The Role of Left Atrial Longitudinal Strain in the Diagnosis of Acute Cellular Rejection in Heart Transplant Recipients.

Our aim was to investigate the role of left atrial longitudinal strain (LALS) in the non-invasive diagnosis of acute cellular rejection (ACR) episodes in heart transplant (HTx) recipients. Methods: We performed successive echocardiographic exams in 18 consecutive adult HTx recipients in their first year after HTx within 3 h of the routine surveillance endomyocardial biopsies (EMB) in a single center. LALS parameters were analyzed with two different software. We investigated LALS association with ACR presence, as well as inter-vendor variability in comparable LALS values. Results: A total of 147 pairs of EMB and echo exams were carried out. Lower values of LALS were significantly associated with any grade of ACR presence. Peak atrial longitudinal strain (PALS) offered the best diagnostic value for any grade of ACR, with a C statistic of 0.77 using one software (95% CI 0.68−0.84, p < 0.0005) and 0.64 with the other (95% CI 0.54−0.73, p = 0.013) (p = 0.02 for comparison between both curves). Reproducibility between comparable LALS parameters was poor (intraclass correlation coefficients were 0.60 for PALS, 95% CI 0.42−0.73, p < 0.0005; and 0.42 for PALS rate, 95% CI −0.13−0.68, p < 0.0005). Conclusions: LALS variables might be a sensitive marker of ACR in HTx recipients, principally discriminating between those studies without rejection and those with any grade of ACR. Inter-vendor variability was significant.

Fulminant myocarditis in a patient with a lung adenocarcinoma after the third dose of modern COVID-19 vaccine. A case report and literature review.

Introduction COVID-19 disease has caused a global health and economic crisis. The introduction of the different COVID-19 vaccines has resulted in a significant decrease in the morbidity and mortality associated with this disease. Adverse effects have been reported, including cardiological ones such as myocarditis or pericarditis after administration. Likewise, tyrosine kinase inhibitor drugs such as osimertinib used in lung cancer patients with epidermal growth factor receptor (EGFR) mutation are associated with heart failure or prolongation of the QT interval. Case report 62-year-old woman diagnosed in September 2019 of lung adenocarcinoma stage IV with bilateral lung and lymph node involvement, carrier of an EGFR mutation (Ex19Del) on treatment with osimertinib. She attended emergency department for fever and hypotension 24 h after administration of the third dose of Moderna® COVID-19 vaccine in the context of acute myocarditis with evidence of severe left ventricular (LV) dysfunction in cardiogenic shock. She required vasoactive support, non-invasive mechanical ventilation, corticotherapy, immunoglobulins and subsequent ventricular support with Impella, with improvement of the clinical picture after 3 days. Cardiac magnetic resonance imaging (MRI) showed evidence of global myocardial oedema compatible with acute myocarditis. Coronary CT showed a lesion in the anterior descending coronary artery requiring revascularization. A few days later, she presented febrile symptoms with isolation of Staphylococcus aureus in the central line catheter and antibiotherapy with cloxacillin was started, with subsequent resolution of the infectious symptoms. Conclusion This is an exceptional and controversial case of fulminant myocarditis probably related to the Modern COVID-19 vaccine in a patient diagnosed with metastatic lung adenocarcinoma on treatment with osimertinib. An increasing number of cases of myocarditis and pericarditis have been reported following vaccination with COVID-19 mRNA vaccines. In addition, retrospective data have shown an increased risk of QT prolongation and heart failure in patients treated with tyrosine kinase inhibitors. Hence, the need for close monitoring of cardiac function during treatment of these patients. Future studies will be necessary to evaluate unknown adverse reactions of these vaccines and their possible interaction with other antineoplastic drugs.

Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter study.

INTRODUCTION AND OBJECTIVES: Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort. METHODS: A prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples. RESULTS: A total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR≥2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR≥2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR≥2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR≥2R. CONCLUSIONS: This study maintained a strong negative predictive value to exclude ACR≥2R after OHT and LVGLS was independently associated with the presence of ACR≥2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR.

Tissue Doppler velocities for ruling out rejection in heart transplant recipients in the context of myocardial strain imaging: a multivariate, prospective, single-center study.

