A simply calculated nutritional index provides clinical implications in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Malnutrition is associated with adverse outcomes in patients with aortic stenosis. The Triglycerides × Total Cholesterol × Body Weight Index (TCBI) is a simple scoring model to evaluate the status of nutrition. However, the prognostic relevance of this index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. This study aimed to evaluate the association of the TCBI with clinical outcomes in patients undergoing TAVR. METHODS: A total of 1377 patients undergoing TAVR were evaluated in this study. The TCBI was calculated by the formula; triglyceride (mg/dL) × total cholesterol (mg/dL) × body weight (kg)/1000. The primary outcome was all-cause mortality within 3 years. RESULTS: Patients with a low TCBI, based on a cut-off value of 985.3, were more likely to have elevated right atrial pressure (p = 0.04), elevated right ventricular pressure (p < 0.01), right ventricular systolic dysfunction (p < 0.01), tricuspid regurgitation ≥ moderate (p < 0.01). Patients with a low TCBI had a higher cumulative 3-year all-cause (42.3% vs. 31.6%, p < 0.01; adjusted HR 1.36, 95% CI 1.05-1.77, p = 0.02) and non-cardiovascular mortality (15.5% vs. 9.1%, p < 0.01; adjusted HR 1.95, 95% CI 1.22-3.13, p < 0.01) compared to those with a high TCBI. Adding a low TCBI to EuroSCORE II improved the predictive value for 3-year all-cause mortality (net reclassification improvement, 0.179, p < 0.01; integrated discrimination improvement, 0.005, p = 0.01). CONCLUSION: Patients with a low TCBI were more likely to have right-sided heart overload and exhibited an increased risk of 3-year mortality. The TCBI may provide additional information for risk stratification in patients undergoing TAVR.

Opportunistic CT-derived analysis of fat and muscle tissue composition predicts mortality in patients with cardiogenic shock.

Prognosis estimation in patients with cardiogenic shock (CS) is important to guide clinical decision making. Aim of this study was to investigate the predictive value of opportunistic CT-derived body composition analysis in CS patients. Amount and density of fat and muscle tissue of 152 CS patients were quantified from single-slice CT images at the level of the intervertebral disc space L3/L4. Multivariable Cox regression and Kaplan-Meier survival analyses were performed to evaluate the predictive value of opportunistically CT-derived body composition parameters on the primary endpoint of 30-day mortality. Within the 30-day follow-up, 90/152 (59.2%) patients died. On multivariable analyses, lactate (Hazard Ratio 1.10 [95% Confidence Interval 1.04-1.17]; p = 0.002) and patient age (HR 1.04 [95% CI 1.01-1.07], p = 0.017) as clinical prognosticators, as well as visceral adipose tissue (VAT) area (HR 1.004 [95% CI 1.002-1.007]; p = 0.001) and skeletal muscle (SM) area (HR 0.987 [95% CI 0.975-0.999]; p = 0.043) as imaging biomarkers remained as independent predictors of 30-day mortality. Kaplan-Meier survival analyses showed significantly increased 30-day mortality in patients with higher VAT area (p = 0.015) and lower SM area (p = 0.035). CT-derived VAT and SM area are independent predictors of dismal outcomes in CS patients and have the potential to emerge as new imaging biomarkers available from routine diagnostic CT.

Impact of transradial versus transfemoral access for preprocedural coronary angiography on TAVR-associated complications.

Background: Vascular injury and bleeding complications remain frequent after transcatheter aortic valve replacement (TAVR). Whether the access-site of preprocedural coronary angiography (CAG) affects TAVR-related complications is not known. The aim of this study was to evaluate the impact of transradial (TRA) versus transfemoral access (TFA) for preprocedural CAG on outcomes in patients undergoing subsequent TAVR. Methods: The study cohort included 1002 patients undergoing transfemoral TAVR, of whom 39.4% (395/1002) had undergone radial and 60.6% (607/1002) femoral access for pre-TAVR CAG. The primary endpoint was a composite of 30-day mortality and major vascular complications after TAVR. Key secondary endpoints included VARC-3-defined complications. Results: The primary endpoint occurred less frequently in patients with prior TRA (3.3%) as compared to patients with prior TFA (6.3%, p = 0.04), which was mainly driven by significantly lower rates of major vascular complications (0.8% vs 2.5%, p = 0.05). Moreover, incidences of periprocedural access-related vascular injury and unplanned endovascular interventions were lower in TRA patients (13.2% vs 18.0%, p = 0.05). The rate of major bleeding tended to be lower in the TRA (1.5%) as compared to the TFA group (3.5%) but was not significantly different (p = 0.07). Moreover, the rate of life-threatening bleeding was comparable between both groups (0.5% vs 0.8%, p = 0.71). Conclusion: Transradial access for preprocedural CAG was associated with significantly lower rates of vascular complications following subsequent TAVR as compared to transfemoral access. However, despite the tendency to lower major bleedings with transradial access, no significant association was detectable between the access-site of coronary angiography and TAVR-related bleeding complications.

