High furosemide dose has detrimental effects on survival of patients with stable heart failure.

INTRODUCTION: High doses of furosemide for heart failure (HF) have been correlated with an increased mortality, though whether they are a marker of disease severity or an independent predictor is unknown. We hypothesized that, in patients presenting with stable HF, the likelihood of long-term major adverse clinical events is increased by higher furosemide doses. METHODS: We retrospectively recorded the doses of furosemide prescribed to 173 consecutive, clinically stable patients during a first ambulatory HF department visit. The low-dose group included 103 patients treated with 80 mg and the high-dose group included 70 patients treated with >80 mg of furosemide daily. Proportional hazard regression analyses were performed with single and multiple variables in search of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: The baseline characteristics of the 2 groups were similar, except for estimated glomerular filtration rate, which was higher in the low- than the high-dose group (72.9 ± 19.4 vs. 60.8 ± 22.0 mL/min/ m2, p<0.001). The 3-year survival free from the composite endpoint was significantly higher in the lowdose group than in the high-dose group (93.1% vs. 60.0%, p<0.001). By multiple variable analysis, highdose furosemide was an independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95% CI:1.06-219.39, p=0.045). The incidence of deterioration of renal function and episodes of hypokalemia during follow up was also higher in the high furosemide dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p<0.001, respectively). CONCLUSIONS: High doses of furosemide administered in order to stabilize HF patients and continued thereafter are associated with an adverse clinical outcome.

Dabigatran etexilate as second-line therapy in patients with a left ventricular assist device.

INTRODUCTION: Administration of anticoagulation is mandatory in patients with left ventricular assist devices (LVADs). Vitamin K antagonists require regular monitoring and dosage adjustment. Dabigatran administered in a standard dose twice daily is more convenient and achieves a stable anticoagulant effect, but its effectiveness and safety in patients with LVADs has not been investigated. The objective of the present study was to evaluate whether dabigatran can be used safely as a second-line anticoagulation option in patients with a HeartMate II (HMII) LVAD. METHODS: The study population consisted of 7 consecutive patients with end-stage heart failure who underwent HMII implantation and sequentially received acenocoumarol and dabigatran. Occurrence of stroke, systematic embolism, device thrombosis and major or life-threatening bleeding were included in the analysis. An acute decrease in plasma hemoglobin >2 g/dL or a need for transfusion of at least 2 units of packed red blood cells (PRBC) was defined as major bleeding, while an acute decrease in plasma hemoglobin >5 g/dL, fatal, symptomatic intracranial bleed, need for transfusion of at least 4 units PRBC, or association with hypotension requiring the use of intravenous inotropic agents or surgical intervention was defined as life-threatening bleeding. RESULTS: The duration of follow up was 1564 ± 292 days. Patients received acenocoumarol for 855 ± 246 days, followed by dabigatran for 708 ± 368 days. The rates of thromboembolic events were similar under dabigatran and acenocoumarol treatment: strokes, 0.094 vs. 0 /patient-year, p=0.36; systemic embolism, no event in either group; and device thrombosis, 0.053 vs. 0.258 events/patient-year, p=0.19, respectively. Compared to an adjusted acenocoumarol dose, the standard dabigatran dose resulted in similar rates of life-threatening bleeding, but significantly lower rates of major bleeding (0.18 vs. 0.27 bleeds/patient-years, p=0.76, and 0.047 vs. 0.547, p<0.001, for dabigatran and acenocoumarol, respectively). CONCLUSIONS: The safe and effective use of dabigatran as a second-line anticoagulation therapy in patients with HMII seems feasible. However, these data must be confirmed in a randomized study.

Afterload-induced left ventricular diastolic dysfunction during myocardial ischaemia and reperfusion.

