The strength-duration curves for left bundle branch area pacing.

BACKGROUND: Despite growing clinical use of left bundle branch pacing (LBBP) there is scarcity of data regarding fundamentals of this pacing modality including chronaxie and rheobase. OBJECTIVE: The aims of this study were to calculate strength-duration curves with chronaxie, rheobase values for LBBP and left ventricular septal myocardial pacing (LVSP), to analyse battery current drain and presence of selective LBBP at very short pulse duration (PD). METHODS: The group of 141 patients with permanent LBBP were studied. The LBBP and LVSP capture thresholds were assessed at 6 different PDs to calculate the strength-duration curves. Battery current drain at these PDs and presence of selective LBBP were determined. For comparison of strength-duration curves between His bundle pacing (HBP) and LBBP, source data from our previous work based on 127 patients with HBP were obtained. RESULTS: The chronaxies for LBBP and LVSP were very similar (0.38 ms vs. 0.39 ms) and the rheobases were identical (0.27V). The chronaxie for LBBP was lower than for HBP (0.38ms vs. 0.53 ms, p < 0.001), whereas rheobases were similar (0.27V vs. 0.26V). A narrow zone of selective capture was present in 19% and 41% of patients at PD of 0.06 ms and 0.03 ms, respectively. When pacing with the safety margin of +1 V, the lowest battery current drain was achieved with PD of 0.2 ms. CONCLUSION: The obtained strength-duration curves for LBBP and LVSP provide insights for optimal programming of LBBAP devices with regard to pulse duration, voltage amplitude, battery longevity and selective capture.

Left bundle branch area pacing improves right ventricle function and synchrony.

BACKGROUND: The impact of left bundle branch area pacing (LBBAP) on right ventricular (RV) function and tricuspid regurgitation (TR) remains unclear. OBJECTIVE: We aimed to assess the long-term effects of LBBAP on RV performance and on TR. METHODS: RV function was evaluated using RV free wall strain (FWS), tricuspid annular plane systolic excursion (TAPSE), fractional area changing (FAC), and systolic (S`) velocity of the lateral tricuspid annulus. The presence of reverse septal flash (RSF) and basal bulge (BB) was used to assess RV motion pattern. The distance between the lead entry site on the interventricular septum and the septal leaflet of the tricuspid annulus was measured (lead-TV distance). RESULTS: The analysis included 122 subjects (62 males, age 76.5±11.4 years) with a median follow-up of 21 months. During follow-up, RV FWS improved significantly (15.2±5.8 vs 16.4±5.5, p < 0.001), while TAPSE, S`, and FAC remained unchanged. Left ventricular ejection fraction was an independent predictor for improved RV function (B: 3.51, CI 1.39 - 8.9, p = 0.01). With LBBAP, RSF disappeared in 22/23 (96%) patients, and BB in 15/22 (68%) patients in whom RSF and BB were present at baseline, respectively. RV function improvement was significantly higher when RSF was present at baseline (14 vs 11 patients, p = 0.02). At follow-up, no significant deterioration in TR occurred for the overall group. However, a lead-TV distance of < 24.5 mm was associated with TR progression. CONCLUSION: LBBAP has a favorable impact on RV function. A basal LBBAP position is associated with worsening TR.

Uncontrolled hypertension and hypertensive urgency: One-year single-center emergency department experience.

BACKGROUND: The prevalence of uncontrolled hypertension remains a significant concern in public healthcare systems, including daily practices of emergency departments (ED). AIM: We aimed to characterize patients admitted to an ED for elevated blood pressure (BP) and to identify factors leading to hospitalization. METHODS: This retrospective analysis included all patients admitted to an ED in a tertiary hospital in 2022 due to an acute BP rise without hypertensive emergencies. RESULTS: The studied group (n = 570) constituted 1.5% of all ED admissions in 2022. The median age was 67 years (Q1-Q3) (52-75), 68.9% were females. Systolic BP (200 mm Hg [180-212]) and diastolic BP (105 mm Hg [100-115]) at home were higher than during triage (173 mm Hg [160-190] and 95 mm Hg [84-103], respectively [P <0.0001]). Thirty-nine percent of the studied population had taken BP-lowering agents before ED admission (captopril in 91.8% of cases). In the ED, nitrendipine (54.2%), captopril (38.1%), furosemide (16.3%), urapidil (10.0%), and nitroglycerine (1.9%) were administered. Eventually, a median of 140/82 mm Hg BP was reached in the median time of 288 minutes (202-400). Hospitalization was necessary in 5.4% of patients. The need for furosemide or urapidil administration in the ED doubled the risk of hospitalization (OR, 2.0; P <0.01). Before ED admission, only 17.0% of patients received guidelines-recommended single-pill combination therapy, and 17.6% had already visited ED for uncontrolled hypertension (median of 388 days earlier). CONCLUSIONS: Elevated BP is a common reason for admission to the ED. Crucially, improvements in long-term hypertension treatment and education are needed to reduce the number of patients seeking ED care for elevated BP.

