Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study.

INTRODUCTION: Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment. METHODS: We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ2 tests of Independence. RESULTS: In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001). CONCLUSION: The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients.

Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients.

In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of ß-adrenergic receptors, ß-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.

Atypical Clinical Presentation of Monkeypox Complicated by Myopericarditis.

We present a case of monkeypox infection in a man presenting with genital and labial ulcers, followed by submandibular lymphadenopathy, fever, and constitutional symptoms. His course was complicated by myopericarditis and an ongoing pleomorphic skin eruption. Viral deoxyribonucleic acid was detected by polymerase chain reaction in skin swabs, nasopharyngeal swab, saliva, and semen.

Exercise rehabilitation in cardiac resynchronization: systematic review and a meta-analysis.

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I2 was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO2 was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I2 = 53%, high quality). AT-VO2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I2 = 0.0%, moderate quality).Peak VO2 and AT-VO2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

Association Between Neurohormone Levels and Exercise Testing Measures in Patients with Mechanical Circulatory Supports.

Continuous-flow left ventricular assist device (CF-LVAD) recipients exhibit impaired exercise capacity. Long-term continuous blood flow also elevates norepinephrine (NE) and aldosterone (Aldo) levels. However, the relationship between exercise capacity and neurohormonal activation has not been elucidated. Our study objective was to assess the association between cardiopulmonary exercise testing (CPT) measures and neurohormonal levels in CF-LVAD recipients. Symptom-limited CPT on a treadmill, using the modified Bruce protocol was performed in 15 CF-LVAD recipients. Norepinephrine and Aldo levels were measured, and the association between their levels and CPT measures were assessed. Peak VO2 (13.6 ml/kg/min) and percent age, sex predicted VO2 max (49.4%), and oxygen pulse (O2 pulse) (9.0 ± 4.0 ml/beat) were low, whereas minute ventilation/carbon dioxide output (VE/VCO2) slope (35) was elevated. In addition, VO2 at anaerobic threshold (VO2 AT), and O2 pulse values negatively correlated with NE levels. Norepinephrine levels positively correlated with chronotropic responses and heart rate (HR) recovery. Aldo levels in CF-LVAD recipients were not related to any CPT measures. Continuous-flow left ventricular assist device recipients exhibited impaired exercise capacity and chronotropic incompetence (CI). Despite the association of NE levels with chronotropic responses at peak exercise, neither NE levels nor chronotropic responses predicted peak VO2. This suggests that CI may not be the primary factor responsible for the low peak VO2. O2 pulse, which is a combined measure for stroke volume and peripheral oxygen extraction during exercise, was an independent predictor of peak VO2. Future studies should examine the contribution of peripheral factors to exercise capacity limitations.

Exercise rehabilitation in ventricular assist device recipients: a meta-analysis of effects on physiological and clinical outcomes.

Exercise rehabilitation in heart failure patients has been shown to improve quality of life (QoL) and survival. It is also recommended in clinical practice guidelines for ventricular assist device (VAD) recipients. However, there have only been two meta-analyses on the effects of exercise rehabilitation in VAD patients, on only two outcomes. The objective of the review was to quantitatively evaluate the effect of exercise rehabilitation in VAD recipients on functional capacity, exercise physiology parameters, chronotropic responses, inflammatory biomarkers and neurohormones, heart structure and function, and clinical outcomes. The following databases were systematically searched: CCTR, CDSR, CINAHL, EMBASE, PsycInfo, and Medline through to November 2015, for studies reporting on VAD recipients receiving ≥ 2 sessions of aerobic training. Citations were considered for inclusion, and data were extracted in included studies as well as quality assessed, each by two investigators independently. Random-effects meta-analyses were performed where possible. The meta-analysis showed that compared to usual care, exercise rehabilitation significantly improved peak VO2 (n = 74, mean difference = 1.94 mL kg-1 min-1, 95% CI 0.63-3.26, p = 0.004) and 6-min walk test distance (n = 52, mean difference = 42.46 m, 95% CI 8.45-76.46, p = 0.01). No significant differences were found for the ventilatory equivalent slope (VE/VCO2) or ventilatory anaerobic threshold (VAT). In the six studies which reported QoL, exercise rehabilitation was beneficial in four, with no difference observed in two studies. Exercise rehabilitation is associated with improved outcomes in VAD recipients, and therefore should be more systematically delivered in this population.

