Heart failure management with ß-blockers: can we do better?

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Endovascular therapeutic hypothermia adjunctive to percutaneous coronary intervention in acute myocardial infarction: realistic simulation as a game changer.

BACKGROUND: Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI. METHODS AND RESULTS: We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System (Zoll Circulation Inc™, San Jose, CA, USA). The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Afterwards, the EHT protocol was successfully validated in a trial randomizing 50 patients for 18 minutes cooling before coronary recanalization at the target temperature of 32 ± 1.0 ∘C or PCI-only. A total of 35 patients underwent ETH (85.7% [30/35] in 90 ± 15 minutes), without delays in the mean door-to-balloon time for primary PCI when compared to 15 control group patients (92.1 minutes versus 87 minutes, respectively; p = 0.509). CONCLUSIONS: Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI. CLINICALTRIALS: gov: NCT02664194.

Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review.

AIMS: This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients. METHODS AND RESULTS: A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4-13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74-0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80-0.84. CONCLUSIONS: There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.

Incremental value of B-type natriuretic peptide for early risk prediction of infective endocarditis.

BACKGROUND: Early and accurate risk prediction is an unmet clinical need in patients with infective endocarditis (IE). The aim of this study was to determine the value of B-type natriuretic peptide (BNP) levels obtained on admission for the prediction of in-hospital death in IE patients. METHODS: Between 2009 and 2011, consecutive patients with IE diagnosed using the revised Duke criteria and admitted to the emergency department were evaluated prospectively. BNP levels were measured on admission. Death during hospitalization was the primary endpoint. RESULTS: Among 104 consecutive patients with IE and with available BNP levels, 34 (32.7%) died in hospital. BNP levels were significantly higher in patients who died as compared to survivors (709.0 pg/ml vs. 177.5 pg/ml, p<0.001). The accuracy of BNP to predict death as quantified by the area under the receiver operating characteristics curve was 0.826 (95% confidence interval (CI) 0.747-0.905). The value of BNP was additive to that provided by clinical, microbiological, and echocardiography assessment. On multivariate analysis, new heart failure (hazard ratio (HR) 2.02, 95% CI 1.15-3.57, p=0.015), sepsis (HR 2.10, 95% CI 1.25-3.55, p=0.005), Staphylococcus aureus endocarditis (HR 2.67, 95% CI 1.60-4.45, p<0.001), left ventricular ejection fraction ≤55% (HR 1.63, 95% CI 1.00-2.65, p=0.047), and BNP (HR 1.04, 95% CI 1.02-1.06, p<0.001) were independent predictors of in-hospital mortality. CONCLUSION: Among patients with IE, BNP levels obtained on admission provide incremental value for early and accurate risk prediction.

Clinical characteristics and in-hospital outcome of patients with acute coronary syndromes and systemic lupus erythematosus.

OBJECTIVE: Due to the chronic inflammation associated with systemic lupus erythematosus (SLE), patients develop premature atherosclerosis and the disease is a risk factor for acute myocardial infarction. The best interventional treatment for acute coronary syndrome (ACS) in these patients is unclear. The objective of this study is to describe the baseline characteristics, clinical manifestations, treatment and in-hospital outcome of patients with SLE and ACS. METHODS: Eleven SLE patients with ACS were analyzed retrospectively between 2004 and 2011. The following data were obtained: age, gender, clinical and electrocardiographic characteristics, Killip class, risk factors for ACS, myocardial necrosis markers (CK-MB and troponin), creatinine clearance, left ventricular ejection fraction, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), drugs used during hospital stay, treatment (medical, percutaneous or surgical) and in-hospital outcome. The statistical analysis is presented in percentages and absolute values. RESULTS: Ten of the patients (91%) were women. The median age was 47 years. Typical precordial pain was present in 91%. Around 73% had positive erythrocyte sedimentation rate. The vessel most often affected was the anterior descending artery, in 73%. One patient underwent coronary artery bypass grafting, seven underwent percutaneous coronary intervention with bare-metal stents and three were treated medically. In-hospital mortality was 18%. CONCLUSIONS: Despite the small number of patients, our findings were similar to those in the literature, showing coronary artery disease in young people with SLE due to premature atherosclerosis and a high mortality rate.

