Shared Decision-Making and Cardiovascular Complications of Androgen Deprivation Therapy: an Educational Initiative for Oncology Team Members in Colorado, USA.

Patients with prostate cancer may experience side effects of androgen deprivation therapy (ADT) such as cardiovascular (CV) complications. Oncology team members should actively communicate with patients about these complications. On the other hand, shared decision-making (SDM) has been shown to improve patient-physician communication. We developed brochures focused on CV complications of ADT and SDM. We proceeded to deliver these brochures to participating oncology offices and then carried out a survey of team members in these offices. We obtained responses from 31 oncology team members. Our survey revealed that about half of the participants (48%) rarely applied SDM in their oncology practice, and only about one-third (32%) sometimes applied SDM. After reading our brochures, the majority of respondents could correctly answer questions about SDM and CV complications of ADT. Improvement in scores after reading our materials was significant for both CV complications of ADT and SDM (e.g., CV complications of ADT: z = 6.153, p-value < 0.001, and SDM z = 6.456, p-value < 0.001). Implementation of SDM and an improved awareness of the CV complications of ADT can lead to significant benefits. It is therefore important to take steps to further raise such implementation and awareness among oncology team members in other geographic locations and clinical settings.

Cardiac Rehabilitation Increases Plasma Klotho Levels.

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.

Non-coronary atherosclerosis: a marker of poor prognosis in patients undergoing coronary artery bypass surgery.

Introduction: The presence of non-coronary atherosclerosis (NCA) in patients with coronary artery disease is associated with a poor prognosis. We have studied whether NCA is also a predictor of poorer outcomes in patients undergoing coronary artery bypass grafting (CABG). Materials and methods: This is an observational study involving 567 consecutive patients who underwent CABG. Variables and prognosis were analysed based on the presence or absence of NCA, defined as previous stroke, transient ischaemic attack (TIA), or peripheral artery disease (PAD) [lower extremity artery disease (LEAD), carotid disease, previous lower limb vascular surgery, or abdominal aortic aneurysm (AAA)]. The primary outcome was a combination of TIA/stroke, acute myocardial infarction, new revascularization procedure, or death. The secondary outcome added the need for LEAD revascularization or AAA surgery. Results: One-hundred thirty-eight patients (24%) had NCA. Among them, traditional cardiovascular risk factors and older age were more frequently present. At multivariate analysis, NCA [hazard ratio (HR) = 1.84, 95% confidence interval (CI) 1.27-2.69], age (HR = 1.35, 95% CI 1.09-1.67, p = 0.004), and diabetes mellitus (HR = 1.50, 95% CI 1.05-2.15, p = 0.025), were positively associated with the development of the primary outcome, while estimated glomerular filtration rate (HR = 0.86, 95% CI 0.80-0.93, p = 0.001) and use of left internal mammary artery (HR = 0.36, 95% CI 0.15-0.82, p = 0.035), were inversely associated with this outcome. NCA was also an independent predictor of the secondary outcome. Mortality was also higher in NCA patients (27.5% vs. 9%, p < 0.001). Conclusions: Among patients undergoing CABG, the presence of NCA doubled the risk of developing cardiovascular events, and it was associated with higher mortality.

Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome.

AIMS: Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. METHODS AND RESULTS: Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high-sensitivity C-reactive protein, and N-terminal-pro-brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow-up was 5.44 (3.03-7.46) years. Two hundred and ninety-four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08-1.29], P < 0.001), calcidiol (HR 0.86 [0.74-1.00], P = 0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28-1.65], P < 0.001) and parathormone (HR 1.06 1.01-1.12]; P = 0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07-1.37], P = 0.002) and calcidiol (HR 0.72 [0.54-0.97), P = 0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate > 60 mL/min/1.73 m2 . CONCLUSIONS: FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease.

The role of bioimpedance analysis in overweight and obese patients with acute heart failure: a pilot study.

AIMS: Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. METHODS AND RESULTS: Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days. CONCLUSIONS: Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.

Absence of High Lipoprotein(a) Levels Is an Independent Predictor of Acute Myocardial Infarction without Coronary Lesions.

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47-68) vs. 61 (52-72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p < 0.001), and had lower rates of diabetes and of Lp(a) > 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) > 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) > 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death.

