Cardiovascular Mortality In High-risk Patients Research Articles

STAT1 regulates neutrophil gelatinase B-associated lipocalin induction in influenza-induced myocarditis

Influenza is a significant public health and economic threat around the world. Epidemiological studies have demonstrated a close association between influenza pandemics and cardiovascular mortality. Moreover, it has been shown that there is a decrease in cardiovascular mortality in high-risk patients following vaccination with the influenza vaccine. Here, we have investigated the role of anti-viral STAT1 signaling in influenza-induced myocarditis. Wild-type mice (C57BL/6) were infected with either influenza A/PR/8/34 or control, and cellular response and gene expression analysis from the heart samples were assessed 7 days later. The expression of interferon response genes STAT1, STAT2, Mx1, OASL2, ISG15, chemokines CCL2, CCL3, CXCL9 and CXCL10, and the frequency of neutrophils (CD45+CD11b+Ly6G+) and CD4+ T cells (CD45+CD4+) were all significantly increased in influenza-infected mice when compared to vehicle controls. These data suggest that influenza infection induces interferons, inflammatory chemokines, and cellular recruitment during influenza infection. We further investigated the role of STAT1 in influenza-induced myocarditis. The frequency of neutrophils and the levels of lipocalin 2 were significantly increased in STAT1−/− mice when compared to WT controls. Finally, we investigated the role of Lcn2 in viral-induced myocarditis. We found that in the absence of Lcn2, there was preserved cardiac function in Lcn2−/− mice when compared to WT controls. These data suggest that the absence of Lcn2 is cardioprotective during viral-induced myocarditis.

Predictive value of overt and non-overt volume overload in patients with high- or low-gradient aortic stenosis undergoing transcatheter aortic valve implantation.

The plasma volume status (PVS) is considered a marker of non-overt cardiac congestion and is of prognostic value. Patients with low-flow, low-gradient (LFLG) aortic stenosis (AS) suffer from impaired left ventricular function and show signs of heart failure (HF). We hypothesized that PVS might predict post-interventional rehospitalization and cardiovascular mortality in high-risk patients undergoing transcatheter aortic valve implantation (TAVI). In this retrospective, observational analysis, PVS before transfemoral TAVI was calculated by a formula taking into account hematocrit and weight. The predictive performance of PVS was compared with that of prior cardiac decompensation (PCD). In the entire cohort of n=2,458 patients, PVS >-4% (high plasma volume) identified patients (n=1,013) with a higher post-interventional 1-year mortality rate than patients (n=1,445) with a PVS ≤-4% (low plasma volume). However, PVS lost prognostic independence when adjusted for anemia, whereas PCD did not. A high PVS and PCD were not correlated, and both parameters similarly revealed a low sensitivity and specificity but a high negative predictive value (NPV) for future HF events. PVS was not different between control patients (n=1,512) and those with intermediate (paradoxical LFLG-AS, n=327) or high risk scores (LFLG-AS, n=239). The accuracy of high PVS in predicting adverse events in these subpopulations was the same as in the study population overall. Kaplan-Maier analyses demonstrated similar prognostic impacts for PVS and PCD. PVS and PCD represent two independent parameters of volume overload with unfavorable prognostic significance. Pre-interventional PVS does not appear to be suitable for predicting clinical outcomes in high-risk patients undergoing TAVI.

FROM NOSE BLOCK TO HEART BLOCK: A CASE OF INFLUENZA A CAUSING COMPLETE HEART BLOCK

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Influenza is associated with cardiac complications such as myocarditis, congestive heart failure, and sudden death in hospitalized patients. It is also known to cause conduction blocks and cardiac arrest secondary to asystole and ventricular fibrillation. This is often overlooked as a cause of rhythm disorders due to the paucity of knowledge, and the rarity of the condition. CASE PRESENTATION: A 58-year-old female with a history first-degree atrioventricular block (AVB) presented with shortness of breath and cough for 3 days. On admission, she was febrile with a temperature of 100.5 degrees F and a normal chest x-ray. She tested positive for influenza A H1 N1. Her electrocardiogram (EKG) showed first-degree AVB with a PR interval of 300ms. However, on day 2, she had a syncopal episode and the telemetry strip revealed bradycardia with a 4.5-second pause. Her EKG showed a second-degree Mobitz type II that degenerated into a complete heart block. Electrophysiology was consulted, she underwent transvenous pacing. Her echocardiogram showed normal systolic function and chamber size, with no valvular abnormalities. She had an FDG positive emission tomography-cardiac sarcoidosis study which found no increased uptake to suggest an inflammatory/infiltrative process. She also had negative ischemia work up 6 months before hospitalization. The AVB was attributed to influenza after ruling out other causes. She subsequently underwent implantation of a dual-chamber his pacemaker with non-selective His bundle pacing. DISCUSSION: The pathogenesis of conduction disorders in influenza is believed to be secondary to myocarditis and inflammatory infiltrates pressing the conduction pathway with consequent necrosis in experimental models. It has also been hypothesized that inflammatory cytokines alter the electrical properties of endothelial cells which could explain why our patient had a complete heart block, without evidence of myocarditis (1). Hypoxia can cause AVB however, our patient was not hypoxic when the syncopal episode occurred. Hence, it is important to keep a close eye on patients admitted with influenza with an already compromised conduction system as there is a risk of potential worsening due to the inflammatory cytokines. Although the treatment of influenza is relatively simple, delay in initiating treatment may be fatal. Epidemiological studies have demonstrated decreased cardiovascular mortality in high-risk patients following influenza vaccination, so it is vital to educate patients about the importance of vaccination (2). CONCLUSIONS: Patients with an already compromised conduction system are at risk of worsening conduction blocks when faced with an inflammatory trigger. Most cases of conduction blocks secondary to influenza are temporary and resolve without a permanent pacemaker, however, cases with high degree block/complete heart block may warrant implantation of a permanent pacemaker. Reference #1: Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis. 2009;9(10):601-10. Reference #2: Mamas MA, Fraser D, Neyses L. Cardiovascular manifestations associated with influenza virus infection. Int J Cardiol. 2008;130(3):304-9. DISCLOSURES: No relevant relationships by Ayesha Azmeen, source=Web Response No relevant relationships by Dimitrios Drekolias, source=Web Response No relevant relationships by Naga Vaishnavi Gadela, source=Web Response No relevant relationships by Jason Jacob, source=Web Response No relevant relationships by Mahati Paravathaneni, source=Web Response

Association between Physical Activity and Mortality in Patients with Claudication.

