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.

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.

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.

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.

Intra-aortic balloon counterpulsation and delayed revascularization for myocardial infarction and shock in the absence of primary angioplasty: a treatment strategy with or without thrombolysis?

OBJECTIVE: When revascularization facilities are not available, thrombolytic therapy (TT) added to intra-aortic balloon counterpulsation (IABC) has been proposed as initial therapy for the management of patients presenting with postmyocardial infarction (MI) cardiogenic shock, followed by prompt transfer to another institution for revascularization. The use of TT in this setting, however, remains controversial. METHODS: We reviewed the records of 81 consecutive patients admitted with cardiogenic shock after acute MI and compared the outcomes of patients initially stabilized, including IABC as an adjunct to TT (IABC+TT group, n=40), with those patients initially stabilized with IABC and no TT (IABC group, n=41). RESULTS: The baseline characteristics of the two study groups were similar. The in-hospital and 6-month survival rates were 47.5 and 33.3% in the IABC+TT group versus 43.9 and 31.6% in the IABC group, respectively (NS). Except for mechanical ventilation more frequently required in the IABC group, other outcome measures were similar in both groups. The in-hospital (76.5 vs. 36.5%, P=0.008) and 6-month (60 vs. 25.4%, P=0.01) survival rates were significantly higher in patients who underwent delayed invasive revascularization, than in patients who underwent no invasive revascularization attempt. CONCLUSION: In patients presenting with acute MI and cardiogenic shock, TT as an adjunct to IABC added no therapeutic benefit when compared with IABC alone. In contrast, the survival of patients was significantly increased by delayed invasive revascularization in both treatment groups. These observations suggest that, when revascularization facilities are not available, stabilization with IABC, followed by prompt transfer for delayed revascularization to a tertiary care hospital, might be the preferred management strategy for patients presenting with post-MI cardiogenic shock.

Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on collagen scaffolds-relevance to tissue engineering.

Mesenchymal stem cells (MSCs) are a promising candidate cell for tissue engineering. Magnetic resonance imaging (MRI) has been proven effective in visualizing iron-labeled stem cells; however, the efficiency of this approach for visualization of cells seeded on scaffolds intended for use as tissue-engineered heart valves has not been assessed. MSCs were labeled by incubating for 48 h with ferumoxide and poly-L-lysine as transfecting agent. Any detrimental effect of iron labeling on cell viability, proliferation, and differentiation was examined using appropriate functional assays. Change in the nuclear magnetic relaxation properties of labeled cells was determined using in vitro relaxometry of cells seeded in 3-dimensional collagen gels. Images of labeled and non-labeled cells seeded onto 1% type I bovine collagen scaffolds were obtained using MRI. The presence of intracellular iron in labeled cells was demonstrated using Prussian blue staining, confocal microscopy, and electron microscopy. Cell viability, proliferation, and differentiation were comparable in labeled and non-labeled cells. The T2 relaxation time was 40% to 50% shorter in ferumoxide-labeled cells. Labeled cells seeded on scaffolds appeared as areas of reduced signal intensity in T2 weighted images. Ferumoxide labeling persisted and remained effective even on scans performed 4 weeks after the labeling procedure. Ferumoxide labeling of human MSCs seeded on collagen scaffolds is an effective, non-toxic technique for visualization of these cells using MRI. This technique appears promising for cell tracking in future tissue-engineering applications.

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.

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.

