ABSTRACT
OBJECTIVES: Parametric mapping constitutes a novel cardiac magnetic resonance (CMR) technique enabling quantitative assessment of pathologic alterations of left ventricular (LV) myocardium. This study aimed to investigate the clinical utility of mapping techniques with and without contrast agent compared to standard CMR to predict adverse LV remodeling following acute myocardial infarction (AMI). MATERIALS AND METHODS: A post hoc analysis was performed on sixty-four consecutively enrolled patients (57 ± 12 years, 54 men) with first-time reperfused AMI. Baseline CMR was obtained at 8 ± 5 days post-AMI, and follow-up CMR at 6 ± 1.4 months. T1/T2 mapping, T2-weighted, and late gadolinium enhancement (LGE) acquisitions were performed at baseline and cine imaging was used to determine adverse LV remodeling, defined as end-diastolic volume increase by 20% at 6 months. RESULTS: A total of 11 (17%) patients developed adverse LV remodeling. At baseline, patients with LV remodeling showed larger edema (30 ± 11 vs. 22 ± 10%LV; p < 0.05), infarct size (24 ± 11 vs. 14 ± 8%LV; p < 0.001), extracellular volume (ECVinfarct; 63 ± 12 vs. 47 ± 11%; p < 0.001), and native T2infarct (95 ± 16 vs. 78 ± 17 ms; p < 0.01). ECVinfarct and infarct size by LGE were the best predictors of LV remodeling with areas under the curve (AUCs) of 0.843 and 0.789, respectively (all p < 0.01). Native T1infarct had the lowest AUC of 0.549 (p = 0.668) and was inferior to edema size by T2-weighted imaging (AUC = 0.720; p < 0.05) and native T2infarct (AUC = 0.766; p < 0.01). CONCLUSION: In this study, ECVinfarct and infarct size by LGE were the best predictors for the development of LV remodeling within 6 months after AMI, with a better discriminative performance than non-contrast mapping CMR. CLINICAL RELEVANCE STATEMENT: This study demonstrates the predictive value of contrast-enhanced and non-contrast as well as conventional and novel CMR techniques for the development of LV remodeling following AMI, which might help define precise CMR endpoints in experimental and clinical myocardial infarction trials. KEY POINTS: ⢠Multiparametric CMR provides insights into left ventricular remodeling at 6 months following an acute myocardial infarction. ⢠Extracellular volume fraction and infarct size are the best predictors for adverse left ventricular remodeling. ⢠Contrast-enhanced T1 mapping has a better predictive performance than non-contrast standard CMR and T1/T2 mapping.
Subject(s)
Contrast Media , Myocardial Infarction , Male , Humans , Contrast Media/pharmacology , Ventricular Remodeling , Magnetic Resonance Imaging, Cine/methods , Predictive Value of Tests , Gadolinium , Myocardial Infarction/complications , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/pathology , Magnetic Resonance Imaging , Myocardium/pathology , Edema/pathology , Ventricular Function, LeftABSTRACT
OBJECTIVE: To determine the influence of arterial hypertension (AHT), sex, and the interaction between both left- and right ventricular (LV, RV) morphology, function, and tissue characteristics. METHODS: The Hamburg City Health Study (HCHS) is a population-based, prospective, monocentric study. 1972 individuals without a history of cardiac diseases/ interventions underwent 3 T cardiac MR imaging (CMR). Generalized linear models were conducted, including AHT, sex (and the interaction if significant), age, body mass index, place of birth, diabetes mellitus, smoking, hyperlipoproteinemia, atrial fibrillation, and medication. RESULTS: Of 1972 subjects, 68% suffered from AHT. 42% with AHT and 49% controls were female. Females overall showed a higher ejection fraction (EF) (LV: regression coefficient +2.4% [95% confidence interval: 1.7; 3.1]), lower volumes and LV mass (-19.8% [-21.3; -18.5]), and prolonged native septal T1 (+22.1 ms [18.3; 25.9])/T2 relaxation times (+1.1 ms [0.9; 1.3]) (all p < 0.001) compared to males. Subjects with AHT showed a higher EF (LV: +1.2% [0.3; 2.0], p = 0.009) and LV mass (+6.6% [4.3; 9.0], p < 0.001) than controls. The interaction between sex and AHT influenced mapping. After excluding segments with LGE, males (-0.7 ms [-1.0; -0.3 | ) and females with AHT (-1.1 ms [-1.6; -0.6]) showed shorter T2 relaxation times than the sex-respective controls (p < 0.001), but the effect was stronger in females. CONCLUSION: In the HCHS, female and male subjects with AHT likewise showed a higher EF and LV mass than controls, independent of sex. However, differences in tissue characteristics between subjects with AHT and controls appeared to be sex-specific. CLINICAL RELEVANCE STATEMENT: The interaction between sex and cardiac risk factors is an underestimated factor that should be considered when comparing tissue characteristics between hypertensive subjects and controls, and when establishing cut-off values for normal and pathological relaxation times. KEY POINTS: There are sex-dependent differences in arterial hypertension, but it is unclear if cardiac MR parameters are sex-specific. Differences in cardiac MR parameters between hypertensive subjects and healthy controls appeared to be sex-specific for tissue characteristics. Sex needs to be considered when comparing tissue characteristics in patients with arterial hypertension to healthy controls.
