-
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 -
JACC. Advances Dec 2023Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction...
BACKGROUND
Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction (HFpEF) is unknown.
OBJECTIVES
The authors investigated the potential of EAT and RV quantification for obesity-related pathophysiology and risk stratification in obese HFpEF patients using cardiovascular magnetic resonance (CMR).
METHODS
A total of 150 patients (obese, body mass index ≥30 kg/m; n = 73, nonobese, body mass index <30 kg/m; n = 77) with a clinical diagnosis of HFpEF undergoing CMR were retrospectively identified. EAT volume surrounding both ventricles were quantified with manual delineation on cine images. Total RV volume (TRVV) was calculated as the sum of RV cavity and mass at end-diastole. The endpoint was the composite of all-cause mortality and first HF hospitalization.
RESULTS
During a median follow-up of 46 months, 39 nonobese patients (51%) and 32 obese patients (44%) experienced the endpoint. EAT was a prognostic biomarker regardless of obesity and was independently correlated with TRVV. In obese HFpEF, EAT correlated with RV longitudinal strain (r = 0.32, = 0.006), and increased amount of EAT and TRVV was associated with greater left ventricular end-diastolic eccentric index (r = 0.36, = 0.002). The integration of RV quantification into EAT provided improved risk stratification with a C-statistic increase from 0.70 to 0.79 in obese HFpEF. Obese patients with EAT<130 ml and TRVV<180 ml had low risk (annual event rate 3.2%), while those with increased EAT ≥130 ml and TRVV ≥180 ml had significantly higher risk (annual event rate 11.8%; < 0.001).
CONCLUSIONS
CMR quantification of EAT and RV structure provides additive risk stratification for adverse outcomes in obese HFpEF.
PubMed: 38938495
DOI: 10.1016/j.jacadv.2023.100730 -
JACC. Advances Dec 2023
PubMed: 38938481
DOI: 10.1016/j.jacadv.2023.100731 -
JACC. Advances Jun 2023Abnormal left ventricular (LV) rotational mechanics in biventricular hearts are associated with adverse outcomes; however, these are less well characterized for hearts...
BACKGROUND
Abnormal left ventricular (LV) rotational mechanics in biventricular hearts are associated with adverse outcomes; however, these are less well characterized for hearts with functionally single ventricles.
OBJECTIVES
The purpose of this study was to characterize ventricular rotational mechanics in the Fontan circulation and their relationship to outcomes.
METHODS
Single-center, retrospective analysis of magnetic resonance examinations for 329 Fontan patients (15 [IQR: 10-21] years) and 42 controls. The ventricular cine short-axis stack was analyzed to derive torsion metrics. Torsion calculated as the difference between apical and basal rotation normalized to ventricular length.
RESULTS
Fontan patients had higher indexed ventricular end-diastolic volume (97 mL/body surface area vs 72 mL/body surface area), lower ejection fraction (53% vs 60%), and lower proportion of basal clockwise rotation (62% vs 93%), apical counterclockwise rotation (77% vs 95%), and positive torsion (82% vs 100%); < 0.001 for all. A composite outcome of death or heart transplant-listing occurred in 31 (9%) patients at a median follow-up of 3.9 years. Torsion metrics were associated with the outcome; although, on multivariate analysis only right ventricular (RV) morphology and indexed ventricular end-diastolic volume were independently associated. LVs with negative torsion, and RVs regardless of torsional pattern, had worse outcomes compared to LVs with positive torsion ( = 0.020).
CONCLUSIONS
Single ventricles in a Fontan circulation exhibit abnormal torsional mechanics, which are more pronounced for RV morphology. Abnormal torsion is associated with death or need for heart transplantation. Fontan patients with LV morphology and preserved torsion exhibit the highest transplant-free survival and torsion may offer incremental prognostic data in this group of patients.
PubMed: 38938250
DOI: 10.1016/j.jacadv.2023.100360 -
BMC Cardiovascular Disorders Jun 2024The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma....
Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.
BACKGROUND
The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.
METHODS
We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.
RESULTS
Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.
CONCLUSIONS
2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
Topics: Humans; Female; Male; Middle Aged; Prospective Studies; Predictive Value of Tests; Aged; Ventricular Function, Left; Radiation Injuries; Risk Assessment; Systole; Cardiotoxicity; Risk Factors; Adult; Time Factors; Thoracic Neoplasms; Radiotherapy; Ventricular Function, Right; Echocardiography; Heart Disease Risk Factors; Stroke Volume
PubMed: 38937716
DOI: 10.1186/s12872-024-03981-1 -
Molecular Medicine (Cambridge, Mass.) Jun 2024Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes....
BACKGROUND
Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes. Ventricular arrhythmias (VAs) following heart failure (HF) are closely linked to ventricular electrical remodeling, yet the specific mechanisms underlying VAs in HF remain inadequately explored. In this study, we examined the impact of USP38 on VAs in pressure overload-induced HF.
METHODS
Cardiac-specific USP38 knockout mice, cardiac-specific USP38 transgenic mice and their matched control littermates developed HF induced by aortic banding (AB) surgery. After subjecting the mice to AB surgery for a duration of four weeks, comprehensive investigations were conducted, including pathological analysis and electrophysiological assessments, along with molecular analyses.
RESULTS
We observed increased USP38 expression in the left ventricle of mice with HF. Electrocardiogram showed that the USP38 knockout shortened the QRS interval and QTc, while USP38 overexpression prolonged these parameters. USP38 knockout decreased the susceptibility of VAs by shortening action potential duration (APD) and prolonging effective refractory period (ERP). In addition, USP38 knockout increased ion channel and Cx43 expression in ventricle. On the contrary, the increased susceptibility of VAs and the decreased expression of ventricular ion channels and Cx43 were observed with USP38 overexpression. In both in vivo and in vitro experiments, USP38 knockout inhibited TBK1/AKT/CAMKII signaling, whereas USP38 overexpression activated this pathway.
