content. Hydroxyproline was measured in LV tissue ,33. BrieEight rats from each group were randomly chosen for serum oxidative stress evaluation. During euthanasia, blood samples were collected and centrifuged at 1,400 g for 10 min. Aliquots of 0.5 mL serum were used to measure lipid hydroperoxide concentration, which was determined in medium containing methanol 90% (v/v), 250 μM ammonium ferrous sulfate, 100 μM xylenol orange, 25 mM sulfuric acid, and 4 mM butylated hydroxytoluene. The solution was incubated for 30 minutes at room temperature and measured at 560 nm .Glutathione peroxidase was assayed in 15 μL of serum using 0.15 M phosphate buffer, pH 7.0, containing 5 mM EDTA, 0.1 mL of 0.0084 M NADPH, 4 μg of GSSG-reductase, 1.125 M sodium azide, and 0.15 M glutathione reduced form in a total volume of 0.3 mL .Superoxide dismutase activity was determined In serum aliquots of 50 μL using its ability to inhibit reduction of nitroblue tetrazolium, in medium containing 50 mM phosphate buffer pH 7.4, 0.1 mM EDTA, 50 μM NBT, 78 μM NADH, and 3.3 μM phenazine methosulfate. One unit of superoxide dismutase was defined as the amount of protein needed to decrease the reference rate to 50% of maximum inhibition .Enzyme activities were analyzed at 25°C using a microplate reader system . All reagents were purchased from Sigma .2O, incubated in DNase I (Invitrogen Life Technologies) to remove any DNA in the sample, and quantified by measuring optical density at 260 nm. RNA purity was ensured by obtaining a 260 / 280 nm optical density ratio of approximately 2.0. One microgram of RNA was reverse transcribed using High Capacity cDNA Reverse Transcription Kit in a total volume of 20 μL, according to standard methods . Aliquots of 2.5 μL (10–100 ng) of cDNA were then submitted to real-time PCR reaction using 10 μL 2× TaqMan® Universal PCR Master Mix (Applied Biosystems) and 1 μL of customized assay (20×) containing sense and antisense primers and TaqMan (Applied Biosystems) probe specific to each gene, sarcoplasmic reticulum calcium ATPase (SERCA) , α-myosin heavy chain isoform (α-MyHC) , β-myosin heavy chain isoform (β-MyHC) , and atrial natriuretic peptide (ANP) . Amplification and analysis were performed using Step One PlusTM Real Time PCR System (Applied Biosystems) according to manufacturer’s recommendation. As diabetes can modulate heart GAPDH content .Serum oxidative stress parameters are presented in Table Gene expression of SERCA, α-MyHC, and β-MyHC was not different between groups. The β-MyHC/α-MyHC ratio and ANP gene expression were higher in SHR-DM Table .In this study we showed that streptozotocin-induced diabetes mellitus activates fetal gene program, increases serum oxidative stress, and impairs left ventricular and myocardial function in senescent spontaneously hypertensive rats.To the best of our knowledge, this is the first study to evaluate the effects of streptozotocin-induced diabetes mellitus on the aged SHR heart. The spontaneously hypertensive rat is a well-established model of genetic hypertension -19. SHR In vivo cardiac structures and systolic and diastolic function were analyzed by echocardiography. Diabetes mellitus increased LV systolic diameter without changing LV diastolic diameter and left atrium diameter in both absolute and values normalized to tibia length. When normalized to body weight, LV diastolic diameter and left atrium diameter were higher in SHR-DM than SHR. Normalization of cardiac structural parameters to body weight can lead to misinterpretation of results as cardiac chambers diameters are not exactly proportional to body weight [y weight . Therefoy weight ,4,42.In this study, diabetes mellitus did not modulate blood pressure, which in accordance with Wienen et al.  in diabe2+ concentration, and isoproterenol added to nutrient solution. Myocardial diastolic function was unchanged. Isolated papillary muscle