Accessory pathway localization with probabilistic density maps generated by a mobile application: Assessment of a full pre-excitation net-vector method.

INTRODUCTION: Precise electrocardiographic localization of accessory pathways (AP) can be challenging. Seminal AP localization studies were limited by complexity of algorithms and sample size. We aimed to create a nonalgorithmic method for AP localization based on color-coded maps of AP distribution generated by a web-based application. METHODS: APs were categorized into 19 regions/types based on invasive electrophysiologic mapping. Preexcited QRS complexes were categorized into 6 types based on polarity and notch/slur. For each QRS type in each lead the distribution of APs was visualized on a gradient map. The principle of common set was used to combine the single lead maps to create the distribution map for AP with any combination of QRS types in several leads. For the validation phase, a separate cohort of APs was obtained. RESULTS: A total of 800 patients with overt APs were studied. The application used the exploratory data set of 553 consecutive APs and the corresponding QRS complexes to generate AP localization maps for any possible combination of QRS types in 12 leads. Optimized approach (on average 3 steps) for evaluation of preexcited electrcardiogram was developed. The area of maximum probability of AP localization was pinpointed by providing the QRS type for the subsequent leads. The exploratory data set was validated with the separate cohort of APs (n = 256); p = .23 for difference in AP distribution. CONCLUSIONS: In the largest data set of APs to-date, a novel probabilistic and semi-automatic approach to electrocardiographic localization of APs was highly predictive for anatomic localization.

Unattended automatic blood pressure measurements versus conventional office readings in predicting hypertension-mediated organ damage.

INTRODUCTION: Hypertension is a leading cardiovascular risk factor. Accurate blood pressure measurement is pivotal in hypertension diagnosis and management. Conventional office measurements (OBP) are error-prone, exacerbated by the white coat effect. Unattended automated office blood pressure measurement (UAOBP) is emerging as an alternative, mitigating the white coat effect. However, its ability to predict hypertension-mediated organ damage (HMOD) remains disputable. OBJECTIVES: This study compares UAOBP with OBP in terms of their association with various HMODs, including left ventricular hypertrophy, left atrial enlargement, left ventricular systolic and diastolic dysfunction, intima-media complex thickening, microalbuminuria and abnormal pulse wave velocity. PATIENTS AND METHODS: A total of 219 hypertensive patients were recruited, interviewed, and examined. Subsequently, blood pressure measurements were conducted in a randomized manner: 1) UAOBP: after 5 minutes of solitary rest in the examination room, the patient's blood pressure was automatically measured three times at 1-minute intervals. 2) OBP: after 5 minutes of rest, a physician performed three consecutive blood pressure measurements at 1-minute intervals. Subsequent evaluations aimed to detect HMODs, including echocardiography, carotid artery ultrasound, pulse wave velocity assessment, and laboratory tests. RESULTS: The blood pressure values in UAOBP were significantly lower than those in OBP (mean (SD) 124.7 (14.4) vs. 128.2 (14.2) mmHg, P <0.001 for systolic, and 73.3 (10.2) vs. 75.2 (10.6) mmHg, P <0.001 for diastolic). Correlation and ROC curve analyses revealed no method's superiority in predicting HMOD. CONCLUSIONS: The UAOBP did not prove superior in predicting HMOD compared to OBP, Further research is warranted to determine the role of UAOBP in clinical practice.

Lead-associated mortality in the US 1999-2020: a time-stratified analysis of a national cohort.