ABSTRACT
BACKGROUND: The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent "unrecognized myocardial scar" (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. METHODS: The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. RESULTS: Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65-0.90), p = 0.002) and LV mass (OR per SD 1.54 (CI 1.31-1.82), p < 0.001). Ischemic UMS was independently associated with LV ejection fraction (OR per SD 0.58 (CI 0.39-0.86), p = 0.007), LV mass (OR per SD 1.74 (CI 1.25-2.45), p = 0.001), and diabetes (OR 4.91 (CI 1.66-13.03), p = 0.002). Non-ischemic UMS was only independently associated with LV mass (OR per SD 1.44 (CI 1.24-1.69), p < 0.001). CONCLUSION: UMS, in particular with a non-ischemic pattern, is frequent in individuals without known cardiac disease and predominantly involves the basal inferolateral LV myocardium. Presence of UMS is independently associated with a lower LVEF, a higher LV mass, and a history of diabetes.
Subject(s)
Cicatrix , Contrast Media , Magnetic Resonance Imaging, Cine , Myocardium , Predictive Value of Tests , Stroke Volume , Ventricular Function, Left , Humans , Female , Male , Middle Aged , Contrast Media/administration & dosage , Cicatrix/diagnostic imaging , Cicatrix/physiopathology , Cicatrix/etiology , Cicatrix/pathology , Aged , Myocardium/pathology , Risk Factors , Prevalence , Germany/epidemiology , Organometallic Compounds/administration & dosage , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Cardiomyopathies/pathology , Cross-Sectional Studies , Prospective Studies , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Asymptomatic DiseasesABSTRACT
OBJECTIVES: This study analyzed the prevalence and pattern of focal and potential diffuse myocardial fibrosis detected by late gadolinium enhancement (LGE) and extracellular volume (ECV) imaging in male and female marathon runners using cardiac magnetic resonance (CMR). METHODS: Seventy-four marathon runners were studied including 55 males (44 ± 8 years) and 19 females (36 ± 7 years) and compared to 36 controls with similar age and sex using contrast-enhanced CMR, exercise testing, and blood samples. RESULTS: Contrast-enhanced CMR revealed focal myocardial fibrosis in 8 of 74 runners (11%). The majority of runners were male (7 of 8, 88%). LGE was typically non-ischemic in 7 of 8 runners (88%) and ischemic in one runner. ECV was higher in remote myocardium without LGE in male runners (25.5 ± 2.3%) compared to male controls (24.0 ± 3.0%, p < 0.05), indicating the potential presence of diffuse myocardial fibrosis. LV mass was higher in LGE + males (86 ± 18 g/m2) compared to LGE- males (73 ± 14 g/m2, p < 0.05). Furthermore, LGE + males had lower weight (69 ± 9 vs 77 ± 9 kg, p < 0.05) and shorter best marathon finishing times (3.2 ± 0.3 h) compared to LGE- males (3.6 ± 0.4 h, p < 0.05) suggesting higher training load in these runners to accomplish the marathon in a short time. CONCLUSION: The high frequency of non-ischemic myocardial fibrosis in LGE + male runners can be related to increased LV mass in these runners. Furthermore, a higher training load could explain the higher LV mass and could be one additional cofactor in the genesis of myocardial fibrosis in marathon runners. KEY POINTS: ⢠A high frequency of myocardial fibrosis was found in marathon runners. ⢠Myocardial fibrosis occurred typically in male runners and was typically non-ischemic. ⢠Higher training load could be one cofactor in the genesis of myocardial fibrosis in marathon runners.
