BACKGROUND:Cardiac implantable electronic device (CIED) infections, particularly CIED-associated infective endocarditis (CIED-associated IE), are associated with a high 1-year mortality rate of 14%-35%, reduced quality of life, and increased burden on the healthcare system. AIMS:In this prospective, single-center, high-volume referral study, we aimed to analyze and compare 3 groups of patients who underwent transvenous lead extraction (TLE): patients with CIED-associated IE, patients with pocket infection (PI), and both. METHODS:This study included all consecutive patients with CIEDs who underwent TLE due to device-related infection at a tertiary referral hospital between 2011 and 2023. Patients were divided into 3 groups (CIED-associated IE, PI, and both indications) based on the modified Duke criteria. RESULTS:A total of 253 consecutive patients underwent TLE. Of these, 135 (53%) were treated for PI, 90 (36%) for CIED-associated IE, and 28 (11%) for both indications. Almost all procedures (97%) were completed without complications. Patients with CIED-associated IE had significantly higher mortality than patients in the CIED-associated IE + PI group, and patients in the PI group had the lowest mortality. One-year, 2-year, and 5-year overall survival rates in the CIED-associated IE group were 61%, 49%, and 32%, respectively, compared with 77%, 73%, and 56% in the CIED-associated IE + PI group and 90%, 86%, and 67% in the PI group (P <0.001). CONCLUSIONS:Patients with CIED-associated IE had almost 4-fold higher 1-year mortality compared to those with PI. Patients with CIED-associated IE and PI had about 2-fold higher 1-year mortality compared to those with PI.

PURPOSE:A high rate of coronary microcirculation dysfunction has been recently demonstrated in coronary artery aneurysm or ectasia (CAAE) in invasive assessment. We sought to analyse the diagnostic value of single-photon emission computed tomography (SPECT/CT) in patients with CAAE and to link it with their angiographic characteristics. METHODS:We analyzed 79 patients with CAAE without coronary artery disease who underwent coronary angiography assessed with quantitative coronary angiography (QCA). In all patients SPECT/CT with technetium agents was performed to assess the presence of reversible myocardial perfusion defect. RESULTS:The presence of reversible defect was found in 27 (34.2%) of the included patients. Patients with reversible defect were characterized by more frequent diabetes (55.6 vs 25%, P = 0.007). They were more often treated with insulin (14.8 vs 1.9%, P = 0.026) and non-insulin hypoglycemic drugs (40.7 vs 19.2%, P = 0.043). In patients with reversible defect there was a higher number of multiple CAAE (14.8 vs 5.8%, P = 0.044) without other significant differences in CAAE diameters. The percentage of reversible perfusion defect was inversely associated with distal reference diameter of CAAE (R = -0.342, P = 0.031). In the multivariable analysis, only diabetes was independently associated with presence of reversible perfusion defect (odds ratio [OR] 3.525, 95% confidence interval [CI] 1.240-10.019, P = 0.018). CONCLUSIONS:As has been shown for the first time in a high percentage of CAAE patients without coronary artery disease, a reversible perfusion defect in SPECT/CT is observed, which may explain their high symptomaticity. Diabetes, but not CAAE diameters, is the independent predictor of reversible perfusion defect.

