Tighter is better: Can a simple and cost-free parameter predict response to cardiac synchronization therapy?

BACKGROUND: Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce nonresponders. AIM: Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation. METHODS: A three-centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured. RESULTS: In a 6-month follow-up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r-squared: 0.48, adjusted r-squared: 0.43, p = .001), and the cut-off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p = .001). At 24 months, a statistically significant difference was found between patients with a QI ≤ 12.25% and those with a QI > 12.25% regarding NYHA class worsening (p = .04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p = .0179). A correlation between pre-CRT QRSd/LVEDV and QI was observed (r = + 0.20; p = .0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p < .0001) at follow-up. CONCLUSIONS: QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict CRT response.

Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence.

INTRODUCTION: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear. METHODS: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist. Aldosterone-renin-ratio (ARR) was measured on actual medication. RESULTS: Women had a higher prevalence of LV hypertrophy (46% vs. 33%) and LA enlargement (79% vs 65%, both p < 0.05) than men, while drug nonadherence (8% vs. 9%, p > 0.514) did not differ. Women were older and had lower serum renin concentration and higher ARR than men, while 24-h systolic BP (141 ± 9 mmHg vs. 142 ± 9 mmHg), and the prevalences of obesity (43% vs. 50%) did not differ (all p > 0.10). In multivariable analyses, female gender was independently associated with a two-fold increased risk of LV hypertrophy (OR 2.01[95% CI 1.30-3.10], p = 0.002) and LA enlargement (OR 1.90 [95% CI 1.17-3.10], p = 0.010), while no association with drug nonadherence was found. Higher ARR was independently associated with LV hypertrophy in men only (OR 2.12 [95% CI 1.12-4.00] p = 0.02). CONCLUSIONS: Among patients with uncontrolled hypertension, the higher prevalence of LV hypertrophy and LA enlargement in women was not explained by differences in drug nonadherence. REGISTRATION: URL:  https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03209154.

Assessment of myocardial strain patterns in patients with left bundle branch block using cardiac magnetic resonance.

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.

Ethnic differences in cardiac structure and function assessed by MRI in healthy South Asian and White European people: A UK Biobank Study.

BACKGROUND: Echocardiographic studies indicate South Asian people have smaller ventricular volumes, lower mass and more concentric remodelling than White European people, but there are no data using cardiac MRI (CMR). We aimed to compare CMR quantified cardiac structure and function in White European and South Asian people. METHODS: Healthy White European and South Asian participants in the UK Biobank Imaging CMR sub-study were identified by excluding those with a history of cardiovascular disease, hypertension, obesity or diabetes. Ethnic groups were matched by age and sex. Cardiac volumes, mass and feature tracking strain were compared. RESULTS: 121 matched pairs (77 male/44 female, mean age 58 ± 8 years) of South Asian and White European participants were included. South Asian males and females had smaller absolute but not indexed left ventricular (LV) volumes, and smaller absolute and indexed right ventricular volumes, with lower absolute and indexed LV mass and lower LV mass:volume than White European participants. Although there were no differences in ventricular or atrial ejection fractions, LV global longitudinal strain was higher in South Asian females than White European females but not males, and global circumferential strain was higher in both male and South Asian females than White European females. Peak early diastolic strain rates were higher in South Asian versus White European males, but not different between South Asian and White European females. CONCLUSIONS: Contrary to echocardiographic studies, South Asian participants in the UK Biobank study had less concentric remodelling and higher global circumferential strain than White European subjects. These findings emphasise the importance of sex- and ethnic- specific normal ranges for cardiac volumes and function.

[Applying of magnetic resonance tomography for assessment of cardiac remodeling and risk stratification in patients with pulmonary arterial hypertension].

Magnetic resonance imaging - is high precision method for diagnosing cardiovascular diseases. Simultaneously with the anatomy and function of the right ventricle, magnetic resonance imaging allows to assess the pulmonary circulation, which leads to the widespread use of this method in the diagnosis and dynamic monitoring of patients with pulmonary arterial hypertension. The article is devoted to the assessment of cardiac remodeling and risk stratification of this group of patients. Special attention is given to new prognostic parameters included in the scale for risk stratification of patients with pulmonary hypertension of the European Society of Cardiology/European Respiratory Society 2022.

Assessment of the elastic stiffness of human cardiac fibres after an apical infarction using finite element simulation.

