Shi J, Wu B, Zhang Y
… +6 more, Yang J, Cui Y, Yu F, Hu D, Ye H, Wang X
Int J Cardiol
· 2026 Jun · PMID 41831490
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BACKGROUND: Atrial and ventricular strains measured via speckle tracking imaging are recognized prognostic indicators for light-chain cardiac amyloidosis (AL-CA); however, the relative prognostic performance of these par...BACKGROUND: Atrial and ventricular strains measured via speckle tracking imaging are recognized prognostic indicators for light-chain cardiac amyloidosis (AL-CA); however, the relative prognostic performance of these parameters in AL-CA remains unclear. METHODS: We divided a retrospective cohort into four groups according to left ventricular longitudinal strain (LVLS) quartiles to characterize the dynamic impairment of multi-chamber strains. Critically elevated brain natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP) was defined as >700 pg/mL for BNP and/or > 8500 pg/mL for NT-proBNP. LASSO and Cox regression analyses were conducted to identify optimal echocardiographic and clinical predictors. RESULTS: Of the 78 patients included in the study, 40 (51.3%) died during follow-up (median 35.6 months, range 2.3-63.2). The prevalence of simultaneous impairment of left atrial and right heart strains increased with declining LVLS: 0% in Group 1(LVLS >14%), 20.0% in Group 2(LVLS ≤14% to >11%), 22.7% in Group 3 (LVLS ≤11% to ≥9%), and 73.6% in Group 4 (LVLS <9%). Among 19 echocardiographic and 5 clinical parameters, left atrial reservoir strain, left ventricular thickness, relative apical sparing longitudinal strain (RAS), right atrial reservoir strain (RASr) and critically elevated BNP/ NT-proBNP were potential prognostic predictors according to LASSO analysis. Multivariable Cox analysis identified RAS (hazard ratio [HR] = 1.654, 95% confidence interval [CI] = 1.001-2.732, P = 0.049), RASr (HR = 0.965, 95%CI = 0.933-0.998, P = 0.039) and critically elevated BNP/NT-proBNP (HR = 2.281, 95%CI = 1.107-4.697, P = 0.025) were independently associated with all-cause mortality in AL-CA. CONCLUSIONS: Concurrent multi-chamber strain impairment was common in AL-CA. RAS, RASr and critically elevated BNP/NT-proBNP were independently associated with all-cause mortality in patients with AL-CA.
Sogo M, Takahashi M, Morimoto T
… +5 more, Tsushima R, Sudo Y, Oka A, Ozaki M, Okawa K
Int J Cardiol
· 2026 Jun · PMID 41831489
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BACKGROUND: The use of an external loop recorder (ELR) has been introduced in the assessment of atrial fibrillation (AF) recurrences after ablation. OBJECTIVES: This study explored the prognostic impact of routine ELR as...BACKGROUND: The use of an external loop recorder (ELR) has been introduced in the assessment of atrial fibrillation (AF) recurrences after ablation. OBJECTIVES: This study explored the prognostic impact of routine ELR assessments after ablation in patients with paroxysmal AF. METHODS: A retrospective cohort study of consecutive patients with paroxysmal AF who underwent their first AF ablation was conducted. Patients were routinely evaluated with ELRs 6 months after the ablation from January 2015 to May 2018. Thereafter, the application of ELRs was discontinued due to clinical overload. According to the era in which the ELRs were routinely used, the participants were divided into two groups. We compared the 2-year incidence of the composite outcome of major adverse cardiovascular events (MACE), which included thromboembolisms, heart failure-related hospitalization, acute coronary syndrome, major bleeding, and cardiovascular-related death, between the ELR and non-ELR era groups. RESULTS: The ELR era group included 407 patients and non-ELR era group 305. The baseline characteristics were similar between the groups. The ELR era group had a significantly lower cumulative incidence of MACE than the non-ELR era group (3.3% vs. 6.6%, log-rank, p = 0.033). The ELR was found to be an independent predictor of MACE (adjusted hazard ratio: 0.46, 95% confidence interval: 0.22-0.97, p = 0.042). CONCLUSIONS: Routine evaluations of AF recurrence using an ELR 6 months after ablation were associated with a lower 2-year incidence of MACE in patients with paroxysmal AF.
