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Background and Objectives@#Aortic valve replacement (AVR) is considered a class I indication for symptomatic severe aortic stenosis (AS). However, there is little evidence regarding the potential benefits of early AVR in symptomatic patients diagnosed with normal-flow, low-gradient (NFLG) severe AS. @*Methods@#Two-hundred eighty-one patients diagnosed with symptomatic NFLG severe AS (stroke volume index ≥35 mL/m 2 , mean transaortic pressure gradient <40 mmHg, peak transaortic velocity <4 m/s, and aortic valve area <1.0 cm 2 ) between January 2010 and December 2020 were included in this retrospective study. After performing 1:1 propensity score matching, 121 patients aged 75.1±9.8 years (including 63 women) who underwent early AVR within 3 months after index echocardiography, were compared with 121 patients who received conservative care. The primary outcome was a composite of all-cause death and heart failure (HF) hospitalization. @*Results@#During a median follow-up of 21.9 months, 48 primary outcomes (18 in the early AVR group and 30 in the conservative care group) occurred. The early AVR group demonstrated a significantly lower incidence of primary outcomes (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.29–0.93; p=0.028); specifically, there was no significant difference in all-cause death (HR, 0.51; 95% CI, 0.23–1.16; p=0.110), although the early AVR group showed a significantly lower incidence of hospitalization for HF (HR, 0.43; 95% CI, 0.19–0.95, p=0.037). Subgroup analyses supported the main findings. @*Conclusions@#An early AVR strategy may be beneficial in reducing the risk of a composite outcome of death or hospitalization for HF in symptomatic patients with NFLG severe AS.Future randomized studies are required to validate and confirm our findings.
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BACKGROUNDOver 20% of cases and 0.4% of deaths from Covid-19 occur in children. Following demonstration of safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial enrolled adolescents. METHODSSafety, immunogenicity, and efficacy of NVX-CoV2373 were evaluated in adolescents aged 12 to <18 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States. Participants were randomized 2:1 to two doses of NVX-CoV2373 or placebo 21 days apart, and followed for a median of 2 months after second vaccination. Primary end points were serologic non-inferiority of neutralizing antibody (NA) responses compared with young adults (18 to <26 years) in PREVENT-19, protective efficacy against laboratory-confirmed Covid-19, and assessment of reactogenicity/safety. RESULTSAmong 2,247 participants randomized between April-June 2021, 1,491 were allocated to NVX-CoV2373 and 756 to placebo. Post-vaccination, the ratio of NA geometric mean titers in adolescents compared to young adults was 1.5 (95% confidence interval [CI] 1.3 to 1.7). Twenty Covid-19 cases (all mild) occurred: 6 among NVX-CoV2373 and 14 among placebo recipients (vaccine efficacy [VE]: 79.5%, 95% CI, 46.8 to 92.1). All sequenced viral genomes (11/20) were identified as Delta variant (Delta variant VE: 82.0% [95% CI: 32.4 to 95.2]). Reactogenicity was largely mild-to-moderate, transient, and more frequent in NVX-CoV2373 recipients and after the second dose. Serious adverse events were rare and evenly distributed between treatments. CONCLUSIONSNVX-CoV2373 was safe, immunogenic, and efficacious in the prevention of Covid-19 and those cases caused by the Delta variant in adolescents. (Funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; PREVENT-19 ClinicalTrials.gov number, NCT04611802).
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In the randomized, placebo-controlled PREVENT-19 phase 3 trial conducted in the U.S. and Mexico of the NVX-CoV2373 adjuvanted, recombinant spike protein nanoparticle vaccine, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks after two doses were assessed as correlates of risk and as correlates of protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID- 19). These immune correlates analyses were conducted in the U.S. cohort of baseline SARS- CoV-2 negative per-protocol participants using a case-cohort design that measured the antibody markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases (Mexico was excluded due to zero breakthrough cases with the efficacy data cut-off date April 19, 2021). In vaccine recipients, the baseline risk factor-adjusted hazard ratio of COVID-19 was 0.36 (95% CI: 0.20, 0.63), p<0.001 (adjusted p-0.005) per 10-fold increase in IgG spike concentration and 0.39 (0.19, 0.82), p=0.013 (adjusted p=0.030) per 10-fold increase in nAb ID50 titer. At spike IgG concentration 100, 1000, and 6934 binding antibody units/ml (100 is the 3rd percentile, 6934 is the 97.5th percentile), vaccine efficacy to reduce the probability of acquiring COVID-19 at 59 days post marker measurement was 65.5% (95% CI: 23.0%, 90.8%), 87.7% (77.7%, 94.4%), and 94.8% (88.0%, 97.9%), respectively. At nAb ID50 titers of 50, 100, 1000, and 7230 IU50/ml (50 is the 5th percentile, 7230 the 97.5th percentile), these estimates were 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), 92.8% (85.1%, 97.4%) and 96.8% (88.3%, 99.3%). The same two antibody markers were assessed as immune correlates via the same study design and statistical analysis in the mRNA-1273 phase 3 COVE trial (except in COVE the markers were measured four weeks post dose two). Spike IgG levels were slightly lower and nAb ID50 titers slightly higher after NVX-CoV2373 than after mRNA-1273 vaccination. The strength of the nAb ID50 correlate was similar between the trials, whereas the spike IgG antibodies appeared to correlate more strongly with NVX-CoV2373 in PREVENT-19, as quantified by the hazard ratio and the degree of change in vaccine efficacy across antibody levels. However, the relatively few breakthrough cases in PREVENT-19 limited the ability to infer a stronger correlate. The conclusion is that both markers were consistent correlates of protection for the two vaccines, supporting potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.
