Cardiac Time Intervals Measured by Tissue Doppler Imaging M-mode:Association With Hypertension, Left Ventricular Geometry, and Future Ischemic Cardiovascular Diseases

BACKGROUND: We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons with hypertension and are strong predictors of future ischemic cardiovascular diseases in the general population. METHODS AND RESULTS: In a large community‐based population study, cardiac function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M‐mode through the mitral leaflet. IVCT/ET, IVRT/ET, and myocardial performance index [MPI=(IVRT+IVCT)/ET] were calculated. After multivariable adjustment for clinical variables the IVRT, IVRT/ET, and MPI, remained significantly impaired in persons with hypertension (n=826) compared with participants without hypertension (n=1082). Additionally, they displayed a significant dose–response relationship, between increasing severity of elevated blood pressure and increasing left ventricular mass index (P<0.001 for all). Further, during follow‐up of a median of 10.7 years, 435 had an ischemic cardiovascular disease (ischemic heart disease, peripheral arterial disease, or stroke). The IVRT/ET and MPI were powerful and independent predictors of future cardiovascular disease, especially in participants with known hypertension. They provide prognostic information incremental to clinical variables from the Framingham Risk Score, the SCORE risk chart, and the European Society of Hypertension/European Society of Cardiology risk chart. CONCLUSION: The cardiac time intervals identify impaired cardiac function in individuals with hypertension, not only independent of conventional risk factors but also in participants with a normal conventional echocardiographic examination. The IVRT/ET and MPI are independent predictors of future cardiovascular disease especially in participants with known hypertension

Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure:A Phase II Danish Multicentre Study

Background. Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems and cryopreserved as an off-the-shelf product ready to use. Study Design. A multicentre, double-blind, placebo-controlled phase II study with direct intramyocardial injections of allogeneic CSCC_ASC in patients with chronic IHF. A total of 81 patients will be randomised at 2 : 1 to CSCC_ASC or placebo. There is no HLA tissue type matching needed between the patients and the donors. Methods. The treatment will be delivered by direct injections into the myocardium. The primary endpoint is change in the left ventricle endsystolic volume at 6-month follow-up. Secondary endpoints are safety and changes in left ventricle ejection fraction, myocardial mass, stroke volume, and cardiac output. Other secondary endpoints are change in clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12 months. Conclusion. The aim of the present study is to demonstrate safety and the regenerative efficacy of the allogeneic CSCC_ASC product from healthy donors in a double-blind, placebo-controlled, multicentre study in patients with IHF

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges

Plasma high-mobility group box 1 levels predict mortality after ST-segment elevation myocardial infarction

ObjectivesWe evaluated the potential association between plasma high-mobility group box 1 (HMGB1) levels and outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention.BackgroundThe positive effect of reperfusion after STEMI may be compromised by ischemic/reperfusion injury. HMGB1 is released by necrotic cells and, in pre-clinical studies, has been implicated to play a role in myocardial ischemic/reperfusion injury.MethodsThe study included 141 STEMI patients, with acute occlusion of the left anterior descending coronary artery successfully treated with percutaneous coronary intervention. Plasma HMGB1 levels were measured by enzyme-linked immunoadsorbent assay at admission. Forty-two healthy individuals served as control subjects.ResultsAfter a median of 10 months of follow-up, 13 STEMI patients died. There were no significant differences with regard to baseline variables between the group of patients who survived and those who died. Baseline HMGB1 levels were increased in STEMI patients when compared with control subjects. Furthermore, the STEMI patients who died had higher HMGB1 levels than those who survived. After adjusting for age, sex, troponin I, and creatine kinase-myocardial band, we found that a doubling of HMGB1 concentrations increased the risk of mortality by 75% (hazard ratio: 1.75; 95% confidence interval: 1.1 to 2.8).ConclusionsPlasma HMGB1 levels are elevated in STEMI patients compared with healthy control subjects. Furthermore, after a follow-up period of 10 months, plasma HMGB1 levels are shown to be independently associated with increased mortality in STEMI patients treated with PCI. These data suggest that plasma HMGB1 may be used as a new prognostic biomarker in STEMI patients