Subject(s)
Cardiomyopathies , Contrast Media , Male , Humans , Female , Marathon Running , Prevalence , Magnetic Resonance Imaging, Cine , Gadolinium , Myocardium/pathology , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Cardiomyopathies/pathology , Fibrosis , Magnetic Resonance Spectroscopy , Predictive Value of TestsABSTRACT
OBJECTIVES: Parametric cardiac magnetic resonance (CMR) techniques have improved the diagnosis of pathologies. However, the primary tool for differentiating non-ST elevation myocardial infarction (NSTEMI) from myocarditis is still a visual assessment of conventional signal-intensity-based images. This study aimed at analyzing the ability of parametric compared to conventional techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns. METHODS: Twenty NSTEMI patients, twenty infarct-like myocarditis patients, and twenty controls were examined using cine, T2-weighted CMR (T2w) and late gadolinium enhancement (LGE) imaging and T1/T2 mapping on a 1.5 T scanner. CMR images were presented in random order to two experienced fully blinded observers, who had to assign them to three categories by a visual analysis: NSTEMI, myocarditis, or healthy. RESULTS: The conventional approach (cine, T2w and LGE combined) had the best diagnostic accuracy with 92% (95%CI: 81-97) for NSTEMI and 86% (95%CI: 71-94) for myocarditis. The diagnostic accuracies using T1 maps were 88% (95%CI: 74-95) and 80% (95%CI: 62-91), 84% (95%CI: 67-93) and 74% (95%CI: 54-87) for LGE, and 83% (95%CI: 66-92) and 73% (95%CI: 53-87) for T2w. The accuracies for cine (72% (95%CI: 52-86) and 60% (95%CI: 38-78)) and T2 maps (62% (95%CI: 40-79) and 47% (95%CI: 28-68)) were significantly lower compared to the conventional approach (p < 0.001 and p < 0.0001). CONCLUSIONS: The conventional approach provided a reliable visual discrimination between NSTEMI, myocarditis, and controls. The diagnostic accuracy of a visual pattern analysis of T1 maps was not significantly inferior, whereas the diagnostic accuracy of T2 maps was not sufficient in this context. CLINICAL RELEVANCE STATEMENT: The ability of parametric compared to conventional CMR techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns can avoid potentially unnecessary invasive coronary angiography and help to shorten CMR protocols and to reduce the need of gadolinium contrast agents. KEY POINTS: ⢠A visual differentiation of ischemic from non-ischemic patterns of myocardial injury is reliably achieved by a combination of conventional CMR techniques (cine, T2-weighted and LGE imaging). ⢠There is no significant difference in accuracies between visual pattern analysis on native T1 maps without providing quantitative values and a conventional combined approach for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls. ⢠T2 maps do not provide a sufficient diagnostic accuracy for visual pattern analysis for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls.
Subject(s)
Myocarditis , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Myocarditis/diagnostic imaging , Myocarditis/pathology , Contrast Media , Non-ST Elevated Myocardial Infarction/pathology , Myocardium/pathology , Magnetic Resonance Imaging, Cine/methods , Gadolinium , ST Elevation Myocardial Infarction/pathology , Predictive Value of TestsABSTRACT
OBJECTIVES: The study aimed to investigate the alterations of myocardial deformation responding to long-standing pressure overload and the effects of focal myocardial fibrosis using feature-tracking cardiac magnetic resonance (FT-CMR) in patients with resistant hypertension (RH). METHODS: Consecutive RH patients were prospectively recruited and underwent CMR at a single institution. FT-CMR analyses based on cine images were applied to measure left ventricular (LV) peak systolic global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). Functional and morphological CMR variables, and late gadolinium enhancement (LGE) imaging were also obtained. RESULTS: A total of 50 RH patients (63 ± 12 years, 32 men) and 18 normotensive controls (57 ± 8 years, 12 men) were studied. RH patients had a higher average systolic blood pressure than controls (166 ± 21 mmHg vs. 116 ± 8 mmHg, p < 0.001) with the intake of 5 ± 1 antihypertensive drugs. RH patients showed increased LV mass index (78 ± 15 g/m2 vs. 61 ± 9 g/m2, p < 0.001), decreased GLS (- 16 ± 3% vs. - 19 ± 2%, p = 0.001) and GRS (41 ± 12% vs. 48 ± 8%, p = 0.037), and GCS was reduced by trend (- 17 ± 4% vs. - 19 ± 4%, p = 0.078). Twenty-one (42%) RH patients demonstrated a LV focal myocardial fibrosis (LGE +). LGE + RH patients had higher LV mass index (85 ± 14 g/m2 vs. 73 ± 15 g/m2, p = 0.007) and attenuated GRS (37 ± 12% vs. 44 ± 12%, p = 0.048) compared to LGE - RH patients, whereas GLS (p = 0.146) and GCS (p = 0.961) were similar. CONCLUSION: Attenuation of LV GLS and GRS, and GCS decline by tendency, might be adaptative changes responding to chronic pressure overload. There is a high incidence of focal myocardial fibrosis in RH patients, which is associated with reduced LV GRS. CLINICAL RELEVANCE STATEMENT: Feature-tracking CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in patients with resistant hypertension. KEY POINTS: ⢠Variations of left ventricular strain are attributable to the degree of myocardial impairment in resistant hypertensive patients. ⢠Focal myocardial fibrosis of the left ventricle is associated with attenuated global radial strain. ⢠Feature-tracking CMR provides additional information on the attenuation of myocardial deformation responding to long-standing high blood pressure.