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With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients’cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.
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Background and Objectives@#This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). @*Methods@#A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). @*Results@#During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. @*Conclusion@#Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.
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BACKGROUNDVaccination using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antigen has been effective in the prevention of coronavirus disease 2019 (Covid-19). NVX-CoV2373 is an adjuvanted, recombinant S protein nanoparticle vaccine that demonstrated clinical efficacy for prevention of Covid-19 in phase 2b/3 trials in the United Kingdom and South Africa. METHODSThis phase 3, randomized, observer-blinded, placebo-controlled trial evaluated the efficacy and safety of NVX-CoV2373 in adults [≥]18 years of age in the United States and Mexico during the first quarter of 2021. Participants were randomized in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary end point was vaccine efficacy (VE) against reverse transcriptase-polymerase chain reaction-confirmed Covid-19 in SARS-CoV-2-naive participants [≥]7 days after the second dose administration. RESULTSOf the 29,949 participants randomized between December 27, 2020, and February 18, 2021, 29,582 (median age: 47 years, 12.6% [≥]65 years) received [≥]1 dose: 19,714 received vaccine and 9868 placebo. In the per-protocol population, there were 77 Covid-19 cases; 14 among vaccine and 63 among placebo recipients (VE: 90.4%, 95% confidence interval [CI] 82.9 to 94.6, P<0.001). All moderate-to-severe cases occurred in placebo recipients, yielding VE of 100% (95% CI 87.0 to 100). Most sequenced viral genomes (48/61, 78.7%) were variants of concern (VOC) or interest (VOI), mainly represented by variant alpha/B.1.1.7 (31/35, 88.6% VOC identified). VE against any VOC/VOI was 92.6% (95% CI 83.6 to 96.7). Reactogenicity was mostly mild-to-moderate and transient, but more frequent in NVX-CoV2373 recipients and after the second dose. Serious adverse events were rare and evenly distributed between treatments. CONCLUSIONSNVX-CoV2373 was well tolerated and demonstrated a high overall VE (>90%) for prevention of Covid-19, with most cases due to variant strains. (Funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; PREVENT-19 ClinicalTrials.gov number, NCT04611802.)
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BackgroundThe safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines has not yet been reported. MethodsA sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomized trial of the safety and efficacy of NVX-CoV2373. The first [~]400 participants meeting main study entry criteria and with no contraindications to influenza vaccination were invited to join the sub-study. After randomization in a 1:1 ratio to receive NVX-CoV2373 (n=217) or placebo (n=214), sub-study participants received an age-appropriate, licensed, open-label influenza vaccine with dose 1 of NVX-CoV2373. Reactogenicity was evaluated via electronic diary for 7 days post-vaccination in addition to monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Influenza haemagglutination inhibition and SARS-CoV-2 anti-spike IgG assays were performed. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed. Comparisons were made between sub-study and main study participants. FindingsSub-study participants were younger, more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in the co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy in the sub-study was 87.5% (95% CI: -0.2, 98.4) while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5). InterpretationThis is the first study to demonstrate the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. The results suggest concomitant vaccination may be a viable immunisation strategy. FundingThis study was funded by Novavax, Inc. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for research articles published from December 2019 until 1 April 2021 with no language restrictions for the terms "SARS-CoV-2", "COVID-19", "vaccine", "co-administration", and "immunogenicity". There were no peer-reviewed publications describing the simultaneous use of any SARS-CoV-2 vaccine and another vaccine. Several vaccine manufacturers had recent publications on phase 3 trials results (Pfizer/BioNTech, Moderna, AstraZeneca, Janssen, and the Gamaleya Research Institute of Epidemiology and Microbiology). Neither these publications nor their clinical trials protocols (when publicly available) described co-administration and they often had trial criteria specifically excluding those with recent or planned vaccination with any licenced vaccine near or at the time of any study injection. Added value of this studyImmune interference and safety are always a concern when two vaccines are administered at the same time. This is the first study to demonstrate the safety and immunogenicity profile and clinical vaccine efficacy of a COVID-19 vaccine when co-administered with a seasonal influenza vaccine. Implications of all the available evidenceThis study provides much needed information to help guide national immunisation policy decision making on the critical issue of concomitant use of COVID-19 vaccines with influenza vaccines.
