Red blood cell distribution width is a significant prognostic marker in advanced heart failure, independent of hemoglobin levels.

INTRODUCTION: Advanced heart failure (HF) is associated with increased morbidity and mortality; traditionally used prognostic factors often fail to predict the outcome. Increased red blood cell distribution width (RDW) has recently been recognized as an important unfavorable prognostic factor in HF, independent of anemia; however, the role of RDW in patients with advanced HF has not yet been investigated. METHODS: Eighty consecutive patients with stage D heart failure, recently hospitalized for HF decompensation, were enrolled. A Cox proportional-hazard model was used to determine whether RDW was independently associated with outcome. RESULTS: At study entry, ejection fraction (EF), pulmonary capillary wedge pressure (PCWP), hemoglobin (Hb) and RDW were 25 ± 8.6%, 27.5 ± 8 mmHg, 12.5 ± 1.9 mg/dL and 18 ± 3.5% (normal <14.5%) respectively. At 6 months, 44 patients (55%) had died. In this patient population, EF (p=0.45), PCWP (p=0.106), age (p=0.54), albumin (0.678), iron (p=0.37), creatinine (p=0.432), iron deficiency defined by bone marrow aspiration (p=0.37), bilirubin (p=0.422), peak VO2 (p=0.057) and Hb (p=0.95) were not significant predictors of a worse outcome. However, RDW was a significant marker for adverse prognosis (p=0.007, HR: 1.14, CI: 1.04-1.24) and retained its prognostic significance even when corrected for Hb values (HR: 1.15, CI: 1.05-1.27, p=0.003). CONCLUSIONS: RDW is a significant prognostic factor for an adverse outcome in patients with advanced stage heart failure who have experienced recent decompensation, independent of the presence of anemia or malnutrition, and is superior to more traditionally used indices. RDW may be associated with severe disease by reflecting subtle metabolic and proinflammatory abnormalities in HF.

Inductive, scaffold-based, regenerative medicine approach to reconstruction of the temporomandibular joint disk.

PURPOSE: A device composed of extracellular matrix (ECM) was investigated as an inductive template in vivo for reconstruction of the temporomandibular joint (TMJ) disk after discectomy. MATERIALS AND METHODS: A scaffold material composed of porcine-derived ECM was configured to mimic the shape and size of the TMJ. This device was implanted in a canine model of bilateral TMJ discectomy. After discectomy, 1 side was repaired with an ECM scaffold material and the contralateral side was left empty as a control. At 6 months after implantation, the joint space was opened, the joints were evaluated for signs of gross pathologic degenerative changes, and newly formed tissue was excised for histologic, biochemical, and biomechanical analysis. RESULTS: The results showed that implantation of an initially acellular material supported the formation of site-appropriate, functional host tissue that resembled that of the native TMJ disk. Furthermore, this prevented gross degenerative changes in the temporal fossa and mandibular condyle. No tissue formation and mild to severe gross pathologic changes were observed in the contralateral controls. CONCLUSIONS: These results suggest that an ECM-based bioscaffold could represent an off-the-shelf solution for TMJ disk replacement.

Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure.

AIMS: Inotrope treatment is often necessary in refractory to optimal management end stage heart failure, when signs of end-organ hypoperfusion appear. The effect of specific inotropes on patient outcome remains controversial. The aim of the study was to compare the effect of levosimendan versus dobutamine, alone or in combination with levosimendan, on the outcome of end-stage heart failure patients, requiring inotropic therapy. METHODS AND RESULTS: We studied 63 patients in NYHA class IV, refractory to optimal medical therapy, recently hospitalized for cardiac decompensation and stabilized by an intravenous inotrope. They were randomly assigned to intermittent infusions of either a) dobutamine, 10mg/kg/min, versus b) levosimendan, 0.3mg/kg/min, versus c) dobutamine, 10mg/kg/min+levosimendan 0.2 mg/kg/min, each administered weekly, for 6h, over a 6-month period. All patients received amiodarone, 400 mg/day, to suppress the proarrhythmic effects of the inotropes. Baseline characteristics of the 3 groups were similar. At 6 months, survival free from death or urgent left ventricular device implantation was 80% in the levosimendan, 48% in the dobutamine (P=0.037 versus levosimendan), and 43% in the levosimendan+dobutamine (P=0.009 versus levosimendan) group. At 3months, NYHA class improved significantly in all 3 groups, whereas pulmonary capillary wedge pressure decreased (27 ± 4 to 19 ± 8 mmHg, P=0.008) and cardiac index increased (1.5 ± 0.3 to 2.1 ± 0.3 l/min/m(2), P=0.002) significantly only in patients assigned to levosimendan. CONCLUSIONS: In patients with refractory end-stage heart failure, intermittent administration of levosimendan conferred survival and hemodynamic benefits in comparison to a regimen of intermittent infusions of dobutamine, alone or in combination with levosimendan.