The Added Value of Exercise Variables in Heart Failure Prognosis.

INTRODUCTION: Diminished exercise capacity is a key symptom in heart failure (HF). Exercise predictors (peak VO2, VE/VCO2 slope, and oxygen uptake efficiency slope [OUES]) are prognostic markers but studied in isolation. We evaluated if these exercise variables offer additional prognostic value to clinical predictors in HF. METHODS AND RESULTS: This was a single-institution retrospective cohort study of 517 consecutive HF patients. We used Cox proportional hazards modeling to determine the additional prognostic value of exercise variables on mortality, HF hospital admissions, and a composite outcome of ventricular assistance device (VAD) implantation, heart transplantation (HT), and death. During a mean follow-up of 2.7 years, 52 deaths, 47 HTs, and 19 VAD implantations occurred. After adjusting for age, New York Heart Association functional class, ejection fraction, body mass index, creatinine, and B-type natriuretic peptide, peak VO2 (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.85-0.96), OUES (HR 0.92, 95% CI 0.87-0.97), and VE/VCO2 (HR 1.03, 95% CI 1.01-1.05) were independent predictors of the composite outcome. Similar discriminatory capacity existed between the exercise variables (c-statistics 0.77, 0.78, and 0.78, respectively). Only VE/VCO2 was an independent predictor of admissions (HR 1.04, 95% CI 1.01-1.07), and only peak VO2 was an independent predictor of mortality (HR 0.90, 95% CI 0.84-0.98). CONCLUSIONS: Peak VO2, OUES, and VE/VCO2 are independent predictors of HF prognosis over recognized clinical variables. However, no single exercise variable was superior.

Increased cyclic guanosine monophosphate levels and continuous-flow left-ventricular assist devices: Implications for gastrointestinal bleeding.

OBJECTIVES: We examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events. METHODS: The levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants. RESULTS: The median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = -0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = -0.53) and healthy participants (u = 4.0; P < .001; r = -0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = -0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = -0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = -0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general. CONCLUSIONS: The primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.

Changes in circulating progenitor cells are associated with outcome in heart failure patients: a longitudinal study.

BACKGROUND: Circulating progenitor cells (CPCs) are involved in the process of endothelial repair and are a prognostic factor in cardiovascular diseases. We evaluated the association between serial measurements of CPCs and functional capacity and outcomes in heart failure (HF). METHODS: We included 156 consecutive consenting ambulatory HF patients (left ventricular ejection fraction < 40%). We evaluated CPCs and functional capacity (peak VO2) every 6 months for up to 2 years. CPCs were measured as early-outgrowth colony-forming units (EO-CFUs) and circulating CD34+, VEGFR2+ and/or CD133+ cells. We recorded mortality, HF hospital admissions, transplant, and ventricular assist device. RESULTS: The mean age was 55 ± 15 years. A decrease in CD34+VEGFR2+ cells was independently associated with increased functional capacity; a 10-cell decrease in CD34+VEGFR2+ cells was associated with an increase of 0.2 mL/kg/min in peak VO2 (P < 0.05). We found an interaction effect (P = 0.02) between EO-CFUs and diabetes: in patients without diabetes, a 10-EO-CFU increase was independently associated with increased peak VO2 of 0.28 mL/kg/min (P = 0.01), and in patients with diabetes, a decrease in EO-CFUs was associated with an increased peak VO2 (P < 0.05). Higher EO-CFUs were associated with reduced mortality (hazard ratio, 0.25; 95% confidence interval, 0.09-0.69). CONCLUSIONS: We noted differential relations between CPCs and outcomes in patients with vs without diabetes. Higher EO-CFUs and lower CD34+VEGFR2+ cells were associated with improved functional capacity and reduced mortality in nondiabetic patients. In patients with diabetes, lower EO-CFUs were associated with improved functional capacity. The basis for these differences requires further examination.

