Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

BACKGROUND: Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). AIM: To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. POPULATION AND METHODS: Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. RESULTS: The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). CONCLUSION: Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Red blood cell distribution width is a survival predictor beyond anemia and Nt-ProBNP in stable optimally medicated heart failure with reduced ejection fraction outpatients.

BACKGROUND: RDW is an automatic value obtained with the blood count, and represents the erythrocytes dimension variation. OBJECTIVE: To evaluate in optimally medicated outpatients with heart failure with reduced ejection fraction (HFrEF) the RDW prognostic value regarding survival in a multivariable model including anemia and Nt-ProBNP. METHODS: 233 consecutive outpatients, LVEF <40%, clinically stable were followed-up for 3-years in an HF Unit. End-point was all-cause death. The RDW categorized according to the tertiles (T1 = <13.9; T2 14-15.2; T3> = 15.3). Anemia classified according to the WHO criteria. Cox survival model adjusted for clinical profile, optimal therapeutic, renal function, Nt-ProBNP, etiology, atrial fibrillation, and anemia. RESULTS: (1) The 3-years death rate was 33.5%, and increased with the RDW tertiles (17.3%; 25%; 61.1%; p < 0.001). (2) The ROC curve for death associated with RDW (AUC 0.73; p < 0.001); (3) The adjusted death risk increased with the tertiles (Hazard-ratio '[HR] = 1.61; IC 95% 1.09-2.39; p = 0.017). RDW> = 15.3 had greater adjusted death risk than T1 (HR = 2.18; 95% CI 0.99-4.8; p = 0.05) and T1+T2 (HR = 1.54; 95% CI 1.13-2.09; p = 0.006). CONCLUSION: RDW determined in optimally medicated outpatients with HFrEF, during dry-state, is a strong, cheap, and independent predictor of long-term survival.

Left atrial function index predicts long-term survival in stable outpatients with systolic heart failure.

AIMS: Left atrial (LA) function index (LAFI) is a rhythm-independent index that combines LA emptying fraction (LAEF), adjusted LA volume (LAVi), and stroke volume. We evaluated LAFI as a predictor of long-term survival in outpatients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: For 3 years, we followed up 203 outpatients with a left ventricular ejection fraction <40%, who were clinically stable and on optimal therapy. The endpoint was all-cause death. LAFI was calculated as LAFI = ([LAEF × left ventricular outflow tract-velocity time integral]/[LAVi]), and was categorized into quartiles (9.26/16.56/31.92) and median (16.57). Incremental Cox regression models adjusted for significant confounders were used for survival analyses. The 3-year death rate was 30%. Higher quartiles had lower death rates (43.1%/45.1%/25.5%/6%, P < 0.001). The receiver operating characteristic curve for death was associated with LAFI (area under curve = 0.695, 95% CI 0.62-0.77, P < 0.001). In the direct comparison with LAVi and LAEF, LAFI (HRcox 0.93, 95% CI 0.89-0.97, P < 0.001) was the only predictor of survival. LAFI (HRcox 0.95, 95% CI 0.88-1.01, P = 0.099), LAFI quartiles (HR 0.29, 95% CI 0.125-0.672, P=0.004), and LAFI ≥16.57 (HRcox 0.62, 95% CI 0.38-1.02, P=0.058) were adjusted predictors of survival. Subgroup analysis by heart rhythm (sinus vs. atrial fibrillation) showed that LAFI per unit increase and LAFI quartiles were independent predictors of death in both subgroups. CONCLUSION: LAFI determination in HFrEF stable outpatients is a predictor of long-term survival and provides increased prognostic value over a wide range of confounder risk factors.

Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a disease of older people, but the target doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are unknown. OBJECTIVE: To evaluate the association of ACEI/ARB dose level with long-term survival in stable older patients (aged >70 years) and octogenarian outpatients with HFrEF. POPULATION AND METHODS: A total of 138 outpatients aged >70 years (35.5 % > 80 years), with an LVEF <40 % and who were clinically stable on optimal therapy were followed up for 3 years. The ACEI/ARB doses were categorized as: none (0), low (1-50 % target dose), and high (50-100 % target dose). The Cox regression survival model was adjusted for age, ischemic etiology, and renal function. RESULTS: ACEIs/ARBs were prescribed to 91.3 % of patients, and 52.9 % received the high dose. Survival improved with increasing ACEI/ARB dose level in the total population (Hazard Ratio [HR] = 0.67; 95 % confidence interval [CI] 0.55-0.82; p < 0.001), older patients aged >70 years (HR = 0.65; 95 % CI 0.51-0.83; p < 0.001), and octogenarians (HR = 0.71; 95 % CI 0.51-0.99; p = 0.045). The low (HR = 0.35; 95 % CI 0.16-0.76; p = 0.008) and high doses (HR = 0.13; 95 % CI 0.06-0.32; p < 0.001) improved survival compared with not receiving ACEIs/ARBs. The high dose was associated with a better survival than the low dose in the total population (HR = 0.35; 95 % CI 0.19-0.67; p = 0.001) and in a propensity score-matched cohort (HR = 0.41; 95 % CI 0.16-1.02; p = 0.056). In octogenarians, all dose levels were associated with improved survival compared with not receiving ACEIs/ARBs, but there was no difference between ACEI/ARB doses. CONCLUSION: The achieved optimal dose of ACEIs/ARBs in ambulatory older people with HFrEF is associated with long-term survival.

Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients.

The availability of biomarkers to evaluate the risk of cardiovascular diseases is limited. High fibrinogen levels have been identified as a relevant cardiovascular risk factor, but the biological mechanisms remain unclear. Increased aggregation of erythrocytes (red blood cells) has been linked to high plasma fibrinogen concentration. Here, we show, using atomic force microscopy, that the interaction between fibrinogen and erythrocytes is modified in chronic heart failure patients. Ischaemic patients showed increased fibrinogen-erythrocyte binding forces compared with non-ischaemic patients. Cell stiffness in both patient groups was also altered. A 12-month follow-up shows that patients with higher fibrinogen-erythrocyte binding forces initially were subsequently hospitalized more frequently. Our results show that atomic force microscopy can be a promising tool to identify patients with increased risk for cardiovascular diseases.

Serial measurements of the Nt-ProBNP during the dry state in patients with systolic heart failure are predictors of the long-term prognosis.

OBJECTIVE: To evaluate the long-term predictive value of serial Nt-ProBNP during dry-state in patients with systolic heart failure (SHF). METHODS: Nt-ProBNP was measured quarterly during a 6-month dry-state period in 40 SHF outpatients. EVENTS: all-cause mortality or hospitalization. FOLLOW-UP: 5 years. RESULTS: The Nt-ProBNP >1000 pg/ml (baseline and 6 months) and the variation rate (VR) >30% were independently associated with the survival and composite endpoint curve. VR >30% added significant prognostic information to the single Nt-ProBNP 1000 pg/ml cut-off. Patients with at least one Nt-ProBNP determination >1000 pg/ml were at greater risk of death. CONCLUSION: Serial Nt-ProBNP measurements in patients with SHF during the dry-state are strong predictors of the long-term prognosis.

The importance of assessing nutritional status in elderly patients with heart failure.

Heart failure (HF) is a syndrome characterized by high morbidity and mortality, despite advances in medical and device therapy that have significantly improved survival. The outcome of HF in elderly patients results from a combination of biological, functional, psychological, and environmental factors, one of which is nutritional status. Malnutrition, as well as HF, is frequently present with aging. Early detection might lead to earlier intervention. It is our goal to review the importance of nutritional status in elderly patients with HF, as well as tools for assessing it. We also propose a simple decision algorithm for the nutritional assessment of elderly patients with HF.

Heart rate reduction with ivabradine in patients with acute decompensated systolic heart failure.

