Showing papers by "Kimon Stamatelopoulos published in 2021"

Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications.

Abstract: Gaining further insights into SARS-CoV-2 routes of infection and the underlying pathobiology of COVID-19 will support the design of rational treatments targeting the life cycle of the virus and/or the adverse effects (e.g., multi-organ collapse) that are triggered by COVID-19-mediated adult respiratory distress syndrome (ARDS) and/or other pathologies. COVID-19 is a two-phase disease being marked by (phase 1) increased virus transmission and infection rates due to the wide expression of the main infection-related ACE2, TMPRSS2 and CTSB/L human genes in tissues of the respiratory and gastrointestinal tract, as well as by (phase 2) host- and probably sex- and/or age-specific uncontrolled inflammatory immune responses which drive hyper-cytokinemia, aggressive inflammation and (due to broad organotropism of SARS-CoV-2) collateral tissue damage and systemic failure likely because of imbalanced ACE/ANGII/AT1R and ACE2/ANG(1–7)/MASR axes signaling. Here we discuss SARS-CoV-2 life cycle and a number of approaches aiming to suppress viral infection rates or propagation; increase virus antigen presentation in order to activate a robust and durable adaptive immune response from the host, and/or mitigate the ARDS-related “cytokine storm” and collateral tissue damage that triggers the severe life-threatening complications of COVID-19.

Prognostic Impact of Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance in Myocarditis: A Systematic Review and Meta-Analysis.

Abstract: Background: Patients with acute myocarditis (AM) are at increased risk of adverse cardiac events after the index episode. Late gadolinium enhancement (LGE) detected by cardiovascular magnetic reson...

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis.

Abstract: Sacubitril/valsartan, vericiguat, and the sodium-glucose co-transporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin proved effective in phase 3 trials on heart failure with reduced ejection fraction (HFrEF). We compared the treatment arms (sacubitril/valsartan, vericiguat, and SGLT2i) with the respective control arms (standard-of-care [SOC]) through a network meta-analysis of the phase 3 trials (PARADIGM-HF, VICTORIA, DAPA-HF, EMPEROR-Reduced), a phase 2 trial on vericiguat and the HFrEF subgroup of DECLARE-TIMI 58. There was a trend towards decreased risk of cardiovascular (CV) death or HF hospitalization with SGLT2i than sacubitril/valsartan (HR 0.92, 95% CI 0.81 to 1.05) and vericiguat (HR 0.83, 95% CI 0.73 to 0.94). A non-significant effect of SGLT2i on CV mortality compared to sacubitril/valsartan (HR 1.04, 95% CI 0.88 to 1.24) and vericiguat (HR 0.88, 95% CI 0.63 to 1.22) was found. SGLT2i demonstrated the greatest effect on HF hospitalization (HR 0.69, 95% CI 0.62 to 0.77) over the SOC, as well as a significant benefit over vericiguat (HR 0.77, 95% CI 0.66 to 0.89), but not over sacubitril/valsartan (HR 0.87, 95% CI 0.75 to 1.02). SGLT2i were ranked as the most effective therapy, followed by sacubitril/valsartan and vericiguat. Based on an indirect comparison, SGLT2i therapy is not associated with a significantly lower risk of CV death or HF hospitalization or CV death alone compared to sacubitril/valsartan or vericiguat. The risk of HF hospitalization does not differ significantly between patients on SGLT2i or sacubitril/valsartan, while dapagliflozin is superior to vericiguat. PROSPERO ID 186351.

Estimated pulse wave velocity improves risk stratification for all-cause mortality in patients with COVID-19.

Abstract: Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.

Timing and impact of a deep response in the outcome of patients with systemic light chain (AL) amyloidosis.

