Portuguese adaptation of the Chronic Heart Failure Knowledge Questionnaire (KQCHF).

BACKGROUND: A patient's knowledge of heart failure (HF) is associated with better outcomes. The more information patients have about their illness, the less likely they are to be readmitted to the hospital. Such knowledge includes the cause, symptoms, probable duration, and expected evolution of the clinical picture. In Portugal, a tool for testing patient knowledge is an unmet need. Therefore, this study aimed to adapt and test the Chronic Heart Failure Knowledge Questionnaire (KQCHF) for the Portuguese context. METHODS: This work includes three cross-sectional studies. In Study 1, subjects were divided between before and after receiving information about HF. In Study 2, participants answered the questionnaire before and after reading the brochure. In Study 3, KQCHF was applied to patients with HF. Studies 1 and 2 were carried out in the general population. Study 3 was carried out with HF outpatients. Convenience sampling was applied to participants in the three studies. RESULTS: In Study 1 (n = 45), those who received information had better scores (9.2 ± 1.9) than those who did not (6.0 ± 2.3). In Study 2 (n = 21), the scores were higher after reading the brochure (10.4 ± 1.7 vs. 6.5 ± 2.9). In Study 3 (n = 169), women had better scores than men (9.1 ± 2.1 vs. 8.3 ± 2.2, overall: 8.5 ± 2.2), and knowledge was correlated with education (r = .340, p < .001) and age (r = -.170, p = .030). CONCLUSION: The Portuguese adaptation of KQCHF captured relevant knowledge about HF and has shown promising results for clinical and research purposes. The questionnaire can be useful in assessing HF patients' knowledge of their disease and as a basis for the implementation of general and personalised educational strategies to improve HF knowledge and, therefore, promote health literacy and self-care.

Associations of medicine use and ejection fraction with the coexistence of frailty and sarcopenia in a sample of heart failure outpatients: a cross-sectional study.

BACKGROUND: Frailty and sarcopenia have been extensively studied in heart failure (HF) patients, but their coexistence is unknown. The aim of this work is to describe the coexistence of these conditions in a sample of HF outpatients and its association with the use of medication and left-ventricular ejection fraction. METHODS: Participants in this cross-sectional study were recruited from a HF outpatients' clinic in northern Portugal. Frailty phenotype was assessed according to Fried et al. Sarcopenia was evaluated according to the revised consensus of the European Working Group on Sarcopenia in Older People. RESULTS: A total of 136 HF outpatients (33.8% women, median age 59 years) integrated this study. Frailty and sarcopenia accounted for 15.4% and 18.4% of the sample, respectively. Coexistence of frailty and sarcopenia was found in 8.1% of the participants, while 17.6% had only one of the conditions. In multivariable analysis (n = 132), increasing age (OR = 1.13;95%CI = 1.06,1.20), being a woman (OR = 65.65;95%CI = 13.50, 319.15), having heart failure with preserved ejection fraction (HFpEF) (OR = 5.61; 95%CI = 1.22, 25.76), and using antidepressants (OR = 11.05; 95%CI = 2.50, 48.82), anticoagulants (OR = 6.11; 95%CI = 1.69, 22.07), furosemide (OR = 3.95; 95%CI = 1.07, 14.55), and acetylsalicylic acid (OR = 5.01; 95%CI = 1.10, 22.90) were associated with increased likelihood of having coexistence of frailty and sarcopenia, while using statins showed the inverse effect (OR = 0.06; 95%CI = 0.01, 0.30). CONCLUSIONS: The relatively low frequency of coexistence of frailty and sarcopenia signifies that each of these two conditions still deserve individual attention from health professionals in their clinical practice and should be screened separately. Being a woman, older age, having HFpEF, using anticoagulants, antidepressants, loop diuretics and acetylsalicylic acid, and not using statins, were associated with having concomitant frailty and sarcopenia. These patients can potentially benefit from interventions that impact their quality of life such as nutritional and mental health interventions and exercise training.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Health-Related Quality of Life and Mortality in Heart Failure: The Global Congestive Heart Failure Study of 23 000 Patients From 40 Countries.

