The role of multimodality imaging in the selection for implantable cardioverter-defibrillators in heart failure: A narrative review.

Advanced pharmacologic and interventional therapies have improved survival in heart failure. Implantable cardioverter-defibrillators (ICD) have been shown to reduce mortality in patients with heart failure, but the benefit appears to be uneven in this population. We reviewed the evidence showing the benefit of ICD therapy in heart failure patients, the main issues arising from these studies, and the possible answers for a better risk stratification. In addition, we showed that multimodality imaging could improve patient selection for the implantation of ICDs, in both primary and secondary prevention, beyond the selection using only the left ventricular ejection fraction, by concentrating on arrhythmic substrate.

How the trabecular layer impacts on left ventricular function.

The ventricular trabecular layer is crucial in embryonic life. In adults, the proportion of trabecular-to-compact myocardium varies substantially between individuals, within individuals over time, and yet exhibits almost no correlation to pump function since most individuals with excessive trabeculation are asymptomatic. The question of how functional is the myocardium of the trabecular layer, relative to the myocardium of the compact layer, has been difficult to answer but it is often assumed to be inferior. An answer is now emerging from recent advances and it can improve our understanding of how the trabecular layer impacts on pathogenicity. This narrative review concerns natural variation in trabeculation, tissue organization, transcriptomics, immunohistochemistry, vascularization, electrical propagation, diastolic function and compliance, systolic function, and ejection fraction. There are no overt transcriptional differences in the adult stage, and the myocardium is equally equipped with sarcomeric proteins, mitochondria, and vascular supply. The similar structural features are consistent with myocardium with a similar stroke work per gram tissue, along with a high ejection fraction of the trabecular layer. In conclusion, the myocardium of the trabecular and compact layers is highly similar and this offers a logical explanation for the reproducible observations that most individuals with excessive trabeculation are asymptomatic.

PFO-spectrum disorder: two different cerebrovascular diseases in patients with PFO as detected by AI brain imaging software.

Background: Patent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions. Patients and methods: Retrospective, case-control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume. Results: Of the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03-0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02-0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes. Discussion: We suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and "silent" WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the "at-risk" PFOs and gain deeper insights into their clinical implications.

Multimodality Imaging and Biomarker Approach to Characterize the Pathophysiology of Heart Failure in Left Ventricular Non-Compaction with Preserved Ejection Fraction.

Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). METHODS: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. RESULTS: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (-21.4 ± 4.4 vs. -24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156-489) vs. 156 (139-257) pg/mL] and Galectin-3 [7.3 (6.0-11.5) vs. 5.6 (4.8-8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). CONCLUSION: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.

New insights into the potential utility of the left atrial function analysis in heart failure with preserved ejection fraction diagnosis.

AIMS: None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. METHODS: We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). RESULTS: LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level. CONCLUSIONS: By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

Febrile episode unmasking neuropsychiatric systemic lupus erythematosus with lytic lesions caused by secondary autoimmune myelofibrosis: Case report.

RATIONALE: Systemic lupus erythematosus (SLE) is characterized by numerous immunological abnormalities that lead to multiorgan involvement. Central and peripheral nervous system manifestations are present in 8% to 92% of the cases of SLE. Furthermore, there have been reported cases of secondary autoimmune myelofibrosis associated with SLE. PATIENT CONCERNS: We present the case of a 64-year-old female who was transferred from the Cardiology Department, where she was admitted for pericardial-pleural-peritoneal effusion after being discharged from another hospital following the resolution of a febrile episode. During hospitalization, she presented multiple oculomotor nerves palsies and weakness in the lower limbs. Serial cerebral magnetic resonance imaging (MRI) revealed extensive cerebral venous thrombosis. Nerve conduction studies showed sensory-motor axonal polyneuropathy. Thoracic MRI revealed a rare finding in patients with SLE - lytic lesions. DIAGNOSES: Extensive clinical, imaging, blood, and urine tests were performed. The patient exhibited pancytopenia, elevated inflammatory markers, hyperhomocysteinemia, mild hypoproteinemia, and severe proteinuria. The Hematology consultation ascertained that the peripheral blood smear and the bone marrow aspiration showed no alterations suggestive for a primary hematological disease and the thoracic vertebral-medullary MRI changes had a very low probability of representing osteolytic lesions in the context of plasma cells dyscrasia, but could not exclude their being result of a secondary autoimmune myelofibrosis. Immunology blood tests highlighted the presence of antinuclear antibodies and lupus anticoagulants. In this context, the Rheumatology consultation established the diagnosis of SLE with multiple complications. INTERVENTIONS: The patient received treatment with cyclophosphamide. OUTCOMES: The ocular motricity problems and the paraparesis showed improvement. However, 1 week later, the patient developed weakness, dyspnea, and right lower quadrant abdominal pain. The abdominal-pelvic computed tomography scan indicated an acute right retroperitoneal hematoma with active bleeding for which she underwent arterial embolization of the spinal lumbar arteries with optimal result, but she died a few days later. LESSONS: We chose to present this case in order to highlight the importance of interdisciplinarity in diagnosing and managing patients with SLE and multiorgan ailments, especially when faced with rare constellations of complications such as extensive cerebral venous thrombosis and osseous lytic lesions caused by secondary autoimmune myelofibrosis.