INTRODUCTION: In patients with acute decompensated systolic heart failure (ADSHF) high resting heart rate (HR) could be either a compensatory mechanism or contribute to worsening heart failure. The aim of this study was to evaluate, in patients with ADSHF and resting HR >70 bpm, the early (within 24 h) and late (at discharge) effects of oral administration of ivabradine on HR reduction. METHODS: Ten consecutive patients with ADSHF, left ventricular ejection fraction <40 % and HR >70 bpm, without other acute conditions or inotropic therapy, began open-label treatment with oral ivabradine according to a pre-established Heart Failure Unit protocol. We obtained clinical and laboratory data at four periods: admission (T0), immediately before initiation of ivabradine (T2), 24 h after initiation of ivabradine (T3), and at discharge (T4). RESULTS: Ivabradine was administered in 60 % of the patients before the second day. HR decreased 10.7 ± 7.2 bpm at T3 (p < 0.001) and 16.3 ± 8.2 bpm at T4 (p = 0.002). The systolic blood pressure decreased at T3 (p = 0.012), returning to baseline values at T4. There was no change in diastolic and mean blood pressure. New York Heart Association (NYHA) class improvement by two levels was associated with lower HR at T4 (p = 0.033). HR and N-terminal pro-brain natriuretic peptide (Nt-ProBNP) at baseline correlated significantly [Spearman correlation coefficient (rs) = 0.789, p = 0.013]. Total Nt-ProBNP reduction correlated with the HR before (r = 0.762, p = 0.028) and after (T3: r = 0.647, p = 0.083; T4: r = 0.738, p = 0.037) ivabradine addition. CONCLUSION: In the present cohort of patients with ADSHF and HR >70 bpm, the selective reduction of HR with oral ivabradine was safe and efficient.

Early NT-proBNP decrease with ivabradine in ambulatory patients with systolic heart failure.

BACKGROUND: Heart rate (HR) reduction in patients with systolic heart failure (HF) is a cornerstone of current therapy. The aim of this study was to evaluate the short-term effect of the HR reduction with ivabradine on N-terminal pro-brain natriuretic peptide (NT-proBNP) in outpatients with systolic HF. HYPOTHESIS: Ivabradine improves survival and promotes left ventricle remodelling by reducing resting heart rate. Nt-ProBNP absolute and trends predict prognosis. We hypothesized a possible association between heart rate decrease and Nt-ProBNP values. METHODS: We included 25 outpatients with systolic HF on optimized medical therapy (80% on angiotensin-converting enzyme inhibitors, 56% on spironolactone, and 88% on ß-blocker therapy), left ventricle ejection fraction <40%, and sinus rhythm and HR >70/bpm. After a 1 month running-out period, to establish the clinical and NT-proBNP stability, patients were started on ivabradine for 3 months. RESULTS: Ivabradine decreased NT-proBNP (P = 0.002) from a median of 2850 pg/mL to 1802 pg/mL, corresponding to a median absolute and percent decrease of 964 pg/mL and 44.5%, respectively. The baseline HR correlated significantly with the baseline NT-proBNP (rs = 0.411, P = 0.041). The absolute and percent HR decrease correlated with the absolute NT-proBNP decrease (rs = 0.442, P = 0.027; rs = 0.395, P = 0.05). The greater the NT-proBNP absolute decrease tertile, the greater the baseline HR (P = 0.023) and the absolute (P = 0.028) and percent (P = 0.064) HR variation. CONCLUSIONS: In outpatients with systolic HF, the NT-proBNP reduction obtained by short-term ivabradine treatment correlates closely with the degree of HR reduction.

[Constrictive pericarditis - new methods in the diagnosis of an old disease: a case report]. / Pericardite constritiva - novos métodos no diagnóstico de uma velha doença: a propósito de um caso clínico.