Comparison of Coronary Intravascular Lithotripsy and Rotational Atherectomy in the Modification of Severely Calcified Stenoses.

Debulking techniques are often necessary for successful lesion preparation in percutaneous coronary intervention. The aim of this study was to compare plaque modification of severely calcified lesions by coronary intravascular lithotripsy (IVL) with that of rotational atherectomy (RA) using optical coherence tomography (OCT). ROTA.shock was a 1:1 randomized, prospective, double-arm, multicenter noninferiority trial designed to compare final minimal stent area after IVL with RA for lesion preparation in percutaneous coronary interventional treatment of severely calcified lesions. On the basis of OCT acquired before and immediately after IVL or RA in 21 of the 70 patients included, we performed a detailed analysis of the modification of the calcified plaque. After RA and IVL, calcified plaque fractures were present in 14 of the patients (67%), with a significantly greater number of fractures after IVL (3.23 ± 0.49) than after RA (1.67 ± 0.52; p < 0.001). Plaque fractures after IVL were longer than after RA (IVL: 1.67 ± 0.43 mm vs RA: 0.57 ± 0.55 mm; p = 0.01), resulting in a greater total volume of the fractures (IVL: 1.47 ± 0.40 mm3 vs RA: 0.48 ± 0.27 mm3; p = 0.003). Use of RA was associated with a greater acute lumen gain than was use of IVL (RA: 0.46 ± 0.16 mm2 vs IVL: 0.17 ± 0.14 mm2; p = 0.03). In conclusion, we were able to show differences in plaque modification of calcified coronary lesions by OCT: although RA leads to a greater acute lumen gain, IVL induces more and longer fractures of the calcified plaque.

Relevance of serum levels of the endoplasmic reticulum stress protein GRP78 (glucose-regulated protein 78 kDa) as biomarker in pulmonary diseases.

Cellular stress and inflammation contribute to the initiation and progression of a variety of pulmonary diseases. Endoplasmic reticulum (ER) stress and its main regulator GRP78 (glucose-regulated protein 78 kDa) appear to be involved in the pathogenesis of pulmonary diseases, and GRP78 was found to be a biomarker in a wide range of inflammatory diseases. The aim of this study was to investigate the relevance of serum GRP78 in pulmonary disorders.In this prospective cohort study, 78 consecutive patients with chronic obstructive pulmonary disease (COPD, n = 28), asthma (n = 38) or interstitial lung disease (ILD, n = 12) underwent measurement of serum GRP78 levels by ELISA.The mean age of patients was 59.8 ± 12.4 years, 48.7% were female. Patients with elevated GRP78 levels (> median) offered a significantly better oxygenation status (capillary pO2: 75.3 ± 11.7 mmHg vs. 67.8 ± 15.9 mmHg, p = 0.02). Significant correlations were observed between GRP78, on the one hand, and haemoglobin, high-sensitivity C-reactive protein (hs-CRP) and eosinophil counts, on the other hand (haemoglobin: Pearson's r = -0.25, hs-CRP: r = 0.30, eosinophils: r = 0.63).Subsequently, we evaluated GRP78 measurements in function of severity stratifiers of the specific underlying pulmonary disease. ILD patients with a severe diffusion impairment (DLCO< 40% of predicted), exhibited a significant decrease in GRP78 levels (p = 0.01). In COPD and asthma, both characterized by obstructive ventilatory defects, a forced expiratory volume in one second (FEV1) <30% of predicted was accompanied by significantly lower GRP78 (p = 0.0075).In both obstructive and restrictive pulmonary disorders, GRP78 protein concentrations were reduced with increasing disease severity. These data suggest a prevalent role of GRP78 in the presently studied pulmonary disorders.