Kok TF, Abou Kamar S, Suthahar N
… +10 more, Wemelsfelder S, Barendse RJ, Holtrop J, Dorresteijn JAN, de Boer RA, van der Boon RMA, van Dalen BM, Bruining N, Boersma E, Kardys I
Int J Cardiol
· 2026 Jun · PMID 41819192
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BACKGROUND: Studies on multiple serially measured blood biomarkers and adverse outcomes in patients with heart failure (HF) are scarce and restricted to research settings. Prognostic estimates based on serial measurement...BACKGROUND: Studies on multiple serially measured blood biomarkers and adverse outcomes in patients with heart failure (HF) are scarce and restricted to research settings. Prognostic estimates based on serial measurements could provide a scientifically substantiated, uniform approach to risk stratification and timing of treatment. We use an exploratory and hypothesis-generating approach to assess the predictive ability of serially measured biomarkers, commonly collected during usual care, for adverse events in a real-world population of ambulant patients with HF with reduced ejection fraction (HFrEF) and HF with mildly reduced ejection fraction (HFmrEF). METHODS: We included ambulatory HFrEF-HFmrEF patients who attended an outpatient hospital visit between 2017 and 2022. Data on blood biomarkers, clinical characteristics and clinical outcome were extracted from electronic health records. Joint modelling was applied to investigate associations between time-varying blood biomarkers and the composite endpoint of mortality, LVAD implantation and heart transplant. RESULTS: We included 1353 patients; 66.8% men; median (P25, P75) age 62 (51, 71) years. During a median follow-up of 3.30 (1.62, 4.65) years, 387 (28.6%) experienced the endpoint. Temporal trajectories of 30 blood biomarkers were significantly associated with the endpoint. After correcting for clinical characteristics, associations persisted in multiple-biomarker models for serially measured NT-proBNP, hs-TnT, and CRP, as well as liver biomarkers, kidney biomarkers, and blood count parameters. Serial measurements increased model performance compared to baseline measurements, with AUCs up to 0.83 for multiple-biomarker models. CONCLUSION: Real-life, serially measured laboratory data predict adverse events in an ambulatory HFrEF-HFmrEF population, with good internal model performance. Thus, making use of laboratory values already present in electronic medical records, could inform risk stratification without any extra effort.
Cosentino N, Velato L, Bonomi A
… +10 more, Morocutti C, Trombara F, Genovese S, Molinari C, Lucci C, Grazi M, Assanelli E, Sorrentino S, Pontone G, Marenzi G
Int J Cardiol
· 2026 Jun · PMID 41819191
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BACKGROUND: Obese patients often show better short-term outcomes in cardiovascular disease, but the impact of severe obesity on acute myocardial infarction (AMI) outcomes is unclear. This study explored the relationship...BACKGROUND: Obese patients often show better short-term outcomes in cardiovascular disease, but the impact of severe obesity on acute myocardial infarction (AMI) outcomes is unclear. This study explored the relationship between severe obesity and in-hospital outcomes in AMI, with a focus on inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP). METHODS: We performed a retrospective analysis of 3887 AMI patients admitted to a tertiary cardiac center from 2010 to 2025. Patients were stratified by body mass index (BMI). The primary endpoint was a composite of in-hospital mortality, acute heart failure, and acute kidney injury. RESULTS: The primary endpoint incidence was similar across BMI groups up to BMI <35 kg/m, then significantly increased in patients with BMI ≥35 kg/m (20% vs. 31%; p = 0.002). Severe obesity (BMI >35 kg/m; n = 158) was associated with a two-fold increased risk of adverse outcomes (OR 2.21, 95%CI 1.04-2.97). After adjusting for admission hs-CRP, the predictive value of severe obesity was lost, while hs-CRP remained a strong independent predictor (OR 1.02, 95%CI 1.01-1.03 for every two-unit increase). Patients with severe obesity and elevated hs-CRP (≥2 mg/dL) had the highest event rate (35%). Path analysis showed that 63% of severe obesity's effect on adverse outcomes was mediated by inflammation. CONCLUSIONS: Our findings show that severe obesity is a significant risk factor for adverse in-hospital outcomes in AMI, challenging the "obesity paradox." This increased risk is largely mediated by systemic inflammation.
Angiolillo DJ, Erlinge D, Gale CP
… +4 more, Gorog DA, Ibañez B, Musumeci G, Valgimigli M
Int J Cardiol
· 2026 Jun · PMID 41819190
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BACKGROUND: The 2023 European Society of Cardiology (ESC) guidelines for acute coronary syndromes (ACS) maintained a Class III recommendation against routine pretreatment with oral P2Y inhibitors in non-ST-segment elevat...BACKGROUND: The 2023 European Society of Cardiology (ESC) guidelines for acute coronary syndromes (ACS) maintained a Class III recommendation against routine pretreatment with oral P2Y inhibitors in non-ST-segment elevation ACS (NSTE-ACS) and downgraded pretreatment in ST-segment elevation myocardial infarction (STEMI) to Class IIb. This study evaluated real-world uptake of these recommendations across Europe. METHODS: READAPT-2 was a cross-sectional survey conducted one year after the release of the 2023 ESC guideline update, involving 1101 cardiologists from 21 European countries. Data from READAPT-2 were compared with those from the earlier READAPT-1 survey to evaluate temporal trends. The survey collected information on physician demographics, hospital characteristics, pretreatment practices, and preferences regarding antiplatelet therapy. RESULTS: Most respondents (83%) reported adhering to the Class III recommendation against routine pretreatment in NSTE-ACS. Overall, pretreatment rates in NSTE-ACS declined in READAPT-2 compared to READAPT-1, suggesting improved adherence to guideline recommendations. Pretreatment in STEMI was variable, with nearly 25% of respondents reporting routine pretreatment. Ticagrelor remains the most widely used oral P2Y inhibitor despite ESC guideline preference for prasugrel for percutaneous coronary intervention. Use of intravenous agents, including cangrelor and GPIIb/IIIa inhibitors, remains limited to around 10% of cases. Overall, there was significant heterogeneity in the implementation of the 2023 ESC recommendations across Europe. CONCLUSION: Findings from READAPT-2 reveal a persistent gap between guideline awareness and clinical practice, highlighting the need for tailored implementation and education strategies to support a broader guideline uptake.
Ozawa T, Goto K, Hirokane A
… +9 more, Mizuno T, Miura K, Kobayashi K, Kikuta Y, Sato K, Taniguchi M, Hiramatsu S, Takebayashi H, Haruta S
Int J Cardiol
· 2026 Jun · PMID 41795855
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BACKGROUND AND AIMS: Coronary spasm may contribute to the pathogenesis of myocardial infarction with obstructive coronary artery disease (MICAD) and warrants close consideration in myocardial infarction with non-obstruct...BACKGROUND AND AIMS: Coronary spasm may contribute to the pathogenesis of myocardial infarction with obstructive coronary artery disease (MICAD) and warrants close consideration in myocardial infarction with non-obstructive coronary arteries (MINOCA). However, data concerning the significance of coronary spasm in acute myocardial infarction (AMI) are limited. We assessed the prognostic significance of provocative spasm tests among MICAD and MINOCA patients. METHODS AND RESULTS: We retrospectively screened 731 consecutive patients with AMI, of whom 267 (MICAD, n = 198; MINOCA, n = 69) underwent an invasive provocative spasm test. The primary endpoint was major adverse cardiac events (MACE). Provocative spasm testing was positive in 143 (72.2%) of MICAD group and 33 (47.8%) of MINOCA group. During a median follow-up of 48 months, MACE occurred in 31 patients (15.7%) in the MICAD group compared with 4 patients (5.8%) in the MINOCA group (p = 0.037). Spasm-positive patients had a significantly higher incidence of MACE compared with spasm-negative patients in both the MICAD group (27 [18.9%] vs. 4 [7.3%]; p = 0.044) and MINOCA group (4 [12.1%] vs. 0 [0%]; p = 0.047). Kaplan-Meier survival analysis of the 4 groups categorized by type of AMI (MICAD or MINOCA) and presence of provoked coronary spasm showed that spasm-positive status was associated with lower MACE-free survival across both AMI subtypes (log-rank p = 0.011). In multivariable analysis, provoked coronary spasm was independently associated with MACE in the MICAD group (hazard ratio, 3.40; 95% confidence interval, 1.20-12.25; p = 0.019). CONCLUSION: Provocative spasm tests could provide prognostic stratification for AMI patients, irrespective of whether they present with MICAD or MINOCA.
Yang X, Wang L, Liu Y
… +6 more, Guan H, Wu Y, Wang B, Zhu L, Zhang S, Li Q
Int J Cardiol
· 2026 Jun · PMID 41795854
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Endothelial cells (ECs), as integral components of the vascular intima, play a pivotal role in the regulation of vascular tone, maintenance of blood flow homeostasis, and control of inflammatory responses. In response to...Endothelial cells (ECs), as integral components of the vascular intima, play a pivotal role in the regulation of vascular tone, maintenance of blood flow homeostasis, and control of inflammatory responses. In response to pathological insults such as oxidative stress, mitochondrial dysfunction, and persistent inflammatory stimulation, ECs undergo senescence-associated phenotypic transitions, characterized by cell cycle arrest, endothelial dysfunction, and the establishment of a chronic pro-inflammatory microenvironment. Senescent ECs exacerbate inflammatory signaling, impair vascular homeostasis, and reshape intercellular communication networks, thereby constituting a fundamental pathological mechanism underlying the development and progression of cardiometabolic diseases, including atherosclerosis (AS), diabetes mellitus (DM), and hypertension (HTN). This review comprehensively summarizes the major triggers, molecular regulatory pathways, and functional consequences of endothelial cell senescence, with a particular focus on the central role of inflammation in mediating senescence-driven cardiometabolic disease progression. Furthermore, potential therapeutic strategies targeting endothelial cell senescence are briefly discussed, providing theoretical insights for the prevention and management of cardiometabolic disorders.