Several research works in the literature have focused on understanding the post-infarction ventricular remodelling phenomenon, but few works have considered the evaluation of the elastic behaviour of the cardiac tissue after a myocardial infarction. This paper presents an investigation focused on predicting the elastic performance of the human heart after a left ventricular apical infarction. The aim is to understand the elastic alterations of the cardiac fibres at different periods after an apical infarct. For this purpose, a hybrid method based on pressure and volume measurements of the left ventricle (LV) at different periods of ventricular remodelling, and the Finite Element Method (FEM), is developed. In addition, several performance indexes are defined to evaluate the heart performance during the ventricular remodelling process. The results show that during the first 2 weeks after a heart infarction, the cardiac fibres must support a much higher structural overload than during normal conditions. This structural overload is proportional to the aneurysm size but diminishes with the time, together with a significant reduction of the ventricular pumping capacity.

Integration of ventricular remodeling, synchrony and filling rate parameters to improve the assessment of left ventricular systolic function.

INTRODUCTION AND OBJECTIVES: The aim of this study is to assess the relationship between structural, remodeling, synchrony, and systolic left ventricular (LV) function parameters using gated-SPECT myocardial-perfusion-images (gSPECT-MPI). In addition, obtaining the cut-off values for end-diastolic LV-shape-index (EDLVsi), end-systolic LV-shape-index (ESLVsi), ECC (eccentricity-index) and PER, and developing a new index to evaluate different patterns of the LV systolic function. METHODS: The study was approved by the Hospital's Ethical-Committee (PR[AG]168.2010), and all patients gave their informed consent. We analyzed prospectively 238 patients (age 63.4 ±â€¯13 years) who underwent stress-rest gSPECT-MPI (control-group, n = 148; patients with previous myocardial infarction [MI], n = 90). RESULTS: In the control group, with regard to remodeling parameters: the end-diastolic-volume-index (EDV) and the ECC were the parameters that influenced the EDLVsi (r2: 0.52, p < 0.001). EDV, PER, men, and the ECC were the parameters (r2: 0.44; p < 0.001) which influenced the ESLVsi. EDLVsi, ESLVsi, LVEF and the stroke-volume were the parameters (r2: 0.62; p < 0.001) which influenced the ECC. With regards to PER: LVEF, heart-rate, bandwidth, and the standard-deviation were the influencing parameters (r2: 0.76; p < 0.001). The cut-off values for EDLVsi, ESLVsi, ECC, and PER were 0.59, 0.42, 0.87, and 3.3, respectively. The PER, the ESLVsi and the bandwidth were the parameters related to patients with previous MI (AUC: 0.89); and they allow the assessment of different patterns of systolic function (PERRS-index: peak-emptying-rate, left ventricular-remodeling and synchrony). CONCLUSIONS: The remodeling, synchrony and the systolic function parameters of the LV should be interpreted together (PERRS-index). In this way, we obtain different patterns of LV systolic function.

Exercise stress cardiac magnetic resonance imaging in the assessment of induced cardiovascular responses in cardiac patients: a scoping review protocol.

OBJECTIVE: This scoping review will describe cardiac magnetic resonance imaging testing protocols used in combination with exercise (Ex-CMR) to assess cardiovascular responses. The review will document the advantages and limitations of these protocols in cardiac patients. INTRODUCTION: Ex-CMR characterizes the heart, differentiating between normal and pathological cardiac remodeling with considerable accuracy. However, there is no review detailing existing Ex-CMR protocols. This is particularly important since not all Ex-CMR protocols seem to induce enough stress to effectively characterize cardiac remodeling, hence the need for a review to report on the current evidence. INCLUSION CRITERIA: This review will consider studies that use Ex-CMR testing protocols to assess cardiovascular responses, revealing cardiac remodeling in patients whose age at the time of the study was ≥ 18 years. METHODS: The review will be conducted in accordance with the JBI methodology for scoping reviews and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The following databases will be searched: PubMed, Embase, ISI Web of Science, OpenGrey, Grey Matters, and OAlster. Articles in English and French will be included and there will be no limitation set for the date of publication. Data will be extracted from papers included in the scoping review by 2 independent reviewers and will be classified in summary tables. REVIEW REGISTRATION: Open Science Framework https://osf.io/hvn75/?view_only=f6cf8fc2112e498d89c39639dbce70d1 .

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

OBJECTIVES: Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. METHODS: In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. RESULTS: In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5 mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). CONCLUSIONS: In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. KEY POINTS: • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.

Approach to optimal assessment of right ventricular remodelling in heart transplant recipients: insights from myocardial work index, T1 mapping, and endomyocardial biopsy.

AIMS: Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients. METHODS AND RESULTS: Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 ± 8.7%) and MWI (403.2 ± 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage. CONCLUSION: Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage.

Association of Left Ventricular Remodeling Assessment by Cardiac Magnetic Resonance With Outcomes in Patients With Chronic Aortic Regurgitation.

