MRI-based strain measurements reflect morphological changes following myocardial infarction: A study on the UK Biobank cohort.

In a porcine experimental model of myocardial infarction, a localised, layer-specific, circumferential left ventricular strain metric has been shown to indicate chronic changes in ventricular function post-infarction more strongly than ejection fraction. This novel strain metric might therefore provide useful prognostic information clinically. In this study, existing clinical volume indices, global strains, and the novel, layer-specific strain were calculated for a large human cohort to assess variations in ventricular function and morphology with age, sex, and health status. Imaging and health data from the UK Biobank were obtained, including healthy volunteers and those with a history of cardiovascular illness. In total, 710 individuals were analysed and stratified by age, sex and health. Significant differences in all strain metrics were found between healthy and unhealthy populations, as well as between males and females. Significant differences in basal circumferential strain and global circumferential strain were found between healthy males and females, with males having smaller absolute values for both (all p ≤ 0.001). There were significant differences in the functional variables left ventricular ejection fraction, end-systolic volume, end-systolic volume index and mid-ventricular circumferential strain between healthy and unhealthy male cohorts aged 65-74 (all p ≤ 0.001). These results suggest that whilst regional circumferential strains may be useful clinically for assessing cardiovascular health, care must be taken to ensure critical values are indexed correctly to age and sex, due to the differences in these values observed here.

Co-Management of COVID-19 and Heart Failure During the COVID-19 Pandemic: Lessons Learned.

The COVID pandemic has brought many new challenges worldwide, which has impacted on patients with chronic conditions. There is an increasing evidence base suggesting an interaction between chronic heart failure (HF) and COVID-19, and in turn the prognostic impact of co-existence of the two conditions. Patients with existing HF appear more prone to develop severe complications on contracting COVID-19, but the exact prevalence in patients with mild symptoms of COVID-19 not requiring hospital admission is poorly investigated. In addition, hospitalization rates for acute HF over the pandemic period appear reduced compared to previous periods. Several key issues remain rather unaddressed and, importantly, a specific algorithm focused on diagnostic differentiation between HF and acute respiratory distress syndrome, a severe complication of COVID-19, is still lacking. Furthermore, recent data suggests potential interaction existing between HF treatment and some anti-viral anti-inflammatory drugs prescribed during the infection, raising some doubts about a universal treatment strategy for all patients with COVID-19. With this manuscript, we aim to review the current literature in this field in light of growing understanding of COVID-19 in the setting of the HF population, its associated morbidity and mortality burden, and the impact on healthcare systems. We hope that this may stimulate a discussion to guarantee a better, more tailored delivery of care for patients with HF in the setting of concomitant COVID-19 infection.

Influence of the arterial input sampling location on the diagnostic accuracy of cardiovascular magnetic resonance stress myocardial perfusion quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference. METHODS: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis. RESULTS: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717). CONCLUSIONS: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques.

The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use.

Deep-Learning-Based Preprocessing for Quantitative Myocardial Perfusion MRI.

BACKGROUND: Quantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particularly the segmentation. PURPOSE: To evaluate the efficacy of an automated deep learning (DL) pipeline for image processing prior to quantitative analysis. STUDY TYPE: Retrospective. POPULATION: In all, 175 (350 MRI scans; 1050 image series) clinical patients under both rest and stress conditions (135/10/30 training/validation/test). FIELD STRENGTH/SEQUENCE: 3.0T/2D multislice saturation recovery T1 -weighted gradient echo sequence. ASSESSMENT: Accuracy was assessed, as compared to the manual operator, through the mean square error of the distance between landmarks and the Dice similarity coefficient of the segmentation and bounding box detection. Quantitative perfusion maps obtained using the automated DL-based processing were compared to the results obtained with the manually processed images. STATISTICAL TESTS: Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess the myocardial blood flow (MBF) obtained using the automated DL pipeline, as compared to values obtained by a manual operator. RESULTS: The mean (SD) error in the detection of the time of peak signal enhancement in the left ventricle was 1.49 (1.4) timeframes. The mean (SD) Dice similarity coefficients for the bounding box and myocardial segmentation were 0.93 (0.03) and 0.80 (0.06), respectively. The mean (SD) error in the RV insertion point was 2.8 (1.8) mm. The Bland-Altman plots showed a bias of 2.6% of the mean MBF between the automated and manually processed MBF values on a per-myocardial segment basis. The ICC was 0.89, 95% confidence interval = [0.87, 0.90]. DATA CONCLUSION: We showed high accuracy, compared to manual processing, for the DL-based processing of myocardial perfusion data leading to quantitative values that are similar to those achieved with manual processing. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1689-1696.

