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Journal of the American Society of... Jun 2024Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall (RVfw) strain is uncertain as an echocardiographic red...
AIMS
Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall (RVfw) strain is uncertain as an echocardiographic red flag. We hypothesized that RVfw strain is of added value for diagnostic and prognostic purposes in patients with transthyretin cardiac amyloidosis (ATTR-CA).
METHOD
ATTR-CA diagnosis required positive Tc-99m pyrophosphate (PYP) scintigraphy and negative serum clonal dyscrasia. Patients with left ventricular hypertrophy (LVH) (interventricular septal thickness ≥1.2cm) by echocardiography and negative PYP scintigraphy served as controls after exclusion of AL-CA. Longitudinal strain was computed with speckle tracking echocardiography.
RESULTS
We studied, 108 subjects with ATTR-CA and 106 controls with LVH, retrospectively. RVfw strain was independently associated with the diagnosis of ATTR-CA after adjusting for classical echocardiographic parameters, namely, relative apical sparing (RAS), e' and E/e'. RVfw strain ≥-16% was incremental to LV RAS in the overall group and in the subgroup without extreme wall thickness (≤1.4 cm) (Harrell's-C, net reclassification improvement (NRI) = 0.213, p<0.001and NRI 0.463, p=0.015, respectively). Major adverse cardiovascular and cerebrovascular events (MACCE: heart failure hospitalization, stroke, death) occurred in 47 ATTR-CA patients, during follow-up (median: 38, range: 6-60 months). RVfw strain ≥-16% was associated with 3-fold increased risk of MACCE in ATTR-CA patients independently of age, comorbidities, BNP and tafamidis treatment. RVfw strain was additive to LVEF for risk stratification (X 10.2, p =0.017).
CONCLUSION
RVfw strain >-16% has incremental value to LV RAS for the differential diagnosis of ATTR-CA among LVH phenotypes, and is associated with poor prognosis.
PubMed: 38942217
DOI: 10.1016/j.echo.2024.06.006 -
The Journal of Heart and Lung... Jun 2024Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that...
BACKGROUND
Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.
METHODS
Consecutive incident PAH patients aged ≥ 18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n=152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n=143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n=201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n=519 patients). Risk stratification was based on on the ESC/ERS 3-strata model and REVEAL 2.0 score.
RESULTS
These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% C.I. 1.6-2.8, p<0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% C.I. 0.18-0.47, p<0.001).
CONCLUSIONS
Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.
PubMed: 38942159
DOI: 10.1016/j.healun.2024.06.003 -
Heart Rhythm Jun 2024The concealed nodoventricular/nodofascicular (NV/NF) pathway is mostly a bystander, retrograde bypass tract connecting right ventricle/right bundle branch (RBB) and slow...
BACKGROUND
The concealed nodoventricular/nodofascicular (NV/NF) pathway is mostly a bystander, retrograde bypass tract connecting right ventricle/right bundle branch (RBB) and slow pathway (SP), which is observed in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its prevalence and characteristics in response to pacing maneuvers have not been fully evaluated.
OBJECTIVE
This study investigated the prevalence and characteristics of AVNRT with a bystander NV/NF-pathway.
METHODS
We retrospectively reviewed 153 consecutive patients undergoing catheter ablation of AVNRT. Excluding 52 patients with inadequate electrophysiological data, 101 patients composed the study population.
RESULTS
Three patients (3.0%) had bystander concealed NV/NF-pathways, all of which were connected to the SP. The tachycardia was typical SP/fast pathway (FP) AVNRT in two patients and atypical FP/SP AVNRT in one patient. In all cases, His-refractory ventricular extra stimuli (VESs) reset the AVNRTs with delay through the NV/NF-pathways. Ventricular overdrive pacing (VOP) in the early-phase also reset the AVNRT with delay. Earlier VESs and middle-phase of VOP did not reset the tachycardia, and further earlier VESs and late-phase of VOP reset the tachycardia with advance through the RBB-His conduction.
CONCLUSION
A bystander NV/NF-pathway was not rare in patients with AVNRT. The VESs and VOP for the AVNRTs with the bystander NV/NF-pathways were characterized by the two-phase resetting phenomenon: initial transient resetting with delay through the NV/NF-pathway, and late resetting with advance through the RBB-His conduction.
PubMed: 38942105
DOI: 10.1016/j.hrthm.2024.06.049 -
The International Journal of... Jun 2024Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve...
Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI. Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed. Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality. V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care.