preparations allow us to properly control preload and afterload and thus analyze intrinsic myocardial function. Therefore, we can conclude that depressed myocardial systolic function in combination with ventricular eccentric remodeling is involved in diabetes-induced LV functional impairment in aged SHR. Myocardial dysfunction has also been reported in adult diabetic hypertensive and normotensive rats [Several pathophysiological mechanisms may be involved in LV dilation and dysfunction during diabetes . Impaireive rats ,45.In diabetes, several myocardial changes can be involved in myocardial dysfunction such as oxidative stress, myocardial fibrosis, fetal gene program activation, myocyte hypertrophy, and extracellular matrix metalloproteinases changes ,46.Cardiac remodeling induced by diabetes and hypertension has been associated with increased oxidative stress ,47. In tIn this study, we observed a significant increase in atrial natriuretic peptide (ANP) gene expression in SHR-DM. Increased ANP gene expression has already been reported in diabetic rats . In our In diabetes as well as in hypertension, the most prominent myocardial histopathological feature is fibrosis, which can be perivascular, interstitial, or both ,51. In tMyocyte diameter was not different between groups. Myocyte hypertrophy is a common finding in cardiomyopathy induced by type 2 diabetes. In streptozotocin-induced diabetes, probably from hypoinsulinemia, myocardial hypertrophy has not commonly been observed .One limitation of this study is that streptozotocin-induced type 1 DM is not the most common clinical situation in hypertensive aged patients. Type 1 and type 2 DM can differentially affect the heart as decreased systolic performance and delayed relaxation is more evident in type 1 DM and increased diastolic stiffness is remarkable in type 2 DM . TherefoIn conclusion, this study shows the adverse effects of type 1 diabetes when combined with genetic hypertension on cardiac remodeling in aged rats. Diabetes mellitus induces left atrium and ventricle dilation, left ventricular eccentric remodeling, and left ventricular and myocardial functional impairment. Cardiac remodeling is associated with increased oxidative stress and activated fetal gene program.ANP: Atrial natriuretic peptide; AO: Aortic diameter; A-wave: Late diastolic mitral inflow velocity; AWT: Left ventricular diastolic anterior wall thickness; BP: Systolic blood pressure; BW: Body weight; CSA: Papillary muscle cross sectional area; DM: Diabetes mellitus; DT: Peak developed tension; -dT/dt: Maximum tension decline rate; +dT/dt: Maximum tension development rate; EDT: E-wave deceleration time; EF: Ejection fraction; E-wave: Early diastolic mitral inflow velocity; FS: Endocardial fractional shortening; HR: Heart rate; IVRT: Isovolumetric relaxation time; LA: Left atrium diameter; Lmax: Length-tension curve; LV: Left ventricular; LVDD: Left ventricular diastolic diameter; LV mass: Left ventricular mass; LVSD: Left ventricular systolic diameter; LVW: Left ventricular weight; MyHC: Myosin heavy chain; PWSV: Posterior wall shortening velocity; PWT: Left ventricular diastolic posterior wall thickness; RT: Resting tension; RT-PCR: Transcription polymerase chain reaction after reverse transcription; RWT: Relative wall thickness; SERCA: Sarcoplasmic reticulum calcium ATPase; SHR: Spontaneously hypertensive rats; SWT: Left ventricular septal wall thickness; T: Tibia length; TPT: Time to peak tension.The authors declare that they have no competing interests.CMR and KO contributed to conception and design of study, acquisition of data, analysis and interpretation of data, and manuscript writing; NPX, DHSC, MDMC, CG, and RG contributed to data collection; AAHF, PFM, and ACC contributed to data collection and analysis; MPO contributed to manuscript writing. All authors have given final approval of the version to be published.