This study aimed to determine the association between light-intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD) limited by claudication followed for up to 18.7 yr. A total of 528 patients with PAD and claudication were screened in Baltimore between 1994 and 2002, and 386 were deemed eligible for the study. At baseline, patients were classified into three physical activity groups: 1) physically sedentary, 2) light intensity, and 3) moderate to vigorous intensity based on a questionnaire. All-cause and cardiovascular mortality of patients through December 2014 was determined using the National Death Index and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository. Median survival time was 9.9 yr (interquartile range, 4.9-15.7 yr; range, 0.38-18.7 yr). During follow-up, 257 patients (66.6%) died, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light-intensity group, and 82/128 (64.0%) from the moderate- to vigorous-intensity group. For all-cause mortality, light-intensity activity status (hazard ratio [HR] = 0.523, P = 0.0007) and moderate- to vigorous-intensity status (HR = 0.425, P < 0.0001) were significant predictors. During follow-up, 125 patients died because of cardiovascular causes (32.4%), in which light-intensity activity status (HR = 0.511, P = 0.0113) and moderate- to vigorous-intensity activity status (HR = 0.341, P = 0.0003) were significant predictors. Light-intensity physical activity is associated with nearly 50% lower risk of all-cause and cardiovascular mortality in high-risk patients with PAD and claudication. Furthermore, moderate- to vigorous-intensity physical activity performed regularly is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The survival benefits associated with light-intensity physical activity make it a compelling behavioral intervention that extends beyond improving ambulation.

Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction

The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. clinicaltrials.gov Identifier: NCT01685840.

Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Azithromycin is not associated with QT prolongation in hospitalized patients with community-acquired pneumonia.

Large data-based studies have reported excess cardiovascular mortality in high-risk patients treated with azithromycin, but whether or not azithromycin causes QT prolongation remains controversial. The purpose of this study was to examine the association of azithromycin treatment on QT prolongation in a cohort of patients hospitalized with community-acquired pneumonia (CAP) METHODS: One-hundred twenty-two hospitalized patients with CAP were enrolled in the study. We compared the baseline QTc, with daily post antibiotic QTc. Other risk factors for QT prolongation such as medication or electrolyte abnormalities were recorded. Ninety (73.8%) patients were treated with azithromycin (usually in combination with ceftriaxone), and 32 (26.2%) patients with other antibiotics (ampicillin-clavulanate, chloramphenicol, doxcycline, or ceftriaxone); 72.1% (88) of the cohort experienced QT lengthening; 72.7% with QT lengthening had a normal baseline QTc. Azithromycin was not associated with the post-antibiotic QTc. Wide (pathological) post-antibiotic QTc was associated with the pneumonia score. Every 10-point increase in the pneumonia score raised the risk for a pathological post antibiotic QTc by 1.249 (95%CI: 1.050-1.486). Analysis of patients with non-pathological baseline QTc revealed that pathological post-antibiotic QTc was only associated with previous stroke and not with the type of antibiotic. Azithromycin treatment was not associated with QT prolongation in patients with severe CAP. Nonetheless, in a large majority of hospitalized CAP patients, QT prolongation and pathological QTc develop regardless of the antibiotic used, especially in patients with previous stroke or a higher pneumonia score.

Usefulness of Abnormal Heart Rate Turbulence to Predict Cardiovascular Mortality in High-Risk Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction (from the EPHESUS Study)

Heart rate turbulence (HRT) is a promising marker for risk of mortality after acute myocardial infarction (AMI). We investigated HRT for risk stratification in high-risk patients after MI. HRT from 24-hour Holter monitoring in 481 hospitalized patients after AMI with heart failure and/or diabetes with left ventricular dysfunction before randomization in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Over a 1-year follow-up, 55 died, 49 of cardiovascular causes. HRT onset (TO) and slope (TS) were calculated using previous and cohort-optimized cutpoints and their independent contribution to risk of cardiovascular death determined. Models were tested with <5 ventricular premature complexes (PVCs) categorized as normal (n = 452) and with <5 VPCs excluded (n = 342). In EPHESUS, optimal cutpoints were TS < or = 3.0 and TO > or = 0.0. The strongest model for predicting cardiovascular mortality used EPHESUS cutpoints excluding subjects with <5 VPCs. On 3-category HRT model multivariate analysis (TS and TO normal, TS or TO abnormal, TS and TO abnormal), both TS and TO abnormal (relative risk 3.64, 95% confidence interval 1.55 to 8.55, p = 0.003) and left ventricular ejection fraction < or =30% (relative risk 1.97, 95% confidence interval 1.04 to 3.73, p = 0.037) independently predicted cardiovascular death. In conclusion, HRT is an independent predictor of cardiovascular death in a high-risk population after AMI, with a possibly higher optimal cutpoint for HRT slope than previously reported.

The T−786C Endothelial Nitric Oxide Synthase Genotype Predicts Cardiovascular Mortality in High-Risk Patients

This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.