Subject(s)
Cardiomyopathies , Hypertension , Male , Humans , Ventricular Function, Left/physiology , Heart Ventricles/diagnostic imaging , Contrast Media/pharmacology , Gadolinium , Hypertension/complications , Hypertension/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Fibrosis , Predictive Value of TestsABSTRACT
AIMS: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. METHODS AND RESULTS: Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. CONCLUSION: RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.
Subject(s)
Arrhythmias, Cardiac , Papillary Muscles , Animals , Sheep , Ventricular Fibrillation/diagnosis , Ventricular Fibrillation/etiology , Heart Ventricles , Action Potentials/physiology , ElectrocardiographyABSTRACT
AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.
Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Humans , SARS-CoV-2 , Stroke Volume , Ventricular Function, LeftABSTRACT
OBJECTIVES: Cardiac adaptation in endurance athletes is a well-known phenomenon, but the acute impact of strenuous exercise is rarely reported on. The aim of this study was to analyze the alterations in biventricular and biatrial function in triathletes after an endurance race using novel feature-tracking cardiac magnetic resonance (FT-CMR). METHODS: Fifty consecutive triathletes (45 ± 10 years; 80% men) and twenty-eight controls were prospectively recruited, and underwent 1.5-T CMR. Biventricular and biatrial volumes, left ventricular ejection fraction (LVEF), FT-CMR analysis, and late gadolinium imaging (LGE) were performed. Global systolic longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were assessed. CMR was performed at baseline and following an endurance race. High-sensitive troponin T and NT-proBNP were determined. The time interval between race completion and CMR was 2.3 ± 1.1 h (range 1-5 h). RESULTS: Post-race troponin T (p < 0.0001) and NT-proBNP (p < 0.0001) were elevated. LVEF remained constant (62 ± 6 vs. 63 ± 7%, p = 0.607). Post-race LV GLS decreased by tendency (- 18 ± 2 vs. - 17 ± 2%, p = 0.054), whereas GCS (- 16 ± 4 vs. - 18 ± 4%, p < 0.05) and GRS increased (39 ± 11 vs. 44 ± 11%, p < 0.01). Post-race right ventricular GLS (- 19 ± 3 vs. - 19 ± 3%, p = 0.668) remained constant and GCS increased (- 7 ± 2 vs. - 8 ± 3%, p < 0.001). Post-race left atrial GLS (30 ± 8 vs. 24 ± 6%, p < 0.0001) decreased while right atrial GLS remained constant (25 ± 6 vs. 24 ± 6%, p = 0.519). CONCLUSIONS: The different alterations of post-race biventricular and biatrial strain might constitute an intrinsic compensatory mechanism following an acute bout of endurance exercise. The combined use of strain parameters may allow a better characterization of ventricular and atrial function in endurance athletes. KEY POINTS: ⢠Triathletes demonstrate a decrease of LV global longitudinal strain by tendency and constant RV global longitudinal strain following an endurance race. ⢠Post-race LV and RV global circumferential and radial strains increase, possibly indicating a compensatory mechanism after an acute endurance exercise bout. ⢠Subgroup analyses of male triathletes with focal myocardial fibrosis did not demonstrate alterations in biventricular and biatrial strain after an endurance race.