Right ventricular (RV) function is of prognostic value in patients with pulmonary hypertension (PH). Eighty percent of RV stroke volume (SV) comes from longitudinal ventricular function in a normal population, while longitudinal function accounts for 60 % of left ventricular (LV) SV. Radial function, consisting of septal and lateral function, accounts for the remaining contribution to SV. Longitudinal, septal and lateral changes in regional function has been seen as pressure is elevated on the right side.The aim of this study was quantify the longitudinal, septal and lateral contributions to SV in patients with PH using cardiac magnetic resonance (CMR), and demonstrate if there is a relationship between pulmonary pressure and these contributors to SV.Twenty patients 11 females) evaluated with right heart catheterization (RHC) for pulmonary hypertension were studied and CMR was used for assessment of cardiac volumes. Longitudinal function of the RV and LV was calculated from atrioventricular plane displacement (AVPD) in long-axis views and area between end-diastole and end-systole  were used as controls for volumes.Systolic and mean pulmonary arterial pressure (sPAP and mPAP) in PH patients were 75±25mmHg and 47±16mmHg with LV and RV ejection fraction of 56±11% and 33±12%, respectively. AVPD in patients were smaller (10.9±3.1mm for LV and 12.2±3.7mm for RV) than in controls . However, longitudinal contribution to RV SV was not different in patients from healthy subjects; explained by larger RV area in patients compared to controls. Regional contribution to RV and LV SV are shown in figure LV pumping in PH patients is affected with decreased longitudinal and increased lateral contribution to LV SV even with normal ejection fraction. In the RV, however, longitudinal and lateral contributions to RV SV are preserved in PH patients. There is a wide range of septal contribution to SV in PH patients. The prognostic implications remains to be determined.The Swedish Research Council, the Swedish Heart-Lung Foundation, the Medical Faculty of Lund University, and the Region of Skåne.


Supplemental Digital Content is available in the text. P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months ; P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling.The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study . Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI  and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; https://www.clinicaltrials.gov. Unique identifier: NCT02072850.URL:  To date, studies of remote zone ECV have included patients with chronic myocardial infarction (MI) as a small subgroup (n<50).Our specific aims were to (1) measure ECV repeatedly in STEMI survivors in a longitudinal cohort study; (2) explore the relationships between remote zone ECV 2 days post STEMI and its absolute change at 6 months from baseline (ΔECV) with clinical characteristics of MI severity; and (3) assess whether remote zone ECV or ΔECV are associated with surrogate left ventricular (LV) outcomes during long-term follow-up.Our objective was to assess the pathophysiological significance of remote zone ECV and LV remodeling in patients after an acute STEMI. We hypothesized that ECV in the remote myocardial regions of patients with STEMI would be associated with measures of severity of MI and 6-month LV volumes. To test this hypothesis, we investigated ECV repeatedly during longitudinal follow-up of STEMI survivors and assessed the associations for remote zone ECV and ΔECV with patient characteristics and LV outcomes.6 into a CMR cohort study in a regional cardiac center between January 3, 2012, and November 22, 2012. The study was approved by the National Research Ethics Service (Reference 10-S0703-28) and was publically registered (NCT020728507). Healthy volunteers also underwent CMR. All the participants provided written informed consent. The Methods section in the online-only Data Supplement provides a detailed description of the protocol and methods.We enrolled invasively managed patients with acute STEMIFor a sample size of 110 subjects, a minimum clinically significant correlation between remote zone ECV at baseline and the within-subject change in LV end-diastolic volume at 6 months from baseline could be detected with 90% power and an α of 0.05.t tests, Mann–Whitney tests, or Fisher tests. Associations between continuous variables were assessed using Pearson correlation coefficient. ECV was compared between segments using t tests. Multivariable linear regression analyses were performed to identify associates of remote zone ECV, ΔECV, and LV outcome. Backward selection was performed, and the remaining variables were included in the multivariable models. Linear regression assumptions were verified using standardized residual plots.Continuous variables are described as mean±SD if normally distributed, and median (Q1–Q3) otherwise. Categorical variables are described as n (%). Variables were described overall and by tertiles of remote zone ECV. Patient and angiographic characteristics and CMR findings were compared across ECV