To investigate the value of tissue Doppler velocities for ruling out treatment-requiring acute cellular rejection (TR-ACR), in the context of myocardial deformation analysis performed by means of speckle tracking echocardiography. We performed serial echocardiograms in 37 heart transplant recipients in their first year post-transplantation within 3 h of the routine surveillance endomyocardial biopsies (EMB). The association of the sum of lateral mitral annulus systolic (s') and early diastolic (e') velocities, in absolute values, measured by tissue Doppler echocardiography (s'+ e'), with TR-ACR (ACR grade ≥ 2R) was investigated by multivariate analysis, including classic echocardiographic parameters and myocardial deformation variables. A total of 251 pairs of EMB and echo exams were performed, 35 (14%) with rejection grade ≥ 2R (TR-ACR). s' + e' was independently associated to TR-ACR (OR 0.80, 95%CI 0.72-0.89, p < 0.0005), with a C statistic of 0.79 (95%CI 0.71-0.87, p < 0.0005) by ROC curve analysis. An s'+ e' value ≥ 23 cm/s, present in 43% of studies, had a negative predictive value of 98% for ruling out TR-ACR. Moreover, in the same patients, s'+ e' significantly decreased when TR-ACR occurred after a study without this condition (- 3.7 ± 3.3 cm/s, p = 0.003), but it was similar when rejection status was the same in the present versus the previous study. A drop in s'+ e' value < 2.7 cm/s from the previous echocardiogram, had a 99% negative predictive value for ruling out TR-ACR. Tissue Doppler velocities, a widely available echo parameter, were found to be a valuable marker for ruling out TR-ACR in this multivariate study which included myocardial deformation variables.

Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness.

PURPOSE: Our objective was to investigate the impact of inter-vendor variability in the ability of myocardial strain analysis to detect acute cellular rejection (ACR) in heart transplant recipients. METHODS: We performed serial echocardiographic examinations in 18 consecutive adult heart transplanted patients, in their first year post-transplantation, within 3 hours of the routine surveillance endomyocardial biopsies (EMB) in a single center. Myocardial strain was analyzed using two software in two different institutions, and inter-vendor variability of strain values and its association with ACR (any grade or grade ≥2R) was investigated. The parameter of comparison was the peak value of the average curve of strain during the entire cardiac cycle. RESULTS: A total of 147 pairs of EMB-echocardiogram were performed, 65 with no ACR, 63 with ACR grade 1R, and 19 with ACR grade ≥2R. Intra-class correlation coefficients for left ventricle longitudinal, radial, and circumferential strain were 0.38, 0.39, and 0.77, respectively, and 0.32 for right ventricular longitudinal strain. Neither software found significant association of left ventricular longitudinal strain with rejection. Grade ≥2R ACR was associated with left ventricular circumferential strain measured with the first software and with left ventricular radial strain with the other; and ACR of any grade was only significantly associated with right ventricle longitudinal strain measured with the first software. CONCLUSIONS: Inter-vendor reproducibility of strain values was low in this study. Some strain parameters were associated to ACR, although these results were inconsistent between two commercially available software. Specific validation of each software is warranted for this clinical indication.

Incremental Utility of Right Ventricular Dysfunction in Patients With Myeloproliferative Neoplasm-Associated Pulmonary Hypertension.

BACKGROUND: Myeloproliferative neoplasm (MPN) has been associated with pulmonary hypertension (PH) on the basis of small observational studies, but the mechanism and clinical significance of PH in MPN are not well established. The aims of this study were to expand understanding of PH in a well-characterized MPN cohort via study of PH-related symptoms, mortality risk, and cardiac remodeling sequalae of PH using quantitative echocardiographic methods. METHODS: The population comprised a retrospective cohort of patients with MPN who underwent transthoracic echocardiography: Doppler-derived pulmonary arterial systolic pressure applied established cutoffs for PH (≥35 mm Hg) and advanced PH (≥50 mm Hg); right ventricular (RV) performance was assessed via conventional indices (tricuspid annular plane systolic excursion [TAPSE], S') and global longitudinal strain. Symptoms and mortality were discerned via standardized review. RESULTS: Three hundred one patients were studied; 56% had echocardiography-demonstrated PH (20% advanced) paralleling a high prevalence (67%) among patients with invasively quantified PASP. PH was associated with adverse left ventricular (LV) remodeling indices, including increased myocardial mass and diastolic dysfunction (P ≤ .001 for all): LV mass and filling pressure (P < .01) were associated with PH independent of LV ejection fraction. RV dysfunction by strain and TAPSE and S' increased in relation to PH (P ≤ .001) and was about threefold greater among patients with advanced PH compared with those without PH. Patients with RV dysfunction were more likely to report dyspnea, as were those with advanced PH (P < .05). During median follow-up of 2.2 years, all-cause mortality was 27%. PH grade (hazard ratio, 1.9; 95% CI, 1.1-3.0; P = .012) and TAPSE- and S'-demonstrated RV dysfunction (hazard ratio, 3.3; 95% CI, 1.3-8.2; P = .01) were independently associated with mortality; substitution of global longitudinal strain for TAPSE and S' yielded similar associations of RV dysfunction with death (hazard ratio, 3.2; 95% CI, 1.5-6.7; P = .003) independent of PH. CONCLUSIONS: PH is highly prevalent in patients with MPN and is linked to LV diastolic dysfunction; echocardiography-quantified RV dysfunction augments risk for mortality independent of PH.

