Background: Paroxysmal atrial fibrillation (PAF) presents significant challenges in management due to its unpredictable recurrence and associated complications. Current prognostic tools lack precision in predicting PAF outcomes, highlighting the need for a comprehensive approach integrating multiple diagnostic modalities. Methods: The PLACEBO pilot study is a prospective observational investigation enrolling 80 adults with PAF from a tertiary hospital. Baseline assessments include cardiopulmonary exercise testing (CPET), a complete echocardiographic evaluation, 24-h ambulatory electrocardiographic monitoring, and plasma biomarker analysis. Participants will be followed for 12 months, with the primary outcome being AF recurrence. Secondary outcomes include cardiovascular events and other clinical indicators relevant to disease progression. Results: The study will assess the feasibility of integrating CPET parameters, echocardiographic indices, and plasma biomarkers into clinical practice for prognostic evaluation. Data analysis will focus on identifying potential associations between these modalities and PAF recurrence, contributing to improved risk stratification. Conclusions: By integrating CPET, echocardiographic parameters, and plasma biomarkers, the PLACEBO pilot study aims to enhance risk stratification and improve the prognostic assessment of patients with PAF. The findings from this study may pave the way for future research, ultimately contributing to the development of personalized management strategies.

Background: Atrial fibrillation is a prevalent arrhythmia with significant morbidity and recurrence challenges. Paroxysmal atrial fibrillation (PAF) is characterized by episodic occurrences and unpredictable recurrences; therefore, it demands innovative diagnostic approaches to predict relapses and guide management. Objectives: This pilot, exploratory study evaluates the feasibility and prognostic value of integrating cardiopulmonary exercise testing (CPET), echocardiographic indices, and plasma biomarkers for predicting PAF recurrence. Methods: The PLACEBO trial is a single-center, prospective observational study of 73 adults with PAF in sinus rhythm at baseline. Comprehensive assessments included CPET, transthoracic echocardiography, 24 h electrocardiographic Holter monitoring with heart rate variability (HRV) metrics, and plasma biomarkers, such as galectin-3 (GAL3). Recurrence was defined as any documented AF episode lasting ≥30 s within 12 months of follow-up. Results: Binary logistic regression revealed that the standard deviation of RR intervals (SDRR) and GAL3 were significant predictors of recurrence. Particularly, higher SDRR [odds ratio (OR): 1.061, p = 0.021] and GAL3 > 10.95 ng/mL (OR: 5.206, p = 0.006) were associated with recurrence. Moreover, lower right ventricular fractional area change (RV FAC) exhibited a marginally significant association with recurrence (OR: 0.927, p = 0.062). CPET parameters demonstrated limited prognostic value in this cohort. Conclusion: This pilot study demonstrates that integrating novel echocardiographic indices, biomarkers, and HRV metrics is feasible and may provide valuable prognostic insights for PAF recurrence. Larger multicenter studies are needed to validate these findings and optimize personalized risk stratification strategies.

A significant number of individuals undergoing Coronary Computed Tomography Angiography (CCTA) for suspected Coronary Artery Disease (CAD) have non-obstructive or no CAD. There is a need for clinically proven models that can predict the pre-test probability (PTP) of stable CAD and help to identify low-risk individuals. Optimizing patient stratification is of paramount importance to improve diagnostic yield and cost-effectiveness. A study is being carried out to determine whether or not each patient needs to undergo CCTA because of suspected CAD. The main objective of the study is to evaluate the clinical performance of an AI-based tool, as well as its utility by medical professionals. Data has been acquired from 750 participants as part of routine clinical practice in AHEPA General Hospital of Thessaloniki. At least two expert cardiologists and two expert radiologists are involved in the study, who provide the ground truth. A trained AI based model embedded in an easy-to-use and user-friendly web application is implemented in practice. Recruitment for the study began in July 2023. Data collection, development, training, deployment of the AI web tool were completed by May 2024, while the analysis of the data is ongoing. The proposed study represents a novel approach of a web-based AI-driven solution for optimizing patient stratification with the goal of improving diagnostic yield and cost-effectiveness of CCTA utilization within the context of cardiology clinical practice.

