BACKGROUND:Nonobstructive hypertrophic cardiomyopathy (nHCM) is associated with significant morbidity with no approved treatment. Aficamten is a cardiac myosin inhibitor targeting excess contractility and diastolic impairment, the predominant mechanism responsible for adverse outcomes in nHCM. In the ACACIA-HCM trial (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints in Adults With Non-Obstructive HCM; URL: https://www.clinicaltrials.gov; Unique identifier: NCT06081894), aficamten significantly improved outcomes in patients with nHCM versus placebo. To contextualize the observed treatment effects, we performed a responder analysis integrating multiple clinically relevant measures. METHODS:Patients with symptomatic nHCM were randomized to daily aficamten (n=258) or placebo (n=259) assessed at week 36, including (1) symptom burden (≥1 improvement in New York Heart Association class or reported improvement in Patient Global Impression of Change); (2) exercise capacity (≥0.5 mL/kg per min in peak oxygen uptake); (3) >10% decrease in left atrial volume index; (4) >10% improvement in septal early diastolic mitral annular velocity (e'); (5) ≥50% reduction in NT-proBNP (N-terminal pro-B-type natriuretic peptide). Overall clinical response was classified by the number of favorable outcomes achieved: nonresponder (none), limited (1 or 2), partial (3 or 4), or complete (all 5). RESULTS:At 36 weeks, a greater proportion of patients treated with aficamten versus placebo experienced improvements in symptom burden (71% versus 53%), peak exercise capacity (45% versus 37%), left atrial volume index (31% versus 23%), septal e' (51% versus 26%), and NT-proBNP (63% versus 5%) (P<0.05 for all except peak oxygen uptake, P=0.1). Number needed to treat for aficamten ranged from 1.7 (NT-proBNP reduction) to 14 (peak oxygen uptake improvement) relative to placebo. A partial or complete clinical response (≥3 outcomes) was achieved in 53% of patients on aficamten versus 14% on placebo (P<0.001). CONCLUSIONS:In patients with nHCM, aficamten was associated with improvements across a broad range of clinically relevant measures including symptom burden and diastolic function. These results underscore a potential benefit of aficamten in the population of patients with nHCM. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06081894.

BACKGROUND:Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. METHODS:In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status). RESULTS:A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively. CONCLUSIONS:Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).

Background/objectives:In recent years, novel echocardiographic parameters, known as myocardial work (MW) parameters, have been introduced into clinical practice for the assessment of contractile function. This study aimed to provide a technical characterization of the interrelations among these MW parameters and evaluate their differences between patients with non-obstructive (nHCM) and obstructive hypertrophic cardiomyopathy (oHCM). Patients and methods:One-hundred-eighteen patients with HCM, including 68 nHCM and 50 oHCM patients were assessed. Global longitudinal strain (GLS) and derived global MW parameters-including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE)-were determined by 2D-speckle tracking echocardiography. Results:In all HCM cohorts, GLS demonstrated a strong, significant correlation with GWI and GCW (r: -0.619 to -0.818), whereas the correlation between GLS and GWW was considerably weaker (r: 0.320 to 0.373), consistent in both univariate correlation and multiple regression analyses. A strong, significant correlation was observed between GWI and GCW, and a significant correlation existed between GWW and GWE. Within HCM subgroups characterized by increasing left ventricular outflow tract (LVOT) gradients, GWI/GCW values exhibited "pseudonormalization" in the obstructive HCM groups, due to the offsetting effects of the nominal decrease in GLS and the nominal increase in LVOT gradient. In contrast, GWW values increased gradually with increasing LVOT gradients, and the difference compared to controls was significant even in the HCM group with LVOT gradients <10 mmHg. Conclusions:Given the strong correlation between GLS and GWI/GCW, it is probable that changes in GLS would result in corresponding changes in GWI/GCW, potentially limiting the incremental discriminatory value of these parameters beyond GLS. GWW appears to be the most independent MW parameter from GLS in patients with hypertrophic cardiomyopathy as it weakly correlates with GLS, unlike GWI/GCW.

