Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.

Economic impact of the use of patiromer in chronic kidney disease or heart failure for the treatment of chronic hyperkalemia in Spain.

INTRODUCTION: Chronic hyperkalemia has negative consequences in the medium and long term, and determines the suspension of nephro and cardioprotective drugs, such as renin-angiotensin-aldosterone system inhibitors (RAASi). There is an alternative to the suspension or dose reduction of these treatments: the administration of potassium chelators. The aim of this study is to estimate the economic impact of the use of patiromer in patients with chronic kidney disease (CKD) or heart failure (HF) and hyperkalemia in Spain. MATERIALS AND METHOD: The annual economic impact of the use of patiromer has been estimated from the perspective of the Spanish society. Two scenarios were compared: patients with CKD or HF and hyperkalemia treated with and without patiromer. The costs have been updated to 2020 euros, using the Health Consumer Price Index. Direct healthcare costs related to the use of resources (treatment with RAASi, CKD progression, cardiovascular events and hospitalization due to hyperkalemia), direct non-healthcare costs (informal care: costs derived from time dedicated by patient's relatives), the indirect costs (productivity loss), as well as an intangible cost (due to premature mortality) were considered. A deterministic sensitivity analysis was performed to validate the robustness of the study results. RESULTS: The mean annual cost per patient in the scenario without patiromer is €9,834.09 and €10,739.37 in CKD and HF, respectively. The use of patiromer would lead to cost savings of over 30% in both diseases. The greatest savings in CKD come from the delay in the progression of CKD. While in the case of HF, 80.1% of these savings come from premature mortality reduction. The sensitivity analyses carried out show the robustness of the results, obtaining savings in all cases. CONCLUSIONS: The incorporation of patiromer allows better control of hyperkalemia and, as a consequence, maintain treatment with RAASi in patients with CKD or HF. This would generate a 32% of annual savings in Spain (€3,127 in CKD; €3,466 in HF). The results support the positive contribution of patiromer to health cost in patients with only CKD or in patients with only HF.

A 3-Biomarker 2-Point-Based Risk Stratification Strategy in Acute Heart Failure.

Introduction and Objectives: Most multi-biomarker strategies in acute heart failure (HF) have only measured biomarkers in a single-point time. This study aimed to evaluate the prognostic yielding of NT-proBNP, hsTnT, Cys-C, hs-CRP, GDF15, and GAL-3 in HF patients both at admission and discharge. Methods: We included 830 patients enrolled consecutively in a prospective multicenter registry. Primary outcome was 12-month mortality. The gain in the C-index, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) was calculated after adding each individual biomarker value or their combination on top of the best clinical model developed in this study (C-index 0.752, 0.715-0.789) and also on top of 4 currently used scores (MAGGIC, GWTG-HF, Redin-SCORE, BCN-bioHF). Results: After 12-month, death occurred in 154 (18.5%) cases. On top of the best clinical model, the addition of NT-proBNP, hs-CRP, and GDF-15 above the respective cutoff point at admission and discharge and their delta during compensation improved the C-index to 0.782 (0.747-0.817), IDI by 5% (p < 0.001), and NRI by 57% (p < 0.001) for 12-month mortality. A 4-risk grading categories for 12-month mortality (11.7, 19.2, 26.7, and 39.4%, respectively; p < 0.001) were obtained using combination of these biomarkers. Conclusion: A model including NT-proBNP, hs-CRP, and GDF-15 measured at admission and discharge afforded a mortality risk prediction greater than our clinical model and also better than the most currently used scores. In addition, this 3-biomarker panel defined 4-risk categories for 12-month mortality.

Ischemic Etiology and Prognosis in Men and Women with Acute Heart Failure.

Coronary heart disease is common in heart failure (HF). Our aim was to determine the impact of ischemic etiology on prognosis among men and women with HF. This study is a prospective national multicenter registry. The primary endpoint was 12-month mortality. Patients with HF and ischemic heart disease were stratified according to sex. A total of 1830 patients were enrolled of which 756 (41.3%) were women. Ischemic etiology was more common in men (446 (41.6%)) than in women (167 (22.2%)). Among patients with ischemic HF, diabetes was more frequent in women than in men. Ischemic etiology was not associated with higher mortality risk, and this was true for women (Hazard Ratio [HR] 1.51, 95% Confidence Interval [CI] 0.98-2.32; p = 0.61) and men (HR 1.14, 95% CI 0.81-1.61; p = 0.46), p-value for interaction: 0.067. Mortality/readmission risk in ischemic HF increased in men with previous readmissions (HR 1.15, 95% CI 1.02-1.29; p = 0.022), chronic obstructive pulmonary disease (HR1.20, 95% CI 1.02-1.41; p = 0.026) and in women with diabetes (HR 2.23, 95% CI 1.05-4.47; p = 0.035). Ischemic etiology was not associated with mortality in HF patients. In ischemic HF, the variables associated with a poor prognosis were diabetes in women and previous readmissions and chronic obstructive pulmonary disease in men.