BACKGROUND: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. METHODS: We used the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. RESULTS: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03-1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21-1.42]; interaction P<0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14-1.19] and HR, 1.14 [95% CI, 1.12-1.17]; interaction P=0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13-1.17] versus 1.09 [95% CI, [1.07-1.11]; interaction P<0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20-1.26] and HR, 1.15 [95% CI, 1.13-1.17]; interaction P<0.0001). CONCLUSION: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078166.

Effects of Serelaxin in Patients with Acute Heart Failure.

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).

An updated systematic review on heart failure treatments for patients with renal impairment: the tide is not turning.

Advanced chronic kidney disease (CKD) frequently aggravates heart failure (HF). However, these patients have inherently been excluded from most HF trials. We aim to provide updated estimates of the representation of patients with advanced CKD and the provision of baseline renal function indices in HF trials with a focused interest on the landmark trials. Updated systematic review was performed from the inception of MEDLINE to 31 December 2019 to identify all chronic HF randomized trials published in the three major cardiology and medical journals, respectively, which included mortality endpoint. The included studies were analysed based on the representativeness of the advanced CKD population and the reporting of baseline renal function. A total of 187 eligible randomized trials with 322,374 participants were included in our analysis. One hundred and six trials (56.7%) had exclusion criteria related to renal function, which remained a continuing trend-55.1% (27/49) from inception-2000, 53.4% (39/73) from 2001-2010 and 61.5% (40/65) from 2011 (P = 0.64). The exclusion criteria, however, have become less restrictive. There was a temporal improvement in the likelihood of HF trials in providing baseline renal function indices (28.6% from inception-2000 versus 53.4% from 2001-2010 and 83.1% from 2011, P < 0.001). Concordant findings were observed in the landmark trials. Patients with advanced CKD remain underrepresented in HF trials in the contemporary era, even though the exclusion criteria have become less restrictive, and the quality of renal function monitoring has improved. The continued underrepresentation of patients with advanced CKD in HF trials merits measured broadening of eligibility in further trial studies.

Statins are associated with reduced likelihood of sarcopenia in a sample of heart failure outpatients: a cross-sectional study.

BACKGROUND: Sarcopenia is prevalent in heart failure (HF) patients, contributing to its poor prognosis. Statin use is postulated as a probable risk for developing sarcopenia, but little is known regarding this association in HF patients. This work aims at classifying and characterising sarcopenia and at describing the association of statin use with sarcopenia in a sample of Portuguese HF outpatients. METHODS: In this cross-sectional study, a sample of 136 HF patients (median age: 59 years, 33.8% women) was recruited from an HF outpatients' clinic of a University Hospital in Portugal. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People 2. Clinical, nutritional, and dietary data were collected. RESULTS: A total of 25 (18.4%) individuals were categorised as sarcopenic, ranging from 12.2% in younger (< 65 years) participants vs. 30.4% in older ones and from 3.3% in men vs. 47.8% in women. Severe sarcopenia accounted for 7.4% of the sample and sarcopenic obesity was identified in 5.1% of the individuals. A total of 65.4% of the participants were statin users. In multivariable analysis (n = 132, 25 sarcopenic), the use of statins was inversely associated with sarcopenia (OR = 0.03; 95% CI = 0.01, 0.30). Each additional age year was associated with a 9% increase in the likelihood of being sarcopenic (OR = 1.09; 95% CI = 1.01, 1.17), and each Kg.m-2 increment in body mass index was associated with a 21% decrease in the likelihood of sarcopenia (OR = 0.79; 95% CI = 0.65, 0.96). The daily use of five or more medicines was also directly associated with sarcopenia (OR = 26.87; 95% CI = 2.01, 359.26). On the other hand, being a man and being physically active were inversely associated with sarcopenia (OR = 0.01; 95% CI = 0.00, 0.07 and OR = 0.09; 95% CI = 0.01, 0.65, respectively). CONCLUSIONS: Contrary to what was expected, patients medicated with statins were less likely to be sarcopenic. Although this finding deserves further research, we hypothesise that this might be related to the pleiotropic effects of statins on endothelial function, contributing to better neuromuscular fitness.

Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes.

AIMS: The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). METHODS AND RESULTS: HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were -4.0 m (-16.0, 6.0; P = 0.42) and 4.0 m (-5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. CONCLUSION: The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

Management of RAASi-associated hyperkalemia in patients with cardiovascular disease.

Renin-angiotensin-aldosterone system inhibitors (RAASi) reduce morbidity and mortality in heart failure (HF) with reduced ejection fraction in a dose-dependent manner. They also have a positive impact in other cardiovascular diseases (CVDs). However, RAASi may induce hyperkalemia, a potentially life-threatening disorder. This risk is further increased in those with concomitant chronic kidney disease, diabetes mellitus, and/or in patients with hypertension. Current treatment guidelines recommend maximal RAASi dosing to improve clinical outcomes; however, this is often limited by the development of hyperkalemia. When this occurs, current guidelines recommend RAASi down-titration/interruption, which, while improving short-term prognosis, is associated with a negative long-term prognostic impact. At present, the European Society of Cardiology suggests the consideration of novel potassium binders (patiromer and sodium zirconium cyclosilicate) for the management of RAASi-associated hyperkalemia. Both drugs can reduce serum potassium levels and prevent recurrent hyperkalemia. Additionally, patiromer showed enabling of RAASi optimization in high-risk patients. Nevertheless, precise recommendations on the use of these drugs are lacking. Building upon current HF guideline recommendations, a multidisciplinary expert panel convened to design an algorithm providing practical guidance on the use of novel potassium binders/patiromer in patients with HF and/or other CVD. As a result of that effort, we present an evidence-based treatment algorithm for the management of hyperkalemia with novel potassium binders/patiromer in patients with HF and/or other CVD receiving RAASi, including the necessary monitoring to avoid induction of hypokalemia. This algorithm aims to maintain or up-titrate RAASi to optimized doses, while maintaining normokalemia, improved clinical outcomes, and long-term prognosis.

Frailty phenotype and associated nutritional factors in a sample of Portuguese outpatients with heart failure.

BACKGROUND AND AIM: Frailty phenotype (FP) is very common in heart failure (HF) and both syndromes worsen one another. The aim of this study is to first describe FP in a sample of Portuguese patients with HF, and to analyse its association with nutritional and clinical statuses, namely, muscle mass, obesity and functional class. METHODS AND RESULTS: In this cross-sectional study, a sample of 136 outpatients with HF (24-81 years, 33.8% women) were randomly selected from the appointments' listings of a HF and Transplant clinic in a Portuguese University Hospital. FP was assessed according to Fried et al. muscle mass was estimated from the mid-upper arm muscle circumference; weight status was assessed using the body mass index; HF functional classes were registered. The association between participants' characteristics and FP categories was analysed using logistic ordinal regression. The frequency of pre-frailty and frailty is 57.4% and 15.4%, respectively. Within frail individuals, 52.4% were under the age of 65. In multivariable analysis, frailty was positively associated with age 70 or older (OR = 3.44) and obesity (OR = 2.66), and negatively associated with muscle mass (OR = 0.77) and HF functional classes I (OR = 0.14) or II (OR = 0.29). CONCLUSION: Muscle mass seems to be an important predictor of frailty in patients with HF and should be taken into account when designing intervention plans that allow for reverting or modifying frailty and pre-frailty. Younger patients should be monitored for the presence and evolution of FP.

Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.