NEW FINDINGS: What is the central question of this study? While the load dependence of the diastolic function is established for the normal heart, little is known about the response of the acutely ischaemic and reperfused myocardium to alterations in afterload. What is the main finding and its importance? Using a model that simulates the clinical scenario of acute ischaemia-reperfusion, we show that increased afterload aggravates diastolic dysfunction during both acute ischaemia and reperfusion. In addition, increased afterload induces diastolic dyssynchrony, which might be the underlying mechanism of the diastolic dysfunction of the ischaemic myocardium. These findings provide us with new information regarding how better to manage patients who undergo revascularization therapy after acute myocardial infarction. The effects of changes in left ventricular (LV) afterload on diastolic function of acutely ischaemic and reperfused myocardium have not been studied in depth. We examined the following factors: (i) the consequences of increasing the LV afterload on LV diastolic function during acute ischaemia and reperfusion; (ii) whether the myocardial response to afterload elevation is stable throughout a 2 h reperfusion period; and (iii) the role of LV wall synchrony in the development of afterload-induced diastolic dysfunction. We instrumented 12 anaesthetized, open-chest pigs with Millar pressure catheters and piezoelectric crystals before ligating mid-left anterior descending coronary artery for 1 h, followed by reperfusion for 2 h. Six of the animals survived throughout the 2 h of reperfusion, and their data were used for comparisons across the different experimental phases. Left ventricular afterload was increased by inflating an intra-aortic balloon. Data were recorded at baseline, after 20 min of coronary occlusion and at 30 and 90 min of myocardial reperfusion. The increased afterload for 2 min lengthened the isovolumic relaxation during ischaemia and during early and late reperfusion but had no significant effect on isovolumic relaxation before coronary artery occlusion. Increasing the afterload aggravated LV diastolic dyssynchrony during coronary artery occlusion, but not during reperfusion. The afterload-induced prolongation of isovolumic relaxation was positively correlated with afterload-induced diastolic dyssynchrony. These observations indicate that, during myocardial ischaemia and throughout reperfusion, LV diastolic function is afterload dependent. Afterload-induced diastolic dyssynchrony might be an underlying mechanism of diastolic dysfunction during acute ischaemia.

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.

Value of apical circumferential strain in the early post-myocardial infarction period for prediction of left ventricular remodeling.

BACKGROUND: Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is related to increased morbidity and mortality. The aim of the present study was to examine whether LV deformational and torsional parameters can predict LV remodeling in patients with AMI. METHODS: Forty-two patients (age 57 ± 14 years) presenting with an anterior ST-elevation AMI and treated with primary percutaneous transluminal coronary angioplasty (PTCA) were included in the study. Four days post MI, LV ejection fraction (EF), LV torsion, longitudinal (4-, 3- & 2-chamber) and circumferential strain of the LV apex were evaluated by conventional and speckle-tracking echocardiography. The echocardiographic study was repeated at 3 months post-AMI and patients with LV remodeling, i.e. an increase >15% in LV end-systolic volume (LVESV), were identified. RESULTS: The 13 patients with LV remodeling had significantly more impaired apical circumferential strain (-7.3 ± 2.2% vs. -18.9 ± 5.2%, p=0.001), EF (42 ± 7% vs. 48.9 ± 6%, p=0.005), LV apical rotation (6.8 ± 4.8° vs. 11.1 ± 4.0°, p=0.027), and LV global longitudinal strain (-9.7 ± 1.9% vs. -12.9 ± 2.9%, p=0.03) on the 4th day post-AMI, in comparison to those without LV remodeling. Apical circumferential strain on the 4th day post-AMI showed the strongest correlation with the LVESV 3 months post-AMI (r=0.76, p=0.001), compared to EF (r=-0.60, p=0.001), global longitudinal strain (r=0.56, p=0.001), and LV apical rotation (r=-0.53, p=0.001). Furthermore, apical circumferential strain demonstrated the highest diagnostic accuracy: area under the receiver operating characteristic (ROC) curve 0.98, with sensitivity 100% and specificity 96% for prediction of LV remodeling, using a cutoff value <-11.0%. CONCLUSION: In patients with anterior AMI, LV apical circumferential strain in the early post-MI period constitutes a significant prognostic factor for LV remodeling at 3 months. Assessment of this parameter may identify patients at high risk for heart failure development.

Modeling and simulation of speed selection on left ventricular assist devices.

