Artificial intelligence in detecting left atrial appendage thrombus by transthoracic echocardiography and clinical features: the Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry.

AIMS: Transoesophageal echocardiography (TOE) is often performed before catheter ablation or cardioversion to rule out the presence of left atrial appendage thrombus (LAT) in patients on chronic oral anticoagulation (OAC), despite associated discomfort. A machine learning model [LAT-artificial intelligence (AI)] was developed to predict the presence of LAT based on clinical and transthoracic echocardiography (TTE) features. METHODS AND RESULTS: Data from a 13-site prospective registry of patients who underwent TOE before cardioversion or catheter ablation were used. LAT-AI was trained to predict LAT using data from 12 sites (n = 2827) and tested externally in patients on chronic OAC from two sites (n = 1284). Areas under the receiver operating characteristic curve (AUC) of LAT-AI were compared with that of left ventricular ejection fraction (LVEF) and CHA2DS2-VASc score. A decision threshold allowing for a 99% negative predictive value was defined in the development cohort. A protocol where TOE in patients on chronic OAC is performed depending on the LAT-AI score was validated in the external cohort. In the external testing cohort, LAT was found in 5.5% of patients. LAT-AI achieved an AUC of 0.85 [95% confidence interval (CI): 0.82-0.89], outperforming LVEF (0.81, 95% CI 0.76-0.86, P < .0001) and CHA2DS2-VASc score (0.69, 95% CI: 0.63-0.7, P < .0001) in the entire external cohort. Based on the proposed protocol, 40% of patients on chronic OAC from the external cohort would safely avoid TOE. CONCLUSION: LAT-AI allows accurate prediction of LAT. A LAT-AI-based protocol could be used to guide the decision to perform TOE despite chronic OAC.

Transcatheter pulmonary denervation in patients with left heart failure with reduced ejection fraction and combined precapillary and postcapillary pulmonary hypertension: A prospective single center experience.

OBJECTIVES: The present study was a prospective, single-center, single-arm study to investigate the efficacy of transcatheter pulmonary artery denervation (TPADN) in patients with combined postcapillary and precapillary PH (Cpc-PH) associated with left heart failure with reduced ejection fraction (HF-rEF). BACKGROUND: Pulmonary hypertension (PH) in patients with left ventricular systolic dysfunction has a negative impact on outcome. METHODS: The combination of pulmonary artery systolic pressure (PAPs) ≥60 mmHg, transpulmonary pressure gradient (TPG) ≥12 mmHg, nonreversible mean PAP, and pulmonary vascular resistance (PVR) ≥3.5 Wood Units was considered as too high risk for heart transplantation (HTx). The clinical efficacy endpoint was an improvement in 6-min walking test and the hemodynamic endpoints were changes in PAPs, PVR, and TPG between baseline and 6 months. Circumferential radiofrequency applications were delivered around distal main, left and right pulmonary arteries. At each ablation point temperature was 45°C and energy 10 W. RESULTS: TPADN was performed in 10 patients. At 6-month in 5 patients we observed reduction in PAP, PVR, TPG, and DPG and then 1 had successful HTx, 2 are on HTx waiting list, 2 received LVADs, 2 patients did not improve, and 3 patients died. CONCLUSIONS: TPADN may be beneficial in selected patients with HF-rEF and Cpc-PH.

Quantification of mitral regurgitation in patients with hypertrophic cardiomyopathy using aortic and pulmonary flow data: impacts of left ventricular outflow tract obstruction and different left ventricular segmentation methods.

BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations. METHODS: The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSVincl) or exclusion (LVSVexcl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvolAoi or MRvolAoe) or MPA (MRvolMPAi or MRvolMPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings. RESULTS: MRvolAoi was higher than MRvolMPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR) = 31.5-60.0 vs. 35.5 ml, IQR = 26.0-51.0; p < 0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR = 16.0-32.0 vs. 24.0 ml, IQR = 15.3-32.0; p = 0.26) or controls (18.0 ml, IQR = 14.3-21.8 vs. 20.0 ml, IQR = 14.3-22.0; p = 0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvolAoi) was higher than pulmonary-based findings (MRvolMPAi) (bias = 9.5 ml; limits of agreement: -11.7-30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSVexcl mirrored those derived using LVSVincl. However, MRvol values calculated using LVSVexcl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p ≤ 0.0001 for all comparisons). CONCLUSIONS: In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

Global area strain is a sensitive marker of subendocardial damage in adults after optimal repair of aortic coarctation: three-dimensional speckle-tracking echocardiography data.