Aim Severe COVID-19 can cause acute respiratory distress syndrome, hypoxia, systemic complications, and increased mortality. Pulmonary hypertension (PH) is a major global health issue associated with worsening symptoms and increased mortality. This systematic review aimed to assess the influence of PH onset among COVID-19 patients on all-cause mortality and intensive care unit (ICU) admission. Method An unrestricted search of five databases up to June 2022 was undertaken. Pulmonary hypertension was assessed using transthoracic echocardiogram, computed tomography, or right heart catheterisation. After duplicate screening, data extraction, and risk of bias assessment, random effects meta-analyses of odds ratios (OR) and their 95% confidence intervals (CI) were performed for all-cause mortality and ICU admission. Results From the 26 studies that were included (3,373 patients, 76% males, median age 62.6 years), PH in COVID-19 patients was significantly associated with higher odds for all-cause mortality (26 studies; OR 3.89; 95% CI 2.85-5.31; p<0.001) < 0.001) and higher odds for ICU admission (six studies; OR 2.50; 95% CI 1.69-3.70; p<0.001). < 0.001). Meta-regression/subgroup analyses by patient demographics, comorbidities, or therapeutic regimens, and sensitivity analyses did not fi nd any differences. Conclusion Evidence from observational studies indicates that PH in COVID-19 patients is associated with increased odds of mortality and ICU admission.

BackgroundCardiopulmonary exercise testing (CPET) is a significant tool for evaluating exercise capacity in healthy individuals and in various pulmonary and cardiovascular conditions, quantifying symptoms and predicting outcomes. Atrial fibrillation (AF) poses a significant burden on patients and health systems; a research marathon is ongoing for discovering the pathophysiologic substrate, natural history, prognostic tools and optimal treatment strategies for AF. Among the plethora of variables measured during CPET, there is a series of parameters of interest concerning AF.MethodsWe conducted a scoping review aiming to identify significant CPET-related parameters linked to AF, as well as indicate the impact of other cardiac disease-related variables. We searched PubMed from its inception to 12 January 2022 for reports underlining the contribution of CPET in the assessment of patients with AF. Only clinical trials, observational studies and systematic reviews were included, while narrative reviews, expert opinions and other forms of manuscripts were excluded.ResultsIn our scoping review, we report a group of heterogeneous, thus noteworthy parameters relevant to the potential contribution of CPET in AF. CPET helps phenotype AF populations, evaluates exercise capacity after cardioversion or catheter ablation, and assesses heart rate response to exercise; peak VO2 and VE/VCO2, commonly measured indices during CPET, also serve as prognostic tools in patients with AF and heart failure.ConclusionsCPET seems to hold a clinically important predictive value for future cardiovascular events both in patients with pre-existing cardiac conditions and in healthy individuals. CPET variables may play a fundamental role in the prediction of future AF-related events.

Background Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmo-nary exercise testing (CPET), in HCM patients.Methods This study included 241 consecutive HCM patients (aged 51.2615.7 years; 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/ predicted oxygen consumption [%peakVO2] <80%) and ventilatory inefficiency (ventilation/carbon di-oxide output [VE/VCO2] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain. Results All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO2 and VE/ VCO2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a sig-nificant predictor of %peakVO2<80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO2>34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%).Conclusion Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO2 and VE/VCO2 slope.

