Determinants and prognostic relevance of aortic stiffness in patients with recent ST-elevation myocardial infarction.

The association between aortic stiffness, cardiovascular risk factors and prognosis in patients with recent ST-elevation myocardial infarction (STEMI) is poorly understood. We analyzed the relationship between cardiovascular risk factors and arterial stiffening and assessed its prognostic significance in patients with recent STEMI. We prospectively enrolled 408 consecutive patients who sustained a first STEMI and underwent primary percutaneous coronary intervention (PPCI). Aortic pulse wave velocity (PWV), the most widely used measure of aortic stiffness, was determined by the transit-time method using velocity-encoded, phase-contrast cardiac magnetic resonance imaging. Patient characteristics were acquired at baseline and major adverse cardiac and cerebrovascular events (MACCE) were assessed at 13 [interquartile range (IQR) 12-31] months. Cox regression- and logistic regression analysis were performed to explore predictors of aortic stiffness and MACCE. Median aortic PWV was 6.6 m/s (IQR 5.6-8.3 m/s). In multivariable analysis, age [odds ratio (OR) 1.10, 95% confidence interval (CI), 1.08-1.14, p < 0.001] and hypertension (OR 2.45, 95% CI, 1.53-3.91, p < 0.001) were independently associated with increased PWV. Sex, diabetes, smoking status, dyslipidemia, and obesity were not significantly associated with PWV in adjusted analysis (all p > 0.05). High PWV significantly and independently predicted occurrence of MACCE in adjusted analysis [hazard ratio (HR) 2.45, 95% CI 1.19-5.04, p = 0.014]. In patients with recent STEMI, the impact of classical cardiovascular risk factors on aortic stiffness is mainly dependent on age and increased blood pressure. Increased aortic stiffness is associated with adverse clinical outcome post-STEMI, suggesting it as a relevant therapeutic target in this population. Trial (NCT04113356).

Prognostic relevance of peri-infarct zone measured by cardiovascular magnetic resonance in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging provides valuable prognostic information in patients with ST-elevation myocardial infarction (STEMI). The peri-infarct zone (PIZ) is a potential marker for post-infarction risk stratification. The aim of this study was to assess the prognostic impact of PIZ in a large multicenter STEMI-trial. METHODS: The study population consisted of 704 consecutive patients undergoing CMR within 10 days after STEMI to assess established parameters of myocardial injury and additionally the extent of PIZ. The primary clinical endpoint was major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure within 1 year after infarction. RESULTS: The median heterogeneous PIZ-volume in the overall population was 14 ml (interquartile range [IQR] 7 to 24 ml). Male sex, infarct size, and left ventricular ejection fraction were identified as independent predictors of larger PIZ alterations. Patients with MACE had a significantly larger PIZ volume compared to patients without adverse events (21 ml [IQR 12 to 35 ml] versus 14 ml [IQR 7 to 23 ml]; p = 0.001). In stepwise multivariable Cox regression analysis, PIZ > median (>14 ml) emerged as an independent predictor of MACE (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.34 to 6.00; p = 0.006) in addition to the Thrombolysis In Myocardial Infarction (TIMI) risk score (HR 1.53; 95% CI 1.19 to 1.53; p < 0.001). Addition of PIZ to a CMR risk model comprising LVEF, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.46 (0.19-0.73, p < 0.001). CONCLUSION: In this currently largest prospective, multicenter CMR study assessing PIZ, the extent of PIZ emerged as an independent predictor of MACE and a potential novel marker for optimized risk stratification in STEMI patients. ClinicalTrials.gov: NCT00712101.

Association of C-Reactive Protein Velocity with Early Left Ventricular Dysfunction in Patients with First ST-Elevation Myocardial Infarction.