Aortic coarctation (CoA) in adults is associated with reduced survival. Despite successful repair, some unfavorable changes in the left ventricular (LV) myocardial function are reported. Three-dimensional speckle-tracking imaging (3D-STE) is a novel method that allows to assess regional myocardial function in all directions simultaneously and to calculate global area strain which integrates longitudinal and circumferential deformation. The aim of our study was to assess whether 3-D STE provides any new characteristics of LV deformation in patients with optimal CoA repair. Adults after CoA correction underwent transthoracic echocardiographic examinations. Patients with significant concomitant lesions were ruled out. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were assessed using 3D-STE (Echopac Software, GE). The data were compared with those obtained from healthy subjects. 26 adults (9F/17M; mean age 24.4 years) with repaired CoA were studied. Despite preserved LVEFs, patients with repaired CoA had decreased GAS compared with controls (-28.8 vs. -31.7 %; p = 0.007). No differences between patients and healthy subjects in terms of GLS, GCS and GRS were observed. We found a significant correlation between mean blood pressure and GAS (R = 0.39; p < 0.05). No significant influence of age at repair, CoA correction method or LV mass on three-dimensional deformation was observed. Summarizing, global area strain derived from 3D-STE may be a sensitive indicator of subclinical LV dysfunction in patients after optimal repair of CoA. Mean blood pressure, but not age at correction seems to determine LV deformation.

Echocardiography vs magnetic resonance imaging in assessing ventricular function and systemic atrioventricular valve status in adults with congenitally corrected transposition of the great arteries.

BACKGROUND: The survival in adults with congenitally corrected transposition of the great arteries (ccTGA) might be reduced due to dysfunction of the systemic right ventricle (sRV). The quantitative echocardiographic assessment of sRV function and tricuspid (systemic atrioventricular valve) regurgitation (TR) is still a diagnostic challenge. Thus, the aim of this study was to compare echocardiographic indices of sRV function and the degree of TR with corresponding MRI (magnetic resonance imaging)-derived parameters in adults with ccTGA. METHODS: A prospective cross-sectional study of adults with ccTGA referred to a tertiary congenital heart disease center was conducted. All patients underwent transthoracic echocardiography and MRI examinations. Thirty-three adults (19F/14M, mean age 34.1 years) were included. RESULTS: We found significantly lower fractional area change (FAC) and global longitudinal strain (GLS) values in patients with MRI-derived RV ejection fraction (EF) <45%. A cutoff GLS<-16.3% identified sRV EF ≥45% with a sensitivity of 77.3% and specificity of 72.7%. A very strong correlation between MRI- and echocardiography-derived TR volume was observed (r=.84; P<.0001). CONCLUSIONS: GLS is the variable with the best sensitivity but less specificity to distinguish between systemic RV EF ≥45% and below 45%, and it seems to be the preferred echocardiographic index of systemic RV function in adults with ccTGA. The quantitative assessment of TR by MRI and echocardiography showed a very strong agreement in patients with ccTGA.

Coronary artery disease in older adults with congenital heart defects: risk factors and pharmacotherapy.

INTRODUCTION: With advancing age, adults with congenital heart disease (ACHD) are at a higher risk of developing atherosclerotic coronary artery disease (CAD). OBJECTIVES: We aimed to determine the prevalence of CAD, its risk factors, and use of guideline­directed pharmacotherapy among older patients with ACHD.  Patients and methods: We studied all ACHD patients aged 60 years or older hospitalized in our department between the years 2013 and 2020. CAD was defined as a history of acute coronary syndrome or coronary revascularization, or more than 50% diameter stenosis on coronary angiography. Data regarding the underlying heart defect, prevalence of cardiovascular risk factors, and drug prescriptions were collected. RESULTS: A total of 198 patients with known coronary artery status (mean [SD] age, 66.2 [5.3] years; 43.3% men) were included in the analysis. Of them, 54 (27.3%) had CAD. The individuals with CAD were more often men, and they were more likely to have a mild heart defect, dyslipidemia, and a history of hypertension and tobacco use. Multivariable analysis showed that male sex (P = 0.001), dyslipidemia (P = 0.003), and hypertension (P = 0.04) were positive independent predictors of CAD, whereas overweight / obesity was identified as a negative independent predictor (P = 0.04). The proportion of CAD patients on antiplatelet and / or anticoagulant drugs was 92.6%. ß­Blockers were prescribed to 87% of the patients, and a lipid­lowering agent to 96% of the study population. CONCLUSIONS: CAD is common in older patients with ACHD. Our results underline the importance of identification and treatment of modifiable CAD risk factors in individuals with ACHD. The obesity paradox might also play a role in this population. The rate of guideline­recommended pharmacotherapy implementation seems to be satisfactory.