The control problem for LVADs is to set pump speed such that cardiac output and pressure perfusion are within acceptable physiological ranges. However, current technology of LVADs cannot provide for a closed-loop control scheme that can make adjustments based on the patient's level of activity. In this context, the SensorART Speed Selection Module (SSM) integrates various hardware and software components in order to improve the quality of the patients' treatment and the workflow of the specialists. It enables specialists to better understand the patient-device interactions, and improve their knowledge. The SensorART SSM includes two tools of the Specialist Decision Support System (SDSS); namely the Suction Detection Tool and the Speed Selection Tool. A VAD Heart Simulation Platform (VHSP) is also part of the system. The VHSP enables specialists to simulate the behavior of a patient׳s circulatory system, using different LVAD types and functional parameters. The SDSS is a web-based application that offers specialists with a plethora of tools for monitoring, designing the best therapy plan, analyzing data, extracting new knowledge and making informative decisions. In this paper, two of these tools, the Suction Detection Tool and Speed Selection Tool are presented. The former allows the analysis of the simulations sessions from the VHSP and the identification of issues related to suction phenomenon with high accuracy 93%. The latter provides the specialists with a powerful support in their attempt to effectively plan the treatment strategy. It allows them to draw conclusions about the most appropriate pump speed settings. Preliminary assessments connecting the Suction Detection Tool to the VHSP are presented in this paper.

Current and future applications of the intra-aortic balloon pump.

PURPOSE OF REVIEW: The intra-aortic balloon pump (IABP) has been used for more than 40 years. Although recommended in a wide variety of clinical settings, most of these indications are not evidence-based. This review focuses on studies challenging these traditional indications and evaluates potentially new applications of intra-aortic counterpulsation. RECENT FINDINGS: Recent studies have failed to confirm an improvement in clinical outcomes conferred by the IABP in patients developing cardiogenic shock after acute myocardial infarction. This issue is in need of further investigations. While conflicting results of several retrospective studies and meta-analyses have been published regarding the performance of the IABP in high-risk percutaneous coronary interventions, it has recently been found to improve the long-term clinical outcomes of patients in whom it was implanted before the procedure. Small, single-center studies have reported the use of the IABP as a bridge to transplantation or candidacy for left-ventricular assist device implantation. The recently reported feasibility and safety of its insertion via the subclavian or axillary arteries will facilitate these applications. SUMMARY: The revisiting of available data and the performance of new, thoughtfully designed trials should clarify the proper indications for the IABP.

Counterpulsation: a concept with a remarkable past, an established present and a challenging future.

The intra-aortic balloon pump (IABP), which is the main representative of the counterpulsation technique, has been an invaluable tool in cardiologists' and cardiac surgeons' armamentarium for approximately half a century. The IABP confers a wide variety of vaguely understood effects on cardiac physiology and mechano-energetics. Although, the recommendations for its use are multiple, most are not substantially evidence-based. Indicatively, the results of recently performed prospective studies have put IABP's utility in the setting of post-infarction cardiogenic shock into question. However, the particular issue remains open to further research. IABP support in high-risk patients undergoing PCI is associated with favorable long-term clinical outcome. In cardiac surgery, the use of IABP in cases of peri-operative low-output syndrome, refractory angina or ischemia-related mechanical complications is a usual, but poorly justified strategy. Anecdotal cases of treatment of incessant ventricular arrhythmias, reversal of right ventricular dysfunction and partial myocardial recovery have also been reported with its use. Converging data demonstrate the potential of safe long-term IABP support as a bridge to decision making or a bridge to transplantation modality in patients with heart failure. The feasibility of IABP insertion via other than the femoral artery sites enhances this potential. Despite the fact that several other counterpulsation devices have been developed and tested overtime none has managed to substitute the IABP, which continues to be most frequently used mechanical assist device.

Elevated left ventricular filling pressures can be estimated with accuracy by a new mathematical model.

