Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Lifelong endurance exercise and its relation with coronary atherosclerosis.

AIMS: The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. METHODS AND RESULTS: The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50-60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143-177) vs. 155 (138-169) vs. 122 (108-138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17-2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24-3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01-2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28-3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12-3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39-5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06-2.99) as compared to a healthy non-athletic lifestyle. CONCLUSION: Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Relating QRS voltages to left ventricular mass and body composition in elite endurance athletes.

PURPOSE: Electrocardiogram (ECG) QRS voltages correlate poorly with left ventricular mass (LVM). Body composition explains some of the QRS voltage variability. The relation between QRS voltages, LVM and body composition in endurance athletes is unknown. METHODS: Elite endurance athletes from the Pro@Heart trial were evaluated with 12-lead ECG for Cornell and Sokolow-Lyon voltage and product. Cardiac magnetic resonance imaging assessed LVM. Dual energy x-ray absorptiometry assessed fat mass (FM) and lean mass of the trunk and whole body (LBM). The determinants of QRS voltages and LVM were identified by multivariable linear regression. Models combining ECG, demographics, DEXA and exercise capacity to predict LVM were developed. RESULTS: In 122 athletes (19 years, 71.3% male) LVM was a determinant of the Sokolow-Lyon voltage and product (ß = 0.334 and 0.477, p < 0.001) but not of the Cornell criteria. FM of the trunk (ß = - 0.186 and - 0.180, p < 0.05) negatively influenced the Cornell voltage and product but not the Sokolow-Lyon criteria. DEXA marginally improved the prediction of LVM by ECG (r = 0.773 vs 0.510, p < 0.001; RMSE = 18.9 ± 13.8 vs 25.5 ± 18.7 g, p > 0.05) with LBM as the strongest predictor (ß = 0.664, p < 0.001). DEXA did not improve the prediction of LVM by ECG and demographics combined and LVM was best predicted by including VO2max (r = 0.845, RMSE = 15.9 ± 11.6 g). CONCLUSION: LVM correlates poorly with QRS voltages with adipose tissue as a minor determinant in elite endurance athletes. LBM is the strongest single predictor of LVM but only marginally improves LVM prediction beyond ECG variables. In endurance athletes, LVM is best predicted by combining ECG, demographics and VO2max.

Histopathological Validation of Dark-Blood Late Gadolinium Enhancement MRI Without Additional Magnetization Preparation.

BACKGROUND: Conventional bright-blood late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) often suffers from poor scar-to-blood contrast due to the bright blood pool adjacent to the enhanced scar tissue. Recently, a dark-blood LGE method was developed which increases scar-to-blood contrast without using additional magnetization preparation. PURPOSE: We aim to histopathologically validate this dark-blood LGE method in a porcine animal model with induced myocardial infarction (MI). STUDY TYPE: Prospective. ANIMAL MODEL: Thirteen female Yorkshire pigs. FIELD STRENGTH/SEQUENCE: 1.5 T, two-dimensional phase-sensitive inversion-recovery radiofrequency-spoiled turbo field-echo. ASSESSMENT: MI was experimentally induced by transient coronary artery occlusion. At 1-week and 7-week post-infarction, in-vivo cardiac MRI was performed including conventional bright-blood and novel dark-blood LGE. Following the second MRI examination, the animals were sacrificed, and histopathology was obtained. Matching LGE slices and histopathology samples were selected based on anatomical landmarks. Independent observers, while blinded to other data, manually delineated the endocardial, epicardial, and infarct borders on either LGE images or histopathology samples. The percentage of infarcted left-ventricular myocardium was calculated for both LGE methods on a per-slice basis, and compared with histopathology as reference standard. Contrast-to-noise ratios were calculated for both LGE methods at 1-week and 7-week post-infarction. STATISTICAL TESTS: Pearson's correlation coefficient and paired-sample t-tests were used. Significance was set at P < 0.05. RESULTS: A combined total of 24 matched LGE and histopathology slices were available for histopathological validation. Dark-blood LGE demonstrated a high level of agreement compared to histopathology with no significant bias (-0.03%, P = 0.75). In contrast, bright-blood LGE showed a significant bias of -1.57% (P = 0.03) with larger 95% limits of agreement than dark-blood LGE. Image analysis demonstrated significantly higher scar-to-blood contrast for dark-blood LGE compared to bright-blood LGE, at both 1-week and 7-weeks post-infarction. DATA CONCLUSION: Dark-blood LGE without additional magnetization preparation provides superior visualization and quantification of ischemic scar compared to the current in vivo reference standard. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Dark-blood late gadolinium enhancement cardiovascular magnetic resonance for improved detection of subendocardial scar: a review of current techniques.

