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Although the ectopic foci responsible for initiating atrial fibrillation (AF) are usually located in the pulmonary veins (PVs), non-PV sources may initiate AF in approximately 11% of unselected patients with paroxysmal or persistent AF. The superior vena cava (SVC) is one of the most frequent non-PV origins for initiating AF. This study aims to investigate the effect of empirical SVC isolation in redo AF ablation procedures.Consecutive patients undergoing redo AF ablation procedures using a high-power short-duration protocol (HPSD) (50 W; ablation index guided; target AI 350 for posterior wall ablation, AI 450 for anterior wall ablation; CARTO 3 mapping system) were included. Patients with SVC isolation were compared to patients without SVC isolation. Periprocedural parameters and complications were recorded and analyzed. Short-term endpoints included intrahospital AF recurrence, midterm endpoint AF freedom after 3 months, and long-term endpoint AF freedom after 12 months.A total of 276 patients underwent repeat ablation for recurrent AF (67 ± 10 years; 57% male; 31.5% paroxysmal AF). The patients were divided into two groups: redo procedures with SVC isolation vs redo procedure without SVC isolation. Additional LA substrate modification was done based on intraprocedural voltage maps. Baseline characteristics did not differ significantly between the two groups. Median procedure time was 85.4 ± 27.1 min with ablation times of 14.0 ± 8.5 min. Intrahospital AF recurrence occurred in 32 patients (12%) with no difference among both groups: 17 patients (13%) SVC vs 15 patients (10%) No-SVC; p = 0.416. At 3-month follow-up, 47 (17%) presented an AF recurrence during the blanking period: 25 patients (19%) SVC vs 22 patients (15%) No-SVC; p = 0.304). After 12 months, 202 (73%) of all patients were in stable sinus rhythm with no significant difference between the two groups: 93 patients (73%) SVC vs 109 patients (74%) No-SVC; p = 0.853). No significant differences were noted when dividing the patients in paroxysmal or persistent AF with and without SVC isolation.In our series of repeat AF ablation procedures, the addition of empirical SVC isolation to Re-PVI and LA substrate modification did not influence AF recurrence rates. This strategy can however be safe and useful in patients in whom SVC is identified as a trigger of AF.

he distribution and prognostic impact of coronary artery disease (CAD) in ES are still under debate.Consecutive ES patients with implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Three analyses were applied to characterize ES patients: (a) ES patients without CAD (non-CAD), (b) ES patients with CAD (CAD), and (c) diagnostic findings assessed by coronary angiography (CA) at the time of ES (immediate CA). CAD was compared with non-CAD ES patients, and progressive CAD was compared with stable CAD ES patients. The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were the composite endpoint of first recurrent ventricular tachyarrhythmias and appropriate ICD therapies, and recurrence of ES (ES-R) at 2.5 years.Within a total of 87 consecutive ES patients. CAD was present in more than two-thirds (67%). However, only 52% patients underwent immediate CA at the time of ES. Here, 84% had CAD, of which 39% revealed progressive CAD with the need of target vessel revascularization (TVR) or cardiac transplantation ( n = 1). At long-term follow-up, neither the presence (or absence) of CAD (41% vs. 34%; log rank P = 0.708) nor of progressive CAD (33% vs. 26%; log rank P = 0.372) was associated with all-cause mortality at 2.5 years, and further secondary endpoints including the composite of recurrent ventricular tachyarrhythmias plus appropriate ICD therapies, or ES-R.In ES patients, CAD was more common than non-CAD-related cardiac diseases, accompanied by an underinvestigated rate of CA despite increasing rates of progressive CAD. CAD had no prognostic impact in ES.

