Reduction In Gradient Research Articles

Comparison between flattening filter and flattening filter-free photon beams in head and neck cancer patients using volumetric modulated arc therapy technique.

This study aimed to evaluate the dosimetric and clinical outcomes of flattening filter (FF) versus flattening filter-free (FFF) beams in head and neck cancer (HNC) patients treated with volumetric modulated arc therapy (VMAT). Twenty-four patients with 70/59.4/54 Gy dose prescribed in 33 fractions with simultaneous integrated boost treatment were retrospectively analyzed to compare treatment delivery efficiency, target coverage, sparing of organs at risk (OARs), and remaining volume at risk (RVR) in two HNC groups (nasopharyngeal and oropharyngeal). Study findings indicate that FFF beams significantly reduce conformity index (CI) and homogeneity index (HI) by p-values (0.008, < 0.001, 0.002, 0.015) for PTV70 CI, PTV70 HI, PTV60 HI, and PTV54 HI, respectively. Gradient dose was significantly improved in FFF mode, and monitor units (MU) were increased (p < 0.001). In terms of OARs, the study revealed superior performance of FFF in most of structures and RVR especially in the oropharyngeal group. OARs sparing is notably enhanced for structures distant from the target (eyes, lenses, and optic pathway). Additionally, brainstem sparing shows significant improvement in oropharyngeal cases when using FFF plans (p = 0.046); however, FF plans demonstrate superior results in nasopharyngeal cases (p = 0.026). It is concluded that both FF and FFF photon beams are effective for treating HNC patients. VMAT plans using FFF mode offer clinically acceptable outcomes, demonstrating a significant reduction in gradient and integral dose. However, FF plans exhibit superior target homogeneity and reduced MU requirements. Therefore, the choice between these techniques should be based on a comprehensive evaluation of all relevant parameters.

Safety and Efficacy of Portal Vein Recanalization with Creation of Intrahepatic Portosystemic Shunt (PVR-TIPS) to Treat Chronic Portal Vein Thrombosis in Non-cirrhotic Patients.

This study assesses the efficacy and safety of Portal Vein Recanalization with Intrahepatic Portosystemic Shunt (PVR-TIPS) in non-cirrhotic patients with chronic portal vein occlusion (CPVO), cavernomatous transformation, and symptomatic portal hypertension (PH) and/or portal vein thrombotic progression. Medical records of 21 non-cirrhotic patients with CPVO and portal cavernoma undergoing PVR-TIPS were analyzed. Hemodynamic (intraprocedural reduction in portosystemic pressure gradient), clinical (data on gastrointestinal bleeding, abdominal pain, ascites, and presence of esophageal varices from imaging exams) and technical success (PVR-TIPS) assessed efficacy. Safety was determined through complications classified according to the CIRSE Classification System. PVR-TIPS was successfully performed in all patients, resulting in a significant reduction in portal pressure gradient by 10mmHg (21.475 ± 9.7mmHg - 11.454 ± 5,4mmHg, p < 0.001), alleviating portal hypertension symptoms without thrombotic progression. Clinical success included resolution or reduction of ascites (p = 0.016), gastroesophageal varices (p = 0.004), abdominal pain (p = 0.0021), and cessation of gastrointestinal bleeding (p = 0.021). Complications occurred in 33% of patients, including six grade III events (1 perioperative liver bleeding, 5 delayed stent occlusions) and one grade VI event resulting in death (4.8%). Primary patency rate was 76% (21.3months, range:0.2-82), secondary patency 100% (4months, range:3.8-40.8). Survival at follow-up was 90.4%, with one unrelated death. One patient underwent liver transplantation, three became eligible post-recanalization. PVR-TIPS proves effective and safe in reducing portal pressure gradient, thereby alleviating PH symptoms without evidence of portal thrombosis progression in non-cirrhotic patients with CPVO and portal cavernoma. It expands therapeutic options, including liver transplantation.

