Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) therapies include both TTR gene silencers and TTR stabilizers. The role of TTR gene silencers added to background TTR stabilizer therapy is unknown, and the effects of silencer treatment in the absence of stabilizer use is unclear. In the CARDIO-TTRansform study, 1,432 patients, (n=135 [9.4%] female and n=1297 [90.6%] male), with ATTR-CM were randomized (1:1) and treated with the antisense oligonucleotide eplontersen (45 mg every 4 weeks) targeting TTR or with placebo for up to 140 weeks. Fifty-seven percent of patients were taking TTR stabilizers at baseline. In the overall study, treatment with eplontersen did not significantly reduce the primary composite endpoint. Here, in a prespecified analysis, we show that the primary endpoint (a composite of cardiovascular mortality and recurrent cardiovascular events) was modified by baseline stabilizer use (Pinteraction = 0.017). Benefit was seen in those patients not on stabilizers at baseline (RR 0.71, 95% CI, 0.54–0.93, P = 0.012), whereas no benefit seen in those on stabilizers at baseline (RR 1.14, 95% CI, 0.85–1.53, P = 0.39). The safety profile of eplontersen was favorable, irrespective of baseline stabilizer use. Treatment with eplontersen versus placebo demonstrated a clinically meaningful benefit among patients not receiving background stabilizers but provided no additional clinical benefit in those on background stabilizer therapy. These findings of a strong treatment effect modification may offer insight for therapeutic decision-making in clinical practice. ClinicalTrials.gov registration: NCT04136171. As presented at the 2026 ESC Congress, in a secondary analysis of the CARDIOTTRansform trial testing the transthyretin-targeting antisense oligonucleotide eplontersen in patients with transthyretin amyloid cardiomyopathy, a beneficial effect was observed in patients who were not on transthyretin stabilizers at baseline, but not in those who were on stabilizers.

BACKGROUND:Transthyretin amyloid cardiomyopathy (ATTR CA) is a rare, fatal disease characterized by the deposition of amyloid fibrils derived from misfolded transthyretin (TTR) protein. This single-center study investigated the clinical characteristics, genetic profile, and geographic distribution of ATTR CA patients in southern Poland, a suspected endemic area. MATERIAL AND METHODS:This prospective study was conducted between 2020 and 2025 involving 100 adults, including a cohort of consecutive index patients with confirmed ATTR CA. Furthermore, all consenting first-degree relatives were invited to undergo targeted assessment through a familial cascade screening approach. The study incorporated clinical data, echocardiography, scintigraphy, genetic testing, and prospective follow-up for five years to assess all-cause mortality. RESULTS:Among 100 participants (27 index patients and 73 relatives), 6 relatives were diagnosed with ATTR CA and 15 were identified as carriers of a pathogenic TTR variant. The most frequently identified TTR variant was Phe53Leu, suggesting a high regional prevalence in southern Poland, alongside Glu109Lys, Glu122Lys, and Glu82Lys. The presence of hereditary ATTR CA was significantly associated with increased risk of all-cause mortality (HR, 7.67; 95% CI, 2.33-25.26; P <0.001). All 33 patients with ATTR CA were eligible for tafamidis; moreover, two patients in this cohort with polyneuropathy were treated with inotersen, representing the first applications of these therapies in Poland. CONCLUSION:A comprehensive diagnostic approach is crucial for timely initiation of disease-modifying therapies. Our study suggests that, in this region, there is a high rate of the Phe53Leu TTR variant; however, further research is needed to validate these findings (NCT05814380).