Despite a few studies evaluating the prognostic impact of coronary chronic total occlusion (CTO) in implantable cardioverter defibrillator (ICD) recipients, the impact of CTO on different types of recurrences of ventricular tachyarrhythmias, as well as their predictors has not yet been investigated in CTO patients. A large retrospective registry was used including all consecutive patients with ventricular tachyarrhythmias undergoing coronary angiography at index from 2002 to 2016. Only ICD recipients with CTO were compared to patients without (non-CTO). Kaplan–Meier and Cox regression analyses were applied for the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years. Secondary end points comprised of the different types of recurrences, first appropriate ICD therapy and all-cause mortality at 5 years. From a total of 422 consecutive ICD recipients with ventricular tachyarrhythmias at index, at least one CTO was present in 25%. CTO was associated with the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years (55% vs. 39%; log rank p = 0.001; HR = 1.665; 95% CI 1.221–2.271; p = 0.001), as well as increased risk of first appropriate ICD therapy (40% vs. 31%; log rank p = 0.039; HR = 1.454; 95% CI 1.016–2.079; p = 0.041) and all-cause mortality at 5 years (26% vs. 16%; log rank p = 0.011; HR = 1.797; 95% CI 1.133–2.850; p = 0.013). Less developed collaterals (i.e., either ipsi- or contralateral compared to bilateral) and a J-CTO score ≥ 3 were strongest predictors of recurrences in CTO patients at 5 years. A coronary CTO even in the presence of less developed collaterals and more complex CTO category is associated with increasing risk of recurrent ventricular tachyarrhythmias at 5 years in consecutive ICD recipients.

Data about atrial fibrillation (AF) ablation using high-power short duration (HPSD) radiofrequency ablation in the elderly population is still scarce. The aim of our study was to investigate the efficacy and safety of HPSD ablation in patients over 75 years compared to younger patients.Consecutive patients older than 75 years with paroxysmal or persistent AF undergoing a first-time AF ablation using 50 W HPSD ablation approach were analyzed in this retrospective observational analysis and compared to a control group75 years. Short-term endpoints included intraprocedural reconnection of at least one pulmonary vein (PV) and intrahospital and AF recurrence during 3 months blanking period, as well as a long-term endpoint of freedom from atrial arrhythmias of antiarrhythmic drugs after 12 months.A total of 540 patients underwent a first AF ablation with HPSD (66 ± 10 years; 58% male; 47% paroxysmal AF). Mean age was 78 ± 2.4 and 63 ± 6.3 years (p .001), respectively. Elderly patients were significantly more often women (p .001). The procedure, fluoroscopy, and ablation were comparable. Elderly patients revealed significantly more often extra-PV low-voltage areas requiring additional left atrial ablations (p .001). Overall complication rates were low; however, elderly patients revealed higher major complication rates mainly due to unmasking sick sinus syndrome (p = .003). Freedom from arrhythmia recurrences was comparable (68% vs. 76%, log-rank p = .087). Only in the subgroup of paroxysmal AF, AF recurrences were more common after 12 months (69% vs. 82%; log-rank p = .040; hazard ratio: 1.462, p = .044) in the elderly patients. In multivariable Cox regression analysis of the whole cohort persistent AF, female gender, diabetes mellitus and presence of left atrium low-voltage areas, but not age75 years were associated with AF recurrences.HPSD AF ablation of patients75 years in experienced centers is safe and effective. Therefore, age alone should not be the reason to withhold AF ablation from vital elderly patients due to only a slightly worse outcome and safety profile. In paroxysmal AF, elderly patients have more recurrences compared to the younger control group.

