Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification.

OBJECTIVE: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. METHODS: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/µL [to convert to cells ×109/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality. RESULTS: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score. CONCLUSION: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.

Turning a New Chapter in Neurosurgery Outpatient Services: Telemedicine A "Savior" in this Pandemic.

BACKGROUND: Teleconsultation services in India, especially in neurosurgery, are relatively new. Despite its large-scale adoption during the COVID-19 pandemic, comprehensive analyses of patients' perspectives and hurdles are lacking. MATERIALS AND METHODS: We conducted an anonymized telephonic survey of consecutive neurosurgical patients who availed telemedicine services at our institute, using a validated, structured questionnaire. To prevent bias, interviewers were not involved in the study design/analyses. Patients' perception of usefulness and performance of teleconsultation was graded on a 5-point Likert scale. RESULTS: Of the 330 patients who availed teleconsultation services, 231 (70%) completed the survey. Even though 91% of the respondents had access to a smartphone, only 10% received a video-based teleconsult. As per respondents, the challenges included poor network (7%), suboptimal communication/discussion (5.6%), lack of physical examination (6%), and misinterpretation of prescription by pharmacists/patients (6%). The majority of the respondents (58%) either agreed/strongly agreed that teleconsultation helped them tide over the medical exigency during the lockdown; however, the clinical diagnosis did not influence this response (P = 0.21). The vast majority of the respondents felt that teleconsultation is beneficial (97%), as it minimizes their exposure to COVID-19. One-third of the patients preferred this service over physical visits and 60% agreed to its continuation till resumption of routine care. Access to video-teleconsultation was the chief suggestion in 39 of 74 suggestions received. CONCLUSIONS: Telemedicine in neurosurgery offers favorable patient satisfaction during this pandemic and may be a satisfactory alternative to physical outpatient services in the future. Video-based teleconsults should be the preferred modality of communication for neurosurgery patients.

Anemia, Mortality, and Hospitalizations in Heart Failure With a Preserved Ejection Fraction (from the TOPCAT Trial).

In this post-hoc analysis of the TOPCAT trial, we evaluated the prognostic role of anemia in adverse cardiovascular (CV) outcomes in heart failure with a preserved ejection fraction (HFpEF). Anemia was defined as hemoglobin of <12 g/dl in females and <13 g/dl in males. The primary outcome was a composite of CV mortality, aborted cardiac arrest (ACA), and heart failure (HF) hospitalization. Secondary outcomes were components of the primary outcome, all-cause, CV and non-CV mortality, cause-specific CV and non-CV mortality, all-cause and HF hospitalization, myocardial infarction, and stroke. Among 1,748 patients from TOPCAT-Americas, patients with anemia had a 52% higher risk of the primary outcome (hazard ratio [HR] 1.52, 95% confidence interval 1.27, 1.83, p<0.05) during a median follow up of 2.4 years. These patients were also at higher risk of all-cause and CV mortality with no difference in non-CV mortality. Among CV causes, patients with anemia had higher risk of sudden cardiac death (SCD)/ACA and presumed CV death with no difference in death due to pump failure. Among non-CV causes, patients with anemia had higher risk of death due to malignancy (HR 2.61, p<0.05). Patients with anemia had higher risk of all-cause and HF hospitalizations (HR 1.26 and 1.56, respectively, p<0.05 for both). There was no difference in the risk of myocardial infarction or stroke. In conclusion, patients with HFpEF and anemia are at higher risk of mortality and hospitalization. Anemia is a significant risk factor for SCD/ACA, death due to presumed CV causes and malignancy in HFpEF.

Intravascular ultrasound-guided vs angiography-guided drug-eluting stent implantation in complex coronary lesions: Meta-analysis of randomized trials.

The relative outcomes of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI with drug-eluting stent (DES) in complex lesions have not been established. We sought to compare the efficacy and safety of IVUS-guided PCI with angiography-guided PCI in patients with complex coronary lesions treated with DES. METHODS: Electronic databases were searched to identify all randomized trials comparing IVUS-guided vs angiography-guided DES implantation. We evaluated major adverse cardiac events (MACE), all-cause and cardiovascular death, myocardial infarction, target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis outcomes at the longest reported follow-up. Random-effects modeling was used to calculate pooled relative risk (RR) and 95% CIs. RESULTS: Eight trials comprising 3,276 patients (1,635 IVUS-guided and 1,641 angiography-guided) enrolling only patients with complex lesions were included. Mean follow-up was 1.4±0.5years. Compared with angiography-guided PCI, patients undergoing IVUS-guided PCI had significantly lower MACE (RR 0.64, 95% CI 0.51-0.80, P=.0001), TLR (RR 0.62, 95% CI 0.45-0.86, P=.004), and TVR (RR 0.60, 95% CI 0.42-0.87, P=.007). There were no significant differences for stent thrombosis, cardiovascular death, or all-cause death. In meta-regression analysis, IVUS-guided PCI was of greatest benefit in reducing MACE in patients with acute coronary syndromes, diabetes, and long lesions. CONCLUSIONS: The present meta-analysis demonstrates a significant reduction in MACE, TVR, and TLR with IVUS-guided DES implantation in complex coronary lesions.