Biophysical Modeling to Determine the Optimization of Left Ventricular Pacing Site and AV/VV Delays in the Acute and Chronic Phase of Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac anatomy and function adapt in response to chronic cardiac resynchronization therapy (CRT). The effects of these changes on the optimal left ventricle (LV) lead location and timing delay settings have yet to be fully explored. OBJECTIVE: To predict the effects of chronic CRT on the optimal LV lead location and device timing settings over time. METHODS: Biophysical computational cardiac models were generated for 3 patients, immediately post-implant (ACUTE) and after at least 6 months of CRT (CHRONIC). Optimal LV pacing area and device settings were predicted by pacing the ACUTE and CHRONIC models across the LV epicardium (49 sites each) with a range of 9 pacing settings and simulating the acute hemodynamic response (AHR) of the heart. RESULTS: There were statistically significant differences between the distribution of the AHR in the ACUTE and CHRONIC models (P < 0.0005 in all cases). The site delivering the maximal AHR shifted location between the ACUTE and CHRONIC models but provided a negligible improvement (<2%). The majority of the acute optimal LV pacing regions (76-100%) and device settings (76-91%) remained optimal chronically. CONCLUSION: Optimization of the LV pacing location and device settings were important at the time of implant, with a reduced benefit over time, where the majority of the acute optimal LV pacing region and device settings remained optimal with chronic CRT.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1-67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28-79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17-32 yr, 3rd quartile: 33-48 yr, and 4th quartile: 49-64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology.

Focal But Not Diffuse Myocardial Fibrosis Burden Quantification Using Cardiac Magnetic Resonance Imaging Predicts Left Ventricular Reverse Modeling Following Cardiac Resynchronization Therapy.

INTRODUCTION: Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT. METHODS AND RESULTS: In a prospective study of 48 consecutive patients (27 ischemic cardiomyopathy, 21 dilated cardiomyopathy) LV scar burdens were quantified (scar core and gray zone using late gadolinium enhancement LGE CMR; interstitial fibrosis using T1 mapping) before CRT implant. LV RR was defined by a ≥ 15% reduction in LV end-systolic volume 6 months postimplant. Twenty-seven (56%) patients were responders with RR. Association between scar quantification and LV RR was assessed using the Poisson regression model. Univariate analysis showed that QRS duration/morphology, scar core, and gray zone volumes expressed as % of LV mass and extracellular volume index (ECV) (a measure of interstitial fibrosis from T1 mapping) to be significant predictors of LV RR. Multivariable-adjusted analyses demonstrated scar core quantification (≥ 13.7% LV mass) to be the only independent predictor of LV RR (prevalence ratio 0.40, P = 0.038). CONCLUSIONS: Focal scar burden detected by LGE CMR is associated with a poor response to CRT. Diffuse interstitial fibrosis assessment by T1 mapping, however, is not independently predictive of CRT response.

Microvascular ischemia in hypertrophic cardiomyopathy: new insights from high-resolution combined quantification of perfusion and late gadolinium enhancement.

BACKGROUND: Microvascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30% of patients with HCM, potentially leading to an overestimation of the ischemic burden. We investigated the effect of left ventricle (LV) scar on the total LV ischemic burden using novel high-resolution perfusion analysis techniques in conjunction with LGE quantification. METHODS: 30 patients with HCM and unobstructed epicardial coronary arteries underwent CMR with Fermi constrained quantitative perfusion analysis on segmental and high-resolution data. The latter were corrected for the presence of fibrosis on a pixel-by-pixel basis. RESULTS: High-resolution quantification proved more sensitive for the detection of microvascular ischemia in comparison to segmental analysis. Areas of LGE were associated with significant reduction of myocardial perfusion reserve (MPR) leading to an overestimation of the total ischemic burden on non-corrected perfusion maps. Using a threshold MPR of 1.5, the presence of LGE caused an overestimation of the ischemic burden of 28%. The ischemic burden was more severe in patients with fibrosis, also after correction of the perfusion maps, in keeping with more severe disease in this subgroup. CONCLUSIONS: LGE is an important confounder in the assessment of the ischemic burden in patients with HCM. High-resolution quantitative analysis with LGE correction enables the independent evaluation of microvascular ischemia and fibrosis and should be used when evaluating patients with HCM.

Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure.

BACKGROUND: Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF. METHODS: A group of 58 patients with heart failure (HF; left ventricular ejection fraction, LVEF ≤ 50%) and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T kt perfusion and voxel-wise Fermi deconvolution. RESULTS: 30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group (p = 0.02; p = 0.04; p = 0.02, respectively). In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments (p = 0.04; p = 0.02 respectively). No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups. CONCLUSIONS: Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF.

Management of heart failure with preserved ejection fraction.

Heart failure affects nearly one million people in the UK. Half of these patients have normal, or near normal, left ventricular ejection fraction and are classified as heart failure with preserved ejection fraction (HFpEF). Newer imaging techniques have confirmed that systolic function in HFpEF patients is not completely normal, with reduced long axis function and extensive but subtle changes on exercise. Patients are likely to be older women with a history of hypertension. Other cardiovascular risk factors, such as diabetes mellitus, atrial fibrillation and coronary artery disease are prevalent in the HFpEF population. Clinical symptoms and signs in HFpEF are often nonspecific although the primary symptoms are breathlessness, fatigue and fluid retention. There is still no single diagnostic test for HFpEF and the cornerstone in the assessment remains a thorough medical history and physical examination. The duration and extent of the symptoms are relevant and it is useful to classify patients according to the NYHA functional assessment. Physical examination should include the patient's BMI and weight, heart rate and rhythm, lying and standing blood pressure and auscultation to rule out valvular disease and pulmonary congestion. Estimating the jugular venous pressure and the presence of peripheral oedema allows assessment of the patient's volume status. Patients with heart failure should be referred to heart failure nurses and have follow-up with local cardiology services as these have both been shown to reduce mortality.

Prevalence of myocardial crypts in a large retrospective cohort study by cardiovascular magnetic resonance.

BACKGROUND: Myocardial crypts are discrete clefts or fissures in otherwise compacted myocardium of the left ventricle (LV). Recent reports suggest a higher prevalence of crypts in patients with hypertrophic cardiomyopathy (HCM) and also within small samples of genotype positive but phenotype negative relatives. The presence of a crypt has been suggested to be a predictor of gene carrier status. However, the prevalence and clinical significance of crypts in the general population is unclear. We aimed to determine the prevalence of myocardial crypts in a large cohort of subjects using clinical cardiovascular magnetic resonance (CMR). METHODS: Consecutive subjects referred for clinical CMR during a 12-month period (n = 1020, age 52.6 ± 17, males: 61%) were included. Crypts were defined as >50% invagination into normal myocardium and their overall prevalence, location and shape was investigated and compared between different patient groups. RESULTS: The overall prevalence of crypts was 64/1020 (6.3%). In a predefined 'normal' control group the prevalence was lower (11/306, 3.6%, p = 0.031), but were equally prevalent in ischemic heart disease (12/236, 5.1%, p = n/s) and the combined non-ischemic cardiomyopathy (NICM) groups (24/373; 6.4%, p = n/s). Within the NICM group, crypts were significantly more common in HCM (9/76, 11.7%, p = 0.04) and hypertensive CM subjects (3/11, 27%, p = 0.03). In patients referred for CMR for family screening of inherited forms of CM, crypts were significantly more prevalent (10/41, 23%, p < 0.001), including a smaller group with a first degree relative with HCM (3/9, 33%, p = 0.01). CONCLUSION: Myocardial crypts are relatively common in the normal population, and increasingly common in HCM and hypertensive cardiomyopathy. Crypts are also more frequently seen in normal phenotype subjects referred because of a family history of an inherited cardiomyopathy and HCM specifically. It is uncertain what the significance of crypts are in this group, and because of variability in the imaging protocols used and their relative frequency within the normal population, should not be used to clinically stratify these patients. Prospective studies are required to confirm the clinical significance of myocardial crypts, as their significance remains unclear.

A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy.

BACKGROUND: Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT. METHODS: CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden). RESULTS: Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group. CONCLUSION: A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not.

