Feasibility and reproducibility of right ventricle stress echocardiography and its capability to assess the right ventricle contractile reserve of patient with at least trivial tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND. Stress echocardiography (SE) is widely used for the assessment of left ventricular (LV) function, diagnostic and prognostic stratification of patients with coronary artery disease and for assessment of mitral and aortic valve disease. However, the assessment of the right ventricle (RV) in general, and in particular in regard to the contractile reserve of the RV in patients with tricuspid valve (TV) disease is an area that has not been previously explored in adult patients. The physiology and function of the RV is different than that of the LV and the use of SE provides the possibility to test both systolic and diastolic function of the RV in response to increased loading conditions. This can potentially be used to assess the RV function prior to surgery and to predict which subset of patients may benefit from intervention on the TV before the RV displays signs of failure PURPOSE. We therefore propose a study to investigate the potential use of SE for the assessment of RV function in adult patients. The aim is to evaluate the feasibility of RV SE in any patients with more than trivial tricuspid regurgitation (TR) and to assess the presence and degree of RV contractile reserve. METHODS. We enrolled 81 patients undergoing a phisical or dobutamine SE for CV risk stratification or chest pain. Inclusion criteria were age≥ 18 years, normal baseline RV function (FAC> 35%, TAPSE> 16 mm). Exclusion criteria were presence of RV dysfunction, pulmonary stress hypertension, positive stress test for left myocardial ischemia, presence of moderate or severe valvular disease, grade III or higher diastolic dysfunction at baseline, severe respiratory, renal or hepatic dysfunction. We evaluated the average values of TAPSE, fractional area change (FAC), S wave, sPAP (pulmonary systolic blood pressure), RV strain during baseline and at the peak of the effort. We also assessed the reproducibility of these measurement between two different expert operators (blind analysis). RESULTS. We were able to measure the RV parameters both during baseline and at the peak of the effort in all patients, demonstrating an excellent feasibility. Differences in parameters collected at baseline and at peak were assessed using paired Wilcoxon signed rank test. All variables showed a statistical significant increase (p < 0.001) at peak compared to the baseline. Average percentage increases at peak were 31.1% for TAPSE, 24,8% for FAC, 50,6% for S wave, 55,2% for PAPS and 39.8 % for RV strain. Bland-Altman method was used to evaluate the agreement between measurements collected by two separate operators and it showed good Intraclass Correlation Coefficients (Figure). CONCLUSIONS. RV SE proved to be feasible and showed little inter-operator variability in patients with at least trivial TR. It provided valuable informations about RV contractile reserve that may help stratifying the risk of RV failure in patients undergoing TV surgery. Abstract Figur

Normal ranges of left atrial volumes and ejection fraction by 3D echocardiography in adults: a systematic review and meta-analysis

Increased sizes and dysfunction of the left atrium have been related to adverse outcomes. 3D-echocardiography is more accurate than 2D-echocardiography in estimating LA volumes and ejection fraction. However, the use of 3DE for LA analysis is limited by the absence of established reference values. We performed a systematic review and meta-analysis to provide reference ranges of LA maximum and minimum volumes indexed for body surface area (LAVi max and LAVi min, respectively), and LA-EF assessed by 3DE in healthy adults. Data search was conducted from inception through September 15, 2021, using the following Medical Subject Heading terms: left atrial/atrium, three-dimensional/3D echocardiography. The study protocol was registered in the PROSPERO database (CRD42021252428). 15 studies including 4,226 healthy adults (51% males) and reporting 3DE values of LAVi max, LAVi min and LA-EF were selected. LAVi max, LAVi min and LA-EF mean and reference values were equal to 25.18 ml/m2 (95% CI 23.10, 27.26), 11.10 ml/m2 (10.01, 12.18) and 55.94% (51.92, 59.96), respectively. No influential studies were identified. Pooled estimates per age group- and sex were also estimated. By meta-regression analyses, we identified variability in LA volumes and LA-EF depending on participants’ age, ethnicity and number of heart cycles at 3D multi-beat acquisition. At individual patient data analysis conducted on 374 subjects, a software effect on LA-EF was shown. This systematic review and meta-analysis provides reference values of LAVi max, LAVi min and LA-EF assessed by 3DE in healthy adults, encouraging 3DE evaluation of the LA evaluation in daily practice. © 2022, The Author(s), under exclusive licence to Springer Nature B.V

Left Atrial Expansion Index for Noninvasive Estimation of Pulmonary Capillary Wedge Pressure: A Cardiac Catheterization Validation Study