Optimal protamine-to-heparin dosing ratio for the prevention of bleeding complications in patients undergoing TAVR-A multicenter experience.

BACKGROUND: Despite major advances, transcatheter aortic valve replacement (TAVR) is still associated with procedure-specific complications. Although previous studies reported lower bleeding rates in patients receiving protamine for heparin reversal, the optimal protamine-to-heparin dosing ratio is unknown. HYPOTHESIS: The aim of this study was a comparison of two different heparin antagonization regimens for the prevention of bleeding complications after TAVR. METHODS: The study included 1446 patients undergoing TAVR, of whom 623 received partial and 823 full heparin antagonization. The primary endpoint was a composite of 30-day mortality, life-threatening, and major bleeding. Safety endpoints included stroke and myocardial infarction at 30 days. RESULTS: Full antagonization of heparin resulted in lower rates of the primary endpoint as compared to partial heparin reversal (5.6% vs. 10.4%, p < .01), which was mainly driven by lower rates of life-threatening (0.5% vs. 1.6%, p = .05) and major bleeding (3.2% vs. 7.5%, p < .01). Moreover, the incidence of major vascular complications was significantly lower in patients with full heparin reversal (3.5% vs. 7.5%, p < .01). The need for red-blood-cell transfusion was lower in patients receiving full as compared to partial heparin antagonization (10.4% vs. 15.9%, p < .01). No differences were observed in the incidence of stroke and myocardial infarction between patients with full and partial heparin reversal (2.2% vs. 2.6%, p = .73 and 0.2% vs. 0.4%, p = .64, respectively). CONCLUSIONS: Full heparin antagonization resulted in significantly lower rates of life-threatening and major bleeding after TAVR as compared to partial heparin reversal. The occurrence of stroke and myocardial infarction was low and comparable between both groups.

ER-stress-induced secretion of circulating glucose-regulated protein 78kDa (GRP78) ameliorates pulmonary artery smooth muscle cell remodelling.

Pulmonary arterial hypertension (PAH) is driven by vascular remodelling due to inflammation and cellular stress, including endoplasmic reticulum stress (ER stress). The main ER-stress chaperone, glucose-regulated protein 78 kDa (GRP78), is known to have protective effects in inflammatory diseases through extracellular signalling. The aim of this study is to investigate its significance in PAH. Human pulmonary arterial smooth muscle cells (PASMC) were stimulated with compounds that induce ER stress, after which the secretion of GRP78 into the cell medium was analysed by western blot. We found that when ER stress was induced in PASMC, there was also a time-dependent secretion of GRP78. Next, naïve PASMC were treated with conditioned medium (CM) from the ER-stressed donor PASMC. Incubation with CM from ER-stressed PASMC reduced the viability, oxidative stress, and expression of inflammatory and ER-stress markers in target cells. These effects were abrogated when the donor cells were co-treated with Brefeldin A to inhibit active secretion of GRP78. Direct treatment of PASMC with recombinant GRP78 modulated the expression of key inflammatory markers. Additionally, we measured GRP78 plasma levels in 19 PAH patients (Nice Group I) and correlated the levels to risk stratification according to ESC guidelines. Here, elevated plasma levels of GRP78 were associated with a favourable risk stratification. In conclusion, GRP78 is secreted by PASMC under ER stress and exhibits protective effects from the hallmarks of PAH in vitro. Circulating GRP78 may serve as biomarker for risk adjudication of patients with PAH. Proposed mechanism of ER-stress-induced GRP78 secretion by PASMC. Extracellular GRP78 can be measured as a circulating biomarker and is correlated with favourable clinical characteristics. Conditioned medium from ER-stressed PASMC reduces extensive viability, ROS formation, inflammation, and ER stress in target cells. These effects can be abolished by blocking protein secretion in donor cells by using Brefeldin A.