Single ventricle palliation in congenitally corrected transposition of the great arteries: An international multicenter study.

BACKGROUND: Single ventricle palliation may be performed in patients with congenitally corrected transposition of the great arteries due to hypoplasia of 1 ventricle or anatomic complexity rendering biventricular repair unfeasible. There have been only a few small studies of the outcomes of single ventricle palliation in the setting of congenitally corrected transposition of the great arteries. METHODS: A multicenter, international, retrospective cohort study of patients with congenitally corrected transposition of the great arteries undergoing single ventricle palliation was conducted in 29 tertiary hospitals in 6 countries from 1990 to 2018. RESULTS: A total of 194 patients with congenitally corrected transposition of the great arteries underwent single ventricle palliation. A functionally univentricular heart was present in 62.4% (121/194). Patients with 2 good-sized ventricles had more laterality defects (50.7% vs 28.1%, P = .002). Fontan completion was achieved in 80.3% (155/194). A tricuspid valve surgery was performed in 9.3% (18/194). Survival was 97.4% (95% CI, 92.1-99.2) at 15 years in the univentricular cohort and 89.8% (95% CI, 78.0-95.5) at 15 years in those with 2 adequate ventricles (P = .05). At last follow-up, 11.5% of patients had heart failure, whereas 6.0% had moderate or greater systemic right ventricle dysfunction and 8.4% exhibited moderate or greater tricuspid regurgitation. In multivariable analysis, aortic coarctation or hypoplasia (hazard ratio, 7.7; P = .005) was associated with mortality. CONCLUSIONS: Single ventricle palliation in patients with congenitally corrected transposition of the great arteries is associated with excellent long-term survival and low rates of heart failure and atrioventricular valve failure. In patients who would require complex surgery to achieve a biventricular repair, single ventricle palliation appears to be a good alternative.

Management of congenitally corrected transposition from fetal diagnosis to adulthood.

INTRODUCTION: Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart defect characterized by atrioventricular and ventriculo-arterial discordance. CcTGA can be diagnosed at any stage of life. The natural history of the disease depends on concomitant anomalies present in most of the cases, progression of systemic ventricular dysfunction and conduction disturbances. AREAS COVERED: This review describes diagnosis of the anomaly and summarizes the current knowledge on etiology and prognosis in ccTGA patients. Furthermore, interventional and pharmacological approaches to ccTGA management are discussed. The areas requiring further research are highlighted. EXPERT OPINION: Although advances in diagnosis and treatment continue to improve outcomes for ccTGA, patients are burdened with significant morbidity and mortality. Optimal approaches to surgical management of the anomaly, as well as prevention and management of heart failure, are still not established. Future research should focus on the long-term effect of anatomic repair, potential benefits of novel pharmacological strategies for heart failure therapy, and the optimal mode of pacing in ccTGA patients. However, the issues might be difficult to address due to rarity of the disease and its heterogenous clinical presentation. As the life-expectancy of ccTGA patients improves, acquired cardiovascular disorders will become another serious concern.

A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. OBJECTIVES: The study aimed to identify predictors of end­stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. PATIENTS AND METHODS: A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin­3 [Gal­3], extracellular matrix metalloproteinases [MMP­2 and MMP­9], N­terminal pro-B­type natriuretic peptide [NT­proBNP], and high­sensitivity troponin T [hs­TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter­defibrillator intervention. RESULTS: During the median (interquartile range) follow­up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT­proBNP concentration (≥890.3 pg/ml), greater right ventricular end­diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. CONCLUSIONS: An NT­proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

Papillary muscle dyssynchrony in patients with systolic left ventricular dysfunction.

