Implications of the Hemodynamic Optimization Approach Guided by Right Heart Catheterization in Patients with Severe Heart Failure

OBJECTIVE: To report the hemodynamic and functional responses obtained with clinical optimization guided by hemodynamic parameters in patients with severe and refractory heart failure. METHODS: Invasive hemodynamic monitoring using right heart catheterization aimed to reach low filling pressures and peripheral resistance. Frequent adjustments of intravenous diuretics and vasodilators were performed according to the hemodynamic measurements. RESULTS: We assessed 19 patients (age = 48±12 years and ejection fraction = 21±5%) with severe heart failure. The intravenous use of diuretics and vasodilators reduced by 12 mm Hg (relative reduction of 43%) pulmonary artery occlusion pressure (P<0.001), with a concomitant increment of 6 mL per beat in stroke volume (relative increment of 24%, P<0.001). We observed significant associations between pulmonary artery occlusion pressure and mean pulmonary artery pressure (r=0.76; P<0.001) and central venous pressure (r=0.63; P<0.001). After clinical optimization, improvement in functional class occurred (P< 0.001), with a tendency towards improvement in ejection fraction and no impairment to renal function. CONCLUSION: Optimization guided by hemodynamic parameters in patients with refractory heart failure provides a significant improvement in the hemodynamic profile with concomitant improvement in functional class. This study emphasizes that adjustments in blood volume result in imme-diate benefits for patients with severe heart failure.

The Role of B-Type Natriuretic Peptide in the Diagnosis of Congestive Heart Failure in Patients Presenting to an Emergency Department with Dyspnea

OBJECTIVE: To determine the utility of B-type natriuretic peptide (BNP) in the diagnosis of congestive heart failure (CHF) in patients presenting with dyspnea to an emergency department (ED). METHODS: Seventy patients presenting with dyspnea to an ED from April to July 2001 were included in the study. Mean age was 72±16 years and 33 (47%) were male. BNP was measured in all patients at the moment of admission to the ED. Emergency-care physicians, blinded to BNP values, were required to assign a probable initial diagnosis. A cardiologist retrospectively reviewed the data (blinded to BNP measurements) and assigned a definite diagnosis, which was considered the gold standard for assessing the diagnostic performance of BNP. RESULTS: The mean BNP concentration was higher in patients with CHF (n=36) than in those with other diagnoses (990±550 vs 80±67 pg/mL, p<0.0001). Patients with systolic dysfunction had higher BNP levels than those with preserved systolic function (1,180±641 vs 753±437 pg/mL, p=0.03). At a blood concentration of 200 pg/mL, BNP showed a sensitivity of 100%, specificity of 97.1%, positive predictive value of 97.3%, and negative predictive value of 100%. The application of BNP could have potentially corrected all 16 cases in which the diagnosis was missed by the emergency department physician. CONCLUSION: BNP measurement is a useful tool in the diagnosis of CHF in patients presenting to the ED with dyspnea.

Assessing Strategies for Heart Failure with Preserved Ejection Fraction at the Outpatient Clinic

Background: Heart failure with preserved ejection fraction (HFPEF) is the most common form of heart failure (HF), its diagnosis being a challenge to the outpatient clinic practice. Objective: To describe and compare two strategies derived from algorithms of the European Society of Cardiology Diastology Guidelines for the diagnosis of HFPEF. Methods: Cross-sectional study with 166 consecutive ambulatory patients (67.9±11.7 years; 72% of women). The strategies to confirm HFPEF were established according to the European Society of Cardiology Diastology Guidelines criteria. In strategy 1 (S1), tissue Doppler echocardiography (TDE) and electrocardiography (ECG) were used; in strategy 2 (S2), B-type natriuretic peptide (BNP) measurement was included. Results: In S1, patients were divided into groups based on the E/E'ratio as follows: GI, E/E'> 15 (n = 16; 9%); GII, E/E'8 to 15 (n = 79; 48%); and GIII, E/E'< 8 (n = 71; 43%). HFPEF was confirmed in GI and excluded in GIII. In GII, TDE [left atrial volume index (LAVI) ≥ 40 mL/m2; left ventricular mass index LVMI) > 122 for women and > 149 g/m2 for men] and ECG (atrial fibrillation) parameters were assessed, confirming HFPEF in 33 more patients, adding up to 49 (29%). In S2, patients were divided into three groups based on BNP levels. GI (BNP > 200 pg/mL) consisted of 12 patients, HFPEF being confirmed in all of them. GII (BNP ranging from 100 to 200 pg/mL) consisted of 20 patients with LAVI > 29 mL/m2, or LVMI ≥ 96 g/m2 for women or ≥ 116 g/m2 for men, or E/E'≥ 8 or atrial fibrillation on ECG, and the diagnosis of HFPEF was confirmed in 15. GIII (BNP < 100 pg/mL) consisted of 134 patients, 26 of whom had the diagnosis of HFPEF confirmed when GII parameters were used. Measuring BNP levels in S2 identified 4 more patients (8%) with HFPEF as compared with those identified in S1. Conclusion: The association of BNP measurement and TDE data is better than the isolated use of those parameters. BNP can be useful in identifying patients whose diagnosis of HF had been previously excluded based only on TDE findings.

I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes

Background:Heart failure (HF) is one of the leading causes of hospitalization in adults in Brazil. However, most of the available data is limited to unicenter registries. The BREATHE registry is the first to include a large sample of hospitalized patients with decompensated HF from different regions in Brazil.Objective:Describe the clinical characteristics, treatment and prognosis of hospitalized patients admitted with acute HF.Methods:Observational registry study with longitudinal follow-up. The eligibility criteria included patients older than 18 years with a definitive diagnosis of HF, admitted to public or private hospitals. Assessed outcomes included the causes of decompensation, use of medications, care quality indicators, hemodynamic profile and intrahospital events.Results:A total of 1,263 patients (64±16 years, 60% women) were included from 51 centers from different regions in Brazil. The most common comorbidities were hypertension (70.8%), dyslipidemia (36.7%) and diabetes (34%). Around 40% of the patients had normal left ventricular systolic function and most were admitted with a wet-warm clinical-hemodynamic profile. Vasodilators and intravenous inotropes were used in less than 15% of the studied cohort. Care quality indicators based on hospital discharge recommendations were reached in less than 65% of the patients. Intrahospital mortality affected 12.6% of all patients included.Conclusion:The BREATHE study demonstrated the high intrahospital mortality of patients admitted with acute HF in Brazil, in addition to the low rate of prescription of drugs based on evidence.

Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.

Ergospirometry and Echocardiography in Early Stage of Heart Failure with Preserved Ejection Fraction and in Healthy Individuals

AbstractBackground:Heart failure with preserved ejection fraction is a syndrome characterized by changes in diastolic function; it is more prevalent among the elderly, women, and individuals with systemic hypertension (SH) and diabetes mellitus. However, in its early stages, there are no signs of congestion and it is identified in tests by adverse remodeling, decreased exercise capacity and diastolic dysfunction.Objective:To compare doppler, echocardiographic (Echo), and cardiopulmonary exercise test (CPET) variables - ergospirometry variables - between two population samples: one of individuals in the early stage of this syndrome, and the other of healthy individuals.Methods:Twenty eight outpatients diagnosed with heart failure according to Framingham’s criteria, ejection fraction > 50% and diastolic dysfunction according to the european society of cardiology (ESC), and 24 healthy individuals underwent Echo and CPET.Results:The group of patients showed indexed atrial volume and left ventricular mass as well as E/E’ and ILAV/A´ ratios significantly higher, in addition to a significant reduction in peak oxygen consumption and increased VE/VCO2 slope, even having similar left ventricular sizes in comparison to those of the sample of healthy individuals.Conclusion:There are significant differences between the structural and functional variables analyzed by Echo and CPET when comparing two population samples: one of patients in the early stage of heart failure with ejection fraction greater than or equal to 50% and another of healthy individuals.

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure

Background:Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.Objective:We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.Methods:Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.Results:Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).Conclusion:These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.

Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry

Abstract Background: The use of aortic counterpulsation therapy in advanced heart failure is controversial. Objectives: To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP) and its impact on 30-day mortality in patients with heart failure. Methods: Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). We analyzed changes in oxygen central venous saturation (ScvO2), arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test. Results: A total of 223 patients (mean age 49 ± 14 years) were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO2 (50.5% vs. 65.5%, p < 0.001) and use of nitroprusside (33.6% vs. 47.5%, p < 0.001), and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001) and use of vasopressors (36.3% vs. 25.6%, p = 0.003) after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008). Conclusion: After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation.

Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure

Background: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (v̇O2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. Objective: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. Methods: Eighty-three patients (58 ± 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (v̇O2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). Results: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 ± 7%) and low peak v̇O2 (15.2 ± 3.1 mL.kg-1.min-1). HRP (113 ± 19 bpm) was higher than HRAT (92 ± 14 bpm; p < 0.05) and HR6MWT (94 ± 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). Conclusion: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

Background: Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective: To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods: The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results: Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion: In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

Abstract Background: Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. Objectives: The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. Methods: A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Results: Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. Conclusions: This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

Abstract Background: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods: Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results: 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions: In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction

Abstract Background: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. Objectives: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Methods: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. Results: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Conclusion: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.