Ventricular arrhythmias in arrhythmic mitral valve syndrome-a prospective continuous long-term cardiac monitoring study.

AIMS: Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias. The incidence, morphology and methods for risk stratification are not well known. This prospective study aimed to describe the incidence and the morphology of ventricular arrhythmia and propose risk stratification in patients with arrhythmic mitral valve syndrome. METHODS: Arrhythmic mitral valve syndrome patients were monitored for ventricular tachyarrhythmias by implantable loop recorders (ILR) and secondary preventive implantable cardioverter-defibrillators (ICD). Severe ventricular arrhythmias included ventricular fibrillation, appropriate or aborted ICD therapy, sustained ventricular tachycardia and non-sustained ventricular tachycardia with symptoms of hemodynamic instability. RESULTS: During 3.1 years of follow-up, severe ventricular arrhythmia was recorded in seven (12%) of 60 patients implanted with ILR [first event incidence rate 4% per person-year, 95% confidence interval (CI) 2-9] and in four (20%) of 20 patients with ICD (re-event incidence rate 8% per person-year, 95% CI 3-21). In the ILR group, severe ventricular arrhythmia was associated with frequent premature ventricular complexes, more non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance (all P < 0.02). CONCLUSIONS: The yearly incidence of ventricular arrhythmia was high in arrhythmic mitral valve syndrome patients without previous severe arrhythmias using continuous heart rhythm monitoring. The incidence was even higher in patients with secondary preventive ICD. Frequent premature ventricular complexes, non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance were predictors of first severe arrhythmic event.

Electrical markers and arrhythmic risk associated with myocardial fibrosis in mitral valve prolapse.

AIMS: We aimed to characterize the substrate of T-wave inversion (TWI) using cardiac magnetic resonance (CMR) and the association between diffuse fibrosis and ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP). METHODS AND RESULTS: TWI was defined as negative T-wave ≥0.1 mV in ≥2 adjacent ECG leads. Diffuse myocardial fibrosis was assessed by T1 relaxation time and extracellular volume (ECV) fraction by T1-mapping CMR. We included 162 patients with MVP (58% females, age 50 ± 16 years), of which 16 (10%) patients had severe VA (aborted cardiac arrest or sustained ventricular tachycardia). TWI was found in 34 (21%) patients. Risk of severe VA increased with increasing number of ECG leads displaying TWI [OR 1.91, 95% CI (1.04-3.52), P = 0.04]. The number of ECG leads displaying TWI increased with increasing lateral ECV (26 ± 3% for TWI 0-1leads, 28 ± 4% for TWI 2leads, 29 ± 5% for TWI ≥3leads, P = 0.04). Patients with VA (sustained and non-sustained ventricular tachycardia) had increased lateral T1 (P = 0.004), also in the absence of late gadolinium enhancement (LGE) (P = 0.008). CONCLUSIONS: Greater number of ECG leads with TWI reflected a higher arrhythmic risk and higher degree of lateral diffuse fibrosis by CMR. Lateral diffuse fibrosis was associated with VA, also in the absence of LGE. These results suggest that TWI may reflect diffuse myocardial fibrosis associated with VA in patients with MVP. T1-mapping CMR may help risk stratification for VA.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

AIMS: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively. CONCLUSION: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

An image fusion tool for echo-guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis.

BACKGROUND: The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic-derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. METHODS: An image fusion tool for echo-guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient-specific LV function in fluoroscopy. A set of coronary venography-derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time-to-peak values from echocardiography speckle-tracking radial strain traces were color-coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo-defined target segments, and CRT response. RESULTS: Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo-suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. CONCLUSIONS: The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery.

Cardiac resynchronization therapy when no lateral pacing option exists: vectorcardiographic guided non-lateral left ventricular lead placement predicts acute hemodynamic response.

Aims: A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Methods and results: Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T-wave were performed at baseline and under BIVP. Based on the observed changes in three-dimensional area and perimeter, ΔQRS-area (responders: -46.7 ± 39.6% vs. non-responders: 1.1 ± 50.9%, P = 0.006) was considered as the preferred parameter. Receiver operating characteristic curve analysis identified -40% as the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed between LV ΔdP/dtmax and ΔQRS-area (R2 = 0.37, P = 0.001). Conclusion: ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.

Can visual analogue scale be used in radiologic subjective image quality assessment?

