Serum biochemical determinants of peripheral congestion assessed by bioimpedance vector analysis in acute heart failure.

BACKGROUND: The pathophysiology of peripheral congestion is poorly investigated in patients with acute heart failure (AHF). OBJECTIVES: to evaluate the relative contribution of serum colloid osmotic pressure (COP), relative plasma volume status (PVS), biomarkers of renal function, electrolytes, haemoglobin, and brain natriuretic peptide (BNP) in peripheral fluid overload using bioimpedance vector analysis (BIVA). METHODS: We retrospectively analysed data from 485 patients with AHF. Hydration status was evaluated by semiquantitative and quantitative approach using BIVA (R/Xc graph) and Hydration Index (HI), respectively. COP was calculated from albumin and total protein concentration, while relative PVS was calculated from validated equations. RESULTS: Congestion assessed by BIVA was observed in 304 (63%) patients and classified as mild (30%), moderate (42%), and severe (28%). On univariate analysis, HI was inversely correlated with COP (P < 0.01), glomerular filtration rate (P < 0.01), and haemoglobin (P < 0.01), while positive correlations were found for relative PVS (P < 0.05), BNP (P < 0.01), and blood urea nitrogen (BUN; P < 0.01). On stepwise multivariate analysis, COP explained 12% of the total variability, while BUN, PVS, haemoglobin, and BNP added a further 6%, 4%, 2%, and 1%, respectively, to the final explanatory model. CONCLUSIONS: COP was the major determinant of the presence and entity of peripheral congestion assessed by BIVA. BUN, PVS, haemoglobin, and BNP revealed reduced influence on congestion as compared with COP. Routine laboratory testing could be useful in peripheral fluid accumulation. Future studies should evaluate the relationship between COP and pharmacological target therapies for the fluid management of AHF patients.

Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

BACKGROUND AND PURPOSE: Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. METHODS: The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. RESULTS: Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ2 was 4.12 (P=0.249) and 1.20 (P=0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ2 was 8.86 (P=0.115) and 34.50 (P=0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P=0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P=0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. CONCLUSIONS: This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management.

Accuracy of bioimpedance vector analysis and brain natriuretic peptide in detection of peripheral edema in acute and chronic heart failure.

OBJECTIVE: To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF). BACKGROUND: BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF. METHODS: 487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests. RESULTS: BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p < 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p < 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was >870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was >216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF. CONCLUSIONS: In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.

Renal dysfunction and accuracy of N-terminal pro-B-type natriuretic peptide in predicting mortality for hospitalized patients with heart failure.

BACKGROUND: Renal dysfunction may confound the clinical interpretation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. This study investigated whether renal dysfunction influences the prognostic accuracy of NT-proBNP in acute decompensated heart failure (ADHF). METHODS AND RESULTS: We studied 908 ADHF patients. The primary outcome was 12-month mortality. Interaction between estimated glomerular filtration rate (eGFR) and NT-proBNP in predicting mortality was tested with the likelihood ratio test. The patients were classified into 3 eGFR strata: ≥60, 30-59, and <30 ml·min(-1)·1.73 m(-2). Cox models were used to calculate the adjusted hazard ratios (HR) for NT-proBNP, modeled as a dichotomous or categorized variable, within each level of eGFR. NT-proBNP was categorized using optimal cut-offs defined in ROC analysis for each eGFR level. A total of 234 patients (25.8%) died. Testing for interaction was not significant (χ(2)=0.29; P=0.5928). The adjusted HR for NT-proBNP >5,180 pg/ml was 2.09 (P<0.001) in the highest, 1.7 (P<0.001) in the intermediate, and 3.33 (P=0.010) in the lowest eGFR level. The adjusted HR for NT-proBNP above the optimal cut-offs defined on ROC analysis were 1.5 (P=0.239), 2.2 (P<0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics. CONCLUSIONS: There was no evidence of interaction between eGFR and NT-proBNP in predicting mortality. The NT-proBNP cut-off of 5,180 ng/L provided independent prognostic information, irrespective of the level of residual renal function.

The ADHF/NT-proBNP risk score to predict 1-year mortality in hospitalized patients with advanced decompensated heart failure.