Mechanical assistance by intra-aortic balloon pump counterpulsation during reperfusion increases coronary blood flow and mitigates the no-reflow phenomenon: an experimental study.

The effects of the intra-aortic balloon pump (IABP) counterpulsation on the extent of myocardial infarction (MI), the no-reflow phenomenon (NRP), and coronary blood flow (CBF) during reperfusion in an ischemia-reperfusion experimental model have not been clarified. Eleven pigs underwent occlusion of the mid left anterior descending coronary artery for 1 h, followed by reperfusion for 2 h. CBF, distal to the occlusion site, was measured. In six experiments, IABP support began 10 min before, and continued throughout reperfusion (IABP Group). Five pigs without IABP support served as controls. At the end of each experiment, the myocardial area at risk (MAR) of infarction and the extent of MI and NRP were measured. Hemodynamic measurements at baseline and during coronary occlusion were similar in both groups. During reperfusion, systolic aortic blood pressure was significantly lower in the IABP Group than in controls. In the IABP Group, CBF reached a peak at 5 min of reperfusion, gradually decreased, but remained higher than at baseline, and significantly higher than in controls throughout the 2 h of reperfusion. In controls, CBF increased significantly above baseline immediately after the onset of reperfusion, then returned to baseline within 90 min. The extent of NRP (37 ± 25% vs. 68 ± 17%, P = 0.047) and MI (39 ± 23% vs. 67 ± 13%, P = 0.036), both expressed as percentage of MAR, was significantly less in the IABP group than in controls. After prolonged myocardial ischemia, IABP assistance started just 10 min before and throughout reperfusion increased CBF and limited infarct size and extent of NRP.

Long-term survival and outcomes after hospitalization for acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Cardiogenic shock is the leading cause of death during hospitalization for acute myocardial infarction (MI). However, little data exist regarding the long-term outcomes of patients who survived the acute phase of MI and were discharged from the hospital. METHODS: We retrospectively reviewed the records of 81 consecutive patients referred for management of acute MI and cardiogenic shock to analyze their in-hospital and long-term outcomes. RESULTS: Mean systemic systolic and central venous pressures at presentation were 74 +/- 15 and 17 +/- 7 mm Hg, respectively. Intra-aortic balloon counterpulsation (IABC) was implemented in all patients for a mean of 88 +/- 83 hours. Thrombolytics were administered in 49% and mechanical ventilation applied in 46% of patients. Primary angioplasty could not be performed in any patient, while 17 patients later underwent myocardial revascularization during hospitalization. There were 37 in-hospital survivors (45.7%). The 1-year survival after discharge from the hospital was 87.6% in the overall population, versus 100% among patients who underwent in-hospital myocardial revascularization, versus 78.9% among nonrevascularized patients (p = 0.079). Over a mean follow-up of 85 +/- 47 mo, survival after discharge from the index hospitalization was 44.9% in the overall population, versus 56.2% among revascularized patients, versus 36.4% among nonrevascularized patients (p = 0.277). Heart failure developed in 51.6% of patients who were discharged from the hospital. CONCLUSIONS: In this single center analysis, the long-term survival after acute MI complicated by cardiogenic shock was high with nearly 50% of patients surviving free from heart failure.

Ventricular-assist devices for the treatment of chronic heart failure.

The role of ventricular-assist devices in the management of end-stage heart failure is growing. Initially developed as a 'bridge to transplantation', they are now implanted permanently in patients who need cardiac replacement but are not candidates for cardiac transplantation ('destination therapy'). Furthermore, observations from expert centers indicate that a significant proportion of patients under long-term mechanical assistance can be weaned from mechanical circulatory support after significant functional recovery of their native heart ('bridge to recovery'). This review discusses the emerging roles of mechanical circulatory support and their direct implications in clinical practice. Evolution of devices, important aspects of candidate selection, challenging issues in the management of ventricular-assist device patients (infection, device malfunction, anticoagulation-thromboembolic complications, psychosocial issues and cost) and ongoing research targeting sustained myocardial recovery are discussed.

The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease.

BACKGROUND: Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI+amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC). METHODS: The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. RESULTS: There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups. The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P=0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P=0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods. CONCLUSIONS: Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.