Relation of Mitral Annulus and Left Atrial Dysfunction to the Severity of Functional Mitral Regurgitation in Patients with Dilated Cardiomyopathy.

METHODS: 56 patients (58 ± 17 years, 42 men) with DCM and FMR and 52 controls, prospectively enrolled, underwent 3DTTE dedicated for mitral valve (MV), LA, and left ventricle (LV) quantitative analysis. RESULTS: Patients with FMR vs. controls presented increased MA size and sphericity during the entire systole, whereas MA fractional area change (MAFAC) and MA displacement were decreased (15 ± 5 vs. 28 ± 5%; and 5 ± 3 vs. 10 ± 2 mm, p < 0.001). In patients with moderate/severe FMR, MA diameters correlated with PISA radius, EROA, and regurgitant volume (Rvol), as also did the MA area (with PISA radius, EROA, and Rvol: r = 0.48, r = 0.58, and r = 0.47, p < 0.05). MAFAC correlated inversely with EROA and Rvol (r = -0.32 and r = -0.35, p < 0.05), with both active and total LA emptying fractions and with LV ejection fraction as well. In a stepwise multivariate regression model, decreased MAFAC and increased LA volume independently predicted patients with severe FMR. CONCLUSIONS: Patients with DCM and FMR have MA geometry remodeling and contractile dysfunction, correlated with the severity of FMR. MA contractile dysfunction correlated with both LA and left LV pumps dysfunctions and predicted patients with severe FMR. Our results provide new insights that might help with better selection of patients for MV transcatheter procedures.

New Myocardial Deformation by 2D Multi-layer Speckle-Tracking Analysis in Healthy Patients: Normal Reference Values and Their Physiologic Determinants.

There are limited data regarding intrinsic changes of the left (LV) and right ventricular (RV) deformation assessed layer-by-layer. We designed a prospective multi-centric study, using a new multi-layer 2D-speckle-tracking-echo (MSTE). We investigated the impact of different physiologic parameters on layer-specific LV/RV myocardial deformation and synchrony, in a large group of healty subjects. 151 subjects were feasible for MSTE, divided in 4 groups: <40 yrs, 41 to 50 yrs, 51 to 60, and >61 yrs. We found a significant higher LV dyssynchrony index with age. In all groups, an endo-epicardial gradient was present in longitudinal LV/RV and circumferential deformation, with higher values in endocardial layer (p<0.001). There were no differences in deformation with age in all layers. We provided normal reference values for a new index of LV dyssynchrony, and also for RV longitudinal, LV circumferential and longitudinal layer-specific deformation, which can be further used when assessing subclinical dysfunction in myocardial diseases.

The added value of three-dimensional echocardiography in the late diagnosis of a pacemaker complication in a patient with severe congestive heart failure: a case report.

BACKGROUND: Three-dimensional echocardiography (3DE) presents an increasingly important role in the management of interventional cardiac procedures, overcoming limitations of conventional two-dimensional echocardiography (2DE). Early use of 3DE might have an added value in the diagnosis of device-related complications, such as lead induced tricuspid regurgitation (LITR), by providing better understanding of its mechanisms and ensuring a prompt and individually tailored treatment strategy. CASE SUMMARY: We report the case of a female patient with repeated hospitalizations for congestive heart failure in the past 2 years, who had a permanent single-chamber ventricular pacemaker (PM) implanted 10 years ago and a misleading diagnosis of severe tricuspid regurgitation (TR) secondary to annular dilation, based on 2DE. Conversely, current 3DE assessment of the TR mechanisms revealed that the PM lead was not placed between the commissures, but in the middle segment of the septal leaflet, causing impingement of the leaflet and severe TR. DISCUSSION: Given the growing indication for cardiac devices, it is necessary to better define LITR and to establish its impact on patient prognosis. Due to lacking in proper diagnostic techniques, LITR is generally recognized as a late complication of PM/ICD implantation. Two-dimensional echocardiography has important limitations, whereas 3DE provides more accurate information on the TV apparatus in relation to the endocardial leads. Our case shows the usefulness of 3DE for a correct diagnosis of a device-related complication. Its utility in the follow-up of patients receiving cardiac devices remains to be determined, as well as its potential value in the guidance of lead insertion.