BACKGROUND: The acute decompensated heart failure/N-terminal pro-B-type natriuretic peptide (ADHF/NT-proBNP) score is a validated risk scoring system that predicts mortality in hospitalized heart failure patients with a wide range of left ventricular ejection fractions (LVEFs). We sought to assess discrimination and calibration of the score when applied to patients with advanced decompensated heart failure (AHF). METHODS: We studied 445 patients hospitalized for AHF, defined by the presence of severe symptoms of worsening HF at admission, severely depressed LVEF, and the need for intravenous diuretic and/or inotropic drugs. The primary outcome was cumulative (in-hospital and post-discharge) mortality and post-discharge 1-year mortality. Separate analyses were performed for patients aged ≤ 70 years. A Seattle Heart Failure Score (SHFS) was calculated for each patient discharged alive. RESULTS: During follow-up, 144 patients (32.4%) died, and 69 (15.5%) underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. After accounting for the competing events (VAD/HT), the ADHF/NT-proBNP score's C-statistic for cumulative mortality was 0.738 in the overall cohort and 0.771 in patients aged ≤ 70 years. The C-statistic for post-discharge mortality was 0.741 and 0.751, respectively. Adding prior (≤6 months) hospitalizations for HF to the score increased the C-statistic for post-discharge mortality to 0.759 in the overall cohort and to 0.774 in patients aged ≤ 70 years. Predicted and observed mortality rates by quartiles of score were highly correlated. The SHFS demonstrated adequate discrimination but underestimated the risk. The ADHF/NT-proBNP risk calculator is available at http://www.fsm.it/fsm/file/NTproBNPscore.zip. CONCLUSIONS: Our data suggest that the ADHF/NT-proBNP score may efficiently predict mortality in patients hospitalized with AHF.

A novel design of ventricular assist device: an in vitro feasibility study.

Left ventricular assist devices (LVADs) work as a bypass between the left ventricular apex and the ascending aorta. The surgical procedure for their insertion requires the opening of the cardiac cavities and the dissection of the great vessels, the blood is constrained to flow through the device components and the risk can be run of thrombogenesis, haemolysis and infections. A possible strategy to overcome this limitation consists in utilizing external systems that assist the heart in its contraction from the outside without directly transporting the blood. In this study we conduct the feasibility analysis of a novel external LVAD design that does not require the opening of the cardiac cavities and the dissection of the great vessels and that allows the removal procedure to be easily achieved. The device, including a stepper motor, three metallic wires and three elastic elements, works alternatively between a contraction condition where it induces an elastic compulsion on the heart and a release condition where it elastically releases the organ. The values of force acting on the wires and the values of current supplied to the motor were measured and utilized for a preliminary study design. The experimental measurements demonstrated the feasibility of the system.

The glucocorticoid in acute decompensated heart failure: Dr Jekyll or Mr Hyde?

Glucocorticoid administration is not recommended in patients with heart failure because of its related sodium and fluid retention. However, previous experimental and clinical studies have demonstrated that glucocorticoids can also induce a diuretic effect and improve renal function in patients with acute decompensated heart failure (ADHF) with refractory diuretic resistance. We report the case of a 65-year-old man with a known diagnosis of aortic stenosis, systolic ventricular dysfunction, and chronic obstructive pulmonary disease who was admitted for ADHF. After 3 days, during which resistance to conventional therapy was observed, intravenous methylprednisolone (60 mg/d) was added to ongoing medical treatment. Three days after the onset of glucocorticoid therapy, daily urine volume progressively increased (up to 5.8 L/d). Concurrently, signs and symptoms of congestion improved, the weight and brain natriuretic peptide plasma levels decreased (−7 kg and −46%, respectively) and glomerular filtration rate increased (+26%). Bioimpedance vector analysis showed a net reduction of fluid content (from 88.4% to 73.6% of hydration at discharge). In conclusion, this case report suggests that in a patient with ADHF and congestion resistant to diuretic therapy, glucocorticoid administration is safe and associated with improvement in congestion, neurohormonal status, and renal function. These data support the possible usefulness of glucocorticoids in this setting.

Inpatient cardiac rehabilitation soon after hospitalization for acute decompensated heart failure: a propensity score study.

