The Potential Role of Salivary NT-proBNP in Heart Failure.

BACKGROUND: Serum natriuretic peptides (NPs) have an established role in heart failure (HF) diagnosis. Saliva NT-proBNP that may be easily acquired has been studied little. METHODS: Ninety-nine subjects were enrolled; thirty-six obese or hypertensive with dyspnoea but no echocardiographic HF findings or raised NPs served as controls, thirteen chronic HF (CHF) patients and fifty patients with acute decompensated HF (ADHF) requiring hospital admission. Electrocardiogram, echocardiogram, 6 min walking distance (6MWD), blood and saliva samples, were acquired in all participants. RESULTS: Serum NT-proBNP ranged from 60-9000 pg/mL and saliva NT-proBNP from 0.64-93.32 pg/mL. Serum NT-proBNP was significantly higher in ADHF compared to CHF (p = 0.007) and in CHF compared to controls (p < 0.05). There was no significant difference in saliva values between ADHF and CHF, or between CHF and controls. Saliva and serum levels were positively associated only in ADHF patients (R = 0.352, p = 0.012). Serum NT-proBNP was positively associated with NYHA class (R = 0.506, p < 0.001) and inversely with 6MWD (R = -0.401, p = 0.004) in ADHF. Saliva NT-proBNP only correlated with age in ADHF patients. CONCLUSIONS: In the current study, saliva NT-proBNP correlated with serum values in ADHF patients, but could not discriminate between HF and other causes of dyspnoea. Further research is needed to explore the value of saliva NT-proBNP.

Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure.

Natriuretic peptides can relieve cardiovascular stress and closely related to heart failure. Besides, these peptides also have preferable interactions of binding to cellular protein receptors, and subsequently mediate various physiology actions. Hence, detection of these circulating biomarkers could be evaluated as a predictor ("Gold standard") for rapid, early diagnosis and risk stratification in heart failure. Herein, we proposed a measurement to discriminate multiple natriuretic peptides via the peptide-protein nanopore interaction. The nanopore single-molecular kinetics revealed that the strength of peptide-protein interactions was in the order of ANP > CNP > BNP, which was demonstrated by the simulated peptide structures using SWISS-MODEL. More importantly, the peptide-protein interaction analyzing also allowed us to measure the peptide linear analogs and structure damage in peptide by single-chemical bond breakup. Finally, we presented an ultra-sensitive detection of plasma natriuretic peptide using asymmetric electrolyte assay, obtaining a detection limit of ∼770 fM for BNP. At approximately, it is 1597 times lower than that of using symmetric assay (∼1.23 nM), 8 times lower than normal human level (∼6 pM), and 13 times lower than the diagnostic values (∼10.09 pM) complied in the guideline of European Society of Cardiology. That said, the designed nanopore sensor is benefit for natriuretic peptides measurement at single molecule level and demonstrates its potential for heart failure diagnosis.

Decongestion Models and Metrics in Acute Heart Failure: ESCAPE Data in the Age of the Implantable Cardiac Pressure Monitor.

The United States Food and Drug Administration restricts the use of implantable cardiac pressure monitors to patients with New York Heart Association (NYHA) class III heart failure (HF). We investigated whether single-pressure monitoring could predict survival in HF patients as part of a model constructed using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial. We validated survival models in 204 patients, using all-cause 180-day mortality. Two levels of model complexity were tested: 1) a simplified 1-pressure model based on pulmonary artery mean pressure ([PAM]1P) (information obtainable from an implanted intracardiac monitor alone), and 2) a pair of 5-variable risk score models based on right atrial pressure (RAP) + pulmonary capillary wedge pressure (PCWP) ([RAP+PCWP]5V) and on RAP + PAM ([RAP+PAM]5V). The more complex models used 5 dichotomous variables: a congestion index above a certain threshold value, baseline systolic blood pressure of <100 mmHg, baseline blood urea nitrogen level of ≥ 34 mg/dL, need for cardiopulmonary resuscitation or mechanical ventilation, and posttreatment NYHA class IV status. The congestion index was defined as posttreatment RAP+PCWP or posttreatment RAP+PAM, with congestion thresholds of 34 and 42 mmHg, respectively (median pulmonary catheter indwelling time, 1.9 d). The 5-variable models predicted survival with areas under the curve of 0.868 for the (RAP+PCWP)5V model and 0.827 for the (RAP+PAM)5V model, whereas the 1-pressure model predicted survival with an area under the curve of 0.718. We conclude that decongestion as determined by hemodynamic assessment predicts survival in HF patients and that it may be the final pathway for treatment benefit despite improvements in pharmacologic intervention since the ESCAPE trial.

