Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

Protein Kinase D Plays a Crucial Role in Maintaining Cardiac Homeostasis by Regulating Post-Translational Modifications of Myofilament Proteins.

Protein kinase D (PKD) enzymes play important roles in regulating myocardial contraction, hypertrophy, and remodeling. One of the proteins phosphorylated by PKD is titin, which is involved in myofilament function. In this study, we aimed to investigate the role of PKD in cardiomyocyte function under conditions of oxidative stress. To do this, we used mice with a cardiomyocyte-specific knock-out of Prkd1, which encodes PKD1 (Prkd1loxP/loxP; αMHC-Cre; PKD1 cKO), as well as wild type littermate controls (Prkd1loxP/loxP; WT). We isolated permeabilized cardiomyocytes from PKD1 cKO mice and found that they exhibited increased passive stiffness (Fpassive), which was associated with increased oxidation of titin, but showed no change in titin ubiquitination. Additionally, the PKD1 cKO mice showed increased myofilament calcium (Ca2+) sensitivity (pCa50) and reduced maximum Ca2+-activated tension. These changes were accompanied by increased oxidation and reduced phosphorylation of the small myofilament protein cardiac myosin binding protein C (cMyBPC), as well as altered phosphorylation levels at different phosphosites in troponin I (TnI). The increased Fpassive and pCa50, and the reduced maximum Ca2+-activated tension were reversed when we treated the isolated permeabilized cardiomyocytes with reduced glutathione (GSH). This indicated that myofilament protein oxidation contributes to cardiomyocyte dysfunction. Furthermore, the PKD1 cKO mice exhibited increased oxidative stress and increased expression of pro-inflammatory markers interleukin (IL)-6, IL-18, and tumor necrosis factor alpha (TNF-α). Both oxidative stress and inflammation contributed to an increase in microtubule-associated protein 1 light chain 3 (LC3)-II levels and heat shock response by inhibiting the mammalian target of rapamycin (mTOR) in the PKD1 cKO mouse myocytes. These findings revealed a previously unknown role for PKD1 in regulating diastolic passive properties, myofilament Ca2+ sensitivity, and maximum Ca2+-activated tension under conditions of oxidative stress. Finally, we emphasized the importance of PKD1 in maintaining the balance of oxidative stress and inflammation in the context of autophagy, as well as cardiomyocyte function.

The impact of diabetes mellitus on the outcome of troponin-positive patients with non-obstructive coronary arteries.

Background: Diabetes mellitus is a major cardiovascular risk factor for the development of coronary artery disease, but knowledge about the impact of diabetes mellitus on the outcome of patients with myocardial infarction with non-obstructive coronary arteries is limited. The aim of this study was to investigate the prognostic impact of diabetes mellitus on in- and out-of-hospital adverse events in troponin-positive patients with non-obstructive coronary arteries. Methods and Results: A total of 373 troponin-positive patients with non-obstructive coronary arteries between 2010 and 2021 at Bergmannsheil University Hospital Bochum were enrolled, including 65 diabetics and 307 nondiabetics. The median follow-up was 6.2 years. The primary study end point was a composite of in-hospital major adverse cardiovascular events (MACE). Secondary endpoints covered MACE during follow-up.Mean age of the study cohort was 62.9 years and 49.3 % were male. Although the overall rate of in-hospital MACE was higher in diabetics (41.5 %) than in non-diabetics (33.9 %), this difference did not reach statistical significance (p = 0.240). The in-hospital mortality rate was low in both groups, 0 % of diabetes group versus 2.9 % of non-diabetic patients. During follow-up, diabetic patients had a significantly higher rate of MACE (51.9 % vs. 31.1 %, p = 0.004) and a significantly higher all-cause mortality rate than non-diabetic patients (42.3 % vs. 20.1 %, p < 0.001). Conclusion: Our study reveals that the impact of diabetes mellitus on cardiovascular outcomes in troponin-positive patients with non-obstructive coronary arteries intensifies over the long term, leading to increased rates of both cardiovascular adverse events and overall mortality.

