No prognostic benefit of multimodality imaging-guided left ventricular lead placement in cardiac resynchronization therapy: Long-term follow-up of the ImagingCRT study

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University, the Danish Heart Foundation, Health Research Foundation of Central Denmark Region, and Gangstedfonden. Background Observational data indicate that left ventricular (LV) lead placement at the latest contracting region and separate from myocardial scar is associated with improved prognosis in cardiac resynchronization therapy (CRT). In a double-blinded, randomized controlled trial (ImagingCRT), we tested the strategy of multimodality imaging-guided LV lead placement towards the latest mechanically activated non-scarred myocardial segment in CRT. Patients were included between 2011 and 2014 and allocated either to (1) imaging-guided LV lead placement using cardiac computed tomography, 99mTechnetium myocardial perfusion imaging, and speckle-tracking echocardiography (imaging group, n = 89) or to (2) routine LV lead implantation in a posterolateral region with late electrical activation (control group, n = 93). The multimodality imaging-guided strategy was found to reduce proportion of non-responders to CRT after 6 months. Impact on long-term clinical outcome is unknown. Purpose To evaluate the long-term effect of individualized multimodality imaging-guided LV lead placement compared to a routine fluoroscopic approach on the composite endpoint of death or heart failure (HF) hospitalization after CRT. Method We reviewed follow-up data until November 2020 for all 182 patients included in the ImagingCRT trial for the occurrence of HF hospitalization and all-cause death. Continuous variables are presented as median (interquartile range) or mean ± standard deviation. We used Kaplan-Meier plot and Cox proportional hazard regression analysis (unadjusted) to assess the risk of HF hospitalization and all-cause death, and used log-rank test for comparison between the two groups. Results All patients had standard CRT indication (left bundle branch block, New York Heart Association functional class II/ III/ IV 84 [46%]/ 92 [51%]/ 6 [3%], LV ejection fraction 25 ± 6%, QRS width 166 ± 22 milliseconds). Mean age was 70 ± 9 years, and 39 (21%) were female. During a median follow-up period of 6.7 years (3.3–7.9 years), the proportion of patients meeting the composite endpoint of HF hospitalization (n = 45 [25%]) or all-cause death (n = 56 [31%]) was 60% (n = 53) in the imaging group compared with 52% (n = 48) in the control group (hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.83–1.81, p = 0.31) (Figure 1). Neither the risk of HF hospitalization (HR 1.11, 95% CI 0.62–1.99, p = 0.72) or of all-cause death differed between the two groups (HR 1.23, 95% CI 0.82–1.85, p = 0.32). Conclusion An individualized multimodality imaging-guided strategy targeting LV lead placement towards the latest mechanically activated non-scarred myocardial segment during CRT implantation did not reduce the composite outcome of HF hospitalization or all-cause death during long-term follow-up. Abstract Figure 1

Surgical management of patient with left ventricular aneurysm and ventricular tachycardia

The management of patients with dilated cardiomyopathy and large anterior ventricular aneurysm presenting with ventricular tachycardia is not well-described. We report the case of 45-year-old male who presented with recurrent episodes of prolonged polymorphic ventricular tachycardia and previously failed medical management and endocardial and epicardial transcatheter ablation. We performed a Dor procedure to exclude the left ventricular aneurysm in conjunction with cryoablation to terminate his ventricular tachycardia. This surgical approach was found to be successful with conversion of the patient into normal sinus rhythm and restoration of the patient’s left ventricular morphology and function. We also propose a methodology for the surgical management of patients with left ventricular aneurysm and intractable ventricular tachycardia focused on a discussion with the patient and the cardiac team about the options for treatment, including surgery or continuing pharmacological and electrical cardioversion therapy, choosing the surgical technique that would exclude the most diseased and akinetic myocardial segment, and being more liberal with the use of cryoablation.

Emidec: A Database Usable for the Automatic Evaluation of Myocardial Infarction from Delayed-Enhancement Cardiac MRI

One crucial parameter to evaluate the state of the heart after myocardial infarction (MI) is the viability of the myocardial segment, i.e., if the segment recovers its functionality upon revascularization. MRI performed several minutes after the injection of a contrast agent (delayed enhancement-MRI or DE-MRI) is a method of choice to evaluate the extent of MI, and by extension, to assess viable tissues after an injury. The Emidec dataset is composed of a series of exams with DE-MR images in short axis orientation covering the left ventricle from normal cases or patients with myocardial infarction, with the contouring of the myocardium and diseased areas (if present) from experts in the domains. Moreover, classical available clinical parameters when the patient is managed by an emergency department are provided for each case. To the best of our knowledge, the Emidec dataset is the first one where annotated DE-MRI are combined with clinical characteristics of the patient, allowing the development of methodologies for exam classification as for exam quantification.