PURPOSE: Postdischarge management of acute decompensated heart failure (ADHF) remains an ongoing challenge. We sought to assess whether inpatient cardiac rehabilitation (CR) soon after hospitalization for ADHF improves outcome. METHODS: Patients (N = 275) hospitalized for ADHF were enrolled. The primary outcome was a composite of all-cause mortality and urgent heart transplantation (UHT) at 1 year. The followup started at the time of discharge from the acute care setting. Because of the observational nature of the study, a propensity score analysis was used to predict the likelihood of undergoing CR. A multivariable Cox regression analysis adjusted for propensity score was used to assess the effect of CR on the primary outcome. RESULTS: Of the 275 patients, 130 underwent CR. Among the baseline variables of the index hospitalization for ADHF, propensity score derivation identified male gender, New York Heart Association Class IV, refractory HF, moderate to severe mitral or tricuspid regurgitation, nonuse of renin-angiotensin-aldosterone system inhibitors, and daily dosage of furosemide, as being independently associated with the likelihood of undergoing CR. No patient was lost to followup. During the 12-month followup, 74 patients died and 3 underwent UHT. The overall incidence of the primary outcome was 28%. On propensity score-adjusted Cox multivariable analysis, the relative risk of the primary outcome for participants in CR compared with nonparticipants in CR was 0.58 (confidence interval [CI]: 0.34-0.99; P = .04). CONCLUSIONS: Results suggest that the strategy of inpatient CR soon after discharge from the acute care setting improves 1-year UHT-free survival of patients with ADHF.

Ventricular repolarization dynamicity provides independent prognostic information toward major arrhythmic events in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this work was to evaluate whether ventricular repolarization dynamicity predicts major arrhythmic events in patients with idiopathic dilated cardiomyopathy (DCM). BACKGROUND: Arrhythmic risk stratification in patients with DCM is still an open issue. Ventricular repolarization analysis should provide relevant information, but QT interval and QT dispersion failed in predicting arrhythmic risk. METHODS: The following parameters were evaluated in 179 consecutive DCM patients without history of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) at enrollment: QRS duration, QT interval corrected for heart rate, and QT dispersion at electrocardiogram (ECG); left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter at echocardiogram; and nonsustained ventricular tachycardia (NSVT), heart rate variability (standard deviation of RR intervals), and ventricular repolarization dynamicity as measured by means of 24-h ECG monitoring, by calculating the slope of linear regression analysis of QT end and RR intervals (QTe-slope) and the value of mean QT end corrected for heart rate. RESULTS: During a mean follow-up of 39 months, 9 patients died suddenly and 15 experienced VT and/or VF. At multivariate analysis, LVEF (p = 0.047), NSVT (p = 0.022), and QTe-slope (p = 0.034) were significantly associated with arrhythmic events. Among the patients with a low LVEF, NSVT and/or steeper QTe-slope identified a subgroup at highest arrhythmic risk. CONCLUSIONS: In patients with DCM, QT dynamicity is independently associated with the occurrence of major arrhythmic events and improves the predictive accuracy of stratifying arrhythmic risk of these patients.

Short-term change in distance walked in 6 min is an indicator of outcome in patients with chronic heart failure in clinical practice.

OBJECTIVES: The purpose of this study was to investigate the prognostic value of change in distance walked in 6 min in chronic heart failure (CHF). BACKGROUND: The strongest indication for the 6-min walking test (6MWT) is for measuring the response to therapeutic interventions in patients with CHF. Whether the increase in distance walked after a therapeutic intervention translates into improved clinical outcome is largely unknwon. METHODS: We studied 476 CHF patients with left ventricular systolic dysfunction who were referred to our institution for adjustment of heart failure therapy because of persisting or worsening symptoms. Adjustment of therapy involved four classes of drugs: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop diuretics, and aldosterone antagonists. A standardized 6MWT was performed at baseline and at discharge. RESULTS: After 15.2 +/- 8 days, the distance walked increased from 326 +/- 107 m to 408 +/- 109 m (+25%; p = 0.001). During a mean follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac transplantation. Among a set of variables, New York Heart Association functional class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and change in distance walked (p = 0.002) were significant independent predictors of survival. When the patients were divided into two subgroups according to the median value of the distance walked at baseline, the increase in walking distance was significantly associated with survival only in the subgroup of patients who walked <340 m at baseline. CONCLUSIONS: Our data indicate that repeating a 6MWT after drug intervention provides independent prognostic information in CHF patients with more compromised exercise capacity.

Deep vein thrombosis among patients entering cardiac rehabilitation after coronary artery bypass surgery.