Subcutaneous cardioverter defibrillator implanted intermuscularly in patients with end-stage renal disease requiring hemodialysis: 5-year follow-up.

BACKGROUND: The aim of the present study was to evaluate the long-term safety and effectiveness of the subcutaneous implantable cardioverter defibrillator (S-ICD) when implanted intermuscularly in patients with end-stage renal disease and hemodialysis. METHODS: This study is a retrospective analysis of 21 consecutive patients implanted with S-ICDs at three experienced centers in Germany with comorbid renal insufficiency requiring hemodialysis, as well as being at risk of sudden cardiac death. The S-ICD was placed intermuscularly in all patients. Follow-ups (FUs) were performed every 6 months. RESULTS: The mean ± standard deviation FU duration was 60.0 ± 11.4 months, with a range of 39 to 78 months. There were no deaths due to arrhythmia, or device-associated infections and complications. Four patients (19.1%) died during FU due to respiratory insufficiency during dialysis, systolic heart failure, septic infection of the urogenital tract, and colorectal cancer, respectively. There were six non-device-related hospitalizations with a duration of 12.7 ± 5.1 days and a hospitalization rate of 4.1 per 100 patient years. CONCLUSIONS: In the long-term FU of this small population of seriously compromised hemodialysis patients at risk of sudden cardiac death, the intermuscularly implanted S-ICD system was safe and effective. No arrhythmic complications, device-associated infections, or complications compromised survival. These data are encouraging and support testing in a larger group of similarly compromised patients.

Ultrasound-assisted endovascular thrombolysis versus large-bore thrombectomy in acute intermediate-high risk pulmonary embolism: The propensity-matched EKNARI cohort study.

BACKGROUND: Ultrasound-assisted thrombolysis (USAT) and large-bore-thrombectomy (LBT) are under investigation for the treatment of intermediate-high and high-risk pulmonary embolisms (PE). Comparative studies investigating both devices are scarce. AIMS: This study aimed to compare the safety and efficacy of the two most frequently used devices for treatment of acute PE. METHODS: This multicenter, retrospective study included 125 patients undergoing LBT or USAT for intermediate- or high-risk PE between 2019 and 2023. Nearest neighbor propensity matching with logistic regression was used to achieve balance on potential confounders. The primary outcome was the change in the right to left ventricular (RV/LV) ratio between baseline and 24 h. RESULTS: A total of 125 patients were included. After propensity score matching, 95 patients remained in the sample, of which 69 (73%) underwent USAT and 26 (27%) LBT. The RV/LV ratio decrease between baseline and 24 h was greater in the LBT than in the USAT group (adjusted between-group difference: -0.10, 95% CI: -0.16 to -0.04; p = 0.001). Both procedures were safe and adverse events occurred rarely (10% following USAT vs. 4% following LBT; p = 0.439). CONCLUSION: In acute intermediate-high and high-risk PE, both LBT and USAT were feasible and safe. The reduction in RV/LV ratio was greater following LBT than USAT. Further randomized controlled trials are needed to confirm these findings.

[Role of German cardiac arrest centers in mediating basic life support]. / Rolle deutscher Cardiac Arrest Center in der Vermittlung von Basisreanimationsmaßnahmen.

BACKGROUND AND OBJECTIVE: Despite a measurable increase in recent years, the bystander resuscitation rate in Germany lags behind the European comparison. Special centers for the care of patients after cardiac arrest, so-called cardiac arrest centers (CAC), have been established. The aim of this work is to evaluate the role of CACs, in addition to in-hospital patient care, in improving the bystander resuscitation rate in Germany and what obstacles exist in the implementation of resuscitation training. MATERIALS AND METHODS: Online survey by the working group cardiopulmonary resuscitation (AG42) of the German Society of Cardiology (DGK) and the German Resuscitation Council (GRC) RESULTS: Of the 74 participating clinics (78.4% certified as CAC), 23 (31.1%) conduct lay resuscitation training. These mainly take place within the framework of action days for resuscitation (82.6%) or in schools (39.1%). Permanent cooperation with at least one school existed in 52.2%. Basic life support (BLS) resuscitation dummies are available in 63.5% of these clinics and an automated external defibrillator (AED) demonstration device in 43.2%. According to the interviewees, the biggest obstacles to the consistent implementation of resuscitation courses in schools include lack of qualified instructors, lack of refinancing and difficulties with regard to coordinating activities between schools and providers. CONCLUSIONS: Direct training of lay rescuers by hospitals faces several obstacles. To increase the bystander resuscitation rate, focusing on targeted training of teachers as multipliers (train-the-trainer) can be a good approach for cardiac arrest centers.