IntroductionThe coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and severe aortic stenosis (AS) presents a diagnostic challenge. This study aimed to determine the prevalence of this dual pathology and to assess the effectiveness of diagnostic models in enhancing detection accuracy.MethodsWe conducted a prospective study of 104 consecutive patients with severe AS (aortic valve area <1 cm2). Comprehensive evaluation included clinical and laboratory assessments, electrocardiography, transthoracic echocardiography, planar whole-body bone scintigraphy, and chest single-photon emission computed tomography/computed tomography using technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid tracer. Patients were grouped according to the presence of ATTR-CA, and the diagnostic utility of the RAISE score, its variations, and the T-AMYLO score was evaluated.ResultsNineteen (18%) patients with AS also had ATTR-CA (ATTR-CA-AS). They were significantly older (82.6 ± 7.4 vs. 76 ± 6.9, p < 0.001), more often had arrhythmic and conduction disorders (atrial fibrillation, implanted pacemakers), and had a reduced left ventricular ejection fraction (44.6% vs. 54.7%, p = 0.03). Patients with ATTR-CA-AS more frequently presented with the low-gradient/low-flow phenotype of AS (73.7%, p = 0.009). Both NT-proBNP and troponin levels were significantly higher in patients with ATTR-CA-AS (4174.0 vs. 1,238 pg/mL; p < 0.001; and 59.6 vs. 23.3 ng/L, p < 0.001, respectively). After a 6-month follow-up, a similar number of deaths occurred in both groups, and no surgical aortic valve replacement was performed in the ATTR-CA-AS population. The eRAISE model demonstrated the highest diagnostic accuracy (AUC=0.948).ConclusionsATTR-CA is commonly observed in patients with severe AS. Implementing risk scores in routine practice could enhance the diagnostic accuracy of ATTR-CA in patients with AS, given their strong diagnostic performance and ease of assessment.

BACKGROUND AND AIMS:Severe tricuspid regurgitation (TR) is associated with increased mortality and hospitalizations for heart failure (HF). Aetiologies of TR include: secondary (atrial or ventricular), primary and cardiac implantable electronic device (CIED)-related. The aim of the study was to assess the prevalence of different TR aetiologies, as well as characteristics and treatment of patients with severe TR in a real-life setting. METHODS:This was a prospective, observational study of patients with severe TR, conducted in 18 cardiology centres. Consecutive adult patients with severe TR were included, regardless of the presence of TR symptoms and the cause of hospital admission. RESULTS:A total of 1295 patients with severe TR were enrolled (median age 76 years, 53% women). The most common reason for admission was HF decompensation (40%). Single TR aetiology was identified in 79% patients. The most frequent overlap between aetiologies included secondary ventricular and atrial TR, and was found in 11% of patients. The most common TR aetiology was secondary atrial (37%), followed by secondary ventricular (25%). Primary and CIED-related TR accounted for 10% and 15%, respectively. In 2.4% TR aetiology was not determined. Patients with secondary atrial and CIED-related TR were the oldest (79 and 78 years, respectively), and those with primary TR the youngest (68 years). Patients with CIED-related and secondary ventricular TR were more often hospitalized for HF decompensation, had more advanced HF symptoms, worse left- and right-ventricular function, worse kidney and liver function, and higher in-hospital mortality. Only 40% of patients underwent evaluation by the Heart Team and 21% were qualified for TR interventions. CONCLUSIONS:In real life, unequivocal identification of TR aetiology remains challenging. Secondary atrial TR is the most common aetiology. There are significant differences in characteristics and outcomes depending on TR aetiology. Too few patients with severe TR undergo evaluation by the Heart Team.

BACKGROUND:Cardiac resynchronization therapy (CRT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) who meet specific electrocardiographic (ECG) criteria of electrical dyssynchrony. Gated single-photon emission computed tomography (G-SPECT) is an imaging method that allows for the assessment of left ventricular mechanical dyssynchrony (LVMD); however, its predictive value for CRT response remains uncertain. This study aimed to evaluate the utility of G-SPECT in identifying LVMD and predicting CRT response in patients with HFrEF. METHODS:Patients with HFrEF and a LVEF <35% were prospectively enrolled and stratified into two groups: 60 patients CRT-eligible (Group 1) and 40 CRT-ineligible (Group 2). All patients underwent ECG, echocardiography, and G-SPECT imaging at baseline and at 6-month follow-up. LVMD was assessed using G-SPECT-derived parameters: (a) histogram bandwidth (HBW), (b) phase standard deviation (PSD), and (c) phase entropy, both at rest and under stress. CRT response was evaluated based on changes in LVEF. RESULTS:At baseline, patients in Group 1 exhibited greater LVMD as assessed by both echocardiography and G-SPECT. All G-SPECT-derived parameters, along with septal-to-posterior wall motion delay on echocardiography, were correlated with QRS duration. After CRT, LVMD significantly improved in Group 1. Super-response, defined as EF normalization, was observed in 11.9% of patients. G-SPECT-derived LVMD parameters, particularly rest PSD and entropy measures, were significant predictors of the favorable outcome of LVEF normalization. CONCLUSIONS:LVMD parameters obtained from G-SPECT were significantly correlated with electrical dyssynchrony as measured by QRS duration. Following CRT implantation, LVMD improved in parallel with increases in LVEF.