Prognostic impact of hyponatraemia and hypernatraemia at admission and discharge in heart failure patients with preserved, mid-range and reduced ejection fraction.

BACKGROUND: Hyponatraemia is common in patients with acute heart failure (HF). AIMS: To determine the impact of sodium disturbances on mortality and readmissions in HF with reduced left ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and mid-range ejection fraction (HFmrEF). METHODS: This study was a prospective multicentre consecutive registry in 20 hospitals, including patients admitted due to acute HF in cardiology departments. Sodium <135 mmol/L was considered hyponatraemia, >145 mmol/L hypernatraemia and 135-145 mmol/L normal. RESULTS: A total of 1309 patients was included. Mean age was 72.0 ± 11.9 years, and 810 (61.9%) were male. Mean serum sodium level was 138.6 ± 4.7 mmol/L at hospital admission and 138.1 ± 4.1 mmol/L at discharge. The evolution of sodium levels was: normal-at-admission/normal-at-discharge 941 (71.9%), abnormal-at-admission/normal-at-discharge 127 (9.7%), normal-at-admission/abnormal-at-discharge 155 (11.8%) and abnormal-at-admission/abnormal-at-discharge 86 (6.6%). Hyponatraemia at discharge was more common in HFrEF (109 (20.7%)) than in HFpEF (79 (13.9%)) and HFmrEF (27 (12%)), P = 0.003. The prevalence of hypernatraemia at discharge was similar in the three groups: HFrEF (10 (1.9%)), HFpEF (12 (2.1%)) and HFmrEF (4 (1.9%)), P = 0.96. In multivariate analysis, abnormal sodium concentrations at hospital admission (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.15-1.76, P = 0.001) and discharge (HR 1.33, 95% CI 1.08-1.64, P = 0.007) were both independently associated with increased mortality and readmissions at 12 months. CONCLUSIONS: Hyponatraemia and hypernatraemia at admission and discharge predict a poor outcome in patients with acute HF regardless of left ventricular ejection fraction. Hyponatraemia at discharge is more frequent in HFrEF than in the other groups.

Sacubitril/Valsartan is useful and safe in elderly people with heart failure and reduced ejection fraction. Data from a real-word cohort.

BACKGROUND: HF elderly patients are underrepresented in Sacubitril/Valsartan HF trials, and the effect of S/V in real-life patients with advanced age is unknown. The aim of this study was to evaluate the use and safety of S/V in a real-word cohort of elderly patients. METHODS: We performed a prospective registry of patients who started S/V in clinical practice. We compared baseline characteristics, adverse events during follow-up and causes of S/V withdrawal according to age. RESULTS: A total of 427 patients started treatment with S/V: 222 (52.0%)<70 years old, 140 (32.8%) between 70 and 79 and 65 (15.2%)≥80. During a mean follow-up of 7.0±0.1months S/V was well tolerated, with no age-related differences in adverse events (26.8%, 25.9%, 23.1% respectively; p=0.83). Symptomatic hypotension tended to be more frequent in the elderly (19.8%, 25.6%, 33.3% respectively; p=0.17). The withdrawal of S/V was more frequent in younger patients (14.4%, 10.0%, 4.6% respectively; p=0.05) and related to poor prognosis (HR 13.51, 95% CI 3.22-56.13, p<0.001). CONCLUSIONS: Sacubitril/Valsartan is useful and safe in elderly people with HF-rEF in real-life clinical practice, and withdrawal is associated to poor prognosis. The doses achieved are lower in elderly people.

Safety of sacubitril/valsartan initiated during hospitalization: data from a non-selected cohort.