Personalized Therapy and Clinical Outcome for Heart Failure.

Heart failure (HF) is a complex clinical syndrome that results from the structural and/or functional impairment of systolic function or ventricular filling, which in turn causes elevated intracardiac pressure and/or inadequate cardiac output at rest and/or during exercise [...].

NT-proBNP Levels Influence the Prognostic Value of Mineral Metabolism Biomarkers in Coronary Artery Disease.

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD. Methods: We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D3), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01−1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01−1.03), p = 0.011), along with age (HR = 1.039 (1.02−1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02−2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19−0.53), p < 0.001), insulin (HR = 2.49 (1.59−4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16−2.56), p = 0.007), nitrates (HR = 1.65 (1.10−2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (1.74−4.36), p < 0.001). In the NT-proBNP ≤ 125 pg/mL subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol (HR = 1.01 (1.00−1.02), p = 0.014) and calcidiol (HR = 0.96 (0.92−0.99), p = 0.045), as well as treatment with verapamil (HR = 11.28 (2.54−50.00), p = 0.001), and dihydropyridines (HR = 3.16 (1.63−6.13), p = 0.001). Conclusion: In patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction.

Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Impacto de la función renal en el valor pronóstico del metabolismo mineral en pacientes con cardiopatía isquémica crónica / Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease

INTRODUCCION: La parathormona (PTH) es un componente del metabolismo mineral (MM) que ha demostrado aportar valor pronóstico en los pacientes con cardiopatía isquémica crónica (CIC) y función renal preservada. Sin embargo, la influencia de la función renal en el papel pronóstico de la PTH en los pacientes con CIC aún no se ha demostrado.ObjetivoEvaluar la influencia del filtrado glomerular renal estimado (FGRe) sobre el papel pronóstico de la PTH y otros marcadores del MM en los pacientes con CIC. MÉTODOS: Analizamos el valor pronóstico de distintos componentes del MM (PTH, klotho, fósforo, calcidiol y factor de crecimiento de fibroblastos-23 [FGF23]) en 964 pacientes con CIC incluidos en 5 hospitales de Madrid en función de si presentaban FGRe <60ml/min/1,73m2 (LFGR) o FGRe≥60ml/min/1,73m2 (HFGR). El objetivo primario fue la combinación de muerte con eventos isquémicos (cualquier síndrome coronario agudo, accidente cerebrovascular isquémico o accidente isquémico transitorio). El FGR se calculó mediante el método Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTADOS: La edad era de 60,0 (52,0-72,0) años y el 76,2% de los casos eran varones, con una mediana del FGRe de 80,4 (65,3-93,1)ml/min/1,73m2. El seguimiento fue de 5,39 (2,81-6,92) años. Setecientos noventa pacientes presentaron HGFR y 174 LGFR. En pacientes con HFGR, los predictores del endpoint combinado fueron los niveles plasmáticos de calcidiol (HR=0,023 [0,94-0,99], p=0,023); FGF23 (HR=1,00 [1,00-1,003], p=0,036); colesterol no-HDL (HR=1,01 [1,00-1,01], p=0,026) y troponina de alta sensibilidad (HR=5,12 [1,67-15,59], p=0,004), junto con la edad (HR=1,03 [1,01-1,05], p=0,01), el tratamiento con estatinas (HR=0,36 [0,19-0,68], p=0,002); nitratos (HR=1,13 [1,07-2,79], p=0,027); dihidropiridinas (HR=1,71 [1,05-2,77], p=0,032); verapamilo (HR=5,71 [1,35-24,1], p=0,018) e inhibidores de la bomba de protones (HR=2,23 [1,36-3,68], p=0,002). [...]

BACKGROUND: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet.PurposeTo assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. METHODS: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR<60ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60ml/min/1.73 m2 (HGFR) included in five hospitals of Madrid. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: Age was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 m2. Median follow-up was 5.39 (2.81-6.92) years. There were 790 pts. with HGFR and 174 with LGFR. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR=0.023 (0.94-0.99) p=0.023], FGF23 [HR=1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR=1.01 (1.00-1.01) p=0.026] and high sensitivity troponin I [HR=5.12 (1.67-15.59) p=0.004], along with age [HR=1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR=1.13 (1.07-2.79) p=0.027], dihydropyridines [HR=1.71 (1.05-2.77) p=0.032], verapamil [HR=5.71 (1.35-24.1) p=0.018], and proton-pump inhibitors [HR=2.23 (1.36-3.68) p= 0.002]. [...]

Prevalence and prognostic value of monoclonal gammopathy in heart failure patients with preserved ejection fraction: A prospective study.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) and monoclonal gammopathy of uncertain significance (MGUS) are two entities that share pathophysiological mechanisms. The aim herein, was to assess the prevalence of MGUS in patients with HFpEF and no left ventricular (LV) hypertrophy, as well as its association with a pre-specified clinical endpoint at 12 months. METHODS: The present study prospectively enrolled 69 patients admitted with HF, with ejection fraction ≥ 50%, and LV wall thickness < 12 mm. All patients were screened for MGUS. Clinical events were determined over a 12 month follow-up. The pre-specified composite clinical endpoint was readmission for HF or death. RESULTS: The prevalence of MGUS in this population was 13%. There were no differences in the incidence of the composite clinical endpoint between patients with and without MGUS. Multivariate analysis showed that treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) was associated with fewer clinical events (HR: 0.153, 95% CI: 0.037-0.622, p = 0.009) and indicated a trend to lower risk of readmission for HF and death. Beta-blockers were associated with lower rates of the composite clinical endpoint (HR: 0.192, 95% CI: 0.05-0.736, p = 0.016), readmission for HF (HR: 0.272, 95% CI: 0.087-0.851, p = 0.025) and indicated a trend to lower mortality. Moreover, potassium serum levels > 5 mEq/L were associated with higher rates of the composite endpoint (HR: 6.074, 95% CI: 1.6-22.65, p = 0.007). CONCLUSIONS: The prevalence of MGUS in patients with HFpEF without hypertrophy was 3-fold that of the general population. There was no significant correlation between clinical outcomes and the presence of MGUS. Beta-blockers and ACEIs/ARBs reduced the composite of mortality and readmissions for HF in HFpEF patients. Hyperpotassemia was related to worse prognosis.

Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease. / Impacto de la función renal en el valor pronóstico del metabolismo mineral en pacientes con cardiopatía isquémica crónica.

BACKGROUND: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet. PURPOSE: To assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. METHODS: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR<60ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60ml/min/1.73 m2 (HGFR) included in five hospitals of Madrid. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: Age was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 m2. Median follow-up was 5.39 (2.81-6.92) years. There were 790 pts. with HGFR and 174 with LGFR. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR=0.023 (0.94-0.99) p=0.023], FGF23 [HR=1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR=1.01 (1.00-1.01) p=0.026] and high sensitivity troponin I [HR=5.12 (1.67-15.59) p=0.004], along with age [HR=1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR=1.13 (1.07-2.79) p=0.027], dihydropyridines [HR=1.71 (1.05-2.77) p=0.032], verapamil [HR=5.71 (1.35-24.1) p=0.018], and proton-pump inhibitors [HR=2.23 (1.36-3.68) p= 0.002]. In the LGFR subgroup, predictors of death or ischemic events were PTH plasma levels, [HR=1.01 (1.00-1.01) p=0.005], eGFR [HR=0.96 (0.94-0.99) p=0.004], age [HR=1.06 (1.02-1.10) p=0.003], caucasian race [HR=0.04 (0.004-0.380) p=0.005], and treatment with insulin [HR=2.6 (1.20-5.63) p=0.015]. CONCLUSIONS: In pts. with SCAD, PTH is an independent predictor of poor outcomes only in those with eGFR<60ml/min/1.73 m2, while in pts. with eGFR≥60ml/min/1.73 m2 calcidiol and FGF23 become the only components of MM that may predict prognosis. Then, renal function influences the predictive power of MM markers in pts. with SCAD.

Enhancing knowledge and awareness of transthyretin cardiac amyloidosis and shared decision-making among cardiology team members in Colorado, USA via an online educational initiative.

