Serum Concentrations of Matrix Metalloproteinase-1 and Procollagen Type I Carboxy Terminal Propeptide Discriminate Infarct-Like Myocarditis and Non-ST-Segment-Elevation Myocardial Infarction.

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.

Sex-specific ventricular morphology, function, and tissue characteristics in arterial hypertension: a magnetic resonance study of the Hamburg city health cohort.

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.

Unrecognized myocardial scar by late-gadolinium-enhancement cardiovascular magnetic resonance: Insights from the population-based Hamburg City Health Study.

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.

Prognostic Relevance of Ischemic Late Gadolinium Enhancement in Apparently Healthy Endurance Athletes: A Follow-up Study Over 5 years.

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.

Contrast-enhanced cardiac MRI is superior to non-contrast mapping to predict left ventricular remodeling at 6 months after acute myocardial infarction.

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.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations.

OBJECTIVES: Long-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging. METHODS: Asymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping. RESULTS: Forty-four survivors (age 44 [interquartile range, IQR 37-52] years; follow-up time 10 [IQR 5-15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50-54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001). CONCLUSION: Based on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors. CLINICAL RELEVANCE STATEMENT: Platinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy. KEY POINTS: • Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement. • Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of  ≥ 200 mg/m2. • Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.

Differentiation of acute non-ST elevation myocardial infarction and acute infarct-like myocarditis by visual pattern analysis: a head-to-head comparison of different cardiac MR techniques.

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.

Left ventricular myocardial strain responding to chronic pressure overload in patients with resistant hypertension evaluated by feature-tracking CMR.

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.

Prevalence and pattern of focal and potential diffuse myocardial fibrosis in male and female marathon runners using contrast-enhanced cardiac magnetic resonance.

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.

Left ventricular diastolic filling patterns in competitive triathletes with and without myocardial fibrosis by cardiac magnetic resonance time-volume analysis.

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.

CMR feature tracking in patients with dilated cardiomyopathy: patterns of myocardial strain and focal fibrosis.

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.

Cardiac magnetic resonance feature tracking global and segmental strain in acute and chronic ST-elevation myocardial infarction.

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.

Impact of Sex and Cardiovascular Risk Factors on Myocardial T1, Extracellular Volume Fraction, and T2 at 3 Tesla: Results From the Population-Based, Hamburg City Health Study.

BACKGROUND: Reliable reference intervals are crucial for clinical application of myocardial T1 and T2 mapping cardiovascular magnetic resonance imaging. This study evaluated the impact of sex and cardiovascular risk factors on myocardial T1, extracellular volume fraction (ECV), and T2 at 3T in the population-based HCHS (Hamburg City Health Study). METHODS: The final study sample consisted of 1576 consecutive HCHS participants between 46 and 78 years without prevalent heart disease, including 1020 (67.3%) participants with hypertension and 110 (7.5%) with diabetes. T1 and T2 mapping were performed on a 3T scanner using 5b(3b)3b modified Look-Locker inversion recovery and T2 prepared, fast-low-angle shot sequence, respectively. Stepwise regression analyses were performed to identify variables with an independent impact on T1, ECV, and T2. Reference intervals were defined as the interval between the 2.5% and 97.5% quantiles. RESULTS: Sex was the major independent influencing factor of myocardial native T1, ECV, and T2. Female patients had significantly higher upper limits of reference intervals for native T1 (1112-1261 versus 1079-1241 ms), ECV (23%-33% versus 22%-32%), and T2 (36-46 versus 35-45 ms) compared with male patients (all P<0.001). Cardiovascular risk factors, such as diabetes and hypertension, did not systematically affect native T1. There was an independent association of T2 by hypertension and, to a lesser degree, by left ventricular mass, heart rate (all P<0.001), and body mass index (P=0.001). CONCLUSIONS: Sex needs to be considered as the major, independent influencing factor for clinical application of myocardial T1, ECV, and T2 measurements. Consequently, sex-specific reference intervals should be used in clinical routine. Our findings suggest that there is no need for specific reference intervals for myocardial T1 and ECV measurements in individuals with cardiovascular risk factors. However, hypertension should be considered as an additional factor for clinical application of T2 measurements. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03934957.