Clinical differences between continuous flow ventricular assist devices: a comparison between HeartMate II and HeartWare HVAD.

BACKGROUND: The HeartWare ventricular assist device (HVAD) is a new generation centrifugal flow VAD recently introduced in Canada. The objective of this study was to compare the HVAD device to the HeartMate II (HMII) axial flow device. Very few studies have compared clinical outcomes between newer generation VADs. METHODS: All perioperative and follow-up data on LVAD recipients were collected prospectively in our institutional database. Between January 2006 and April 2012, 46 consecutive patients underwent implantation of either an HVAD (n=13) or a HMII (n=33) device. Pre-implant demographics, perioperative and postoperative clinical outcomes were reviewed between groups. RESULTS: Overall, the baseline characteristics, demographics, co-morbidities and laboratory values were comparable between the two groups. The majority of the patients were Interagency Registry for Mechanical Assisted Circulatory Support 3-4 (92% in both groups) and most of the patients were bridge to transplant (75% in HMII vs. 79% in HVAD). Survival and the incidence of perioperative bleeding, renal dysfunction, liver dysfunction, and infection were similar between the groups. However, HVAD devices had a significantly higher incidence of gastrointestinal (GI) bleeding (31% vs. 0% in HMII patients, p<0.01) and stroke (44% vs. 10% in HMII patients, at one year p=0.04). Hemorrhagic strokes were more frequent in patients with HVAD (three of the five episodes vs. one of the three episodes in HMII patients, p=0.06). CONCLUSION: While device complications were comparable, patients with HVAD experienced a significantly higher incidence of stroke and GI bleeding and therefore refinement in patients' management may decrease incidence of these complications.

Circulating proangiogenic progenitor cells independently predict functional capacity in heart failure patients.

BACKGROUND: Endothelial dysfunction is an important underlying mechanism in the pathophysiology of heart failure (HF). Circulating proangiogenic progenitor cells (CPCs) are endothelial and hematopoietic progenitor cells involved in the process of vasculogenesis repairing damaged and dysfunctional endothelium. Our aim was to evaluate whether an independent association exists between CPCs and functional capacity in HF patients. METHODS: This cross-sectional study included 121 ambulatory HF patients with reduced left ventricular ejection fraction seen at a single institution. We analyzed the association between CPCs, measured as circulating CD34+VEGFR2+ cells and early outgrowth colony forming units (EO-CFUs), and patients' functional capacity measured as peak oxygen consumption (VO2). RESULTS: The mean age was 55 ± 11 years; 96 patients (79%) were male. Forty-three patients (36%) had ischemic cardiomyopathy. Patients were taking optimal HF therapy (96% taking ß-blockers, 91% taking renin-angiotensin inhibitors, and 60% had an implanted internal cardiac defibrillator). In univariate analyses, CD34+VEGFR2+ cells were inversely associated with peak VO2 (P = 0.02) while EO-CFUs showed a positive association with peak VO2 (P < 0.01). These associations persisted after adjusting for sex, New York Heart Association class, body mass index, diabetes, cardiac resynchronization therapy, ischemic cardiomyopathy and b-type natriuretic peptide levels. CONCLUSIONS: Cultured EO-CFUs may represent a measure of functional capacity and vasculogenesis potential while CD34+VEGFR2+ cells represent the mobilized cells in response to endothelial damage. Our study suggests that lower EO-CFUs (worse cell function) and higher CD34+VEGFR2+ cells are associated with poorer functional capacity.