Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail. To this end, changes in sarcomere length and intracellular Ca²⁺ levels were monitored in parallel, in enzymatically isolated canine cardiomyocytes, and detailed echocardiographic examinations were performed in anesthetized rats in the absence or presence of danicamtiv. The systolic and diastolic sarcomere lengths decreased; contraction and relaxation kinetics slowed down with increasing danicamtiv concentrations without changes in intracellular Ca²⁺ transients in vitro. Danicamtiv evoked remarkable increases in left ventricular ejection fraction and fractional shortening, also reflected by changes in systolic strain. Nevertheless, the systolic ejection time was significantly prolonged, the ratio of diastolic to systolic duration was reduced, and signs of diastolic dysfunction were also observed upon danicamtiv treatment in vivo. Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations.

Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40–160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias.

Background/Objectives: Heart transplantation (HTX) is the definitive treatment for advanced heart failure (AdHF). The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) has been shown to reduce heart failure (HF) hospitalizations and mortality when compared to conventionally administered HF medications (i.e. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)). Nevertheless, limited data are available on the hemodynamic (HD) effects of ARNI in patients with AdHF. Therefore, the aim of the present study was to compare echocardiographic, laboratory, and HD parameters relevant to HF before and after switching to ARNI in patients with AdHF awaiting HTX. Methods: A retrospective analysis was conducted utilizing available data on HD parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, data on kidney function, HF therapy, and comorbidities. The study cohort comprised 13 AdHF patients (3 women, 10 men; mean age 56.4 ± 9 years) of whom 53.8% presented with non-ischemic and 46.2% with ischemic etiology. All patients were awaiting heart transplantation (HTX) and were transitioned to ARNI therapy between 2018 and 2021. Results: After switching to ARNI, we observed significant improvements: in left ventricular ejection fraction (LVEF: 27.27 ± 1.04% vs. 23.65 ± 1.02%, p = 0.03; data are given as mean ± SEM after vs. before ARNI therapy, respectively), cardiac output (CO: 4.90 ± 0.35 L/min vs. 3.83 ± 0.24 L/min, p = 0.013), and stroke volume (SV: 70.9 ± 5.9 mL vs. 55.5 ± 4.12 mL, p = 0.013). Significant reductions in systemic vascular resistance (SVR: 1188 ± 79.8 vs. 1600 ± 100 DS/cm⁵, p = 0.004) and pulmonary vascular resistance (PVR: 232.5 ± 34.8 vs. 278.9 ± 31.7 DS/cm⁵, p = 0.04) were also noted. Central venous pressure (CVP), pulmonary arterial systolic and diastolic pressures (PAPs and PAPd), pulmonary capillary wedge pressure (PCWP), and NT-proBNP levels did not exhibit significant changes upon ARNI administration. Conclusions: Early transition to ARNI therapy offers significant benefits for invasively measured hemodynamic parameters in patients with AdHF, potentially aiding in the stabilization and improvement of this vulnerable patient population.

Background/Objectives: Conduction system pacing (CSP) is a potential alternative to biventricular pacing (BVP) in heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB) or non-LBBB. Available data also suggest that unlike BVP, CSP may improve clinical outcome in patients with right bundle branch block (RBBB), although its effects on cardiac mechanics and energetics are ill-defined. Herein, we report on echocardiographic and clinical outcomes of CSP in this patient cohort. Methods: CSP either with His bundle pacing or LBB area pacing was attempted as a primary strategy in patients with RBBB, QRS duration ≥ 130 ms, LVEF < 35% and NYHA II-IV symptoms after optimized medical therapy for 6 months. Data on functional status, NT-proBNP and echocardiographic parameters were collected at baseline and 6 months after CSP. Results: CSP performed in 16 patients reduced QRS duration from 155.3 ± 12.8 ms to 130 ± 16.5 ms (p < 0.001), increased LVEF from 27 ± 7% to 33 ± 9% (p = 0.01), improved LV global longitudinal strain from −7 ± 3% to −10 ± 4% (p = 0.004) and improved LV peak strain dispersion from 126 ± 28 ms to 96 ± 23 ms (p = 0.004). Global myocardial work index increased from 582 ± 277 mmHg% to 840 ± 306 mmHg% (p = 0.003), as did global constructive work (900 ± 374 mmHg% to 1203 ± 393 mmHg%; p = 0.006) and global work efficiency (from 71 ± 7% to 77 ± 8%; p = 0.004). NYHA class (12.5% with NYHA II, 87.5% with NYHA III before vs. 25% with NYHA I, 50% with NYHA II and 25% with NYHA III at 6 months; p = 0.002) and 6 min walk distance (from 354 ± 88 m to 411 ± 95 m; p = 0.003) improved, while NT-proBNP decreased (from 4093 ± 7215 ng/L to 2087 ± 2872 ng/L, p = 0.003). Conclusions: CSP improved functional capacity and echocardiographic parameters related to cardiac functions and myocardial work in HFrEF patients with RBBB. Nevertheless, these results await further confirmation by large-scale, multi-center randomized trials.