AIMS: Sacubitril/valsartan is safe when initiated during hospitalization in a clinical trial setting. Its safety in real-life population is not stablished. We compared the initiation of sacubitril/valsartan during hospitalization in a non-selected population, in the PIONEER-HF trial, and in non-selected outpatients. METHODS AND RESULTS: Multicentre registry included 527 patients: 100 were started on sacubitril/valsartan during hospitalization (19.0%) and 427 as outpatients (81.0%). Compared with those in the pivotal trial, inpatients in our cohort were older (71 ± 12 vs. 61 ± 14 years; P < 0.001); had more frequently Functional Class II (41 [41.0%] vs. 100 [22.7%]; P < 0.001), higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2013 [1002-4132] pg/mL; P < 0.001), better glomerular filtration rate (63.5 [51.0-80.0] vs. 58.4 [47.5-71.5] mL/min; P = 0.01), and higher systolic blood pressure (121 [110-136] vs. 118 [110-133] mmHg; P = 0.03); and received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more frequently (92 [92.0%] vs. 208 [52.7%]; P < 0.001). Compared with non-selected outpatients, inpatients were older (71 ± 12 vs. 68 ± 12 years, P = 0.02), had more frequent Functional Class III-IV (58 [58.0%] vs. 129 [30.3%], P < 0.001), had higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2182 [1134-4172]; P < 0.001), and were receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers target dose less frequently (55 [55.0%] vs. 335 [78.5%]; P < 0.001). They also started sacubitril/valsartan with a low dose (50 mg/12 h) more frequently (80 [80.0%] vs. 209 [48.8%], P < 0.001). The initiation of sacubitril/valsartan in outpatients was an independent predictor of high-dose use (OR 3.1; 95% confidence interval 1.7-5.6, P < 0.001). The follow-up time in both cohorts, including all patients enrolled, was similar (7.0 ± 0.1 vs. 7.2 ± 2.6 months, P = 0.72). All-cause admissions during follow-up were more frequent in inpatients (30 [30.0%] vs. 68 outpatients [15.9%], P = 0.001), with no relevant differences in all-cause mortality. There was no significant difference in sacubitril/valsartan withdrawal rate (17 inpatients [17.0%] vs. 49 outpatients [11.5%], P = 0.13). The incidence of adverse effects was also similar: hypotension (16 inpatients [16.0%] vs. 71 outpatients [16.7%], P = 0.88), worsening renal function (7 inpatients [7.0%] vs. 29 outpatients [6.8%], P = 0.94), and hyperkalaemia (1 inpatient [1.0%] vs. 21 outpatients [4.9%], P = 0.09). We did not register any case of angioedema. CONCLUSIONS: It is safe to initiate sacubitril/valsartan during hospitalization in daily clinical practice. Inpatients have a higher risk profile and receive low starting doses more frequently than outpatients.

Discharge treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker after a heart failure hospitalisation is associated with a better prognosis irrespective of left ventricular ejection fraction.

BACKGROUND: Medical therapy could improve the prognosis of real-life patients discharged after a heart failure (HF) hospitalisation. AIM: To determine the impact of discharge HF treatment on mortality and readmissions in different left ventricular ejection fraction (LVEF) groups. METHODS: Multicentre prospective registry in 20 Spanish hospitals. Patients were enrolled after a HF hospitalisation. RESULTS: A total of 1831 patients was included (583 (31.8%) HF with reduced ejection fraction (HFrEF); 227 (12.4%) HF with midrange ejection fraction (HFmrEF); 610 (33.3%) HF with preserved ejection fraction (HFpEF), and 411 (22.4%) with unknown LVEF). Angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB) at discharge were independently associated with a reduction in: (i) all-cause mortality: hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41-0.74, P < 0.001, with a similar effect in the four groups; (ii) mortality due to refractory HF HR 0.45, 95% CI 0.29-0.64, P < 0.001, with a similar effect in the three groups with known LVEF; (iii) mortality/HF admissions (HR 0.61; 95% CI: 0.50-0.74), more evident in HFrEF (HR 0.54; 95% CI: 0.38-0.78) compared with HRmEF (HR 0.64; 95% CI 0.40-1.02), or HFpEF (HR 0.70; 95% CI 0.53-0.92). In patients with HFrEF triple therapy (ACE inhibitor/ARB + beta blocker + mineralocorticoid receptor antagonist) was associated with the lowest mortality risk (HR 0.21; 95% CI: 0.08-0.57, P = 0.002) compared with patients that received none of these drugs. CONCLUSIONS: Discharge treatment with ACE inhibitor/ARB after a HF hospitalisation is associated with a reduction in all-cause and refractory HF mortality, irrespective of LVEF.

TBC: A simple algorithm to rule out abnormalities in electrocardiograms of patients with pacemakers.

BACKGROUND: The aim of the study was to create a straightforward method to rule out abnormalities in electrocardiograms (ECGs) performed in patients with pacemakers. METHODS: The TBC method screens the ECG for any of the following findings: Tachycardia with pacing spikes, Bradycardia without spikes and Chaos with spikes unrelated to QRS-T complexes. T was considered to advise for patient assessment and B and C to require referral for urgent pacemaker evaluation. The diagnostic accuracy of the algorithm was validated using a cohort of 151 ECGs with normal and dysfunctional pacemakers. The effect of the algorithm was then evaluated for diagnostic skills and management of patients with pacemakers by non-cardiologists, comparing their diagnostic accuracy before and after teaching the algorithm. RESULTS: The TBC algorithm had a sensitivity of 86% and a specificity of 94% in diagnosing a malfunctioning pacemaker. The diagnostic skills and patient referral were significantly improved (74.8% vs. 89.5%, p < 0.001; and 57.4% vs. 83%, p < 0.001). CONCLUSIONS: TBC is an easy to remember and apply method to rule out severe abnormalities in ECGs of patients with pacemakers. TBC algorithm has a very good diagnostic capability and is easily applied by non-expert physicians with good results.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry.