Current Use and Impact on 30-Day Mortality of Pulmonary Artery Catheter in Cardiogenic Shock Patients: Results From the CardShock Study.

BACKGROUND: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). METHODS: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. RESULTS: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices (P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. CONCLUSIONS: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.

Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry.

Aim: To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF < 40%), mid-range (HFmrEF 40-49%), and preserved (HFpEF ≥ 50%) ejection fraction (EF). Methods and results: Data from the observational, prospective, HF long-term registry of the European Society of Cardiology were analysed. A total of 14 964 HF patients (age 66 ± 13 years, 67% male; 53% HFrEF, 21% HFmrEF, 26% HFpEF) were enrolled. The prevalence of AF was 27% in HFrEF, 29% in HFmrEF, and 39% in HFpEF. Atrial fibrillation was associated with older age, lower functional capacity, and heightened physical signs of HF. Crude rates of mortality and HF hospitalization were higher in patients with AF compared to SR, in each EF subtype. After multivariable adjustment, the hazard ratio of AF for HF hospitalizations was: 1.036 (95% CI 0.888-1.208, P = 0.652) in HFrEF, 1.430 (95% CI 1.087-1.882, P = 0.011) in HFmrEF, and 1.487 (95% CI 1.195-1.851, P < 0.001) in HFpEF; and for combined all-cause death or HF hospitalizations: 0.957 (95% CI 0.843-1.087, P = 0.502), 1.302 (95% CI 1.055-1.608, P = 0.014), and 1.365 (95% CI 1.152-1.619, P < 0.001), respectively. In patients with HFrEF, AF was not associated with worse outcomes in those presenting with either an acute or a chronic presentation of HF. Conclusions: The prevalence of AF increases with increasing EF but its association with worse cardiovascular outcomes, remained significant in patients with HFpEF and HFmrEF, but not in those with HFrEF.

The Evolving Role of the Cardiologist in the Management of Type 2 Diabetes.

PURPOSE OF REVIEW: To evaluate the treatment of type 2 diabetes from a cardiologist's view. RECENT FINDINGS: A new era in the treatment of type 2 diabetes began for the cardiologist in 2015 with the publication of the EMPA-REG outcome trial finding a significant reduction in CV death with empagliflozin (oral sodium-glucose co-transporter-2 [SGLT2] inhibitor) in patients with type 2 diabetes at increased cardiovascular risk. Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke). Both classes have demonstrated significant renal protection when added to usual care. Moreover, there may be some exciting new benefits of SGLT2 inhibitors for patients with heart failure. These research studies are underway. These two new classes of cardiovascular drugs for type 2 diabetes usher in a new era for the cardiologist who sees greater than 50% of patients with diabetes. The off-target effect of these agents is different as with all new cardiovascular compounds. While safety profiles in these populations are consistent with the known effects of these classes, new off-target effects have been seen with some agents in this class. Ongoing collaboration between cardiologists and other care providers remains important in the implementation of the evidence and care of patients with type 2 diabetes.

Predictive value of the baseline electrocardiogram ST-segment pattern in cardiogenic shock: Results from the CardShock Study.

BACKGROUND: The most common aetiology of cardiogenic shock (CS) is acute coronary syndrome (ACS), but even up to 20%-50% of CS is caused by other disorders. ST-segment deviations in the electrocardiogram (ECG) have been investigated in patients with ACS-related CS, but not in those with other CS aetiologies. We set out to explore the prevalence of different ST-segment patterns and their associations with the CS aetiology, clinical findings and 90-day mortality. METHODS: We analysed the baseline ECG of 196 patients who were included in a multinational prospective study of CS. The patients were divided into 3 groups: (a) ST-segment elevation (STE). (b) ST-segment depression (STDEP). (c) No ST-segment deviation or ST-segment impossible to analyse (NSTD). A subgroup analysis of the ACS patients was conducted. RESULTS: ST-segment deviations were present in 80% of the patients: 52% had STE and 29% had STDEP. STE was associated with the ACS aetiology, but one-fourth of the STDEP patients had aetiology other than ACS. The overall 90-day mortality was 41%: in STE 47%, STDEP 36% and NSTD 33%. In the multivariate mortality analysis, only STE predicted mortality (HR 1.74, CI95 1.07-2.84). In the ACS subgroup, the patients were equally effectively revascularized, and no differences in the survival were noted between the study groups. CONCLUSION: ST-segment elevation is associated with the ACS aetiology and high mortality in the unselected CS population. If STE is not present, other aetiologies must be considered. When effectively revascularized, the prognosis is similar regardless of the ST-segment pattern in ACS-related CS.