Subject(s)
Magnetic Resonance Imaging, Cine , Ventricular Function, Left , Adult , Female , Fibrosis , Humans , Magnetic Resonance Imaging, Cine/methods , Male , Middle Aged , Myocardium/pathology , Predictive Value of Tests , Stroke Volume , Troponin TABSTRACT
BACKGROUND: To analyze the effect of myocardial fibrosis on left ventricular (LV) function evaluated by feature-tracking strain analysis by cine cardiac magnetic resonance (CMR) in competitive male triathletes with normal ejection fraction (EF).MethodsâandâResults:78 asymptomatic male triathletes with >10 weekly training hours (43±11 years) and 28 male age-matched controls were studied by late gadolinium enhancement (LGE) and cine CMR. Global and segmental radial, longitudinal and circumferential strains were analyzed using feature-tracking cine CMR. Focal non-ischemic LGE was observed in 15 of 78 triathletes (19%, LGE+) with predominance in the basal inferolateral segments. LVEF was normal in LGE+ (62±6%) and LGE- triathletes (62±5%, P=0.958). In contrast, global radial strain was lower in LGE+ triathletes at 40±7% compared with LGE- triathletes (45±7%, P<0.05). Reduced segmental radial strain occurred either in LGE+ segments or in directly adjacent segments. Strain analysis revealed regional differences in controls, with the highest radial and longitudinal strain in the inferolateral segments, which were typically affected by fibrosis in LGE+ triathletes. CONCLUSIONS: Reduced global and regional radial strain suggests a negative effect of myocardial fibrosis on LV function in LGE+ triathletes with normal EF. The observed regional differences in controls with the highest radial and longitudinal strain in the inferolateral segments may explain the typical occurrence of fibrosis in this myocardial region in triathletes.
Subject(s)
Athletes , Cardiomyopathies , Magnetic Resonance Imaging, Cine , Myocardium , Stroke Volume , Ventricular Function, Left , Adolescent , Adult , Aged , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Fibrosis , Humans , Male , Middle AgedABSTRACT
BACKGROUND: The purpose of this work is to describe the objectives and design of cardiovascular magnetic resonance (CMR) imaging in the single center, prospective, population-based Hamburg City Health study (HCHS). The HCHS aims at improving risk stratification for coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF). METHODS: The HCHS will finally include 45,000 inhabitants of the city of Hamburg (Germany) between 45 and 74 years who undergo an extensive cardiovascular evaluation and collection of biomaterials. Risk-scores for CAD, AF and HF are used to create enriched subpopulations who are invited for CMR. A total number of approximately 12,362 subjects will undergo CMR and incident CAD, AF and HF will be assessed after 6 years follow-up. The standard CMR protocol includes cine-CMR, T1 and T2 mapping, aortic/mitral valve flow measurements, Late gadolinium enhancement, angiographies and measurements of aortic distensibility. A stress-perfusion scan is added in individuals at risk for CAD. The workflow of CMR data acquisition and analyses was evaluated in a pilot cohort of 200 unselected subjects. RESULTS: The obtained CMR findings in the pilot cohort agree with current reference values and demonstrate the ability of the established workflow to accomplish the objectives of HCHS. CONCLUSIONS: CMR in HCHS promises novel insights into major cardiovascular diseases, their subclinical precursors and the prognostic value of novel imaging biomarkers. The HCHS database will facilitate combined analyses of imaging, clinical and molecular data ("Radiomics").
Subject(s)
Atrial Fibrillation/diagnostic imaging , Coronary Artery Disease/diagnostic imaging , Heart Failure/diagnostic imaging , Magnetic Resonance Imaging, Cine , Research Design , Aged , Atrial Fibrillation/epidemiology , Atrial Fibrillation/physiopathology , Contrast Media/administration & dosage , Coronary Artery Disease/epidemiology , Coronary Artery Disease/physiopathology , Female , Follow-Up Studies , Germany/epidemiology , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Incidence , Male , Meglumine/administration & dosage , Middle Aged , Organometallic Compounds/administration & dosage , Pilot Projects , Predictive Value of Tests , Prognosis , Prospective Studies , Reproducibility of Results , Time Factors , WorkflowABSTRACT
BACKGROUND: In many cardiac diseases, myocardial scar tissue detected by late gadolinium enhancement (LGE) is a risk factor for cardiac arrhythmia and sudden cardiac death. Previous studies in athletes reported an increased risk for cardiac events in this group of ostensibly healthy subjects. However, the currently available longitudinal studies on this topic included fairly old marathon runners with a mean age of 57 ± 6 years or represent a case-control study in athletes with preexisting ventricular arrhythmia. The purpose of this prospective study was to analyze the prognostic relevance of LGE cardiac magnetic resonance (CMR) in middle-aged endurance athletes without known preexisting cardiac disorders. METHODS: Three-hundred and twelve apparently healthy athletes were prospectively enrolled. Inclusion criteria were a training for a minimum of 10 h per week and regularly participation in competitions. LGE CMR was obtained at baseline in all athletes and presence of LGE was classified visually according to established criteria as ischemic LGE, major or minor non-ischemic LGE or absent LGE. Follow-up consisted of a standardized questionnaire and an additional phone call in case of incomplete data. An event was defined as fatal myocardial infarction, ventricular tachycardia, ventricular fibrillation or sudden cardiac death (SCD). RESULTS: Complete follow-up was available for 293/312 athletes (94%) including 145 triathletes, 74 marathon runners and 74 cyclists after a median of 5.6 [quartiles 4,3, 6,4] years. Median age was 44 [35, 50] years at study enrollment. Spiroergometry did not reveal heart rhythm disturbances or significant ECG changes in the study population. LGE CMR revealed myocardial scar/focal fibrosis in 80 of 293 athletes (27%) including 7 athletes (2%) with ischemic subendocardial LGE of the left ventricle (LV), 16 athletes (6%) with major non-ischemic LGE of the LV and 57 athletes (19%) with minor non-ischemic LGE. During follow-up, two athletes experienced SCD. One marathon runner died during a training run and one cyclist died suddenly at rest. Both athletes had ischemic LGE of the LV. The event rate for SCD was 0.7% in the entire study population and 28% in the 7 athletes with ischemic LGE (p < 0.001 compared to athletes without LGE). CONCLUSIONS: Our findings indicate that athletes with ischemic LGE due to unrecognized myocardial infarction are at increased risk for SCD. Our findings highlight the value of LGE CMR to detect occult ischemic scar in asymptomatic apparently healthy athletes, which is of importance, since current guidelines do not recommend to incorporate routine cardiac imaging in pre-participation screening. Athletes with ischemic myocardial scar should at least consider to refrain from high-level exercise as an individual decision.
