Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction.

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. In recognizing inflammation's pivotal role in AMI, this manuscript systematically traces the historical studies spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed, and this review includes the key trials, as well as examines their designs, patient demographics, and primary outcomes. Efficacies and challenges are analyzed, thereby shedding light on the translational implications of trial outcomes. This article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered by providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.

The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral Regurgitation.

Mitral regurgitation (MR), a primary cause of valvular disease in adults, affects millions and is growing due to an ageing population. Cardiovascular magnetic resonance (CMR) has emerged as an essential tool, offering insights into valvular and myocardial pathology when compared to the primary imaging modality, echocardiography. This review highlights CMR's superiority in high-resolution volumetric assessment and tissue characterization, including also advanced techniques like late gadolinium enhancement imaging, parametric mapping, feature tracking and 4D flow analysis. These techniques provide a deeper understanding of MR's pathophysiology and its effect on cardiac chambers, enabling CMR to surpass echocardiography in predicting hard clinical outcomes and left ventricular (LV) remodelling post mitral valve surgery. Despite its advantages, CMR's application faces limitations like cost, lack of standardization, and susceptibility to arrhythmia artifacts. Nonetheless, as technological advancements continue and new evidence emerges, CMR's role in MR assessment is set to expand, offering a more nuanced and personalized approach to cardiac care. This review emphasizes the need for further research and standardized protocols to maximize CMR's potential in MR management.

Moving from left ventricular ejection fraction to deformation imaging in mitral valve regurgitation.

The increasing prevalence of valvular heart diseases, specifically mitral regurgitation (MR), underscores the need for a careful and timely approach to intervention. Severe MR, whether primary or secondary, when left untreated leads to adverse outcomes, emphasizing the critical role of a timely surgical or transcatheter intervention. While left ventricular ejection fraction (LVEF) remains the guideline-recommended measure for assessing left ventricle damage, emerging evidence raises concerns regarding its reliability in MR due to its volume-dependent nature. This review summarizes the existing literature on the role of LVEF and deformation imaging techniques, emphasizing the latter's potential in providing a more accurate evaluation of intrinsic myocardial function. Moreover, it advocates the need for an integrated approach that combines traditional with emerging measures, aiming to optimize the management of patients with MR. It attempts to highlight the need for future research to validate the clinical application of deformation imaging techniques through large-scale studies.

Multimodality imaging for the global evaluation of aortic stenosis: The valve, the ventricle, the afterload.

Aortic stenosis (AS) is the most common valvular heart disease growing in parallel to the increment of life expectancy. Besides the valve, the degenerative process affects the aorta, impairing its elastic properties and leading to increased systemic resistance. The composite of valvular and systemic afterload mediates ventricular damage. The first step of a thorough evaluation of AS should include a detailed assessment of valvular anatomy and hemodynamics. Subsequently, the ventricle, and the global afterload should be assessed to define disease stage and prognosis. Multimodality imaging is of paramount importance for the comprehensive evaluation of these three elements. Echocardiography is the cornerstone modality whereas Multi-Detector Computed Tomography and Cardiac Magnetic Resonance provide useful complementary information. This review comprehensively examines the merits of these imaging modalities in AS for the evaluation of the valve, the ventricle, and the afterload and ultimately endeavors to integrate them in a holistic assessment of AS.

Funny coronary arteriole perforation causes tamponade post-primary percutaneous coronary intervention.

An emergency transradial coronary angiography in a 68-year-old woman demonstrated sub-total occlusion of the proximal left anterior descending artery.

Tough balloon with a vulnerable shaft: an unexpected device failure.

A 73-year-old man, with a previous long drug-eluting stent (DES) from the mid-portion of the left main stem artery (LMS) to proximal left anterior descending artery (LAD), underwent elective coronary angiogram due to worsening anginal symptoms and an abnormal myocardial perfusion single photon emission computed tomography (SPECT) showing ischemia in the LAD territory.

Serum prolactin levels and mortality in adults without prolactinoma: A meta-analysis.