C-reactive protein velocity (CRPv) has been proposed as a very early and sensitive risk predictor in patients with ST-elevation myocardial infarction (STEMI). However, the association of CRPv with early left ventricular (LV) dysfunction after STEMI is unknown. The aim of this study was to investigate the relationship between CRPv and early LV dysfunction, either before or at hospital discharge, in patients with first STEMI. This analysis evaluated 432 STEMI patients that were included in the prospective MARINA-STEMI (Magnetic Resonance Imaging In Acute ST-elevation Myocardial Infarction. ClinicalTrials.gov Identifier: NCT04113356) cohort study. The difference of CRP 24 ± 8 h and CRP at hospital admission divided by the time (in h) that elapsed during the two examinations was defined as CRPv. Cardiac magnetic resonance (CMR) imaging was conducted at a median of 3 (IQR 2-4) days after primary percutaneous coronary intervention (PCI) for the determination of LV function and myocardial infarct characteristics. The association of CRPv with the CMR-derived LV ejection fraction (LVEF) was investigated. The median CRPv was 0.42 (IQR 0.21-0.76) mg/l/h and was correlated with LVEF (rS = -0.397, p < 0.001). In multivariable linear as well as binary logistic regression analysis (adjustment for biomarkers and clinical and angiographical parameters), CRPv was independently associated with LVEF (ß: 0.161, p = 0.004) and LVEF ≤ 40% (OR: 1.71, 95% CI: 1.19-2.45; p = 0.004), respectively. The combined predictive value of peak cardiac troponin T (cTnT) and CRPv for LVEF ≤ 40% (AUC: 0.81, 95% CI 0.77-0.85, p < 0.001) was higher than it was for peak cTnT alone (AUC difference: 0.04, p = 0.009). CRPv was independently associated with early LV dysfunction, as measured by the CMR-determined LVEF, revealing an additive predictive value over cTnT after acute STEMI treated with primary PCI.

C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction.

BACKGROUND: The role of C-reactive protein velocity (CRPv) as an early and sensitive marker of an excessive inflammatory response in the setting of acute ST-elevation myocardial infarction (STEMI) is only poorly understood. The aim of this study was to investigate, in patients with STEMI treated with primary percutaneous coronary intervention (PCI), the association of CRPv with microvascular infarct pathology. METHODS AND RESULTS: This prospective cohort study included a total of 316 patients with STEMI undergoing PCI. CRPv was defined as the difference between CRP 24 ± 8 h and CRP at hospital admission, divided by the time (in h) that have passed during the two examinations. The association of biomarker levels with cardiac magnetic resonance (CMR)-determined microvascular obstruction (MVO) was evaluated. CMR was performed at a median of 3 [interquartile range 2-4] days after PCI. After adjustment for cardiac troponin T (cTnT), anterior infarction and TIMI flow pre and post-PCI, CRPv (odds ratio 2.70, 95% confidence interval (CI) 1.54-4.73; p = 0.001) remained significantly associated with the occurrence of MVO. CRPv (area under the curve [AUC] 0.76, 95% CI 0.71-0.81; p < 0.001) was a better predictor for MVO compared to 24 h CRP (AUC difference: 0.03, p = 0.002). The addition of CRPv to peak cTnT resulted in a higher AUC for MVO prediction than peak cTnT alone (AUC 0.86, 95% CI 0.82-0.90; p < 0.001 vs. AUC 0.84, 95% CI 0.79-0.88; p < 0.001. AUC difference: 0.02, p = 0.042). CONCLUSIONS: In patients with STEMI treated with primary PCI, CRPv was associated with microvascular infarct pathology with a predictive value incremental to cTnT, suggesting CRPv as an early and sensitive biomarker for more severe infarct pathology and outcome.

Estimating the extent of myocardial damage in patients with STEMI using the DETERMINE score.

BACKGROUND: Recently, a simple ECG score (DETERMINE score) has been proposed for estimating myocardial scar in patients with ischaemic cardiomyopathy. We sought to evaluate the usefulness of the DETERMINE score for the assessment of myocardial infarct size (IS) as well as microvascular obstruction (MVO), in the setting of ST-elevation myocardial infarction (STEMI). METHODS: This observational study enrolled 423 patients with STEMI (median age 56, 17% women), revascularised by primary percutaneous coronary intervention (PCI). For evaluation of the DETERMINE and Selvester scoring system (an established but complex ECG score for IS estimation), ECG was conducted before discharge (median: 4 (IQR 2-6) days). Cardiac magnetic resonance (CMR) was conducted within a week after infarction for determination of IS and MVO. RESULTS: Median DETERMINE score of the overall cohort was 8 points (IQR 5-11). A higher DETERMINE score was significantly associated with a larger IS (21% vs 11% of left ventricular myocardial mass (LVMM), p<0.001) as well as larger MVO (1.2% vs 0.0% of LVMM, p<0.001). In linear and binary multivariable logistic regression analysis, the DETERMINE score remained independently associated with IS (OR 1.09, 95% CI 1.02 to 1.17, p=0.014) and MVO (OR 1.12, 95% CI 1.04 to 1.21, p=0.003), after adjustment for Selvester score and clinical indicators of IS (high-sensitivity cardiac troponin T, high-sensitivity C reactive protein, N-terminal pro-B-type natriuretic peptide, TIMI flow pre-interventional and post-interventional PCI, anterior infarct localisation). CONCLUSIONS: In patients undergoing PCI for STEMI, the DETERMINE score provides an easy and inexpensive tool for appropriate estimation of infarct severity as determined by CMR.