BACKGROUND:Tricuspid regurgitation (TR) is becoming more commonly recognized as an important contributor to adverse cardiovascular outcomes. Right ventricular (RV) dysfunction influences TR progression and prognosis. RV free wall longitudinal strain (FWLS) is a valuable marker of RV function, though its prognostic significance in TR requires further study. METHODS:We conducted a comprehensive search of studies assessing the role of RV strain in patients with severe TR, heart failure (HF), and those undergoing tricuspid valve interventions, using MEDLINE, EMBASE, and Cochrane databases to identify relevant studies. Retrospective and prospective clinical studies were included, while case reports, case series, and animal studies were excluded. RESULTS:A decrease in RVFWLS was consistently associated with mortality, HF-related hospitalizations, adverse clinical outcomes in severe TR and in TR valve repair. Several studies have demonstrated that reduced RVFWLS may be an independent predictive factor for poor prognosis, proving to have a superior prognostic value than conventional RV function parameters such as TAPSE and FAC. A number of studies show that assessing RV strain appears critical for optimizing the strategy for percutaneous and surgical treatment of TR. Implementing this parameter in routine echocardiographic evaluation could contribute to more precise timing of interventional treatment, thus improving long-term outcomes and prognosis. CONCLUSIONS:RV strain assessment, particularly RVFWLS, may provide valuable prognostic information in patients with severe TR and help optimize treatment strategies. Implementing RVFWLS into routine echocardiographic evaluation could improve patient selection and timing of interventions.

Fabry disease (FD) belongs to the group of lysosomal storage diseases (LSD), characterized by insufficient enzyme activity responsible for the intra-lysosomal breakdown of various substrates. The result is an uncontrolled accumulation of by-products of cellular metabolism. Lysosomal storage diseases are inherited and transmitted mainly in an autosomal recessive fashion. Without a positive family history, an early diagnosis can often be missed. In addition, the age of clinical manifestation can range from infancy to adulthood - a distinction is made between severe "classic" variants of the disorders, presenting in childhood, and forms with late onset. Some of the conditions in this group may not show typical signs of tissue storage, such as liver and spleen enlargement, especially in subtypes associated with neurodegenerative changes. The aim of this expert opinion of the Polish Cardiac Society and the Polish Forum for Fabry Disease is to summarize the current knowledge on FD, present advances in diagnosis and therapy, and disseminate known diagnostic and therapeutic algorithms for this group of patients.

Objective: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity, which can manifest as left ventricular hypertrophy (LVH). We aimed to assess the prevalence of FD in an unselected cohort of patients with unexplained LVH. Methods and results: We screened 202 unrelated adults with LVH using enzymatic assays for α-galactosidase A in dried blood spots. Patients with low activity underwent GLA gene sequencing. Echocardiographic parameters were evaluated according to ESC guidelines. FD was diagnosed in 4 women (2%), each carrying distinct pathogenic GLA mutations. All affected individuals showed normal or borderline enzyme activity. Cardiac, renal, or neurological symptoms were observed variably among patients. Echocardiographic findings revealed slightly lower wall thickness and preserved systolic function in FD patients compared to those without FD. Cascade genetic screening identified 16 additional family members with the same mutations. One patient (0.5%) was incidentally diagnosed with Gaucher disease based on syndromic features and enzymatic testing. Conclusions: FD was identified in 2% of patients with unexplained LVH, who were females. Enzyme-based screening followed by targeted genetic testing is a cost-effective strategy for FD detection. Early diagnosis is essential for prompt treatment and family counselling, underscoring the importance of routine FD screening in patients with LVH of unclear aetiology. Our findings support the use of targeted screening for Fabry disease in patients with LVH and systemic features, and highlight the potential to identify other lysosomal disorders in selected cases.

ObjectivesCardiac resynchronization therapy (CRT) is an intervention for heart failure patients with reduced ejection fraction who exhibit specific electrocardiographic indicators of electrical dyssynchrony. However, electrical dyssynchrony does not universally correspond to left ventricular mechanical dyssynchrony (LVMD). Gated single-photon emission computed tomography (SPECT) myocardial perfusion allows for the assessment of LVMD, yet its role in the CRT selection process remains debated.MethodsWe conducted a systematic literature review to critically evaluate the evidence for the prediction and prognostic utility of SPECT for LVMD in assessing LVMD among CRT candidates. The review adhered to PRISMA 2020 Statement criteria and included articles from PubMed, Embase, and Cochrane databases. The quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation framework.ResultsFrom an initial pool of 1055 records, 33 met the inclusion criteria and provided original data on the predictive value of myocardial perfusion SPECT for LVMD. Most of them measured LVMD according to established recommendations, focusing on phase histogram bandwidth (HBW) and phase histogram standard deviation (PSD). Out of 2066 patients from 27 studies, 62% (n = 1214) were qualified as CRT responders. Five studies reported SPECT-based cutoffs for predicting CRT response (HBW ranging 55 degrees-152 degrees and for PSD 20 degrees-54 degrees). Only five studies assessed the prognostic implications of baseline SPECT-measured LVMD, indicating that elevated baseline HBW and PSD values are associated with poorer outcomes.ConclusionThe objective and reproducible measurement of LVMD provided by SPECT underscores its potential as a valuable tool. Such assessment seems to be emerging as a promising adjunctive technique with potential to enhance CRT outcomes.