A 34-year-old woman with no significant past medical history was admitted to our hospital complaining of shortness of breath on exertion, which had worsened over the last 6 months, a fever of up to 37.5oC, malaise, and postural dizziness. Laboratory examination showed an erythrocyte sedimentation rate of 33 mm/hr, a C-reactive protein level of 5.1 mg/dL, and elevated N-terminal pro B-type natriuretic peptide (615 pg/mL). Transthoracic echocardiogram revealed a dilated and hypokinetic right ventricle, with impaired systolic function, and an estimated right ventricular systolic pressure of 65 mmHg (Videos S1 and S2). Turbulence within the pulmonary artery was noted (Video S3). A computed tomography (CT) pulmonary angiogram demonstrated pulmonary arterial wall thickening and narrowing of the left and right pulmonary artery branches (Figure 1A and B ). A positron emission tomography (PET)–CT scan revealed increased 18F-fluorodeoxyglucose (18FDG) accumulation at the pulmonary artery (Figure 1C), aorta, and right ventricular free wall (Figure 1D). A diagnosis of Takayasu arteritis was made, and medical therapy with corticosteroids and methotrexate was initiated. Echocardiography at 9 months showed improved right ventricular function (Video S4).

BACKGROUND:The effect of acute preload reduction during haemodialysis on left ventricle (LV) and right ventricle (RV) function is not well understood. This study aimed to evaluate acute changes in novel echocardiographic and tissue Doppler-derived indices of LV and RV function during the first and a standard weekly dialysis session and to examine the possible effect of acute intradialytic volume changes in LV and RV diastolic function and pulmonary circulation loading.METHODS:Forty-one adult patients receiving standard thrice-weekly haemodialysis participated in this study. Two-dimensional echocardiographic and tissue Doppler imaging (TDI) studies were performed with a standard cardiac ultrasound device (Vivid 7 or Vivid e, GE, Horton, Norway) shortly before and after the first weekly and a standard dialysis session. Multiple linear regression analysis was applied to assess the effect of volume changes on peak early mitral (E) and tricuspid (E RV) velocities changes.RESULTS:Significant reductions from pre- to post-haemodialysis were noted in body weight and systolic blood pressure. Post-haemodialysis left and right atrial, LV and RV sizing echocardiographic parameters were lower. LV systolic function, represented by LV ejection fraction, cardiac output and mean peak systolic LV and RV velocities at the annulus level, was unchanged. Diastolic function indices such as E (first session: 0.96 ± 0.28 versus 0.75 ± 0.27 m/s, P < 0.001; standard session: 0.89 ± 0.24 versus 0.78 ± 0.29, P < 0.001) and E RV (first session: 0.89 ± 0.26 versus 0.67 ± 0.25 m/s, P < 0.001; standard session: 0.86 ± 0.24 versus 0.77 ± 0.31, P < 0.001), E/A LV ratio, TDI peak early mitral (E') velocity and E'/A' RV ratio were reduced after haemodialysis. Pulmonary circulation loading, represented by RV systolic pressure, was significantly improved. In multiple regression model analysis, intradialytic weight loss was independently associated with changes in E [β = 0.042 (95% CI 0.018-0.066)] and E RV [β = 0.084 (95% CI 0.057-0.110)].CONCLUSIONS:This study shows that haemodialysis deteriorates cardiac diastolic function indices and improves pulmonary circulation loading, while systolic function remains unchanged. High intradialytic volume removal may affect cardiac diastolic function.

Background: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to identify the clinical impact and prognostic significance of AF on a large cohort of patients with HCM. Methods: Echocardiographic and clinical correlates, risk factors for AF and thromboembolic stroke and the prognostic significance of AF were evaluated in 509 patients with an established diagnosis of HCM. Results: A total of 119 patients (23.4%) were diagnosed with AF during the index evaluation visit. AF patients had a higher prevalence of stroke and presented with worse functional impairment. Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40). AF was an important risk factor for overall mortality (HR=3.4, 95% CI: 1.7-6.5), HCM-related mortality (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even after adjusting for statistically significant clinical and demographic risk factors. However, AF did not affect the risk for sudden death. Conclusions: LA size is an independent predictor of both AF and thromboembolic stroke. Moreover, patients with AF, regardless of type, have significantly higher mortality rates than patients without AF.

BACKGROUND:The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel.METHODS:A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria.RESULTS:At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group.CONCLUSION:The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).

Aims The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population. Methods and results 161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg−1 min−1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted. Conclusions In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.