End-procedural adherence to recommended hemodynamic targets does not improve the outcome of elective tips in cirrhotic patients.

In clinical practice, the reduction of porto-caval pressure gradient (PCPG) following trans-jugular intra-hepatic porto-systemic shunt (TIPS) does not always meet the recommendation of current guidance. We evaluated the impact of different degrees of PCPG reduction, measured at the end of an elective TIPS, on ascites control, recurrence of portal hypertension-related bleeding (PHRB) and survival. Cirrhotic patients receiving TIPS for refractory ascites (RA) or for the secondary prophylaxis of PHRB were consecutively enrolled. Reduction in PCPG was defined inadequate (IHR) in patients not achieving a PCPG <12mm Hg for both secondary prophylaxis of PHRB and RA, or a reduction of at least 50% only for PHRB. Four-hundred-fifteen patients were analyzed. An adequate hemodynamic response (AHR) was achieved in 66%. Fifty percent of patients received an under-dilated (≤7mm) endoprosthesis. No significant differences between patients with IHR and AHR were observed in rebleeding rate and ascites control, while overt hepatic encephalopathy was higher in AHR. Regardless of TIPS indication, survival was not significantly different between IHR and AHR, while advanced age and liver function before TIPS were significantly associated with a higher cumulative incidence of liver-related death. Notably, the cumulative incidence of liver-related mortality was higher in RA patients when AHR was defined as a post-TIPS PCPG <12mm Hg or a reduction ≥50%. AHR measured at the end of an elective TIPS may not be essential to define the eventual outcome, while a marked drop in PCPG could negatively affect the prognosis of patients with RA.

Identification of optimal portal pressure decrease to control ascites while minimizing hepatic encephalopathy after TIPS: A multicenter study.

Clinically-significant portal hypertension (CSPH) in liver cirrhosis patients can lead to refractory ascites. A transjugular-intrahepatic-portosystemic shunt (TIPS) treats CSPH but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) via TIPS to control ascites without raising oHE risk. This multicenter study screened 1509 patients from three European centers (Hannover, Vienna, Hamburg) undergoing TIPS-implantation between 2000-2023. Patients with TIPS-indications other than refractory ascites/hepatic hydrothorax, vascular-liver-disease, hepatocellular-carcinoma or insufficient PPG data were excluded. PPG was measured before and after TIPS insertion. Outcome data was assessed up to one year after TIPS-insertion. Analyses were conducted utilizing a modern machine leaning model, namely a competing-risk (CR) random survival forest (RSF), partial-dependence-plots (PDP) and CR-analyses with liver transplantation/death as competitors. The cohort was divided into a 60% derivation and 40% validation cohort. Overall, 729 patients (median MELD: 13 (IQR 10-16), 66% male, 23% oHE before TIPS) were analyzed. The derivation cohort comprised 438 and validation cohort 291 patients. The optimal PPG reduction, determined by maximally selected Grays-statistic and PDP of the RSF, was 60-80%. In this range, patients showed significantly fewer hepatic decompensations due to ascites (HDA) (sHR: 0.7 [0.52-0.96]) with similar oHE incidences (sHR: 0.92 [0.67-1.27]). The PPG range was confirmed in the validation cohort (HDA: sHR: 0.66 [0.46-0.96]; oHE: sHR: 0.89 [0.61-1.32]). A targeted PPG reduction of 60-80% showed significantly reduced HDA without increased oHE risk. Therefore, PPG reduction within this range could be a valid reduction target.