CONCLUSION
Our data indicates that USP38 increases susceptibility to VAs after HF through TBK1/AKT/CAMKII signaling pathway, Consequently, USP38 may emerge as a promising therapeutic target for managing VAs following HF.
Topics: Animals; Mice; Mice, Knockout; Ventricular Remodeling; Heart Failure; Ubiquitin-Specific Proteases; Disease Models, Animal; Male; Arrhythmias, Cardiac; Heart Ventricles; Mice, Transgenic; Signal Transduction; Electrocardiography
PubMed: 38937697
DOI: 10.1186/s10020-024-00846-3 -
The Annals of Thoracic Surgery Jun 2024This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double outlet right ventricle...
BACKGROUND
This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double outlet right ventricle with discordant atrioventricular connection.
METHODS
This single-center retrospective study included 146 patients who underwent biventricular repair of corrected transposition of the great arteries or double outlet right ventricle with discordant atrioventricular connections from 1972 to 2023. Survival rate, freedom from reoperation, NYHA classification and incidence of systemic ventricular dysfunction in the long-term were compared between physiological repair group (PR group) and anatomical repair group (AR group).
RESULTS
PR group consisted of 55 patients with median age at repair of 10.3 years. Thirty-one patients underwent conventional Rastelli procedure and 24 patients underwent atrial and/or ventricular septal defect closure. AR group consisted of 91 patients with median age at repair of 5.8 years. Seventy-two patients underwent atrial switch plus Rastelli procedure and 19 patients underwent atrial plus arterial switch operation. The 30-year survival was 63.5% in PR group and 72.3% in AR group (p=0.448). The 30-year freedom from reoperation was 71.9% in PR group and 62.2% in AR group (p=0.220). There was a significant difference in incidence of systemic ventricular dysfunction between the groups (87.5% in PR group and 35.3% in AR group: p<0.001) and long-term survivors' NYHA classification (mean NYHA class of 1.9 in PR group and 1.5 in AR group: p=0.009).
CONCLUSIONS
The systemic ventricular function and general status in the long-term were significantly better in anatomical repair patients, suggesting the potential advantage of anatomical repair.
PubMed: 38936589
DOI: 10.1016/j.athoracsur.2024.06.010 -
JACC. Clinical Electrophysiology Jun 2024Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS).
BACKGROUND
Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS).
OBJECTIVES
The aim of this study was to evaluate the usefulness of dynamic changes in ventricular activation during exercise to improve disease phenotyping and diagnosis of BrS.
METHODS
Digital 12-lead electrocardiograms during stress testing were analyzed retrospectively at baseline, peak exercise, and recovery in 53 patients with BrS and 52 controls. Biventricular activation was assessed from QRS duration (QRSd), whereas right ventricular activation was assessed from S wave duration in the lateral leads (I and V) and terminal R wave duration in aVR. Exercise-induced changes in QRS parameters to predict a positive procainamide response were assessed in separate test and validation cohorts with suspected BrS.
RESULTS
Baseline electrocardiogram parameters were similar between BrS and controls. QRSd shortened with exercise in all controls but prolonged in all BrS (-6.1 ± 6.0 ms vs 7.1 ± 6.5 ms [P < 0.001] in V). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V; P = 0.002). Both groups demonstrated exercise-induced S duration prolongation in V6, with greater prolongation in BrS (8.2 ± 14.3 ms vs 1.2 ± 12.4 ms; P < 0.001). Any exercise-induced QRSd prolongation in V differentiated those with a positive vs negative procainamide response with 100% sensitivity and 95% specificity in the test cohort, and 87% sensitivity and 93% specificity in the validation cohort.
CONCLUSIONS
Exercise-induced QRSd prolongation is ubiquitous in BrS primarily owing to delayed right ventricular activation. This electrocardiogram phenotype predicts a positive procainamide response and may provide a noninvasive screening tool to aid in the diagnosis of BrS before drug challenge.
PubMed: 38934974
DOI: 10.1016/j.jacep.2024.04.016 -
Journal of the American Heart... Jun 2024Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance,...
BACKGROUND
Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients.
METHODS AND RESULTS
The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (NAC I-L, n=14), NAC I with high levels NT-proBNP (NAC I-H, n=20), and NAC II-III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I-L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I-H (Diff. -2.4, 95% CI (-4.2: -0.7), =0.00) and the NAC II-III group (Diff: -3.1 L/min, 95% CI (-5.2: -1.1), =0.00) compared with the NAC I-L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I-L and NAC II-III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, =0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity.
CONCLUSIONS
An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early-stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure-flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.
PubMed: 38934860
DOI: 10.1161/JAHA.124.034213 -
Cardiology in Review Jun 2024Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with...
Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with diuretic therapies without any significant mortality benefit. The underlying cause of TR can be primary, coming from structural issues with tricuspid valve and more commonly secondary, arising from conditions affecting the right ventricle or the pulmonary circulation. Management of TR has seen few improvements until recently. Traditionally, valve replacement and surgical repair were the therapeutic options available. Tricuspid valve is a complex cardiac structure with many technical challenges for surgical intervention. Transcatheter valve interventions have proven to be safe and effective novel therapeutic options for severe TR, which reduce the severity of TR with associated improvement in quality of life. In this review, we will provide an overview of the management of severe TR utilizing transcatheter edge-to-edge repair with the TriClip device (Abbott, Santa Clara, CA).
PubMed: 38934619
DOI: 10.1097/CRD.0000000000000740