Multiparametric PET and MRI of myocardial damage after myocardial infarction: correlation of integrin αvβ3 expression and myocardial blood flow

Purpose Increased angiogenesis after myocardial infarction is considered an important favorable prognostic parameter. The αvβ3 integrin is a key mediator of cell-cell and cell-matrix interactions and an important molecular target for imaging of neovasculature and repair processes after MI. Thus, imaging of αvβ3 expression might provide a novel biomarker for assessment of myocardial angiogenesis as a prognostic marker of left ventricular remodeling after MI. Currently, there is limited data available regarding the association of myocardial blood flow and αvβ3 integrin expression after myocardial infarction in humans. Methods Twelve patients were examined 31 ± 14 days after MI with PET/CT using [18F]Galacto-RGD and [13N]NH3 and with cardiac MRI including late enhancement on the same day. Normal myocardium (remote) and areas of infarction (lesion) were identified on the [18F]Galacto-RGD PET/CT images by correlation with [13N]NH3 PET and cardiac MRI. Lesion/liver-, lesion/blood-, and lesion/remote ratios were calculated. Blood flow and [18F]Galacto-RGD uptake were quantified and correlated for each myocardial segment (AHA 17-segment model). Results In 5 patients, increased [18F]Galacto-RGD uptake was notable within or adjacent to the infarction areas with a lesion/remote ratio of 46% (26–83%; lesion/blood 1.15 ± 0.06; lesion/liver 0.61 ± 0.18). [18F]Galacto-RGD uptake correlated significantly with infarct size (R = 0.73; p = 0.016). Moreover, it correlated significantly with restricted blood flow for all myocardial segments (R = − 0.39; p < 0.0001) and even stronger in severely hypoperfused areas (R = − 0.75; p < 0.0001). Conclusion [18F]Galacto-RGD PET/CT allows the visualization and quantification of myocardial αvβ3 expression as a key player in angiogenesis in a subset of patients after MI. αvβ3 expression was more pronounced in patients with larger infarcts and was generally more intense but not restricted to areas with more impaired blood flow, proving that tracer uptake was largely independent of unspecific perfusion effects. Based on these promising results, larger prospective studies are warranted to evaluate the potential of αvβ3 imaging for assessment of myocardial angiogenesis and prediction of ventricular remodeling.

Speckle-Tracking Echocardiography in Cardio-Oncology and Beyond

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer therapy, but also in patients with a variety of other clinical conditions. This review and case series examine the clinical applications and overall usefulness of speckle-tracking echocardiography in cardio-oncology and, more broadly, in clinical cardiology.

Contrast Echocardiography with a Quantitative Assessment of Myocardial Perfusion in Patients with Previous Q-Wave Myocardial Infarction

Objective. To assess possibilities of contrast echocardiography with quantitative evaluation of myocardial perfusion in patients with previous Q-wave myocardial infarction.Materials and Methods. We examined 15 men (42-72 years) with coronary artery disease and previous myocardial infarction, and pathological Q-wave in 2 or more ECG leads. Quantification of left ventricular (LV) myocardial perfusion was performed by calculating of the ultrasound signal tissue intensity from the LV myocardial segments during intravenous administration of the ultrasound contrast agent (SonoVue). The Tissue intensive curve (TIC) analysis was done in the end-diastolic period before and on the fourth cardiac cycle after applying the "flash". Changes in the intensity of myocardial perfusion (A4, dB) was estimated as the difference between the intensity values of the ultrasound signal in the myocardial segment during the period of filling the contrast bubbles on 4-th cardiac cycle and before applying the «flash». Measurements were performed in 16 segments of the LV. A contrast cardiac magnetic resonance imaging (contrast MRI) was performed in order to verify the LV scar. Fibrotic changes of 50% of myocardial wall or more were considered as signs of post-infarction scar.Results. The dynamics of perfusion and scar presence in 240 myocardial segments were evaluated. The median A4 was 1 dB (range, -20 to 10 dB). MRI revealed 82 of 240 segments with the large-focal scar. The effectiveness of the diagnostic test (quantitative contrast perfusion echocardiography with A4 assessment) to detect myocardial scar was investigated. ROC curve analysis showed good model quality, AUC=0,787 (0,730-0,837); sensitivity 82.9%; specificity 75.3%; p<0.01. The cut-off point for A4 was -1.Conclusion. A new approach to quantitative contrast assessment of perfusion allows to identify perfusion disorders with high efficiency in patients with previous Q-wave myocardial infarction.