Aims Pulmonary vein isolation (PVI) using radiofrequency (RF) ablation is an effective treatment option for patients with atrial fibrillation (AF). This study aims to investigate the safety of high-power short duration (HPSD) with emphasis on oesophageal lesions after PVI. Methods and results Consecutive patients undergoing AF ablation with HPSD (50 W; ablation index (AI)-guided; target AI 350 for posterior wall ablation, AI 450 for anterior wall ablation) using the ThermoCool SmartTouch SF catheter were included. Patients underwent post-ablation oesophageal endoscopy to detect and categorize thermal oesophageal injury (EDEL). Occurrence and risk factors of oesophageal lesions and perforating complications were analysed. A total of 1033 patients underwent AF ablation with HPSD. Of them, 953 patients (67.6 ± 9.6 years; 58% male; 43% paroxysmal AF; 68% first PVI) underwent post-procedural oesophageal endoscopy and were included in further analyses. Median procedure time was 82.8 ± 24.4 min with ablation times of 16.1 ± 9.2 min. Thermal oesophageal injury was detected in 58 patients (6%) (n = 29 Category 1 erosion, n = 29 Category 2 ulcerous). One patient developed oesophageal perforation (redo, 4th AF ablation). No patient died. Using multivariable regression models, increased total ablation time [odds ratio (OR) 1.029, P = 0.010] and history of stroke (OR 2.619, P = 0.033) were associated with increased incidence of EDEL after AF ablation, whereas increased body mass index was protective (OR 0.980, P = 0.022). Conclusion Thermal oesophageal lesions occur in 6% of HPSD AF ablations. The risk for development of perforating complications seems to be low. Incidence of atrio-oesophageal fistula (0.1%) is comparable to other reported series about RF ablation approaches.

Purpose Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. Methods In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson’s test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). Results In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p

OBJECTIVES The study sought to assess the prognostic impact of recurrences of electrical storm (ES-R) on mortality, rehospitalization and major adverse cardiac events (MACE). BACKGROUND Data on the prognostic impact of ES-R is rare. METHODS All consecutive ES patients with an implantable cardioverter defibrillator (ICD) were included retrospectively from 2002 to 2016. Patients with ES-R were compared to patients without ES-R. The primary endpoint was all-cause mortality, secondary endpoints were in-hospital mortality, rehospitalization and MACE. RESULTS A total of 87 consecutive ES patients with an ICD were included, of which 26% presented with ES-R at 2.5 years of follow-up. ES-R patients revealed lower LVEF compared to non-ES-R patients (91% vs. 61%; p = .081). There was a numerically higher rate of the primary endpoint of all-cause mortality at 2.5 years (50% vs. 32%; log-rank p = .137). Furthermore, ES-R was associated with increasing rates of rehospitalization (64% vs. 37%; p = .031; HR 1.985; 95% CI 1.025-3.845; log-rank p = .042), especially of acute heart failure (32% vs. 12%; p = .001; HR 3.262; 95% CI 1.180-9.023; log rank p = .023). MACE were higher in ES-R patients (55% vs. 35%; p = .113; log rank p = .141). ES patients with LVEF ≤35% were 12.4 times more likely to develop ES-R (HR 12.417; 95% CI 1.329-115.997; p = .027). CONCLUSION At long-term follow-up of 2.5 years, ES-R was associated with numerically higher rates of long-term all-cause mortality and significantly higher rates of rehospitalization due to acute heart failure. LVEF ≤35% was associated with increased risk of ES-R. Condensed Abstract This study examined retrospectively the impact of recurrences of electrical storm (ES-R) on survival in 87 patients. ES-R was associated with numerically higher long-term all-cause mortality, whereas significantly higher rates of rehospitalization, respectively of acute heart failure were observed. Highlights ES-R is associated with numerically higher rates of all-cause mortality at long-term follow-up. ES-R is associated with significantly higher rates of rehospitalization and numerically higher rates of MACE at long-term follow-up, mainly due to acute heart failure. Patients with LVEF ≤35% were 12.4 times more likely to develop ES-R.

Background: Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare. Objectives: This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R). Methods: All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R. Results: A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981–3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247–4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277–11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704). Conclusion: In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF.

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00864-w.

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance., Frontiers in Endocrinology, 12, ISSN:1664-2392

Background Data is limited evaluating novel biomarkers in right ventricular dysfunction. Normal right heart function improves the prognosis of patients with heart failure. Therefore, this study investigates the association between the novel biomarker copeptin and right heart function compared to NT-proBNP. Methods Patients undergoing routine echocardiography were enrolled prospectively. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and further right ventricular and atrial parameters. Exclusion criteria were age under 18 years, left ventricular ejection fraction Results Ninety-one patients were included. Median values of copeptin increased significantly according to decreasing values of TAPSE ( P = 0.001; right heart function grade I: tricuspid annular plane systolic excursion; TAPSE > 24 mm: 5.20 pmol/L; grade II: TAPSE 18–24 mm: 8.10 pmol/L; grade III: TAPSE Conclusions This study demonstrates that the novel biomarker copeptin reflects longitudinal right heart function assessed by standardized transthoracic echocardiography compared with NT-proBNP.

Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold exposure. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so-called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. We assessed DIT, cold-induced thermogenesis (CIT), and maximum BAT activity at three separate study visits within 2 wk. DIT was measured by indirect calorimetry during an oral glucose tolerance test. CIT was assessed as the difference in EE after cold exposure of 2-h duration as compared with warm conditions. Maximal activity of BAT was assessed by 18-F-fluoro-deoxyglucose (18F-FDG) 18F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with mirabegron. Seventeen healthy men (mean age = 23.4 yr, mean body mass index = 23.2 kg/m2) participated in the study. EE increased from 1,908 (±181) kcal/24 h to 2,128 (±277) kcal/24 h (P < 0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1,911 (±165) kcal/24 h to 2,096 (±167) kcal/24 h at 60 min (P < 0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R2 = 0.43, P = 0.004). However, DIT was not associated with BAT activity (R2 = 0.015, P = 0.64). DIT after an oral glucose load was not associated with stimulated 18F-FDG uptake into BAT, suggesting that DIT is independent from BAT activity in humans (Clinicaltrials.gov Registration No. NCT03189511).NEW & NOTEWORTHY Cold-induced thermogenesis (CIT) was related to BAT activity as determined by FDG-PET/MRI after stimulation of BAT. Diet-induced thermogenesis (DIT) was not related to stimulated BAT activity. Supraclavicular skin temperature was related to CIT but not to DIT. DIT in humans is probably not a function of BAT.

OBJECTIVE The study sought to assess the prognostic impact of treatment with mineralocorticoid receptor antagonists (MRA) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients with systolic heart failure (HF). BACKGROUND Data regarding the outcome of patients with ventricular tachyarrhythmias treated with MRA is limited. METHODS A large retrospective registry was used including consecutive ICD recipients with systolic HF (i.e., left ventricular ejection fraction

This study sought to assess the prognostic impact of treatment with single beta-blocker (BB) compared to combined therapy with BB plus amiodarone (BB-AMIO) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients. A large retrospective registry was used including consecutive ICD recipients with index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with BB were compared to patients treated with BB-AMIO. Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary end-point defined as first recurrences of ventricular tachyarrhythmias at five years. Secondary end-points comprised first appropriate ICD therapies, first cardiac rehospitalization and all-cause mortality at five years. Among 512 ICD recipients, 81% were treated with BB and 19% with BB-AMIO. BB and BB-AMIO were associated with comparable risk of first recurrences of ventricular tachyarrhythmias (46% vs. 43%; log rank P = .941; HR = 1.013; 95% CI 0.725-1.415; P = .941) and appropriate ICD therapies (35% vs. 37%; log rank P = .389; HR = 0.852; 95% CI 0.591-1.228; P = .390). BB was associated with decreased long-term all-cause mortality within an univariable analysis only (20% vs. 28%; log rank p = 0.023). In conclusion, BB and BB-AMIO were associated with comparable risks regarding recurrences of ventricular tachyarrhythmias at five years.

Summary Background Data regarding recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients according to atrial fibrillation is limited. Objective To assess the prognostic impact of atrial fibrillation on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients. Methods A large retrospective registry was used, including all ICD recipients with episodes of ventricular tachycardia or fibrillation from 2002 to 2016. Patients with atrial fibrillation were compared to those without atrial fibrillation. The primary endpoint was first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised recurrences of ICD-related therapies, first cardiac rehospitalization and all-cause mortality at 5 years. Cox regression, Kaplan-Meier and propensity score-matching analyses were applied. Results A total of 592 consecutive ICD recipients were included (33% with atrial fibrillation). Atrial fibrillation was associated with reduced freedom from recurrent ventricular tachyarrhythmias (42% vs. 50%, log-rank P = 0.004; hazard ratio 1.445, 95% confidence interval 1.124–1.858), mainly attributable to recurrent ventricular fibrillation in secondary-preventive ICD recipients. Accordingly, atrial fibrillation was associated with reduced freedom from first appropriate ICD therapies (31% vs. 42%, log-rank P = 0.001; hazard ratio 1.598, 95% confidence interval 1.206–2.118). Notably, the primary endpoint of freedom from first episode of recurrent ventricular tachyarrhythmias was still reduced in those with atrial fibrillation compared to those without atrial fibrillation after propensity score matching. Regarding secondary endpoints, patients with atrial fibrillation still showed a trend towards reduced freedom from appropriate ICD therapies. Conclusions Atrial fibrillation was associated with increased rates of recurrent ventricular tachyarrhythmias and appropriate device therapies in ICD recipients with ventricular tachyarrhythmias.

Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods: Retrospective institutional review board approved single-centre analysis of patients who had undergone 68Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC. Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis. Results: 120 PSMA-PET scans in 74 patients were available for this analysis. Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml (IQR 0.32-4.27). Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity. The percentage of PSMA-negative tumour area on IHC (PSMA%neg) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association (p = 0.73). The positive predictive value of PSMA%neg ≥ 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA%neg of 80% or more, 100% (9/9). Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA%neg ≥ 50%.

Only few data evaluating the prognostic impact of blood-derived potassium levels (K) on arrhythmic endpoints in patients with implantable cardioverter-defibrillators (ICD) is available. Therefore, this study evaluates the prognostic impact of potassium levels on recurrences of ventricular tachyarrhythmias in consecutive ICD recipients.A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016 at one institution. Patients were divided into three subgroups: hypokalemia (i.e., K3.3 mmol/L), normokalemia (i.e., K 3.3 - 4.5 mmol/L), and hyperkalemia (i.e., K4.5 mmol/L). Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary endpoint of first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised of first appropriate ICD therapy, first cardiac rehospitalization, and all-cause mortality at one year.Five hundred and thirty ICD recipients with a median potassium level of 4.23 mmol/L were included (67%: normokalemia, 27%: hyperkalemia, and 6%: hypokalemia). Whereas hyperkalemia was not associated with increasing risk of recurrent ventricular tachyarrhythmias, hypokalemia was associated with decreasing freedom from recurrent ventricular tachyarrhythmias (HR = 2.135; 95% CI 1.158 - 3.937; p = 0.015), even after mul-tivariable adjustment (HR = 2.577; 95% CI 1.236 - 5.372; p = 0.012). Higher risk of recurrences was especially attributed to higher rates of electrical storm in the presence of hypokalemia (15% vs. 3 - 4%). Negative impact of hypokalemia was mainly attributed to secondary preventive ICD (HR = 2.637; 95% CI 1.325 - 5.248; p = 0.006). Moreover, hypokalemia was associated with increasing risk of appropriate ICD therapies (HR = 1.920; 95% CI 0.912 - 4.042; statistical trend: p = 0.086), which was still demonstrated after multivariable adjustment. In contrast, risk of first cardiac rehospitalization and all-cause mortality were not affected by potassium levels.In consecutive ICD recipients with ventricular tachyarrhythmias at index, hypokalemia - but not hyperkalemia - was associated with increasing risk of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Background Recent studies have reported the additive value of combined gallium 68 (

Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention (n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes. Electronic supplementary material The online version of this article (10.1007/s00395-019-0740-3) contains supplementary material, which is available to authorized users.

Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance ofIn this retrospective analysis, 116 patients who underwentThe primary tumour was positive onInformation from

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Background Because data on electrical storm (ES) is limited, this study sought to compare the prognosis of patients with ES to those with ventricular tachyarrhythmias on mortality, rehospitalization and major adverse cardiac events (MACE). Methods In this retrospective study consecutive implantable cardioverter defibrillator (ICD) recipients presenting with ES were compared to patients surviving ventricular tachyarrhythmias (ventricular tachycardia (VT) or fibrillation (VF); non-ES) on admission from 2002 to 2016. The primary endpoint was all-cause mortality, secondary endpoints were rehospitalization and MACE at 2.5 years of follow-up. Results 764 consecutive patients with an ICD were included (11% with ES, 89% with VTA). ES was associated with higher rates of all-cause mortality (37% vs. 20%, log-rank p = 0.001; HR 2.084; 95% CI 1.416–3.065, p = 0.001). However, only in secondary preventive ICD recipients, ES remained significantly associated with mortality (39% vs. 20%; log rank p = 0.001; HR 2.235, 95% CI 1.378–3.625, p = 0.001). Furthermore, ES was associated with higher rates of rehospitalization (44% vs. 12%, log-rank p = 0.001; HR 4.763, 95% CI 3.237–7.009, p = 0.001), mainly due to VT (22% vs. 4%, p = 0.001) and acute heart failure (AHF) (17% vs. 4%, p = 0.001) and higher rates of MACE (40% vs. 23%; log rank p = 0.001; HR 1.838; 95% CI 1.273–2.654, p = 0.002). Increasing risks of death and rehospitalization were still observed even after multivariable adjustment. Conclusion ES was associated with increased rates of all-cause mortality, rehospitalization, respectively due to VT and AHF, as well as MACE at 2.5 years compared to patients with ventricular tachyarrhythmias apart from ES.

Objective: The study sought to assess the long-term prognostic impact of different pharmacotherapies, including angiotensin-converting enzyme inhibitor-inhibitor/angiotensin receptor blocker (ACEi/ARB), statins, and amiodarone in patients with electrical storm (ES). Background: Data regarding the outcome of patients with ES is limited. Methods: Consecutive patients with ES from 2002 to 2016 were included. Patients on ACEi/ARB were compared to patients without ACEi/ARB, respectively, for statin and amiodarone therapy. The primary prognostic endpoint was all-cause mortality at 4 years. Secondary endpoints comprised ES recurrences, rehospitalization, and major adverse cardiac events (MACE) at 4 years. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied. Results: A total of 84 consecutive patients surviving episodes of ES was included. Beta-blocker was given in 95%, ACEi/ARB in 80%, statin in 60%, and amiodarone in 54%. ACEi/ARB patients were associated with improved all-cause mortality at 4 years (mortality rate 34 vs. 65%, log rank p = 0.018; HR 0.428; 95% CI 0.208–0.881; p = 0.021), as well as improved freedom from MACE. In contrast, statin and amiodarone therapy had no impact on long-term outcomes in ES patients. Conclusion: ACEi/ARB therapy is associated with improved survival and MACE in patients with ES, whereas statins and amiodarone therapy had no impact on long-term prognostic endpoints.

The study sought to assess retrospectively the prognostic impact of left ventricular ejection fraction (LVEF) in patients with electrical storm (ES). Data regarding the prognostic impact of impaired LVEF in ES patients is rare. Consecutive patients presenting with ES from 2002 to 2016 were included retrospectively. Patients with LVEF ≤ 35% were compared to patients with LVEF > 35%. The primary prognostic endpoint was long-term all-cause mortality, and secondary endpoints were rates of in-hospital mortality, rehospitalization, major adverse cardiac events (MACE), and ES recurrences (ES-R) at long-term follow-up. A total of 80 patients with ES were included at 2.5 years of follow-up. 69% of patients suffered from LVEF ≤ 35%. ES patients with LVEF ≤ 35% were associated with higher rates of the primary endpoint of all-cause mortality (53% versus 8%, log-rank p = 0.0001; HR 8.524; 95% CI 2.030–35.793, p = 0.003), as well as the secondary endpoints of MACE (53% versus 20%; log rank p = 0.011; HR 3.213, 95% CI 1.241–8.316, p = 0.016) and ES-R (35% versus 8%; log rank p = 0.019; HR 4.821, 95% CI 1.122–20.706, p = 0.034). Furthermore, ES patients with LVEF ≤ 35% showed higher rates of rehospitalization due to acute heart failure (24% versus 8%, statistical trend p = 0.096). Notably, ES patients with LVEF > 35% were associated with increased rates of rehospitalization due to ventricular tachycardia (36% versus 18%, statistical trend p = 0.083). ES patients with LVEF ≤ 35% were associated with increased rates of all-cause mortality, MACE, ES-R and heart failure-related rehospitalization at long-term follow-up. This study evaluated retrospectively the prognostic impact of LVEF in patients with ES. LVEF ≤ 35% was associated with increased long-term all-cause mortality (53% versus 8%; HR 8.524; 95% CI 2.030–35.793, p = 0.003), MACE (53% versus 20%; HR 3.213, 95% CI 1.241–8.316, p = 0.016), and ES recurrences (35% versus 8%; HR 4.821, 95% CI 1.122–20.706, p = 0.034), while trends were observed for higher rates of heart-failure related rehospitalization (24% versus 8%, p = 0.096) and MACE (49% versus 28%; p = 0.081).

Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.

The fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority ofOf 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence byThe high rate of recurrence detection by PSMA PET was confirmed and PSMA PET led to a change in management in 60% of patients. Focal therapy for PSMA-positive lesions is a promising approach with complete responses in 45% of patients.

Restaging local recurrence after high-intensity focused ultra-sound (HIFU) is based on multiparametric MRI (mpMRI). However, postinterventional changes of the tissue, such as edema or hemorrhage, are limiting tumor detection on mpMRI. We present a case of a rising prostate-specific antigen values, negative mpMRI, and a Gleason score of 4+4 on template biopsy after HIFU. On F-choline PET/MR, high focal uptake was detected at the location of positive biopsy. Re-HIFU based on the fused F-choline PET/MR images was performed, followed by a recurrence-free period of 11 months. Thus, F-choline PET/MR could improve guiding retreatment in patients with recurrence after HIFU.

Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest inWe retrospectively analysed all patients who underwent a stagingOf 283 consecutive patients scanned withOur results suggest that higher

Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently establishedWe retrospectively analyzed a cohort of 56 consecutive patients who underwent aOverall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA 0.2 ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA between 0.2 and 0.5 ng/mL, suspicious lesions were detected (two local recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients with a PSA 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with a PSA between 0.5 and 2.0 ng/mL, suspicious lesions were detected (four local recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients (95.2%) with a PSA2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645-0.947).Our data show that

Follow-up of patients with oral cavity squamous cell carcinoma (OCSCC) after tumor resection and reconstruction with tissue transfer is challenging. We compared contrast-enhanced computed tomography (ceCT), (18) F-fluorodeoxyglucose-positron emission tomography combined with noncontrast enhanced CT ((18) F-FDG-PET/CT), and (18) F-FDG-PET combined with ceCT ((18) F-FDG-PET/ceCT) to determine the accuracy for detection of residual/recurrent disease after flap reconstruction for OCSCC.Two readers (R1, R2) retrospectively reviewed a total of 27 (18) F-FDG-PET/ceCT scans in patients after resection of stage II to IV OCSCC. They recorded the presence of local persistence/recurrence (LR), lymph node metastasis, or distant metastasis independently for ceCT, (18) F-FDG-PET/CT, and (18) F-FDG-PET/ceCT. Histological workup, imaging follow-up, or clinical follow-up served as the standard of reference. Maximum standardized uptake value (SUVmax) was evaluated to discriminate between physiological uptake and LR.The highest accuracy to detect LR was achieved with (18) F-FDG-PET/ceCT, with a sensitivity/specificity of 88%/89% and 88%/79% for R1 and R2, respectively, as compared to ceCT with 75%/79% for R1 and 88%/68% for R2 and (18) F-FDG-PET/CT with 88%/58% for both R1 and R2. Receiver-operating-characteristic analysis determined a cutoff value for SUVmax of 7.2, yielding a sensitivity and specificity of 75% and 94%, respectively, to distinguish LR from physiological (18) F-FDG uptake.(18) F-FDG-PET/ceCT seems to be the most reliable tool for locoregional surveillance of OCSCC patients after resection and reconstruction.4.