Abstract Background Sarcomere gene mutations is hypertrophic cardiomyopathy (HCM) can have prognostic value and role in risk assessment, according to numerous studies. In our previous investigations, we confirmed that echocardiographic parameters of left ventricular (LV) myocardial work (MW) derived from the non-invasive pressure-strain curve were reduced in patients with HCM, especially in the case of clinical features with advanced disease. The aim of our present work was to investigate the MW parameters in genotyped HCM patients. Patients and Methods We examined 75 genotyped HCM patients [48 men (64%), age 51±12 years], who underwent standard and 2D-speckle tracking echocardiography. The patients were divided into sarcomere mutation positive (P/LP+, n=32) and mutation negative (P/LP-, n=43) groups based on carrying a pathogenic/probably pathogenic (P/LP) sarcomere gene variant. Later we extended our examination to patients with variants of unknown significance (VUS). Results There was no significant difference between the demographic (age, gender, BMI, BSA) and laboratory (troponin T, NTproBNP) parameters of the P/LP+ and P/ LP- groups. Also, no significant difference was found in most echocardiographic parameters (LAV, LAVI, LVmax, EF, SV, SV index, TAPSE) between the two groups, except that the proportion of obstructive patients was higher in the P/LP group (p=0.026) and the resting (p= 0.004) and provoked (p=0.0082) LVOT gradients were higher. Despite of no difference in the GLS value in the two groups (p=0.850), the P/LP+ group had lower global work index [GWI: p=0.0035), global constructive work (GCW: p=0.0006), and global wasted work (GWW: p=0.0098), while global work efficiency (GWE: p=0.485) did not differ. The differences remained even when patients carrying variants of unknown significance (VUS+) were examined in a separate group (GWI: p=0.013; GCW: p=0.001; GWW: p=0.005). Summary These results indicate that the pathological gene mutation underlying HCM, leads to lower myocardial work values, even with a similar morphological or functional appearance. The latter observation further confirms the possible role of MW parameters in the prognosis of HCM.

AIMS:The Central/Eastern Europe (CEE) Quality of Care Centres (QCC) Survey evaluated the implementation of guideline-directed medical therapies (GDMT) and device use at discharge after heart failure (HF) hospitalization in CEE, where GDMT underutilization remains a concern. METHODS AND RESULTS:Between March 2024 and January 2025, 2251 patients (mean age 70.0 years, 60.4% male) were enrolled at discharge from 21 centres across 12 CEE countries. The patient population included HF with reduced ejection fraction (HFrEF) (55.5%), HF with mildly reduced ejection fraction (15.3%) and HF with preserved ejection fraction (27.9%). In the total population, from admission to discharge there was a increase in the use of angiotensin receptor-neprilysin inhibitor (ARNI) (17.1% to 34.3%), beta-blockers (69.4% to 92.4%), mineralocorticoid receptor antagonists (MRA) (44.0% to 82.1%) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) (30.8% to 79.9%), with a reduction in angiotensin-converting enzyme inhibitor (ACEI) use (all p < 0.05). Similar trends were observed across HF phenotypes, including HFrEF (increased use of ARNI, 26.3% to 55.1%, beta-blockers, 69.8% to 95.3%, MRA 49.5% to 89.0%, and SGLT2I 36.2% to 79.8%, and lower ACEI use, all p < 0.05). At discharge, 53.5% of patients received quadruple therapy (63.9% with HFrEF), while ≥50% target doses of titratable drugs were achieved in 18.8% (17.8% in HFrEF). Predictors of GDMT underuse included older age, lower education, living alone, non-ischaemic HF, higher ejection fraction, chronic kidney disease, hypotension, hyperkalaemia, prolonged hospitalization, and residual oedema. Among eligible HFrEF patients, 21.3% were discharged with, or referred for implantable cardioverter-defibrillator, and 17.4% for cardiac resynchronization therapy. CONCLUSIONS:The CEE-QCC Survey highlights substantial in-hospital GDMT implementation and up-titration, though device use remains limited. Targeted strategies are needed to enhance guideline implementation and ensure optimal HF care across the CEE region.