Introduction:A persistent patent foramen ovale (PFO) is a congenital heart defect that predisposes to crossed embolism resulting in stroke. The defect can be accompanied by endothelial dysfunction. One marker reflecting endothelial dysfunction is serotonin, the concentration of which can be increased by passing through the PFO, thus bypassing degradation in the lungs. Aim:To study the potential association between endothelial dysfunction and the occurrence of cryptogenic stroke in patients with PFO, compared with patients without PFO and without a history of cryptogenic stroke. Material and methods:Seventy-nine patients were recruited, including 51 (64.65%) women and 28 (35.44%) men, who underwent PFO closure surgery within the Clinical Department of Cardiovascular Diseases of the John Paul II Specialized Hospital of Krakow, Poland, for a history of cryptogenic stroke between 2009 and 2021. The mean age was 48.34 ±13.13 years. The control group consisted of 79 patients (male and female) without a stroke history. Patients underwent the following examinations: subject and physical examination, transthoracic and transesophageal echocardiography, and laboratory tests including serotonin levels collected before the PFO closure procedure. Results:There was a statistically significant difference between serotonin levels in the study group and the control group (1645.55 ±801.26 vs. 856.98 ±781.63; p < 0.001). There was no correlation between serotonin concentration and channel length and width (r = 0.082; p = 0.471; r = 0.085; p = 0.455). Conclusions:Serotonin levels appear to be significantly higher in patients with PFO after cryptogenic stroke compared with patients without PFO and stroke history. The length and width of the PFO canal may not correlate with serotonin levels.

Background Accurate assessment of ventricular involvement in transthyretin cardiac amyloidosis (ATTR-CA) is essential for diagnosis and management. This study evaluated left and right ventricular (LV and RV) involvement in patients with ATTR-CA using single-photon emission computed tomography/computed tomography (SPECT/CT) witch Technetium-99m and 3,3-diphosphono-1,2-propanodicarboxylic acid ([99mTc]Tc-DPD). Methods This prospective, single-centre study enrolled 100 adults from 2020 to 2024 (NCT05814380). Participants underwent clinical assessment, genetic testing, electrocardiography, echocardiography, and [99mTc]Tc-DPD SPECT/CT. Volumetric and regional analyses of LV and RV amyloid burden were conducted. Patients were prospectively observed for 5 years to assess all-cause mortality. Results Overall, RV uptake was observed in 91 % of patients with ATTR-CA. Radiotracer uptake was detected in the interventricular septum of all ATTR-CA patients, with apical involvement being less common (24 % hereditary ATTR vs. 31 % wild-type ATTR, p = 0.62). Notably, RV uptake was associated with RV thickness, LV global longitudinal strain, and N-terminal pro-brain natriuretic peptide levels (p = 0.00007, p = 0.00022, p = 0.00007; respectively). Multivariate analysis identified increased LV mass index and NYHA class as predictors of RV involvement (area under curve: 0.96). Volumetric LV and RV SPECT uptake measurements and apical sparing correlated with all-cause mortality (p < 0.001). Conclusions The presented findings confirm that SPECT/CT evaluation provides insights into both LV and RV involvement in patients with ATTR-CA and is associated with prognosis. Detailed assessment of RV involvement, through SPECT/CT, reveals significant structural and functional changes associated with disease severity. The presence of RV uptake is associated with advanced cardiac involvement, emphasising the importance of comprehensive biventricular evaluation in this patient population.