Effect of bifocal soft contact lenses in combination with instillations of the combined drug (Phenylephrine 5% and Tropicamide 0.8%) on the anatomical and functional parameters of the eyes and progression of myopia in pediatric patients

AIM: The study aimed to assess the influence of combined optical and pharmacological effects on the anatomical and functional parameters of the eyes and changes in refraction in pediatric patients with progressive myopia. MATERIAL AND METHODS: Bifocal soft contact lenses (BSCL) Prima BIO Bifocal were prescribed to 43 pediatric patients. At the start of the study, the average age of the children was 10.42±0.26 years, and the average myopia was 3.43±0.19 D. The effect of a combination of optical and medicinal products on the visual apparatus of children was evaluated, namely, bifocal SCLs that form peripheral myopic defocus and instillations of a combined drug containing 0.8% tropicamide and 5% phenylephrine. The combined eye drops, which contained 0.8% tropicamide and 5% phenylephrine, was prescribed once a day at night for 1 month to 23 pediatric patients after wearing the lenses for 1 month (group 1). In group 2 (n=20), patients did not receive any additional treatment, except for optical exposure. RESULTS: The habitual tone of accommodation (HTA) slightly increased after 1 month of using BSCL. In group 1, the HTA decreased to the initial level after 6 and 12 months, whereas it remained high in group 2. Over the year, refraction increased by 0.39 D in group 1 and 0.18 D in group 2 (p 0.05). The annual progression gradient decreased by 2.3 times in group 1 and 5.2 times in group 2. Over the year, the anteroposterior axis increased by 0.13 mm in group 1 and 0.05 mm in group 2. Choroidal thickness increased by 19.09 and 24.77 µm, relative accommodation reserve increased by 0.98 and 1.24 D, and the accommodation amplitude increased by 1.28 and 1.05 D, respectively. CONCLUSION: BSCLs contribute to the reduction of the annual gradient of progression (AGP) and increase in accommodation and choroidal thickness. Instillations of the drug while using BSCL help reduce the habitual tone of accommodation (HTA).

Upscaling drag reduction of rotational rheometer to linear pipe flow

Drag reduction (DR) is a phenomenon associated with adding small amounts of drag-reducing agents to reduce friction causing a reduction in the pressure gradient needed for pumping a solution under turbulent conditions. Traditionally, DR has been measured with linear flow devices, such as flow loops. Recent developments in rheological measurement techniques have enabled the evaluation of DR using rotational rheometers. However, due to differences in flow nature and length scale, direct comparison between outcomes is not possible. This study introduces nondimensional quantities, namely dimensionless pressure difference for pipe flow and dimensionless torque for rheometers, as the basis for comparing the DR results of linear and rotational flow. Theoretically, the DR expressions derived from these dimensionless quantities showed similar structures, featuring a factor with quadratic viscosity and linear density terms. Experimentally, DR tests were carried out using an industrial-scale pipe flow and a laboratory-scale rotational rheometer, using solutions of tap water with high-viscosity partially hydrolyzed polyacrylamide at two molecular weights. Samples tested with the rheometer were collected from flow loop experiments, ensuring the same polymer solutions were tested with both devices. Results showed that DR, expressed as a function of Reynolds number using nondimensional measurements, follows similar behavior for both instruments. The experimental DR results from the rheometer were extrapolated to the pipe flow scale, showing overall agreement between extrapolated and experimental results. These findings suggest that rotational rheometers could effectively replace linear flow instruments for screening polymer solutions in DR applications.

Functional Mitral Regurgitation Post-Isolated Aortic Valve Replacement.

Background: The management of mitral regurgitation during aortic valve replacement remains a complex question. Secondary mitral regurgitation often improves post-aortic valve replacement without mitral valve surgery, but residual mitral regurgitation can significantly affect long-term outcomes. This study investigates the natural history of mitral regurgitation following isolated aortic valve replacement and identifies prognostic factors for persistent mitral regurgitation. Methods: A retrospective study was conducted on 108 patients who underwent isolated aortic valve replacement. Patients were categorized based on mitral regurgitation improvement. Additionally, patients were divided into patient-prosthesis mismatch and non-patient-prosthesis mismatch groups based on the aortic prosthesis. Preoperative and postoperative echocardiographic data were analyzed. Results: In total, 63% of patients showed mitral regurgitation improvement. The improved functional MR group showed significant reductions in peak and mean transvalvular pressure gradients. In contrast, the patient-prosthesis mismatch group had persistent mitral regurgitation improvement in 59.2% of patients. The non-patient-prosthesis mismatch group exhibited significant structural improvements and a reduction in mitral regurgitation severity in 68.6% of patients. Conclusions: The study shows that aortic valve replacement could significantly improve MR when patient-prosthesis mismatch is avoided. This approach maximizes hemodynamic outcomes, mitigates the risk of residual or worsening mitral regurgitation, and potentially reduces the need for additional mitral valve interventions.