High sensitivity C-reactive protein is associated with worse infarct healing after revascularized ST-elevation myocardial infarction.

BACKGROUND: The inflammatory response due to myocardial tissue injury in the setting of acute ST-elevation myocardial infarction (STEMI) is essential for proper local infarct healing. However, an excessive inflammatory response may aggravate myocardial damage and hampers infarct healing processes. The present study aimed to investigate the association of systemic inflammatory biomarkers with infarct size (IS) dynamics post-STEMI, using cardiac magnetic resonance (CMR) imaging. METHODS: This prospective observational study included 245 STEMI patients treated with primary percutaneous coronary intervention (pPCI). Peak values of high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBCc) and fibrinogen were determined serially until 96 h after pPCI. Infarct healing, defined as relative IS reduction from baseline to 4 months after STEMI, was assessed using late gadolinium enhanced CMR imaging. RESULTS: IS significantly decreased from 16% of left ventricular mass (LVM) (Interquartile range [IQR]:8-24) at baseline to 10% (IQR:5-17) at 4 months (p < 0.001). Relative IS reduction was 35% (IQR:8-50). Whereas peak WBCc (p = 0.926) and peak fibrinogen (p = 0.161) were not significantly associated with relative IS reduction, peak hs-CRP showed a significant association with IS reduction (p = 0.003). In multivariable logistic regression analysis, the association between peak hs-CRP and relative IS reduction remained significant after adjustment for baseline IS, hypertension, hs-cardiac troponin T and N-terminal pro B-type natriuretic peptide (odds ratio:0.35 [95% confidence interval:0.19-0.63]; p = 0.001). CONCLUSIONS: In STEMI patients treated with pPCI, hs-CRP was independently associated with 4 months IS reduction as determined by CMR, suggesting a pathophysiological interplay between inflammation and adverse infarct healing in survivors of acute STEMI.

Role of Cardiac Magnetic Resonance to Improve Risk Prediction Following Acute ST-Elevation Myocardial Infarction.

Cardiac magnetic resonance (CMR) imaging allows comprehensive assessment of myocardial function and tissue characterization in a single examination after acute ST-elevation myocardial infarction. Markers of myocardial infarct severity determined by CMR imaging, especially infarct size and microvascular obstruction, strongly predict recurrent cardiovascular events and mortality. The prognostic information provided by a comprehensive CMR analysis is incremental to conventional risk factors including left ventricular ejection fraction. As such, CMR parameters of myocardial tissue damage are increasingly recognized for optimized risk stratification to further ameliorate the burden of recurrent cardiovascular events in this population. In this review, we provide an overview of the current impact of CMR imaging on optimized risk assessment soon after acute ST-elevation myocardial infarction.