For almost 20 years, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been the reference standard for the non-invasive assessment of myocardial viability. Since the blood pool often appears equally bright as the enhanced scar regions, detection of subendocardial scar patterns can be challenging. Various novel LGE methods have been proposed that null or suppress the blood signal by employing additional magnetization preparation mechanisms. This review aims to provide a comprehensive overview of these dark-blood LGE methods, discussing the magnetization preparation schemes and findings in phantom, preclinical, and clinical studies. Finally, conclusions on the current evidence and limitations are drawn and new avenues for future research are discussed. Dark-blood LGE methods are a promising new tool for non-invasive assessment of myocardial viability. For a mainstream adoption of dark-blood LGE, however, clinical availability and ease of use are crucial.

Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Importance: Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects. Objective: To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF. Design, Setting, and Participants: Randomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded. Interventions: Patients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise). Main Outcomes and Measures: Primary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months. Results: Among 180 patients who were randomized (mean age, 70 years; 120 women [67%]), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs -0.6 mL/kg/min (difference, 1.5 [95% CI, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs -0.6 mL/kg/min (difference, 2.0 [95% CI, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, -0.4 [95% CI, -1.4 to 0.6]). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%). Conclusions and Relevance: Among patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT02078947.

Clinical value of dark-blood late gadolinium enhancement cardiovascular magnetic resonance without additional magnetization preparation.

BACKGROUND: For two decades, bright-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been considered the reference standard for the non-invasive assessment of myocardial viability. While bright-blood LGE can clearly distinguish areas of myocardial infarction from viable myocardium, it often suffers from poor scar-to-blood contrast, making subendocardial scar difficult to detect. Recently, we proposed a novel dark-blood LGE approach that increases scar-to-blood contrast and thereby improves subendocardial scar conspicuity. In the present study we sought to assess the clinical value of this novel approach in a large patient cohort with various non-congenital ischemic and non-ischemic cardiomyopathies on both 1.5 T and 3 T CMR scanners of different vendors. METHODS: Three hundred consecutive patients referred for clinical CMR were randomly assigned to a 1.5 T or 3 T scanner. An entire short-axis stack and multiple long-axis views were acquired using conventional phase sensitive inversion recovery (PSIR) LGE with TI set to null myocardium (bright-blood) and proposed PSIR LGE with TI set to null blood (dark-blood), in a randomized order. The bright-blood LGE and dark-blood LGE images were separated, anonymized, and interpreted in a random order at different time points by one of five independent observers. Each case was analyzed for the type of scar, per-segment transmurality, papillary muscle enhancement, overall image quality, observer confidence, and presence of right ventricular scar and intraventricular thrombus. RESULTS: Dark-blood LGE detected significantly more cases with ischemic scar compared to conventional bright-blood LGE (97 vs 89, p = 0.008), on both 1.5 T and 3 T, and led to a significantly increased total scar burden (3.3 ± 2.4 vs 3.0 ± 2.3 standard AHA segments, p = 0.015). Overall image quality significantly improved using dark-blood LGE compared to bright-blood LGE (81.3% vs 74.0% of all segments were of highest diagnostic quality, p = 0.006). Furthermore, dark-blood LGE led to significantly higher observer confidence (confident in 84.2% vs 78.4%, p = 0.033). CONCLUSIONS: The improved detection of ischemic scar makes the proposed dark-blood LGE method a valuable diagnostic tool in the non-invasive assessment of myocardial scar. The applicability in routine clinical practice is further strengthened, as the present approach, in contrast to other recently proposed dark- and black-blood LGE techniques, is readily available without the need for scanner adjustments, extensive optimizations, or additional training.

Late gadolinium enhancement CMR in primary mitral regurgitation.

AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. METHODS: We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39 ± 4 vs. 34 ± 5 mm, P = 0·002; LV end-diastolic diameter 57 ± 5 vs. 50 ± 5 mm, P = 0·001). There was a trend towards a higher indexed left atrial volume (55 ± 21 vs. 44 ± 13 mL/m², P = 0·06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.