PURPOSE: Prolactin is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data outlines the potential prognostic value of prolactin in various clinical settings. This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum prolactin levels and risk of mortality in adults without prolactinoma. METHODS: A systematic literature search was conducted up to June 10, 2023 to identify studies reporting the association of serum prolactin levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death during follow-up. RESULTS: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum prolactin levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23,596 individuals. Each unit of prolactin increase was independently associated with increased risk of all-cause (pooled aHR=1.17 [1.08-1.27]; I2=48%) and cardiovascular mortality (pooled aHR=1.54 [1.14-2.09]; I2=89%). Individuals belonging to the highest prolactin category had significantly higher risk for all-cause (pooled aHR=1.81 [1.43-2.30]; I2=65%) and cardiovascular (pooled aHR=1.59 [1.04-2.42]; I2=82%) mortality compared to their lowest prolactin category counterparts. The association between prolactin levels and in-hospital death did not reach statistical significance. CONCLUSIONS: Prolactin levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk stratification tool can be delineated in clinical practice.

Atrial Fibrillation Ablation in Congenital Heart Disease: Therapeutic Challenges and Future Perspectives.

The increasing prevalence of atrial fibrillation (AF) in adults with congenital heart disease raises significant questions regarding its management. The unique underlying anatomic and physiological background further adds to the difficulty in eliminating the AF burden in these patients. Herein, we provide an overview of the current knowledge on the pathophysiology and risk factors for AF in adult congenital heart disease, with a special focus on the existing challenges in AF ablation. Emerging imaging modalities and ablation techniques might have a role to play. Evidence regarding the safety and efficacy of AF ablation in adult congenital heart disease is summarized, especially for patients with an atrial septal defect, Ebstein anomaly of the tricuspid valve, tetralogy of Fallot, and Fontan circulation. Finally, any remaining gaps in knowledge and potential areas of future research are highlighted.

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. METHODS AND RESULTS: A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR < 60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR ≥ 60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup < 60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). CONCLUSION: Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

The prognostic impact of diastolic dysfunction after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Diastolic dysfunction (DD) is a long-established marker of disease progression in patients with aortic valve stenosis (AS), indicating valvular myocardial damage. Recently, substantial observational data have emerged demonstrating that worse pre-operative DD assessed using echocardiography is associated with adverse long-term clinical outcomes after transcatheter aortic valve replacement (TAVR). AIM: To systematically appraise and quantitatively synthesize current evidence on the prognostic impact of echocardiographic severe DD derived by echocardiography before TAVR. METHODS: A systemic literature review was undertaken in electronic databases to identify studies reporting the predictive value of severe DD in AS subjects undergoing TAVR. A random-effects meta-analysis was conducted to quantify the adjusted and unadjusted hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACEs) for the presence of severe DD. RESULTS: Ten studies were deemed eligible for inclusion. Of those, 9 provided appropriate quantitative data for the meta-analysis, encompassing a total of 4,619 patients. The presence of severe DD was associated with increased risk for all-cause mortality (pooled unadjusted HR=2.56 [1.46-4.48]; p<0.01; I2=76 %) and MACEs (pooled unadjusted HR=1.82 [1.29-2.58]; p<0.01; I2=86 %). When adjusted for clinically-relevant parameters, the presence of severe DD retained independent association with all-cause mortality (pooled adjusted HR=2.35 [1.26-4.37]; p<0.01; I2=79 %) and MACEs (pooled adjusted HR= 2.52 [1.72-3.65]; p<0.01; I2=0 %). In subgroup analysis there was no difference on post-TAVR risk between the use of different diastolic function grading scores. CONCLUSION: Presence of severe DD assessed by echocardiography pre-TAVR is a major determinant of long-term adverse outcomes after the procedure.

The prognostic impact of right ventricular-pulmonary arterial coupling in heart failure: a systematic review and meta-analysis.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

Prognostic implications of thyroid disease in patients with atrial fibrillation.

