Aortic valve implantation-induced conduction block as a framework towards a uniform electrocardiographic definition of left bundle branch block

IntroductionNew-onset left bundle branch block (LBBB) following transcatheter or surgical aortic valve replacement (LBBB_AVI) implies a proximal pathogenesis of LBBB. This study compares electrocardiographic characteristics and concordance with LBBB definitions between LBBB_AVI and non-procedure-induced LBBB controls (LBBB_control).MethodsAll LBBB_AVI patients at Ghent University Hospital between 2013 and 2019 were enrolled in the study. LBBB_AVI patients were matched for age, sex, ischaemic heart disease and ejection fraction to LBBB_control patients in a 1:2 ratio. For inclusion, a non-strict LBBB definition was used (QRS duration ≥ 120 ms, QS or rS in V1, absence of Q waves in V5-6). Electrocardiograms were digitally analysed and classified according to three LBBB definitions: European Society of Cardiology (ESC), Strauss and American Heart Association (AHA).ResultsA total of 177 patients (59 LBBB_AVI and 118 LBBB_control) were enrolled in the study. LBBB_AVI patients had more lateral QRS notching/slurring (100% vs 85%, p = 0.001), included a higher percentage with a QRS duration ≥ 130 ms (98% vs 86%, p = 0.007) and had a less leftward oriented QRS axis (−15° vs −30°, p = 0.013) compared to the LBBB_control group. ESC and Strauss criteria were fulfilled in 100% and 95% of LBBB_AVI patients, respectively, but only 18% met the AHA criteria. In LBBB_control patients, concordance with LBBB definitions was lower than in the LBBB_AVI group: ESC 85% (p = 0.001), Strauss 68% (p < 0.001) and AHA 7% (p = 0.035). No differences in electrocardiographic characterisation or concordance with LBBB definitions were observed between LBBB_AVI and LBBB_control patients with lateral QRS notching/slurring.ConclusionNon-uniformity exists among current LBBB definitions concerning the detection of proximal LBBB. LBBB_AVI may provide a framework for more consensus on defining proximal LBBB.Supplementary InformationThe online version of this article (10.1007/s12471-021-01565-8) contains supplementary material, which is available to authorized users.     

Transcatheter aortic valve implantation amid the COVID-19 pandemic: a nationwide analysis of the first COVID-19 wave in the Netherlands

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI.MethodsWe used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes.ResultsWe examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively).ConclusionsDuring the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality.Supplementary InformationThe online version of this article (10.1007/s12471-022-01704-9) contains supplementary material, which is available to authorized users.     

Conservative initial postoperative anticoagulation strategy after HeartMate 3 left ventricular assist device implantation

IntroductionAlthough anticoagulation therapy is mandated after implantation of a left ventricular assist device (LVAD), postoperative bleedings and reoperations occur relatively frequently and are associated with worse outcomes. We evaluated the use of a conservative postoperative anticoagulation protocol in patients implanted with a HeartMate 3 (HM3) LVAD.MethodsIn a single-centre retrospective analysis of postoperative outcomes after HM3 LVAD implantation, a standard (old) anticoagulation protocol (i.e. early, full-dose anticoagulation with low-molecular weight heparin and overlapping vitamin K antagonist) was compared with a new conservative anticoagulation protocol (i.e. slow initiation of vitamin K antagonists without overlapping heparin). Main outcomes were changes in international normalised ratio (INR), lactate dehydrogenase (LDH), bleeding and/or tamponade events requiring reoperation, length of stay and adverse events.ResultsIn total, 73 patients (48 in old vs 25 in new protocol group) were evaluated. Mean age was 56 years (standard deviation 13) and most patients (78%) were males. Changes in INR and LDH in the first 14 days were similar in both groups (p = 0.50 and p = 0.997 for interaction, respectively). Number of bleeding/tamponade events requiring reoperation was lower in the new than in the old protocol group (4% vs 33%, p = 0.005). Postoperative 30-day mortality was similar, and we observed no thromboembolic events. Median (25th–75th percentiles) total length of postoperative hospital stay (27 (25–41) vs 21 (19–27) days, p < 0.001) and length of intensive care unit stay (5 (2–9) vs 2 (2–5) days, p = 0.022) were significantly shorter in the new protocol group.ConclusionThese retrospective data suggest that conservative slow initiation of anticoagulation therapy after HM3 LVAD implantation is associated with less bleeding/tamponade events requiring reoperation, a similar safety profile and a shorter duration of stay than the currently advised standard anticoagulation protocol.Supplementary InformationThe online version of this article (10.1007/s12471-022-01671-1) contains supplementary material, which is available to authorized users.     

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe

BackgroundAs coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS).AimThe aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe.MethodsThis retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well.ResultsThere was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4–50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients.ConclusionsThese findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.     

Characteristics of chest pain in COVID-19 patients in the emergency department

IntroductionPatients with coronavirus disease 2019 (COVID-19) can present with chest pain. However, the characteristics of this chest pain are unknown. We performed a single-centre observational study to review and summarise chest pain characteristics in COVID-19 patients at first presentation to the emergency department (ED).MethodsWe collected data on characteristics of ‘chest pain’ reported by COVID-19 patients who attended the ED of Bernhoven Hospital, the Netherlands from 4 through 30 March 2020.ResultsWe included 497 COVID-19 patients, of whom 83 (17%) reported chest pain upon presentation to the ED. Chest pain characteristics were: present since disease onset (88%), retrosternal location (43%), experienced as compressing/pressure pain (61%), no radiation (61%) and linked to heavy coughing (39%). Patients who reported chest pain were younger than those without chest pain (61 vs 73 years; p < 0.001). Patients with syncope were older (75 vs 72 years; p = 0.017), had a shorter duration of symptoms (5 vs 7 days; p < 0.001) and reported fewer respiratory complaints (68% vs 90%; p < 0.001) than those without syncope. Patients with new-onset atrial arrhythmias presented with a shorter duration of symptoms (5 vs 7 days; p = 0.013), experienced fewer respiratory complaints (72% vs 89%; p = 0.012) and more frequently had a history of cardiovascular disease (79% vs 50%; p = 0.003) than patients who presented without arrythmias.ConclusionChest pain and other cardiac symptoms were frequently observed in COVID-19 patients. Treating physicians should be aware that chest pain, arrhythmias and syncope can be presenting symptoms of COVID-19.Supplementary InformationThe online version of this article (10.1007/s12471-022-01730-7) contains supplementary material, which is available to authorized users.     

A single-centre prospective evaluation of left bundle branch area pacemaker implantation characteristics

BackgroundLeft bundle branch area pacing (LBBAP) has recently been introduced as a physiological pacing technique with synchronous left ventricular activation. It was our aim to evaluate the feasibility and learning curve of the technique, as well as the electrical characteristics of LBBAP.Methods and resultsLBBAP was attempted in 80 consecutive patients and electrocardiographic characteristics were evaluated during intrinsic rhythm, right ventricular septum pacing (RVSP) and LBBAP. Permanent lead implantation was successful in 77 of 80 patients (96%). LBBAP lead implantation time and fluoroscopy time shortened significantly from 33 ± 16 and 21 ± 13 min to 17 ± 5 and 12 ± 7 min, respectively, from the first 20 to the last 20 patients. Left bundle branch (LBB) capture was achieved in 54 of 80 patients (68%). In 36 of 45 patients (80%) with intact atrioventricular conduction and narrow QRS, an LBB potential (LBB_pot) was present with an LBB_pot to onset of QRS interval of 22 ± 6 ms. QRS duration increased significantly more during RVSP (141 ± 20 ms) than during LBBAP (125 ± 19 ms), compared to 130 ± 30 ms without pacing. An even clearer difference was observed for QRS area, which increased significantly more during RVSP (from 32 ± 16 µVs to 73 ± 20 µVs) than during LBBAP (41 ± 15 µVs). QRS area was significantly smaller in patients with LBB capture compared to patients without LBB capture (43 ± 18 µVs vs 54 ± 21 µVs, respectively). In patients with LBB capture (n = 54), the interval from the pacing stimulus to R‑wave peak time in lead V6 was significantly shorter than in patients without LBB capture (75 ± 14 vs 88 ± 9 ms, respectively).ConclusionLBBAP is a safe and feasible technique, with a clear learning curve that seems to flatten after 40–60 implantations. LBB capture is achieved in two-thirds of patients. Compared to RVSP, LBBAP largely maintains ventricular electrical synchrony at a level close to intrinsic (narrow QRS) rhythm.Supplementary InformationThe online version of this article (10.1007/s12471-022-01679-7) contains supplementary material, which is available to authorized users.     

Decision making in treatment of symptomatic severe aortic stenosis: a survey study in Dutch heart centres

AimTo provide insight into the basic characteristics of decision making in the treatment of symptomatic severe aortic stenosis (SSAS) in Dutch heart centres with specific emphasis on the evaluation of frailty, cognition, nutritional status and physical functioning/functionality in (instrumental) activities of daily living [(I)ADL].MethodsA questionnaire was used that is based on the European and American guidelines for SSAS treatment. The survey was administered to physicians and non-physicians in Dutch heart centres involved in the decision-making pathway for SSAS treatment.ResultsAll 16 Dutch heart centres participated. Before a patient case is discussed by the heart team, heart centres rarely request data from the referring hospital regarding patients’ functionality (n = 5), frailty scores (n = 0) and geriatric consultation (n = 1) as a standard procedure. Most heart centres ‘often to always’ do their own screening for frailty (n = 10), cognition/mood (n = 9), nutritional status (n = 10) and physical functioning/functionality in (I)ADL (n = 10). During heart team meetings data are ‘sometimes to regularly’ available regarding frailty (n = 5), cognition/mood (n = 11), nutritional status (n = 8) and physical functioning/functionality in (I)ADL (n = 10). After assessment in the outpatient clinic patient cases are re-discussed ‘sometimes to regularly’ in heart team meetings (n = 10).ConclusionsDutch heart centres make an effort to evaluate frailty, cognition, nutritional status and physical functioning/functionality in (I)ADL for decision making regarding SSAS treatment. However, these patient data are not routinely requested from the referring hospital and are not always available for heart team meetings. Incorporation of these important data in a structured manner early in the decision-making process may provide additional useful information for decision making in the heart team meeting.Supplementary InformationThe online version of this article (10.1007/s12471-022-01676-w) contains supplementary material, which is available to authorized users.     

Initial experience,feasibility and safety of permanent left bundle branch pacing: results from a prospective single-centre study

BackgroundLeft bundle branch (LBB) pacing is a novel pacing technique which may serve as an alternative to both right ventricular pacing for symptomatic bradycardia and cardiac resynchronisation therapy (CRT). A substantial amount of data is reported by relatively few, highly experienced centres. This study describes the first experience of LBB pacing in a high-volume device centre.MethodsSuccess rates (i.e. the ability to achieve LBB pacing), electrophysiological parameters and complications at implant and up to 6 months of follow-up were prospectively assessed in 100 consecutive patients referred for various pacing indications.ResultsThe mean age was 71 ± 11 years and 65% were male. Primary pacing indication was atrioventricular (AV) block in 40%, CRT in 42%, and sinus node dysfunction or refractory atrial fibrillation prior to AV node ablation in 9% each. Baseline left ventricular ejection fraction was < 50% in 57% of patients, mean baseline QRS duration 145 ± 34 ms. Overall LBB pacing was successful in 83 of 100 (83%) patients but tended to be lower in patients with CRT pacing indication (69%, p = ns). Mean left ventricular activation time (LVAT) during LBB pacing was 81 ms and paced QRS duration was 120 ± 19 ms. LBB capture threshold and R‑wave sense at implant was 0.74 ± 0.4 mV at 0.4 ms and 11.9 ± 5.9 V and remained stable at 6‑month follow-up. No complications occurred during implant or follow-up.ConclusionLBB pacing for bradycardia pacing and resynchronisation therapy can be easily adopted by experienced implanters, with favourable success rates and safety profile.     

Coronary CT angiography for suspected acute coronary syndrome: sex-associated differences

AimThe optimal diagnostic test in the work-up of suspected acute coronary syndrome (ACS) may differ between men and women. The aim of this study was to compare sex-associated differences between using a diagnostic strategy including early coronary computed tomography angiography (CCTA) and standard of care (SOC).MethodsIn total, 500 patients who presented with symptoms suggestive of ACS at the emergency department were randomised between a diagnostic strategy supplemented with early CCTA and SOC.ResultsWomen were generally older than men (mean ± standard deviation 56 ± 10 vs 53 ± 10 years, p < 0.01) and were less often admitted to hospital (33% vs 44%, p = 0.02). Obstructive coronary artery disease on CCTA (> 50% luminal narrowing) was less frequently seen in women (14% vs 26%, p = 0.02), and ACS was diagnosed less often in women (5% vs 10%, p = 0.03). Women underwent less outpatient testing when early CCTA was used in the emergency department evaluation of suspected ACS (p = 0.008).ConclusionWomen had a lower incidence of obstructive CAD on CCTA and were less often admitted to hospital than men. They were subjected to less outpatient testing when early CCTA was used in the emergency department evaluation of suspected ACS.Supplementary InformationThe online version of this article (10.1007/s12471-021-01607-1) contains supplementary material, which is available to authorized users.     

Performance of a simplified HEART score and HEART-GP score for evaluating chest pain in urgent primary care

BackgroundChest pain is a common symptom in urgent primary care. The distinction between urgent and non-urgent causes can be challenging. A modified version of the HEART score, in which troponin is omitted (‘simplified HEART’) or replaced by the so-called ‘sense of alarm’ (HEART-GP), may aid in risk stratification.MethodThis study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale, out-of-hours, regional primary care facility in the Netherlands, with 6‑week follow-up for major adverse cardiac events (MACEs). The outcome of interest is diagnostic accuracy, including positive predictive value (PPV) and negative predictive value (NPV).ResultsWe included 664 patients; MACEs occurred in 4.8% (n = 32). For  simplified HEART and HEART-GP, we found C‑statistics of 0.86 (95% confidence interval (CI) 0.80–0.91) and 0.90 (95% CI 0.85–0.95), respectively. Optimal diagnostic accuracy was found for a simplified HEART score ≥2 (PPV 9%, NPV 99.7%), HEART-GP score ≥3 (PPV 11%, NPV 99.7%) and HEART-GP score ≥4 (PPV 16%, NPV 99.4%). Physicians referred 157 patients (23.6%) and missed 6 MACEs. A simplified HEART score ≥2 would have picked up 5 cases, at the expense of 332 referrals (50.0%, p < 0.001). A HEART-GP score of ≥3 and ≥4 would have detected 5 and 3 MACEs and led to 293 (44.1%, p < 0.001) and 186 (28.0%, p = 0.18) referrals, respectively.ConclusionHEART-score modifications including the physicians’ ‘sense of alarm’ may be used as a risk stratification tool for chest pain in primary care in the absence of routine access to troponin assays. Further validation is warranted.Supplementary InformationThe online version of this article (10.1007/s12471-020-01529-4) contains supplementary material, which is available to authorized users.     

Echocardiographic estimation of pulmonary hypertension in COVID-19 patients

IntroductionCoronavirus disease 2019 (COVID-19) is the cause of a devastating global pandemic and is not likely to be fully resolved in the near future. In most cases COVID-19 presents with mild symptoms, but in a minority of patients respiratory and multi-organ failure may ensue. Previous research has focused on the correlation between COVID-19 and a variety of cardiovascular complications. However, the effect of COVID-19 on pulmonary hypertension (PH) and correlated cardiovascular parameters has not been evaluated extensively.MethodsThis study was designed as a single-centre, semi-quantitative analysis. PH was considered to be present if echocardiographic measurements estimated right ventricular systolic pressure at rest to be 36 mm Hg or higher in combination with indirect indicators of right ventricular overload.ResultsIn total, 101 patients (67.3% male) were included in this study, with a mean age of 66 years (range 23–98 years). PH was diagnosed by echocardiographic estimation in 30 patients (29.7%). Echocardiographically estimated PH (eePH) was not correlated with a diagnosis of heart failure or pulmonary embolism. Mortality was significantly higher among COVID-19 patients with eePH (p = 0.015). In all 10 of 20 surviving eePH patients in whom echocardiographic follow-up was obtained, echocardiographic estimations of pulmonary pressures showed a significant decrease after a median of 144 ± 72 days.ConclusioneePH is frequently observed in COVID-19 patients and is correlated with increased mortality. COVID-19-related eePH appears to be reversible after recovery. Vigilant attention and a low threshold for performance of echocardiography in COVID-19 patients seems warranted, as eePH may be applicable as a prognostic risk factor.     

Major threats to early safety after transcatheter aortic valve implantation in a contemporary cohort of real-world patients

IntroductionDespite considerable advances in the last decade, major adverse events remain a concern after transcatheter aortic valve implantation (TAVI). The aim of this study was to provide a detailed overview of their underlying causes and contributing factors in order to identify key domains for quality improvement.MethodsThis observational, prospective registry included all patients undergoing TAVI between 31 December 2015 and 1 January 2020 at the St. Antonius Hospital in Nieuwegein and the University Medical Centre in Utrecht. Outcomes of interest were all-cause mortality, stroke, major bleeding, life-threatening or disabling bleeding, major vascular complications, myocardial infarction, severe acute kidney injury and conduction disturbances requiring permanent pacemaker implantation within 30 days after TAVI, according to the Valve Academic Research Consortium‑2 criteria.ResultsOf the 1250 patients who underwent TAVI in the evaluated period, 146 (11.7%) developed a major complication. In 54 (4.3%) patients a thromboembolic event occurred, leading to stroke in 36 (2.9%), myocardial infarction in 13 (1.0%) and lower limb ischaemia in 11 (0.9%). Major bleeding occurred in 65 (5.2%) patients, most frequently consisting of acute cardiac tamponade (n = 25; 2.0%) and major access-site bleeding (n = 21; 1.7%). Most complications occurred within 1 day of the procedure. Within 30 days a total of 54 (4.3%) patients died, the cause being directly TAVI-related in 30 (2.4%). Of the patients who died from causes that were not directly TAVI-related, 14 (1.1%) had multiple hospital-acquired complications.ConclusionA variety of underlying mechanisms and causes form a wide spectrum of major threats affecting early safety in 11.7% of patients undergoing TAVI in a contemporary cohort of real-world patients.Supplementary InformationThe online version of this article (10.1007/s12471-021-01638-8) contains supplementary material, which is available to authorized users.     

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation

BackgroundCryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI.MethodsWe included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response.ResultsFollowing PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p < 0.001), and to 71.9 ± 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 ± 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 ± 10.6 bpm (pre-ablation), 84.6 ± 9.8 bpm (3 months), 80.1 ± 6.5 bpm (6 months) and 76.3 ± 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation.ConclusionFew patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.     

Final benefit of primary percutaneous coronary intervention for ST-elevation myocardial infarction in older patients: long-term results of a randomised trial

BackgroundAlthough the short-term benefit of primary percutaneous coronary intervention (PCI) in elderly patients with ST-elevation myocardial infarction (STEMI) has been demonstrated, the final long-term survival benefit is as yet unknown.AimTo assess the final survival benefit of primary PCI as compared to thrombolytic therapy in patients over 75 years of age.MethodsPatients > 75 years with STEMI were randomised to either primary PCI or thrombolysis. Long-term data on survival were available for all patients.ResultsA total of 46 patients were randomised to primary PCI, 41 to thrombolysis. There were no significant differences in baseline variables. After a maximum of 20 years’ follow-up, all patients had passed away. The patients randomised to thrombolysis died after a mean follow-up duration of 5.2 years (SD 4.9) compared to 6.7 years (SD 4.8) in patients randomised to primary PCI (p = 0.15). Thus, the mean final survival benefit of primary PCI was 1.5 years.ConclusionThe final survival benefit of primary PCI as compared to thrombolysis in elderly patients with STEMI is 1.5 years and their life expectancy increases by 28.8%.     

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma,follicular lymphoma,or Richter's transformation

We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter''s transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs. 3/16 [18.8%]; p = 0.065; complete response 37.5% vs. 0%; p = 0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5% and 29.6%); FL (46.2% and 43.5%); RT (76.5% and 81.3%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0% vs. 6.2%; p = 0.055), KLHL14 (30.0% vs. 0%; p = 0.046), and LRP1B (30.0% vs. 6.2%; p = 0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88, or TNFRSF14, while the frequency of these mutations in nonresponders ranged from 12.5% to 18.8%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0% vs. 28.6%; p = 0.047) and ROS1 (0% vs. 50.0%; p = 0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell–like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.     

The effect of adding concurrent chemotherapy to radiotherapy for stage II nasopharyngeal carcinoma with undetectable pretreatment Epstein-Barr virus DNA: Retrospective analysis with a large institutional-based cohort

Little is known about the value of adding concurrent chemotherapy (CC) to radiotherapy for stage II nasopharyngeal carcinoma (NPC) with undetectable (0 copies/mL) pretreatment Epstein-Barr Virus (EBV) DNA in the intensity-modulated radiotherapy (IMRT) era. To address this question, the present study retrospectively reviewed 514 patients with newly diagnosed stage II NPC and undetectable pretreatment EBV DNA from Sun Yat-sen University Cancer Center between March 2008 and October 2016. Clinical characteristics and survival outcomes between concurrent chemoradiotherapy (CCRT) and IMRT alone groups were compared. Propensity score matching analysis was conducted to control for confounding factors. Although CCRT group had significantly higher proportions of stage N1 disease than IMRT alone group before matching (85% vs. 61%, p < 0.001), no statistically significant differences were noted for OS (97.8% vs. 98.1%, p = 0.700), DFS (93.4% vs. 94.5%, p = 0.846), DMFS (96.0% vs. 96.9%, p = 0.762), and LRFS (97.3% vs. 98.1%, p = 0.701). After 1:1 propensity-score matching, 177 pairs were identified. Patients in each group were found to be well balanced in baseline characteristics and risk factors (all P > 0.05). The five-year OS (96.9% vs. 98.2%, p = 0.302), DFS (92.0% vs. 95.2%, p = 0.777), DMFS (95.2% vs. 97.6%, p = 0.896), and LRFS (97.3% vs. 97.6%, p = 0.328) rates remain comparable for both CCRT and RT alone groups. Additionally, subgroup analysis still failed to observe any significant survival benefit for the addition of CC to IMRT for N1 disease (P>0.05 for all). Our results indicated that IMRT alone appeared to achieve comparable survival to CCRT for stage II NPC with undetectable pretreatment EBV DNA.Keyword: Nasopharyngeal carcinoma, Epstein–Barr virus DNA, Survival, Intensity-modulated radiotherapy, Concurrent chemotherapy, Effect     

Determining the optimal interval for imaging surveillance of ascending aortic aneurysms

BackgroundCardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs.MethodsA total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred.ResultsThe mean growth rate in our population was 0.2 ± 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 ± 0.5 vs 0.2 ± 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40–49 mm in diameter and yearly imaging of those measuring 50–54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%.ConclusionsIn our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach.     

Introduction of a new scoring tool to identify clinically stable heart failure patients

IntroductionHeart failure (HF) poses a burden on specialist care, making referral of clinically stable HF patients to primary care a desirable goal. However, a structured approach to guide patient referral is lacking.MethodsThe Maastricht Instability Score—Heart Failure (MIS-HF) questionnaire was developed to objectively stratify the clinical status of HF patients: patients with a low MIS-HF (0–2 points, indicating a stable clinical condition) were considered for treatment in primary care, whereas high scores (> 2 points) indicated the need for specialised care. The MIS-HF was evaluated in 637 consecutive HF patients presenting between 2015 and 2018 at Maastricht University Medical Centre.ResultsOf the 637 patients, 329 (52%) had a low score and 205 of these 329 (62%) patients were referred to primary care. The remaining 124 (38%) patients remained in secondary care. Of the 308 (48%) patients with a high score (> 2 points), 265 (86%) remained in secondary care and 41 (14%) were referred to primary care. The primary composite endpoint (mortality, cardiac hospital admissions) occurred more frequently in patients with a high compared to those with a low MIS-HF after 1 year of follow-up (29.2% vs 10.9%; odds ratio (OR) 3.36, 95% confidence interval (CI) 2.20–5.14). No significant difference in the composite endpoint (9.8% vs 12.9%; OR 0.73, 95% CI 0.36–1.47) was found between patients with a low MIS-HF treated in primary versus secondary care.ConclusionThe MIS-HF questionnaire may improve referral policies, as it helps to identify HF patients that can safely be referred to primary care.Supplementary InformationThe online version of this article (10.1007/s12471-021-01654-8) contains supplementary material, which is available to authorized users.