Association of NT-proBNP and hs-cTnT with Imaging Markers of Diastolic Dysfunction and Focal Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

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.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

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.

Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy-related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT.

OBJECTIVES: Cancer therapy-related cardiac dysfunction (CTRCD) is a relevant clinical problem and needs early prediction. This study aimed to analyze myocardial injury using serial laboratory and cardiac magnetic resonance imaging (CMR) parameters after epirubicin-based chemotherapy compared with left-sided radiotherapy and to study their value for early prediction of CTRCD. METHODS: Sixty-six consecutive women (53 ± 13 years) including n = 39 with epirubicin-based chemotherapy and n = 27 with left-sided radiotherapy were prospectively studied by 3 T CMR including left ventricular (LV) mass and volumes for ejection fraction (LVEF), as well as feature-tracking with global longitudinal strain (GLS) and T1/T2 mapping. CMR was performed at baseline, at therapy completion (follow-up 1, FU1), and after 13 ± 2 months (FU2). CTRCD was defined as LVEF decline of at least 10% to < 55% or a > 15% GLS change at FU2. RESULTS: T1 and T2 increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. CTRCD occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. T1 at FU1 was the best single parameter to predict CTRCD with an area under the curve (AUC) of 0.712 (CI 0.587-0.816, p = 0.005) with excellent sensitivity (100%, 66-100%), but low specificity (44%, 31-58%). Combined use of increased T1 and LVEF ≤ 60% at FU1 improved AUC to 0.810 (0.695-0.896) resulting in good sensitivity (78%, 44-95%) and specificity (84%, 72-92%). CONCLUSION: Only epirubicin-based chemotherapy, but not left-sided radiotherapy, resulted in increased T1/T2 myocardial relaxation times as a marker of myocardial injury. Combined use of CMR parameters may allow an early prediction of subsequent CTCRD. KEY POINTS: • Myocardial T1 and T2 relaxation times increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. • Cancer therapy-related cardiac dysfunction (CTRCD) occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. • Combined use of increased T1 and reduced LVEF had an AUC of 0.810 (0.695-0.896) to predict CTRCD with good sensitivity (78%, 44-95%) and specificity (84%, 72-92%).

Acute impact of an endurance race on biventricular and biatrial myocardial strain in competitive male and female triathletes evaluated by feature-tracking CMR.

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.

Cardiovascular magnetic resonance demonstrates structural cardiac changes following transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension in patients with liver cirrhosis. The exact cardiac consequences of subsequent increase of central blood volume are unknown. Cardiovascular magnetic resonance (CMR) imaging is the method of choice for quantifying cardiac volumes and ventricular function. The aim of this study was to investigate effects of TIPS on the heart using CMR, laboratory, and imaging cardiac biomarkers. 34 consecutive patients with liver cirrhosis were evaluated for TIPS. Comprehensive CMR with native T1 mapping, transthoracic echocardiography, and laboratory biomarkers were assessed before and after TIPS insertion. Follow-up (FU) CMR was obtained in 16 patients (47%) 207 (170-245) days after TIPS. From baseline (BL) to FU, a significant increase of all indexed cardiac chamber volumes was observed (all P < 0.05). Left ventricular (LV) end-diastolic mass index increased significantly from 45 (38-51) to 65 (51-73) g/m2 (P = < 0.01). Biventricular systolic function, NT-proBNP, high-sensitive troponin T, and native T1 time did not differ significantly from BL to FU. No patient experienced cardiac decompensation following TIPS. In conclusion, in patients without clinically significant prior heart disease, increased cardiac preload after TIPS resulted in increased volumes of all cardiac chambers and eccentric LV hypertrophy, without leading to cardiac impairment during follow-up in this selected patient population.