The cardiomyopathies: Hypertrophic, dilated, restrictive, and right ventricular

The term cardiomyopathy is used to describe heart muscle disease unexplained by abnormal loading conditions (hypertension, valve disease, and others), congenital cardiac abnormalities, and ischaemic heart disease. The current classification is based on the predominant phenotype, that is, hypertrophic, dilated, arrhythmogenic right ventricular, restrictive, and unclassifiable (including left ventricular non-compaction), and— where possible— incorporating inheritance and genotype. The diagnosis of hypertrophic cardiomyopathy is based on the demonstration of unexplained myocardial hypertrophy, defined as a wall thickness measurement exceeding two standard deviations above normal for gender and age. In practice, in an adult of normal size, the presence of a left ventricular myocardial segment of 1.5 cm or greater in thickness is diagnostic. Less stringent criteria should be applied to first-degree relatives of an unequivocally affected individual.

Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy

ObjectiveIn patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM.Methods101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE.ResultsIn HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R2 for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001).ConclusionsMicrovascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker.

P2606Analysis of myocardial work: a potential new tool for a better assessment of left ventricular function

Background Left ventricular (LV) deformation is dependent on mechanical load and does not reflect directly the myocardial energy consumption. Thus, measurement of global and regional myocardial work might be alternative and complementary methods for the assessment of myocardial function. However, there is no data regarding myocardial work changes during the heart failure continuum, from normal to diastolic dysfunction (DD), and to heart failure with preserved ejection fraction (HFpEF). Methods We assessed 80 subjects by 2D conventional and speckle tracking echocardiography (2DSTE): 25 patients with DD, 30 with HFpEF, and 25 normal, control subjects. We measured NTproBNP, LV ejection fraction (EF), and E/E' ratio. We used a new approach to calculate myocardial work, during mechanical systole and isovolumetric relaxation, by 2DSTE: global constructive work (GCW), as the “positive” work of the heart; global wasted work (GWW), as the “negative” work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. Similarly, a regional, segmental analysis was performed (18 segments model) (Figure 1). Results GCW increases in patients with DD, probably as a compensatory mechanism to preserve LV function against an increased after load, and decreases back to the normal values in HFpEF, while GWE significantly decreases from normal subjects to patients with DD, and then further in patients with HFpEF (table). Meanwhile, GWW increases from normal subjects to patients with DD, and then further in patients with HFpEF. As expected, GWI does not change significantly. By segmental analysis, first segment affected in terms of myocardial work is basal antero-septal segment, with low WE and higher WW (figure), probably due to the flat shape (based on the Laplace law), with a compensatory increased CW in the apical segments. NTproBNP level and E/E' ratio correlated only with GWW (r=0.4, p=0.013). Comparative global myocardial work Group LVEF (%) E/E' NTproBNP (pg/ml) GWI (mmHg%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls 58±6 7.3±2.4 – 2102±303 95.5±1.8 2295±279 87.9±39.6 DD 57±8 7.7±2.4 36±25 2296±431 94.8±2.3 2550±463 108±50 HFpEF 63±7 10.3±3.1 349±418 2074±485 93.5±2.5 2300±535 125±51 P (Anova) 0.004 <0.001 <0.001 0.12 0.008 0.05 0.019 Figure 1. Myocardial Work Conclusion Myocardial work efficiency decreases and wasted work increases in parallel with the severity of LV dysfunction. The first myocardial segment affected is basal antero-septal. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better assessment of LV function in patients with DD or HFpEF. Acknowledgement/Funding This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III

Hypertrophic cardiomyopathy: diagnosis and assessment of symptoms

The diagnosis of hypertrophic cardiomyopathy (HCM) in adults is based on the presence of left ventricular wall thickness greater than 15 mm using any imaging modality on at least one myocardial segment and not explained solely by abnormal cardiac loading conditions; a 13 mm threshold should be applied for familial screening in first-degree relatives. Diagnosis in children, in the elderly, in hypertensive individuals, and in elite athletes may be challenging. Initial evaluation should include a family pedigree, evaluation of signs and symptoms, electrocardiogram, and 48 h Holter electrocardiogram monitoring, exercise testing, imaging, and biochemistry. The presence of an intraventricular left ventricular obstruction, present in two-thirds of the patients at rest, during Valsalva or exercise, should be systematically evaluated using echocardiography. Cardiovascular magnetic resonance imaging with late gadolinium enhancement should always be considered, particularly to assess apical hypertrophy, left ventricular aneurysms, and fibrosis. This systematic approach is recommended to assist in the detection of HCM not caused by mutations in cardiac sarcomere protein genes (up to 10% of patients). Genetic tests should be performed and interpreted after a careful and complete clinical evaluation and genetic counselling. HCM is characterized by symptoms of dyspnoea, fatigue, chest pain, palpitations, and syncope, which are highly variable. Functional limitation may be difficult to evaluate and often necessitates cardiopulmonary exercise testing.