Abstract Introduction Decompensated acute heart failure (HF) in patients with reduced ejection fraction (HFrEF) signifies a pivotal stage in the progression of chronic HF. This condition is closely linked to increased rates of rehospitalization and a higher risk of mortality and morbidity due to inadequate decongestion. Recently, the field of quantitative echocardiography has experienced significant advancements, particularly in myocardial work analysis (MWA), which measures the energy the heart uses during each cardiac cycle. Purpose This study aimed to investigate the immediate effects of levosimendan on myocardial mechanics and to determine if these effects can predict the composite endpoint of HF-related rehospitalization and cardiovascular mortality. Methods 60 patients with HFrEF have been enrolled in the present study (age: 63.8±14.1, 46 males, 25 ischemic HFrEF, 35 non-ischemic HFrEF). or all patients, detailed baseline echocardiography, including strain imaging and myocardial work analysis (MWA), was conducted. Follow-up echocardiography was performed an average of 13.1±12.5 days after levosimendan administration. The clinical follow-up period lasted 496±191 days. Results Before levosimendan administration there was no significant difference in baseline echocardiographic, strain imaging and MWA parameters between ischemic and non-ischemic HFrEF groups. After the drug administration, left ventricular global wasted work (179±89 Hgmm% vs. 319±220 Hgmm%, p <0.05) was higher in the ischemic HFrEF group compared to non-ischemic HFrEF group. Among advanced echocardiographic parameters, global longitudinal strain (GLS) showed no significant improvement, however out of the MWA parameters, global work index (376±215 Hgmm% vs. 460±272 Hgmm%, p <0.05) improved significantly. The prognostic role of hemodynamic and novel echocardiographic parameters has been also assessed. Kaplan-Meier analysis revealed that LV stroke volume index improvement of 0.145 ml/m2 (p=0.01), LVEF improvement of at least 10% or more (p=0.032), LV GLS improvement of 0.85% (p=0.018) and lastly global constructive work improvement of 100 Hgmm% or more (p=0.021) resulted in significantly better event-free survival during the follow up period. Conclusion Levosimendan administration produces substantial immediate effects on hemodynamic parameters, myocardial deformation, and MWA metrics. These alterations appear to hold significant long-term prognostic value for predicting the composite endpoint and event-free survival.

BACKGROUND:Nexilin (NEXN)-related cardiomyopathies (CMPs) are largely unexplored. OBJECTIVES:This study investigated the causative role of NEXN in CMPs, examining its phenotypic expression and prognostic profile. METHODS:Twelve referral centers collected phenotypic/genotypic data of patients with NEXN variants. Variant rarity was determined according to gnomAD allele frequency in CMPs. Burden enrichment tested rare NEXN variants in hypertrophic (HCM) and dilated cardiomyopathy (DCM)/nondilated left ventricular cardiomyopathy (NDLVC) CMPs against gnomAD non-Finnish Europeans (NFE). Outcomes of validated variants were detailed, with prognostic comparisons to Titin (TTN)- and Filamin C (FLNC)-related CMP cohorts. RESULTS:Involving 60 NEXN carriers with rare, protein-altering variants, a significant enrichment of NEXN-truncating variants (tvs) was found in the DCM/NDLVC cohort (0.39% vs 0.09% in gnomAD NFE; P = 0.0001), whereas no association was observed with HCM. Patients with DCM/NDLVC with NEXNtv (n = 17; median age: 45 years [Q1-Q3: 36-55 years], 88% probands, 53% male) showed mild left ventricular dilatation (indexed end-diastolic volume 69 mL [Q1-Q3: 46-87 mL]), mildly reduced left ventricular ejection fraction (44% [Q1-Q3: 31%-53%]), and myocardial fibrosis (64%). NYHA functional class I was common (71%). During a 45-month median follow-up (Q1-Q3: 11-130 months), 53% of patients were implanted with an implantable cardioverter-defibrillator and 25% had malignant ventricular arrhythmias (MVAs). Compared with TTN-CMP, NEXN-CMP exhibited earlier and more frequent MVAs at higher ejection fractions, and no significant differences were found against FLNC-CMP. CONCLUSIONS:NEXNtvs were significantly associated with DCM/NDLVC, characterized by mild cardiac abnormalities, infrequent heart failure, common fibrosis, and arrhythmias. This largest NEXN variant carrier cohort to date contributes to defining the causative role of this rare genotype and its associated phenotype.