Abstract: A rapid and deep haematologic response is fundamental in order to improve outcomes of patients with AL amyloidosis. We evaluated the impact of timing and depth of haematologic response at early time points (at 1 and 3 months from the start of therapy) in 227 consecutive previously untreated AL patients, who received bortezomib-based primary therapy. After 1 month of therapy, 30.5% had ≥VGPR, 28% PR and 36% no response (NR), with 11% having iFLC <20 mg/L and 15% dFLC <10 mg/L. Deep haematologic response at 1 month (either ≥VGPR or iFLC <20 mg/L or dFLC <10 mg/L), was associated with a high organ response rate. The survival of patients with ≥VGPR was significantly better than those with PR and NR at 1-month landmark (p < .001) but this benefit was mainly driven by those with iFLC <20 mg/L. The depth of haematologic response at 1 month was significant across all Mayo stages. At 3 months, 46% of the patients had not significantly improved the depth of their response but even patients that improved their response from an iFLC ≥20 mg/L at 1 month to iFLC <20 mg/L at 3 months still had inferior outcome to those with an early deep response. Thus, in patients with AL amyloidosis, a very rapid and deep response is crucial, especially for those at high risk, targeting very low FLC levels within the first month of therapy.

The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study.

Abstract: AIMS Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. METHODS AND RESULTS Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. CONCLUSIONS The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population.

Sirtuin 5 promotes arterial thrombosis by blunting the fibrinolytic system.

Abstract: AIMS Arterial thrombosis as a result of plaque rupture or erosion is a key event in acute cardiovascular events. Sirtuin 5 (SIRT5) belongs to the lifespan-regulating sirtuin superfamily and has been implicated in acute ischemic stroke and cardiac hypertrophy. This project aims at investigating the role of SIRT5 in arterial thrombus formation. METHODS AND RESULTS Sirt5 transgenic (Sirt5Tg/0) as well as knock-out (Sirt5-/-) mice underwent photochemically-induced carotid endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with SIRT5 silencing-RNA (si-SIRT5) as well as peripheral blood mononuclear cells (PBMCs) from acute coronary syndrome (ACS) patients and non-ACS controls (case-control study, total n = 171) were used to increase the translational relevance of our data. Compared to WT controls, Sirt5Tg/0 mice displayed accelerated arterial thrombus formation following endothelial-specific damage. Conversely, in Sirt5-/-mice arterial thrombosis was blunted. Platelet function was unaltered, as assessed by ex vivo collagen-induced aggregometry. Similarly, activation of the coagulation cascade as assessed by vascular and plasma tissue factor (TF) and TF pathway inhibitor (TFPI) expression was unaltered. Increased thrombus embolization episodes and circulating D-dimer levels suggested augmented activation of the fibrinolytic system in Sirt5-/- mice. Accordingly, Sirt5-/- mice showed reduced plasma and vascular expression of the fibrinolysis inhibitor plasminogen activator inhibitor (PAI)-1. In HAECs, SIRT5-silencing inhibited PAI-1 gene and protein expression in response to TNF-α. This effect was mediated by increased AMPK activation and reduced phosphorylation of the MAP kinase ERK 1/2, but not JNK and p38 as shown both in vivo and in vitro. Lastly, both PAI-1 and SIRT5 gene expression are increased in ACS patients compared to non-ACS controls after adjustment for cardiovascular risk factors, while PAI-1 expression increased across tertiles of SIRT5. CONCLUSIONS SIRT5 promotes arterial thrombosis by modulating fibrinolysis through endothelial PAI-1 expression. Hence, SIRT5 may be an interesting therapeutic target in the context of atherothrombotic events. TRANSLATIONAL PERSPECTIVES This study illustrates a novel role for Sirtuin 5 in arterial thrombosis by regulating fibrinolysis through plasminogen activator inhibitor 1 (PAI-1). These results shed new light onto the pathophysiology of arterial thrombus formation which underlies most of the acute atherosclerotic complications. Also, they further affirm the intrinsic relationship between lifespan regulating genes, vascular dysfunction and age-related cardiovascular disease, thus indicating these genes as potential targets for cardiovascular prevention and therapy. Further studies will be needed to assess the predictive ability of SIRT5 in patients with acute cardiovascular or cerebrovascular events. Also, the design of specific SIRT5 inhibitors will allow trials aiming at investigating the efficacy of SIRT5 blockage in the clinical setting.

Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study.

Abstract: Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p 40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29–11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.

Echocardiography versus computed tomography and cardiac magnetic resonance for the detection of left heart thrombosis: a systematic review and meta-analysis.

Abstract: Accurate and reproducible diagnostic techniques are essential to detect left-sided cardiac thrombi [either in the left ventricle (LV) or in the left atrial appendage (LAA)] and to guide the onset and duration of antithrombotic treatment while minimizing the risk for thromboembolic and hemorrhagic events. We conducted a systematic review and meta-analysis aiming to compare the diagnostic performance of transthoracic echocardiography (TTE) vs. cardiac magnetic resonance (CMR) for the detection of LV thrombi, and transesophageal echocardiography (TEE) vs. computed tomography (CT) for the detection of LAA thrombi. Six studies were included in the first meta-analysis (TTE vs. CMR for LV thrombosis). Pooled sensitivity and specificity values were 62% [95% confidence interval (CI), 37–81%] and 97% (95% CI, 94–99%). The shape of the hierarchical summary receiver operating characteristic (HSROC) curve and the area under the curve (AUC) of 0.96 suggested a high accuracy. Ten studies were included in the second meta-analysis (CT versus TEE for LAA thrombosis). The pooled values of sensitivity and specificity were 97% (95% CI, 77–100%) and 94% (95% CI, 87–98%). The pooled diagnostic odds ratio (DOR) was 500 (95% CI, 52–4810), and the pooled likelihood ratios (LR + and LR−) were 17% (95% CI, 7–40%) and 3% (95% CI, 0–28%). The shape of the HSROC curve and 0.99 AUC suggested a high accuracy of CT vs. TEE. TTE is a fair alternative to DE-CMR for the identification of LV thrombi, while CT has a good accuracy compared to TEE for the detection of LAA thrombosis. CRD42020185842.

Activate-2: a double-blind randomized trial of bcg vaccination against covid19 in individuals at risk

Abstract: SUMMARY BCG vaccination induces heterologous protection against respiratory tract infections, and in children improves survival independently of tuberculosis prevention. The phase III ACTIVATE-2 study assessed whether BCG could also protect against COVID19 in the elderly. In this double-blind, randomized trial, elderly Greek patients were randomized (1:1) to receive either BCG revaccination or placebo at hospital discharge, followed by 6 months observation for incidence of COVID19 infection. BCG revaccination resulted in 68% risk reduction for total COVID19 clinical and microbiological diagnoses (OR 0.32, 95% CI 0.13-0.79). Five patients in the placebo group and one in the BCG-vaccinated group had severe COVID19 that necessitated hospitalization. 3 months after BCG vaccination 1.3% of placebo and 4.7% of BCG-vaccinated volunteers had anti-SARS-CoV-2 antibodies. These data argue that BCG revaccination is safe and protects the elderly against COVID19. BCG revaccination may represent a viable preventive measure against COVID19.

Circulating Amyloid Beta 1-40 Is Associated with Increased Rate of Progression of Atherosclerosis in Menopause: A Prospective Cohort Study.

Abstract: Background Accumulating evidence suggests that circulating amyloidβ 1–40 (Αβ1–40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Αβ1–40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). Methods In this prospective study, Αβ1–40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. Results At baseline, high Αβ1–40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p Conclusion In postmenopausal women, a pattern of increasing or persistently high Αβ1–40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Αβ1–40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD.

A Bayesian meta-analysis on early tobacco exposure and vascular health: From childhood to early adulthood.

Abstract: BackgroundSmoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse ...

Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.

Abstract: Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) (n = 14) or Kd (n = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics (p > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit (p < 0.05). A significant group interaction (p < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.

Right drug, wrong dosage: insights from the PAVE-AF antithrombotic study in older patients with atrial fibrillation.

Abstract: Optimal antithrombotic treatment of older patients is usually impeded by several prevailing misconceptions. The aim of our study was to assess the type, dosage and predictors of antithrombotic therapy in older patients with non-valvular atrial fibrillation (NVAF). PAVE-AF was a prospective, cross-sectional study, including NVAF patients ≥ 80 years from 30 participating centers. Demographic data, comorbidities and treatment patterns were documented in a single visit. Patients treated with non-vitamin K oral anticoagulants (NOACs) were further classified into three dosing categories (recommended, underdosing and overdosing). Among 1018 patients (85.4±4.0 years), 88.4% received anticoagulants (AC), 8% antiplatelets (AP) and 3.6% no treatment. The primary reason for AP administration was physician concern of bleeding followed by patient denial. Patients ≥90 years had two times greater probability to receive AP therapy compared to patients < 90 years. Among patients treated with AC, one third received vitamin K antagonists, while two thirds received NOACs [34.6% apixaban, 9.5% dabigatran and 22.6% rivaroxaban]. Independent predictors of AC prescription over AP or no treatment were low HAS-BLED score, hypertension, labile INR, permanent AF, absence of uncontrolled hypertension, prior stroke/systemic embolism, age and male gender. In total, 37% of NOAC recipients received inappropriate dosage, while the number of patients receiving recommended dosing differed significantly among NOAC subgroups (p < 0.001). In our study, a minority of older NVAF patients received AP or no therapy for stroke prevention. Among patients treated with anticoagulants, two thirds were on NOAC treatment, though with a considerable proportion of inappropriate dosing.

Prognostic value of admission high-sensitivity troponin in patients with ST-elevation myocardial infarction.

Abstract: Background and aim Although the diagnostic usefulness of high-sensitivity cardiac troponin T (hs-cTnT) is well established in ST-segment elevation myocardial infarction (STEMI), its prognostic relevance in risk stratification of patients with STEMI remains obscure. This study sought to determine the prognostic value of pre-reperfusion (admission) and post-reperfusion (12-hour) hs-cTnT in patients with STEMI treated with primary percutaneous coronary intervention (PPCI). Methods Retrospective observational longitudinal study including consecutive patients with STEMI treated with PPCI at a university hospital in the northeast of England. hs-cTnT was measured at admission to the catheterisation laboratory and 12 hours after PPCI. Clinical, procedural and laboratory data were prospectively collected during patient hospitalisation (June 2010–December 2014). Mortality data were obtained from the UK Office of National Statistics. The study endpoints were in-hospital and overall mortality. Results A total of 3113 patients were included. Median follow-up was 53 months. Admission hs-cTnT >515 ng/L (fourth quartile) was independently associated with in-hospital mortality (HR=2.53 per highest to lower quartiles; 95% CI: 1.32 to 4.85; p=0.005) after multivariable adjustment for a clinical model of mortality prediction. Likewise, admission hs-cTnT >515 ng/L independently predicted overall mortality (HR=1.27 per highest to lower quartiles; 95% CI: 1.02 to 1.59; p=0.029). Admission hs-cTnT correctly reclassified risk for in-hospital death (net reclassification index (NRI)=0.588, p Conclusion Admission, but not 12-hour post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support a prognostic role for admission hs-cTnT while challenge the cost-effectiveness of routine 12-hour hs-cTnT measurements in patients with STEMI.

Consumption of Fruits, Vegetables and Bladder Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Abstract: We examined the association between fruit/vegetable consumption and bladder cancer (BC) risk in a systematic review and meta-analysis of prospective cohort studies stratifying results by gender, smoking status and geographical region. Eligible studies were sought in MEDLINE and EMBASE up to April 20, 2020. Random-effects (DerSimonian-Laird) models were implemented for the calculation of pooled relative risks (RRs) and 95% confidence intervals (CI). Fifteen eligible studies were identified (1,993,881 subjects, 11,097 BC cases). Vegetable consumption (pooled RR = 0.95, 95% CI: 0.87-1.04, n = 10) as well as combined fruit/vegetable consumption was not associated with BC risk. Regarding fruit intake, the overall protective trend did not reach significance (pooled RR = 0.91, 95%CI: 0.81-1.02, n = 11); we found however a significant association in East Asians. A trend toward a protective association with citrus fruit consumption was also noted (pooled RR = 0.83, 95%CI: 0.69-1.01, n = 6), once again with a significant effect in East Asians. Moreover, no association was found regarding the subgroups of leafy vegetables, dark green vegetables, and berries. Single studies pointed to a reduced BC risk in never smoking males consuming cruciferous vegetables and East Asians consuming yellow vegetables. In conclusion, our study reveals possible protective effects; larger studies are needed to investigate the emerging trends.

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome

Abstract: Objective Amyloid-beta1-40 (Aβ40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aβ40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state. Methods Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aβ40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aβ40 performance to detect arterial thrombotic APS-related events. Results Higher Aβ40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aβ40 levels. Importantly, Aβ40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-β2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aβ40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. Conclusion In APS, Aβ40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aβ40 in APS merits further investigation.

Utilization and tolerance of beta-blockers among patients with AL amyloidosis.

Abstract: BACKGROUND The utilization and clinical impact of beta-blockers (BBs) in cardiac amyloidosis (CA) is largely unexplored. METHODS We conducted a retrospective, single-center analysis of indications, timing of initiation, types and doses of BB used, reasons to discontinue BB and association between BB tolerance and outcomes in a cohort of patients with immunoglobulin light chain amyloidosis (AL). RESULTS We reviewed 236 patients with AL CA and identified 53 patients taking BB (22.5%). Most patients presented in New York Heart Association Class (NYHA) II or III (74.5%) and 24% presented in Mayo stage IIIB. The most frequent indications for BB initiation were atrial fibrillation (AF) and coronary artery disease (CAD). In most cases (59%) BB was started before the diagnosis of CA. The median duration of BB treatment was 9 months (interquartile range [IQR] 3-24 months). Among patients receiving BB, 28 tolerated BB during follow-up whereas 25 patients discontinued BB. The main causes of BB discontinuation were hypotension and heart failure (HF) exacerbation. Patients intolerant to BB presented with more advanced NYHA class, worse performance status and lower median left ventricular ejection fraction (LVEF) at baseline. At median follow-up duration of 17.7 months, patients who did not tolerate BB had a poor survival. CONCLUSIONS Although some patients with CA may have indications for treatment with BB, their use is uncommon and those with more advanced disease tolerate BB poorly. Intolerance to BB in patients with cardiac AL is an indicator of poorer outcome.

Wenckebach cycle length: A novel predictor for AV block in AVNRT patients treated with ablation.

Abstract: BACKGROUND Radiofrequency catheter ablation remains the most effective management option for atrioventricular nodal reentry tachycardia (AVNRT). The risk of atrioventricular (AV) block requiring permanent pacemaker is substantial, but, currently, a reliable method to predict this complication is lacking. METHODS The electrophysiologic studies (EPS) and baseline characteristics of patients who underwent catheter ablation for the treatment of AVNRT were retrospectively analyzed to investigate predisposing factors for AV block after treatment. Patients were followed for AV block at one month and one year after hospital discharge. RESULTS Among 784 patients treated with catheter ablation for AVNRT between 1999 to 2019, 15 developed AV block. Patients with AV block were older (p = .001). Among the recorded EPS parameters, patients with AV block had significantly higher Atrial His interval (120 vs. 110 ms, p = .049), Wenckebach cycle length (WCL) (400 vs. 353 ms, p < .001) and tachycardia CL (400 vs. 387 ms, P = .01) during the ablation compared to their peers without AV block. Additionally, only WCL (OR = 1.1, 95% CI 1.02-1.19, p = .017) remained significant after adjustment for age, gender, ERP, AH interval, and HR. This association was confirmed by comparing patients with (n = 15) and without (n = 15) AV block using propensity score-matching. A WCL≥400ms was associated with a 4-fold higher incidence of AV block (4.79% vs. 1.25%). CONCLUSION Increased pre-procedural WCL was associated with a high risk for AV block after catheter ablation treatment for AVNRT. These findings suggest that this readily available EPS-derived parameter may be a novel marker of risk for severe complications in these patients.