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BackgroundCovid-19 vaccines are urgently needed, especially against emerging variants. NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 rS) nanoparticle vaccine containing trimeric full-length SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant. MethodsA phase 3, randomized, observer-blinded, placebo-controlled trial was conducted in adults 18-84 years old who received two intramuscular 5-{micro}g doses, 21 days apart, of NVX-CoV2373 or placebo (1:1) across 33 sites in the United Kingdom. The primary efficacy endpoint was virologically confirmed symptomatic Covid-19 with onset 7 days after second vaccination in serologically negative participants. ResultsA total of 15,187 participants were randomized, of whom 7569 received NVX-CoV2373 and 7570 received placebo; 27.2% were 65 years or older, 44.7% had comorbidities and 4.2% had baseline serological evidence of SARS-CoV-2. There were 10 cases of Covid-19 among NVX-CoV2373 recipients and 96 cases among placebo recipients, with symptom onset at least 7 days after second vaccination; NVX-CoV2373 was 89.7% (95% confidence interval, 80.2 to 94.6) effective in preventing Covid-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8 to 99.5) and 86.3% (71.3 to 93.5) against the prototype strain and B.1.1.7 variant, respectively. Vaccine efficacy was similar across subgroups, including participants with comorbidities and those [≥]65 years old. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. ConclusionA two-dose regimen of NVX-CoV2373 conferred 89.7% protection against a blend of prototype and variant Covid-19, demonstrated high efficacy against the B.1.1.7 variant, and had a reassuring safety profile. (Funded by Novavax, Inc. EudraCT number, 2020-004123-16).
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BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. MethodsIn this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 {micro}g recombinant spike protein with 50 {micro}g Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy [≥]7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. ResultsA total of 4387 participants were randomized and dosed at least once, 2199 with NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX-CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: - 0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373; serious adverse events were rare in both groups. ConclusionsThe NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS-CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)
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BackgroundNVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. MethodsThe phase 2 component of our randomized, placebo-controlled, phase 1-2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late phase studies in younger (18-59 years) and older (60-84 years) participants and was based on immunogenicity and safety data through day 35 (14 days after the second dose). Participants were randomly assigned to receive either one or two intramuscular doses of 5-{micro}g or 25-{micro}g NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response. ResultsAfter randomization, approximately 250 participants each were assigned to one of four vaccine groups or placebo. Of these, approximately 45% were older participants. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose, and occurred less frequently and was of lower intensity in older participants. The two-dose regimen of 5-{micro}g NVX-CoV2373 induced robust geometric mean titer (GMT) IgG anti-spike protein (65,019 and 28,137 EU/mL) and wild-type virus neutralizing antibody (2201 and 981 titers) responses in younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in convalescent sera for both age groups. ConclusionsThe study confirmed that the two-dose regimen of 5-{micro}g NVX-CoV2373 is highly immunogenic and well tolerated in both younger and older participants. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number: NCT04368988).
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Objective@#Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM). @*Materials and Methods@#Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test. @*Results@#The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785). @*Conclusion@#Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.
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Objective@#Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM). @*Materials and Methods@#Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test. @*Results@#The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785). @*Conclusion@#Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.
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BackgroundSeveral candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known. MethodsFollowing vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers. This reconstruction allows estimation of both vaccine durability and potential vaccine-associated enhanced disease. ResultsPost-crossover estimates of vaccine efficacy can provide insights about durability, identify waning efficacy, and identify late enhancement of disease, but are less reliable estimates than those obtained by a standard trial where the placebo cohort is maintained. As vaccine efficacy estimates for post-crossover periods depend on prior vaccine efficacy estimates, longer pre-crossover periods with higher case counts provide better estimates of late vaccine efficacy. Further, open-label crossover may lead to riskier behavior in the immediate crossover period for the unblinded vaccine arm, confounding vaccine efficacy estimates for all post-crossover periods. ConclusionsWe advocate blinded crossover and continued follow-up of trial participants to best assess vaccine durability and potential delayed enhancement of disease. This approach allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain participants on placebo, yet still allows important insights about immunological and clinical effectiveness over time.