Prognostic Value of 6-Minute Walk Distance in Patients Undergoing Percutaneous Coronary Intervention: a Veterans Affairs Prospective Study.

The 6-minute walk distance (6MWD) test is a useful prognostic tool in chronic heart failure. Its usefulness after percutaneous coronary intervention is unknown. In a prospective observational study, patients underwent a 6MWD test within 2 weeks after percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular events (MACE) (death, acute coronary syndrome, and heart failure admission) at one year. Receiver operating characteristic curves and area under the curve were used to determine the 6MWD test's predictive power, and the Youden index was used to measure its effectiveness. A total of 212 patients were enrolled (98% men; mean age, 65 ± 9 yr). Major comorbidities were hypertension in 187 patients (88%), dyslipidemia in 186 (88%), and diabetes mellitus in 95 (45%). Among the 176 patients (83%) who completed the 6MWD test, the incidence of MACE at one year was 22% (acute coronary syndrome in 17%; heart failure admission in 4%; and death in 3%). The area under the curve for MACE was 0.59, and 6MWD was shorter for patients with MACE than for those without (290 vs 326 m; P=0.03). For 39 patients with previous heart failure who completed the 6MWD test, the area under the curve was 0.64 for MACE and 0.78 for heart failure admission. The 6MWD test predicted reasonably well the incidence of MACE one year after percutaneous coronary intervention. In a subgroup of patients with previous heart failure, it fared even better in predicting heart failure admission. Larger studies are needed to confirm these findings.

Do Patients With Acute Heart Failure and Preserved Ejection Fraction Have Heart Failure at Follow-Up: Implications of the Framingham Criteria.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) may be misdiagnosed. We assessed prevalence and consistency of Framingham criteria signs and symptoms in acute vs subsequent stable HFpEF. METHODS: Three hundred ninety-nine patients with acute HFpEF according to Framingham criteria were re-assessed in stable condition. Four definitions of HFpEF at follow-up: (1) Framingham criteria alone, (2) Framingham criteria and natriuretic peptides (NPs), (3) Framingham criteria, NPs, and European Society of Cardiology HF guidelines echocardiographic criteria, (4) Framingham criteria, NPs, and the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON) trial echocardiographic criteria. RESULTS: At follow-up, HFpEF was still present in 27%, 22%, 21%, and 22%, respectively. Most prevalent in acute HFpEF were dyspnea at exertion (90%), pulmonary rales (71%), persisting at follow-up in 70% and 13%, respectively. Characteristics at acute HF with greater or lesser odds of stable HFpEF; (1) jugular venous distention (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.13-2.87; P = .013) and pleural effusion (OR 0.45, 95% CI 0.24-0.85; P = .014) and (4), older age (1.04, 95% CI 1.01-1.08; P = .014) and tachycardia (>100 bpm) 0.52, 95% CI 0.27-1.00; P = .048). CONCLUSIONS: In patients with acute HFpEF, one-quarter met the HF definition according to Framingham criteria at ambulatory follow-up. The proportion of patients with postdischarge HFpEF was largely unaffected by additional echocardiographic or NP criteria Older age and jugular venous distention at acute presentation predicted persistent HFpEF at follow-up, whereas pleural effusion and tachycardia may yield false HFpEF diagnoses. This finding has implications for HFpEF trial design.

Catastrophic Antiphospholipid Syndrome Presenting as Congestive Heart Failure in a Patient with Thrombotic Microangiopathy.

Thrombotic microangiopathic syndromes are characterized by thrombus formation leading to microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury that most often affects the kidney and brain. Patients with thrombotic microangiopathy can also present with cardiac involvement, which has been shown to worsen their prognosis. We describe the case of a 46-year-old woman who presented with acute congestive heart failure as a manifestation of catastrophic antiphospholipid syndrome, which is characterized by rapidly progressing multiorgan involvement. Targeted therapy improved our patient's cardiomyopathy and saved her life. Increased recognition of thrombotic microangiopathy as an underlying pathophysiologic mechanism in heart failure and initiation of timely treatment may help to prevent death in patients with thrombotic microangiopathy.