tertiles using 1-way ANOVA, Kruskal–Wallis tests, or Fisher tests. Variables were compared between patients and healthy volunteers using Random effects models were used to compute inter-rater reliability measures (interclass correlation coefficient) for the reliability of remote zone ECV values measured independently by 2 observers in 20 randomly selected patients from the cohort. Root mean square error was calculated. Bland–Altman plots were assessed for interobserver reliability and for agreement between synthetic and conventional ECV measures.Cox proportional hazards regression was used to explore potential associations between ECV and health outcome. The proportional hazards assumption was verified using log-minus-log plots. For these plots, continuous variables were categorized as above and below the median.P values were 2 sided. A P value >0.05 indicated the absence of a statistically significant effect. The natural log was used in transformations of variables. Analyses were performed using SPSS version 22 for Windows .All online-only Data Supplement.One hundred and forty patients with STEMI underwent CMR including pre- and postcontrast T1-mapping at 2.3±1.9 days post revascularization. One hundred and thirty-two patients (94%) had 6-month CMR, of whom 131 (94%) had pre- and postcontrast T1-mapping allowing for the measurement of ECV. Clinical case examples are shown in Figure The characteristics of patients with remote zone ECV measurement at baseline n=140) are described in Table 40 are deP=0.797). In healthy volunteers, ECV was associated with myocardial T2-relaxation time . Further analysis of healthy volunteer ECV is included in Results in the online-only Data Supplement. The results of interobserver agreement of remote zone ECV measurements are shown in Figure S2.Fifteen sex-matched healthy volunteers  also underwent CMR assessment of ECV. Remote zone ECV was similar in patients with STEMI (25.6±2.8%) and healthy volunteers , and body mass index  reduced with increasing ECV tertile: .The tertiles of remote zone ECV were ≤24.2% (n=46), >24.2 to ≤26.4% (n=47), and >26.4% (n=47). The proportion of men decreased with increasing tertile of ECV . The upper tertile of remote zone ECV had values that overlapped with ECV values observed in the infarct zone  are summarized in Table ne Table . Remote ne Table .P=0001), diabetes mellitus , BMI (kg/m2) , and LV ejection fraction at baseline (%)  were multivariable associates of remote zone ECV. The extent of myocardial edema (% LV mass) was also a multivariable associate of remote zone ECV .The multivariable associates of remote zone ECV at baseline are described in Table S2. Male sex . The within-subject ΔECV in the remote zone varied markedly (ΔECV 0.1±2.6%). The correlation between remote zone ECV and ΔECV is shown in Figure The 6-month CMR findings are described in Table ΔECV 0.1±.6%. The At 6 months, LV end-diastolic volume increased on average±SD by 2±25 mL . ΔECV in the remote zone was not associated with the change in remote zone T2 . Remote zone T1 did not change over time.Remote zone T2 was marginally higher at follow-up , no ST-segment resolution , and extent of myocardial edema  were independently associated with ΔECV.The multivariable associates of ΔECV in the remote zone are shown in Table S3. A 1-U increase in BMI  results were available in 82 subjects. The characteristics of these patients were similar to the whole cohort (data not shown).P=0.007). This relationship remained after adjustment for LV function and volumes. NT-proBNP at baseline was also associated with ΔECV  after adjustment for baseline remote zone ECV and independently of LV function and volumes.Remote zone ECV and NT-proBNP were associated at baseline , including 1 death and 6 heart failure episodes. Three patients (2%) experienced an event post discharge. In a preliminary analysis, remote zone ECV was not associated with all-cause death and heart failure hospitalization (n=7).The main findings are as follows: (1) remote zone ECV 2 days post MI is associated with male sex, BMI, and a history of diabetes mellitus; (2) ΔECV is related to the extent of injury as revealed by myocardial edema; (3) ΔECV was positively associated with changes in LV end-diastolic volume; (4) remote zone ECV and ΔECV were associated with NT-proBNP at baseline. We conclude that in STEMI survivors, an increase in remote zone ECV over time post STEMI is associated with an increase in LV end-diastolic volume, further implicating remote zone interstitial fibrosis in the pathophysiology of adverse LV remodeling.8 The results from the current study extend these findings in several ways. First, ECV early post MI is inversely associated with the change in ECV over time. Our results indicate that remote zone ECV is likely to remain persistently elevated in patients with a large MI, implying replacement fibrosis and LV remodeling. The absence of an association between remote zone ΔECV and changes in remote zone T2 (ms) over time implies that the persistent elevation in ECV is not explained by edema, indicating that extracellular