Background: Alcohol consumption, even in moderate amounts, is associated with complex changes in blood biochemistry, involving abnormalities of many markers affecting cardiovascular risk. Methods: A total of 100 patients with documented alcohol abuse were included in the study. Demo- graphic data and information on alcohol consumption were collected using a standardized questionnaire. All patients underwent biochemical tests. The following parameters were evaluated: PAI-1, vWF, TNF-alpha, VCAM-1, adiponectin, fibrinogen, lipid profile, and hsCRP. The results were compared with a control group of 25 healthy subjects. Results: A significant adverse effect of alcohol abuse was observed for markers such as PAI-1, TNF-alpha, VCAM-1, adiponectin, and fibrinogen. Moreover, most of the subjects showed elevated TC, LDL-C, and TG levels. There was a significant relationship between vWF and average daily alcohol consumption, a positive relationship between adiponectin levels and age, and between fibrinogen and the number of cigarettes smoked. No significant correlations were observed between the other markers and age, gender, place of residence, daily alcohol consumption, and total time of alcohol abuse. Conclusions: Several abnormalities in most of the analyzed markers were observed in persons abus- ing alcohol, with no significant correlation with the daily amount of alcohol consumed and the total time of alcohol abuse, which may indicate permanent and irreversible damage to many tissues and organs as a result of chronic alcohol consumption. Further studies in this area with a larger group of patients are necessary to clarify the mechanisms leading to cardiovascular damage in the course of alcohol abuse.

Introduction:Atrial septal defects (ASD) are prevalent congenital heart anomalies found in the adult population. Percutaneous ASD closure has become a routine clinical practice. Elevation of postprocedural transient cardiac biomarkers and exacerbation of supraventricular arrhythmias have been reported in the subject literature. Aim:To explore the relationship between cardiac troponin I (cTnI) elevation and supraventricular ectopy (SVE) following percutaneous closure of secundum atrial septal defect (ASD) in adult patients. Material and methods:600 consecutive patients who underwent successful transcatheter ASD secundum closure were analyzed. Serum levels of cTnI were measured before and within 72 h of device implantation. 24-hour Holter monitoring was performed before the procedure, at 1 month, and at 6 months of follow-up. Results:SVE burden increased 1 month after the procedure (median 1021.00; min.-max. 11.00-29 862.00) compared to baseline values (median 146.00; min.-max. 0-1865.00; p < 0.01). 61.7% of patients demonstrated a cTnI rise exceeding 50% of the upper reference limit within 24 h of the procedure. A statistically significant positive correlation between SVE burden 1 month after the procedure and periprocedural cTnI increase (p < 0.05, r = 0.41) was observed, while cTnI levels significantly correlated with procedure and fluoroscopy time (p < 0.001), device size (p < 0.001) and maximal ASD diameter (p < 0.001). Conclusions:A significant increase of cTnI is noted frequently after transcatheter ASD closure and seems to predict exacerbation in SVE burden on short-term follow up. The independent risk factors of cTnI rise are prolonged procedure duration and larger device sizes.

Purpose Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. Methods From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography (SPECT/CT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing. Results Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E’, right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the ''5-5-5'' sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve (AUC) of 0.99, including LV mass, GLS and RV thickness. Conclusion This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening.

Background: Dilated cardiomyopathy (DCM) is distinguished by left ventricle (LV) dilation accompanied by systolic dysfunction. However, some studies suggested also a high prevalence of LV diastolic dysfunction (LVDD), similar to a general cohort of heart failure (HF) with reduced ejection fraction (LVEF). The bulk of evidence, mostly arising from basic studies, suggests a causative link between cardiac fibrosis (CF) and LVDD. However, still, there remains a scarcity of data on LVDD and CF. Therefore, the aim of the study was to investigate the association between CF and LVDD in DCM patients. Methods: The study population was composed of 102 DCM patients. Replacement CF was evaluated qualitatively (late gadolinium enhancement - LGE) and quantitively (LGE extent); interstitial cardiac fibrosis was assessed via extracellular volume (ECV). Based on echocardiography patients were divided into normal and elevated left atrial pressure (nLAP, eLAP) groups. Results: 42 % of patients had eLAP. They displayed higher troponin and NT-proBNP. Both groups did not differ in terms of LGE presence and extent; however, eLAP patients had larger ECV: 30.1 +/- 5.6 % vs. 27.8 +/- 3.9 %, p = 0.03. Moreover, ECV itself was found to be an independent predictor of LVDD (OR = 0.901; 95 %CI 0.810-0.999; p = 0.047; normalised for LVEF and RVOT diameter). Conclusions: More than two-in-five DCM patients had at least moderate LVDD. The mere presence or extent of replacement cardiac fibrosis is similar in patients with nLAP and eLAP. On the other hand, interstitial cardiac fibrosis is more pronounced in those with a higher grade of LVDD. ECV was found to be an independent predictor of LVDD in DCM.

Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an increased risk of arrhythmias and conduction disorders. This article reviews the current understanding and management strategies for these cardiac complications, with a focus on recent advancements and clinical challenges. The prevalence and impact of atrial arrhythmias, particularly atrial fibrillation, are examined, along with considerations for stroke risk and anticoagulation therapy. The article also addresses the complexities of managing rate and rhythm control, outlining the utility and limitations of pharmacological agents and interventions such as catheter ablation. Furthermore, it reviews the challenges in the treatment of ventricular arrhythmias, including the contentious use of implantable cardioverter-defibrillators for primary and secondary prevention. Individualized approaches, considering the unique characteristics of cardiac amyloidosis, are paramount. Continuous research and clinical exploration are essential to refine treatment strategies and improve outcomes in this challenging patient population.

We would like to thank Dr. Imamura for their interest in our study and their valuable comments on diagnostics and risk stratification in Brugada syndrome (BrS) [...]

AbstractAimsThe prognostic significance of left ventricular (LV) diastolic dysfunction (LVDD) severity in patients with dilated cardiomyopathy (DCM) remains uncertain. This study aimed to evaluate the association of LVDD severity and elevated left atrial pressure (eLAP) with patient outcomes in stable, non‐acutely decompensated patients with DCM.MethodsThis single‐centre, retrospective, observational study involved 740 DCM patients (either inpatients or outpatients) managed at our tertiary cardiac centre between 2010 and 2021. Due to incomplete data, 96 patients were excluded. LVDD and eLAP were assessed using echocardiography according to the 2016 guidelines of the European Association of Cardiovascular Imaging (EACVI). The primary outcomes were all‐cause mortality and heart failure (HF)‐related mortality.ResultsThe final cohort comprised of 644 DCM patients [mean age: 52 ± 12 years, LV ejection fraction (LVEF): 26 ± 10%]. Over a median follow‐up period of 41 (18.5–66.7) months, 105 (16.3%) patients died: 8 (5.3%) patients in the normal left atrial pressure (nLAP) group and 97 (19.6%) patients in the eLAP group. eLAP was identified as an independent prognostic factor for both all‐cause mortality [hazard ratio (HR) 2.0; 95% confidence interval (CI) 1.1–3.7; P = 0.01] and HF‐related mortality (HR 2.5; 95% CI 1.01–6.5; P = 0.04), even after adjusting for LVEF and atrial fibrillation (AF) presence. Additionally, HF‐related mortality rates were significantly higher in patients with moderate to severe LVDD compared with those with mild LVDD [5 (3.3%) vs. 67 (13.6%), P < 0.05].ConclusionsThis study's findings highlight the importance of assessing the severity of LVDD in patients with DCM, which provides incremental prognostic information over LVEF.

AIMS:Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime-labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance. METHODS AND RESULTS:Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370-740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009). CONCLUSION:The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and β or pharmacological oral chaperone migalastat. Migalastat is a low-molecular-mass iminosugar, that reversibly binds to active site of amenable enzyme variants, stabilizing their molecular structure and improving trafficking to the lysosome. Migalastat was approved in the EU in 2016 and is an effective therapy in the estimated 35–50% of all patients with FD with amenable GLA gene variants. This position statement is the first comprehensive review in Central and Eastern Europe of the current role of migalastat in the treatment of FD. The statement provides an overview of the pharmacology of migalastat and summarizes the current evidence from the clinical trial program regarding the safety and efficacy of the drug and its effects on organs typically involved in FD. The position paper also includes a practical guide for clinicians on the optimal selection of patients with FD who will benefit from migalastat treatment, recommendations on the optimal selection of diagnostic tests and the use of tools to identify patients with amenable GLA mutations. Areas for future migalastat clinical research have also been identified.