BACKGROUND: Although the clinical assessment of jugular venous pressure (JVP) provides accurate estimate of right atrial pressure (RAP), there is no reliable non-invasive method for assessing pulmonary capillary wedge pressure (PCWP). Our objective was to evaluate the sensitivity and specificity for detecting elevated left ventricular filling pressures using a model for PCWP estimation, based on the clinical assessment of RAP and association between RAP and PCWP, which is unique for each patient, identified in a recent right heart catheterization (RHC). METHODS: The study included 377 patients (age, 54.3 ± 13 years) with heart failure with reduced ejection fraction (left ventricular ejection fraction of 30.5 ± 10.8%) who underwent 2 RHCs within 1 year. In Group A (189 randomly selected patients), hemodynamic variables with significant correlation with the current wedge pressure (PCWP(2)) were identified and an equation estimating PCWP(2) based on these variables was formed. The validity of the equation was evaluated in the remaining 188 patients (Group B). The equation was also evaluated, prospectively in 39 new patients where RAP was estimated clinically, by physicians blinded to the results of the RHC. RESULTS: PCWP(2) in Group A correlated with RAP(1), systolic pulmonary artery pressure (SPAP(1)), and PCWP(1) of the first RHC and with RAP(2) and SPAP(2) of the second. The equation is PCWP(2) = [3RAP(2) + (PCWP(1) - RAP(1)) + 4]/2. In Group B, the sensitivity and specificity of estimated PCWP(2) for diagnosis of elevated LV filling pressures (invasive values >18 mm Hg) was significant, reflected by an area under the curve (AUC) of 0.954 (p < 0.001). In the prospective sub-group, where JVP was entered in the formula as an estimate of RAP(2), correlation between estimated and measured PCWP(2) was r = 0.803 (p < 0.001). CONCLUSIONS: The current PCWP of a patient with heart failure can be estimated accurately by a simple equation based on measurements of a previous RHC and the current value of clinically assessed JVP.

Effects of L-NAME on coronary blood flow, infarct size and the extent of the no-reflow phenomenon.

BACKGROUND: NOS inhibitors are a potential treatment for patients with cardiogenic shock during acute myocardial infarction. Despite hemodynamic efficacy, their effects on the extent of myocardial infarction (MI) and the no-reflow phenomenon (NRP) have not been clarified. METHODS: Sixteen pigs underwent occlusion of the mid left anterior descending coronary artery for 1h followed by reperfusion for 2h. Coronary blood flow (CBF), distal to the occlusion site, was measured. In eight experiments, L-NAME (non selective NO synthetase inhibitor) administration began 10 min before the onset of reperfusion and continued for 2h (loading dose 1mg/kg, perfusion rate: 1mg/kg/h) (L-NAME group). Eight pigs received similarly normal saline (controls). At the end of each experiment, the myocardial area at risk (MAR) and extent of MI and NRP were measured. RESULTS: Hemodynamics at baseline and during ischemia were similar in both groups. During reperfusion, the mean aortic blood pressure was significantly higher in the l-NAME group. In both groups, CBF reached a peak at 5 min of reperfusion, (no difference between groups). CBF gradually returned to baseline levels within 60 min of reperfusion in both groups. No statistically significant differences in the extent of the NRP (51.8 ± 19.7 vs 60.9 ± 11.4 p=0.35) and MI (77.9 ± 13.9 vs 77.1 ± 8.8 p=0.92), both expressed as a percentage of MAR, were observed between the L-NAME group and the control group. CONCLUSIONS: L-NAME administration started immediately before and maintained throughout reperfusion has no effect on NRP and MI size. L-NAME might stabilize patients with post-MI cardiogenic shock without adverse effects on infarct size.

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.

The challenge of treating congestion in advanced heart failure.

Volume overload is a common manifestation of heart failure decompensation. Interaction between impaired renal and heart function constitutes an important pathophysiologic mechanism that leads to congestion. In addition to improving symptoms and volume status, reduction of rehospitalization rates, maintenance of renal function and improvement of survival are all important goals of every therapeutic strategy. Currently, the use of diuretics, vasodilators, inotropes and ultrafiltration, together with investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, constitute the main therapeutic options for the congested heart failure patient.

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.

Reverse electrophysiologic remodeling after cardiac mechanical unloading for end-stage nonischemic cardiomyopathy.