BACKGROUND: Assessment of qualitative or subjective image quality in radiology is traditionally performed using a fixed-point scale even though reproducibility has proved challenging. OBJECTIVE: Image quality of 3-T coronary magnetic resonance (MR) angiography was evaluated using three scoring methods, hypothesizing that a continuous scoring scale like visual analogue scale would improve the assessment. MATERIALS AND METHODS: Adolescents corrected for transposition of the great arteries with arterial switch operation, ages 9-15 years (n=12), and healthy, age-matched controls (n=12), were examined with 3-D steady-state free precession magnetic resonance imaging. Image quality of the coronary artery origin was evaluated by using a fixed-point scale (1-4), visual analogue scale of 10 cm and a visual analogue scale with reference points (figurative visual analogue scale). Satisfactory image quality was set to a fixed-point scale 3=visual analogue scale/figurative visual analogue scale 6.6 cm. Statistical analysis was performed using Cohen kappa coefficient and agreement index. RESULTS: The mean interobserver scores for the fixed-point scale, visual analogue scale and figurative visual analogue scale were, respectively, in the left main stem 2.8, 5.7, 7.0; left anterior descending artery 2.8, 4.7, 6.6; circumflex artery 2.5, 4.5, 6.2, and right coronary artery 3.2, 6.3, 7.7. Scoring with a fixed-point scale gave an intraobserver κ of 0.52-0.77 while interobserver κ was lacking. For visual analogue scale and figurative visual analogue scale, intraobserver agreement indices were, respectively, 0.08-0.58 and 0.43-0.71 and interobserver agreement indices were up to 0.5 and 0.65, respectively. CONCLUSION: Qualitative image quality evaluation with coronary 3-D steady-state free precession MR angiography, using a visual analogue scale with reference points, had better reproducibility compared to a fixed-point scale and visual analogue scale. Image quality, being a continuum, may be better determined by this method.

The cartilaginous Eustachian tube: Reliable CT measurement and impact of the length.

PURPOSE: Balloon dilation of the Eustachian tube is a treatment option for obstructive Eustachian tube dysfunction. The desired balloon position is in the cartilaginous portion. However, the balloon catheter may slide into the bony portion without the surgeon's knowledge. Knowing the length of the cartilaginous portion may improve catheter positioning, but there is no published research on measuring this portion selectively or on whether the length has an impact on development of disease or treatment outcome. To evaluate whether a measurement obtained from CT images is valuable and accurate, to standardize the manner of which the length is measured, and to compare our radiologic measurements to procedural findings, we designed a combined study. Further, we tested the length's influence on development of disease and treatment outcome. METHODS: Anatomical end points of the cartilaginous part of the Eustachian tube were unambiguously defined. The length was retrospectively measured bilaterally in 29 CT examinations by two radiologists, and repeated by one after two weeks. New reformats and measurements were made after 18 months for 10 of the patients. Prospectively 10 patients were included in a study where the length measured on CT was compared to per-procedural measurements based on catheter insertion depth to isthmus. Various parameters including length and treatment outcome were measured in 69 patients and 34 controls. RESULTS: Correlation was adequate to excellent in all comparisons. The length of the cartilaginous Eustachian tube did not predict treatment outcome or disease development. The lengths were significantly shorter in females. CONCLUSION: Measuring the cartilaginous portion of the Eustachian tube on CT images is precise and reproducible, and reflects the length measured intraoperatively. However, it does not seem have a prognostic value.

Insertion Depth in Cochlear Implantation and Outcome in Residual Hearing and Vestibular Function.

OBJECTIVES: It has long been known that cochlear implantation may cause loss of residual hearing and vestibular function. Different insertion depths may cause varying degrees of intracochlear trauma in the apical region of the cochlea. The present study investigated the correlation between the insertion depth and postoperative loss of residual hearing and vestibular function. DESIGN: Thirty-nine adults underwent unilateral cochlear implantation. One group received a Med-El +Flex electrode array (24 mm; n = 4), 1 group received a Med-El +Flex electrode array (28 mm; n = 18), and 1 group received a Med-El +Flex electrode array (31.5 mm; n = 17). Residual hearing, cervical vestibular-evoked myogenic potentials, videonystagmography, and subjective visual vertical/horizontal were explored before and after surgery. The electrode insertion depth and scalar position were examined with high-resolution rotational tomography after implantation in 29 subjects. RESULTS: There was no observed relationship between the angular insertion depth (405° to 708°) and loss of low-frequency pure-tone average. Frequency-specific analysis revealed a weak relationship between the angular insertion depth and loss of hearing at 250 Hz (R= 0.20; p = 0.02). There was no statistically significant difference in the residual hearing and vestibular function between the +Flex and the +Flex electrode array. Eight percent of the cases had vertigo after surgery. The electrode arrays were positioned inside the scala tympani and not scala vestibuli in all subjects. In 18% of the cases, the +Flex electrode array was not fully inserted. CONCLUSIONS: The final outcome in residual hearing correlates very weakly with the angular insertion depth for depths above 405°. Postoperative loss of vestibular function did not correlate with the angular insertion depth or age at implantation. The surgical protocol used in this study seems to minimize the risk of postoperative vertigo symptoms.

Long axis strain by MRI and echocardiography in a postmyocardial infarct population.