Predictive value of the Fibrosis-4 index in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Liver dysfunction is associated with an increased risk of mortality after cardiac interventions. The Fibrosis-4 (FIB-4 index), a marker of hepatic fibrosis, has been associated with a worse prognosis in heart failure. The prognostic relevance of the index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. The aim of this study was to evaluate the clinical implications associated with the FIB-4 index in patients undergoing TAVR. METHODS: Between May 2012 and June 2019, 941 patients undergoing TAVR were stratified into a low or high FIB-4 index group, based on a cutoff value that was determined according to a receiver operating characteristic curve predicting 1-year all-cause mortality. RESULTS: Patients with a high FIB-4 index (n = 480), based on the cutoff value of 1.82, showed higher rates of pulmonary hypertension (43.8% vs. 31.8%, p < 0.01), right-ventricular systolic dysfunction (29.5% vs. 19.2%, p < 0.01) and larger inferior vena cava diameter (1.6 ± 0.6 cm vs. 1.3 ± 0.6 cm, p < 0.01) than patients with a low FIB-4 index (n = 461). Furthermore, a high FIB-4 index was associated with a significantly higher cumulative 1-year all-cause mortality (17.5% vs. 10.2%, p < 0.01) and non-cardiovascular mortality (12.1% vs. 2.5%, p < 0.01), compared to a low FIB-4 index. Multivariable analysis revealed that a high FIB-4 index was independently associated with all-cause mortality (HR: 1.75 [95% CI: 1.18-2.59], p < 0.01). CONCLUSIONS: A high FIB-4 index is associated with right-sided heart overload and an increased risk of mortality in patients undergoing TAVR. The FIB-4 index may be useful as an additional predictor of outcomes in these patients.

Coronary lithotripsy for the treatment of underexpanded stents: the international & multicentre CRUNCH registry.

BACKGROUND: Stent underexpansion increases the risk of cardiac adverse events. At present, there are limited options to treat refractory stent underexpansion. In this context, the intravascular lithotripsy (IVL) system might be a safe and effective strategy. AIMS: We aimed to evaluate the safety and efficacy of IVL in addressing resistant stent underexpansion due to heavy underlying calcification. METHODS: This was an international multicentre registry including patients receiving IVL therapy to treat stent underexpansion from December 2017 to August 2020. Angiographic and intracoronary imaging data were collected. The efficacy endpoint was device success (technical success with a final percentage diameter stenosis <50%). The safety endpoint was in-hospital major adverse cardiac events (MACE). RESULTS: Seventy patients were included, the mean age was 73±9.2 years and 76% were male. The median time from stent implantation to IVL therapy was 49 days (0-2,537). Adjuvant treatment with non-compliant balloon dilatations pre- and post-IVL was performed in 72.3% and 76.8% of patients, respectively, and additional stenting was performed in 22.4%. Device success was 92.3%. Minimum lumen diameter increased from 1.49±0.73 mm to 2.41±0.67 mm (p<0.001) and stent expansion increased by 124.93±138.19% (p=0.016). No IVL-related procedural complications or MACE were observed. The use of bailout IVL therapy directly after stenting and the presence of ostial underexpanded lesions negatively predicted lumen diameter gain. CONCLUSIONS: Coronary lithotripsy is safe and effective in increasing lumen and stent dimensions in underexpanded stents secondary to heavily calcified lesions.

Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation.

AIMS: Intracranial haemorrhage (ICH) is one of the most serious complications of adult patients treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) and is associated with increased morbidity and mortality. However, the prevalence and risk factors of ICH in this cohort are still insufficiently understood. We hypothesized that a considerable proportion of patients undergoing VA-ECMO support suffer from ICH and that specific risk factors are associated with the occurrence of ICH. Therefore, the purpose of this study was to further investigate the prevalence and associated mortality as well as to identify risk factors for ICH in VA-ECMO patients. METHODS AND RESULTS: We conducted a retrospective multicentre study including adult patients (≥18 years) treated with VA-ECMO in cardiac intensive care units (ICUs) at five German clinical sites between January 2016 and March 2020, excluding patients with ICH upon admission. Differences in baseline characteristics and clinical outcome between VA-ECMO patients with and without ICH were analysed and risk factors for ICH were identified. Among the 598 patients included, 70/598 (12%) developed ICH during VA-ECMO treatment. In-hospital mortality in patients with ICH was 57/70 (81%) and 1-month mortality 60/70 (86%), compared to 332/528 (63%) (P = 0.002) and 340/528 (64%) (P < 0.001), respectively, in patients without ICH. Intracranial haemorrhage was positively associated with diabetes mellitus [odds ratio (OR) 2, 95% confidence interval (CI) 1.11-3.56; P = 0.020] and lactate (per mmol/L) (OR 1.06, 95% CI 1.01-1.11; P = 0.020), and negatively associated with platelet count (per 100 G/L) (OR 0.32, 95% CI 0.15-0.59; P = 0.001) and fibrinogen (per 100 mg/dL) (OR 0.64, 95% CI 0.49-0.83; P < 0.001). CONCLUSION: Intracranial haemorrhage was associated with a significantly higher mortality rate. Diabetes mellitus and lactate were positively, platelet count, and fibrinogen level negatively associated with the occurrence of ICH. Thus, platelet count and fibrinogen level were revealed as potentially modifiable, independent risk factors for ICH. The findings address an area with limited data, provide information about risk factors and the epidemiology of ICH, and may be a starting point for further investigations to develop effective strategies to prevent and treat ICH.