Benefit of primary and secondary prophylactic implantable cardioverter defibrillator in elderly patients.

BACKGROUND: The benefit of implantable cardioverter-defibrillator (ICD) in elderly patients has been questioned. In the present study, we aimed to analyse the outcome of patients of different age groups with ICD implantation. METHODS: We included all patients who received an ICD in our hospital from 2011 to 2020. Primary endpoints were (1) death from any cause and (2) appropriate ICD therapy (antitachycardia pacing/shock). A "benefit of ICD implantation" was defined as appropriate ICD therapy before death from any cause/or survival. "No benefit of ICD implantation" was defined as death from any cause without prior appropriate ICD therapy. RESULTS: A total of 422 patients received an ICD (primary prophylaxis n = 323, secondary prophylaxis n = 99). At the time of implantation, 35 patients (8%) were >80 years and 106 patients were >75 years (25%). During the study period of 4.2 ± 3 years, benefit of ICD occurred in 89 patients (21%) and no benefit in 84 patients (20%). In primary prevention, the proportion of patients who had a benefit from ICD implantation decreased with increasing age, and there were no patients who benefited from ICD therapy in the group of patients >80 years. In secondary prophylaxis, the proportion of patients with a benefit from ICD implantation ranged from 20% to 30% in all age groups. CONCLUSION: Our study suggests that the indication of primary prophylactic ICD in elderly and very old patients should be critically assessed. On the other hand, no patient should be denied secondary prophylactic ICD implantation because of age.

In-hospital triggers of takotsubo syndrome: a case report on witnessing sudden death in a hospital roommate.

Background: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, mimicking an acute myocardial infarction, in the absence of obstructed coronary arteries. It is often triggered by physical or emotional stress, with catecholamines playing a central role in its pathophysiology. Recent advances have been made in categorizing TTS patients based on trigger events and comorbidities, as well as proposed classifications differentiating primary and secondary TTS. In-hospital triggers for (secondary) TTS appear to be quite common, and our aim is to bring attention of this prevalent phenomenon. Case summary: We present the clinical course of an 80-year-old man who developed TTS after witnessing the sudden death of his roommate during his hospital stay. Initially hospitalized for bradycardia and complete atrioventricular block, the patient was discharged after a pacemaker implantation. However, he returned to the hospital 3 days later with chest pain and other symptoms indicative of TTS. Diagnostic tests confirmed apical ballooning consistent with TTS, and subsequent echocardiograms showed a substantial improvement in left ventricular function. Discussion: The case is classified as in-hospital TTS, occurring unexpectedly during medical care, and suggests that secondary TTS could represent a certain 'basic risk' for hospitalized patients. We want to emphasize the importance of reducing pain and fear in the hospital setting and encourage further research to understand the association between TTS and medical procedures and therapies. Overall, this case underscores the need for strategies to reduce the frequency of TTS in hospitalized patients.

Stepwise Approach for Transvenous Lead Extraction in a Large Single Centre Cohort.