Developing a disease management program for the improvement of heart failure outcomes: the do's and the don'ts.

INTRODUCTION: Heart failure is a highly prevalent condition affecting approximately 2% of people worldwide. Heart failure disease management programs (DMP) have shown a reduction in mortality and reduced hospitalization and are an established part of clinical guidelines; however, their presence is not widespread. Focusing on the application of proven therapies, patient education, diagnosis with work up of cause and easy access for clinical deterioration should be fundamental to the structure of the DMP. Multidisciplinary team care with early and timely recognition of potentially critical patients is essential, along with the inclusion of patients diagnosed in hospital as well as the community. Areas covered: The fundamental structure of a DMP along with the current gaps in evidence is outlined. Current challenges with the heart failure condition along with the current best evidence are covered. Articles were searched using MEDLINE containing the keywords; Chronic Heart Failure, Disease Management Program. We have also provided clinical opinion. Expert opinion: A multidisciplinary approach to disease management programs is essential to providing adequate care to patients. DMPs are an established part of current guidelines and should be a benchmark of treatment. Future resources should be focused on identifying patients at risk and early prevention.

Heart failure in sub-Saharan Africa: review of the aetiology of heart failure and the role of point-of-care biomarker diagnostics.

Within Africa, the burden of heart failure is significant. This arises from the increase in cardiovascular disease and associated risk factors such as hypertension and diabetes, as well as causes of heart failure which are particular to sub-Saharan Africa, such as endomyocardial fibrosis. The lack of access to echocardiography and other imaging modalities, from a cost and technical perspective, combined with the predominantly rural nature of many countries with poor transport links, means that the vast majority of people never obtain an appropriate diagnosis. Similarly, research has been limited on the causes and treatment of heart failure in Africa and in particular endemic causes such as EMF and rheumatic heart disease. This review outlines the burden of heart failure in Africa and highlights the opportunity to expand diagnosis through the use of biomarkers, in particular natriuretic peptides. This builds on the success of point-of-care testing in human immunodeficiency virus and tuberculosis which have been extensively deployed in community settings in Africa.

Determining the optimal cutoff values of plasma N-terminal pro-B-type natriuretic peptide levels for the diagnosis of heart failure in children of age up to 14 years.

BACKGROUND: Plasma N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of heart failure (HF). However, the optimal cutoff value of plasma NT-proBNP for the diagnosis of HF in children is unknown. The objective of this study was to determine the appropriate cutoff value of plasma NT-proBNP for the diagnosis of HF in children ≤14 years old. METHODS AND RESULTS: Plasma NT-proBNP concentrations were detected in pediatric HF patients using standard clinical assays. Patients were stratified into 4 groups by age: 0-1 year, 1-3 years, 4-7 years, and 8-14 years. Case-matched healthy children were recruited as control subjects. HF was diagnosed with the use of the modified Ross score. The optimal cutoff value of plasma NT-proBNP for the diagnosis of HF was determined by analyzing receiver operating characteristic (ROC) curves and the resulting sensitivity, specificity, and Youden index (J). In healthy children, plasma NT-proBNP level and age were negatively correlated (r = -0.739; P < .001). In HF patients aged 0-1 year, 1-3 years, 4-7 years, and 8-14 years, respectively, areas under the ROC curves were 0.795, 0.786, 0.783, and 0.696; 95% confidence intervals were 0.689-0.901, 0.669-0.903, 0.662-0.904, and 0.487-0.905; and J values were 0.715, 0.708, 0.706, and 0.679. Optimal cutoff values of plasma NT-proBNP for the diagnosis of HF were 502 ng/L, 456 ng/L, 445 ng/L, and.355 ng/L. CONCLUSIONS: Age-stratified analysis of plasma NT-proBNP levels in children provides new parameters for diagnosing HF.

Improving care for patients with acute heart failure: before, during and after hospitalization.

Acute heart failure (AHF) is a common and serious condition that contributes to about 5% of all emergency hospital admissions in Europe and the USA. Here, we present the recommendations from structured discussions among an author group of AHF experts in 2013. The epidemiology of AHF and current practices in diagnosis, treatment, and long-term care for patients with AHF in Europe and the USA are examined. Available evidence indicates variation in the quality of care across hospitals and regions. Challenges include the need for rapid diagnosis and treatment, the heterogeneity of precipitating factors, and the typical repeated episodes of decompensation requiring admission to hospital for stabilization. In hospital, care should involve input from an expert in AHF and auditing to ensure that guidelines and protocols for treatment are implemented for all patients. A smooth transition to follow-up care is vital. Patient education programmes could have a dramatic effect on improving outcomes. Information technology should allow, where appropriate, patient telemonitoring and sharing of medical records. Where needed, access to end-of-life care and support for all patients, families, and caregivers should form part of a high-quality service. Eight evidence-based consensus policy recommendations are identified by the author group: optimize patient care transitions, improve patient education and support, provide equity of care for all patients, appoint experts to lead AHF care across disciplines, stimulate research into new therapies, develop and implement better measures of care quality, improve end-of-life care, and promote heart failure prevention.

Isolated cardiac involvement in primary amyloidosis: presenting as sick sinus syndrome and heart failure.

Cardiac amyloidosis is an infiltrative cardiomyopathy with a grave prognosis. Its clinical manifestations include restrictive cardiomyopathy, diastolic heart failure, conduction defects, and arrhythmias. Isolated cardiac involvement and significant conduction disturbances are reported very infrequently. We report a rare case of isolated cardiac involvement in primary amyloidosis, in a 76-year-old man who initially presented with sick sinus syndrome that necessitated permanent pacemaker insertion. Subsequent symptoms of heart failure led to additional evaluation, including an endomyocardial biopsy that revealed primary cardiac amyloidosis. Medical therapy improved the patient's symptoms, and he was discharged from the hospital in stable condition. In addition to discussing the patient's case, we review the relevant medical literature.

Peripartum cardiomyopathy: a review.

Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of any determinable heart disease during the last month of pregnancy or the first 5 months postpartum. The incidence varies worldwide but is high in developing nations; the cause of the disease might be a combination of environmental and genetic factors. Diagnostic echocardiographic criteria include left ventricular ejection fraction <0.45 or M-mode fractional shortening <30% (or both) and end-diastolic dimension >2.7 cm/m(2). Electrocardiography, magnetic resonance imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis and management of peripartum cardiomyopathy. Cardiac protein assays can also be useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin, tumor necrosis factor-α, interleukin-6, interferon-γ, and C-reactive protein in peripartum cardiomyopathy. The prevalence of mutations associated with familial dilated-cardiomyopathy genes in patients with peripartum cardiomyopathy suggests an overlap in the clinical spectrum of these 2 diseases.Treatment for peripartum cardiomyopathy includes conventional pharmacologic heart-failure therapies-principally diuretics, angiotensin-converting enzyme inhibitors, vasodilators, digoxin, ß-blockers, anticoagulants, and peripartum cardiomyopathy-targeted therapies. Therapeutic decisions are influenced by drug-safety profiles during pregnancy and lactation. Mechanical support and transplantation might be necessary in severe cases. Targeted therapies (such as intravenous immunoglobulin, pentoxifylline, and bromocriptine) have shown promise in small trials but require further evaluation. Fortunately, despite a mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset.

Amiloidosis cardíaca con obstrucción dinámica subaórtica / Cardiac Amyloidosis with Dynamic Subaortic Obstruction

La amiloidosis es una enfermedad infiltrativa sistémica que compromete el corazón y representa una causa importante de miocardiopatía restrictiva. En esta presentación se describe el caso de una paciente con insuficiencia cardíaca (IC) secundaria a miocardiopatía infiltrativa por depósito amiloide y obstrucción dinámica del tracto de salida del ventrículo izquierdo. El diagnóstico hematológico fue de mieloma múltiple por cadenas livianas y se demostró amiloidosis en dos tejidos extracardíacos. El ecocardiograma reveló aumento de los espesores parietales con obstrucción dinámica subaórtica significativa y la resonancia cardíaca mostró un patrón compatible con infiltración amiloide. La biopsia endomiocárdica confirmó la amiloidosis cardíaca. La publicación de este caso constituye la primera comunicación en nuestro país de esta forma de presentación atípica de amiloidosis cardíaca.