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BackgroundNVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. MethodsThis is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. ResultsParticipants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean [≤]2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5g NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. ConclusionsNVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).
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Intradialytic blood pressure abnormalities are associated with adverse outcomes in patients with end-stage renal disease on dialysis. Vascular calcification is a common complicating feature, but whether this complication results in intradialytic blood pressure abnormalities remains uncertain. Therefore, this study investigated the relationship between coronary artery calcium score and intradialytic blood pressure abnormalities in patients with end-stage renal disease on maintenance hemodialysis. Thirty-six patients who received nongated chest computed tomography scans were included. Intradialytic hypotension was defined as a minimum intradialytic systolic blood pressure of <100 mmHg or a pre-dialysis blood pressure – minimum intradialytic systolic blood pressure >30 mmHg. Intradialytic hypertension was defined as >10 mmHg increase in systolic blood pressure (pre- to post-dialysis). Patients were classified as 22 (61.1%) with coronary artery calcium score <400 and 14 (38.9%) with coronary artery calcium score ≥400. Median systolic and diastolic blood pressures were equivalent, but median pulse pressure was higher in patients with coronary artery calcium score ≥400 than in those with scores <400. Coronary artery calcium score was comparable according to both intradialytic hypotension and hypertension, and had no correlation with systolic blood pressure fall and nadir systolic blood pressure. Coronary artery calcium score predicted the occurrence of cardiovascular events and all-cause mortality (hazard ratio 1.001 and 1.001; p=0.058 and 0.010). Coronary vascular calcification could be irrelevant to intradialytic blood pressure abnormalities in patients with end-stage renal disease on dialysis.
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Humanos , Presión Sanguínea , Calcio , Vasos Coronarios , Diálisis , Hipertensión , Hipotensión , Fallo Renal Crónico , Mortalidad , Diálisis Renal , Tórax , Calcificación VascularRESUMEN
OBJECTIVE: Previous studies have shown that fenofibrate therapy increases serum creatinine level and that there is a return of serum creatinine to baseline level after the discontinuation of the drug. We evaluated the effect of long-term fenofibrate therapy on creatinine levels and its reversibility in patients with hypertension and hypertriglyceridemia. METHODS: This retrospective study enrolled 54 hypertensive and hypertriglyceridemic patients taking fenofibrate for 3–6 years (Fenofibrate group) and 30 control patients with similar age, sex, follow-up duration, and creatinine levels (Control group). In 23 patients taking fenofibrate with low triglyceride level and/or with high creatinine levels, fenofibrate was discontinued, and creatinine levels were measured after 2 months. RESULTS: Creatinine levels increased in both the fenofibrate group (from 0.91±0.18 mg/dL to 1.09±0.23 mg/dL, p < 0.001) and the control group (from 0.94±0.16 mg/dL to 0.98±0.16 mg/dL, p=0.04) compared to baseline. However, the elevation was more pronounced in the fenofibrate group than in the control group (21.1±15.4% vs. 4.5±11.3%, p < 0.001). The discontinuation of fenofibrate lowered creatinine levels (from 1.39±0.32 mg/dL to 1.15±0.24 mg/dL, p < 0.001) which were still higher than pre-treatment levels (p=0.013). CONCLUSION: Long-term fenofibrate therapy significantly increased creatinine levels in hypertensive and hypertriglyceridemic patients. The effect of fenofibrate on creatinine level was partially reversible. This finding suggests that follow-up creatinine level is necessary with fenofibrate therapy.
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Humanos , Creatinina , Fenofibrato , Estudios de Seguimiento , Hipertensión , Hipertrigliceridemia , Estudios Retrospectivos , TriglicéridosRESUMEN
BACKGROUND: To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. METHODS: We retrospectively enrolled 812 (59 +/- 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. RESULTS: The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 +/- 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). CONCLUSION: CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA.
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Angina Inestable , Angiografía , Enfermedad de la Arteria Coronaria , Muerte , Electrocardiografía , Estudios de Seguimiento , Infarto del Miocardio , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Electric cardioversion has been successfully used in terminating symptomatic atrial fibrillation (AF). Nevertheless, largescale study about the acute cardiovascular events following electrical cardioversion of AF is lacking. This study was performed to evaluate the incidence, risk factors, and clinical consequences of acute cardiovascular events following electrical cardioversion of AF. MATERIALS AND METHODS: The study enrolled 1100 AF patients (mean age 60+/-11 years) who received cardioversion at four tertiary hospitals. Hospitalizations for stroke/transient ischemic attack, major bleedings, and arrhythmic events during 30 days post electric cardioversion were assessed. RESULTS: The mean duration of anticoagulation before cardioversion was 95.8+/-51.6 days. The mean International Normalized Ratio at the time of cardioversion was 2.4+/-0.9. The antiarrhythmic drugs at the time of cardioversion were class I (45%), amiodarone (40%), beta-blocker (53%), calcium-channel blocker (21%), and other medication (11%). The success rate of terminating AF via cardioversion was 87% (n=947). Following cardioversion, 5 strokes and 5 major bleedings occurred. The history of stroke/transient ischemic attack (OR 6.23, 95% CI 1.69-22.90) and heart failure (OR 6.40, 95% CI 1.77-23.14) were among predictors of thromboembolic or bleeding events. Eight patients were hospitalized for bradyarrhythmia. These patients were more likely to have had a lower heart rate prior to the procedure (p=0.045). Consequently, 3 of these patients were implanted with a permanent pacemaker. CONCLUSION: Cardioversion appears as a safe procedure with a reasonably acceptable cardiovascular event rate. However, to prevent the cardiovascular events, several risk factors should be considered before cardioversion.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/complicaciones , Bradicardia/epidemiología , Enfermedades Cardiovasculares/epidemiología , Cardioversión Eléctrica/métodos , Insuficiencia Cardíaca/epidemiología , Incidencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Non-calcified plaque (NCP) identified by coronary CT angiography (CCTA) has been reported in up to 10% of individuals with coronary artery calcium score (CACS) of zero. However, clinical risk factors and the prognostic value of NCP in asymptomatic subjects with CACS of zero are unknown. SUBJECTS AND METHODS: The study population consisted of consecutive asymptomatic subjects (48+/-8 years, 57% men) who underwent CCTA from December 2005 to January 2008 as part of a general health evaluation. RESULTS: Among 4491 of overall asymptomatic individuals with CACS of zero, 313 subjects (7%) had NCP: 279 patients (6%) with non-obstructive and 34 (1%) with obstructive. In multivariable analyses, age, male gender, diabetes, hypertension, and dyslipidemia were significantly associated with presence of NCP (all p<0.05). During the median follow-up duration of 22 months (interquartile percentile: 18 to 28 months) of subjects with NCP (n=313) and age, gender, and CCTA date matched individuals without NCP (n=313), there was no clinical event including all-cause death nor composite outcome of cardiac death, myocardial infarct, unstable angina requiring hospitalization, and revascularization after 90 days from index CCTA in both groups. CONCLUSION: In the largest series of asymptomatic individuals with CACS of zero undergoing CCTA, age, male gender, diabetes, hypertension, and dyslipidemia were independently associated with NCP. However, a future risk of exclusive NCP in asymptomatic subjects with CACS of zero was negligible.
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Humanos , Masculino , Angina Inestable , Angiografía , Calcio , Vasos Coronarios , Muerte , Dislipidemias , Estudios de Seguimiento , Hospitalización , Hipertensión , Infarto del Miocardio , Placa Aterosclerótica , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Family history (FHx) of coronary heart disease (CHD) is a well-known risk factor for CHD. However, the prognostic implication of FHx has not been established clearly in patients with acute myocardial infarction (AMI). METHODS: In total, 11,612 patients (8,132 males [70%], age 63 +/- 13 years) with first-onset AMI between November 2005 and June 2008 in a nationwide, prospective, multicenter, online registry (the Korea AMI Registry) were analyzed. Clinical characteristics and outcomes (cardiac death and major adverse cardiac events [MACEs]) were assessed according to the presence of FHx. RESULTS: The patients with FHx were younger and included more males. Male patients with FHx included more current smokers and individuals with poor lipid profiles. In all patients, after adjustment using the Cox proportional hazard model, FHx was related to the risk of MACEs (hazard ratio [HR], 1.41; p = 0.009) and cardiac death (HR, 1.56; p = 0.080). The poor prognostic implication of FHx was further augmented in females and a low risk subset of patients. A significant interaction was only found between male and female patients for composite MACEs (p for interaction = 0.057), and between patients with more risk factors (> or = 2 risk factors) and fewer risk factors for cardiac deaths (p for interaction = 0.008). CONCLUSIONS: FHx may be an independent prognostic predictor, especially in female patients and patients with low-risk profile.