Propensity-score-matched comparison of safety, efficacy, and outcome of intravascular lithotripsy versus high-pressure PTCA in coronary calcified lesions.

BACKGROUND: Data regarding safety, efficacy, and outcome of intravascular lithotripsy (IVL) in comparison to standard techniques are lacking. This study sought to compare IVL with non-compliant high-pressure balloon percutaneous coronary angioplasty (PTCA). METHODS AND RESULTS: We performed a retrospective propensity-score-matched study to compare procedural success in 57 consecutive patients who received IVL-guided PCI in calcified coronary lesions with 171 matched patients who were treated with high-pressure PTCA with a non-compliant (NC)-balloon. The mean minimal lumen diameter (MLD) for the IVL group was 1.08 ± 0.51 mm, and the median percent diameter stenosis on quantitative angiography was 70.2% (interquartile range, 60.2-78.6%). MLD in the high-pressure dilatation group was 0.97 ± 0.43 mm, and the median percent diameter stenosis was 71.5% (interquartile range, 58.5-77.0%). IVL-guided PCI reduced median stenosis to 17.5% (interquartile range, 9.3-19.8%) with an acute gain of 0.93 ± 0.7 mm. High-pressure dilatation resulted in a final median stenosis of 19.3% (interquartile range, 13.33-28.5%). Procedural success was significantly higher (82.5% vs. 61.4%; p: 0.0035) in the IVL group. MACE through 12 months occurred in 10.5% of cases in the IVL group and in 11.1% of the high-pressure group (p = 0.22). Angiographic complications (coronary dissection, slow or no reflow, new coronary thrombus formation, abrupt vessel closure) were very low (0.2% vs. 0.12%). CONCLUSION: IVL resulted in a significantly higher rate of procedural success compared to high- pressure NC-balloon dilatation in patients with calcified coronary lesions. The rate of MACE through 12 months was similar to the standard therapy.

Vitamin K Epoxide Reductase Complex Subunit 1-Like 1 (VKORC1L1) Inhibition Induces a Proliferative and Pro-inflammatory Vascular Smooth Muscle Cell Phenotype.

Background: Vitamin K antagonists (VKA) are known to promote adverse cardiovascular remodeling. Contrarily, vitamin K supplementation has been discussed to decelerate cardiovascular disease. The recently described VKOR-isoenzyme Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) is involved in vitamin K maintenance and exerts antioxidant properties. In this study, we sought to investigate the role of VKORC1L1 in neointima formation and on vascular smooth muscle cell (VSMC) function. Methods and Results: Treatment of wild-type mice with Warfarin, a well-known VKA, increased maladaptive neointima formation after carotid artery injury. This was accompanied by reduced vascular mRNA expression of VKORC1L1. In vitro, Warfarin was found to reduce VKORC1L1 mRNA expression in VSMC. VKORC1L1-downregulation by siRNA promoted viability, migration and formation of reactive oxygen species. VKORC1L1 knockdown further increased expression of key markers of vascular inflammation (NFκB, IL-6). Additionally, downregulation of the endoplasmic reticulum (ER) membrane resident VKORC1L1 increased expression of the main ER Stress moderator, glucose-regulated protein 78 kDa (GRP78). Moreover, treatment with the ER Stress inducer tunicamycin promoted VKORC1L1, but not VKORC1 expression. Finally, we sought to investigate, if treatment with vitamin K can exert protective properties on VSMC. Thus, we examined effects of menaquinone-7 (MK7) on VSMC phenotype switch. MK7 treatment dose-dependently alleviated PDGF-induced proliferation and migration. In addition, we detected a reduction in expression of inflammatory and ER Stress markers. Conclusion: VKA treatment promotes neointima formation after carotid wire injury. In addition, VKA treatment reduces aortal VKORC1L1 mRNA expression. VKORC1L1 inhibition contributes to an adverse VSMC phenotype, while MK7 restores VSMC function. Thus, MK7 supplementation might be a feasible therapeutic option to modulate vitamin K- and VKORC1L1-mediated vasculoprotection.

