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.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

BACKGROUND: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. METHOD: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. RESULTS: The 11 848 participants from 13 cohorts (age 53 ±â€Š16 years, 50% men) were followed for up for 13.7 ±â€Š6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. CONCLUSION: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.

Long-term outcomes following drug-eluting balloon or thin-strut drug-eluting stents for treatment of in-stent restenosis stratified by duration of dual antiplatelet therapy (DEB-Dragon Registry).

Introduction: Data regarding the duration of dual antiplatelet therapy (DAPT) in patients with drug-eluting stent restenosis (DES-ISR) treated with percutaneous coronary intervention (PCI) and drug-eluting balloons (DEB) or DES are not unambiguous. Aim: To evaluate the relationship between long-term outcomes and the length of DAPT in patients treated with PCI due to DES-ISR with DEB or DES. Material and methods: Overall, a total of 1,367 consecutive patients with DES-ISR, who underwent PCI with DEB or DES between 2008 and 2019 entered the study. The mean length of the follow-up was 1,298.7 ±794 days. We assessed study endpoints according to the duration of DAPT (≤ 3 vs. > 3 and ≤ 6 vs. > 6 months) before and after propensity score matching (PSM): stroke, target lesion revascularisation (TLR), target vessel revascularisation (TVR), myocardial infarction (MI), death and device oriented composite endpoints (DOCE). Kaplan-Meier estimates were created to differentiate long-term outcomes. Results: Pairwise contrast analysis considering type of PCI (DES vs. DEB) and duration of DAPT (≤ 6 vs. > 6 months) before PSM revealed superiority of DES + DAPT > 6 months vs. DEB + DAPT > 6 months for DOCE (p < 0.001), TVR (p = 0.02) and TLR (p = 0.01). Also, DES + DAPT ≤ 6 months was found to be superior compared to DEB + DAPT ≤ 6 months for DOCE (p < 0.001), TVR (p = 0.02) and TLR (p = 0.01). Kaplan-Meier estimate analysis confirmed that DAPT > 6 months is related to a higher stroke rate (p = 0.01) when compared to ≤ 6 months. Conclusions: Treatment with DAPT in patients with DES-ISR is related to better long-term outcomes in the case of PCI with DES than DEB. DAPT > 6 months is related to the greater rate of strokes, independently of the type of treatment (DES and DEB) than DAPT ≤ 6 months.

Risk Stratification by Cross-Classification of Central and Brachial Systolic Blood Pressure.

BACKGROUND: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension. METHODS: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software. RESULTS: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1-111.8), 120.2 (119.4-121.0), 130.0 (129.6-130.3), and 149.5 (148.4-150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58-2.94) for isolated brachial hypertension, 2.28 (1.21-4.30) for isolated central hypertension, and 2.02 (1.41-2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37-10.06) and 2.60 (1.35-5.00), respectively. CONCLUSIONS: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.

Risk of Death and Ischemic Stroke in Patients with Atrial Arrhythmia and Thrombus or Sludge in Left Atrial Appendage at One-Year Follow-Up.

Thrombus in the left atrial appendage is a contraindication for cardioversion. Sludge is considered similarly as threatening as thrombus; however, the risk of death and ischemic stroke in patients with atrial arrhythmia and thrombus or sludge is not well-known. This study focused on assessing the risk of death and ischemic stroke at one-year follow-up in patients with atrial arrhythmia and thrombus or sludge, as well as the effectiveness of anticoagulation in thrombus resolution. 77 out of 267 (29%) of patients who were scheduled for cardioversion were diagnosed with thrombus or sludge. The annual mortality in patients with thrombus or sludge was 23%. In the group without thrombus, the annual mortality was 1.6%. Overall, 17% of patients with thrombus or sludge experienced ischemic stroke. In patients without thrombus, the risk of stroke was 1%. Sludge increased risk of stroke compared to those without thrombus or sludge by 11% vs. 1%, respectively. No differences in mortality or stroke prevalence were observed between sludge and thrombus. Thrombus or sludge in the LAA have a poor prognosis. A diagnosis of sludge has a similar impact on risk of ischemic strokes as does a diagnosis of thrombus.