BACKGROUND: Little information is available about the prevalence of deep vein thrombosis (DVT) after discharge from cardiac surgery units and its impact on rehabilitation programs. OBJECTIVES: To estimate the rate of DVT, in relation to different thromboprophylaxis strategies, in patients with a recent coronary artery bypass graft (CABG) entering cardiac rehabilitation. METHODS: Two hundred seventy consecutive patients admitted to three rehabilitation facilities after CABG surgery from 19 cardiac surgery units (male patients, 81%; mean +/- SD age, 64 +/- 9 years; interval after operation, 4 to 19 days) underwent serial leg venous ultrasound examination on admission to three rehabilitative units. RESULTS: At admission, antiplatelet treatment was present in all patients except 10 with absolute contraindications. In 171 patients (63%), heparin prophylaxis (low-molecular-weight heparin once daily, 87%; unfractionated heparin twice daily, 13%) was reported, limited to the early postoperative period (< or = 3 days) in 102 patients (38%). DVT was detected in 47 patients (17.4%). The rate of proximal and isolated distal DVT was 2.6% (7 cases) and 14.8% (40 cases), respectively. DVT was complicated in two cases (0.7%) by symptomatic pulmonary embolism, fatal in one case (0.4%). Clots were found in the leg contralateral to the saphenous vein harvest site in half of all DVT cases. Forty-three DVT cases (91%) were diagnosed at admission, while serial ultrasound testing allowed diagnosis of an additional 4 distal DVT cases. At multivariate analysis, female sex (p < 0.001) and length of stay in the surgery unit > 8 days (p < 0.05) were independently associated with risk of DVT in the rehabilitation setting. The adoption of heparin prophylaxis until discharge predicted the absence of DVT after adjustment for immobility (p < 0.05). CONCLUSIONS: This study showed a high rate of DVT in patients entering cardiac rehabilitation after CABG surgery. Wearing unilateral graded compression stockings after CABG surgery had limited efficacy, as clots were often localized in legs contralateral to the saphenous vein harvest site.

QT-interval prolongation in right precordial leads: an additional electrocardiographic hallmark of Brugada syndrome.

OBJECTIVES: The aim of this study was to evaluate whether the occurrence of the Brugada Syndrome typical electrocardiogram (ECG) pattern (i.e., right bundle branch block, coved-type ST-segment elevation, and T-wave inversion in the right precordial leads) is characterized by a concomitant lengthening of QT intervals in the right precordial leads. BACKGROUND: It has been suggested that the typical ECG pattern of Brugada syndrome is due to a decreased net inward current during phase 1 of the action potential, which also leads to its prolongation in the right epicardium. METHODS: Thirty-two subjects (19 males) age 37 +/- 15 years with a suspicious baseline ECG, or who were relatives of Brugada syndrome patients, underwent 12-lead ECG before and after the administration of flecainide. RESULTS: The flecainide test was negative in 14 and positive in 18 subjects. After flecainide administration, the positive ECGs were characterized by a greater QT interval corrected for heart rate (QTc) prolongation in the right precordial leads than that in the negative ECGs (78.2 +/- 35.5 ms vs. 22.0 +/- 28.4 ms in V(1) and 107.1 +/- 43.8 ms vs. 26.7 +/- 30.1 ms in V(2); p < 0.01), whereas there was no difference in the QTc prolongation in the left precordial leads (55.2 +/- 25.3 ms vs. 35.1 +/- 28.1 ms in V(5) and 53.1 +/- 32.8 ms vs. 27.3 +/- 22.4 ms in V(6); p = NS). CONCLUSIONS: In accordance with the electrophysiological background, the typical ECG pattern of Brugada syndrome is also characterized by a considerable prolongation of the QT interval in right precordial leads.

Enhanced reflex response to baroreceptor deactivation in subjects with tilt-induced syncope.