Tumour necrosis factor-alpha serum level is an independent predictor of medium-term all-cause mortality after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a suitable treatment for patients with severe aortic stenosis and severely increased operative risk. There is need for a better preoperative risk assessment for TAVI candidates. AIM: To determine whether Tumour necrosis factor-alfa (TNFα) is an independent predictor of survival 500 days after TAVI. METHODS: Sixty patients undergoing TAVI were enrolled in the study. TNFα was determined. The CT measured low-density muscle fraction (LDM%) of the psoas muscle was determined. Operative risk assessment by Logistic EuroSCORE, EuroSCORE II, and STS score was performed. Frailty scores (FRAIL scale and Barthel index) were determined. RESULTS: Mean age was 81.01 ± 7.54 years. Twenty-six (43.3%) of the patients were males. In the univariable analyses, FRAIL scale and Barthel index were no predictors of survival after TAVI. In the multivariable analysis, including EuroSCORE II, LDM% and TNFα serum concentration, TNFα serum level was an independent predictor of survival 500 days after TAVI (HR: 3.167; 95%: 1.279-7.842; p = 0.013). The multivariable analysis, including TNFα as a categorical variable, showed that compared to patients in the conjugated first and second TNFα serum level tertile, patients in the third tertile had a hazard ratio (HR) of 10.606 (95%CI: 1.203 - 93.467) (p = 0.033). CONCLUSION: TNFα is an incremental independent predictor of long-term survival after TAVI.

The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Quantification of myocardial scar of different etiology using dark- and bright-blood late gadolinium enhancement cardiovascular magnetic resonance.

Dark-blood late gadolinium enhancement (LGE) has been shown to improve the visualization and quantification of areas of ischemic scar compared to standard bright-blood LGE. Recently, the performance of various semi-automated quantification methods has been evaluated for the assessment of infarct size using both dark-blood LGE and conventional bright-blood LGE with histopathology as a reference standard. However, the impact of this sequence on different quantification strategies in vivo remains uncertain. In this study, various semi-automated scar quantification methods were evaluated for a range of different ischemic and non-ischemic pathologies encountered in clinical practice. A total of 62 patients referred for clinical cardiovascular magnetic resonance (CMR) were retrospectively included. All patients had a confirmed diagnosis of either ischemic heart disease (IHD; n = 21), dilated/non-ischemic cardiomyopathy (NICM; n = 21), or hypertrophic cardiomyopathy (HCM; n = 20) and underwent CMR on a 1.5 T scanner including both bright- and dark-blood LGE using a standard PSIR sequence. Both methods used identical sequence settings as per clinical protocol, apart from the inversion time parameter, which was set differently. All short-axis LGE images with scar were manually segmented for epicardial and endocardial borders. The extent of LGE was then measured visually by manual signal thresholding, and semi-automatically by signal thresholding using the standard deviation (SD) and the full width at half maximum (FWHM) methods. For all quantification methods in the IHD group, except the 6 SD method, dark-blood LGE detected significantly more enhancement compared to bright-blood LGE (p < 0.05 for all methods). For both bright-blood and dark-blood LGE, the 6 SD method correlated best with manual thresholding (16.9% vs. 17.1% and 20.1% vs. 20.4%, respectively). For the NICM group, no significant differences between LGE methods were found. For bright-blood LGE, the 5 SD method agreed best with manual thresholding (9.3% vs. 11.0%), while for dark-blood LGE the 4 SD method agreed best (12.6% vs. 11.5%). Similarly, for the HCM group no significant differences between LGE methods were found. For bright-blood LGE, the 6 SD method agreed best with manual thresholding (10.9% vs. 12.2%), while for dark-blood LGE the 5 SD method agreed best (13.2% vs. 11.5%). Semi-automated LGE quantification using dark-blood LGE images is feasible in both patients with ischemic and non-ischemic scar patterns. Given the advantage in detecting scar in patients with ischemic heart disease and no disadvantage in patients with non-ischemic scar, dark-blood LGE can be readily and widely adopted into clinical practice without compromising on quantification.

Assessment of left ventricular volumes and primary mitral regurgitation severity by 2D echocardiography and cardiovascular magnetic resonance.

BACKGROUND: Two-dimensional transthoracic echocardiography (2DTTE) remains the first-line diagnostic imaging tool to assess primary mitral regurgitation although cardiovascular magnetic resonance (CMR) has proven to establish left ventricular function more accurately and might evaluate mitral regurgitation severity more reliably. We sought to compare routine evaluation of left ventricular function and mitral regurgitation severity by 2DTTE with assessment by CMR in moderate to severe primary mitral regurgitation without overt left ventricular dysfunction. METHODS: We prospectively included 38 patients (79% of male, age 57 ± 14 years) with at least moderate primary mitral regurgitation, a left ventricular ejection fraction ≥60% and a left ventricular end-systolic diameter ≤45 mm. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for 2DTTE and CMR. RESULTS: Left ventricular end-diastolic and end-systolic volumes were significantly underestimated by 2DTTE in comparison with CMR, although there was a strong correlation (Pearson r = 0.81, p < 0.00001 and r = 0.7, p < 0.00001, respectively). Measurement of the regurgitant orifice was similar between 2DTTE PISA method and planimetry by CMR (47 ± 24 vs. 42 ± 16 mm2, p = 0.12) with a strong correlation between both imaging techniques (Pearson r = 0.76, p < 0.0001). By contrast, assessment of the regurgitant volume by 2DTTE and by phase contrast velocity mapping by CMR showed poor agreement. CONCLUSIONS: In moderate to severe primary mitral regurgitation without overt left ventricular dysfunction, 2DTTE significantly underestimates left ventricular remodelling in comparison to CMR. Measurement of the regurgitant orifice with planimetry by CMR shows good agreement with the PISA method by 2DTTE and thus may be a valuable alternative to assess mitral regurgitation severity.

Computed tomography measured epicardial adipose tissue and psoas muscle attenuation: new biomarkers to predict major adverse cardiac events and mortality in patients with heart disease and critically ill patients. Part II: Psoas muscle area and density.

Sarcopenia is a syndrome characterised by loss of skeletal muscle mass, loss of muscle quality, and reduced muscle strength, resulting in low performance. Sarcopenia has been associated with increased mortality and complications after medical interventions. In daily clinical practice, sarcopenia is assessed by clinical assessment of muscle strength and performance tests and muscle mass quantification by dual-energy X-ray absorptio-metry (DXA) or bioelectrical impedance analysis (BIA). Assessment of the skeletal muscle quantity and quality obtained by abdominal computed tomography (CT) has gained interest in the medical community, as abdominal CT is performed for various medical reasons, and quantification of the psoas and skeletal muscle can be performed without additional radiation load and dye administration. The definitions of CT-derived skeletal muscle mass quantification are briefly reviewed: psoas muscle area (PMA), skeletal muscle area (SMA), and transverse psoas muscle thickness (TPMT). We explain how CT attenuation coefficient filters are used to determine PMA and SMA, resulting in the psoas muscle index (PMI) and skeletal muscle index (SMI), respectively, after indexation to body habitus. Psoas muscle density (PMD), a biomarker for skeletal muscle quality, can be assessed by measuring the psoas muscle CT attenuation coefficient, expressed in Hounsfield units. The concept of low-density muscle (LDM) is explained. Finally, we review the medical literature on PMI and PMD as predictors of adverse outcomes in patients undergoing trauma or elective major surgery, transplantation, and in patients with cardiovascular and internal disease. PMI and PMD are promising new biomarkers predicting adverse outcomes after medical interventions.

Computed tomography measured epicardial adipose tissue and psoas muscle attenuation: new biomarkers to predict major adverse cardiac events (MACE) and mortality in patients with heart disease and critically ill patients. Part I: Epicardial adipose tissue.

Over the last two decades, the potential role of epicardial adipocyte tissue (EAT) as a marker for major adverse cardiovascular events has been extensively studied. Unlike other visceral adipocyte tissues (VAT), EAT is not separated from the adjacent myocardium by a fascial layer and shares the same microcirculation with the myocardium. Adipocytokines, secreted by EAT, interact directly with the myocardium through paracrine and vasocrine pathways. The role of the Randle cycle, linking VAT accumulation to insulin resistance, and the relevance of blood flow and mitochondrial function of VAT, are briefly discussed. The three available imaging modalities for the assessment of EAT are discussed. The advantages of echocardiography, cardiac CT, and cardiac magnetic resonance (CMR) are compared. The last section summarises the current stage of knowledge on EAT as a clinical marker for major adverse cardiovascular events (MACE). The association between EAT volume and coronary artery disease (CAD) has robustly been validated. There is growing evidence that EAT volume is associated with computed tomography coronary angiography (CTCA) assessed high-risk plaque features. The EAT CT attenuation coefficient predicts coronary events. Many studies have established EAT volume as a predictor of atrial fibrillation after cardiac surgery. Moreover, EAT thickness has been independently associated with severe aortic stenosis and mitral annular calcification. Studies have demonstrated that EAT volume is associated with heart failure. Finally, we discuss the potential role of EAT in critically ill patients admitted to the intensive care unit. In conclusion, EAT seems to be a promising new biomarker to predict MACE.

Histopathological validation of semi-automated myocardial scar quantification techniques for dark-blood late gadolinium enhancement magnetic resonance imaging.