Atrial fibrillation (AF) is often accompanied by thyroid disease (THD). This study aimed to explore the relationship between THD and the occurrence of significant clinical outcomes in patients with AF. This post hoc analysis utilized data from the MISOAC-AF trial (NCT02941978), which enrolled hospitalized patients with AF. Patients were categorized based on their THD history into hyperthyroidism, hypothyroidism, or euthyroidism. Cox regression models were employed to calculate unadjusted and adjusted hazard ratios (aHRs). The primary outcomes of interest included all-cause mortality, cardiovascular death, and hospitalizations during the follow-up period. The study included 496 AF patients (mean age 73.09 ± 11.10 years) with available THD data, who were followed-up for a median duration of 31 months. Among them, 16 patients (3.2%) had hyperthyroidism, 141 (28.4%) had hypothyroidism, and 339 (68.4%) had no thyroid disease. Patients with hypothyroidism exhibited higher rates of hospitalization during follow-up (aHR: 1.57, 95% CI 1.12 to 2.20, p = 0.025) compared to the euthyroid group. Elevated levels of thyroid-stimulating hormone (TSH) were correlated with an increased risk of cardiovascular mortality (aHR: 1.03, 95% CI 1.01 to 1.05, p = 0.007) and hospitalizations (aHR: 1.06, 95% CI 1.01 to 1.12, p = 0.03). Conversely, lower levels of triiodothyronine (T3) were associated with higher risks of all-cause mortality (aHR: 0.51, 95% CI 0.31 to 0.82, p = 0.006) and cardiovascular mortality (aHR: 0.42, 95% CI 0.23 to 0.77, p = 0.005). Among patients with AF, hypothyroidism was associated with increased hospitalizations. Furthermore, elevated TSH levels and decreased T3 levels were linked to higher cardiovascular and all-cause mortality risks, respectively.

Temporal Trends in Diagnostic Hemodynamics and Survival of Patients with Pulmonary Hypertension: A Single-Center Study.

Advances in the diagnosis and treatment of pulmonary hypertension (PH) have gradually improved the disease course. This retrospective cohort study aims to explore the diagnostic hemodynamic profile and survival of PH patients and their temporal changes, as well as investigate potential prognostic factors. Overall, 257 adult patients were diagnosed with PH following right heart catheterization (RHC) from January 2008 to June 2023 according to the hemodynamic cut-off values proposed by the corresponding ESC/ERS guidelines at the time RHC was performed. Of these patients, 46.3% were Group 1, 17.8% Group 2, 14.0% Group 3, 18.0% Group 4, and 3.0% Group 5 PH. Temporal improvement in both diagnostic hemodynamic profile and survival of patients with PH and pulmonary arterial hypertension (PAH) was identified after 2013. Survival analysis demonstrated 5-year survival rates of 65% in Group 1 PH (90.3% in idiopathic PAH) and 77% in Group 4 PH. PAH patients being at low risk at diagnosis presented a similar 1-year all-cause mortality rate (12.4%) with high-risk ones (12.8%), primarily due to non-PH-related causes of death (62%), while high-risk patients died mostly due to PH (67%). The observed improvements in diagnostic hemodynamic profiles and overall survival highlight the importance of timely diagnosis and successful treatment strategies in PH.

Pulmonary vasodilators and exercise in Fontan circulation: a systematic review and meta-analysis.

OBJECTIVE: In Fontan circulation, pulmonary arterial hypertension (PAH)-targeted therapies could improve the patients' exercise capacity. This study aimed to investigate the effects of PAH agents on different exercise parameters in stable Fontan patients by synthesising evidence of randomised controlled trials (RCTs). METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases, as well as of ClinicalTrials.gov, was performed. Primary outcomes were specific cardiopulmonary exercise test parameters: peak oxygen uptake (peak VO2), peak heart rate (peak HR), the minute ventilation/produced carbon dioxide (VE/VCO2) slope and the oxygen uptake, both measured at the anaerobic threshold (VO2@AT). RESULTS: Five RCTs were included in the analysis including 573 Fontan patients (mean age 21.2 years, 60% male). PAH-targeted therapies did not affect peak VO2 (mean difference (MD) 0.72, 95% CI -0.25 to 1.70) or peak HR (MD -0.67, 95% CI -3.81 to 2.47), but resulted in a small, significant improvement in VO2@AT (standardised MD 0.24, 95% CI 0.02 to 0.47). VE/VCO2 slope at the anaerobic threshold was also reduced (MD -1.13, 95% CI -2.25 to -0.01). CONCLUSIONS: Although PAH-targeted therapies did not affect exercise parameters at maximal effort, they induced slight improvements in indices of submaximal effort, measured at the anaerobic threshold. Pharmacological improvement of submaximal exercise seems to be a more suitable indicator of Fontan individuals' exercise capacity. Larger RCTs, recruiting specific subpopulations and focusing also on the anaerobic threshold, are warranted to draw more robust conclusions. PROSPERO REGISTRATION NUMBER: CRD42022306674.