PubMed: 38940965
DOI: 10.1007/s10554-024-03165-0 -
Development (Cambridge, England) Jul 2024During heart development, the embryonic ventricle becomes enveloped by the epicardium, which adheres to the outer apical surface of the heart. This is concomitant with...
During heart development, the embryonic ventricle becomes enveloped by the epicardium, which adheres to the outer apical surface of the heart. This is concomitant with onset of ventricular trabeculation, where a subset of cardiomyocytes lose apicobasal polarity and delaminate basally from the ventricular wall. Llgl1 regulates the formation of apical cell junctions and apicobasal polarity, and we investigated its role in ventricular wall maturation. We found that llgl1 mutant zebrafish embryos exhibit aberrant apical extrusion of ventricular cardiomyocytes. While investigating apical cardiomyocyte extrusion, we identified a basal-to-apical shift in laminin deposition from the internal to the external ventricular wall. We find that epicardial cells express several laminin subunits as they adhere to the ventricle, and that the epicardium is required for laminin deposition on the ventricular surface. In llgl1 mutants, timely establishment of the epicardial layer is disrupted due to delayed emergence of epicardial cells, resulting in delayed apical deposition of laminin on the ventricular surface. Together, our analyses reveal an unexpected role for Llgl1 in correct timing of epicardial development, supporting integrity of the ventricular myocardial wall.
Topics: Animals; Laminin; Zebrafish; Pericardium; Heart Ventricles; Zebrafish Proteins; Myocytes, Cardiac; Cell Polarity; Mutation
PubMed: 38940292
DOI: 10.1242/dev.202482 -
JACC. Advances Apr 2024There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
BACKGROUND
There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
OBJECTIVES
The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV.
METHODS
The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America. All components of the composite outcome, that is, atrial arrhythmias, thromboembolic events, cardiac transplantation, and death, were reviewed and classified by a blinded adjudicating committee. Time-to-event analyses were performed that accounted for competing risks.
RESULTS
A total of 384 patients were followed for 10.5 ± 5.9 years. The composite outcome occurred in 3.7 vs 1.7 cases per 100 person-years for uRV (N = 171) vs uLV (N = 213), respectively ( < 0.001). In multivariable analyses, uRV conferred a >2-fold higher risk of the composite outcome (HR: 2.17, 95% CI: 1.45-3.45, < 0.001). In secondary analyses of components of the primary outcome, uRV was significantly associated with a greater risk of cardiac transplantation or death (HR: 9.09, 95% CI: 2.17-38.46, < 0.001) and atrial arrhythmias (HR: 2.17, 95% CI: 1.20-4.00, = 0.010) but not thromboembolic events (HR: 1.64, 95% CI: 0.86-3.16, = 0.131).
CONCLUSIONS
Fontan patients with uRV vs uLV morphology have a higher incidence of adverse cardiovascular events, including atrial arrhythmia, cardiac transplantation, and all-cause mortality.
PubMed: 38939676
DOI: 10.1016/j.jacadv.2024.100871 -
JACC. Advances Feb 2024
PubMed: 38939395
DOI: 10.1016/j.jacadv.2023.100771 -
JACC. Advances Feb 2024The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available...
BACKGROUND
The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era.
OBJECTIVES
The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events.
METHODS
A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined.
RESULTS
At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2).
CONCLUSIONS
TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.
PubMed: 38939383
DOI: 10.1016/j.jacadv.2023.100772 -
JACC. Advances Feb 2024Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of...
BACKGROUND
Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood.
OBJECTIVES
The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function.
METHODS
The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization.
RESULTS
Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, < 0.001) and undergo Fontan completion (7% vs 53%, < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition.
CONCLUSIONS
Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.
PubMed: 38939382
DOI: 10.1016/j.jacadv.2023.100811 -
JACC. Advances Mar 2024Patients with likely pathogenic/pathogenic desmoplakin () variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular...
BACKGROUND
Patients with likely pathogenic/pathogenic desmoplakin () variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting.
OBJECTIVES
The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (-TFC+).
METHODS
-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics.
RESULTS
Among 252 -TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank = 0.0239). History of nonsustained VT (aHR 2.097; = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age ( = 0.723) nor male sex ( = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]).
CONCLUSIONS
-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in -TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, -TFC+ patients with nonsustained VT should be considered as high-risk.
PubMed: 38938828
DOI: 10.1016/j.jacadv.2024.100832