OBJECTIVES: Papillary muscles (PM) dyssynchrony is among the crucial mechanisms leading to mitral valve regurgitation (MR). The purpose of this study was to find a potential relationship between the level of PM asynchrony and the degree of MR in patients with ischemic and nonischemic cardiomyopathies (ICM and nICM, respectively). DESIGN: Twenty-one ICM and ten nICM patients with EF ≤ 35% and sinus rhythm were enrolled in the study. The parameters describing the degree of MR and the deformation of mitral apparatus and PM function were obtained using standard echocardiography and tissue Doppler imaging, respectively. The difference of 65 ms and more in time to peak strain (ε) between anterolateral and postero-medial PM was considered indicative of PM dyssynchrony. RESULTS: PM dyssynchrony correlated with mitral tenting area and left atrial area. The correlation between nICM PM dyssynchrony and nICM LAA was stronger and far exceeded the one observed for ICM patients. The relationship between the PM asynchrony and the remainder of the indices characterizing the degree of MR was weak. CONCLUSIONS: PM dyssynchrony did not reflect the degree of MR but seems to be associated with the deformation of mitral apparatus measured by tenting area. The level of haemodynamic consequences of MR can be better characterized by PM dyssynchrony in nICM than in ICM patients.

Predictors of COVID-19 outcomes in adult congenital heart disease patients - anatomy versus function.

BACKGROUND: It is unclear whether patients with adult congenital heart disease (ACHD) should be considered as an increased risk population with poor outcomes when suffering from COVID-19. AIMS: This study aimed to collect clinical outcome data and to identify risk factors of a complicated course of COVID-19 among ACHD patients. METHODS: Among all outpatients who came to medical attention via telemedicine or direct physician contact at our institution between September 1, 2020 and March 31, 2021, we included all with a COVID-19 diagnosis. The incidence of COVID-19, a clinical course of the disease, and outcome were determined. RESULTS: One hundred and four (8.7%) out of 1 197 patients who were seen at our outpatient clinic for ACHD patients met the definition of COVID-19. Most of them reported a mild course of COVID-19 (99 [95.5%]). Five patients (4.5%) experienced severe symptoms and needed hospitalization. Two patients (1.9% of all with a confirmed diagnosis, 40% with severe infection) died. In the multivariable analysis, decreased systemic ventricular systolic function and any significant valve stenosis were predictors of a complicated disease course. CONCLUSIONS: Our study confirmed previous results showing that a physiology-based model, rather than an anatomy-based model, better predicted COVID-19 outcomes among ACHD patients, which is of importance for patients and healthcare providers during the COVID-19 pandemic.

Innovative medical technologies in the percutaneous treatment of tricuspid regurgitation in Poland.

Tricuspid regurgitation (TR) usually develops secondarily to left-sided heart diseases, whereas primary lesions to the valve apparatus is less common. Untreated severe TR has a poor prognosis and surgical treatment, i.e., valve repair or replacement, is the only treatment option with class I recommendation. However, cardiac surgical procedures may be associated with a high risk of complications. Recent advances in percutaneous approaches to managing structural heart diseases, especially mitral valve diseases, have enabled the implementation of this therapeutic strategy in the population of patients with TR. This paper presents data on the clinical efficacy, cost-effectiveness and expected population size for one of these procedures, namely the TriClip TTVr System procedure. Its efficacy was assessed in the TRILUMINATE study involving 85 patients with co-morbidities and at high surgical risk. After 1 year of follow-up, the reduction in the TR grade was reported in 71% of patients. Clinical improvement in New York Heart Association functional class, a 6-minute walk test, and the quality of life were also observed. A published analysis comparing percutaneous treatment modalities with a drug therapy based on data from medical registers was utilized, and propensity score matching was also employed. Percutaneous treatment reduced 1-year mortality and rehospitalization risk. The economic analysis showed the use of TriClip TTVr System is cost-effective: the cost of an additional quality-adjusted life year ranged from approximately PLN 85,000 to PLN 100,000, which is below the official threshold in Poland. The potential annual number of candidates for this treatment modality in Poland is estimated at 265.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Is right ventricular myocardial deformation affected by degree of interatrial shunt in adults?