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).

Transthyretin amyloidosis (ATTR) is a fatal disorder, thus early detection of cardiac involvement is crucial for improved clinical outcomes. This study investigated the utility of left ventricular (LV) speckle-tracking-derived mechanical dispersion as a potential marker for the assessment of cardiac amyloidosis (CA) in patients with ATTR and their first-degree relatives. This prospective, single-centre study enrolled 100 adults from 2020 to 2024 (ClinicalTrials NCT05814380). Participants underwent clinical assessment, genetic testing, and [99mTc]Tc-DPD SPECT/CT. Global longitudinal strain (GLS) and mechanical dispersion were evaluated using speckle-tracking echocardiography. Patients with ATTR CA exhibited significantly impaired GLS and increased mechanical dispersion (p < 0.001). Mechanical dispersion exhibited correlations with age, New York Heart Association class, LV mass index, E/E', LV ejection fraction, GLS, levels of N-terminal pro-brain natriuretic peptide and Perugini grade (p < 0.05 for all). In univariable Cox regression, mechanical dispersion (Hazard ratio (HR) = 1.03, 95% confidence intervals (CI) 1.01-1.06, p = 0.004), normalised to heart rate mechanical dispersion (HR = 1.43, 95% CI 1.14-1.81, p = 0.002) were significant predictors of all-cause mortality. In our study increased mechanical dispersion was associated with advanced disease stages and mortality. These findings suggest that it may serve as a marker of ATTR CA.Registration: ClinicalTrials.gov Identifier: NCT05814380.

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.

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:Dilated cardiomyopathy (DCM) is a highly heterogenous condition, resulting from both genetic and non-genetic mechanisms. However, little is known about the amount, pattern, and time course profile of fibrosis in DCM patients with different etiologies. AIMS:To evaluate the type, pattern, and course of fibrosis assessed with late gadolinium enhancement (LGE) and extracellular volume (ECV) on cardiovascular magnetic resonance (CMR) in patients with DCM of different etiologies. MATERIAL AND METHODS:We prospectively enrolled 102 DCM patients (87.3% male, mean age 45.2 [11.8] years). Patients were divided into 5 etiological sub-groups: toxic, inflammatory, tachyarrhythmic, genetic, and idiopathic. All patients underwent two CMR scans at baseline and after 12 months, assessing replacement fibrosis via LGE and interstitial fibrosis via ECV. RESULTS:The distribution of etiologies was as follows: toxic (26.5%), idiopathic (26.5%), genetic (23.5%), inflammatory (13.7%), and tachyarrhythmic (9.8%). At baseline, LGE was present in 45 (44.1%) patients and in 46 out of 92 (50%) patients at 12 months. Ten patients did not complete follow-up CMR (3 died, 1 underwent heart transplantation, and 6 received implantable cardiac devices). The predominant LGE pattern was linear mid-wall (57.8%), followed by transmural (17.8%), sub-endocardial (8.9%), patchy mid-wall (6.7%), right ventricular insertion points (4.4%), and mixed pattern (4.4%). No differences in LGE presence, pattern, and localization were observed among the etiology-based DCM sub-groups. Similarly, ECV values did not differ significantly between groups. The analysis between baseline and the 12-month parameters showed that only in genetic DCM did LGE mass and extent significantly increase (6.8 [2.1-10.9] vs. 7.4 [2.5-16.9] g; and 3.0 [0.9-5.9] vs. 3.3 [1.4-9.4]%; both P <0.05). CONCLUSIONS:In DCM, LGE presence, pattern, and localization did not differ across etiological subgroups. However, myocardial fibrosis progression, reflected by increased LGE mass and extent, occurred exclusively in patients with genetic DCM.

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.