OBJECTIVES: We undertook time-stratified analyses of the National Health and Nutrition Examination Survey in the US to assess time trends (1999-2020) in the associations of blood lead (BL) with blood pressure, mortality, the BL-associated population attributable fraction (PAF). METHODS: Vital status of participants, 20-79 years old at enrolment, was ascertained via the National Death Index. Regressions, mediation analyses and PAF were multivariable adjusted and standardized to 2020 US Census data. RESULTS: In time-stratified analyses, BL decreased from 1.76 µg/dl in 1999-2004 to 0.93 µg/dl in 2017-2020, while the proportion of individuals with BL < 1 µg/dl increased from 19.2% to 63.0%. Total mortality was unrelated to BL (hazard ratio (HR) for a fourfold BL increment: 1.05 [95% confidence interval, CI: 0.93-1.17]). The HR for cardiovascular death was 1.44 (1.01-2.07) in the 1999-2000 cycle, but lost significance thereafter. BL was directly related to cardiovascular mortality, whereas the indirect BL pathway via BP was not significant. Low socioeconomic status (SES) was directly related to BL and cardiovascular mortality, but the indirect SES pathway via BL lost significance in 2007-2010. From 1999-2004 to 2017-2020, cardiovascular PAF decreased (P < 0.001) from 7.80% (0.17-14.4%) to 2.50% (0.05-4.68%) and number of lead-attributable cardiovascular deaths from 53 878 (1167-99 253) to 7539 (160-14 108). CONCLUSION: Due to implementation of strict environmental policies, lead exposure is no longer associated with total mortality, and the mildly increased cardiovascular mortality is not associated with blood lead via blood pressure in the United States.

Predicting acute kidney injury onset using a random forest algorithm using electronic medical records of COVID-19 patients: the CRACoV-AKI model.

INTRODUCTION: Acute kidney injury (AKI) is a serious and common complication of SARS-CoV-2 infection. Most risk assessment tools for AKI have been developed in the intensive care unit or elderly population. As the COVID-19 pandemic is transitioning into an endemic state, there is an unmet need for prognostic scores tailored to this population. OBJECTIVES: Development of a robust predictive model for the occurrence of AKI in hospitalized patients with COVID-19. PATIENTS AND METHODS: Electronic medical records of all adult inpatients admitted between March 2020 and January 2022 were extracted from a large, tertiary care center with reference status in Lesser Poland. We screened 5806 patients with SARS-CoV-2 infection confirmed with polymerase chain reaction test. After excluding subjects with absent serum creatinine values or mild disease course (less than 7 days of inpatient care), 4630 patients were recruited. Data was randomly split into a training (N = 3462) and test (N = 1168) cohort. A random forest model was tuned with feature engineering based on expert advice and metrics evaluated in nested cross-validation to reduce bias. RESULTS: Nested cross-validation yielded an AUC (area under the curve) with a range of 0.793-0.807 and an average performance of 0.798. Model explanation techniques from a global perspective suggest respiratory support, chronic kidney disease and procalcitonin are among the most important variables in permutation tests. CONCLUSIONS: The CRACoV-AKI model enables AKI risk stratification among hospitalized patients with COVID-19. Machine learning-based tools may thus offer additional decision-making support for specialist providers.

The Significance of Coronary Artery Calcification for Percutaneous Coronary Interventions.

The prevalence of calcium deposits in coronary arteries grows with age. Risk factors include, e.g., diabetes and chronic kidney disease. There are several underlying pathophysiological mechanisms of calcium deposition. Severe calcification increases the complexity of percutaneous coronary interventions. Invasive techniques to modify the calcified atherosclerotic plaque before stenting have been developed over the last years. They include balloon- and non-balloon-based techniques. Rotational atherectomy has been the most common technique to treat calcified lesions but new techniques are emerging (orbital atherectomy, intravascular lithotripsy, laser atherectomy). The use of intravascular imaging (intravascular ultrasound and optical coherence tomography) is especially important during the procedures in order to choose the optimal strategy and to assess the final effect of the procedure. This review provides an overview of the role of coronary calcification for percutaneous coronary interventions.

Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis.

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

The sodium-chloride difference: A marker of prognosis in patients with acute myocardial infarction.

BACKGROUND: The difference between serum sodium and chloride ion concentrations (SCD) may be considered as a surrogate of a strong ion difference and may help to identify patients with a worse prognosis. We aimed to assess SCD as an early prognostic marker among patients with myocardial infarction. METHODS: Data of 594 consecutive patients with acute myocardial infarction treated with PCI (44.9% STEMI patients; 70.7% males) was analysed for SCD in relation to their 30-day mortality. A restricted cubic spline regression model was used to study the relationship between mortality and SCD. Cox regression models were used to assess the association between SCD and the mortality risk. RESULTS: Patients with Killip class ≥3 had lower SCD values in comparison to patients with Killip class ≤2: (32.0 [30.0-34.0] vs. 33.0 [31.0-36.0], p = .006). The overall 30-day mortality was 7.7% (n = 46). There was a significant difference in SCD values between survivors and non-survivors groups of patients (median (IQR): (33.0 [31.0-36.0] vs. 31.5 [28.0-34.0] (mmol/L), p = .002). The restricted cubic splines model confirmed a non-linear association between SCD and mortality. Patients with SCD <30 mmol/L (in comparison to SCD ≥30 mmol/L) had an increased mortality risk (unadjusted HR 2.92, 95% CI 1.59-5.36, p = .001; and an adjusted HR 2.30, 95% CI 1.02-5.19, p = .04). CONCLUSIONS: Low SCD on admission is associated with an increased risk of 30-day mortality in patients with acute myocardial infarction treated with PCI and may serve as a useful prognostic marker for these patients.

Angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists modulate sodium handling based on endogenous lithium clearance.

BACKGROUND: Numerous studies based on assessment of lithium clearance demonstrated higher sodium reabsorption in renal proximal tubules in individuals with hypertension, overweight, obesity, metabolic syndrome, or diabetes. AIMS: We aimed to assess the influence of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II-receptor antagonists (ARB) treatment on sodium handling. METHODS: In a sample of 351Caucasian subjects without diuretic treatment with prevailing sodium consumption, we studied associations between renal sodium reabsorption in proximal (FPRNa) and distal (FDRNa) tubules assessed by endogenous lithium clearance and daily sodium intake measured by 24-hour excretion of sodium (UNaV), in the context of obesity and long-term treatment with ACE-I or ARB. RESULTS: In the entire study population, we found a strong negative association between FPRNa and ACE-I/ARB treatment (b = -19.5; SE = 4.9; P <0.001). Subjects with FPRNa above the median value showed a significant adverse association between FPRNa and age (b = -0.06; SE = 0.02; P = 0.003), with no association with ACE-I/ARB treatment (P = 0.68). In contrast, in subjects with FPRNa below the median value, we found a strongly significant adverse relationship between FPRNa and ACE-I/ARB treatment (b = -30.4; SE = 8.60; P <0.001), with no association with age (P = 0.32). CONCLUSIONS: ACE-I/ARB long-term treatment modulates FPRNa in the group with lower reabsorption, but not in that with higher than median value for the entire study population.

Association of Air Pollution with a Urinary Biomarker of Biological Aging and Effect Modification by Vitamin K in the FLEMENGHO Prospective Population Study.

BACKGROUND: A recently developed urinary peptidomics biological aging clock can be used to study accelerated human aging. From 1990 to 2019, exposure to airborne particulate matter (PM) became the leading environmental risk factor worldwide. OBJECTIVES: This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age, and whether this association is modified by other risk factors. METHODS: In a Flemish population, the urinary peptidomic profile (UPP) age (UPP-age) was derived from the urinary peptidomic profile measured by capillary electrophoresis coupled with mass spectrometry. UPP-age-R was calculated as the residual of the regression of UPP-age on chronological age, which reflects accelerated aging predicted by UPP-age, independent of chronological age. A high-resolution spatial-temporal interpolation method was used to assess each individual's exposure to PM10, PM2.5, black carbon (BC), and nitrogen dioxide (NO2). Associations of UPP-age-R with these pollutants were investigated by mixed models, accounting for clustering by residential address and confounders. Effect modifiers of the associations between UPP-age-R and air pollutants that included 18 factors reflecting vascular function, renal function, insulin resistance, lipid metabolism, or inflammation were evaluated. Direct and indirect (via UPP-age-R) effects of air pollution on mortality were evaluated by multivariable-adjusted Cox models. RESULTS: Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP ≥4.26µg/L (median), an interquartile range (IQR) higher level in PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. DISCUSSION: Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories. https://doi.org/10.1289/EHP13414.

Serial echocardiographic evaluation of COVID-19 patients without prior history of structural heart disease: a 1-year follow-up CRACoV-HHS study.

Background: It is a well-known fact that COVID-19 affects the cardiovascular system by exacerbating heart failure in patients with preexisting conditions. However, there is a poor insight into the cardiovascular involvement and sequelae in patients without preexisting conditions. The aim of the study is to analyse the influence of COVID-19 on cardiac performance in patients without prior history of structural heart disease. The study is part of the CRACoV project, which includes a prospective design and a 12-month follow-up period. Material and methods: The study included 229 patients hospitalised with a diagnosis of COVID-19 (median age of 59 years, 81 were women). A standard clinical assessment and laboratory tests were performed in all participants. An extended echocardiographic image acquisition was performed at baseline and at a 3-, 6-, and 12-month follow-up. All analyses were performed off-line. A series of echocardiographic parameters was compared using repeated measures or Friedman analysis of variance. Results: In all subjects, the left ventricular (LV) ejection fraction at baseline was preserved [63.0%; Q1:Q3 (60.0-66.0)]. Elevated levels of high-sensitivity cardiac troponin T were detected in 21.3% of the patients, and elevated NT-proBNP levels were detected in 55.8%. At the 1-year follow-up, no significant changes were observed in the LV diameter and volume (LV 48.0 ± 5.2 vs. 47.8 ± 4.8 mm, p = 0.08), while a significant improvement of the parameters in the biventricular strain was observed (LV -19.1 ± 3.3% vs. -19.7 ± 2.5%, p = 0.01, and right ventricular -19.9 ± 4.5% vs. -23.2 ± 4.9%, p = 0.002). In addition, a decrease in the LV wall thickness was also observed (interventricular septum 10.4 ± 1.6 vs. 9.7 ± 2.0 mm, p < 0.001; LV posterior wall 9.8 ± 1.4 vs. 9.1 ± 1.5 mm, p < 0.001). Conclusions: In an acute phase of COVID-19, the elevation of cardiac biomarkers in patients with normal left ventricular ejection fraction is a frequent occurrence; however, it does not translate into clinically significant cardiac dysfunction after 1 year. The serial echocardiographic evaluations conducted in patients without preexisting structural heart disease demonstrate an overall trend towards an improved cardiac function and a reduced myocardial thickening at 1-year follow-up. This suggests that the acute cardiac consequences of COVID-19 are associated with systemic inflammation and haemodynamic stress in patients without preexisting conditions.

Does the incidence of infectious endocarditis show seasonal patterns? - a single center retrospective study.

I n t r o d u c t i o n: Seasonal variation has been observed for bacterial and viral infections (e.g., COVID-19 [1]), but also for numerous cardiac problems. However, little information is available on the seasonality of infectious endocarditis (IE), a rare disease that is usually linked to a bacterial origin. Data from the Polish population are lacking. Materials and M e t h o d s: Our retrospective study focused on the identification of patients with IE, who were hospitalized at the University Hospital in Krakow between 2005-2022. For this purpose, we searched the medical records system using the ICD-10 code. We decided to divide our patients into four groups (winter, spring, summer, autumn), based on the date of admission to the hospital. Comparison of the distribution of IE incidents by season was performed with the ch2 test. R e s u l t s: One hundred and ten patients were included in the study (median age 62.5 years (range 20-94), 72 men (65.45%)). The left native valve IE was diagnosed in 49% of the patients, the prosthetic valve IE in 16%, the right valve IE in 27% and the implantable cardiac electronic devices IE in 12% of the subjects. The outcomes comprised of cardiac surgery (n = 53), embolism (n = 16), death (n = 15) and metastatic infections (n = 5). No differences in the incidence of IE by season were observed. C o n c l u s i o n s: In the preliminary observation of IE cases of patients admitted to the University Hospital in Krakow, Poland no seasonal pattern of IE was detected. Therefore, IE should be taken into account in the differential diagnosis at any time of the year.

Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

Neutrophil-activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation.

Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF). We recruited 237 consecutive patients with AF (mean age, 68 ± 11 years; median CHA2DS2VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (> 796 ng/ml) were characterized by higher neutrophil count (+ 31.7%), fibrinogen (+ 20.8%), citH3 (+ 86%), and 3-nitrotyrosine (+ 111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1 ng/ml ß = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100 ng/ml ß = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced Ks. Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF.

The role of stress hyperglycemia and hyperlactatemia in non-diabetic patients with myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: Stress hyperglycemia and lactates have been used separately as markers of a severe clinical condition and poor outcomes in patients with myocardial infarction (MI). However, the interplay between glucose and lactate metabolism in patients with MI have not been sufficiently studied. The aim in the present study was to examine the relationship of glycemia on admission (AG) and lactate levels and their impact on the outcome in non-diabetic MI patients treated with percutaneous coronary intervention (PCI). METHODS: A total of 405 consecutive, non-diabetic, MI patients were enrolled in this retrospective, observational, single-center study. Clinical characteristic including glucose and lactate levels on admission and at 30-day mortality were assessed. RESULTS: Patients with stress hyperglycemia (AG ≥ 7.8 mmol/L, n = 103) had higher GRACE score (median [interquartile range]: 143.4 (115.4-178.9) vs. 129.4 (105.7-154.5), p = 0.002) than normoglycemic patients (AG level < 7.8 mmol/L, n = 302). A positive correlation of AG with lactate level (R = 0.520, p < 0.001) was observed. The coexistence of both hyperglycemia and hyperlactatemia (lactate level ≥ 2.0 mmol/L) was associated with lower survival rate in the Kaplan-Meier estimates (p < 0.001). In multivariable analysis both hyperglycemia and hyperlactatemia were related to a higher risk of death at 30-day follow-up (hazard ratio [HR] 3.21, 95%, confidence interval [CI] 1.04-9.93; p = 0.043 and HR 7.08; 95% CI 1.44-34.93; p = 0.016, respectively) CONCLUSIONS: There is a relationship between hyperglycemia and hyperlactatemia in non-diabetic MI patients treated with PCI. The coexistence of both hyperglycemia and hyperlactatemia is associated with lower survival rate and are independent predictors of 30-day mortality in MI patients and these markers should be evaluated simultaneously.

Left bundle branch area pacing prevents pacing induced cardiomyopathy in long-term observation.

BACKGROUND: Left bundle branch area pacing (LBBAP) is one of the methods to deliver conduction system pacing which potentially avoids the negative impact of conventional right ventricular pacing. OBJECTIVE: To assess echocardiographic outcomes in a long-term observation in patients with LBBAP implemented for bradyarrhythmia indications. METHODS AND RESULTS: A total of 151 patients with symptomatic bradycardia and LBBAP pacemaker implanted, were prospectively included in the study. Subjects with left bundle branch block and CRT indications (n = 29), ventricular pacing burden <40% (n = 11), and loss of LBBAP (n = 10) were excluded from further analysis. At baseline and the last follow-up visit, echocardiography with global longitudinal strain (GLS) assessment, 12-lead ECG, pacemaker interrogation, and blood level of NT-proBNP were performed. The median follow-up period was 23 months (15.5-28). None of the analyzed patients fulfilled the criteria for pacing induced cardiomyopathy (PICM). Improvement in left ventricular ejection fraction (LVEF) and GLS was observed in patients with LVEF <50% at baseline (n = 39): 41.4 ± 9.2% versus 45.6 ± 9.9%, and 12.9 ± 3.6% versus 15.5 ± 3.7%, respectively. In the subgroup with preserved EF (n = 62), LVEF and GLS remained stable at follow-up: 59.3 ± 5.5% versus 60 ± 5.5%, and 19 ± 3.9% versus 19.4 ± 3.8%, respectively. CONCLUSION: LBBAP prevents PICM in patients with preserved LVEF and improves left ventricle function in subjects with depressed LVEF. LBBAP might be the preferred pacing modality for bradyarrhythmia indications.