Primary amyloidosis is a systemic infiltrative disease that compromises the heart and represents an important cause of restrictive cardiomyopathy. We describe the case of a patient with heart failure secondary to an infiltrative cardiomyopathy with amyloid deposition and dynamic left ventricular outflow tract obstruction. The hematological diagnosis was light chain multiple myeloma with presence of amyloidosis in two extracardiac tissues. The echocardiogram revealed substantial wall thickening with significant dynamic subaortic obstruction; the magnetic resonance imaging showed a pattern suggestive of amyloid infiltration. An endomyocardial biopsy confirmed the diagnosis of cardiac amyloidosis. This is the first case of this atypical presentation of cardiac amyloidosis reported in our country.

Usefulness of the Echocardiographic Multi-Parameter Score (EMPS) in evaluating left ventricular global heart function.

In this study, we established a new index by combining several echocardiographic parameters to quantify heart failure. We selected 233 consecutive patients who underwent both echocardiographic and plasma B-type natriuretic peptide (BNP) tests within 24 hours after referral for suspected heart failure. The echocardiographic parameters included systolic function, diastolic function, left ventricular chamber remodeling, valvular lesions, systolic pulmonary arterial pressure, and regional wall-motion abnormality. Each factor was scored from 1 to 3 points according to its severity. The total point from these 6 factors is the echocardiographic multi-parameter score (EMPS).The EMPS for 37, 51, 77, and 38 patients from New York Heart Association (NYHA) functional classes I, II, III, and IV, respectively, were 1.24 ± 1.25, 2.98 ± 1.83, 5.96 ± 2.38, and 7.21 ± 1.99, which were significantly different from the mean score of our 30 normal patients (P <0.001). Sensitivity, specificity, and accuracy of an EMPS ≥2 for diagnosis of NYHA classes II to IV were 93%, 83%, and 89%, respectively. The area under the receiver operating characteristic curve was 0.94 (95% confidence interval, 0.92-0.98; P <0.001). There were significant correlations between logBNP and EMPS (r=0.81, P <0.001) or Tei index (r=0.48, P <0.001). In multilinear regression analysis, EMPS, early/late transmitral flow, and peak systolic velocity from tissue Doppler were entered into the model (P <0.001). The standardized regression coefficient (r=0.68) of EMPS was much higher than those of the other 2 factors, which suggests that EMPS is a powerful predictor of BNP levels.

Ultrassonografia pulmonar na insuficiência cardíaca agudamente descompensada / Pulmonary ultrasonography in acute decompensated heart failure

Objetivos: revisar dados da literatura relacionados ao uso da ultrassonografia pulmonar como método diagnóstico na insuficiência cardíaca agudamente descompensada. Fonte de Dados: artigos pesquisados na base de dados PubMed e edições recentes de livros. Síntese dos Dados: a insuficiência cardíaca descompensada consiste em uma síndrome altamente prevalente nos serviços de emergência. Frequentemente, o diagnóstico diferencial com outras síndromes associadas à insuficiência respiratória aguda representa uma tarefa complexa para o médico da sala de emergência, visto que a análise clínica e a radiografia de tórax não apresentam suficiente especificidade. A ultrassonografia pulmonar vem sendo estudada como uma nova técnica para o diagnóstico de insuficiência cardíaca aguda. Conclusões: a ultrassonografia pulmonar possui boa sensibilidade e especificidade para edema pulmonar intersticial, além de ter baixo custo e ser de fácil aprendizado. Portanto, apresenta boa aplicabilidade para direcionamento diagnóstico, tanto para confirmação de edema intersticial, quanto para exclusão de outras morbidades.

Aims: To review literature data concerning the use of pulmonary ultrasonography as a diagnostic method in acute decompensated heart failure. Source of Data: Articles found in the PubMed database and recent editions of books. Summary of Findings: Acute decompensated heart failure is a highly prevalent condition in the emergency room. The differential diagnosis from other syndromes associated with acute respiratory failure often represents a complex task for the emergency room physician, since clinical examination and chest radiography do not have sufficient specificity. Pulmonary ultrasonography has been studied as a new technique for the diagnosis of acute heart failure. Conclusions: Pulmonary ultrasonography has good sensitivity and specificity for pulmonary interstitial edema, in addition to low cost and ease of learning. Hence it has a good applicability for targeting diagnosis, both for confirmation of interstitial edema and for excluding other illnesses.