PURPOSE: To compare long axis strain (LAS) by magnetic resonance imaging (MRI) and echocardiography in a postinfarct patient population. Long axis left ventricle (LV) function is a sensitive index of incipient heart failure by echocardiography, but is less well established in MRI. LAS is an index of global LV function, which is easily assessed in cine loops provided by most cardiac MRI protocols. MATERIALS AND METHODS: In all, 116 patients (57 ± 9 years) were studied the same day using echocardiography and MRI 7.4 ± 4.1 months after a first myocardial infarction. LV length was measured in end diastole and end systole in conventional cine images with a temporal resolution of 50 msec or less, and LAS (%) was calculated as the change in LV length, relative to end diastole. Infarct mass was assessed by contrast-enhanced MRI. RESULTS: LAS was progressively reduced in patients with larger infarcts, and demonstrated good correlations with infarct mass (r = 0.55, P < 0.01). There was a good agreement between LAS assessed by echocardiography and MRI (r = 0.77, P < 0.01), and between LAS by MRI and speckle tracking strain by echocardiography (r = 0.74, P < 0.01). CONCLUSION: LAS is an index that allows measurement of LV long axis function by conventional cine MRI.

Scalar position in cochlear implant surgery and outcome in residual hearing and the vestibular system.

OBJECTIVE: To evaluate the effect of the intracochlear electrode position on the residual hearing and VNG- and cVEMP responses. DESIGN: Prospective pilot study. STUDY SAMPLE: Thirteen adult patients who underwent unilateral cochlear implant surgery were examined with high-resolution rotational tomography after cochlear implantation. All subjects were also tested with VNG, and 12 of the subjects were tested with cVEMP and audiometry before and after surgery. RESULTS: We found that although the electrode was originally planned to be positioned inside the scala tympani, only 8 of 13 had full insertion into the scala tympani. Loss of cVEMP response occurred to the same extent in the group with full scala tympani positioning and the group with scala vestibuli involvement. There was a non-significant difference in the loss of caloric response and residual hearing between the two groups. Interscalar dislocation of the electrode inside the cochlea was observed in two patients. A higher loss of residual hearing could be seen in the group with electrode dislocation between the scalae. CONCLUSIONS: Our findings indicate that intracochlear electrode dislocation is a possible cause to loss of residual hearing during cochlear implantation but cannot be the sole cause of postoperative vestibular loss.

Differentiation of Myocardial Properties in Physiological Athletic Cardiac Remodeling and Mild Hypertrophic Cardiomyopathy.

Clinical differentiation between athletes' hearts and those with hypertrophic cardiomyopathy (HCM) can be challenging. We aimed to explore the role of speckle tracking echocardiography (STE) and cardiac magnetic resonance imaging (CMR) in the differentiation between athletes' hearts and those with mild HCM. We compared 30 competitive endurance elite athletes (7% female, age 41 ± 9 years) and 20 mild phenotypic mutation-positive HCM carriers (15% female, age 51 ± 12 years) with left ventricular wall thickness 13 ± 1 mm. Mechanical dispersion (MD) was assessed by means of STE. Native T1-time and extracellular volume (ECV) were assessed by means of CMR. MD was higher in HCM mutation carriers than in athletes (54 ± 16 ms vs. 40 ± 11 ms, p = 0.001). Athletes had a lower native T1-time (1204 (IQR 1191, 1234) ms vs. 1265 (IQR 1255, 1312) ms, p < 0.001) and lower ECV (22.7 ± 3.2% vs. 25.6 ± 4.1%, p = 0.01). MD > 44 ms optimally discriminated between athletes and HCM mutation carriers (AUC 0.78, 95% CI 0.65-0.91). Among the CMR parameters, the native T1-time had the best discriminatory ability, identifying all HCM mutation carriers (100% sensitivity) with a specificity of 75% (AUC 0.83, 95% CI 0.71-0.96) using a native T1-time > 1230 ms as the cutoff. STE and CMR tissue characterization may be tools that can differentiate athletes' hearts from those with mild HCM.

No adverse association between exercise exposure and diffuse myocardial fibrosis in male endurance athletes.

The potential association between endurance exercise and myocardial fibrosis is controversial. Data on exercise exposure and diffuse myocardial fibrosis in endurance athletes are scarce and conflicting. We aimed to investigate the association between exercise exposure and markers of diffuse myocardial fibrosis by cardiovascular magnetic resonance imaging (CMR) in endurance athletes. We examined 27 healthy adult male competitive endurance athletes aged 41 ± 9 years and 16 healthy controls in a cross sectional study using 3 Tesla CMR including late gadolinium enhancement and T1 mapping. Athletes reported detailed exercise history from 12 years of age. Left ventricular total mass, cellular mass and extracellular mass were higher in athletes than controls (86 vs. 58 g/m2, 67 vs. 44 g/m2 and 19 vs. 13 g/m2, all p < 0.01). Extracellular volume (ECV) was lower (21.5% vs. 23.8%, p = 0.03) and native T1 time was shorter (1214 ms vs. 1268 ms, p < 0.01) in the athletes. Increasing exercise dose was independently associated with shorter native T1 time (regression coefficient - 24.1, p < 0.05), but expressed no association with ECV. Our results indicate that diffuse myocardial fibrosis has a low prevalence in healthy male endurance athletes and do not indicate an adverse dose-response relationship between exercise and diffuse myocardial fibrosis in healthy athletes.