Prognostic value of iodine-123-metaiodobenzylguanidine myocardial uptake and heart rate variability in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Autonomic nervous system dysfunction is common in congestive heart failure (CHF) and is believed to predispose patients to an increased risk of death. This study aimed to assess the prognostic significance of heart rate variability (HRV) measurements in conjunction with scintigraphic imaging using metaiodobenzylguanidine (MIBG) labeled with iodine-123 (I-123-MIBG), which detects abnormalities in autonomic nervous activity, in patients with stable CHF during optimal medical treatment. The study population included 52 patients (56 +/- 12 years of age) with a mean left ventricular ejection fraction of 31 +/- 12%. All underwent I-123-MIBG scanning and 24-hour ambulatory electrocardiographic monitoring for the analysis of HRV on entrance into the study. The heart/mediastinum MIBG uptake ratio was calculated. HRV analysis included the assessment of time- and frequency-domain variables. During the 2-year follow-up, 14 patients (27%) died. MIBG uptake at 1 hour was less (1.39 +/- 0.10) in nonsurvivors than in survivors (1.50 +/- 0.16; p = 0.013). In univariate Cox regression analysis, MIBG uptake was a significant prognostic factor (p = 0.038, hazard ratio [HR] 0.017, 95% confidence interval [CI] 0.00 to 0.79). Time- and frequency-domain variables were similar in survivors and nonsurvivors. However, high-frequency power was associated with an increased risk for sudden death (HR 0.310, 95% CI 0.101 to 0.954, p = 0.041) but not with all-cause mortality. In conclusion, cardiac I-123-MIBG imaging identifies patients with CHF at high risk of dying and may be a more reliable predictor of overall mortality than HRV.

Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone.

Thirty-six consecutive patients in New York Heart Association functional class IV, who were resistant to 24-hour continuous dobutamine infusion, were treated with continuous infusions of dobutamine 10 microg/kg/min for > or =48 hours (group I, n = 18), followed by weekly intermittent 8-hour infusions or more often if needed. In group II (n = 18), after the initial 24-hour infusion of dobutamine, a 24-hour levosimendan infusion was added followed by biweekly 24-hour infusions. The addition of intermittent levosimendan infusions prolonged the survival of patients with advanced heart failure refractory to intermittent dobutamine infusions (45-day survival rates were 6% and 61% in groups I and II, respectively; p = 0.0002, log-rank test).

Myocardial ischaemic preconditioning in the pig has no effect on the ventricular fibrillation and defibrillation thresholds.

INTRODUCTION: The effects of myocardial ischaemia preconditioning in pigs on the vulnerability to ventricular fibrillation during subsequent ischaemic events are controversial. This study examined the time course of changes in ventricular fibrillation (VFT) and defibrillation (DFT) thresholds during transient myocardial ischaemia after a 45 min preconditioning period. METHODS AND RESULTS: In five open-chest pigs, VFT was measured after 3 min of regional myocardial ischaemia, at time 0, 2, 15, 30, 60 and 90 min (Control group). In seven other pigs (Test group), VFT was measured before (time 0) and 2, 15, 30, 60 and 90 min after ischaemic preconditioning by three consecutive 5 min periods of regional coronary occlusion, followed by 10 min of reperfusion. DFT was measured by increasing the stored energy systematically until successful defibrillation. Ischaemic preconditioning caused no significant change in the effective refractory period (ERP), VFT or DFT over the 90 min of the experiments. In the Control group, ERP remained stable for 30 min, though was significantly lower at 90 min (178 +/- 28 ms) than at baseline (204 +/- 32 ms, P = 0.007). VFT and DFT remained unchanged throughout the experiments, and no difference was observed in ERP, VFT and DFT between the two groups at any time during the experiment. CONCLUSION: No changes were observed in the refractory duration, ventricular vulnerability or defibrillation energy requirements up to 90 min after ventricular ischaemic preconditioning in the pig.

Spontaneous coronary artery dissection as a cause of acute myocardial infarction in the postpartum period.

Spontaneous coronary dissection is an infrequent cause of acute myocardial infarction, and several cases have been presented during the peripartum period. We present a case of acute myocardial infarction resulting from spontaneous coronary artery dissection, in a 37-year-old woman during the postpartum period. Thrombolytic treatment was administered in the emergency room uneventfully but without symptom resolution. Diagnosis was subsequently established by coronary arteriography. The patient's in-hospital and long-term clinical course and prognosis are described and the potential pathogenetic mechanisms are discussed. Finally, the treatment options for this rare entity are presented.

Comparison of pulsatile with nonpulsatile mechanical support in a porcine model of profound cardiogenic shock.