Background Ebstein's anomaly of the tricuspid valve often results in biventricular dysfunction and functional deterioration. Little is known about the relation between exercise capacity, disease severity and outcome in adults with Ebstein's anomaly. Methods Data on all patients with Ebstein's anomaly of the tricuspid valve who underwent cardiopulmonary exercise testing in our tertiary center were collected. The relation between exercise parameters, anatomic severity (Glasgow outcome score) and the combined end-point of death, non-elective hospitalization and surgical repair was studied using Cox regression analysis. Results A total of 51 adult patients fulfilled inclusion criteria (49% male, mean age 37.8±13.6 years). Mean peak oxygen uptake (peak VO2) was 63.2±18.7% of predicted, the slope of ventilation per unit of carbon dioxide output (VE/VCO2 slope) 37.4±11.4, heart rate reserve (HRR) 23.6±22.7 bpm. A significantly lower peak VO2 was found in patients with a higher Glasgow outcome score, higher cardiothoracic ratio and documented atrial shunt. Peak VO2 (HR for value <60% of predicted 3.47, 95% CI: 1.28–9.44, p=0.015) and HRR (HR for value <25 bpm 3.07, 95% CI: 1.24–7.61, p=0.016) were significant predictors of outcome, the former being the strongest on multivariable analysis. Conclusions Reduced exercise capacity in patients with Ebstein's anomaly relates to severity of the underlying disease and is a strong and independent predictor of outcome. Cardiopulmonary exercise testing should be incorporated in the follow-up and risk stratification of patients with this relatively uncommon and challenging cardiac defect.

Introduction: The aim of the present study was to examine the value of the right atrial volume index (RAVI) as predictor of functional capacity in patients with heart failure.Methods: A total of 51 patients with stable chronic heart failure of ischaemic or non-ischaemic aetiology were prospectively enrolled. The systolic function of the right ventricle was quantified using the tricuspid annular plane systolic excursion (TAPSE). Right atrial volume was measured in the apical 4-chamber view and was indexed to body surface area. The functional capacity was assessed by the Duke Activity Status Index (DASI).Results: Patients with a low functional capacity (DASI<10) had lower TAPSE (1.4 +/- 0.3 cm versus 2.0 +/- 0.4 cm, p<0.001), higher RAVI (42 +/- 15 ml/m(2) versus 22 +/- 9 ml/m(2), p<0.001), higher estimated right ventricular systolic pressure (61 +/- 13 mmHg versus 40 +/- 16 mmHg, p<0.001), larger right ventricular end-diastolic diameter (4.7 +/- 0.8 cm versus 3.6 +/- 0.7 cm, p<0.001) and lower left ventricular ejection fraction (26 +/- 6% versus 30 +/- 7%, p=0.022). Multivariate analysis revealed that TAPSE was the single independent predictor of DASI. In the subgroup of patients with reduced right ventricular systolic function (TAPSE<2 cm), RAVI was the single independent predictor of low DASI. In the overall population RAVI >= 30.6 ml/m(2) had 75% sensitivity and 83% specificity in predicting DASI<10. Within the subgroup of patients with TAPSE<2 cm, RAVI >= 30.6 ml/m(2) had better sensitivity and specificity (79% and 90% respectively) in predicting DASI<10.Conclusions: Increased right atrial volume index predicts low functional capacity quantified by the Duke Activity Status Index in patients with stable chronic heart failure.