Bevezetés: A szívelégtelenség a cardiovascularis morbiditás és mortalitás egyik fő oka, a betegség nagymértékben rontja a betegek életminőségét. Az SGLT2-gátlók randomizált, kontrollált klinikai vizsgálatok alapján jelentősen javítják a kimeneteleket és csökkentik a tüneteket. Ugyanakkor a való életből származó adatok kulcsfontosságúak e gyógyszercsoport hatásosságának és biztonságosságának pontosabb megítéléséhez. Célkitűzés: A nemzetközi Emp-Activity vizsgálat magyarországi kohorszában az empagliflozinkezelés életminőségre és funkcionális statusra gyakorolt hatásának értékelése, valamint biztonságosságának vizsgálata a szívelégtelenség spektrumában. Módszer: A prospektív, beavatkozással nem járó, multicentrikus megfigyeléses vizsgálatba 11 hazai centrumból összesen 106, tünetes szívelégtelen beteg került bevonásra, akik közül 101 az empagliflozint kapó kohorszba, 5 beteg pedig a nem empagliflozint kapó kohorszba került. A betegek a rutin-szívelégtelenségterápia részeként empagliflozinkezelést kaptak, és a vizsgálat kezdetén, valamint 24 hét elteltével kitöltötték a Kansas City Cardiomyopathy Questionnaire (KCCQ-12) kérdőívet. A funkcionális statust a New York Heart Association (NYHA) osztályozása alapján értékelték. Eredmények: A vizsgálat empagliflozinkohorszába bevont 101 beteg mediánéletkora 69 év volt, 28,7%-uk nő, funkcionális stádiumuk NYHA II. és III. A betegek 57%-a a HFrEF-, 19%-a HFmrEF-, 22%-a pedig a HFpEF-fenotípusba tartozott. A szívelégtelenség hátterében a leggyakrabban (42%) ischaemiás etiológia állt. A leggyakoribb társbetegségek a hypertonia (58%), a pitvarfibrilláció (33%), a cukorbetegség (26%) és a hyperlipidaemia (25%) voltak. A KCCQ-12 összpontszámában jelentős javulás volt megfigyelhető (74,3 ± 19,5 vs. 67,1 ± 19,5 pont, p<0,01). Klinikailag szignifikáns javulás (≥5 pontos növekedés) a betegek 53%-ában következett be. A NYHA-stádium jelentősen javult. A systolés vérnyomás csökkent (131 ± 16 Hgmm vs. 127 ± 17 Hgmm, p = 0,02), míg a diastolés vérnyomás, a szérumkreatinin- és -káliumszint nem változott a 24 hetes kezelés során. Következtetés: A szívelégtelenségben szenvedő magyarországi betegek körében a 24 hetes empagliflozinkezelés az életminőség és a funkcionális kapacitás szignifikáns javulásával járt, emellett a kezelés jól tolerálhatónak bizonyult. A vizsgálat eredményei megerősítik az empagliflozin alkalmazásának hatékonyságát és biztonságosságát a mindennapi klinikai gyakorlatban. Orv Hetil. 2026; 167(7): 257–264.