The aim of this study was to examine whether pulsatility by intraaortic balloon counterpulsation (IABP) is an important adjunct to the treatment of profound cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was inserted in the aortic arch through the right external carotid artery, and the inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was subsequently placed in the descending aorta through the left external carotid artery. CS was induced by occlusion of coronary arteries and the infusion of propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic end diastolic pressure, left ventricular end diastolic pressure, right atrial pressure, and heart rate were monitored. Cardiac output and left anterior descending artery flow were measured with a transit time ultrasound flowmeter. During profound CS, life sustaining hemodynamics were maintained only with the support of the assist devices. Hemodynamic support with the CP was associated with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP. Compared with the hemodynamic support offered by the CP alone, addition of the IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p = 0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and left anterior descending artery flow from 26 +/- 10 to 39 +/- 14 ml/min (p = 0.001). In profound CS, mechanical support provided by a continuous flow CP is enhanced by the added pulsatility of the IABP.

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.

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.

Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone.

A 24-hour infusion of levosimendan was added to dobutamine in 18 patients (aged 63 +/- 9 years) hospitalized for management of decompensated New York Heart Association functional class IV heart failure refractory to a continuous 24-hour infusion of dobutamine (10 microg/kg/min) and furosemide (10 mg/hour); the primary study end point was a >or=40% increase in cardiac index and a >or=25% decrease in pulmonary capillary wedge pressure compared with pretreatment measurements. The primary end point was reached in one of the patients treated with dobutamine alone versus 7 patients (39%) treated with levosimendan and dobutamine combined (p = 0.008), whereas at 24 hours, the combined treatment was associated with a 0.76 +/- 0.78 L/min/m(2) (p = 0.001) mean increase in cardiac index and a 6.4 +/- 7.3 mm Hg (p = 0.002) mean decrease in pulmonary capillary wedge pressure compared with measurements obtained after 24 hours of dobutamine infusion alone. Symptoms were alleviated in all patients, and all but 3 were discharged from the hospital.

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.

Moderate systemic hypotension during reperfusion reduces the coronary blood flow and increases the size of myocardial infarction in pigs.

STUDY OBJECTIVE: s: To examine the effects of low arterial BP (ABP) during reperfusion on the extent of myocardial infarction and on coronary blood flow (CBF) in an occlusion/reperfusion experimental model. DESIGN: Prospective, randomized animal study. SETTING: University hospital. PARTICIPANTS: Normal pigs that were anesthetized, intubated, and mechanically ventilated. INTERVENTIONS: Twenty-seven open-chest pigs underwent occlusion of the mid left anterior descending (LAD) coronary artery for 1 h followed by reperfusion for 2 h. During reperfusion, the animals were randomly assigned to either continuous infusion of nitroglycerin in therapeutic doses and fluid infusion at rates to maintain a mean ABP >or= 80 mm Hg (group 1, n = 13), or continuous nitroglycerin infusion at rates to maintain a mean ABP between 60 mm Hg and 75 mm Hg (group 2, n = 14). MEASUREMENTS AND RESULTS: The hemodynamics and the coronary ABP distal to the occlusion were recorded throughout the experiment. In addition, the LAD CBF and peak hyperemia CBF before occlusion and during reperfusion periods were measured by transit-time flowmetry. At the end of the experiment, the infarcted left ventricular myocardial size was measured. There were no significant hemodynamic differences, including the distal coronary arterial pressure, between the two groups before or during the LAD artery occlusion period. During reperfusion, mean ABP was 90 +/- 3 mm Hg in group 1 vs 69 +/- 3 mm Hg in group 2 (p < 0.001). In group 1, the infarcted myocardium represented 50.3 +/- 4.3% of the myocardium at risk, vs 69.4 +/- 7.2% in group 2 (p < 0.001). During reperfusion, CBF and peak hyperemia CBF were significantly higher in group 1 than in group 2. CONCLUSIONS: Low ABP during reperfusion increases the size of myocardial infarction and decreases CBF.

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.