Early onset of menopause is associated with increased peripheral atherosclerotic plaque volume and progression.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of death in western countries. One risk factor unique to women is the menopausal status. The aim of this study was to analyse the influence of the onset of menopause (MP) on the extent and progression of atherosclerotic plaque volume (PV). METHODS: Postmenopausal women with at least one cardiovascular risk factor (CVRF) but without established CVD were included. Quantification of PV was performed in peripheral arteries using a three - dimensional (3D) ultrasound (US) technique. Follow-up examination to assess PV progression was performed after 19 (±8) months. RESULTS: 110 consecutive postmenopausal women (mean age 65.5) were included. Females with an earlier onset of MP (<45 years) had a significantly higher PV than those with an intermediate (45-52 years) or later onset of menopause (>52 years), irrespective of other CVRF (244 mm³ vs. 193 mm³ vs. 73 mm³, respectively, p = 0.023). In addition, women with an earlier onset of MP had a higher PV progression compared to women with an intermediate or late onset (40 mm³ vs. 35 mm³ vs. 8.5 mm³; p = 0.002, respectively). Moreover, these results were confirmed in multivariate regression, where only onset of MP (OR 0.88; 95%CI 0.81-0.96; p = 0.004) and age (OR 1.06; 95%CI 1.08-1.13; p = 0.025) were significant predictors for a higher atherosclerotic progression. CONCLUSIONS: An earlier onset of MP was associated with an increase in atherosclerotic PV and accelerated progression, independent of other CVRF.

Complete versus simplified Selvester QRS score for infarct severity assessment in ST-elevation myocardial infarction.

BACKGROUND: Complete and simplified Selvester QRS score have been proposed as valuable clinical tool for estimating myocardial damage in patients with ST-elevation myocardial infarction (STEMI). We sought to comprehensively compare both scoring systems for the prediction of myocardial and microvascular injury assessed by cardiac magnetic resonance (CMR) imaging in patients with acute STEMI. METHODS: In this prospective observational study, 201 revascularized STEMI patients were included. Electrocardiography was conducted at a median of 2 (interquartile range 1-4) days after the index event to evaluate the complete and simplified QRS scores. CMR was performed within 1 week and 4 months thereafter to determine acute and chronic infarct size (IS) as well as microvascular obstruction (MVO). RESULTS: Complete and simplified QRS score showed comparable predictive value for acute (area under the curve (AUC) = 0.64 vs. 0.67) and chronic IS (AUC = 0.63 vs. 0.68) as well as for MVO (AUC = 0.64 vs. 0.66). Peak high sensitivity cardiac troponin T (hs-cTnT) showed an AUC of 0.88 for acute IS and 0.91 for chronic IS, respectively. For the prediction of MVO, peak hs-cTnT represented an AUC of 0.81. CONCLUSIONS: In reperfused STEMI, complete and simplified QRS score displayed comparable value for the prediction of acute and chronic myocardial as well as microvascular damage. However, both QRS scoring systems provided inferior predictive validity, compared to peak hs-cTnT, the clinical reference method for IS estimation.

Relationship between admission Q waves and microvascular injury in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Using comprehensive cardiac magnetic resonance (CMR) imaging in patients suffering from ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), we sought to investigate the association of admission Q waves with microvascular injury (microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH)). METHODS: This prospective observational study included 195 STEMI patients treated with pPCI. Admission 12-lead electrocardiography was evaluated for the presence of pathological Q waves, defined as a Q wave duration of >30 ms and a depth of >0.1 mV. CMR was performed at 3 (interquartile range: 2-5) days after pPCI to determine infarct characteristics including MVO (late gadolinium enhancement) and IMH (T2* mapping). RESULTS: Admission Q waves were observed in 53% of patients (n = 104). These patients had a significantly lower BMI (p = 0.005), more frequent left anterior descending artery as culprit lesion (p = 0.005), were less frequent smokers (p = 0.048) and had higher rates of pre-interventional TIMI flow 0 (p = 0.018). Patients with Q waves showed a significantly larger infarct size (19%vs.12% of left ventricular mass,p < 0.001), lower ejection fraction (49%vs.54%,p = 0.001), worse global strain parameters (all p < 0.005) and more severe microvascular injury (MVO: 68%vs.34%,p < 0.001; IMH: 40%vs.20%,p = 0.002). Q waves remained associated with both MVO (odds ratio: 5.23, 95% confidence interval: 2.58 to 10.58,p < 0.001) and IMH (odds ratio: 3.94, 95% confidence interval: 1.83 to 8.46,p < 0.001) after adjusting for potential confounders (culprit lesion, pre-interventional TIMI flow 0, total ischemia time, ST-segment elevation). CONCLUSIONS: Admission Q waves, derived from the readily available ECG, emerged as independent early markers of CMR-determined microvascular injury in STEMI patients undergoing pPCI.