Arcari L, Camastra G, Sclafani M
… +6 more, Ciolina F, Belmonte E, Castiello T, Danti M, Sbarbati S, Cacciotti L
Int J Cardiol
· 2026 Jun · PMID 41791554
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BACKGROUND: SGLT2 inhibitors are approved for heart failure treatment, however, few data are available in patients with takotsubo syndrome (TTS). We aim to evaluate the safety, tolerability and effects of SGLT2 inhibitor...BACKGROUND: SGLT2 inhibitors are approved for heart failure treatment, however, few data are available in patients with takotsubo syndrome (TTS). We aim to evaluate the safety, tolerability and effects of SGLT2 inhibitors therapy on myocardial recovery and inflammation in acute TTS. METHODS: We compared n = 22 SGLT2 inhibitors treated TTS patients (Dapagliflozin n = 13, Empagliflozin n = 9) with n = 44 1:2 propensity-score matched untreated. Treated patients were mostly consecutively enrolled after implementation of 2023 ESC heart failure guidelines. All underwent cardiac magnetic resonance (CMR) imaging with T2 mapping within 7 days of hospital admission. SGLT2 inhibitors were first administered within 6 h of admission. The primary endpoint was myocardial edema burden as measured by CMR septal T2 mapping. Secondary endpoints were global T2 mapping and left ventricular ejection fraction (LVEF). RESULTS: After matching, all variables associated with recovery of LV function and edema were proportionally distributed between groups, including age, sex, echocardiographic LVEF on admission, comorbidities and time from admission to CMR imaging. At CMR imaging, treated patients showed similar basal (p = 0.956) while significantly lower septal (56 ms vs 59 ms, p = 0.034) and global (55 ms vs 57 ms, p = 0.049) T2 mapping values, and higher LVEF (55% vs 50%, p = 0.048) compared to controls. We observed no drug-related adverse effects during hospitalization, discontinuation rate at follow-up was 4.5%. CONCLUSIONS: In acute TTS, SGLT2 inhibitors treatment was safe and well tolerated. CMR within one week of hospitalization showed lower myocardial edema burden and higher LVEF in SGLT2 inhibitors treated patients, suggesting quicker recovery of myocardial function.
Bellisario I, Aimo A, Todiere G
… +13 more, Alderotti B, Gueli IA, Grigoratos C, Ricci F, De Gori C, Muca M, Botto N, Vittorini S, Gallina S, Passino C, Emdin M, Clemente A, Barison A
Int J Cardiol
· 2026 Jun · PMID 41785971
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BACKGROUND: Dilated cardiomyopathy (DCM) and non-dilated left ventricular (LV) dysfunction (NDLVD) comprise patients with heterogeneous genetics and prognosis. This study aimed to investigate genotype-phenotype relations...BACKGROUND: Dilated cardiomyopathy (DCM) and non-dilated left ventricular (LV) dysfunction (NDLVD) comprise patients with heterogeneous genetics and prognosis. This study aimed to investigate genotype-phenotype relationship and prognosis in DCM and NDLVD. METHODS: Patients with a comprehensive clinical, genetic and CMR assessment, with LV ejection fraction (LVEF) <57% were included. Patients were categorized into DCM or NDLVD according to LV dilation (end-diastolic volume >96 ml/m in women, >105 ml/m in men). Patients with coronary artery disease, valvular, congenital, hypertrophic, inflammatory or infiltrative disease were excluded. The primary endpoint was a composite of cardiovascular death, sustained ventricular arrhythmias or appropriate defibrillator intervention. The secondary endpoint included also heart failure hospitalizations. RESULTS: The cohort included 249 patients (age 53±14 years, 166 males) with median LVEF 45% (IQ range 33-51%), divided in 143 DCM and 106 NDLVD patients. Pathogenic/likely pathogenic mutations were present in 67 (27%), but were neither associated with phenotype, nor with prognosis. During a 72 (35-119) month follow-up, 54 patients (22%) experienced the composite event, 67 patients (27%) the secondary endpoint. At multivariate analysis, male sex, disease duration, natriuretic peptides, non-sustained ventricular arrhythmias, LVEF, left atrial volume and CMR-derived LV filling pressure predicted the primary endpoint (p<0.05). Moreover, disease duration, natriuretic peptides, non-sustained ventricular arrhythmias, right ventricular ejection fraction and CMR-derived LV filling pressure predicted the secondary endpoint (p<0.05). CONCLUSIONS: In this cohort of patients with non-ischaemic cardiomyopathy, biventricular systolic function, left atrial volume and CMR-derived LV filling pressure were predictors of poor prognosis, while gene mutations were not.
Linderhof MHC, Freriks AI, van Doorn ECH
… +9 more, Zhang C, Dai L, Nguyen HH, Nguyen DT, Stindt TDA, Taverne YJHJ, van Schie MS, de Groot NMS, van den Bosch AE
Int J Cardiol
· 2026 Jun · PMID 41785970
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BACKGROUND: Non-invasive assessment of arrhythmogenic substrates underlying persistent atrial fibrillation (AF) could potentially provide patient-tailored ablation therapy. Speckle Tracking Echocardiography (STE) is an i...BACKGROUND: Non-invasive assessment of arrhythmogenic substrates underlying persistent atrial fibrillation (AF) could potentially provide patient-tailored ablation therapy. Speckle Tracking Echocardiography (STE) is an imaging modality, which can be used to assess atrial biomechanical function. As biomechanical dysfunction is driven by electrical dysfunction, STE may serve as a diagnostic tool to detect AF-related arrhythmogenic substrates. PURPOSE: To investigate which non-invasive STE-derived measurements correlate best with invasively determined electrophysiological properties as a first step towards developing a novel, non-invasive diagnostic tool. METHODS: Intraoperative epicardial mapping during sinus rhythm was performed in adult patients (n = 19, mean age: 63 ± 13 years) undergoing cardiac surgery. Potential voltages, potential morphology, conduction velocity (CV), conduction block (CB: ≥12 ms) and uninterrupted lines of conduction delay (CD: ≥7 ms) and CB (CDCB) were quantified. Atrial end-diastolic reservoir and contractile strain values were used to calculate area under the curve, and the slopes of both the reservoir and contractile phases. RESULTS: Steeper LA reservoir strain slopes were associated with more CDCB, greater CV variation and lower overall CV around the pulmonary veins (ρ = 0.55, p < 0.001; ρ = 0.64, p = 0.004; ρ = -0.55, p = 0.019). A larger right atrial volume indexed correlated with more CDCB, fractionated potentials and reduced CV on Bachmann's Bundle (ρ = 0.64, p = 0.008; ρ = 0.52, p = 0.037; ρ = -0.61, p = 0.011). Right atrial end-systolic time strongly correlated with CB, low-voltage area's and fractionated potentials on Bachmann's Bundle (ρ = 0.68, p < 0.001; ρ = -0.63, p = 0.009; ρ = 0.53, p = 0.020). CONCLUSION: STE timing and slope parameters correlated most strongly with atrial electrophysiological properties, supporting their potential as non-invasive markers for arrhythmogenic substrates and patient-tailored ablation therapy.
Boursiquot BC, Khan MA, Teruya S
… +2 more, Hanna M, Maurer MS
Int J Cardiol
· 2026 Jun · PMID 41780692
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INTRODUCTION: Black individuals have significantly lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than White individuals in the general population. Racial differences in NT-proBNP have not been...INTRODUCTION: Black individuals have significantly lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than White individuals in the general population. Racial differences in NT-proBNP have not been well-studied in transthyretin amyloid cardiomyopathy (ATTR-CM), but these differences may be clinically relevant since the NT-proBNP cut-offs used for disease staging and clinical trial inclusion are irrespective of race. METHODS: This is a multicenter retrospective study of Black and White patients diagnosed with wild type ATTR-CM from January 2018 through September 2025. The baseline NT-proBNP level was obtained within 2 months of diagnosis. Linear regression models were used to assess the association between race and baseline NT-proBNP. RESULTS: We included 1350 patients (1224 White and 126 Black). Compared to the White group, the Black group had a higher proportion of female patients, a lower prevalence of AF, higher loop diuretic requirements, and worse left ventricular systolic function. The Black group also had a significantly higher unadjusted geometric mean NT-proBNP level than the White group, but this difference was attenuated after multivariable adjustment (relative difference 16%, P = 0.08). CONCLUSIONS: In this study of Black and White patients with wild type ATTR-CM, racial differences in NT-proBNP levels were explained in part by differences in clinical characteristics that may reflect ATTR-CM disease severity.