Comparison of Carvedilol and Propranolol in Reducing the Portal Vein Pressure

Introduction and Objectives: The portal vein pressure higher than 10 mm Hg in patients with hepatic cirrhosis is more likely to have serious complications and poor prognosis. Nonselective receptor blockers (NSBBs) can reduce the portal vein pressure; however, the efficacy and safety of different NSBBs in reducing portal vein pressure were unconsistent. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of carvedilol versus propranolol in reducing portal vein pressure in this study. Materials and Methods: We assessed Randomized controlled trials (RCTs) through PubMed, Web of science, Embase, and Cochrane library up to January 2024. Data from eligible studies were pooled in fixed-effect or random-effect meta-analysis models, using RevMan software. Two researchers screened articles, extracted data, and assessed the study quality independently according to the PRISMA guidelines. The primary outcomes were the reduction of hepatic venous pressure gradient (HVPG), the hemodynamic response rate, and the incidence of adverse events. Secondary outcomes were mean artery pressure (MAP) and heart rate (HR). Results: A total of 7 RCTs, including 351 patients, were included in our meta-analysis. The results indicated that the magnitude of reduction in HVPG was greater in carvedilol compared with propranolol (MD: 1.08; 95% CI: 0.61 to 1.54; I 2=0%, P&lt;0.00001) in short-term follow-up. Carvedilol’s hemodynamic response rate was higher than that of propranolol (OR: 0.44; 95% CI: 0.27 to 0.72; I 2=0%, P = 0.001) Conclusions: Our meta-analysis indicated that compared with propranolol, carvedilol was better in lowering portal hypertensive and had higher response rate in patients with hepatic cirrhosis. There was no obvious difference in safety between the 2 medications.

Effect of rib width on the thermo-electro-mechanical behavior of solid oxide fuel cells

In this study, a three-dimensional multi-physics coupled model is employed to investigate the effects of the rib width of the cathode-side interconnect on the flow characteristics, electrochemical performance, temperature distribution and stress distribution of solid oxide fuel cells (SOFCs) under cross-flow conditions based on a fixed gas channel-electrode interface area. The results show that as the rib width is reduced, there is a marked improvement in the uniformity of gas distribution and gas flow velocity within the channels, leading to an increase in the output power density of the SOFC stack, a reduction in the temperature gradient of the cell and a reduction in the thermal stress carried by the cell. However, if the ribs are of insufficient width, the pressure drop within the channels will be significantly increased, reducing the static pressure head of the gas and leading to a decrease in the gas flow velocity within the electrodes. This, in turn, will result in an increase in concentration polarization and higher manufacturing costs. The simulation results facilitate a more detailed comprehension of the internal reaction processes of SOFCs, thereby offering valuable guidance for the structural optimization of interconnects.

The sedimentology and multi-stage evolution of a Pleistocene esker on soft substratum, a case from North Central Poland