Clinical manifestations and pulmonary histopathological analysis related to different diseases in patients with fatal pulmonary thromboembolism: an autopsy study.

BACKGROUND: To correlate underlying diseases, in autopsies of patients with pulmonary thromboembolism (PTE) to histological findings and manifestations reviewed in the medical records. METHODS: The autopsy records between 2001 and 2008 of 291 patients whose cause of death was PTE were reviewed. The following data were obtained: age, sex, clinical "in vivo" manifestations, postmortem pathological patterns, and main associated underlying diseases, cancers, and surgeries performed in the last hospitalization. The pulmonary histopathological changes were categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoid interstitial pneumonia. Odds ratios of positive relations were obtained by logistic regression and were considered significant when P<0.05. RESULTS: The median age was 64 years old. About 64% of patients presented cardiovascular illness associated with PTE. The most prevalent pulmonary finding was pulmonary edema. Only 13% of cases had clinical suspicion of PTE. Acute respiratory failure was positively related to pulmonary edema, alveolar hemorrhage, and diffuse alveolar damage as well as hemodynamic instability to alveolar hemorrhage and diffuse alveolar damage. CONCLUSION: We found important relations between clinical data and histological findings of patients with fatal PTE. A greater understanding of the pulmonary physiopathological mechanisms involved with each disease associated to PTE could improve its diagnosis and treatment.

[Serum NT-proBNP levels are a prognostic predictor in patients with advanced heart failure]. / O nível sérico de NT-proBNP é um preditor prognóstico em pacientes com insuficiência cardíaca avançada.

OBJECTIVE: To verify if the determination of NT-proBNP values would help predict the prognosis in advanced heart failure (HF) patients. METHODS: One hundred and five subjects with average age of 52.4 years were evaluated, 66.6% of them males. Thirty-three (32.0%) subjects were outpatients and 70 (67.9%) were inpatients (functional class III/IV) admitted to the hospital for cardiac compensation. All patients had left ventricular systolic dysfunction and a mean ejection fraction of 0.29. The NT-proBNP levels were measured in all patients and they were followed-up over a period from 2 to 90 days (average 77 days). A ROC curve was drawn to determine the best cut-off point, as well as the corresponding Kaplan-Meyer survival curves. RESULTS: During the follow-up period, 22 patients died. The average NT-proBNP value of the patients who remained alive was 6,443.67+/-6,071.62 pg/ml, whereas that of those who died was 14,609.66+/-12,165.15 pg/ml (p=0.001). The ROC curve identified a cut-off point at 6,000 pg/ml with 77.3% sensitivity (area under the curve: 0.74). The survival curve for values below and above 6,000 pg/ml was significantly different (p=0.002): patients with values below 6,000 pg/ml had a 90.2% 90-day survival, and those patients with values above, a 66% survival. CONCLUSION: Patients with advanced HF, especially those admitted to the hospital for cardiac compensation, had much higher NT-proBNP values, with a two-fold increase among those who died during the follow-up period. Values above 6,000 pg/ml identify the patients most likely to die within 90 days after hospital discharge.

[Score for nutritional status evaluation: the role played in the prognostic stratification of dilated cardiomyopathy and advanced heart failure patients]. / Escore para avaliação do estado nutricional: seu valor na estratificação prognóstica de portadores de cardiomiopatia dilatada e insuficiência cardíaca avançada.

OBJECTIVE: Develop a method for the evaluation of patients nutritional status through a score that expresses universal nutritional status, as well as investigate if that score would be efficient for the prognostic stratification of advanced heart failure (HF) pts. METHODS: The score was reached by the selection of evaluation methods that would quantify nutritional status: ideal body weight percentage, thickness of tricipital skinfold, percentiles for arm muscular mass circumference, albumin serum level, lymphocyte total count. In order to be validated, the score was applied to a group of 95 pts. Pts were under 65 years old no evidence of consumptive diseases. The score was analyzed to confirm whether it would keep correlation with HF clinical data and whether it would stratify its prognostic. RESULTS: Nutritional status suggesting moderate or severe malnutrition could be observed in 31/95 (32.6%). No correlation was found between nutritional score values and the duration of symptoms, or the level of ventricular dysfunction. Pts with high nutritional score showed a trend towards higher mortality rate (p=0.0606). CONCLUSION: Those data suggest malnutrition is reported by 1/3 of pts with advanced HF. A score comprising 5 parameters for nutritional status showed good correlation with the clinical, global evaluation of pts with HF. A score over 8 identified pts with higher probability of death as outcome, confirming that pts under higher malnutrition exhibit worse evolution.