Sources of variability in the measurement of perfusion defect size using commercially available software programs: Are there gender differences?

We recently showed that Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox (ECTb) and 4-Dimension-Myocardial SPECT (4DM) yielded discordant results in the assessment of perfusion defect size (PDS) in patients with known or suspected coronary artery disease. In this report, we examined the sources of variability in the measurement of PDS using ECTb (VarECTb), 4DM (Var4DM) and QPS (VarQPS) and found that gender is a source of variability in the assessment of PDS. In 120 patients, VarECTb was lower in men, compared with women, whereas Var4DM and VarQPS were similar between both genders. Among men, VarECTb was lowest, compared with VarQPS and Var4DM, whereas, VarECTb, VarQPS, and Var4DM were not different among women. Future studies should account for gender differences when comparing the 3 software programs.

Catheter-directed treatment for acute pulmonary embolism: Systematic review and single-arm meta-analyses.

BACKGROUND: We sought to estimate the efficacy and safety outcomes of catheter-directed treatment (CDT) for patients with acute pulmonary embolism (PE). METHODS: We searched SCOPUS for studies reporting outcomes after CDT for acute PE. Studies were categorized in three groups for analyses due to heterogeneity in the classification of acute PE: 1) patients with PE causing right ventricular dysfunction and haemodynamic instability: unstable haemodynamic status, 2) patients with PE causing right ventricular dysfunction where study outcomes were not stratified by haemodynamic status: stable and unstable haemodynamic status, and 3) patients with PE causing right ventricular dysfunction who remained haemodynamically stable: stable haemodynamic status. Efficacy and safety outcomes were estimated and presented as point estimates with 95% confidence intervals. RESULTS: In 35 studies with 1253 patients, 1277 CDTs were performed. The in-hospital mortality rates for the unstable haemodynamic status, stable and unstable haemodynamic status, and stable haemodynamic status groups were 18.1% (7.3-38.2%), 7.1% (5.0-10.1%), and 2.6% (0.8-7.3%), respectively. The major bleeding rates across the groups were estimated to be 4.5, 8.5 and 3.9 per 100 CDTs, respectively. Minor bleeding occurred in 6.2, 11.9 and 9.1 per 100 CDTs, respectively. After CDT, all groups had improvements in mean pulmonary artery pressure and right ventricular function. CONCLUSIONS: We provide descriptive measures of efficacy and safety for patients who underwent CDT for acute PE.

Comparison of Approaches for Stroke Prophylaxis in Patients with Non-Valvular Atrial Fibrillation: Network Meta-Analyses of Randomized Controlled Trials.

BACKGROUND: Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation. MATERIALS AND METHODS: We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy. RESULTS: Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last. CONCLUSIONS: Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies.

Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin.

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.

Safety of hydrophilic guidewires used for side-branch protection during stenting and proximal optimization technique in coronary bifurcation lesions.

BACKGROUND AND PROPOSE: In coronary bifurcation lesions (CBL), hydrophilic guidewires used for side-branch (SB) protection can be withdrawn from underneath the stent easier than other wires. However, the safety of which has not been investigated. METHODS/MATERIALS: We performed scanning electron microscopic (SEM) examination of hydrophilic wires - the Whisper and Runthrough wires - used for SB protection during stenting and proximal optimization technique (POT) in 30 patients with CBL. The distal 15cm of the wire was examined every 1mm by SEM and 4500 segments were analyzed to investigate for wire fracture, polymer shearing (PS), and its correlations with post-stenting creatine kinase (CK)-MB release. RESULTS: SEM examination showed no evidence for wire fracture. The total area of PS and the largest defect on the wire were significantly larger with the Whisper wire versus the Runthrough wire (0.15±0.04mm2 vs. 0.026±0.01mm2 and 0.04±0.05mm2 vs. 0.01±0.01mm2; P<0.05, respectively). The total length of PS and the longest defect on the wire were significantly longer with the Whisper wire vs. the Runthrough wire (12.1±14.5mm vs. 2.7±3.0mm and 2.9±4.2mm vs. 1.0±1.2mm; P<0.05, respectively), but there were weak correlations between the extents of PS with CK-MB release. CONCLUSIONS: Hydrophilic guidewires may be safely used for SB protection during stenting and POT in CBLs. The extent of PS was significantly greater with the Whisper wire than with the Runthrough wire, but its correlation with post-stenting CK-MB release was weak.