AIMS: To evaluate the performance of various semi-automated techniques for quantification of myocardial infarct size on both conventional bright-blood and novel dark-blood late gadolinium enhancement (LGE) images using histopathology as reference standard. METHODS AND RESULTS: In 13 Yorkshire pigs, reperfused myocardial infarction was experimentally induced. At 7 weeks post-infarction, both bright-blood and dark-blood LGE imaging were performed on a 1.5 T magnetic resonance scanner. Following magnetic resonance imaging (MRI), the animals were sacrificed, and histopathology was obtained. The percentage of infarcted myocardium was assessed per slice using various semi-automated scar quantification techniques, including the signal threshold vs. reference mean (STRM, using 3 to 8 SDs as threshold) and full-width at half-maximum (FWHM) methods, as well as manual contouring, for both LGE methods. Infarct size obtained by histopathology was used as reference. In total, 24 paired LGE MRI slices and histopathology samples were available for analysis. For both bright-blood and dark-blood LGE, the STRM method with a threshold of 5 SDs led to the best agreement to histopathology without significant bias (-0.23%, 95% CI [-2.99, 2.52%], P = 0.862 and -0.20%, 95% CI [-2.12, 1.72%], P = 0.831, respectively). Manual contouring significantly underestimated infarct size on bright-blood LGE (-1.57%, 95% CI [-2.96, -0.18%], P = 0.029), while manual contouring on dark-blood LGE outperformed semi-automated quantification and demonstrated the most accurate quantification in this study (-0.03%, 95% CI [-0.22, 0.16%], P = 0.760). CONCLUSION: The signal threshold vs. reference mean method with a threshold of 5 SDs demonstrated the most accurate semi-automated quantification of infarcted myocardium, without significant bias compared to histopathology, for both conventional bright-blood and novel dark-blood LGE.

Effect of Training on Vascular Function and Repair in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Exercise training improves peak oxygen uptake (V.O2peak) in heart failure with preserved ejection fraction (HFpEF). Multiple adaptations have been addressed, but the role of circulating endothelium-repairing cells and vascular function have not been well defined. OBJECTIVES: The authors investigated effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and repair in HFpEF. METHODS: This study is a subanalysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure) study randomizing patients with HFpEF (n = 180) to HIIT, MICT, or guideline control. At baseline, 3, and 12 months, the authors measured peripheral arterial tonometry (valid baseline measurement in n = 109), flow-mediated dilation (n = 59), augmentation index (n = 94), and flow cytometry (n = 136) for endothelial progenitor cells and angiogenic T cells. Abnormal values were defined as outside 90% of published sex-specific reference values. RESULTS: At baseline, abnormal values (%) were observed for augmentation index in 66%, peripheral arterial tonometry in 17%, flow-mediated dilation in 25%, endothelial progenitor cells in 42%, and angiogenic T cells in 18%. These parameters did not change significantly after 3 or 12 months of HIIT or MICT. Results remained unchanged when confining analysis to patients with high adherence to training. CONCLUSIONS: In patients with HFpEF, high augmentation index was common, but endothelial function and levels of endothelium-repairing cells were normal in most patients. Aerobic exercise training did not change vascular function or cellular endothelial repair. Improved vascular function did not significantly contribute to the V.O2peak improvement after different training intensities in HFpEF, contrary to previous studies in heart failure with reduced ejection fraction and coronary artery disease. (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure [OptimEx-Clin]; NCT02078947).

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

Left Ventricular Remodeling in Non-syndromic Mitral Valve Prolapse: Volume Overload or Concomitant Cardiomyopathy?

Mitral valve prolapse (MVP) is a common valvular disorder that can be associated with mitral regurgitation (MR), heart failure, ventricular arrhythmias and sudden cardiac death. Given the prognostic impact of these conditions, it is important to evaluate not only mitral valve morphology and regurgitation, but also the presence of left ventricular (LV) function and remodeling. To date, several possible hypotheses have been proposed regarding the underlying mechanisms of LV remodeling in the context of non-syndromic MVP, but the exact pathophysiological explanation remains elusive. Overall, volume overload related to severe MR is considered the main cause of LV dilatation in MVP. However, significant LV remodeling has been observed in patients with MVP and no/mild MR, particularly in patients with bileaflet MVP or Barlow's disease, generating several new hypotheses. Recently, the concept of "prolapse volume" was introduced, adding a significant volume load to the LV on top of the transvalvular MR volume. Another possible hypothesis is the existence of a concomitant cardiomyopathy, supported by the link between MVP and myocardial fibrosis. The origin of this cardiomyopathy could be either genetic, a second hit (e.g., on top of genetic predisposition) and/or frequent ventricular ectopic beats. This review provides an overview of the different mechanisms and remaining questions regarding LV remodeling in non-syndromic MVP. Since technical specifications of imaging modalities impact the evaluation of MR severity and LV remodeling, and therefore might influence clinical decision making in these patients, this review will also discuss assessment of MVP using different imaging modalities.