VE/VCO2 slope is associated with abnormal resting haemodynamics and is a predictor of long-term survival in chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) present with exercise-induced hyperpnea, but its pathophysiological mechanism has not been thoroughly investigated. We aimed to determine the relationship between exercise-induced hyperpnea, resting haemodynamic measurements and the validity of ventilatory response (V(E)/V(CO(2)) slope) as a mortality predictor in CHF patients. METHODS: Ninety-eight CHF patients (90M/8F) underwent a symptom-limited treadmill cardiopulmonary exercise test (CPET). Right heart catheterization and radionuclide ventriculography were performed within 72 h of CPET. RESULTS: Twenty-seven patients died from cardiac causes during 20+/-6 months follow-up. Non-survivors had a lower peak oxygen consumption (V(O(2)p)), (16.5+/-4.9 vs. 20.2+/-6.1, ml/kg/min, p=0.003), a steeper V(E)/V(CO(2)) slope (34.8+/-8.3 vs. 28.9+/-4.8, p<0.001) and a higher pulmonary capillary wedge pressure (PCWP) (19.5+/-8.6 vs. 11.7+/-6.5 mm Hg, p=0.008) than survivors. By multivariate survival analysis, the V(E)/V(CO(2)) slope as a continuous variable was an independent prognostic factor (chi(2): 8.5, relative risk: 1.1, 95% CI: 1.03-1.18, p=0.004). Overall mortality was 52% in patients with V(E)/V(CO(2)) slope > or =34 and 18% in those with V(E)/V(CO(2)) slope <34 (log rank: 18.5, p<0.001). In a subgroup of patients (V(O(2)p): 10-18 ml/kg/min), V(E)/V(CO(2)) slope was a significant predictor of mortality (relative risk: 6.2, 95% CI: 1.7-22.2, p=0.002). Patients with high V(E)/V(CO(2)) slope had higher resting PCWP (19.9+/-9.1 vs. 11.3+/-5.7 mmHg, p<0.001) and V(E)/V(CO(2)) slope correlated significantly with PCWP (r: 0.57, p<0.001). CONCLUSIONS: The V(E)/V(CO(2)) slope, as an index of ventilatory response to exercise, improves the risk stratification of CHF patients. Interstitial pulmonary oedema may be a pathophysiological mechanism of inefficient ventilation during exercise in these patients.

Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy.

BACKGROUND: The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF). METHODS: This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up. RESULTS: A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006). CONCLUSIONS: In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.

Ventilatory response to exercise and kinetics of oxygen recovery are similar in cardiac transplant recipients and patients with mild chronic heart failure.

BACKGROUND: Exercise capacity, assessed by cardiopulmonary exercise treadmill testing (CPET), does not return to normal following heart transplantation. This study evaluated the ventilatory response to exercise and the kinetics of oxygen (O(2)) recovery in heart transplant recipients (HTR) compared to healthy volunteers (HV) and heart failure patients. METHODS: Eighteen patients with end-stage heart failure (ESHF), 12 with mild heart failure (MHF) matched for peak oxygen consumption (Vo(2)) with the HTR, 12 HTR and 12 HV underwent CPET for measurements of peak Vo(2), Vo(2) at anaerobic threshold (AT), first-degree slope of Vo(2) decline during early recovery (Vo(2)/t-slope), time required for a 50% fall from peak Vo(2) (T(1/2) of Vo(2)) and the slopes of VE/Vco(2) and VE/Vo(2). RESULTS: The MHF and HTR groups had similar ventilatory responses to exercise and O(2) recovery kinetics. Peak Vo(2) (18.5 +/- 5.7 vs 9.4 +/- 0.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 6.7 +/- 1.8 ml/kg/min, p < 0.001) and Vo(2)/t-slope (0.6 +/- 0.2 vs 0.3 +/- 0.2 liter/min/min, p = 0.055) were higher in the HTR than in the ESHF group. In contrast, HTR had lower VE/Vco(2)-slope (31.4 +/- 3.8 vs 39.2 +/- 9.9, p = 0.015) and T(1/2) Vo(2) (1.5 +/- 0.3 vs 2.4 +/- 1.1 minute, p = 0.014) than the ESHF group. Compared to HV, HTR had lower Vo(2) peak (18.5 +/- 5.7 vs 28.4 +/- 6.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 19.8 +/- 4.5 ml/kg/min, p = 0.04), Vo(2)/t-slope (0.6 +/- 0.2 vs 1.0 +/- 0.4 liter/min/min, p = 0.005) and steeper VE/Vco(2) slope (31.4 +/- 3.8 vs 23.6 +/- 2.7, p = 0.062). Heart rate deceleration during recovery was significantly slower in HTR than in all other groups. CONCLUSIONS: Exercise intolerance and delayed O(2) recovery kinetics were only partially reversed after heart transplantation. This finding suggests that some of the pathophysiologic mechanisms of heart failure persist after heart transplantation.

Long-term intermittent dobutamine infusion, combined with oral amiodarone for end-stage heart failure: a randomized double-blind study.