BACKGROUND:Real-world data on the efficacy of mavacamten, indicated for the treatment of obstructive hypertrophic cardiomyopathy (oHCM), are relatively scarce, particularly in patients with extreme left ventricular outflow tract (LVOT) gradients and concerning its short-term effects. PATIENTS/METHODS:We investigated a cohort of twenty-five oHCM patients [15 men (60 %), mean age: 55 ± 11 years], with a resting or provoked LVOT gradient of >100 mmHg, receiving mavacamten treatment. Patients underwent a complete standard and 2D-speckle tracking echocardiographic examination after one week (W1) of treatment initiation and at subsequent four-week intervals. RESULTS:After only one week of mavacamten therapy, both the resting peak LVOT gradient (from 121 to 87 mmHg) and the Valsalva gradient (from 167 to 129 mmHg) significantly decreased (all p < 0.001), showing further decrease (resting gradient: to 67 mmHg at W4, and to 56 mmHg at W8; Valsalva gradient to 102 mmHg at W4, and to 80 mmHg at W8, all p < 0.001). NTproBNP levels also significantly decreased already at W1 (-1467 pg/ml), showing further decrease during treatment (-1735 pg/ml at W4, and - 2048 pg/ml at W8; all p < 0.001). NYHA functional class, 6-min walk distance, parameters of myocardial work and many of the assessed diastolic parameters showed significant improvements and no change in LV ejection fraction or global longitudinal strain was observed. CONCLUSIONS:Mavacamten effectively reduced even >100 mmHg LVOT gradients and led to significant gradient reduction already in one week. Besides favourable changes in LVOT obstruction, structural and functional echocardiographic parameters, functional capacity, and cardiac biomarkers, it also led to significant improvement in myocardial work parameters.