[Economy class syndrome after long duration bus travel]. / Síndrome da classe econômica após longas viagens de ônibus.

A 65 year-old man with heart failure due to hypertensive and ischemic heart disease was admitted to the hospital with dyspnea, bloody sputum and pleuritic chest pain after a 52-hour bus trip. Clinical and laboratory evaluation included chest helical tomography that demonstrated a filling defect of the right main branch of the pulmonary artery and a regular peripheral opacity of triangular shape in the inferior lobe of the lower lung. The diagnosis of pulmonary thromboembolism was made and therapy with heparin, followed by warfarin was introduced. The patient was discharged from the hospital. The diagnosis of pulmonary embolism should be considered in patients with complaints like this patient after long-distance bus travel.

[Nutritional repercussion in advanced heart failure and its value in prognostic assessment]. / Repercussão nutricional na insuficiência cardíaca avançada e seu valor na avaliação prognóstica.

OBJECTIVE: To analyze the nutritional repercussion in heart failure and its relations with left ventricular dysfunction and mortality. METHODS: A series of nutritional parameters in a group of 95 patients with advanced chronic heart failure, arising out of dilated cardiomyopathy and age < 65 years old, without concomitant diseases was studied. The duration of symptons, final diastolic diameter and left ventricular ejection fraction were verified. The nutritional assessment, included the ideal percentage of weight the triceps skin fold thickness, percentiles of circumference of muscular mass of the arm, the albumin serum levels and the lymphocytes global count. RESULTS: The nutritional situation was alterated in 45.3% to 94.7% of the patients in accordance to the assessment parameter used. There was neither correlation between the nutritional parameters and the length of symptoms, nor with the ventricular dysfunction level. That group of patients had a homogenous evolution, and 75.8% of them died in an average time of 21.86 weeks. The left ventricular diastolic diameter and ejection fraction did not allow for the prediction of survival. A diminished body mass identified a group with higher risk of death. The ideal percentage of the body mass was predictive of survival (p=0.0352), the patients with less than 80% of ideal weight had a higher relative risk of death of 1.99 (1.12-3.02) (p=0.0132). CONCLUSION: Malnutrition is frequent in patients with advanced heart failure and dilated cardiomyopathy. The reduced body mass was a better predictor of survival than the left ventricular ejection fraction in patients under advanced stage of myocardial compromising.

ProBNP for stratifying patients with heart failure.

OBJECTIVE: To verify whether the serum levels of N-Terminal ProBNP fraction (ProBNP) allow us to identify with accuracy the clinical functional status of patients with heart failure (HF), because the clinical diagnosis of this syndrome is based basically on clinical data when the complementary tests have lower specificity. METHODS: Sixty-nine patients with a history of HF were studied. Their mean age of was 53.5 years and 78.3% were males. All underwent clinical and echocardiographic evaluations and a test to determine the serum dosage of ProBNP. According to clinical manifestation, patients were in the following functional classes (FC), 14% FC I, 40.6% FC II, 28.1% FC III, and 23.4% FC IV. The mean ejection fraction (EF) was 0.28. RESULTS: ProBNP did not differ according to age, sex, and cause of cardiopathy. No correlation existed between EF and the ProBNP serum level. ProBNP levels were significantly lower in patients in FC I than those in FC II (42 vs 326.7 pmol/L; P=0.0001), and in FC II than those in FC III (P=0.01). ProBNP levels did not differ statically between FC III and IV patients (888.1 vs 1082.8 pmol/L; P=0.25). ProBNP values greater than 100 pmol/L identify patients with decompensated HF with a sensitivity of 98%. CONCLUSION: ProBNP values over 100 pmol/L were indicative of HF, and patients with advanced HF had values over 270 pmol/L. A ProBNP dosage test was an excellent auxiliary in the clinical characterization of patients with HF.