OBJECTIVES: Our project aimed to increase knowledge of noninvasive diagnostic modalities (including bone radiotracer scintigraphy), raise suspicion of transthyretin cardiac amyloidosis (ATTR-CA), and improve cardiology team member's awareness and knowledge of shared decision-making (SDM), as well as the quality of SDM communication between cardiology team members and patients. METHODS: An online educational module and survey was developed and cardiology team members in Colorado, USA, were invited to participate. This online educational module included various important topics related to ATTR-CA (e.g., the cause of ATTR-CA, endomyocardial biopsy, and noninvasive methods to diagnose ATTR-CA) and SDM (e.g., benefits of SDM, the role of SDM in the diagnosis of ATTR-CA, implementation of SDM in cardiology practice, and the 3-talk model). RESULTS: There were 34 survey respondents, over one-third of whom were cardiologists. Most respondents agreed on the importance of diagnosing ATTR-CA at an early stage, and about three-quarters of the survey takers agreed that bone scintigraphy can reliably diagnose ATTR-CA without the need for endomyocardial biopsy. Concern over increased time commitment was the leading barrier to the implementation of SDM in respondents' clinical practice. The majority of respondents identified the correct answer regarding ATTR-CA and SDM after reading the online educational module. This improvement in scores after exposure to the online educational module was statistically significant. CONCLUSION: Baseline knowledge and awareness of various issues related to ATTR-CA was relatively low among cardiology team members. Participants' knowledge was enhanced through our effective online educational program. Prospective educational projects focused on various methods of detecting ATTR-CA as well as other amyloid conditions in diverse clinical settings will remain important.

N-Terminal Pro-Brain Natriuretic Peptide Plasma Levels Are Associated with Intermediate-Term Follow-Up Cancer in Coronary Patients.

N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper, we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the intermediate-term follow-up. We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. This sample represents a re-analysis of a previous work expanding the sample size and the follow-up. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. After 5.40 (2.81-6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015-1.056) per increase in 100 pg/mL; p = 0.001], previous atrial fibrillation (HR 3.140 CI (1.196-8.243); p = 0.020), and absence of previous heart failure (HR 0.067 CI (0.006-0.802); p = 0.033) were independent predictors of receiving a CD in the first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. The number of patients developing heart failure during follow-up was 0 (0.0%) in patients receiving CD in the first three years of follow-up, 2 (6.9%) in those receiving a CD diagnosis beyond this time, and 40 (4.4%) in patients not developing cancer (p = 0.216). These numbers suggest that future heart failure was not a confounding factor. In patients with coronary artery disease, NT-proBNP was an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers.

Practical Decision Algorithms for the Use of the Cardiovascular Polypill in Secondary Prevention in Europe.

The main objective of cardiovascular disease (CVD) prevention is to reduce morbidity and mortality. Despite recommendations on evidence-based pharmacological treatment and lifestyle changes, the control of CV risk factors such as hypertension or dyslipidaemia is not optimal. The use of a CV polypill, including guideline-recommended drugs, as a baseline therapy, may contribute to improving risk factors control either by improving the treatment adherence or by the synergistic effect of its components. The CNIC-Polypill is the first CV polypill approved in Europe as an effective strategy for secondary prevention, which contains acetylsalicylic acid, atorvastatin (in two optional doses), and ramipril (in three optional doses) in a single pill. The present practical clinical document aims to provide a guide for patient management after an acute coronary syndrome (ACS) or with chronic CVD (CCVD) with a strategy based on the CNIC-Polypill, also considering the need to add other therapies for a personalized treatment. The most suitable clinical scenarios for the CNIC-Polypill use are discussed: (a) in patients after an ACS at discharge, (b) in patients with CCVD (chronic coronary syndrome, stroke, or peripheral artery disease) with uncontrolled low-density lipoprotein cholesterol (LDL-c) and/or blood pressure levels and (c) in patients with CCVD with well-controlled risk factors to simplify treatment and reduce polypharmacy in the context of CCVD prevention.

Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy.