Biomarker assessment for early infarct size estimation in ST-elevation myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) represents the biomarker of choice for infarct size (IS) estimation in patients with acute ST-elevation myocardial infarction (STEMI). However, admission values of hs-cTnT are only weakly associated with IS. The aim of this study was to investigate the incremental value of different biomarkers measured on admission for IS estimation in STEMI patients. METHODS: In this prospective observational study, we included 161 consecutive STEMI patients treated with primary percutaneous coronary intervention (pPCI). The following biomarkers were assessed on admission: hs-cTnT, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and neutrophil/lymphocyte ratio (NLR). IS was determined by cardiac magnetic resonance (CMR) imaging 3 (Interquartile range [IQR] 2 to 4) days after the index event. RESULTS: Patients with large IS (>19% of left ventricular myocardium) showed significantly higher levels of admission hs-cTnT (399.6 vs. 53.4 ng/L, p < .001), NT-pro-BNP (140 vs. 86 ng/L, p = .008) and NLR (6.4 vs. 4.1, p < .001). The combination of hs-cTnT, NT-pro-BNP and NLR on admission resulted in a significantly higher area under the curve (0.78; 95% CI 0.704 to 0.838, (p = .01)) for the prediction of large IS than admission hs-cTnT alone (0.69; 95% CI 0.619 to 0.767). CONCLUSIONS: In STEMI patients undergoing pPCI, a comprehensive biomarker approach on admission including hs-cTnT, NT-pro-BNP and NLR was significantly better for immediate infarct severity estimation as compared to hs-cTnT alone.

Prognosis-based definition of left ventricular remodeling after ST-elevation myocardial infarction.

OBJECTIVES: Cardiac magnetic resonance (CMR) is the gold-standard modality for the assessment of left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI) patients. However, the commonly used remodeling criteria have never been validated for hard clinical events. We therefore aimed to define clear CMR criteria of LV remodeling following STEMI with proven prognostic impact. METHODS: This observational study included 224 patients suffering from acute STEMI. CMR was performed within 1 week and 4 months after infarction to evaluate different remodeling criteria including relative changes in LV end-diastolic volume (%∆LVEDV), end-systolic volume (%∆LVESV), ejection fraction (%∆LVEF), and myocardial mass (%∆LVMM). Primary endpoint was the occurrence of major adverse cardiovascular events (MACE) including all-cause death, re-infarction, stroke, and new congestive heart failure 24 months following STEMI. Secondary endpoint was defined as composite of primary endpoint and cardiovascular hospitalization. The Mann-Whitney U test was applied to assess differences in LV remodeling measures between patients with and without MACE. Values for the prediction of primary and secondary endpoints were assessed by c-statistics and Cox regression analysis. RESULTS: The incidence of MACE (n = 13, 6%) was associated with higher %∆LVEDV (p = 0.002) and %∆LVMM (p = 0.02), whereas %∆LVESV and %∆LVEF were not significantly related to MACE (p > 0.05). The area under the curve (AUC) for the prediction of MACE was 0.76 (95% confidence interval [CI], 0.65-0.87) for %∆LVEDV (optimal cut-off 10%) and 0.69 (95%CI, 0.52-0.85) for %∆LVMM (optimal cut-off 5%). From all remodeling criteria, %∆LVEDV ≥ 10% showed highest hazard ratio (8.68 [95%CI, 2.39-31.56]; p = 0.001) for MACE. Regarding secondary endpoint (n = 35, 16%), also %∆LVEDV with an optimal threshold of 10% emerged as strongest prognosticator (AUC 0.66; 95%CI, 0.56-0.75; p = 0.004). CONCLUSIONS: Following revascularized STEMI, %∆LVEDV ≥ 10% showed strongest association with clinical outcome, suggesting this criterion as preferred CMR-based definition of post-STEMI LV remodeling. KEY POINTS: • CMR-determined %∆LVEDV and %∆LVMM were significantly associated with MACE following STEMI. • Neither %∆LVESV nor %∆LVEF showed a significant relation to MACE. • %∆LVEDV ≥ 10 was revealed as LV remodeling definition with highest prognostic validity.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

BACKGROUND: Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. METHODS: In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. RESULTS: Patients with left ventricular remodeling (n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). CONCLUSIONS: Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.