Mitral valve geometrical echocardiographic analysis and 3D computational modeling of a normal mitral valve.

Aim: This research aims to develop a consistent computational model of a normal mitral valve (MV) and describe mitral regurgitation (MR) geometry based on Carpentier's classification. Materials & methods: MV geometry was assessed by 2D transthoracic echocardiogram in 100 individuals. A 3D parametric geometric model of the MV was developed. A computational model of a normal MV was performed. Results: The simulation of the valve function was successfully accomplished and its kinematics was analyzed. Differences in geometry were revealed between normal and type III MR. Conclusion: 3D computational models of the normal MV can be constructed relying on standard measurements performed by 2D echocardiography. Certain geometrical differences exist among the normal and the most severe type of MR.

Diagnostic Puzzles and Cause-Targeted Treatment Strategies in Myocardial Infarction with Non-Obstructive Coronary Arteries: An Updated Review.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a distinct subtype of myocardial infarction (MI), occurring in about 8-10% of spontaneous MI cases referred for coronary angiography. Unlike MI with obstructive coronary artery disease, MINOCA's pathogenesis is more intricate and heterogeneous, involving mechanisms such as coronary thromboembolism, coronary vasospasm, microvascular dysfunction, dissection, or plaque rupture. Diagnosing MINOCA presents challenges and includes invasive and non-invasive strategies aiming to differentiate it from alternative diagnoses and confirm the criteria of elevated cardiac biomarkers, non-obstructive coronary arteries, and the absence of alternate explanations for the acute presentation. Tailored management strategies for MINOCA hinge on identifying the underlying cause of the infarction, necessitating systematic diagnostic approaches. Furthermore, determining the optimal post-MINOCA medication regimen remains uncertain. This review aims to comprehensively address the current state of knowledge, encompassing diagnostic and therapeutic approaches, in the context of MINOCA while also highlighting the evolving landscape and future directions for advancing our understanding and management of this intricate myocardial infarction subtype.

Prognostic Implications of Clinical, Laboratory and Echocardiographic Biomarkers in Patients with Acute Myocardial Infarction-Rationale and Design of the ''CLEAR-AMI Study''.

BACKGROUND: Acute myocardial infarction (AMI) remains a major cause of death worldwide. Survivors of AMI are particularly at high risk for additional cardiovascular events. Consequently, a comprehensive approach to secondary prevention is necessary to mitigate the occurrence of downstream complications. This may be achieved through a multiparametric tailored risk stratification by incorporating clinical, laboratory and echocardiographic parameters. METHODS: The ''CLEAR-AMI Study'' (ClinicalTrials.gov Identifier: NCT05791916) is a non-interventional, prospective study including consecutive patients with AMI without a known history of coronary artery disease. All patients satisfying these inclusion criteria are enrolled in the present study. The rationale of this study is to refine risk stratification by using clinical, laboratory and novel echocardiographic biomarkers. All the patients undergo a comprehensive transthoracic echocardiographic assessment, including strain and myocardial work analysis of the left and right heart chambers, within 48 h of admission after coronary angiography. Their laboratory profile focusing on systemic inflammation is captured during the first 24 h upon admission, and their demographic characteristics, past medical history, and therapeutic management are recorded. The angioplasty details are documented, the non-culprit coronary lesions are archived, and the SYNTAX score is employed to evaluate the complexity of coronary artery disease. A 24-month follow-up period will be recorded for all patients recruited. CONCLUSION: The ''CLEAR-AMI" study is an ongoing prospective registry endeavoring to refine risk assessment in patients with AMI without a known history of coronary artery disease, by incorporating echocardiographic parameters, biochemical indices, and clinical and coronary characteristics in the acute phase of AMI.