BACKGROUND: Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart. METHODS: We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD. RESULTS: After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms (p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms (p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms (p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms (p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours (p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours (p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD. CONCLUSIONS: The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

Anemia in heart failure: should we supplement iron in patients with chronic heart failure?

Anemia has been identified as an independent prognostic factor of both morbidity and mortality for patients with congestive heart failure (CHF). The association between anemia and adverse outcomes has raised the hypothesis that anemia correction might lead to an improvement in the prognosis of patients with CHF. Nevertheless, data from large randomized trials about the effect of anemia correction on patient outcome are still lacking. Numerous clinical studies, randomized and nonrandomized, have evaluated the efficacy of erythropoietin or iron supplementation for treating anemia in patients with CHF, and their effect on patient symptoms and functional status. The superiority of any of these approaches has not been established yet. This review will discuss different treatment options for anemic patients with CHF, with emphasis on the correction of iron deficiency.

Myocardial sympathetic innervation and long-term left ventricular mechanical unloading.

OBJECTIVES: The purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart. BACKGROUND: Ventricular unloading by LVADs seems to cause reverse remodeling of the failing heart, but little is known about the sympathetic nerve activity during long-term mechanical unloading. METHODS: We studied the effects of LVADs on myocardial sympathetic innervation, by iodine 123-meta-iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1) heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic measurements were made 3 months apart in 6 other heart failure patients not treated with an LVAD. RESULTS: After 3 months of LVAD support, the mean left ventricular ejection fraction had increased from 19+/-6% to 29 +/- 9% (p=0.006), peak oxygen consumption increased from 9+/-4 ml/kg/min to 13+/-3 ml/kg/min (p=0.058), serum sodium increased from 135+/-4 mEq/l to 140+/-2 mEq/l (p=0.014), whereas the left ventricular end-diastolic diameter decreased from 72+/-7 mm to 56+/-3 mm (p=0.002), pulmonary capillary wedge pressure decreased from 30+/-6 mm Hg to 5+/-3 mm Hg (p=0.012), serum creatinine decreased from 1.5+/-0.6 mg/dl to 1.0+/-0.4 mg/dl (p=0.011), and B-type natriuretic peptide decreased from 2,279+/-1,900 pg/ml to 102+/-5 pg/ml (p=0.003). After 3 months of LVAD, the H/M ratio increased on delayed images from 1.25+/-0.18 to 1.43+/-0.13 (p=0.01) and on early images from 1.35+/-0.19 to 1.44+/-0.11 (p=0.028), and the washout rate decreased from 51.0+/-23.2% to 30.6+/-8.7%, (p=0.015). There was a significant correlation between the late H/M mIBG ratio and B-type natriuretic peptide (R=0.77, p=0.01) and systolic pulmonary pressure (R=0.7, p=0.05). No significant scintigraphic, functional or hemodynamic change was observed between the 2 evaluations in the 6 patients not treated with an LVAD. CONCLUSIONS: Ventricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.

Assessment and optimization of cell engraftment after transplantation into the heart.

Myocardial regeneration using stem and progenitor cell transplantation in the injured heart has recently become a major goal in the treatment of cardiac disease. Experimental studies and clinical applications have generally been encouraging, although the functional benefits that have been attained clinically are modest and inconsistent. Low cell retention and engraftment after myocardial delivery is a key factor limiting the successful application of cell therapy, irrespective of the type of cell or the delivery method. To improve engraftment, accurate methods for tracking cell fate and quantifying cell survival need to be applied. Several laboratory techniques (histological methods, real-time quantitative polymerase chain reaction, radiolabeling) have provided invaluable information about cell engraftment. In vivo imaging (nuclear medicine modalities, bioluminescence, and MRI) has the potential to provide quantitative information noninvasively, enabling longitudinal assessment of cell fate. In the present review, we present several available methods for assessing cell engraftment, and we critically discuss their strengths and limitations. In addition to providing insights about the mechanisms mediating cell loss after transplantation, these methods can evaluate techniques for augmenting engraftment, such as tissue engineering approaches, preconditioning, and genetic modification, allowing optimization of cell therapies.