matrix remodeling and fibrosis is a plausible alternative explanation. Second, the changes over time in remote zone T2 (<1 ms) were biologically insignificant, and remote zone T1 (ms) was unchanged, indicating that the changes in ECV are much more likely because of progressive interstitial fibrosis than interstitial edema. In our previous work, remote zone native T1 was not associated with NT-proBNP,8 which is in contrast to the positive association between remote zone ECV and NT-proBNP. These results may be explained by the fact that ECV is a more specific biomarker of the extracellular space, whereas native T1 reflects both intracellular and extracellular compartments. Finally, for the first time, we have reported changes in remote zone ECV over time post MI and the associations with clinical characteristics and LV remodeling. In agreement with previous observations,8 the absence of an association between remote zone ECV and the number of stenosed arteries suggest that ischemia is not a factor in remote zone remodeling. In linear regression analyses, λ had similar associations as ECV (data not shown), implying these variables are closely associated.We recently observed that remote zone tissue characteristics, as revealed by the native myocardial longitudinal relaxation time (T1), were multivariable associates of acute systemic inflammation and subsequent adverse outcomes in the longer term, including LV remodeling and all-cause death or heart failure.4 and healthy subjects.10 Sado et al10 also found height to be related to ECV, which agrees with our finding of the link between BMI and ECV. In contrast to findings by Ugander et al,3 we observed that remote zone ECV overlapped with the lower limits of infarct zone ECV. The possible explanations for this result include (1) large sample of an unselected real-world STEMI population in our study compared with a smaller sample (n=36) of patients studied by Ugander et al; (2) time between MI and CMR, which was not specified by Ugander et al and may have resulted in higher remote zone ECV in our study because of global edema and inflammatory cell influx, although the overlap persisted at 6-month follow-up.In this study, remote zone ECV exhibited a sex variation. This is in keeping with studies of remote zone ECV in patients with cardiovascular disease8 Although the effect size of the changes in ECV limits clinical use, the result is nonetheless important from the perspective of the pathophysiology and mechanisms of LV remodeling. On the contrary, we also observed that the size of infarction was a similar predictor of LV remodeling than remote zone ECV. Whether drugs that inhibit LV remodeling, for example, mineralocorticoid receptor antagonists, might have differential effects in patients according to their baseline ECV status (within the infarct and/or remote zones) merits further research. Wong et al11 observed that patients treated with renin-aldosterone-angiotensin system blockade had lower ECV.Our findings are evidence of associations between tissue characteristics in the myocardial remote zone and LV remodeling post STEMI.Postcontrast T1 maps were not acquired in all patients because of time constraints in our busy clinical service. CMR was performed at a single time point early post MI; therefore, we lack results on the temporal evolution of ECV post reperfusion. Angiotensin-converting enzyme inhibitors were prescribed in almost all patients with STEMI in our cohort (98%), and mineralocorticoid receptor antagonists were prescribed in the minority (4%); therefore, it was not possible to assess for associations between these therapies and ECV post MI. The relationship between remote zone ECV and health outcomes in STEMI survivors merits further study in a larger population. We have undertaken the largest longitudinal study of remote zone ECV in patients after an acute STEMI. Nonetheless, the results do not provide evidence of causality.In STEMI survivors, remote zone ECV is associated with sex, BMI, and a history of diabetes mellitus. Remote zone ECV at baseline and ΔECV are associated with the severity of MI including NT-proBNP. Only ΔECV was associated with LV remodeling, as revealed by CMR. ΔECV is implicated in the pathophysiology of LV remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling.Our findings provide further evidence of the pathophysiological importance of remote zone tissue characteristics and LV remodeling in survivors of acute STEMI. Future research is warranted into the association between remote zone ECV and longer-term health outcomes. Remote zone ECV is implicated in the pathophysiology of LV remodeling.We thank the patients and the staff in the Cardiology and Radiology Departments. We thank Peter Weale and Patrick Revell .This study was supported by a Project Grant from the British Heart Foundation  and the Chief Scientist Office. C. Berry was supported by a Senior Fellowship from the Scottish Funding Council. P. Welsh is supported by BHF Fellowship FS/12/62/29889. This project was also supported by a research agreement with Siemens Healthcare.None.