CHA2DS2-VASC score predicts coronary artery disease progression and mortality after ventricular arrhythmia in patients with implantable cardioverter-defibrillator.

AIM: The CHA2DS2-VASC score has expanded its use beyond the initial purpose of predicting the risk of stroke in patients with atrial fibrillation. We aimed to investigate the value of the CHA2DS2-VASC score as a risk assessment tool to predict relevant coronary artery disease (CAD) leading to percutaneous coronary intervention (PCI), and all-cause mortality after detected ventricular arrhythmia (VA) in patients with an Implantable Cardioverter-Defibrillator (ICD). METHODS: A total of 183 ICD-patients who underwent coronary angiography after VA were included and classified according to their CHA2DS2-VASC score in a low(1-3), intermediate(4-5) and high(6-8) score group. We evaluated the predictive value of CHA2DS2-VASC score for the presence of relevant CAD leading to percutaneous coronary intervention (PCI), as well as late all-cause mortality. RESULTS: A total of 60 patients (32.8%) had significant CAD and underwent successful PCI. After adjustment for relevant parameters such as ischemic cardiomyopathy, angina pectoris, left ventricular ejection fraction, CHA2DS2-VASC score remained the only independent predictor of CAD leading to PCI [HR 1.73 (1.07-2.80)]. The Area under curve was 0.64 (0.56-72, p = 0.002). Kaplan-Meier analysis and log-rank showed an increased three-year mortality of ICD-patients with an intermediate or high score after VA (p = 0.003). Multivariate cox-regression analysis revealed that CHA2DS2-VASC score was also independently associated with all-cause mortality following adjustment for clinically relevant variables (HR 2.20, 1.17-4.14). CONCLUSIONS: CHA2DS2-VASC score can be a predictor of CAD leading to PCI in ICD-patients after VA. ICD-Patients with a high score have an increased risk for reduced three-year all-cause mortality after VA.

Circulating chaperones in patients with aortic valve stenosis undergoing TAVR: impact of concomitant chronic kidney disease.

Chronic kidney disease (CKD) is a frequent comorbidity of aortic valve stenosis (AVS). Circulating chaperones have emerged as both effectors and prognostic markers for various diseases. We investigated the role of circulating chaperones in patients with severe AVS undergoing transcatheter aortic valve replacement (TAVR). In this observational cohort study, 159 consecutive patients undergoing TAVR were included and serum levels of Glucose-regulated protein 78 (GRP78) and heat shock protein 27 (HSP27) were measured by ELISA. The primary end point was defined as 1-year mortality. Patients with lower levels of circulating GRP78 (<1347 ng/mL) had an increased 1-year mortality rate compared to patients with higher levels of GRP78 (25.0% vs 10.3%, P = 0.026). GRP78 was associated with lower 1-year mortality in a univariate analysis (HR 0.354, P = 0.047). After adjusting for age, sex, several comorbidities and biomarkers, GRP78 (HR 0.295, P = 0.024) and CKD (HR 2.809, P = 0.044) remained independent predictors of the primary end point of 1-year mortality in a multivariate analysis. Patients with concomitant CKD had significantly higher levels of HSP27 compared to patients without CKD (1690 pg/mL vs 1076 pg/mL, P = 0.0109). In patients with CKD, elevated HSP27 was identified as a protective marker (1-year mortality: 9.6% vs 31.4%, log-rank P = 0.0166). Using cut-off values for GRP78 and HSP27 we were able to stratify patients with CKD undergoing TAVR into 4 groups with distinct mortality rates (50% vs 22.2% vs 24% vs 7.9%, log-rank P = 0.0170). GRP78 is an overall predictor of mortality after TAVR, while the combination of GRP78 and HSP27 helps to predict mortality in patients with CKD receiving TAVR.