Abstract Introduction Mavacamten is a novel therapy for hypertrophic obstructive cardiomyopathy. Left ventricular (LV) ejection fraction (EF) has been used for monitoring of left ventricular systolic function during therapy. Currently there is limited data on advanced functional parameters based on speckle tracking strain values, such as global longitudinal strain (GLS) , myocardial work (MW) or 3D echocardiography. MW is an emerging method which incorporates left ventricular pressure and provides multiple parameters based on a LV pressure-strain loop. This study aimed to provide some insights into temporal changes of left ventricular deformation during mavacamten therapy. Purpose The purpose of this study was to examine left ventricular global and segmental strains and myocardial work parameters during mavacamten therapy. Methods The study involved 10 (5 women, 50%; aged 57±11 years) cases of mavacamten initiation and echocardiographic follow up (10 patients followed up to visit 1: 48±4.3 days, and 9 patients followed up to visit 2: 129±2.9 days). Comprehensive 2D and 3D resting echocardiography was performed. Speckle tracking based left ventricular strain values were measured. With a previously validated method left ventricular pressure was corrected for measurement of myocardial work parameters. The regional 2D based, LV strain and MW parameters were also examined. Results At the first follow up left ventricular obstruction gradient was already significantly lower compared to baseline and remained decreased at the second follow up (113±36 vs. 37±35 vs. 20±19 mmHg). EF or GLS did not differ significantly between visits (63.8±5.1 vs. 62.5±4.7 vs. 60.9±4.4 %, and -14.5±2.9 vs. -13.9±2.3 vs. -15.6±2.3 % respectively). Global Work Index (GWI) (2026±364 vs. 1588±351 vs. 1578±219 mmHg) and Global Constructive Work (2617±395 vs. 2010±400 vs. 1959±296 mmHg) significantly reduced at both visits when compared to baseline, but not between follow up visits. Global Wasted Work (GWW) (280±117 vs. 245±125 vs. 186±49) and Global Work Efficiency (GWE) (85.6±3.9 vs. 86.6±5.2 vs. 88.8±7.2 %) did not change significantly during follow up, similarly to no changes in 3D based strain, and rotational parameters. Peak Strain Dispersion, (102.8±40.7 vs. 93.8±35.3 vs. 75.9±29.8 ms). 3D based LV Mass (257±75 vs. 248±44 vs. 226±71 g) and Mass Index (137±44 vs. 131±42 vs. 119±41 g/m2) decreased at visit 2, but not at visit 1. The segmental analysis proved significant changes during follow-up compared to baseline in longitudinal strain (2 segments), MW (12 segments) wasted work (1 segment) and work efficiency (2 segments). Conclusions Among left ventricular functional parameters myocardial work has shown the most statistically significant differences during follow up, highlighting the reduction of the LV workload. The analysis of segmental data has shown a heterogeneous pattern of changes, primarily in MW.

Abstract Introduction Mavacamten is a selective, allosteric and reversible cardiac myosin inhibitor indicated for the treatment of symptomatic (NYHA II-III class) adult patients with obstructive [≥ 50 mmHg resting or provokable left ventricular outflow tract (LVOT) peak gradient] hypertrophic cardiomyopathy (HOCM). Patients and Methods Ten patients with HOCM [5 men (50%), mean age: 57±11 years) were treated with mavacamten. In 9 patients the resting or provoked gradient was >100 Hgmm. In addition to recording the main demographic, clinical parameters, complete standard and 2D-speckle tracking echocardiographic examination was performed in the patients after 1 week (1W) and 16 weeks (16W) of treatment. Results After 1W from initiation of mavacamten therapy, the resting peak LVOT gradient decreased by an average of -38 mmHg, from 113±36 mmHg to 75±36 mmHg (p=0.0028); which decreased further at 16W (mean difference -89 Hgmm, p=0.0002). The LVOT gradient provoked by the Valsalva maneuver decreased by -49 mmHg at 1W, from 150±43 mmHg to 107±50 mmHg (p=0.001), which further decreased at 16W (mean difference -107 Hgmm, p=0,0001). As the LVOT gradient decreased, patients' NTpBNP levels decreased at 1W by -690 pg/ml (p=0,0244), from 1270 (IQR: 636-2247) pg/ml to 756 (IQR: 377-1343) pg/ml, which further decreased at 16W (mean difference: -1103 pg/ml; p=0,0078). The ejection fraction and global longitudinal strain remained unchanged at 1W (EF: +0,7 %; p=0,6537; GLS: +0,5%; p=0.4303) and at 16W (EF: -2%; p=0.4499; GLS: 0%; p=0.9885). As the gradient decreased, the global work index and global constitutive work decreased at 1W (GWI: 2026±365 vs. 1675±382 mmHg%; p=0.0009; GCW: 2618±395 vs. 2091±468 mmHg%; p=0.0062) and at 16W (mean difference, GWI: : -406mmHg%; p=0,0062; GCW: -572 mmHg%; p=0,0018). Left atrial volume values showed a favorable regression trend at 1W (LAV: 137±30 vs. 124±25 ml; p=0.1513; LAVI: 71±13 vs. 64±12 ml/m2; p=0.1528) which became significant at 16W (mean difference, LAV: -35 ml; p=0,01; LAVI: -17 ml/m2, p=0,0092). Conclusion The direct myosin inhibitor mavacamten effectively reduces even extreme (>100 Hgmm) LVOTO gradients and has a beneficial effect on other structural and functional cardiac parameters. It has an effect even in the short term.