BACKGROUND: Infection, lead dysfunction and system upgrades are all reasons that transvenous lead extraction is being performed more frequently. Many centres focus on a single method for lead extraction, which can lead to either lower success rates or higher rates of major complications. We report our experience with a systematic approach from a less invasive to a more invasive strategy without the use of laser sheaths. METHODS: Consecutive extraction procedures performed over a period of seven years in our electrophysiology laboratory were included. We performed a stepwise approach with careful traction, lead locking stylets (LLD), mechanical non-powered dilator sheaths, mechanical powered sheaths and, if needed, femoral snares. RESULTS: In 463 patients (age 69.9 ± 12.3, 31.3% female) a total of 780 leads (244 ICD leads) with a mean lead dwelling time of 5.4 ± 4.9 years were identified for extraction. Success rates for simple traction, LLD, mechanical non-powered sheaths and mechanical powered sheaths were 31.5%, 42.7%, 84.1% and 92.6%, respectively. A snare was used for 40 cases (as the primary approach for 38 as the lead structure was not intact and stepwise approach was not feasible) and was successful for 36 leads (90.0% success rate). Total success rate was 93.1%, clinical success rate was 94.1%. Rate for procedural failure was 1.1%. Success for less invasive steps and overall success for extraction was associated with shorter lead dwelling time (p < 0.001). Major procedure associated complications occurred in two patients (0.4%), including one death (0.2%). A total of 36 minor procedure-associated complications occurred in 30 patients (6.5%). Pocket hematoma correlated significantly with uninterrupted dual antiplatelet therapy (p = 0.001). Pericardial effusion without need for intervention was associated with long lead dwelling time (p = 0.01) and uninterrupted acetylsalicylic acid (p < 0.05). CONCLUSION: A stepwise approach with a progressive invasive strategy is effective and safe for transvenous lead extraction.

Success and safety of deep sedation as a primary anaesthetic approach for transvenous lead extraction: a retrospective analysis.

There is a rising number in complications associated with more cardiac electrical devices implanted (CIED). Infection and lead dysfunction are reasons to perform transvenous lead extraction. An ideal anaesthetic approach has not been described yet. Most centres use general anaesthesia, but there is a lack in studies looking into deep sedation (DS) as an anaesthetic approach. We report our retrospective experience for a large number of procedures performed with deep sedation as a primary approach. Extraction procedures performed between 2011 and 2018 in our electrophysiology laboratory have been included retrospectively. We began by applying a bolus injection of piritramide followed by midazolam as primary medication and would add etomidate if necessary. For extraction of leads a stepwise approach with careful traction, locking stylets, dilator sheaths, mechanical rotating sheaths and if needed snares and baskets has been used. A total of 780 leads in 463 patients (age 69.9 ± 12.3, 31.3% female) were extracted. Deep sedation was successful in 97.8% of patients. Piritramide was used as the main analgesic medication (98.5%) and midazolam as the main sedative (94.2%). Additional etomidate was administered in 15.1% of cases. In 2.2% of patients a conversion to general anaesthesia was required as adequate level of DS was not achieved before starting the procedure. Sedation related complications occurred in 1.1% (n = 5) of patients without sequalae. Deep sedation with piritramide, midazolam and if needed additional etomidate is a safe and feasible strategy for transvenous lead extraction.

In-hospital Outcomes of Rotational Atherectomy in ST-Elevation Myocardial Infarction: Results From the Multicentre ROTA-STEMI Network.

BACKGROUND: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI). METHODS: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed. RESULTS: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001). CONCLUSIONS: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality.

Stress-Mediated Abnormalities in Regional Myocardial Wall Motion in Young Women with a History of Psychological Trauma.

BACKGROUND: Psychosocial stress has been associated with the development and progression of atherosclerotic cardiovascular disease (CVD). Previously, we reported subtle differences in global longitudinal strain in somatically healthy women with a psychiatric diagnosis of borderline personality disorder (BPD). This study aimed to investigate the impact of BPD on segmental myocardial wall motion using speckle tracking echocardiography (STE) analysis. METHODS: A total of 100 women aged between 18 and 38 years were included in this study. Fifty patients meeting the diagnostic criteria for BPD were recruited from the Department of Psychiatry (LWL-University Hospital Bochum) and compared with fifty age-matched healthy control subjects without previous cardiac disease. Laboratory tests and STE were performed with segmental wall motion analysis. RESULTS: The BPD group had a higher prevalence of risk factors for CVD, with smoking and obesity being predominant, when compared with the control group. Other cardiovascular parameters such as blood pressure, glucose, and cholesterol levels were also elevated, even though not to pathological values. Moreover, in the STE analysis, the BPD group consistently exhibited decreased deformation in nine myocardial wall regions compared with the control group, along with a shift toward higher values in the distribution of peak pathological segments. Additionally, significantly higher values of free thyroxine concentration and thyroid's secretory capacity were observed in the BPD group, despite falling within the (high-) normal range. CONCLUSIONS: BPD is associated with chronic stress, classical risk factors, and myocardial wall motion abnormalities. Further exploration is warranted to investigate the relationship between high-normal thyroid metabolism, these risk factors, and myocardial function in BPD patients. Long-term follow-up studies would be valuable in confirming the potential for predicting adverse events.

Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.

Background Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (P<0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (P=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. Conclusions Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.

Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure.

Background: The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure. The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in patients with reduced ejection fraction (HFrEF). Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. A total of 25 patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication; the other 25 patients did not receive empagliflozin and were considered the control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: The baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p < 0.001), in distance in the 6-min walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p < 0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/mL vs. 13.7 ± 15.8 pg/mL; p = 0.008). There was no significant change of these or other parameters in the control group (p > 0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, anti-inflammatory effects may contribute to the benefits of SGLT-2-inhibitors in heart failure.

Incidence of atrial and ventricular arrhythmias in obese patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

AIM: To compare clinical outcomes among patients with heart failure and reduced ejection fraction (HFrEF) according to body mass index (BMI) after initiating treatment with an angiotensin-receptor neprilysin inhibitor (ARNI). METHODS: We gathered data from 2016 to 2020 at the University Medical Center Mannheim; 208 consecutive patients were divided into two groups according to BMI (< 30 kg/m2 ; n = 116, ≥ 30 kg/m2 ; n = 92). Clinical outcomes, including mortality rate, all-cause hospitalizations and congestion, were systematically analysed. RESULTS: At the 12-month follow-up, the mortality rate was similar in both groups (7.9% in BMI < 30 kg/m2 vs. 5.6% in BMI ≥ 30 kg/m2 ; P = .76). All-cause hospitalization before ARNI treatment was comparable in both groups (63.8% in BMI < 30 kg/m2 vs. 57.6% in BMI ≥ 30 kg/m2 ; P = .69). After ARNI treatment, the hospitalization rate was also comparable in both groups at the 12-month follow-up (52.2% in BMI < 30 kg/m2 vs. 53.7% in BMI ≥ 30 kg/m2 ; P = .73). Obese patients experienced more congestion compared with non-obese patients at follow-up, without statistical significance (6.8% in BMI < 30 kg/m2 vs. 15.5% in BMI ≥ 30 kg/m2 ; P = .11). Median left ventricular ejection fraction (LVEF) improved in both groups, but significantly more in non-obese compared with obese patients at the 12-month follow-up (from 26% [3%-45%] [min.-max.] vs. 29% [10%-45%] [min.-max.] [P = .56] to 35.5% [15%-59%] [min.-max.] vs. 30% [13%-50%] [min.-max.] [P = .03], respectively). The incidence of atrial fibrillation (AF), non-sustained (ns) and sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) was less in non-obese than in obese patients after initiation of sacubitril/valsartan at the 12-month follow-up (AF: 43.5% vs. 53.7%; P = .20; nsVT: 9.8% vs. 28.4%; P = .01; VT: 14.1% vs. 17.9%; P = .52; VF: 7.6% vs. 13.4%; P = .23). CONCLUSIONS: The incidence of congestion in obese patients was higher compared with non-obese patients. LVEF improved significantly more in non-obese compared with obese HFrEF patients. Furthermore, AF and the ventricular tachyarrhythmia rate were revealed more in obesity compared with those without obesity at the 12-month follow-up.

Urokinase versus Alteplase in Patients with Intermediate-High-Risk Pulmonary Embolism Treated with Ultrasound-Accelerated Endovascular Thrombolysis.