Hospital admissions during Covid-19 lock-down in Germany: Differences in discretionary and unavoidable cardiovascular events.

BACKGROUND: A decline in hospitalization for cardiovascular events and catheter laboratory activation was reported for the United States and Italy during the initial stage of the Covid-19 pandemic of 2020. We report on the deployment of emergency services for cardiovascular events in a defined region in western Germany during the government-imposed lock-down period. METHODS: We examined 5799 consecutive patients who were treated by emergency services for cardiovascular events during the Covid-19 pandemic (January 1 to April 30, 2020), and compared those to the corresponding time frame in 2019. Examining the emergency physicians' records provided by nine locations in the area, we found a 20% overall decline in cardiovascular admissions. RESULTS: The greatest reduction could be seen immediately following the government-imposed social restrictions. This reduction was mainly driven by a reduction in discretionary admissions for dizziness/syncope (-53%), heart failure (-38%), exacerbated COPD (-28%) and unstable angina (-23%), while unavoidable admissions for ST-elevation myocardial infarction (STEMI), cardiopulmonary resuscitation (CPR) and stroke were unchanged. There was a greater decline in emergency admissions for patients ≥60 years. There was also a greater reduction in emergency admissions for those living in urban areas compared to suburban areas. CONCLUSIONS: During the Covid-19 pandemic, a significant decline in hospitalization for cardiovascular events was observed during the government-enforced shutdown in a predefined area in western Germany. This reduction in admissions was mainly driven by "discretionary" cardiovascular events (unstable angina, heart failure, exacerbated COPD and dizziness/syncope), but events in which admission was unavoidable (CPR, STEMI and stroke) did not change.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. METHODS: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort. RESULTS: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). CONCLUSIONS: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Health-related factors on tobacco consumption in Turkey / Fatores relacionados com a saúde e o consumo de tabaco na Turquia

ABSTRACT: In this study, we analyzed the role of individuals' health-related factors along with socio-demographic and economic characteristics on both the likelihood of tobacco consumption and quantity demanded levels using two competitive econometric methods: double hurdle model versus hyperbolic sine double-hurdle model. Statistical tests confirmed the dependency errors between the prevalence rate of smoking and the consumption level, whilst the inverse-hyperbolic sine double-hurdle model data fits best in describing the normalization of the data and the two data generating processes: the probability and consumption levels of cigarettes. Also, the variance-covariance of the selected model as a function of additional exogenous variables are confirmed, while the error terms between the likelihood to smoke and the consumption levels are positive and statistically significant, indicating that holding control variables fixed, the uncontrolled variables out of the system that increase the prevalence rate of smoking also boost the consumption level, or vice versa. Many individual disease variables are significant in both equations, breaking new grounds in literature for identifying how both the prevalence rate of smoking and amount have shaped.

RESUMO: Neste estudo, analisamos o papel dos fatores relacionados à saúde dos indivíduos, juntamente com as características sócio-demográficas e econômicas, tanto na probabilidade de consumo de tabaco quanto nos níveis de quantidade demandada, usando dois métodos econométricos competitivos: modelo de obstáculo duplo versus modelo de obstáculo duplo seno hiperbólico. Os testes estatísticos confirmaram os erros de dependência entre a taxa de prevalência de tabagismo e o nível de consumo, enquanto o modelo de seno duplo inverso-hiperbólico se ajusta melhor aos dados para descrever a normalização dos dados e os dois processos geradores de dados: os níveis de probabilidade e consumo de cigarros. Também são confirmadas a covariância de variância do modelo selecionado em função de variáveis exógenas adicionais, enquanto os termos de erro entre a probabilidade de fumar e os níveis de consumo são positivos e estatisticamente significativos, indicando que, mantendo variáveis de controle fixas, as variáveis não controladas são do sistema que aumenta a taxa de prevalência do tabagismo e também cresce o nível de consumo, ou vice-versa. Muitas variáveis individuais da doença são encontradas significativamente em ambas as equações, abrindo novos caminhos na literatura para identificar como a taxa de prevalência de tabagismo e a quantidade se moldaram.