AIMS: Data on right ventricle (RV) regional function in adults with interatrial shunt are scarce. The aim of the study was to assess the regional RV deformation in the population of adults with uncorrected atrial left-to-right shunt and to establish a potential relationship between its magnitude and RV regional deformation. METHODS AND RESULTS: We studied 40 adults (30F/10M; mean age 39.2 years) with atrial septal defect (ASD) [average pulmonary-to-systemic blood flow ratio (Qp/Qs) 2.1 ± 0.7]. Standard echocardiographic evaluation was completed with right ventricular dimensions, parameters of its global [tricuspid annular plane systolic excursion (TAPSE), fractional area change, myocardial performance index], and regional [strain/strain rate (ε/SR)] function. Among echocardiographic indices describing RV global function, only TAPSE was increased when compared with healthy subjects. No differences in RV deformation data (ε/SR) between ASD patients and control group were found. Non-linear relationship between the differing Qp/Qs and maximal ε in the mid-segments of the RV free wall was observed. In patients with moderate shunt, maximal ε values were higher when compared with the values obtained in mild and large shunts. CONCLUSION: Regional RV deformation (ε/SR) does not differ significantly in the group of patients with various degrees of the left-to-right shunts when compared with healthy subjects. However, a non-linear correlation between Qp/Qs and ε could be observed. The affected region of the RV wall is the mid-segment and the highest values of ε were recorded in patients with moderate left-to-right shunts.

The burden of cardiovascular risk factors among seniors with congenital heart disease: A single tertiary center experience.

BACKGROUND: The number of adults with congenital heart disease (ACHD) surviving to old age is increasing worldwide. Acquired cardiovascular comorbidities may complicate the course and treatment of the underlying congenital disease and worsen the prognosis. AIMS: The study aimed to assess the burden of cardiovascular (CV) risk factors among elderly patients with ACHD. METHODS: A retrospective analysis of data on all patients ≥60 years of age hospitalized in a tertiary clinic for ACHD was performed from July 2013 to March 2020. We collected information on smoking status, body mass index, and the presence of dyslipidemia, systemic hypertension, and diabetes. RESULTS: The most common CV risk factors among 322 patients ≥60 years of age (median age 66 years; 34% men) were: being overweight/obesity (65.5%), dyslipidemia (64.9%), and arterial hypertension (60.6%). Over 21% of patients suffered from diabetes, and 25.8% were smokers. Over 54% of patients had two or 3 CV risk factors. Patients above 70 years of age were healthier in terms of being overweight/obesity, dyslipidemia, and smoking status. Patients with mild ACHD were more likely hypertensive compared to individuals with complex defects. The highest CV burden was noted in younger men with mild ACHD. CONCLUSIONS: We demonstrated a high burden of CV risk factors in seniors with ACHD. Special attention should be paid to the identification and control of classical CV risk factors in order to prevent acquired CV disease in this population.

Comparison of mitral regurgitation severity assessments based on magnetic resonance imaging and echocardiography in patients with hypertrophic cardiomyopathy.

Mitral regurgitation (MR), which is one of the factors responsible for heart failure symptoms and the development of atrial fibrillation, is an important feature of hypertrophic cardiomyopathy (HCM), and its presence affects which treatment options are chosen. Although cardiac magnetic resonance imaging (MRI) is considered the reference standard for assessing the regurgitant volume (RV) and fraction (RF), echocardiography is the most common method for assessing MR severity. Accordingly, the aim of this study was to compare the results of echocardiography and cardiac MRI for assessing MR severity in a cohort of patients with HCM. MR severity was assessed in 53 patients using cardiac MRI by determining the mitral RV (MRV) and mitral RF (MRF). The results were graded according to thresholds recommended in current guidelines. MR severity assessed by echocardiography was graded by integrating indices of severity. Greater than mild MR, as assessed using echocardiography, was present in 22 patients (41.5%) with HCM and in none of the control patients (p = 0.001). In all, 31 patients (58.5%) had no more than mild MR. When MR severity was assessed using different methods, either moderate (kappa = 0.44, 95% confidence interval = 0.21-0.67), poor or no agreement was found between MRI-derived and echocardiography-derived grades. HCM patients with echocardiography-derived moderate and severe MR had similar median MRVs and MRFs (p = 0.59 and p = 0.11, respectively). In HCM patients, cardiac MRI and echocardiography were at most in modest agreement in assessing MR severity. Importantly, echocardiography-derived moderate and severe MR were not distinguishable by either MRV or MRF.

Sudden cardiac death risk in hypertrophic cardiomyopathy: comparison between echocardiography and magnetic resonance imaging.

In hypertrophic cardiomyopathy (HCM) patients, left ventricular (LV) maximal wall thickness (MWT) is one of the most important factors determining sudden cardiac death (SCD) risk. In a large unselected sample of HCM patients, we aimed to simulate what changes would occur in the calculated SCD risk according to the European HCM Risk-SCD calculator when MWT measured using echocardiography was changed to MWT measured using MRI. All consecutive patients with HCM who underwent cardiac MRI were included. MWT measured with echocardiography and MRI were compared, and 5-year SCD risk according to the HCM Risk-SCD calculator was computed using four different models. The final population included 673 patients [389 (57.8%) males, median age 50 years, interquartile range (36-60)]. The median MWT was lower measured by echocardiography than by MRI [20 (17-24) mm vs 21 (18-24) mm; p < 0.0001]. There was agreement between echocardiography and MRI in the measurement of maximal LV wall thickness in 96 patients (14.3%). The largest differences between echo and MRI were - 13 mm and + 9 mm. The differences in MWT by echocardiography and MRI translated to a maximal difference of 8.33% in the absolute 5-year risk of SCD, i.e., the echocardiography-based risk was 8.33% lower than the MRI-based estimates. Interestingly, 13.7% of patients would have been reclassified into different SCD risk categories if MRI had been used to measure MWT instead of echocardiography. In conclusion, although there was high general intermodality agreement between echocardiography and MRI in the MWT measurements, the differences in MWT translated to significant differences in the 5-year risk of SCD.

Quantitative structure-activity relationship studies of threo-methylphenidate analogs.

Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to identify a test set for 2D- and 3D-QSAR model validation. Comparative Molecular Field Analysis (CoMFA) contour maps based on the structure-activity data of the training set indicate that the 2' position of the phenyl ring cannot tolerate much steric bulk and that addition of electron-withdrawing groups to the 3' or 4' positions of the phenyl ring leads to improved DAT binding affinity. In particular, the optimal substituents were found to be those whose bulk is mainly in the plane of the phenyl ring. Substituents with significant bulk above or below the plane of the ring led to decreased binding affinity. Suggested alterations to be explored in the design of new compounds are the placement at the 3' and 4' position of the phenyl ring of electron-withdrawing groups that lie chiefly in the plane of the ring, for example, halogen substituents on the 3',4'-benzo analog, 79. A complementary 2D-QSAR approach-partial least squares analysis using a reduced set of Molconn-Z descriptors-supports the CoMFA structure-activity interpretation that phenyl ring substitution is a major determinant of DAT binding affinity. The potential usefulness of the CoMFA models was demonstrated by the prediction of the binding affinity of methyl 2-(naphthalen-1-yl)-2-(piperidin-2-yl)acetate, an analog not in the original data set, to be in good agreement with the experimental value.

Predictors of right ventricular function and size in patients with hypertrophic cardiomyopathy.

We investigated factors associated with right ventricular (RV) function and size in hypertrophic cardiomyopathy (HCM) patients. Two hundred fifty-three consecutive HCM patients and 20 healthy volunteers underwent cardiac magnetic resonance examination. In addition to measuring RV function (ejection fraction-RVEF) and size (end-diastolic volume-RVEDV), each image was inspected for the presence of RV and left ventricular (LV) hypertrophy, and the maximal wall thickness of the left and right ventricles was recorded. HCM patients had higher RVEF and lower RVEDV than healthy volunteers and similar RV mass. The mean RV wall thickness was higher in HCM patients than in controls. LV late gadolinium enhancement (LGE) was present in 89.7% of patients, and RV LGE was present in 3.1% of patients (p < 0.0001). Univariate and multivariable analyses revealed that LVEF, peak LV outflow tract gradient, LV LGE, maximal LV wall thickness, and tricuspid regurgitation (TR) volume by magnetic resonance imaging were positive predictors of RVEF. In addition to TR volume, the only independent predictor of RVEF < 45% was LVEF (odds ratio = 0.80, 95% confidence interval 0.67-0.95). Multivariable analysis revealed that LVEDV and TR volume were positive predictors of RVEDV, whereas negative predictors were RVEF, maximal RV wall thickness, LV LGE, and age. Neither estimated systolic pulmonary artery pressure nor TR grade by echocardiography proved to be predictors of RVEF. There were no differences in either the maximal RV wall thickness or the maximal left ventricular (LV) wall thickness in patients stratified according to NYHA functional class (p = 0.93 and p = 0.15, respectively). There were no differences in mean RV wall thickness in patients categorised based on the number of clinical risk factors for sudden cardiac death (SCD), i.e., non-sustained ventricular tachycardia, family history of SCD, or unexplained syncope (p = 0.79). On the other hand, there was a weak positive association between RV hypertrophy and the estimated probability of SCD at 5 years (rho = 0.16, p = 0.01). RV systolic dysfunction measured as decreased RVEF was uncommon in HCM and was associated with poor LV systolic function. LV also had a significant impact on RV size.