Ascending aorta in tetralogy of Fallot: Beyond echocardiographic dimensions.

BACKGROUND: Late after tetralogy of Fallot (TOF) repair some patients exhibit aortic dilatation and stiffness. Noninvasive assessment of aortic stiffness could contribute to understand this aortopathy and may be important in risk stratification for major aortic event. METHODS: We included prospectively 82 adults after TOF repair and 41 age- and sex-matched normal controls. Aortic diameters were measured by two-dimensional transthoracic echocardiography and the aortic z-score was estimated. Aortic deformation was assessed by M-mode strain and global peak circumferential ascending aortic strain (CAAS), derived from two-dimensional speckle tracking echocardiography (2D-STE). Corrected CAAS was calculated as CAAS/pulse pressure. Ascending aorta (AAo) distensibility and stiffness index were calculated. RESULTS: TOF patients (age 29.7 ± 8.4 years; follow-up since TOF repair 23.0 ± 6.8 years) had smaller body surface area but a larger aorta compared to controls. TOF patients had lower AAo distensibility (2.2 [0.0-21.0] vs 5.6 [0.0-12.5] cm2 dyne-1 10-6 , P < .01), higher aortic stiffness index (9.5 [2.7-98.4] vs 7.1 [2.3-20.4], P = .02) and lower CAAS (6.0 ± 3.9 vs 8.1 ± 4.4%, P = .01) compared to controls. CAAS showed a better correlation with AAo z-score (r = -.25, P = .03) compared to M-mode strain. Systemic arterial compliance, arterial stiffness and corrected CAAS (ß = -0.23, P = .02) were independently associated with AAo diameter. CONCLUSIONS: TOF patients have a larger and stiffer AAo compared to controls. CAAS derived from 2D-STE allows a routine noninvasive method for assessing AAo stiffness, with advantages over M-mode strain, and may be used as predictor of major aortic or cardiovascular events.

Left Ventricular Mechanical Reverse Remodelling Not Followed by Electrical Reverse Remodelling: A Case Report.

Patients with severely depressed left ventricular ejection fractions (LVEFs) receive implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden death. However, in some patients, LVEFs may improve or even normalize over time, and these patients would no longer be qualified for ICD implantation based on the original criteria for which they have initially received an ICD. We report a patient with idiopathic dilated cardiomyopathy whose LVEF recovered to normal values after pharmacological therapy. Meanwhile, the patient had life-threatening ventricular fibrillation, aborted by the ICD. We reflect on the pathological features of left ventricular reverse remodelling and ventricular arrhythmogenesis, where the myocardial substrate appears to play an important role. Also, after LVEF improvement in a patient with a cardiac device, there is still a debate on whether we should perform a battery replacement.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

BACKGROUND: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. METHODS: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. RESULTS: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. CONCLUSION: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure.

AIMS: Although active-controlled trials with renin­angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. METHODS AND RESULTS: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34­50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21­44%; P < 0.0001) and heart failure hospitalization (49%, 39­58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15­39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27­48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16­45%; P < 0.0001) for cardiovascular death, 46% (33­56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11­39%; P < 0.0001) for all-cause mortality. CONCLUSION: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.