Comparison of failure rates of crossing side branch with pressure vs. coronary guidewire: a meta-analysis.

OBJECTIVES: The aim of this study was to compare the failure rates of crossing side branch (SB) with pressure guidewire vs. coronary guidewire after main vessel (MV) stenting in coronary bifurcation lesions (CBL). BACKGROUND: Percutaneous coronary intervention of CBL is technically difficult. The European Bifurcation Club recommends performing either fractional flow reserve (FFR) estimation of the SB or final kissing balloon inflation (FKBI) after the MV stenting when a significant SB ostial stenosis is present. Even though FFR is recommended in CBL, there is concern about SB crossing with pressure guidewire among interventionists. MATERIALS AND METHODS: We undertook a comprehensive literature search to identify all relevant studies reporting the failure rates of SB crossing after MV stenting with either pressure or coronary guidewire. A random effects model was used to compare the failure rates between the two approaches. RESULTS: Our search identified six studies that reported failure rates of SB crossing with a pressure guidewire (n = 648) and 11 studies that reported failure rates of SB crossing with a coronary guide-wire (n = 2601). Estimated pooled failure rate was 3·9% (95% CI: 1·5% to 9·6%) for inability to cross SB with pressure guidewire. Estimated pooled failure rate of SB crossing with coronary guidewire was 3·1% (95% CI: 1·5% to 6·2%). There was no significant difference between the failure rates in the two groups (P = 0·70). CONCLUSION: The failure rates of SB crossing after MV stenting are low with both pressure and coronary guidewire procedures, with no significant difference between the two approaches.

Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies.

OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.

Comparison of Approaches to Revascularization in Patients With Multivessel Coronary Artery Disease Presenting With ST-Segment Elevation Myocardial Infarction: Meta-analyses of Randomized Control Trials.

BACKGROUND: Significant controversy exists regarding the best approach for nonculprit vessel revascularization in patients with multivessel coronary artery disease presenting with ST-segment elevation myocardial infarction. We conducted a systematic investigation to pool data from current randomized controlled trials (RCTs) to assess optimal treatment strategies in this patient population. METHODS AND RESULTS: A comprehensive search of SCOPUS from inception through May 2015 was performed using predefined criteria. We compared efficacy and safety outcomes of different approaches by categorizing the studies into 3 groups: (1) complete revascularization (CR) versus culprit lesion revascularization (CL) at index hospitalization, (2) CR at index hospitalization versus staged revascularization (SR) of nonculprit vessels at a separate hospitalization, and (3) comparison of SR versus CL. Eight eligible RCTs met the inclusion criteria: (1) CR versus CL (6 RCTs, n=1727) (2) CR versus SR (3 RCTs, n=311), and (3) SR versus CL (1 RCT, n=149). We observed significantly lower rates of major adverse cardiovascular events, revascularization, and repeat percutaneous coronary interventions among patients treated with CR and SR compared with a CL approach (P<0.05). The rates of all-cause mortality, cause-specific mortality, major bleeding, reinfarction, stroke, and contrast-induced nephropathy did not differ in the CR arm compared with the CL arm. The rates of these outcomes were similar in the CR and SR arms. CONCLUSION: Results suggest that CR and SR compared with CL reduce major adverse cardiovascular event and revascularization rates primarily by lowering repeated percutaneous coronary intervention rates. We did not observe any increase in the rate of adverse events while using a CR or SR strategy compared with a CL approach. Current guidelines discouraging CR need to be reevaluated, and clinical judgment should prevail in treating multivessel coronary artery disease patients with ST-segment elevation myocardial infarction as data from larger RCTs accumulate.

Beta-blockers in heart failure with preserved ejection fraction: a meta-analysis.