Eskers are one of the meltwater landforms that enable the reconstruction of the nature of subglacial drainage systems. Therefore, they play a significant role in the study of palaeo ice sheets. While the spatial distribution of subglacial tunnels and their geometry resulting from the geomorphological features of eskers are relatively well known, the course and time of sedimentation processes taking place inside the subglacial conduits are understood only to a certain extent, especially in the case of eskers developed on soft substrata. The paper presents an example of an esker that developed on a soft substratum from Central-North Poland, which was formed in several stages. In the initial stage, meltwater drainage took place through a channel that dissected the substratum (N-channel). Its development was associated with intense flow under pressure, but the sediments filling the channel were already deposited under atmospheric pressure when the flow used only part of the available space of the conduit. The high frequency of large-scale, cross-stratified lithofacies indicates significant flow depth and sediment deposition under a lower flow regime. The succession filling the channel resembles the sediments of a low-sinuosity open river systems with varied channel morphology, however, it also contains deposits like the point bar succession. Later, the R-channel developed, dominated by deposition from supercritical flows, probably of a much smaller depth. The sediments were deposited from a traction carpet or a highly turbulent suspension. The massive structure of many lithofacies indicates that flow overload was common. The transformation of the system from N-channel to R-channel was probably related to the decrease in the slope of the ice sheet surface during ablation, which resulted in a reduction of the potential hydraulic pressure gradient. The final stage of esker sedimentation was associated with deposition in an open channel, which indicates the passive nature of the marginal part of the ice sheet.

Clinical assessment of patient outcomes post percutaneous pulmonary valve implantation: Insights from a single tertiary centre

Background: Percutaneous pulmonary valve implantation (PPVI) has emerged as a promising treatment for congenital right ventricular outflow tract (RVOT) dysfunction and restoring conduit graft viability. Methods: This is a single-centre retrospective study of 41 patients (18 men, 23 women; mean age 26.1±10.2 years) who underwent PPVI between December 2007 and November 2014 and were evaluated for right ventricular pressures and exercise tolerance. Results: PPVI significantly reduced mean baseline RVOT gradients across different pathologies: stenosis (45 vs 18.4 mmHg), regurgitation (19.2 vs 7.6 mmHg), and mixed disease (32.5 vs 12 mmHg). Furthermore, mean right ventricular (RV) systolic pressures decreased from 61.6±2.3 to 41.9±2 mmHg (p&lt;0.001), while RV diastolic pressures decreased by about 60% from 14.3±1.1 to 8.6±1.4 mmHg (p&lt;0.001). Echocardiography revealed significant improvements in pulmonary and tricuspid valve velocities (p for trend&lt;0.01). Additionally, there was a consistent reduction in the main pulmonary artery maximum pressure gradient measured pre-procedure. No significant changes were observed in PR, QRS, or QTc interval duration on follow-up electrocardiograms. Similarly, no changes were noted in cardiopulmonary exercise test performance during follow-up. Conclusion: The study highlights the effectiveness of PPVI using Medtronic Melody and Edwards SAPIEN valves in patients with various pulmonary diseases. Immediate improvements in right ventricular pressures and functional outcomes suggest that PPVI is a valuable treatment option for individuals with RVOT dysfunction. Multi-centre collaborations are crucial for further elucidating the long-term effects of PPVI on cardiac function, exercise tolerance, and quality of life in RVOT dysfunction.

Follow-Up Study of Percutaneous Intramyocardial Septal Radiofrequency Ablation in the Treatment of Hypertrophic Obstructive Cardiomyopathy With HFpEF.

The study aimed to evaluate the changes of left ventricular diastolic function and the improvement of clinical symptoms in hypertrophic cardiomyopathy (HCM) patients with heart failure with preserved ejection fraction (HFpEF) after percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). This study enrolled 31 adult HCM patients with HFpEF who underwent PIMSRA treatment. Electrocardiogram, imaging, and blood biochemical examinations were performed on these patients during a 6-month follow-up. Compared with the baseline, at 6 months after PIMSRA, patients showed significant reductions in peak left ventricular outflow tract pressure gradients (resting gradient: from a mean of 83.24 to 23.40mmHg, p < 0.001; postexercise gradient: from a mean of 109.70 to 33.39mmHg, p< 0.001). The interventricular septal thickness reduced from a mean of 22.90 to 17.48mm, p < 0.001. The E/e' decreased from a median of 18.67 to 11.54, p < 0.001. The 6-minute walk distance (6MWD) increased from a mean of 359.03 to 435.81 m, p < 0.001. The Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OS) increased from a mean of 57.57 to 71.93, p < 0.001. The number of HFpEF patients diagnosed according to the European Society of Cardiology's Heart Failure Association HFA-PEFF score decreased from 31 to 23. None of the patients had new-onset bundle branch block or complete heart block after PIMSRA. PIMSRA is a safe and effective treatment. It can improve left ventricular diastolic function and quality of life in HCM patients.

