Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center ...study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists.
This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information.
A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up.
Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004).
This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.
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The present study aims to assess the clinical and hemodynamic impact of percutaneous edge-to-edge mitral valve repair with MitraClip in patients with atrial functional mitral regurgitation (A-FMR) ...compared with ventricular functional mitral regurgitation (V-FMR). Mitral regurgitation (MR) grade, functional status (New York Heart Association class), and major adverse cardiac events (MACE; all-cause mortality or hospitalization for heart failure) were evaluated in 52 patients with A-FMR and in 307 patients with V-FMR. In 56 patients, hemodynamic assessment during exercise echocardiography was performed before and 6 months after intervention. MR reduction after MitraClip implantation was noninferior in A-FMR compared with V-FMR (MR grade ≤2 at 6 months in 94% vs 82%, respectively, p <0.001 for noninferiority) and was associated with improvement of functional status (New York Heart Association class ≤2 at 6 months in 90% vs 80%, respectively, p = 0.2). Hemodynamic assessment revealed that cardiac output at 6 months was higher in A-FMR at rest (5.1 ± 1.5 L/min vs 3.8 ± 1.5 L/min, p = 0.002) and during peak exercise (7.9 ± 2.4 L/min vs 6.1 ± 2.1 L/min, p = 0.02). In addition, the reduction in systolic pulmonary artery pressure at rest was more pronounced in A-FMR: Δ SPAP −13.1 ± 15.1 mm Hg versus −2.2 ± 13.3 mm Hg (p = 0.03). MACE rate at follow-up was significantly lower in A-FMR versus V-FMR, with an adjusted odds ratio of 0.46 (95% confidence interval 0.24 to 0.88), which was caused by a reduction in hospitalization for heart failure. In conclusion, percutaneous edge-to-edge mitral valve repair with MitraClip is at least as effective in A-FMR as in V-FMR in reducing MR. However, the hemodynamic improvement and reduction of MACE were significantly better in A-FMR.
In heart failure patients with significant secondary mitral regurgitation:•Left ventricular end systolic dimension (LVESD) may define baseline LV remodeling.•Higher LVESD (advanced remodeling) does ...not affect MitraClip safety nor efficacy.•Higher LVESD (advanced remodeling) does not affect MitraClip symptomatic response.•Higher LVESD (advanced remodeling) attenuates prognostic benefit of MitraClip.•LVESD may be a valuable parameter for heart failure MitraClip patient selection.
Recent MitraClip heart failure (HF) trials suggest that baseline left ventricular (LV) remodeling may be critical for patient selection. We, therefore, investigated whether baseline LV remodeling affects safety, efficacy, and clinical outcomes in HF patients with symptomatic secondary mitral regurgitation (MR) undergoing percutaneous mitral valve repair using MitraClip. LV remodeling was assessed by LV end-systolic dimension index (LVESDi) on transthoracic baseline echocardiography. Early and late outcome was reported using Mitral Valve Academic Research Consortium-criteria. A total of 107 consecutive HF patients (73 ± 10 years, 70% male) who underwent MitraClip intervention for secondary MR were studied. The study population was stratified by median LVESDi between nonadvanced (<28 mm/m², n = 49) and advanced LV remodeling (≥28 mm/m², n = 58). Both groups had similar acute procedural success, in hospital bleeding and nonbleeding complications and significant improvement in MR severity and symptoms, sustained up to 36 months (all p >0.05). LVESDi, but not LV end-diastolic diameter index nor LV ejection fraction, independently related to HF hospitalization (hazard ratio 1.11, 95% confidence interval 1.05 to 1.16, p <0.001) and mortality (hazard ratio 1.11, 95% confidence interval 1.06 to 1.17, p <0.001). At 1 and 3 years, survival free of HF hospitalization was higher in patients without versus with advanced LV remodeling (89% vs 66% and 65% vs 37%, p = 0.002) and mortality was lower (9% vs 24% and 36% vs 47%, p = 0.074), respectively. Annual HF hospitalization rate only decreased in the nonadvanced LV remodeling group (−43%, p = 0.025). Advanced LV remodeling, assessed by LVESDi, in HF patients who underwent MitraClip therapy does not influence therapeutic safety nor efficacy, but implies increased HF hospitalization and mortality risk. This parameter may be valuable for MitraClip therapy patient selection.
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
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.
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.
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.
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).
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.
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 (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.
The field of inflammatory disease of the heart or "cardio-immunology" is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In ...acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.
Abstract
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.
Structured Graphical Abstract
Structured Graphical Abstract
The Master@Heart study compared the prevalence of calcified, mixed, and non-calcified coronary plaques by computed tomography between 176 controls, 191 late-onset endurance athletes, and 191 lifelong endurance athletes, in the absence of established risk factors for coronary artery disease. Lifelong endurance athletes had the highest coronary plaque burden regardless of plaque types.
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