BACKGROUND: Ultrasound-accelerated thrombolysis (USAT) is a safe and effective treatment for patients with intermediate-high-risk pulmonary embolism (PE). In all studies investigating USAT in the setting of PE, the recombinant tissue-plasminogen activator (rt-PA) alteplase or actilyse was used. Currently, there is a shortage of alteplase (Alteplase, Boehringer Ingelheim) in Europe. It is unknown whether the efficacy of urokinase (UK) is comparable with alteplase for USAT in patients with PE. METHODS: Patients with intermediate-high-risk PE undergoing USAT with urokinase and alteplase were included in this study. One-to-one nearest neighbour matching was performed to account for baseline differences. We identified one patient treated with USAT and UK (n = 9) for each patient treated with USAT and alteplase (n = 9). RESULTS: A total of 56 patients underwent USAT. The treatment was successful in all patients. The propensity score matched the identified nine pairs of patients. There were no statistically significant differences in the change in right ventricle-to-left ventricle (RV/LV) ratio (0.4 ± 0.3 versus 0.5 ± 0.4, p = 0.54), systolic pulmonary artery pressure (17.3 ± 8.0 versus 18.1 ± 8.1, p = 0.17), or improvement of RV function (5.8 ± 3.8 versus 5.1 ± 2.6, p = 1.0). The complication rates were comparable (11% in both groups, p = 0.55). There were no deaths in hospital or during 90 days in either group. CONCLUSIONS: In this case-matched comparison, the short-term clinical and echocardiographic outcomes showed comparable results between USAT-UK and USAT-rt-PA.

Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats.

Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding of HFpEF, effective treatments are still limited. In the current study we attempted to unravel the molecular basis of sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female and male transgenic (TG) rats homozygous for the rat Ren-2 renin gene (mRen2) characterized with hypertension and diastolic dysfunction and compared it to age-matched female and male wild type rats (WT) served as control. Cardiomyocytes from female and male TG rats exhibited an elevated titin-based stiffness (Fpassive), which was corrected to control level upon treatment with reduced glutathione indicating titin oxidation. This was accompanied with high levels of oxidative stress in TG rats with more prominent effects in female group. In vitro supplementation with heat shock proteins (HSPs) reversed the elevated Fpassive indicating restoration of their cytoprotective function. Furthermore, the TG group exhibited high levels of proinflammatory cytokines with significant alterations in apoptotic and autophagy pathways in both sexes. Distinct alterations in the expression of several proteins between both sexes suggest their differential impact on disease development and necessitate distinct treatment options. Hence, our data suggested that oxidative stress and inflammation distinctly drive diastolic dysfunction and remodeling in female and male rats with HFpEF and that the sex-dependent mechanisms contribute to HF pathology.

The Safety and Efficacy of Ultrasound-Accelerated Catheter-Directed Thrombolysis in Patients with Intermediate-High-Risk Pulmonary Embolism: Bo-NE-Experience.

Ultrasound-accelerated thrombolysis (USAT) is an advanced interventional therapy for patients with intermediate-high-risk pulmonary embolism (PE) who deteriorated on anticoagulation or for high-risk patients for whom systemic thrombolysis is contraindicated. The aim of this study is to investigate the safety and efficacy of this therapy with a focus on the improvement of vital signs and laboratory parameters. Seventy-nine patients with intermediate-high-risk PE were treated with USAT from August 2020 to November 2022. The therapy significantly decreased the mean RV/LV ratio from 1.2 ± 0.22 to 0.9 ± 0.2 (p < 0.001) as well as the mean PAPs from 48.6 ± 11 to 30.1 ± 9.0 mmHg (p < 0.001). The respiratory and heart rate decreased significantly (p < 0.001). Serum creatinine decreased significantly from 1.0 ± 0.35 to 0.9 ± 0.3 (p < 0.001). There were 12 access-associated complications, which could be treated conservatively. One patient had haemothorax after the therapy and had to be operated on. USAT is an effective therapy for patients with intermediate-high-risk PE, with favourable hemodynamic, clinical, and laboratory outcomes.