Nexilin (NEXN)-related cardiomyopathies (CMPs) are largely unexplored. This study investigated the causative role of NEXN in CMPs, examining its phenotypic expression and prognostic profile. Twelve referral centers collected phenotypic/genotypic data of patients with NEXN variants. Variant rarity was determined according to gnomAD allele frequency in CMPs. Burden enrichment tested rare NEXN variants in hypertrophic (HCM) and dilated cardiomyopathy (DCM)/nondilated left ventricular cardiomyopathy (NDLVC) CMPs against gnomAD non-Finnish Europeans (NFE). Outcomes of validated variants were detailed, with prognostic comparisons to Titin (TTN)- and Filamin C (FLNC)-related CMP cohorts. Involving 60 NEXN carriers with rare, protein-altering variants, a significant enrichment of NEXN-truncating variants (tvs) was found in the DCM/NDLVC cohort (0.39% vs 0.09% in gnomAD NFE; P = 0.0001), whereas no association was observed with HCM. Patients with DCM/NDLVC with NEXNtv (n = 17; median age: 45 years [Q1-Q3: 36-55 years], 88% probands, 53% male) showed mild left ventricular dilatation (indexed end-diastolic volume 69 mL [Q1-Q3: 46-87 mL]), mildly reduced left ventricular ejection fraction (44% [Q1-Q3: 31%-53%]), and myocardial fibrosis (64%). NYHA functional class I was common (71%). During a 45-month median follow-up (Q1-Q3: 11-130 months), 53% of patients were implanted with an implantable cardioverter-defibrillator and 25% had malignant ventricular arrhythmias (MVAs). Compared with TTN-CMP, NEXN-CMP exhibited earlier and more frequent MVAs at higher ejection fractions, and no significant differences were found against FLNC-CMP. NEXNtvs were significantly associated with DCM/NDLVC, characterized by mild cardiac abnormalities, infrequent heart failure, common fibrosis, and arrhythmias. This largest NEXN variant carrier cohort to date contributes to defining the causative role of this rare genotype and its associated phenotype.

A mineralokortikoidreceptor-antagonista (MRA) szerek randomizált klinikai vizsgálatok alapján nagyon hatékony terápiás lehetőségnek bizonyultak a csökkent ejekciós frakciójú szívelégtelenségben (HFrEF) szenvedő betegek kezelésében. Ezekben a betegekben a jelenlegi bizonyítékok azt mutatják, hogy az MRA-k csökkentik a szívelégtelenségben szenvedő betegek morbiditását és mortalitását. A három nagy, HFrEF-betegeket bevonó vizsgálat (RALES, EPHESUS, EMPHASIS-HF) eredményei alapján mind a spironolakton, mind az eplerenon bekerült a HFrEF-betegcsoport stratégiai fontosságú gyógyszerei közé, és adásuk I. osztályú indikáció az ESC és az ACC/AHA szívelégtelenség-ajánlása alapján is. Az MRA-k maladaptív remodellációt és fi brózist gátló hatásaik kiterjeszthetik az MRA-k klinikai hasznosságát a szélesebb kardiovaszkuláris betegpopulációra, például a tünetmentes HFrEF-betegekre, illetve a HFpEF-betegek bizonyos populációira. Utóbbival kapcsolatban a TOPCAT-vizsgálat igazolta azt, hogy bár a vizsgálat primer végpontja negatív volt, a spironolakton igazoltan csökkentette a szívelégtelenség (SZE) miatti hospitalizációt a mortalitásra gyakorolt negatív hatás nélkül. Remélhetőleg a jövőbeli prospektív tanulmányok eredményei, amelyek a legújabb fejlesztésű, harmadik generációs MRA-kal (fi nerenon) való vizsgálatokat is magukba foglalják, bővíteni fogják ennek a gyógyszerosztálynak a klinikai indikációit.