Background: Pulmonary capillary wedge pressure (PCWP) plays a pivotal role in cardiac disease diagnosis and management. Right heart catheterization (RHC) invasively provides accurate PCWP measurement, but it is impractical for widespread use in all patients. The left atrial expansion index (LAEI), measured on transthoracic echocardiography, describes the relative left atrial volume increase during the left atrial reservoir phase. The aim of this study was to validate LAEI as a noninvasive parameter for PCWP estimation. Methods: A total of 649 chronic cardiac patients (mean age, 66 \ub1 14 years; mean PCWP, 14 \ub1 7.6 mm Hg; mean left ventricular ejection fraction, 50 \ub1 15%) who underwent both clinically indicated RHC and transthoracic echocardiography within 24 hours were retrospectively enrolled. Patients were randomly divided into derivation (n = 509) and validation (n = 140) cohorts. PCWP was measured during RHC and defined as elevated when >12 mm Hg. Transthoracic echocardiographic parameters and LAEI were measured offline, blinded to RHC results. Results: In the derivation cohort, LAEI correlated logarithmically with PCWP, and the log-transformed LAEI (lnLAEI) correlated linearly with PCWP (r = 120.73, P < .001). lnLAEI showed an independent and additive predictive role for PCWP estimation over clinical and diastolic dysfunction (DD) parameters. The diagnostic accuracy of lnLAEI for elevated PCWP identification (area under the curve = 0.875, P < .001; optimal lnLAEI cutoff < 4.02) was higher than either the single DD parameters or their combination. In the validation cohort, lnLAEI cutoff < 4.02 showed higher accuracy than the 2016 DD algorithm (88% vs 74%) for elevated PCWP identification. Finally, the equation PCWP = 38.3 12 6.2 7 lnLAEI, obtained from the derivation cohort, predicted invasively measured PCWP in the validation cohort. Conclusions: In a cohort of patients with various chronic cardiac diseases, lnLAEI performed better than DD parameters and the 2016 DD algorithm for PCWP estimation. lnLAEI might be a useful echocardiographic parameter for noninvasive PCWP estimation

Identification of unique adaptive immune system signature in acute coronary syndromes

Several studies have consistently demonstrated that inflammation plays a key role in the pathogenesis of acute coronary syndromes (ACS). More recent studies have highlighted the importance of adaptive immunity in ACS. In particular, profound abnormalities have been observed in specific subsets of T-cells, including CD4+CD28nullT-cells, a subset of cytotoxic CD4+T-lymphocytes producing large amount of interferon-\u3b3 (IFN-\u3b3), naturally occurring regulatory T-cells (Treg)and interleukin (IL)-17-producing T-cells (Th17). Our group systematically investigated the clinical relevance of adaptive immunity alterations, in a sizeable population of patients with non-ST elevation (NSTE)-ACS (n = 95), as compared with patients presenting chronic stable angina (SA) (n = 80) and individuals without overt cardiovascular diseases (controls) (n = 70). Our data show for the first time that about half of patients with ACS exhibit a unique immune profile, associated with a worse outcome at 1-year follow-up, which is very rarely found in SA and never in healthy controls. In this subset of ACS patients, the failure to mount a counter regulatory response to the activation of aggressive T-cells might play a key pathogenetic role and might represent an attractive therapeutic target [17]. The remaining half of ACS patients consisted of a small subset with an immune profile similar to that found in SA and in controls, and of a larger subset exhibiting a heterogeneous immune profile. In these subsets, coronary instability is unlikely to be caused by an inflammatory outburst

Feasibility and role of right ventricular stress echocardiography in adult patients

Background: The great technological advancements in the field of echocardiography have led to applications of stress echocardiography (SE) in almost all diagnostic fields of cardiology, from ischemic heart disease to valvular heart disease and diastolic function. However, the assessment of the right ventricle (RV) in general, and in particular in regard to the contractile reserve of the RV, is an area that has not been previously explored. We, therefore, propose a study to investigate the potential use of SE for the assessment of RV function in adult patients. Aims and objectives: The primary aim is to evaluate the feasibility of right ventricular SE. The secondary aim is to assess right ventricular contractile reserve. Matherials and Methods: Eighty-one patients undergoing a physical or dobutamine stress echocardiogram for cardiovascular risk stratification or chest pain were the subject of the study. An exercise leg cycle using a standard WHO protocol was used to simultaneously assess the right and left ventricular global and regional function as well as acquiring Doppler data. Whereas the patient had limitations in mobility, a dobutamine SE was be performed. We evaluated the average values of tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), S-wave, systolic pulmonary artery pressure (sPAP), and right ventricle global longitudinal (free wall) strain (RVGLS) during baseline and at the peak of the effort. RV contractile reserve was defined as the change in RVGLS from rest to peak exercise. We also assessed the reproducibility of these measurements between two different expert operators (blind analysis). Results: At least 3 over 5 RV function parameters were measurable both during baseline and at the peak of the effort in 95% of patients, while all 5 parameters in 65% of our population, demonstrating an excellent feasibility. All RV-studied variables showed a statistically significant increase (P < 0.001) at peak compared to the baseline. The average percentage increases at peak were 31.1% for TAPSE, 24.8% for FAC, 50.6% for S-wave, 55.2% for PAPS, and 39.8% for RV strain. The reproducibility between operators at baseline and peak was excellent. Our study demonstrates that TAPSE, FAC, and S-wave are highly feasible at rest and at peak, while TAPSE, S-wave, and sPAP are the most reliable measurements during RV stress echo. Conclusion: RVGLS is useful in the assessment of RV contractile reserve in patients with good acoustic window. Further studies are needed to evaluate the impact of contrast echocardiography in improving RV contractile reserve assessment during SE