Importance: Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload, which results in progressive LV remodeling negatively affecting outcomes. Whether cardiac magnetic resonance (CMR) volumetric quantification can provide incremental risk stratification over standard clinical and echocardiographic evaluation in patients with chronic moderate or severe AR is unknown. Objective: To compare LV remodeling measurements by CMR and echocardiography between patients with and without heart failure symptoms and to verify the association of remodeling measurements of patients with chronic moderate or severe AR but no or minimal symptoms with clinical outcomes receiving medical management. Design, Setting, and Participants: This multicenter retrospective cohort study included consecutive patients with at least moderate chronic native AR evaluated by 2-dimensional transthoracic echocardiography and CMR examination within 90 days from each other between January 2012 and February 2020 at Allina Health System. Data were analyzed from June 2021 to January 2022. Exposures: Clinical evaluation and risk stratification by CMR. Main Outcomes and Measures: The end point was a composite of death, heart failure hospitalization, or progression of New York Heart Association functional class while receiving medical management, censoring patients at the time of aortic valve replacement (when performed) or at the end of follow-up. Results: Of the 178 included patients, 119 (66.9%) were male, 158 (88.8%) presented with no or minimal symptoms (New York Heart Association class I or II), and the median (IQR) age was 58 (44-69) years. Compared with patients with no or minimal symptoms, symptomatic patients had greater LV end-systolic volume index (LVESVi) by CMR (median [IQR], 66 [46-85] mL/m2 vs 42 [30-58] mL/m2; P < .001), while there were no significant differences by echocardiography (LVESVi: median [IQR], 38 [30-58] mL/m2 vs 27 [20-42] mL/m2; P = .07; LV end-systolic diameter index: median [IQR], 21 [17-25] mm/m2 vs 18 [15-22] mm/m2; P = .17). During the median (IQR) follow-up of 3.3 (1.6-5.8) years, 50 patients with no or minimal symptoms receiving medical management developed the composite end point, which, in multivariate analysis adjusted for age and EuroSCORE II, was independently associated with LVESVi of 45 mL/m2 or greater and aortic regurgitant fraction of 32% or greater, the latter adding incremental prognostic value to CMR volumetric assessment. Conclusions and Relevance: In patients with chronic moderate or severe AR, patients presenting with heart failure symptoms have greater LVESVi by CMR than those with no or minimal symptoms. In patients with no or minimal symptoms, CMR quantification of LVESVi and AR severity may identify those at risk of death or incident heart failure and therefore should be considered in the clinical evaluation and decision-making of these patients.

Effects of diabetes mellitus on left ventricular function and remodeling in hypertensive patients with heart failure with reduced ejection fraction: assessment with 3.0 T MRI feature tracking.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear. METHODS: A total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM-]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses. RESULTS: Despite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM-) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM-) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [ß = - 0.189; p = 0.011], GCPS [ß = 0.217; p = 0.005], GLPS [ß = 0.237; p = 0.002]). HTN was associated with impaired GLPS (ß = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05). CONCLUSIONS: DM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.

Relationship Between Left Ventricular Strain Assessment by Cardiac Magnetic Resonance Imaging and Response to Cardiac Resynchronization Therapy.

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions.

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).

Imaging techniques for the assessment of adverse cardiac remodeling in metabolic syndrome.

Metabolic syndrome (MetS) includes different metabolic conditions (i.e. abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension) that concour in the development of cardiovascular disease and diabetes. MetS individuals often show adverse cardiac remodeling and myocardial dysfunction even in the absence of overt coronary artery disease or valvular affliction. Diastolic impairment and hypertrophy are hallmarks of MetS-related cardiac remodeling and represent the leading cause of heart failure with preserved ejection fraction (HFpEF). Altered cardiomyocyte function, increased neurohormonal tone, interstitial fibrosis, coronary microvascular dysfunction, and a myriad of metabolic abnormalities have all been implicated in the development and progression of adverse cardiac remodeling related to MetS. However, despite the enormous amount of literature produced on this argument, HF remains a leading cause of morbidity and mortality in such population. The early detection of initial adverse cardiac remodeling would enable the optimal implementation of effective therapies aiming at preventing the progression of the disease to the symptomatic phase. Beyond conventional imaging techniques, such as echocardiography, cardiac tomography, and magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this review, we summarize the pathophysiology of MetS-related cardiac remodeling and illustrate the relevance of state-of-the-art multimodality cardiac imaging to identify and quantify the degree of myocardial involvement, prognosticate long-term clinical outcome, and potentially guide therapeutic strategies.

Role of Echocardiography for Assessment of Cardiac Remodeling in Congenitally Corrected Transposition of Great Arteries.