Constrictive pericarditis is a rare clinical entity that can pose diagnostic problems. The gold standard for diagnosis is cardiac catheterization with analysis of intracavitary pressure curves, which are high and, in end-diastole, equal in all chambers. The diastolic profile in both ventricles presents the classic dip-and-plateau pattern and the difference between the diastolic pressures of both ventricles should not exceed 3-5mmHg. Unfortunately, these traditional criteria are not always present and in fact the sensitivity and specificity of equalization of diastolic pressures are relatively low and of limited value in individual patients. This highlights the need to use new cardiac imaging techniques to resolve any doubts. The case described here is a good example.

[Takotsubo syndrome or acute myocarditis? The role of cardiac magnetic resonance imaging]. / Síndroma de takotsubo ou miocardite aguda? O papel da ressonância magnética cardíaca.

Acute myocarditis is often misdiagnosed, and its evolution is not always benign; correct and prompt diagnosis is therefore essential. We report the case of a 62-year-old woman with chest pain after a stressful event and ST-segment elevation on the electrocardiogram, in whom urgent cardiac catheterization showed normal coronary arteries and left ventricular apical ballooning, suggesting takotsubo syndrome. However, cardiac magnetic resonance imaging showed lesions typical of acute myocarditis, thus suggesting this diagnosis. We highlight the diagnostic difficulty in patients with chest pain, elevated troponin and normal coronary arteries, and the key role of cardiac magnetic resonance in differential diagnosis.

Thrombosed aneurysm of the left sinus of valsalva presenting as an intramyocardial mass.

Aneurysms of the sinuses of Valsalva are uncommon in clinical practice. Most are congenital, but secondary causes are also recognized. Congenital aneurysms of the left sinus of Valsalva are particularly rare. The authors report a fatal case in which a nonruptured aneurysm of the left sinus of Valsalva dissected into the interventricular septum and presented as heart failure. The concurrent presence of dilated cardiomyopathy and the mechanisms that may have led to it are discussed on the basis of the anatomic and histologic features found at autopsy.

Behind heart failure syndrome: remember AL amyloidosis. Two case-reports.

Amyloidosis is a systemic disease that is a consequence of extracellular deposition of insoluble fibrils composed of subunits of low molecular weight (5-25 kD) derived from a variety of plasma proteins. Identification of the amyloidogenic protein determines the type of amyloidosis. In primary systemic amyloidosis (classically called AL amyloidosis), the amyloid protein is composed of light chains resulting from plasma-cell dyscrasia. Cardiac manifestations are the most common clinical presentation of this type of amyloidosis, occurring in 50% of patients. The authors describe two cases in which hospitalization was due to decompensated heart failure, which were similar in their etiology (multiple myeloma/amyloid cardiomyopathy) and evolution (sudden death). The authors wish to draw attention to an entity that is rarely encountered in clinical practice and that requires a high index of suspicion.

Acquired left ventricular-to-right atrial shunt (Gerbode defect) due to infective endocarditis.

Left ventricular-to-right atrial communications are a rare type of ventricular septal defect, known as the Gerbode defect. They are usually congenital, but rare cases have been described secondary to bacterial endocarditis. The authors present a rare case of Gerbode defect and severe pericardial effusion secondary to Staphylococcus aureus endocarditis, in a patient with alcoholic liver cirrhosis.

Left ventricular non-compaction: a new mutation predisposing to reverse remodeling?

Left ventricular non-compaction (LVNC) is a rare disorder of endomyocardial morphogenesis that results in multiple trabeculations and deep intertrabecular recesses filled with direct blood flow from the left ventricular cavity. LVNC is attracting increasing interest as a model for the study of cardiomyopathies, since it is a genetically heterogeneous disorder which varies greatly in clinical presentation and age of onset. The authors present the case of a young black male with progressive congestive heart failure of 2-3 years' evolution. The investigation, which included transthoracic echocardiography (contrast and 3D), transesophageal echocardiography and cardiac magnetic resonance imaging, showed LVNC and severe aortic regurgitation, with severe left ventricular systolic dysfunction. The family history was suggestive of genetically transmitted disease and genetic study of the TAZ gene at locus Xq28 identified the mutation p.Phe128Ser (c.383T>C), the first description of this mutation in a patient with LVNC. The patient underwent aortic valve replacement, with excellent clinical evolution, regression of left ventricular dimensions and global systolic functio Aortic regurgitation (not related to LVNC) was the determining factor in the clinical expression. However, the excellent reverse remodeling that occurred after surgery highlights the heterogeneity of myocardial behavior in LVNC patients.