STUDY OBJECTIVES: To examine the effects of long-term intermittent dobutamine infusion, combined with oral amiodarone in patients with congestive heart failure (CHF) refractory to standard medical treatment. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: Inpatient and outpatient heart failure clinic in a university teaching hospital. PATIENTS AND INTERVENTIONS: Thirty patients with end-stage CHF refractory to standard medical treatment who could be weaned from dobutamine therapy after a first 72-h infusion were randomized in a double-blind manner to receive IV infusions of placebo (group 1; 14 patients) vs dobutamine in a dose of 10 micro g/kg/min (group 2; 16 patients) for 8 h every 14 days. All patients received standard medical therapy and also were treated with oral amiodarone, 400 mg/d, which was started at least 2 weeks before randomization. MEASUREMENTS AND RESULTS: Kaplan-Meier survival analysis showed a 60% reduction in the risk of death from any cause in the group treated with the combination of dobutamine and amiodarone, compared with the group treated with placebo and amiodarone (hazard ratio, 0.403; 95% confidence interval, 0.164 to 0.992; p = 0.048). The 1-year and 2-year survival rates were 69% and 44%, respectively, in the dobutamine-treated group, vs 28% and 21%, respectively, in the placebo-treated group (p < 0.05 for both comparisons). Median survival times were 574 and 144 days, respectively, for groups 2 and 1. At 6 months, the New York Heart Association functional class was significantly improved in the patients who survived from both groups. CONCLUSIONS: Long-term intermittent dobutamine infusion combined with amiodarone added to the conventional drugs improved the survival of patients with advanced CHF that was refractory to conventional treatment.

White-coat effect in normotension and hypertension.

OBJECTIVES: The difference between clinic and daytime ambulatory blood pressure is referred to as the white-coat effect. In this study, we investigated (i) the magnitude of the white-coat effect in subjects with different daytime ambulatory blood pressure levels, and (ii) the association of the white-coat effect with left ventricular mass. METHODS: A total of 1581 subjects underwent clinic blood pressure readings, 24-h ambulatory blood pressure monitoring and left ventricular echocardiographic assessment. Their mean daytime systolic blood pressure varied from 88.0 to 208.9 mmHg and their mean daytime diastolic blood pressure from 40.3 to 133.0 mmHg. RESULTS: A negative correlation was found between the systolic or diastolic white-coat effect and the systolic or diastolic daytime ambulatory blood pressure (r = -0.22, P < 0.000 and r = -0.50, P < 0.000, respectively). Left ventricular mass significantly correlated with ambulatory blood pressure (P < 0.001), but there was no association between left ventricular mass and clinic blood pressure or white-coat effect. Furthermore, the white-coat effect was reversed at the highest level of systolic or diastolic daytime ambulatory blood pressure (systolic over 170 mmHg or diastolic over 100 mmHg) when systolic or diastolic daytime ambulatory blood pressure was higher than systolic or diastolic clinic blood pressure (ambulatory blood pressure hypertension). CONCLUSIONS: The white-coat effect shows an inverse association with daytime ambulatory blood pressure level (systolic or diastolic), being significantly more prominent for levels below 140/80 mmHg for systolic/diastolic daytime ambulatory blood pressure and reversed with daytime ambulatory blood pressure levels above 170/100 mmHg.

Model-based processing scheme for quantitative 4-D cardiac MRI analysis.

In this paper, we present an integrated model-based processing scheme for cardiac magnetic resonance imaging (MRI), embedded in an interactive computing environment suitable for quantitative cardiac analysis, which provides a set of functions for the extraction, modeling, and visualization of cardiac shape and deformation. The methods apply four-dimensional (4-D) processing (three spatial and one temporal) to multiphase multislice MRI acquisitions and produce a continuous 4-D model of the myocardial surface deformation. The model is used to measure diagnostically useful parameters, such as wall motion, myocardial thicking, and myocardial mass measurements. The proposed model-based shape extraction method has the advantage of integrating local information into an overall representation and produces a robust description of cardiac cavities. A learning segmentation process that incorporates a generating-shrinking neural network is combined with a spatiotemporal parametric modeling method through functional basis decomposition. A multiscale approach is adopted, which uses at each step a coarse-scale model defined at the previous step in order to constrain the boundary detection. The representation accuracy starts from a coarse but smooth estimation of the approximate cardiac shape and is gradually increased to the desired detail. The main advantages of the proposed methods are efficiency, lack of uncertainty about convergence, and robustness to image artifacts. Experimental results obtained from application to clinical multislice multiphase MRI examinations of normal volunteers and patients with medical record of myocardial infarction were satisfactory in terms of accuracy and robustness.