ABSTRACT
BACKGROUND: Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need. METHODS AND RESULTS: A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P=0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance. CONCLUSIONS: MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.
Subject(s)
Biomarkers , Matrix Metalloproteinase 1 , Myocarditis , Non-ST Elevated Myocardial Infarction , Peptide Fragments , Procollagen , Humans , Male , Female , Biomarkers/blood , Middle Aged , Matrix Metalloproteinase 1/blood , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Procollagen/blood , Peptide Fragments/blood , Myocarditis/blood , Myocarditis/diagnosis , Diagnosis, Differential , Aged , Case-Control Studies , Adult , Predictive Value of Tests , Magnetic Resonance Imaging, Cine/methods , ROC CurveABSTRACT
The extracellular matrix protein reelin controls radial migration and layer formation of cortical neurons, in part by modulation of cytoskeletal dynamics. A stabilizing effect of reelin on the actin cytoskeleton has been described recently. However, it is poorly understood how reelin modulates microtubule dynamics. Here, we provide evidence that reelin increases microtubule assembly. This effect is mediated, at least in part, by promoting microtubule plus end dynamics in processes of developing neurons. Thus, we treated primary neuronal cultures with nocodazole to disrupt microtubules. After nocodazole washout, we found microtubule reassembly to be accelerated in the presence of reelin. Moreover, we show that reelin treatment promoted the formation of microtubule plus end binding protein 3 (EB3) comets in developing dendrites, and that EB3 immunostaining in the developing wild-type neocortex is most intense in the reelin-rich marginal zone where leading processes of radially migrating neurons project to. This characteristic EB3 staining pattern was absent in reeler. Also reassembly of nocodazole-dispersed dendritic Golgi apparati, which are closely associated to microtubules, was accelerated by reelin treatment, though with a substantially slower time course when compared to microtubule reassembly. In support of our in vitro results, we found that the subcellular distribution of α-tubulin and acetylated tubulin in reeler cortical sections differed from wild-type and from mice lacking the very low density lipoprotein receptor (VLDLR), known to bind reelin. Taken together, our results suggest that reelin promotes microtubule assembly, at least in part, by increasing microtubule plus end dynamics.
Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Extracellular Matrix Proteins/metabolism , Microtubules/metabolism , Nerve Tissue Proteins/metabolism , Neurons/cytology , Neurons/metabolism , Serine Endopeptidases/metabolism , Animals , Cell Adhesion Molecules, Neuronal/genetics , Cells, Cultured , Extracellular Matrix Proteins/genetics , Mice , Mice, Neurologic Mutants , Microtubule-Associated Proteins/analysis , Microtubule-Associated Proteins/metabolism , Nerve Tissue Proteins/genetics , Rats , Rats, Wistar , Reelin Protein , Serine Endopeptidases/genetics , Tubulin/analysis , Tubulin/metabolismABSTRACT
Cardiac manifestation of classical Fabry disease (cFD) varies with sex and presence of left ventricular hypertrophy. p.D313Y/p.A143T variants (vFD) represent milder late-onset phenotypes, however, data on vFD are scarce. Patients with FD (cFD = 37;vFD = 14) and 14 healthy controls underwent 1.5 T CMR including Cine, LGE, native T1 mapping(nT1) and myocardial strain(CMR-FT). CMR-FT was assessed using ventricular longitudinal, circumferential, radial (LV-GLS/RV-GLS, LV-GCS/LV-GRS), and atrial longitudinal strain (LA/RATotal, LA/RAConduit, LA/RABooster). In cFD reduced myocardial strain (LV-GLS: -20 ± 4 vs. -24 ± 3%,p = 0.007; LV-GCS: -20 ± 4 vs. -26 ± 4%,p = 0.002, LA Total -GLS: 29 ± 10 vs. 37 ± 6%,p = 0.007; LA Conduit -GLS: 15 ± 10 vs. 23 ± 5%,p = 0.003) and nT1 values (951 ± 51 ms vs. 1036 ± 20 ms, p < 0.001) were observed compared to controls. In vFD findings were comparable to controls. LV-GCS provided the closest Area under the curve (AUC) to nT1 (0.84 vs. 0.92, p > 0.05) for discrimination of cFD versus controls. Significantly lower LV-GLS/LV-GCS was found in male compared to female cFD (-19 ± 4 vs. -22 ± 4%, p = 0.03). In six non-hypertrophied female cFD with normal nT1 LATotal -GLS was the only discriminating parameter with an accuracy of 86%. LV-GLS, LV-GCS and LATotal -GLS can detect impaired cardiac mechanics of cFD besides nT1. LATotal -GLS might identify non-hypertrophied female cFD. Variants p.D313Y/p.A143T did not reveal cardiac involvement by multiparametric CMR.
Subject(s)
Fabry Disease , Ventricular Function, Left , Male , Female , Humans , Magnetic Resonance Imaging, Cine , Heart Ventricles/diagnostic imaging , Hypertrophy, Left Ventricular , Myocardium , Fabry Disease/diagnostic imaging , Fabry Disease/genetics , Predictive Value of TestsABSTRACT
PURPOSE: To investigate the influence of myocardial fibrosis on left ventricular (LV) diastolic filling patterns in triathletes compared to sedentary controls by cardiac magnetic resonance (CMR) imaging. METHOD: 101 male triathletes (43 ± 11 years) and 28 controls (41 ± 10 years) were recruited and underwent 1.5 T CMR including cine SSFP series, late gadolinium enhancement (LGE) imaging and T1 mapping. Functional and morphological parameters were obtained, and CMR-based LV diastolic filling parameters such as the early peak-filling rate (EPFR), atrial peak-filling rate (APFR) and peak-filling rate ratio (PFRR = EPFR/APFR) were determined by time-volume analysis of the cine series. RESULTS: Non-ischemic LGE was detected in 20 triathletes (20 %) and in none of the controls. Compared to controls LGE-negative (LGE-) triathletes showed similar EPFR (216 ± 58 ml/s/m2 vs 224 ± 69 ml/s/m2, P = 0.52) but lower APFR (120 ± 46 ml/s/m2 vs 147 ± 55 ml/s/m2, P < 0.05), resulting in higher PFRR (2.1 ± 1 vs 1.6 ± 0.5, P < 0.01). LGE-positive (LGE + ) triathletes had similar EPFR (212 ± 73 ml/s/m2, P = 0.798), but higher APFR (149 ± 50 ml/s/m2, P < 0.05) and decreased PFRR (1.6 ± 0.7, P < 0.05) compared to LGE- triathletes. LGE + triathletes had increased LV mass index (88 ± 10 g/m2 vs 80 ± 12 g/m2, P < 0.01) and extracellular volume (ECV) fraction (26.2 ± 2.7 % vs 24.4 ± 1.7 %, P < 0.001) compared to LGE- triathletes. CONCLUSIONS: Athletic activity leads to "supernormal" LV diastolic filling pattern in LGE- triathletes, which may be attributable to increased LV myocardial flexibility and elasticity. However, LGE + triathletes demonstrate a pseudo-normalization characterized by compensatory increase of atrial contraction. Possibly, due to reduced passive elasticity associated myocardial fibrosis.