Spanjersberg TCF, Hassanzada F, Jongbloed JDH
… +8 more, Dooijes D, van Tintelen JP, Asselbergs FW, van der Harst P, van Steenbeek FG, Harakalova M, van Spaendonck-Zwarts KY, van Vugt M
Int J Cardiol
· 2026 Jun · PMID 41780691
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BACKGROUND: The TNNT2 (NM_001276345.2):c.862C>T, p.Arg288Cys variant has conflicting pathogenicity classifications. It is reported in individuals with severe hypertrophic cardiomyopathy (HCM) yet also occurs in the gener...BACKGROUND: The TNNT2 (NM_001276345.2):c.862C>T, p.Arg288Cys variant has conflicting pathogenicity classifications. It is reported in individuals with severe hypertrophic cardiomyopathy (HCM) yet also occurs in the general population at a frequency challenging its presumed pathogenicity and creating uncertainty for genetic counseling. Therefore, the aim of this study was to evaluate its clinical relevance. METHODS: We analyzed 592 carriers, 3,096 matched non-carriers, and 641 individuals with HCM from the UK Biobank, assessing cardiac imaging, electrocardiography, and clinical data. In addition, we provide a detailed description of seven Dutch probands and their relatives. RESULTS: HCM prevalence was 0.5% (3/592) in carriers versus 0.1% (3/3,096) in non-carriers (p = 0.032). Carriers showed preserved cardiac structure but higher mitral and tricuspid annular plane systolic excursion, suggesting subtle functional differences. Dutch families demonstrated variable expressivity and incomplete HCM penetrance. Under TNNT2-specific ACMG/ClinGen criteria, the variant does not meet thresholds for pathogenicity because of its population frequency, limited segregation evidence, and only modest functional data. These findings highlight the challenge of applying traditional Mendelian frameworks to variants with low penetrance. CONCLUSION: Although ACMG/ClinGen criteria classify TNNT2 p.Arg288Cys as likely benign, integrating population imaging, functional data, and family observations provides a more nuanced interpretation. Together, these findings support its classification as an intermediate-effect variant that modulates HCM risk in the presence of additional genetic or clinical factors.
Kwiatkowski G, Czyzynska-Cichon I, Gdula AM
… +5 more, Zakrzewska A, Tyrankiewicz U, Sitek B, Jasztal A, Chłopicki S
Int J Cardiol
· 2026 Jun · PMID 41765145
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BACKGROUND: Coronary microvascular dysfunction (CMD) is increasingly recognized as a mechanistically relevant contributor to HFpEF, yet the temporal and causal relationship between early functional CMD, coronary microvas...BACKGROUND: Coronary microvascular dysfunction (CMD) is increasingly recognized as a mechanistically relevant contributor to HFpEF, yet the temporal and causal relationship between early functional CMD, coronary microvascular endothelial barrier injury, and fibrotic remodeling remains incompletely defined. The primary aim was to test whether CMD causally contributes to HFpEF-like remodeling and functional impairment in an isoprenaline (ISO) mouse model. A secondary aim was to determine whether empagliflozin (SGLT2i) or resolvin D2 modulates inflammatory and endothelial mechanisms of CMD. METHODS: Mice received Control, ISO, ISO + empagliflozin, or ISO + resolvin D2 (n = 5-6/group). ISO (100 mg·kg·day, s.c.) was given for 5 days. On days 7, 14, and 21 we assessed LV structure/function by cine-MRI, CFR by Doppler, diastolic indices by Doppler, and endothelial permeability/NO-dependent function by dynamic contrast-enhanced MRI (gadolinium-albumin) and L-NAME T mapping. Treatments were given days 7-21. RESULTS: ISO caused hypertrophy with preserved ejection fraction, diastolic dysfunction, and reduced exercise capacity. Resting coronary flow increased by day 7 with preserved hyperemic flow, lowering CFR before fibrosis or endothelial barrier failure. By day 21, permeability rose with inflammatory activation, blunted NO-mediated response, and perivascular/interstitial fibrosis. Empagliflozin lowered resting flow, normalized CFR, reduced endothelial permeability and inflammatory signaling, limited fibrosis, and improved diastolic indices and LV strain. Resolvin D2 reduced inflammatory markers but did not consistently restore CFR, permeability, or diastolic indices. CONCLUSIONS: Short-term ISO causes progressive CMD, and empagliflozin reverses key CMD features, supporting direct coronary microvascular modulation as a mechanism of SGLT2i benefit in HFpEF in this animal model.
Cheng A, Wu Y, Mou F
… +26 more, Zhou J, Gao H, Hu T, Sun D, Wang Q, Jiang H, Yin Z, Wen S, Jin Y, Chen H, Zhong L, Hu S, Liu J, Fu G, Zhang R, He X, Zhu B, Jiang Z, Xia J, Garg S, Wang D, Onuma Y, Serruys PW, Wang R, Gao C, Tao L
Int J Cardiol
· 2026 May · PMID 41765144
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BACKGROUND: The safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of proximal left anterior descending (LAD) lesions remain unclear. We aim to assess the prognosis of DCB versus drug-eluting...BACKGROUND: The safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of proximal left anterior descending (LAD) lesions remain unclear. We aim to assess the prognosis of DCB versus drug-eluting stent (DES) in treating de novo proximal LAD lesions. METHODS: In this prespecified, exploratory subgroup analysis of the investigator-initiated, multicenter, randomized, non-inferiority REC-CAGEFREE I trial, 2272 patients were stratified into two groups based on whether target lesion was located in proximal LAD. The primary endpoint was device-oriented composite endpoint (DoCE, a composite of cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization) at 2 years. RESULTS: Of 2272 patients randomized, 688 (30.3%) had target lesion in proximal LAD. In patients with proximal LAD lesions, compared to DES treatment, DCB treatment had a higher risk of 2-year DoCE (8.8% versus 3.4%, HR:2.68, 95%CI:1.34-5.35, P = 0.008). Similar results were observed in patients with non-proximal LAD lesions (DCB versus DES: 5.4% versus 3.3%, HR:1.72, 95%CI:1.04-2.85, P = 0.038). No significant interaction was observed between the lesion location and the treatment strategy (DES/DCB) (P = 0.257). In patients with DCB treatment, proximal LAD had a higher risk of DoCE compared to non-proximal LAD (8.8% vs. 5.4%, HR:1.68, 95%CI:1.01-2.81, P = 0.049). CONCLUSIONS: For patients with de novo, non-complex coronary artery disease, DCB was associated with a higher 2-year risk of DoCE than DES across all lesion locations, with a numerically larger effect in proximal LAD. Due to the exploratory nature of the analysis, the results should be interpreted cautiously and considered hypothesis-generating.
Sans-Roselló J, Fernández-Peregrina E, Kuku KO
… +9 more, Torres-Ruiz G, Sionis A, Ribas-Closa A, Fernández-Martínez J, Kardenass AE, Cahís-Vela J, Cabrera-Fernández MA, Martínez-Rubio A, García-García HM
Int J Cardiol
· 2026 Jun · PMID 41765143
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BACKGROUND: Takotsubo syndrome (TTS) may be complicated by cardiogenic shock (CS), a life-threatening condition that worsens prognosis. Whether the timing of CS onset-at admission or during hospitalization-provides progn...BACKGROUND: Takotsubo syndrome (TTS) may be complicated by cardiogenic shock (CS), a life-threatening condition that worsens prognosis. Whether the timing of CS onset-at admission or during hospitalization-provides prognostic information beyond shock severity remains uncertain. METHODS: We conducted a retrospective multicenter cohort study including 1079 consecutive patients with TTS admitted between 2012 and 2024. Patients were classified as having CS at admission, CS developing during hospitalization, or no CS. Shock severity was assessed using the Society for Cardiovascular Angiography and Interventions (SCAI) classification. The primary endpoint was 1-year major adverse cardiac events (MACE), including all-cause death, heart failure events, rehospitalization for arrhythmias, stroke, or myocardial infarction. Kaplan-Meier and multivariable Cox regression evaluated the association between CS timing and outcomes. RESULTS: CS occurred in 191 patients (17.7%), including 107 at admission and 84 during hospitalization. In-hospital mortality was higher in patients with CS than in those without CS (13.2% vs 1.6%; p < 0.001). Patients with CS at admission had higher in-hospital mortality and 1-year MACE compared with those who developed CS during hospitalization and those without CS. After adjustment, CS at admission remained an independent predictor of 1-year MACE (HR 2.91, 95% CI 1.54-5.48; p = 0.001), whereas CS developing during hospitalization was not independently associated with long-term outcomes. CONCLUSIONS: CS at admission identifies a high-risk TTS phenotype with sustained prognostic impact, whereas CS during hospitalization does not independently influence long-term outcomes. Integrating CS timing into early assessment may improve risk stratification and guide monitoring and escalation strategies in acute TTS.
Yamamoto MH, Mizukami T, Mori H
… +29 more, Kobayashi N, Takano M, Kondo S, Sugiyama T, Kakuta T, Wakabayashi K, Suwa S, Dohi T, Suzuki H, Kimura S, Yamaguchi M, Nakamura S, Naganuma T, Higuma T, Yamaguchi J, Yonetsu T, Ikari Y, Yamashita J, Kondo T, Honye J, Ashikaga T, Ochiai M, Mitsumata K, Yasuhara S, Otake H, Hibi K, Nanasato M, Shinke T, TACTICS Investigators
Int J Cardiol
· 2026 Jun · PMID 41765142
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BACKGROUND: Stent expansion is a crucial determinant of chronic coronary syndrome outcomes; however, its clinical impact and factors limiting optimal expansion in acute coronary syndrome (ACS) treated with optical cohere...BACKGROUND: Stent expansion is a crucial determinant of chronic coronary syndrome outcomes; however, its clinical impact and factors limiting optimal expansion in acute coronary syndrome (ACS) treated with optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) remain unclear. METHODS: This post-hoc analysis of the prospective, multicenter TACTICS registry included 581 patients with OCT-identified atherothrombotic ACS. Suboptimal OCT findings were defined as minimum stent area (MSA) ≤ 4.5 mm, MSA < 70% of the mean reference lumen area, reference lumen narrowing, stent-edge dissection, stent malapposition, or tissue protrusion. The primary endpoint was 2-year device-oriented cardiovascular events (DoCE)-cardiovascular death, target-vessel myocardial infarction (TVMI), or ischemia-driven target lesion revascularization (TLR)-adjudicated by an independent committee. RESULTS: DoCE occurred in 5.3% of patients, and among suboptimal OCT parameters, only MSA ≤ 4.5 mm was associated with DoCE (hazard ratio, 2.31; 95% confidence interval 1.14-4.68; P = 0.020). Patients with MSA ≤ 4.5 mm had a higher incidence of DoCE than those with MSA > 4.5 mm (8.9% vs. 4.0%; log-rank P = 0.017), mainly driven by ischemia-driven TLR (5.1% vs. 1.9%; log-rank P = 0.032), with a trend toward higher incidence of TVMI (2.5% vs. 0.7%; log-rank P = 0.069). In multivariable logistic regression analysis, independent predictors of MSA ≤ 4.5 mm were smaller distal reference lumen area, maximum calcium arc ≥180°, and non-ST-segment elevation myocardial infarction. CONCLUSION: In patients with ACS undergoing OCT-guided PCI, an MSA ≤ 4.5 mm was independently associated with higher DoCE risk. Predictors of suboptimal stent expansion may underlie the increased risk of adverse outcomes despite OCT guidance. CLINICAL TRIAL REGISTRATION:URL: https://www.umin.ac.jp/ctr/index.htm; unique identifier: UMIN000039050.
Imazio M, Jahnsen V, Merlo M
… +21 more, Aimo A, Autore C, Barison A, Bauce B, Biagini E, Bobbio E, Cappelli F, Castelletti S, Collini V, D'Ascenzi F, De Gregorio C, Grottaglie SD, Marzo F, Musumeci B, Ricci F, Venturelli F, Pedrinelli R, Paolillo S, Perrone-Filardi P, Limongelli G, Sinagra G
Int J Cardiol
· 2026 May · PMID 41747776
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Inflammatory cardiomyopathy (iCMP) usually represents the chronic, hypokinetic phenotype within the myocarditis spectrum, characterized by persistent myocardial inflammation, systolic ventricular dysfunction, and adverse...Inflammatory cardiomyopathy (iCMP) usually represents the chronic, hypokinetic phenotype within the myocarditis spectrum, characterized by persistent myocardial inflammation, systolic ventricular dysfunction, and adverse remodelling. It frequently evolves from prior acute or subacute myocarditis and is associated with significantly worse outcomes, including progression to dilated cardiomyopathy, heart failure, and arrhythmias. The condition arises from heterogeneous causes-infectious, autoimmune, or idiopathic-and may be influenced by genetic susceptibility, supporting a two-hit model in which environmental triggers interact with pathogenic variants. Diagnosis requires a multimodal approach. While clinical presentation is variable and often non-specific, cardiac magnetic resonance (CMR) provides essential tissue characterization, enabling detection of inflammation and fibrosis. Endomyocardial biopsy (EMB) remains critical for defining histologic subtype, identifying viral genomes, and guiding targeted therapy, especially in intermediate- or high-risk cases. Genetic testing assists in differentiating inherited CMPs and recognizing forms with distinctive inflammatory behavior, such as desmoplakin CMP. Management focuses on guideline-directed medical therapy for heart failure and treatment of underlying aetiologies. In biopsy-proven, virus-negative iCMP, immunosuppressive therapy may improve ventricular function and limit adverse remodelling, while antiviral strategies remain reserved for selected virus-positive cases. Arrhythmia management, including ICD implantation, is essential in patients with substantial fibrotic burden or arrhythmias. Prognosis depends on ventricular function, extent of fibrosis, viral persistence, arrhythmic burden, and recurrence of inflammatory "hot phases." Lifelong follow-up is warranted. This position paper provides a comprehensive framework for the diagnosis, risk stratification, and management of iCMP, highlighting current evidence, guideline alignment, and remaining gaps.