Isolated ventricular noncompaction: a case report.

Isolated ventricular noncompaction is an extremely rare cardiomyopathy, not fully clarified.It is characterized by persistent embryonic myocardium morphology without associated cardiac abnormalities.Since first description in 1984, few clinical studies were done. Data in the literature are lacking and most reports consist on a few case studies.Doppler ecocardiogram is considered the reference method for diagnosis.Diagnosis remains difficult since there are similarities with other cardiac defects, clinical manifestations are non-specific and echocardiographic criteria are not universally accepted.As a consequence diagnosis may be easily missed.Moreover, clinical and echocardiographic features were just recently clarified.Treatment is directed towards important clinical manifestations (heart failure, arrhythmias and embolic events).We present a clinical case of severe cardio-respiratory failure in previously healthy and asymptomatic young male, which was the initial presentation of an isolated ventricular noncompaction.A brief review of available literature is done concerning to this case study.

Evaluation of the clinical, hemodynamic and neurohormonal response to levosimendan administration in decompensated heart failure patients. One-month follow-up.

INTRODUCTION: Levosimendan is an inodilatory drug with hemodynamic effects in patients with decompensated chronic heart failure. AIM: Short-term (one month) evaluation of clinical, hemodynamic and neurohormonal changes in patients with decompensated chronic heart failure undergoing levosimendan therapy. METHODS: Twenty-six (21 male) consecutive patients were studied, corresponding to 32 levosimendan administrations (bolus + 24h infusion), aged 56.7+/-13.0 years, with decompensated chronic heart failure, in NYHA functional class III-IV (78.1% in class IV), and cardiac index (CI) <2.5 l/min/m2. Clinical (NYHA class), non-invasive hemodynamic (echocardiography) and neurohormonal (Elecsys ECLIA NT-ProBNP) evaluations were performed before levosimendan administration and on days 1, 4, 10 and 30. RESULTS: 1) Until day 10, there was a progressive decrease in NT-ProBNP values and weight (p<0.001), with an increase in CI (p<0.001); 2) NYHA functional class improved progressively, with 76% of the patients in NYHA class II at day 30; 3) NT-ProBNP values at day 1 correlated inversely (r=-0.414; p=0.024) with CI at day 4; and 4) the absolute decrease in NT-ProBNP values at day 4 (relative to baseline values) correlated with weight loss at day 4 (r=0.495, p=0.005), day 10 (r=0.424, p=0.031) and day 30 (r=0.486, p=0.030). CONCLUSION: Levosimendan therapy in patients with decompensated chronic heart failure contributes to progressive NYHA class improvement. The variations seen in NYHA class and hemodynamics was reflected in changes in NT-ProBNP.

Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction.

The objective of this study was to evaluate the long-term predictive value of the haemostatic, inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 +/- 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leukoactivity, leukocyte count, membrane fluidity, prognosis cyte count (7833.0 +/- 1696.0 vs. 10294.0 +/- 3129.0; p = 0.011), lower PtC (100.65 +/- 19.08 vs.81.25 +/- 19.95; p = 0.002), and lower erythrocyte aggregation (14.26 +/- 5.94 vs. 11.47 +/- 3.45; p = 0.031) in relation to the ones without events; (ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045-0.628; p = 0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 - 0.393; p = 0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 - 0.876; p = 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances, at hospital discharge, are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.