OBJECTIVES: We sought to evaluate whether changes in resting baroreflex control of heart rate are a distinctive feature of healthy subjects with a history of syncope prone to a positive tilt-test response. BACKGROUND: The mechanisms involved in the pathogenesis of vasovagal syncope (VVS) are still poorly understood; in particular, the contribution of arterial baroreflex control of heart rate is matter of discussion. METHODS: A passive tilt-table test was performed in 312 consecutive, otherwise healthy subjects (age 36 +/- 15 years) with unexplained syncope and 100 control subjects. At baseline, spontaneous baroreflex sensitivity (BRS; ms/mm Hg) and the baroreflex effectiveness index (BEI) were assessed using the sequence method. RESULTS: The study population showed normal baroreflex function. Tilt-induced VVS in 94 subjects who were younger than both the tilt-negative and control subjects (30 +/- 14, 38 +/- 15, and 37 +/- 14 years, respectively; p = 0.00005) showed greater BRS (17.4 +/- 9.8, 13.2 +/- 7.9, and 12.8 +/- 8.2 ms/mm Hg, respectively; p = 0.0001), but had a similar BEI (0.59 +/- 0.18, 0.56 +/- 0.19, and 0.58 +/- 0.2, respectively; p = NS). On Cox multivariate analysis, the occurrence of VVS during tilt was inversely related to age (hazard ratio 0.97; p = 0.0004) and directly related to the BRS slope of sequences, implying a baroreceptor deactivation (hazard ratio 1.05; p = 0.02), but not of sequences characterized by arterial baroreceptor stimulation. CONCLUSIONS: Subjects with tilt-induced VVS showed greater resting BRS but had a normal BEI. The enhanced reflex tachycardic response to arterial baroreceptor deactivation at rest may represent a characteristic feature of subjects prone to tilt-induced VVS.

Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony.

OBJECTIVES: The value of interventricular and intraventricular echocardiographic asynchrony parameters in predicting reverse remodeling after cardiac resynchronization therapy (CRT) was investigated. BACKGROUND: Cardiac resynchronization therapy has been suggested as a promising strategy in patients with severe heart failure and left bundle branch block (LBBB), but the entity of benefit is variable and no criteria are yet available to predict which patients will gain. METHODS: Interventricular and intraventricular mechanical asynchrony was evaluated in 20 patients (8 men and 12 women, 63 +/- 10 years) with advanced heart failure caused by ischemic (n = 4) or nonischemic dilated cardiomyopathy (n = 16) and LBBB (QRS duration of at least 140 ms) using echocardiographic Doppler measurements. Left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were calculated before and one month after CRT. Patients with a LVESVI reduction of at least 15% were considered as responders. RESULTS: Cardiac resynchronization therapy significantly improved ventricular volumes (LVEDVI from 150 +/- 53 ml/m(2) to 119 +/- 37 ml/m(2), p < 0.001; LVESVI from 116 +/- 43 ml/m(2) to 85 +/- 29 ml/m(2), p < 0.0001). At baseline, the responders had a significantly longer septal-to-posterior wall motion delay (SPWMD), a left intraventricular asynchrony parameter; only QRS duration and SPWMD significantly correlated with a reduction in LVESVI (r = -0.54, p < 0.05 and r = -0.70, p < 0.001, respectively), but the accuracy of SPWMD in predicting reverse remodeling was greater than that of the QRS duration (85% vs. 65%). CONCLUSIONS: In patients with advanced heart failure and LBBB, baseline SPWMD is a strong predictor of the occurrence of reverse remodeling after CRT, thus suggesting its usefulness in identifying patients likely to benefit from biventricular pacing.

Shortened head-up tilting test guided by systolic pressure reductions in neurocardiogenic syncope.

BACKGROUND: Asymptomatic reductions in arterial pressure have been reported to occur before the onset of tilt-induced syncope. We investigated the predictive value of these reductions for a positive tilt result. METHODS AND RESULTS: In a first study, 238 consecutive healthy subjects with unexplained syncope underwent a passive tilt table test. Finger systolic arterial pressure (SAP) recordings made it possible to calculate how many of the beat-to-beat SAP values during the first 15 minutes of tilt were lower than the lowest value recorded at baseline. Neurocardiogenic syncope was diagnosed in 73 subjects; 28 fainted after 15 minutes of tilt and experienced more pressure reductions than did the subjects with a negative test (328+/-400 versus 119+/-284; P<0.01). More than 14 SAP reductions during the first 15 minutes of tilt allowed us to predict a positive test with 93% sensitivity, 58% specificity, and positive and negative predictive values of 28% and 98%, respectively. In a second prospective study (80 consecutive subjects), the online analysis of this criterion by visually inspecting a Finapres monitor showed 80% sensitivity, 85% specificity, and positive and negative predictive values of 57% and 94%. CONCLUSIONS: In healthy subjects with unexplained syncope, the evaluation of SAP reductions during the first 15 minutes of tilt is a marker of systolic pressure instability preceding syncope and constitutes a simple and good predictor of tilt outcome that could be used to guide test duration.