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. METHODS: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S', fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. RESULTS: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S' (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87-0.99]|0.91[0.84-0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). CONCLUSION: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR.

Echocardiography-quantified myocardial strain-a marker of global and regional infarct size that stratifies likelihood of left ventricular thrombus.

BACKGROUND: Myocardial strain provides a novel means of quantifying subtle alterations in contractile function; incremental utility post-MI is unknown. OBJECTIVES: To test longitudinal-quantified by postprocessing routine echo-for assessment of MI size measured by cardiac magnetic resonance (CMR) and conventional methods, and assess regional and global strain (GLS) as markers of LV thrombus. METHODS: The population comprised of patients with anterior ST-segment MI who underwent echo and CMR prospectively. Preexisting echoes were retrieved, re-analyzed for strain, and compared to conventional MI markers as well as CMR-evidenced MI, function, and thrombus. RESULTS: Seventy-four patients underwent echo and CMR 4 ± 1 weeks post-MI; 72% had abnormal GLS. CMR-quantified MI size was 2.5-fold larger and EF lower among patients with abnormal GLS, paralleling 2.6-3.1 fold differences in Q-wave size and CPK (all P ≤ .002). GLS correlated with CMR-quantified MI (r = .66), CPK (r = .52) and Q-wave area (r = .44; all P ≤ .001): Regional strain was lower in the base, mid, and apical LV among patients with CMR-defined transmural MI in each territory (P < .05) and correlated with cine-CMR regional EF (r = .53-.71; P < .001) and echo wall motion (r = .45-.71; P < .001). GLS and apical strain were ~2-fold lower among patients with LV thrombus (P ≤ .002): Apical strain yielded higher diagnostic performance for thrombus (AUC: 0.83 [0.72-0.93], P = .001) than wall motion (0.73 [0.58-0.88], P = .02), as did global strain (0.78 [0.65-0.90], P = .005) compared to LVEF (0.58 [0.45-0.72], P = .41). CONCLUSIONS: Echo-quantified longitudinal strain provides a marker of MI size and improves stratification for post-MI LV thrombus beyond conventional indices.

Utility of cardiac magnetic resonance for evaluation of mitral regurgitation prior to mitral valve surgery.

Mitral regurgitation (MR) is a common cause of morbidity worldwide and an accepted indication for interventional therapies which aim to reduce or resolve adverse clinical outcomes associated with MR. Cardiac magnetic resonance (CMR) provides highly accurate means of assessing MR, including a variety of approaches that can measure MR based on quantitative flow. Additionally, CMR is widely accepted as a reference standard for cardiac chamber quantification, enabling reliable detection of subtle changes in cardiac chamber size and function so as to guide decision-making regarding timing of mitral valve directed therapies. Beyond geometric imaging, CMR enables tissue characterization of ischemia and infarction in the left ventricular (LV) myocardium as well as within the mitral valve apparatus, thus enabling identification of structural substrates for MR. This review provides an overview of established and emerging CMR approaches to measure valvular regurgitation, including relative utility of different approaches for patients with primary or secondary MR. Clinical outcomes studies are discussed with focus on data demonstrating advantages of CMR for guiding diagnosis, risk stratification, and management of patients with known or suspected MR. Comparative data is reviewed with focus on diagnostic performance of CMR in comparison to conventional assessment via echocardiography (echo). Emerging literature is reviewed concerning potential new approaches that utilize CMR tissue characterization to guide clinical decision-making in order to improve therapeutic outcomes and clinical prognosis for patients with MR.