Aims: In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. Methods: From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. Results: A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). Conclusion: According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that NOAC use is increasing and there is a significant decrease in VKA use.

Internet-based training of coronary artery patients: the Heart Cycle Trial.

Low adherence to cardiac rehabilitation (CR) might be improved by remote monitoring systems that can be used to motivate and supervise patients and tailor CR safely and effectively to their needs. The main objective of this study was to evaluate the feasibility of a smartphone-guided training system (GEX) and whether it could improve exercise capacity compared to CR delivered by conventional methods for patients with coronary artery disease (CAD). A prospective, randomized, international, multi-center study comparing CR delivered by conventional means (CG) or by remote monitoring (IG) using a new training steering/feedback tool (GEx System). This consisted of a sensor monitoring breathing rate and the electrocardiogram that transmitted information on training intensity, arrhythmias and adherence to training prescriptions, wirelessly via the internet, to a medical team that provided feedback and adjusted training prescriptions. Exercise capacity was evaluated prior to and 6 months after intervention. 118 patients (58 ± 10 years, 105 men) with CAD referred for CR were randomized (IG: n = 55, CG: n = 63). However, 15 patients (27 %) in the IG and 18 (29 %) in the CG withdrew participation and technical problems prevented a further 21 patients (38 %) in the IG from participating. No training-related complications occurred. For those who completed the study, peak VO2 improved more (p = 0.005) in the IG (1.76 ± 4.1 ml/min/kg) compared to CG (-0.4 ± 2.7 ml/min/kg). A newly designed system for home-based CR appears feasible, safe and improves exercise capacity compared to national CR. Technical problems reflected the complexity of applying remote monitoring solutions at an international level.

2013 update on congenital heart disease, clinical cardiology, heart failure, and heart transplant.

This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices.

Subjective well-being in heart failure patients: influence of coping and depressive symptoms.

BACKGROUND: Psychological factors play a crucial role in the well-being of chronically ill patients. PURPOSE: This research examined coping, depressive symptoms and subjective well-being (SWB) in patients with heart failure (HF). The study also analysed whether depressive symptoms mediated the association between coping strategies and SWB. METHOD: Participants (N = 60, 68.3 % men, aged between 40 and 89 years old) diagnosed with HF were recruited from the cardiology service of a general hospital. Coping strategies were assessed with 16 items of the Brief COPE Scale. The items were organised, according to theoretical and empirical data, into four types of coping: task-focused, seeking social support, maladaptive emotion-focused and acceptance coping. Depressive symptoms were assessed with the corresponding subscale of the Hospital Anxiety and Depression Scale. SWB was assessed considering the Satisfaction with Life Scale and the Positive and Negative Affect Schedule. RESULTS: The multiple regression analyses carried out indicated that SWB was positively associated with task-focused coping and inversely related to maladaptive strategies and depressive symptoms. Gender was also a significant predictor of SWB, with male patients reporting higher well-being than female patients. The mediational analysis showed that depressive symptoms partially mediated the relationships between task-focused coping and SWB. CONCLUSION: Results were discussed in the light of the importance of gender, depression and coping in patients with HF since these factors may affect subjective well-being and contribute to severe physical impairment.

Can information technology improve the performance of remote monitoring systems?

Despite some clinical, economic, and other qualitative advantages associated with remote cardiac device monitoring systems, one of the main challenges concerns the management of the out-of-hospital data. Manual updating of hospital databases with the data stored in the manufacturers' servers increases time requirements and may introduce mistakes in the entries. The use of communication standards such as Health Level 7 for data interchange could provide a safe and easy way to access patient and device information. The present study of 38 patients was carried out with the Carelink® remote monitoring technology. A formal process for remote cardiac device monitoring was established, including some features in the Arrhythmias Information System: mobile phone and e-mail were included for communication between patients and hospital, with a new gateway for automatic message sending. Device reports generated through the manufacturer's application were attached to the patient's record. Once the information concerning the transmission session was reviewed, the physician made a medical report, which was sent via post and e-mail to the patient. A new interface was created for Health Level 7 communication with the manufacturers' applications, so that the Arrhythmias Information System could automatically interchange information concerning the device and/or the patient when this kind of communication system is available. The volume of data generated by system warning alerts and transmission sessions makes it very difficult to meet the hospital database updating requirements. Standard-based communication between hospital and manufacturers' applications is fundamental to automatic and reliable update of data.