Beta-blockers are established drugs in heart failure with reduced ejection fraction, but their role in heart failure with preserved ejection fraction (HFpEF) is not established. Hence, we undertook a meta-analysis to evaluate the efficacy of beta-blockers on mortality and morbidity in HFpEF patients. A systematic search using PubMed, Embase, Scopus and Cochrane databases was performed to identify all relevant studies on beta-blockers and HFpEF. A random-effects model was performed to assess the role of beta-blockers on all-cause mortality and HF hospitalization. Overall 15 observational studies and two randomized control trial involving a total of 27,099 patients were included in the analysis. In the observational studies, beta-blocker therapy was associated with lower all-cause mortality [RR 0.81 (0.72-0.90), p < 0.001], but not HF hospitalization [RR 0.79 (0.57-1.10), p < 0.001]. However, in the two RCTs, the use of beta-blocker was not associated with all-cause mortality [RR 0.94 (0.67-1.32), p = 0.72] or HF hospitalization [0.90 (0.54-1.49), p = 0.68]. The results were consistent by geographic region (USA vs. rest of world) and ejection fraction subgroups. Subgroup analysis revealed that the beneficial survival effect of beta-blocker was limited to studies with mean age <75 years. Observational studies showed a significant benefit from the use of beta-blockers for all-cause mortality, but not for HF hospitalization. Beta-blockers in the two RCTs were not associated with significant reduction in all-cause mortality or HF hospitalization; however, both the trials were not adequately powered and had high loss to follow-up rates. Further large sampled well-conducted randomized trials are warranted to confirm the effects of beta-blockers on mortality and hospitalization.

Pre-morbid body mass index and mortality after incident heart failure: the ARIC Study.

BACKGROUND: Although obesity is an independent risk factor for heart failure (HF), once HF is established, obesity is associated with lower mortality. It is unclear if the weight loss due to advanced HF leads to this paradoxical finding. OBJECTIVES: This study sought to evaluate the prognostic impact of pre-morbid obesity in patients with HF. METHODS: In the ARIC (Atherosclerosis Risk In Communities) study, we used body mass index (BMI) measured ≥6 months before incident HF (pre-morbid BMI) to evaluate the association of overweight (BMI 25 to <30 kg/m(2)) and obesity (BMI ≥30 kg/m(2)) compared with normal BMI (18.5 to <25 kg/m(2)) with mortality after incident HF. RESULTS: Among 1,487 patients with incident HF, 35% were overweight and 47% were obese by pre-morbid BMI measured 4.3 ± 3.1 years before HF diagnosis. Over 10-year follow-up after incident HF, 43% of patients died. After adjustment for demographics and comorbidities, being pre-morbidly overweight (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.58 to 0.90; p = 0.004) or obese (HR: 0.70; 95% CI: 0.56 to 0.87; p = 0.001) had a protective association with survival compared with normal BMI. The protective effect of overweight and obesity was consistent across subgroups on the basis of a history of cancer, smoking, and diabetes. CONCLUSIONS: Our results, for the first time, demonstrate that patients who were overweight or obese before HF development have lower mortality after HF diagnosis compared with normal BMI patients. Thus, weight loss due to advanced HF may not completely explain the protective effect of higher BMI in HF patients.

Impact of atrial fibrillation and heart failure, independent of each other and in combination, on mortality in community-dwelling older adults.

Atrial fibrillation (AF) and heart failure (HF), common in older adults, are associated with poor outcomes. However, little is known about their impact, independent of each other. We studied 5,673 community-dwelling adults aged ≥ 65 years in the Cardiovascular Health Study. Baseline prevalent AF and HF were centrally adjudicated, and 116 patients had AF only, 219 had HF only, 39 had both, and 5,263 had neither. The Cox proportional hazards model was used to estimate age-gender-race-adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) for all-cause, cardiovascular (CV), and non-CV mortalities. Participants had a mean age of 73 years (± 6 years), 58% were women, and 15% African-American. During 13 years of follow-up, all-cause mortality occurred in 43%, 66%, 74%, and 85% of those with neither, AF only, HF only, and both, respectively. Compared with neither, aHR (95% CIs) for all-cause mortality associated with AF only, HF only, and both was 1.36 (1.08 to 1.72), 2.31 (1.97 to 2.71), and 3.04 (2.15 to 4.29), respectively. Similar associations were observed with CV mortality, but HF only also had greater non-CV mortality (aHR 1.72, 95% CI 1.35 to 2.18). Compared with AF alone, aHR (95% CIs) associated with HF alone for all-cause, CV, and non-CV mortalities was 1.69 (1.29 to 2.23), 1.73 (1.20 to 2.51), and 1.64 (1.09 to 2.46), respectively. Compared with HF alone, those with both conditions had greater CV but not all-cause mortality. In conclusion, community-dwelling older adults with AF have greater mortality than those without but lesser than those with HF, and both conditions were associated with greater CV and all-cause mortalities, whereas only those with HF had greater non-CV mortality.

Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions.

Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF.

Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging.

BACKGROUND: The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. METHODS AND RESULTS: In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score ≥4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's ρ = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (ρ = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. CONCLUSION: There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging.