The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated ...differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age = 61 ± 8 years) and 5 age/gender matched controls (age = 56 ± 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities < 10 cm/s, and kinetic energy (KE). Furthermore, LA global strain values were derived from b-SSFP cine images using dedicated CMR feature-tracking software. Even in sinus rhythm, LA mean and peak flow velocities over the entire cardiac cycle were significantly lower in paroxysmal AF patients compared to controls (13.1 ± 2.4 cm/s vs. 16.7 ± 2.1 cm/s, p = 0.01) and (19.3 ± 4.7 cm/s vs. 26.8 ± 5.5 cm/s, p = 0.02), respectively. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 ± 10.8% vs. 27.8 ± 7.9%, p = 0.01) and in the LA appendage (73.3 ± 5.7% vs. 52.8 ± 16.2%, p = 0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.
To characterize the temporal alterations in native T1 and extracellular volume (ECV) of remote myocardium after acute myocardial infarction (AMI), and to explore their relation to left ventricular ...(LV) remodeling.
Forty-two patients with AMI successfully treated with primary PCI underwent cardiovascular magnetic resonance after 4-6 days and 3 months. Cine imaging, late gadolinium enhancement, and T1-mapping (MOLLI) was performed at 1.5T. T1 values were measured in the myocardial tissue opposite of the infarct area. Myocardial ECV was calculated from native- and post-contrast T1 values in 35 patients, using a correction for synthetic hematocrit.
Native T1 of remote myocardium significantly decreased between baseline and follow-up (1002 ± 39 to 985 ± 30ms, p<0.01). High remote native T1 at baseline was independently associated with a high C-reactive protein level (standardized Beta 0.32, p = 0.04) and the presence of microvascular injury (standardized Beta 0.34, p = 0.03). ECV of remote myocardium significantly decreased over time in patients with no LV dilatation (29 ± 3.8 to 27 ± 2.3%, p<0.01). In patients with LV dilatation, remote ECV remained similar over time, and was significantly higher at follow-up compared to patients without LV dilatation (30 ± 2.0 versus 27 ± 2.3%, p = 0.03).
In reperfused first-time AMI patients, native T1 of remote myocardium decreased from baseline to follow-up. ECV of remote myocardium decreased over time in patients with no LV dilatation, but remained elevated at follow-up in those who developed LV dilatation. Findings from this study may add to an increased understanding of the pathophysiological mechanisms of cardiac remodeling after AMI.
This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization ...therapy defibrillator (CRT-D) and compared the results with invasive volume measurements.
Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure-volume measurements were performed, matching the CRT settings used during CMR.
Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% (
< 0.01), and the strain assessment showed the abolition of the left bundle branch block contraction pattern. Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated.
Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.
Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ...ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT‐off during follow‐up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT.
Lack of gadolinium-contrast wash-in on first-pass perfusion imaging, early gadolinium-enhanced imaging, or late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging after ...revascularized ST-elevation myocardial infarction (STEMI) is commonly referred to as microvascular obstruction (MVO). Additionally, T2-weighted imaging allows for the visualization of infarct-related oedema and intramyocardial haemorrhage (IMH) within the infarction. However, the exact histopathological correlate of the contrast-devoid core and its relation to IMH is unknown.
In eight Yorkshire swine, the circumflex coronary artery was occluded for 75 min by a balloon catheter. After 7 days, CMR with cine imaging, T2-weighted turbospinecho, and LGE was performed. Cardiovascular magnetic resonance images were compared with histological findings after phosphotungstic acid-haematoxylin and anti-CD31/haematoxylin staining. These findings were compared with CMR findings in 27 consecutive PCI-treated STEMI patients, using the same scanning protocol. In the porcine model, the infarct core contained extensive necrosis and erythrocyte extravasation, without intact vasculature and hence, no MVO. The surrounding-gadolinium-enhanced-area contained granulation tissue, leucocyte infiltration, and necrosis with morphological intact microvessels containing microthrombi, without erythrocyte extravasation. Areas with IMH (median size 1.92 0.36-5.25 cm(3)) and MVO (median size 2.19 0.40-4.58 cm(3)) showed close anatomic correlation intraclass correlation coefficient (ICC) 0.85, r = 0.85, P = 0.03. Of the 27 STEMI patients, 15 had IMH (median size 6.60 2.49-9.79 cm(3)) and 16 had MVO (median size 4.31 1.05-7.57 cm(3)). Again, IMH and MVO showed close anatomic correlation (ICC 0.87, r = 0.93, P < 0.001).
The contrast-devoid core of revascularized STEMI contains extensive erythrocyte extravasation with microvascular damage. Attenuating the reperfusion-induced haemorrhage may be a novel target in future adjunctive STEMI treatment.
Abstract
Aims
The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of ...this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI).
Methods and results
In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, 15OH2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P = 0.03) and MRI (64%, 57–72%, P = 0.052). Using FFR < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI).
Conclusion
In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.
Structured Graphical Abstract
Structured Graphical Abstract
In this prospectively conducted study, every patient underwent myocardial perfusion imaging with SPECT, PET, and MRI (left panel) with subsequent ICA and FFR measurements in all vessels regardless of imaging results and stenosis severity (middle panel). This resulted in modest diagnostic performances of whom PET revealed the greatest AUC on a per-patient and per-vessel level (right panel). In this case example, qualitative SPECT shows a reversible defect during stress in the inferior wall with an SDS of 5. The quantitative PET polar map depicts abnormal absolute myocardial blood flow during stress in the RCA territory of 1.22 mL/min/g myocardial tissue, indicative for ischaemia. Qualitative MRI showed a stress perfusion defect without myocardial scar, suggestive of ischaemia in the inferior wall. The ICA revealed a haemodynamically significant lesion in the proximal RCA as indicated by an abnormal FFR of 0.44.
AUC, area under the receiver operating characteristic curve; Cx, circumflex artery; FFR, fractional flow reserve; ICA, invasive coronary angiography; LAD, left anterior descending artery; MRI, magnetic resonance imaging; PET, positron emission tomography; RCA, right coronary artery; ROC, receiver operating characteristic curve; SDS, summed difference score; and SPECT, single-photon emission computed tomography.
In patients with ST-segment elevation myocardial infarction (STEMI), the importance of a well-balanced inflammatory reaction has been recognized for years. Monocytes play essential roles in ...regulating inflammation. Hence, we investigated the association between inflammatory characteristics of monocytes and myocardial injury and functional outcome in patients with STEMI.
Using flow cytometry, the levels of classical (CD14(++)CD62L(+)) and nonclassical (CD14(+)CD62L(-)) monocytes were analyzed in peripheral blood in 58 patients with STEMI at a median of 5 days (4-6 days) after primary percutaneous coronary intervention. In addition, the monocytic expression of several surface molecules and formation of monocyte-platelet complexes were measured. All patients underwent cardiovascular magnetic resonance imaging at baseline and 4-month follow-up.
At baseline, patients with high levels of classical monocytes had impaired left ventricular (LV) ejection fraction (P = .002), larger infarct size (P = .001), and, often, presence of microvascular obstruction (P = .003). At follow-up, high levels of classical monocytes were negatively associated with the regional systolic LV function independent of the transmural extent of infarction. In contrast, positive associations for the levels of nonclassical monocytes were observed. Finally, up-regulation of macrophage 1 by blood monocytes and increased formation of monocyte-platelet complexes were associated with enhanced myocardial injury at baseline and impaired LV function at follow-up.
This study shows an association between a proinflammatory monocyte response, characterized by high levels of classical monocytes, and severe myocardial injury and poor functional outcome after STEMI. Future studies are required to investigate the biologic nature of this association and therapeutic implications.
Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts in monocytes that ...relate to post-MI healing and evaluated intervention with the observed gene activity in a rat MI model. In 51 MI patients treated by primary percutaneous coronary intervention (PCI), the change in LV end-diastolic volume index (EDVi) from baseline to 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating monocytes were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066–1070,
2015
; Cell Stem Cell 16:477–487,
2015
; Curr Med Chem 13:1877–1893,
2006
) after primary PCI for transcriptome analysis. Transcriptional profiling and pathway analysis revealed that patients with a decreased LV EDVi showed an induction of type I interferon (IFN) signalling (type I IFN pathway:
P
value < 0.001; false discovery rate < 0.001). We subsequently administered 15,000 Units of IFN-α subcutaneously in a rat MI model for three consecutive days following MI. Cardiac function was measured using echocardiography and infarct size/cardiac inflammation using (immuno)-histochemical analysis. We found that IFN-α application deteriorated ventricular dilatation and increased infarct size at day 28 post-MI. Moreover, IFN-α changed the peripheral monocyte subset distribution towards the pro-inflammatory monocyte subset whereas in the myocardium, the presence of the alternative macrophage subset was increased at day 3 post-MI. Our findings suggest that induction of type I IFN signalling in human monocytes coincides with adverse LV remodelling. In rats, however, IFN-α administration deteriorated post-MI healing. These findings underscore important but also contradictory roles for the type I IFN response during cardiac healing following MI.
Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor ...agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.
Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by
OH
O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using
Cacetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.
T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism. Trial registration NCT00766857.
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