Intravascular Lithotripsy in Calcified Coronary Lesions: A Prospective, Observational, Multicenter Registry.

BACKGROUND: Optimal plaque preparation of calcified coronary lesions is key to prevent stent failure. The purpose of this study was to determine the strategy success and safety of intravascular lithotripsy (IVL) in calcified lesions of an all-comers cohort. METHODS: Patients with calcified coronary lesions were screened in 3 centers. Seventy-one patients were eligible for IVL. Patients were assigned to (group A) primary IVL therapy for patients with calcified de-novo lesions (n=39 lesions), (group B) secondary IVL therapy for patients with calcified lesions in which noncompliant balloon dilatation failed (n=22 lesions), and (group C) tertiary IVL therapy in patients with stent underexpansion after previous stenting (n=17 lesions). Primary end point was strategy success (stent expansion with <20% in-stent residual stenosis) and safety outcomes (procedural complications, in-hospital major adverse cardiovascular event). RESULTS: Seventy-eight calcified lesions were treated using the Shockwave C2 balloon. Mean diameter stenosis of calcified lesions was 71.8±13.1% at baseline, decreased to 45.1±17.4% immediately after IVL, and to 17.5±15.2% after stenting. Mean minimal lumen diameter was 1.01±0.49 mm at baseline and increased to 1.90±0.61 after IVL, and to 2.88±0.56 mm after stenting. The primary end point of strategy success was reached in 84.6% (group A), 77.3% (group B), and 64.7% (group C). Device delivery and IVL treatment were possible in all lesions. Four type b dissections were observed without further sequelae. No patient suffered from in-hospital major adverse cardiovascular event. Seven Shockwave balloons ruptured during treatment without any sequelae. CONCLUSIONS: IVL provides a valid strategy for lesion preparation in severely calcified coronary lesions with high success rate, low procedural complications, and low major adverse cardiovascular event rates.

Genetic disruption of multidrug resistance-associated protein 1 improves endothelial function and attenuates atherosclerosis in MRP1-/- LDLr-/- double knockout mice.

INTRODUCTION: Multidrug resistance-associated protein 1 (MRP1) is an anion transporter which is implicated in the efflux of the intracellular antioxidant anion glutathione as well as leukotrienes. Pharmacological inhibition of MRP1 exhibits antioxidative and anti-atherosclerotic effects both in vitro and in vivo. However, pharmacological inhibitors of MRP1 lack selectivity, which prompted us to study the in vivo impact of a genetic disruption of MRP1 on endothelial dysfunction, reactive oxygen species formation and atherogenesis in an atherosclerotic mouse model. MATERIAL AND METHODS: MRP1-/- LDLr-/- double knockout mice. were fed a high-fat and cholesterol-rich diet for 7 weeks. Thereafter, endothelial function was assessed in isolated aortic rings. Reactive oxygen species were quantified by L-012 chemiluminescence, and the atherosclerotic plaque burden was measured following oil red O staining. RESULTS: Endothelium-dependent vasodilation of MRP1-/- LDLr-/- double knockout mice was significantly improved compared to MRP1-competent LDLr-/- single knockout mice (0.56 ±0.06 vs. 0.78 ±0.08; n = 10; p = 0.048). This improvement was accompanied by a significant reduction in reactive oxygen species formation within the aortic tissue (102 ±27 RLU/s/mg vs. 315 ±78 RLU/s/mg, n = 9-11, p = 0.03). Moreover, the atherosclerotic plaque burden of MRP1-/- LDLr-/- double knockout mice was significantly reduced (0.06 ±0.01 vs. 0.12 ±0.02; n = 6; p = 0.047). Finally, arterial blood pressure was significantly reduced in MRP1-/- LDLr-/- double knockout mice (93 ±5 mm Hg vs. 128 ±4 mm Hg; n = 8-12; p < 0.001). CONCLUSIONS: Genetic disruption of MRP1 appears to reduce blood pressure and vascular oxidative stress in vivo, which leads to improved endothelial function and a reduced plaque burden in atherosclerotic mice. Therefore, MRP1 might represent a promising therapeutic target to improve endothelial function in patients suffering from atherosclerosis.