Outcomes of audio-instructed and video-instructed dispatcher-assisted cardiopulmonary resuscitation: a systematic review and meta-analysis.

BACKGROUND: The present meta-analysis of clinical and simulation trials aimed to compare video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (V-DACPR) with conventional audio-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (C-DACPR). METHODS: We searched PubMed, Embase, Web of Science, Cochrane Collaboration databases and Scopus from inception until June 10, 2021. The primary outcomes were the prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with a good neurological outcome for clinical trials, and chest compression quality for simulation trials. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) indicated the pooled effect. The analyses were performed with the RevMan 5.4 and STATA 14 software. RESULTS: Overall, 2 clinical and 8 simulation trials were included in this meta-analysis. In clinical trials, C-DACPR and V-DACPR were characterised by, respectively, 11.8% vs. 24.3% of prehospital ROSC (OR = 0.46; 95% CI: 0.30, 0.69; I2 = 66%; p < .001), 10.7% vs. 22.3% of survival to hospital discharge (OR = 0.46; 95% CI: 0.30, 0.70; I2 = 69%; p < .001), and 6.3% vs. 16.0% of survival to hospital discharge with a good neurological outcome (OR = 0.39; 95% CI: 0.23, 0.67; I2 = 73%; p < .001). In simulation trials, chest compression rate per minute equalled 91.3 ± 22.6 for C-DACPR and 107.8 ± 12.6 for V-DACPR (MD = -13.40; 95% CI: -21.86, -4.95; I2 = 97%; p = .002). The respective values for chest compression depth were 38.7 ± 14.3 and 41.8 ± 12.5 mm (MD = -2.67; 95% CI: -8.35, 3.01; I2 = 98%; p = .36). CONCLUSIONS: As compared with C-DACPR, V-DACPR significantly increased prehospital ROSC and survival to hospital discharge. Under simulated resuscitation conditions, V-DACPR exhibited a higher rate of adequate chest compressions than C-DACPR.Key messagesBystander cardiopulmonary resuscitation parameters significantly depend on the dispatcher's support and the manner of the support provided.Video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation can increase the rate of prehospital return of spontaneous circulation and survival to hospital discharge.Video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation improves the quality of chest compressions compared with dispatcher-assisted resuscitation without video instruction.

Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

BACKGROUND: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). METHODS: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). RESULTS: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. CONCLUSIONS: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

How to Distinguish Marfan Syndrome from Marfanoid Habitus in a Physical Examination-Comparison of External Features in Patients with Marfan Syndrome and Marfanoid Habitus.

Marfan Syndrome (MFS) is a systemic disorder caused by mutations in fibrillin-1. The most common cause of mortality in MFS is dissection and rupture of the aorta. Due to a highly variable and age-dependent clinical spectrum, the diagnosis of MFS still remains sophisticated. The aim of the study was to determine if there exist phenotypic features that can play the role of "red flags" in cases of MFS suspicion. The study population included 306 patients (199 children and 107 adults) who were referred to the Department of Pediatric Cardiology due to suspicion of MFS. All patients underwent complete clinical evaluation in order to confirm the diagnosis of MFS according to the modified Ghent criteria. MFS was diagnosed in 109 patients and marfanoid habitus in 168 patients. The study excluded 29 patients with other hereditary thoracic aneurysm syndromes. Comparative analysis between patients with Marfan syndrome and marfanoid habitus was performed. Symptoms with high prevalence and high positive likelihood ratio were identified (pectus carinatum, reduced elbow extension, hindfoot deformity, gothic palate, downslanting palpebral fissures, lens subluxation, myopia ≥ 3 dioptres remarkably high stature). The differentiation between patients with MFS and marfanoid body habitus is not possible by only assessing external body features; however, "red flags" could be helpful in the screening phase.

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants.

OBJECTIVE: To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS: Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS: The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th-95th percentile interval, 1.3-12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS: IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.

Long-Term Outcomes Following Drug-Eluting Balloons Versus Thin-Strut Drug-Eluting Stents for Treatment of In-Stent Restenosis (DEB-Dragon-Registry).

[Figure: see text].

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol.

BACKGROUND: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. METHODS: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. EXPECTED OUTCOMES: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients.

Characteristics and outcomes of in-hospital cardiac arrest in COVID-19. A systematic review and meta-analysis.

BACKGROUND: The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period. METHODS: A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with cardiac arrest. RESULTS: Survival to hospital discharge for the pre-pandemic and pandemic period was reported in 3 studies (n =1432 patients) and was similar in the pre-pandemic vs. the pandemic period, 35.6% vs. 32.1%, respectively (odds ratio [OR] 1.72; 95% confidence interval [CI] 0.81-3.65; p = 0.16; I2 = 72%). Return of spontaneous circulation was reported by all 4 studies and were also similar in the pre and during COVID-19 periods, 51.9% vs. 48.7% (OR 1.27; 95% CI 0.78-2.07; p = 0.33; I2 = 71%), respectively. Pooled analysis of cardiac arrest recurrence was also similar, 24.9% and 17.9% (OR 1.60; 95% CI 0.99-2.57; p = 0.06; I2 = 32%) in the pre and during COVID-19 cohorts. Survival with Cerebral Performance Category 1 or 2 was higher in pre vs. during pandemic groups (27.3 vs. 9.1%; OR 3.75; 95% CI 1.26-11.20; p = 0.02). Finally, overall mortality was similar in the pre vs. pandemic groups, 65.9% and 67.2%, respectively (OR 0.67; 95% CI 0.33-1.34; p = 0.25; I2 = 76%). CONCLUSIONS: Compared to the pre-pandemic period, in hospital cardiac arrest in COVID-19 patients was numerically higher but had statistically similar outcomes.

Impact of Coronavirus Disease 2019 on Out-of-Hospital Cardiac Arrest Survival Rate: A Systematic Review with Meta-Analysis.

Out-of-hospital cardiac arrest (OHCA) is a challenge for medical staff, especially in the COVID-19 period. The COVID-19 disease caused by the SARS-CoV-2 coronavirus is highly infectious, thus requiring additional measures during cardiopulmonary resuscitation (CPR). Since CPR is a highly aerosol-generating procedure, it carries a substantial risk of viral transmission. We hypothesized that patients with diagnosed or suspected COVID-19 might have worse outcomes following OHCA outcomes compared to non-COVID-19 patients. To raise awareness of this potential problem, we performed a systematic review and meta-analysis of studies that reported OHCA in the pandemic period, comparing COVID-19 suspected or diagnosed patients vs. COVID-19 not suspected or diagnosed group. The primary outcome was survival to hospital discharge (SHD). Secondary outcomes were the return of spontaneous circulation (ROSC), survival to hospital admission or survival with favorable neurological outcomes. Data including 4210 patients included in five studies were analyzed. SHD in COVID-19 and non-COVID-19 patients were 0.5% and 2.6%, respectively (odds ratio, OR = 0.25; 95% confidence interval, CI: 0.12, 0.53; p < 0.001). Bystander CPR rate was comparable in the COVID-19 vs. not COVID-19 group (OR = 0.88; 95% CI: 0.63, 1.22; p = 0.43). Shockable rhythms were observed in 5.7% in COVID-19 patients compared with 37.4% in the non-COVID-19 group (OR = 0.19; 95% CI: 0.04, 0.96; p = 0.04; I2 = 95%). ROSC in the COVID-19 and non-COVID-19 patients were 13.3% vs. 26.5%, respectively (OR = 0.67; 95% CI: 0.55, 0.81; p < 0.001). SHD with favorable neurological outcome was observed in 0% in COVID-19 vs. 3.1% in non-COVID-19 patients (OR = 1.35; 95% CI: 0.07, 26.19; p = 0.84). Our meta-analysis suggests that suspected or diagnosed COVID-19 reduces the SHD rate after OHCA, which seems to be due to the lower rate of shockable rhythms in COVID-19 patients, but not due to reluctance to bystander CPR. Future trials are needed to confirm these preliminary results and determine the optimal procedures to increase survival after OHCA in COVID-19 patients.