AIMS: As evidenced by scintigraphy imaging, the prevalence of transthyretin (TTR) cardiac amyloidosis in heart failure patients with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH) ranges between 13% and 19%. The natural evolution of cardiac amyloidosis begins with the deposition of amyloid material in the myocardium, with LVH ensuing at later stages. With current imaging modalities, it is possible to detect TTR cardiac amyloidosis before the hypertrophic stage. The aim of this study was to determine the prevalence of TTR cardiac amyloidosis in HFpEF patients without LVH. METHODS AND RESULTS: The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. Transthyretin gene sequencing was performed in positive patients. From July 2017 to January 2020, 329 patients with HFpEF and LV thickness <12 mm were identified. After exclusions, 58 patients completed the study with cardiac scintigraphy (79 years, 54% men; median LVEF 60% and LV wall thickness 10.5 mm). Three patients (5.2%) were positive for TTR cardiac amyloidosis; genetic analysis excluded the presence of hereditary TTR amyloidosis. Positive patients baseline characteristics (84 years, 67% men, LVEF 60%, and LV wall thickness 11 mm) were similar to patients without TTR, except for troponin levels (0.05 vs. 0.02 ng/mL, P = 0.03) and glomerular filtration rate (82 vs. 60 mL/min, P = 0.032), which were higher in TTR patients. CONCLUSIONS: In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Early diagnosis of cardiac involvement in TTR amyloidosis (before manifest LVH) would seem recommendable because newly approved specific treatments can prevent additional deposition of amyloid material.

Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients.

AIMS: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. METHODS AND RESULTS: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52-72) years. Median glomerular filtration rate was 80.4 (65.3-93.1) mL/min/1.73 m2 . One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021-1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012-1.028]; P < 0.001) were independent predictors of the primary outcome but also for the secondary outcome of heart failure or death (HR 1.066 [CI 1.016-1.119]; P = 0.009 and HR 1.024 [CI 1.014-1.034]; P < 0.001, respectively). PTH was the only biomarker that predicted ischaemic events (HR 1.052 [1.010-1.096]; P = 0.016). Patients were divided in two subgroups according to FGF23 plasma levels. PTH retained its prognostic value only in patients with FGF23 levels above the median (>85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. CONCLUSIONS: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.

MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation.

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39-7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.

First and Second Waves of Coronavirus Disease 2019 in Madrid, Spain: Clinical Characteristics and Hematological Risk Factors Associated With Critical/Fatal Illness.

OBJECTIVES: This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. DESIGN: Retrospective observational study. SETTING: A single tertiary-care center in Madrid. PATIENTS: Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). INTERVENTIONS: Treatment with a hospital-approved drug cocktail during hospitalization. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75-78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25-80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143-6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006-5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229-6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432-13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737-3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832-4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. CONCLUSIONS: Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient's prognosis on arrival to hospital.

Statin use is associated with reduced mortality after respiratory viral infection.

BACKGROUND: Several studies suggest that statins, besides reducing cardiovascular disease, have anti-inflammatory properties which might provide a benefit in downregulating the immune response after a respiratory viral infection (RVI) and, hence, decreasing subsequent complications. We aim to analyse the effect of statins on mortality after RVI. METHODS: A single-centre, observational and retrospective study was carried out including all adult patients with a RVI confirmed by PCR tests from October 2, 2017 to May 20, 2018. Patients were divided between statin users and non-statin users and followed-up for 1 year, and all causes of death were recorded. In order to analyse the effect of statin treatment on mortality after RVI we planned two different approaches, a multivariate Cox regression model with the overall population and a univariate Cox model with a propensity-score matched population. RESULTS: We included 448 patients, 154 (34.4%) of whom were under statin treatment. Statin users had a worse clinical profile (older population with more comorbidities). During the 1-year follow-up, 67 patients died, 17 (11.0%) in the statin group and 50 (17.1%) in the non-statin group. Multivariate Cox analysis showed that statins were associated with mortality benefit (HR 0.47, 95% CI 0.26-0.83; p=0.01). In a matched population (101 statins users and 101 non-statins users) statins also remained associated with mortality benefit (HR 0.32, 95% CI 0.14-0.72; p=0.006). Differences were mainly driven by non-cardiovascular mortality (HR 0.31, 95% CI 0.13-0.73; p=0.004). CONCLUSIONS: Chronic statin treatment was associated with reduced 1-year mortality in patients with laboratory-confirmed RVI. Further studies are needed to determine the exact role of statin therapy after RVI.