Mineralocorticoid receptor antagonists (MRAs) have proven to be highly effective therapeutic options in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) based on randomized clinical trials. Current evidence in these patients clearly indicates that MRAs reduce morbidity and mortality in heart failure patients. Results from the three major trials involving HFrEF patients (RALES, EPHESUS, EMPHASIS-HF) have led both spironolactone and eplerenone to become pivotal drugs in the management of HFrEF patients, with class I indications according to ESC and ACC/AHA heart failure guidelines. The anti-remodeling and anti-fibrotic effects of MRAs may extend their clinical utility to a broader cardiovascular patient population, such as asymptomatic HFrEF patients and certain populations of HFpEF patients. Regarding the latter, the TOPCAT trial demonstrated that although the primary endpoint of the trial was negative, spironolactone significantly reduced heart failure-related hospitalizations without a detrimental effect on mortality. Hopefully, results from future prospective studies, which include investigations with the latest third-generation MRAs (finerenone), will expand the clinical indications of this drug class.

AIMS:The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose. METHODS:We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I < 0.55 mV (I < 0.55); QRS amplitude in lead aVR < 0.5 mV (aVR < 0.5); average QRS amplitude of leads I + aVR < 0.575 mV [(I + aVR) < 0.575]; average QRS amplitude of leads I + aVR/average QRS amplitude of leads V1-4 < 0.375 [(I + aVR)/(V1-4) < 0.375]; average QRS amplitude of leads I + aVR/longest intrinsicoid deflection in leads I,aVL,V1-6 < 0.0115 [(I + aVR)/I,aVL,V1-6ID < 0.0115]. RESULTS:The I < 0.55, aVR < 0.5, (I + aVR) < 0.575, (I + aVR)/(V1-4) < 0.375, (I + aVR)/I,aVL,V1-6ID < 0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64-80%, SE: 66-81.3%, SP: 55-78.3%, PPV: 33-83.9%, NPV: 41-75%, AUC: 0.62-0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%). CONCLUSIONS:The novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V1-4) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand-alone criteria to diagnose CA in the future.

Az Európai Kardiológus Társaság (European Society of Cardiology, ESC) akut és krónikus szívelégtelenség (SZE) diagnosztizálására és kezelésére vonatkozó 2021. évi irányelvének közzététele óta számos randomizált, kontrollált klinikai vizsgálat eredményét publikálták. Utóbbi vizsgálatok olyan ismeretanyagot szolgáltattak, amelyeknek közvetlen kihatásuk van a napi klinikai gyakorlatra az SZE-betegek kezelését illetően. Ezen megfontolás alapján szükségesnek tűnt az SZE-betegek kezelésére vonatkozó ajánlások frissítése, még a következő tervezett teljes irányelv publikálása előtt. Fentiek alapján a 2023-as fókuszált irányelv frissítése az eredeti ajánlás SZE kezelésére vonatkozó fejezeteinek szükséges változásaival foglalkozik. Az ESC 2021-es SZE-irányelvének következő szakaszaira vonatkozó ajánlásokat frissítették: 1) krónikus SZE: enyhén csökkent ejekciós frakcióval (HFmrEF) és megtartott ejekciós frakcióval járó SZE (HFpEF); 2) akut SZE; 3) társbetegségek és az SZE megelőzése. Jelen közleményben az aktualizált ajánlásokat és azon vizsgálatok eredményeit ismertetjük, amelyek alapul szolgáltak a frissített ajánlásokhoz.