Objective: The wide spectrum of intracardiac anatomy and reparative surgery available for adults with congenital heart disease (ACHD) makes uniform measurement of cardiac size and disease severity challenging. The aim of this study was to assess the prognostic potential of cardiothoracic ratio, a simple marker of cardiomegaly, in a large cohort of ACHD.Patients and setting: Chest radiographs from 3033 ACHD patients attending our institution between 1998 and 2007 and 113 normal controls of similar age were analyzed blindly.Design: Cardiothoracic ratio derived from plain postero-anterior chest radiographs, was compared between ACHD patients and controls, different diagnostic subgroups and different functional classes. Relationship between cardiothoracic ratio and survival was assessed using Cox regression.Results: Average cardiothoracic ratio in ACHD was 52.0 +/- 7.6% (over 50% in 56.4%), significantly higher in all ACHD diagnostic subgroups compared to controls (42.3 +/- 4.0%, p<0.0001) and highest in the "complex" cardiac anatomy, Ebstein's anomaly and Eisenmenger subgroups. Cardiothoracic ratio related to functional class, but was high even in asymptomatic patients. During a median follow-up of 4.2 years, 164 patients died. Patients with a cardiothoracic ratio > 55% had an 8-fold increased risk of death compared to those in the lowest tertile (b48%). Even patients withmildly increased cardiothoracic ratio (48-55%) had an adjusted 3.6-fold increased mortality compared to the lowest tertile.Conclusions: Cardiothoracic ratio derived from postero-anterior chest radiographs is a simple, and reproducible marker, which relates to functional class and predicts independently mortality risk in ACHD patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Background: Atrial tachyarrhythmias are a known complication late after Fontan operation. Limited information is available on their prognostic value.Methods: All patients with previous Fontan operation followed at our institution since 1999 were identified from the electronic database and included in this study. Demographic and clinical characteristics including history of atrial tachyarrhythmias were recorded at the earliest full clinical assessment and patients were followed thereafter for all-cause mortality and hospitalization.Results: A total of 98 patients, mean age 31.5 +/- 8.9 years, 43.8% male, 31.6% with a total cavopulmonary connection (TCPC) were identified. A history of atrial tachyarrhythmia was present at baseline in 60.2% of patients who were older (33.0 +/- 8.3 vs 29.1 +/- 9.4 years, p = 0.002), less likely to have a TCPC (13.5% vs 58.9%, p<0.001), and more symptomatic in terms of NYHA class (51.9% vs 26.7%, p=0.007) compared to arrhythmia-free patients. During a median follow-up of 6.7 years 18 patients died and 64 patients were hospitalized. Even after adjustment for baseline clinical characteristics, atrial tachyarrhythmia was an independent predictor of death (propensity score adjusted HR 9.35, 95% CI: 1.10-79.18, p=0.04, c-statistic 0.88) and composite of death or hospitalization (propensity score adjusted HR 5.00, 95% CI: 2.47-10.09, p<0.0001).Conclusions: In adult patients with a Fontan-type operation, the presence of atrial tachyarrhythmias is associated with higher morbidity and mortality at mid-term follow-up. Whether early arrhythmia targeting intervention may improve clinical outcome needs to be studied in a prospective manner. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

7 P. Sindika St. 546 43 Thessaloniki, Greece e-mail: tkelpis@gmail.com

Objective To assess the relationship between elevated levels of B-type natriuretic peptide (BNP) and outcome in patients with Eisenmenger syndrome. Design Retrospective study. Setting Tertiary centre for adult congenital heart disease. Patients All patients with Eisenmenger syndrome (n=181, age 36.9±12.1 years, 31% with Down syndrome) in whom BNP concentrations were measured as part of routine clinical care were included. Main outcome measures The study end point was all cause mortality. Results During a median follow-up period of 3.3 years, 20 patients (7 with Down syndrome) died. Higher BNP concentrations were predictive of all cause mortality on univariate analysis in patients with or without Down syndrome. On multivariable Cox proportional hazard analysis, BNP predicted survival independently of renal function, Down syndrome, or 6 min walk test distance (p=0.004). Temporal increases in BNP concentration were also found to predict mortality. Treatment with disease targeting therapies was associated with a significant reduction in BNP concentrations. Conclusions BNP concentrations predict outcome in contemporary Eisenmenger patients. Increases in BNP concentrations over time are also of prognostic significance. In addition, disease targeting therapies may help to reduce BNP concentrations in this population, while treatment-naïve patients have static or rising BNP concentrations.

This chapter contains sections titled: Transposition of the great arteries Congenitally corrected transposition of the great arteries Isolated ventricular inversion Further reading