Perfusion MRI at rest in subacute and chronic myocardial infarct.

BACKGROUND: Perfusion magnetic resonance imaging (MRI) and delayed contrast-enhanced MRI (DE-MRI) serve as tools for tissue characterization. PURPOSE: To assess and compare semi-quantitative parameters of myocardial infarct (MI) in the subacute and chronic phase, and to correlate these parameters with qualitative enhancement analysis. MATERIAL AND METHODS: Perfusion MRI at rest and DE-MRI were performed in 63 patients with anterior wall MI at 2-3 weeks after revascularization and repeated after 6 months. Descriptive enhancement parameters of contrast arrival time, initial upslope, enhancement at normal tissue peak (TTPn) and wash-out slope, and kinetic tissue parameters rBF, K (trans), k ep and v e were calculated. Subacute infarct tissue was compared to normal myocardium and chronic infarct tissue. Patients were stratified at baseline according to a qualitative grading of hypoenhancement based on first-pass enhancement and presence of microvascular obstruction (MO) at perfusion MRI and on persistent MO at DE-MRI. The qualitative grade was correlated to semi-quantitative perfusion MRI parameters. RESULTS: Initial upslope, enhancement at TTPn, rBF, and k ep were decreased and wash-out slope and v e were increased in infarct tissue (P < 0.001 for all analyses). Infarct tissue v e decreased from baseline to 6 months (P = 0.045). At baseline infarct tissue with persistent MO revealed decreased K (trans) and delayed contrast arrival, and more pronounced decrease of enhancement at TTPn, rBF and k ep compared to other enhancement groups (P < 0.008 for pairwise analyses). CONCLUSION: Perfusion is decreased in subacute reperfused infarct tissue compared to normal tissue. K (trans) is not decreased, consistent with increased surface area of the vascular bed of the subacute infarct. Infarct tissue v e is increased, and decreases with scarring. The presence of persistent MO correlates to more pronounced perfusion reduction and results in delayed contrast arrival, indicating microvascular collateral circulation.

Does the clot burden as assessed by the Mean Bilateral Proximal Extension of the Clot score reflect mortality and adverse outcome after pulmonary embolism?

Background: Rapid diagnosis and risk stratification are important to reduce the risk of adverse clinical events and mortality in acute pulmonary embolism (PE). Although clot burden has not been consistently shown to correlate with disease outcomes, proximally located PE is generally perceived as more severe. Purpose: To explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome. Methods: This was a single center retrospective cohort study. 1743 patients with computed tomography pulmonary arteriography (CTPA) verified PE diagnosed between 2005 and 2020 were included. Patients with active malignancy were excluded. The PE clot burden was assessed with MBPEC score: The most proximal extension of PE was scored in each lung from 1 = sub-segmental to 4 = central. The MBPEC score is the score from each lung divided by two and rounded up to nearest integer. Results: We found inconsistent associations between higher and lower MBPEC scores versus mortality. The all-cause 30-day mortality of 3.9% (95% CI: 3.0-4.9). The PE-related mortality was 2.4% (95% CI: 1.7-3.3). Patients with MBPEC score 1 had higher all-cause mortality compared to patients with MBPEC score 4: Crude Hazard Ratio (cHR) was 2.02 (95% CI: 1.09-3.72). PE-related mortality was lower in patients with MBPEC score 3 compared to score 4: cHR 0.22 (95% CI: 0.05-0.93). Patients with MBPEC score 4 did more often receive systemic thrombolysis compared to patients with MBPEC score 1-3: 3.2% vs. 0.6% (p < .001). Patients with MBPEC score 4 where more often admitted to the intensive care unit: 13% vs. 4.7% (p < .001). Conclusion: We found no consistent association between the MBPEC score and mortality. Our results therefore indicate that peripheral PE does not necessarily entail a lower morality risk than proximal PE.

Cardiac Magnetic Resonance Identifies Responders to Cardiac Resynchronization Therapy with an Assessment of Septal Scar and Left Ventricular Dyssynchrony.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab.

BACKGROUND: Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size. METHODS: STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24-36, 72-168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months. RESULTS: Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=-0.29, -0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=-0.09,-0.14, respectively). CONCLUSIONS: Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients. TRIAL REGISTRATION NUMBER: NCT03004703.