Subject(s)
Atrial Fibrillation , Cardiomyopathies , Humans , Male , Contrast Media , Magnetic Resonance Imaging, Cine , Gadolinium , Cardiomyopathies/pathology , Myocardium/pathology , Fibrosis , Magnetic Resonance Spectroscopy , Ventricular Function, Left , Predictive Value of TestsABSTRACT
Serum biomarkers such as N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) and cardiac troponins are elevated in patients with hypertrophic cardiomyopathy (HCM). At present, it is not clear if these markers are associated with distinct clinical alterations in HCM, such as left ventricular hypertrophy, outflow tract obstruction, myocardial fibrosis and/or diastolic dysfunction (DD), which are associated with adverse cardiovascular outcome. Here we evaluate the association of NT-proBNP and high sensitivity cardiac troponin T (hs-cTnT) to a variety of cardiac imaging parameters in HCM patients in a multivariable regression analysis. This retrospective cross-sectional study included 366 HCM patients who underwent transthoracic echocardiography (TTE), 218 of whom also obtained cardiovascular magnetic resonance (CMR) to assess focal myocardial fibrosis by LGE. Multivariable regression analyses revealed the strongest association of the DD parameters E/E' mean and E/E' septal with NT-proBNP (b = 0.06, 95%-CI [0.05−0.07], p < 0.001, R2 = 0.28; b = 0.08, 95%-CI [0.06−0.1], p < 0.001, R2 = 0.25) and LGE size showed the strongest association with hs-cTnT (b = 0.20, 95%-CI [0.15−0.24], p < 0.001, R2 = 0.28). This study indicates that NT-proBNP and hs-cTnT are associated with structural and functional alterations in HCM. NT-proBNP is a stronger predictor for DD, while hs-cTnT is associated with the extent of focal myocardial fibrosis. Both biomarkers might be useful in the diagnostic procedure in addition to imaging parameters.
ABSTRACT
Strain is an important imaging parameter to determine myocardial deformation. This study sought to 1) assess changes in left ventricular strain and ejection fraction (LVEF) from acute to chronic ST-elevation myocardial infarction (STEMI) and 2) analyze strain as a predictor of late gadolinium enhancement (LGE). 32 patients with STEMI and 18 controls prospectively underwent cardiac magnetic resonance imaging. Patients were scanned 8 [Formula: see text] 5 days and six months after infarction (± 1.4 months). Feature tracking was performed and LVEF was calculated. LGE was determined visually and quantitatively on short-axis images and myocardial segments were grouped according to the LGE pattern (negative, non-transmural and transmural). Global strain was impaired in patients compared to controls, but improved within six months after STEMI (longitudinal strain from -14 ± 4 to -16 ± 4%, p < 0.001; radial strain from 38 ± 11 to 42 ± 13%, p = 0.006; circumferential strain from -15 ± 4 to -16 ± 4%, p = 0.023). Patients with microvascular obstruction showed especially attenuated strain results. Regional strain persisted impaired in LGE-positive segments. Circumferential strain could best distinguish between LGE-negative and -positive segments (AUC 0.73- 0.77). Strain improves within six months after STEMI, but remains impaired in LGE-positive segments. Strain may serve as an imaging biomarker to analyze myocardial viability. Especially circumferential strain could predict LGE.
Subject(s)
ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/pathology , Contrast Media , Magnetic Resonance Imaging, Cine/methods , Gadolinium , Magnetic Resonance Imaging , Myocardium/pathology , Ventricular Function, Left , Magnetic Resonance Spectroscopy , Predictive Value of TestsABSTRACT
BACKGROUND: There is a paucity of data on cardiovascular magnetic resonance feature tracking (CMR-FT) in patients with dilated cardiomyopathy (DCM). We aimed at describing global and segmental myocardial strain patterns and a potential association with the presence of focal myocardial scarring in DCM patients by CMR-FT. METHODS: Thirty-nine patients with DCM and reduced left ventricular (LV) ejection fraction (mean 21±8%) underwent CMR including standard cine steady-state free precession (SSFP) sequences and late gadolinium enhancement (LGE). We measured global LV longitudinal as well as global and segmental circumferential and radial strain. The presence of focal myocardial fibrosis was assessed on LGE images. RESULTS: Nineteen patients had focal myocardial fibrosis on LGE images with the highest prevalence in the basal septal segments II and III, which were affected in 12 (63%) and 13 (68%) patients. Furthermore, there was a significantly lower average short-axis LV radial strain (LVSAX-RS) in these segments (4.89 (-1.55 to 11.34) %) compared with the average of the other myocardial segments (21.20 (17.36 to 25.05)%; p<0.001) after adjusting for LGE and left-bundle branch block (LBBB). In general, LV segments with LGE had lower model-based mean LVSAX-RS values (17.65 (10.37 to 24.93) %) compared with those without LGE (19.40 (15.43 to 23.37) %), but this effect was not significant after adjusting for the presence of LBBB (p=0.630). CONCLUSION: Our findings revealed a coincidence of impaired radial strain and focal myocardial fibrosis in the basal septal LV myocardial segments of patients with DCM. Regardless of this pattern, we did not find a general, significant effect of myocardial fibrosis on strain in our cohort. Future studies are required to assess the potential prognostic implications of myocardial strain patterns in addition to the assessment of myocardial fibrosis in patients with DCM.