The clinical spectrum of CASQ1-related myopathy.

OBJECTIVE: To identify and characterize patients with calsequestrin 1 (CASQ1)-related myopathy. METHODS: Patients selected according to histopathologic features underwent CASQ1 genetic screening. CASQ1-mutated patients were clinically evaluated and underwent muscle MRI. Vacuole morphology and vacuolated fiber type were characterized. RESULTS: Twenty-two CASQ1-mutated patients (12 families) were identified, 21 sharing the previously described founder mutation (p.Asp244Gly) and 1 with the p.Gly103Asp mutation. Patients usually presented in the sixth decade with exercise intolerance and myalgias and later developed mild to moderate, slowly progressive proximal weakness with quadriceps atrophy and scapular winging. Muscle MRI (n = 11) showed a recurrent fibrofatty substitution pattern. Three patients presented subclinical cardiac abnormalities. Muscle histopathology in patients with p.Asp244Gly showed vacuoles in type II fibers appearing empty in hematoxylin-eosin, Gomori, and nicotinamide adenine dinucleotide (NADH) tetrazolium reductase stains but strongly positive for sarcoplasmic reticulum proteins. The muscle histopathology of p.Gly103Asp mutation was different, showing also NADH-positive accumulation consistent with tubular aggregates. CONCLUSIONS: We report the clinical and molecular details of the largest cohort of CASQ1-mutated patients. A possible heart involvement is presented, further expanding the phenotype of the disease. One mutation is common due to a founder effect, but other mutations are possible. Because of a paucity of symptoms, it is likely that CASQ1 mutations may remain undiagnosed if a muscle biopsy is not performed

Impact of the “atherosclerotic pabulum” on in-hospital mortality for SARS-CoV-2 infection. Is calcium score able to identify at-risk patients?

Background: Although the primary cause of death in COVID-19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID-19 is associated with a high incidence of thrombotic complications. Hypothesis: Evaluate if the coronary artery calcium (CAC) score was useful to predict in-hospital (in-H) mortality in patients with COVID-19. Secondary end-points were needed for mechanical ventilation and intensive care unit admission. Methods: Two-hundred eighty-four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved. Results: Patients with CAC had a higher inflammatory burden at admission (d-dimer, p =.002; C-reactive protein, p =.002; procalcitonin, p =.016) and a higher high-sensitive cardiac troponin I (HScTnI, p = 200 ng/dl was a better determinant of all outcomes in both univariate (p = <.001) and multivariate analysis (p = <.001). Conclusion: The main finding of our research is that CAC was positively related to in-H mortality, but it did not completely identify all the population at risk of events in the setting of COVID-19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS-CoV-2 infection

The clinical spectrum of CASQ1-related myopathy

To identify and characterize patients with calsequestrin 1 (CASQ1)-related myopathy

Adaptive immunity, inflammation, and cardiovascular complications in type 1 and type 2 diabetes mellitus

Diabetes mellitus (DM) is a pandemics that affects more than 170 million people worldwide, associated with increased mortality and morbidity due to coronary artery disease (CAD). In type 1 (T1) DM, the main pathogenic mechanism seems to be the destruction of pancreatic \u3b2 -cells mediated by autoreactive T-cells resulting in chronic insulitis, while in type 2 (T2) DM primary insulin resistance, rather than defective insulin production due to \u3b2 -cell destruction, seems to be the triggering alteration. In our study, we investigated the role of systemic inflammation and T-cell subsets in T1- and T2DM and the possible mechanisms underlying the increased cardiovascular risk associated with these diseases