Development and translation of thiometallate sulfide donors using a porcine model of coronary occlusion and reperfusion.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p < 0.05). Blood troponin T levels were significantly (p < 0.05) lower in ATTM-treated animals while myocardial glutathione peroxidase activity, an antioxidant selenoprotein, was elevated (p < 0.05). Overall, our study represents a significant advance in the development of sulfides as therapeutics and underlines the potential of ATTM as a novel adjunct therapy for reperfusion injury. Mechanistically, our study suggests that modulating selenoprotein activity could represent an additional mode of action of sulfide-releasing drugs.

Intramyocardial immunomodulation with human CD16+ monocytes to treat myocardial infarction in pig: a blind randomized preclinical trial.

Background: Human CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI). Methods and results: A total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; -55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; -30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-ß were observed in the hCD16+ Ms group. Conclusions: The use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-ß at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.

CMR reclassifies the majority of patients with suspected MINOCA and non MINOCA.

AIMS: In ∼5-15% of all cases of acute coronary syndromes (ACS) have unobstructed coronaries on angiography. Cardiac magnetic resonance (CMR) has proven useful to identify in most patients the underlying diagnosis associated with this presentation. However, the role of CMR to reclassify patients from the initial suspected condition has not been clarified. The aim of this study was to assess the proportion of patients with suspected MINOCA, or non-MINOCA, that CMR reclassifies with an alternative diagnosis from the original clinical suspicion. METHODS AND RESULTS: A retrospective cohort of patients in a tertiary cardiology centre was identified from a registry database. Patients who were referred for CMR for investigation of suspected MINOCA, and a diagnosis pre- and post-CMR was recorded to determine the proportion of diagnoses reclassified. A total of 888 patients were identified in the registry. CMR reclassified diagnosis in 78% of patients. Diagnosis of MINOCA was confirmed in only 243 patients (27%), whilst most patients had an alternative diagnosis (73%): myocarditis n = 217 (24%), Takotsubo syndrome n = 115 (13%), cardiomyopathies n = 97 (11%), and normal CMR/non-specific n = 216 (24%). CONCLUSION: In a large single-centre cohort of patients presenting with ACS and unobstructed coronary arteries, most patients had a non-MINOCA diagnosis (73%) (myocarditis, Takotsubo, cardiomyopathies, or normal CMR/non-specific findings), whilst only a minority had confirmed MINOCA (27%). Performing CMR led to reclassifying patients' diagnosis in 78% of cases, thus confirming its important clinical role and underscoring the clinical challenge in diagnosing MINOCA and non MINOCA conditions.

Altered Aortic Hemodynamics and Relative Pressure in Patients with Dilated Cardiomyopathy.

Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic resonance imaging, with aortic relative pressure derived using physics-based image processing and a virtual cohort utilized to assess the impact of cardiovascular properties on aortic behaviour. Subjects with reduced left ventricular systolic function had significantly reduced aortic relative pressure, increased aortic stiffness, and significantly delayed time-to-pressure peak duration. From the virtual cohort, aortic stiffness and aortic volumetric size were identified as key determinants of aortic relative pressure. As such, this study shows how advanced flow imaging and aortic hemodynamic evaluation could provide novel insights into the manifestation of DCM, with signs of both altered aortic structure and function derived in DCM using our proposed imaging protocol.

Stem cell therapy for heart diseases.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Despite the advances in medical and catheter-based therapy for acute myocardial infarction the 1-year mortality remains as high as 13% and the 5-year prognosis for patients with heart failure remains as high as 50%. Left ventricular systolic dysfunction, a major determinant of prognosis, is associated with significant loss of cardiomyocytes which was previously thought to be irreversible as the heart was considered a post-mitotic organ. SOURCES OF DATA: Review of literature published in peer reviewed journals and ClinicalTrials.Gov website. AREAS OF AGREEMENT: There is now growing evidence that the human heart is capable of undergoing repair and in recent years there has been an increase in basic and clinical research with the aim of harnessing the regenerative properties of stem cells in order to facilitate restoration of myocardial function. AREAS OF CONTROVERSY: The mechanisms of action of cell therapy with regards to cardiac repair remain unsatisfactorily understood and the magnitude of benefit demonstrated in animal models is yet to be fully translated in humans. GROWING POINTS: The number of clinical trials continues to increase and include treating patients with acute myocardial infarction and chronic heart failure secondary to ischaemic heart disease or dilated cardiomyopathy. AREAS TIMELY FOR DEVELOPING RESEARCH: The future of this field of research will require closer collaboration between scientists and clinicians to understand how cell therapy works and to define the ideal cell type and method of delivery to be able to derive maximum benefit.