BACKGROUND: The purpose of this study was to assess the role of echocardiography for a comprehensive assessment of cardiac remodeling, and the relationship between indices of cardiac remodeling and cardiovascular events (defined as the composite end point of heart failure hospitalization, heart transplant, or cardiovascular death) in adults with congenitally corrected transposition of great arteries (cc-TGA). METHODS: This is a retrospective study of adults with cc-TGA who underwent echocardiogram (2003-2020). Offline image analysis was performed in all patients. Chamber (atrial and ventricular) function and size were assessed by strain imaging and 2-dimensional echocardiography. RESULTS: Of 233 patients with cc-TGA (40±15 years), 123 (55%) had at least one cardiac procedure before baseline echocardiogram. Of 233 patients, 76% and 61% had left atrial dysfunction and systemic right ventricular dysfunction, respectively; while 43% and 11% had right atrial dysfunction and left ventricular dysfunction, respectively. During a median follow-up of 8.9 years, 114 (49%) underwent additional cardiac procedures, and 66 (28%) had cardiovascular events. Left atrial reservoir strain, right ventricular global longitudinal strain, right atrial reservoir strain, left ventricular systolic pressure, and left ventricular global longitudinal strain were independently associated with cardiovascular events. CONCLUSIONS: In addition to the clinical importance of right ventricular systolic dysfunction in cc-TGA that is already well described, the current study demonstrated, for the first time, that biatrial dysfunction was common and was associated with clinical outcomes. Since there are currently no effective therapies for atrial and ventricular dysfunction in patients with cc-TGA, there is a need for research to identify novel strategies to prevent atrial and ventricular dysfunction in this population.

Assessment of proarrhythmic ventricular electrophysiological remodeling in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is related to cardiovascular disease and results in increased mortality rates. Ischemia, autonomic nervous system dysfunction, impaired cardiac ionic currents, and genetic predisposition may be the underlying mechanisms. Proarrhythmic ventricular electrophysiological remodeling detected on the basis of Tp­e interval, Tp-e/QT, and Tp-e/QTc ratios plays a key role in the prognosis. Our aim was to assess proarrhythmic ventricular electrophysiological remodeling in patients with RA, a well-known chronic inflammatory disorder. MATERIALS AND METHODS: A total of 163 patients with RA and 47 patients as a control group were included in this retrospective study. Proarrhythmic ventricular electrophysiological remodeling markers were evaluated in both groups along with baseline demographic and clinical variables. Patients using medication or with chronic disorders that can affect ventricular repolarization markers were excluded. RESULTS: The patients with RA had prolonged Tp­e interval (66 ms [44-80]; 80 ms [78-96], p < 0.001) and increased Tp-e/QT ratio (0.18 [0.12-0.22]; 0.22 [0.20-0.24], p < 0.001) and Tp-e/QTc ratio (0.16 [0.11-0.19]; 0.20 [0.17-0.22], p < 0.001) compared to the control group. CONCLUSION: The Tp­e interval and Tp-e/QT ratio, which may help to clarify the pathophysiological mechanisms of ventricular arrhythmias, were increased in patients with RA.

Assessment of sacubitril/valsartan effects on left ventricular dynamics using 3D echocardiography and 3D strain in heart failure with reduced ejection fraction patients.

BACKGROUND: Three-dimensional (3D) echocardiography and 3D strain parameters have been used for a comprehensive quantitative assessment of left ventricular (LV) myocardial dynamics. So far, there are no data on sacubitril/valsartan effects on cardiac functions and LV reverse remodeling using 3D echocardiography. This study aimed to evaluate the effects of sacubitril/valsartan on the LV functions using two-dimensional (2D) echocardiography, 3D echocardiography, and the 3D strain parameters. METHODS: A single-center prospective cohort study which included 100 heart failure with reduced ejection fraction (HFrEF) patients with guidelines-approved indications for sacubitril/valsartan treatment. Patients received a short course (3-month) of sacubitril/valsartan. 3-month follow-up 2D, 3D echocardiographic parameters, and 3D strain were compared to baseline parameters. RESULTS: The results of the study revealed a significant improvement in left ventricular dynamic functions at 3-month follow-up with an improvement in left ventricular systolic function (mean left ventricular ejection fraction (LVEF) increased from 27.65±4.98% to 32.89±6.03%, P<0.001). Comparison of HFrEF patients with ischemic and non-ischemic etiologies showed that echocardiographic parameters significantly improved in both groups after 3 months of sacubitril/valsartan treatment. There was no statistically significant difference between both groups regarding echocardiographic parameters at baseline and 3-month follow-up. CONCLUSIONS: In a single-center prospective observational cohort study evaluating the effects of short-term (3-month course) sacubitril/valsartan treatment on LV dynamics assessed by 3D echocardiography and 3D strain, sacubitril/valsartan was associated with a significant improvement of LV systolic functions and reverse remodeling effects in both ischemic and non-ischemic HFrEF patients.