Estudio comparativo del tratamiento quirúrgico de la miocardiopatía hipertrófica obstructiva en función del empleo o no de un modelo 3D. Experiencia de nuestro centro

Introduction and aimSurgical treatment of hypertrophic cardiomyopathy faces challenges related to the extend and depth of septal resection. Three-dimensional printing presents itself as a useful tool in surgical planning, providing a visual and tangible representation of the surgical field. This study aims to compare surgical outcomes in patients with hypertrophic obstructive cardiomyopathy, depending on whether or not a 3D model was used. MethodsA retrospective observational study was performed in 55 patients with surgical indication for obstructive hypertrophic cardiomyopathy between May 2017 and May 2022 at Cruces University Hospital (Spain). A homogeneity analysis was performed between groups, followed by a comparative analysis to assess surgical success according to improvement in functional class, presence of complications associated with septal myectomy, reduction in interventricular gradient and mortality. ResultsA 3D model was used as a complementary tool in 18 patients. Functional class improved in both groups, but was more pronounced in the 3D model group. No patient in the 3D group showed a significant interventricular gradient, whereas 20% of the no-model group did. Complications were more prevalent in the no 3D model group (40.54% vs. 11.11%). At 30 days, mortality was lower in the 3D model group (5.56% vs. 11.16%). ConclusionsThe use of 3D models improves surgical planning and reduces complications in septal myectomy.

Crack-free manufacture of single weld tracks on aluminum alloy 6013 with the usage of laser beam shaping and oscillation strategies

The present paper investigates the application of laser beam shaping and laser beam oscillations (wobbling) for laser processing of the crack-prone aluminum alloy 6013, used in automotive and aerospace applications. A comparison of different laser beam profiles, such as the commonly used Gaussian profile, a ring-core distribution with the intensity of 50 % in the ring and 50 % in the core, and a ring-shaped beam profile shows different cracking behavior of the material. The ring-shaped beam profile shows the most promising results due to a reduction of the thermal gradient G and an enhancement of the growth rate R, which isalso stated by the state of the art. A combination of laser beam shaping and laser beam oscillations shows reproducible crack-free processing of Al6013 sheets at all three beam profiles at different parameter combinations. The crack elimination can be attributed to the emergence of a more pronounced equiaxed grain structure in the fusion zone of the weld with the application of laser beam oscillations and laser beam shaping. Thus, the temperature gradient G, the growth rate R and, therefore, the cooling rate can be controlled with the presented variation of the laser beam shapes and scanning strategies. Furthermore, the penetration depth of the laser at a Gaussian beam profile can be reduced using laser beam shaping, showing shallower melt pools with a lower depth-to-width aspect ratio, also suitable for the process of powder bed fusion of metals using a laser-based system (PBF-LB/M).

Effect of the sintering temperature on the electrical properties of Y–Al‐doped ZnO varistors

AbstractTo investigate the relationship between the electrical properties of Y–Al doped ZnO varistors and sintering temperature, in this study, we measured the voltage–current characteristics and electrical performance parameters of samples sintered at –. Scanning electron microscopy observations revealed that as the sintering temperature increased, the grain size grew significantly, leading to a reduction in voltage gradient. Through characteristic testing, X‐ray diffraction and energy dispersive X‐ray spectroscopy analysis, it was found that the increase in sintering temperature promoted the formation of interface negative charge and defect reactions by , increasing and ; tends to aggregate in the grain area, further increasing ; the volatilization of gradually increases, causing a decrease in ; the first increases and then decreases with the changes in and , resulting in a U‐shaped variation characteristic of the nonlinear coefficient and leakage current density. At a sintering temperature of , the performance of ZnO varistors is optimal.

Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: A Patient with a High LVOT Gradient

Background: Hypertrophic obstructive cardiomyopathy is a type of cardiomyopathy. The presence of a pressure gradient between the mid ventricle and LVOT on the hemodynamic evaluation revealed by echocardiography serves as the basis for the diagnosis. Objective: To Perform Alcohol Septal Ablation in patient with Hypertrophic Cardiomyopathy Method: Under both Echocardiography and Fluoroscopy first septal branch of LAD is identified and alcohol is injected to cause necrosis of the selected myocardial tissue to reduce the outflow gradient. Result: A reduction of the outflow gradient measured after the procedure indicates that it wassuccessful. J Inv Clin Cardiol 2023; 5(2): 56-59

Efficacy and safety of the ultraslow low-dose thrombolytic regimen for mechanical prosthetic valve thrombosis: a prospective cohort study

Abstract Background Mechanical prosthetic valve thrombosis (MPVT) remains a significant and life-threatening complication. While surgery is here considered the gold standard therapy, it has a high perioperative risk in the acute setting. Preliminary evidence suggests that an ultraslow low-dose thrombolytic regimen may offer a safer and equally effective alternative compared to both conventional fast-infusion thrombolytic approaches or surgical options. Purpose We aimed at evaluating efficacy and safety of a previously described ultraslow low-dose thrombolytic regimen for treating acute MPVT in hospitalized adult patients. Methods This prospective single-center cohort study included all consecutive adult patients with acute MPVT treated with our ultraslow low-dose thrombolytic regimen. Patients with contraindication to thrombolytic therapy or left-sided MPVT with a minimum thrombus size of 0.8 cm2 or severe dyspnea with NYHA FC IV were excluded, and considered candidate to surgery. The regimen here used consisted of 25 mg rtPA infused over 25 hours. If initially failed, a repeat 6-hour infusion of 25 mg rtPA was administered up to a maximum total cumulative dose of 150 mg or until an adverse event occurred. The primary objective was the rate of complete MPVT resolution, defined as &amp;gt;75% reduction in the obstructive gradient by transthoracic echocardiography, less than 10 degrees residual constraint in opening and closing valve motion angles as quantified by fluoroscopy, and alleviation of patients’ thrombosis-associated symptoms or signs. Results From April 2018 to November 2023, 135 infusions of thrombolytic therapy were administered in 118 patients (median age: 35 years (IQR, 25-49); 59 [50%] women) (Table 1). 12 patients had more than one episode of MPVT during the study period. Obstructive prosthetic valve thrombosis occurred in 89.6% (121/135) of cases. Pulmonary valves were most frequently affected (n = 84, 62.2%), followed by tricuspid (n = 34, 25.2%), mitral (n = 10, 7.4%), and aortic (n = 7, 5.2%) valves. A complete thrombolysis success was achieved in 119/135 episodes of thrombolytic therapy (88.1%); of these, 47/119 patients (39.5%) responded after the first thrombolytic dose. The median total dose administered was 50 mg (IQR, 25-75) over a median infusion duration of 30 hours (IQR, 25-36). Four patients responded partially to the regimen, six patients were candidates for bailout surgery, and only one fatal intracranial bleeding occurred. No other thromboembolic or bleeding adverse events were observed. Conclusion This is the largest prospective evaluation on the safety and efficacy of the ultraslow low-dose thrombolytic regimen, which proved highly effective - in this prospective cohort - in achieving prosthetic valve thrombosis resolution with minimal complications. Further larger clinical trials are warranted.Table 1- baseline CharacteristicsStudy Outcomes

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p&amp;lt;0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to &amp;lt;50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p&amp;gt;0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p&amp;gt;0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p&amp;gt;0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p&amp;lt;0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p&amp;lt;0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p &amp;lt; 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient &amp;gt; 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p &amp;lt; 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality