Mycophenolate and sirolimus as calcineurin inhibitor-free immunosuppression improves renal function better than calcineurin inhibitor-reduction in late cardiac transplant recipients with chronic renal failure.

BACKGROUND: Calcineurin-inhibitor-(CNI)-induced renal failure is one major cause of morbidity in cardiac transplantation (HTx). In this prospective, randomized, multicenter trial, the impact of immunosuppressive conversion toward CNI-free (mycophenolate mofetil [MMF] and sirolimus) or a CNI-reduced immunosuppressive regimen on renal function, efficacy, and safety was evaluated. METHODS: Since 2004, 63 HTx-patients (0.5-18.4 years after HTx) with CNI-based immunosuppression and reduced creatinine clearance less than 60 mL/min (39+/-15 mL/min) were included in this trial. Patients in the CNI-free-Group (group 1) were converted to sirolimus that was started with 2 mg/day until target trough levels (8-14 ng/mL) were achieved. Subsequently, CNIs were withdrawn. In CNI-reduction-Group (group 2), CNI target trough levels were reduced by 40%. In both groups MMF was continued and trough level adjusted (1.5-4 microg/mL). RESULTS: Patients demographics and survival (mean follow-up time: 16.7+/-9 months) was equal (100%). Renal function improved significantly after complete CNI withdrawal while remaining unchanged with CNI-reduction (Creatinine clearance after 12 months: 53+/-24 mg/dL [group 1] vs. 38+/-20 mg/dL [group 2], P=0.01). End-stage renal failure (hemodialysis) was avoided by CNI-withdrawal and occurred only after CNI reduction (n=6; P=0.01). Acute rejection episodes were more common in group 2 (4 vs. 2). Graft function remained stable (echocardiography) within both groups. Adverse events were more common in group 1 (65%) than in group 2 (n=40%) and were responsible for discontinuation in 4 and 0 cases, respectively. CONCLUSIONS: Conversion toward a CNI-free immunosuppression (Mycophenolate, sirolimus) is superior to CNI-reduced immunosuppression in improving renal failure in late HTx-recipients. However, this benefit is relativized by the increased incidence and severity of sirolimus/MMF-associated side effects.

The Munich score: a clinical index to predict survival in ambulatory patients with chronic heart failure in the era of new medical therapies.

BACKGROUND: Risk stratification in patients with congestive heart failure (CHF) is an obligatory part of the heart transplantation (HTx) selection process. New medical therapies and the predictive value of hemodynamic changes over time have not been adequately taken into account in previous stratification models. In this study we assessed the prognostic value of 55 variables at baseline and 9 variables representing changes of hemodynamic parameters over time. METHODS: A total of 178 patients with CHF were examined on 3.4 +/- 2.6 occasions (mean follow-up 19 +/- 19 months). Using the Cox proportional hazards model, univariate and multivariate relative risks (RRs) with 95% confidence intervals (CI) were determined for predicting event-free survival. A prognostic score (Munich score) was derived from the multivariate Cox model and three risk groups were derived. RESULTS: During follow-up, 23 patients (13%) died and 63 (35%) underwent HTx. The univariate analysis yielded 21 statistically significant (p < 0.05) predictors of event-free survival. However, only four baseline variables (etiology of ischemic cardiomyopathy, systolic blood pressure, left ventricular [LV] end-diastolic diameter, maximal workload) and the change over 12 months in fractional shortening remained statistically significant (p < 0.05) in the multivariate Cox model and were used for the prognostic score. Within 12 months, no event occurred in the low-risk group, 8.1% in the intermediate, and 30.1% in the high-risk group. CONCLUSIONS: The incorporation of changes over time in hemodynamic parameters allowed for an improved baseline risk stratification model for the HTx selection process, especially in the era of new medical therapies such as beta-blocker therapy. All significant variables of the Munich score can be obtained in routinely performed non-invasive tests.

Quantitative assessment of cardiac allograft vasculopathy by real-time myocardial contrast echocardiography: a comparison with conventional echocardiographic analyses and [Tc99m]-sestamibi SPECT.

AIM: To evaluate the additional benefit of visual and quantitative perfusion measurements compared with conventional real-time myocardial contrast echocardiography (MCE) in the detection of CAV. METHODS AND RESULTS: Thirty patients (26 males, age 58 +/- 9.6 years) underwent dobutamine stress echocardiography (DSE) and myocardial perfusion imaging (MPI) as well as coronary angiography (CA) with intravascular ultrasound (IVUS). Ultrasound images were analysed off-line, evaluating (1) wall motion and thickening at high mechanical index ('conventional evaluation'), (2) the MCE loops stored during continuous infusion of contrast agent with regard to visual changes (stress vs. rest, 'visual grading'), and (3) the replenishment curves of the contrast agent at low mechanical index after bubble destruction ('quantitative grading'). CA/IVUS plus MPI showed ischaemia in seven and myocardial scars in nine patients. Sensitivity, specificity, NPV, PPV and accuracy for the detection of ischaemia representing functionally relevant CAV were, respectively, 0.71, 0.83, 0.90, 0.55 and 0.80 for the conventional evaluation alone, 0.71, 0.91, 0.91, 0.71 and 0.87 for additional visual grading and 0.86, 0.91, 0.95, 0.75 and 0.90 for additional quantitative grading. CONCLUSION: Real-time MCE including visual and quantitative analysis is feasible for screening patients after HTX and is highly accurate in the diagnosis of haemodynamically relevant CAV.

Effects of calcium supplementation on bone loss and fractures in congestive heart failure.

BACKGROUND: Cross-sectional studies have shown that more than 50% of patients with congestive heart failure (CHF) have decreased bone mineral density (BMD). There is limited knowledge about the longitudinal changes of BMD and how to treat bone loss in patients with CHF. METHODS: The present study was a prospective, longitudinal trial in which 33 male patients with CHF (ejection fraction (EF): 30+/-11%) were assigned to 1000 mg calcium supplementation or no supplementation. BMD was measured at the lumbar spine (LS) and the femoral neck (FN) by dual-energy X-ray absorptiometry at baseline and after 12 months. RESULTS: Osteopenia (LS 33% and FN 36%) and osteoporosis (LS 15% and FN 6%) were frequently seen in these patients; 70% showed impaired renal function, 42% secondary hyperparathyroidism, and 33% hypogonadism. Bone resorption markers were strongly elevated and correlated negatively with the EF. Patients without calcium supplementation revealed a reduction of BMD (LS 1.7% and FN 1.9%) within 12 months. The fracture incidence was 6%. Patients with calcium supplementation also demonstrated a 6% fracture incidence and a decrease in BMD (LS 1.2% and FN 1.6%), which was not significantly different from the untreated group. Loss of BMD at FN was only seen in patients with impaired renal function. CONCLUSIONS: Patients with CHF demonstrate a progressive decrease in BMD when compared with age-matched healthy individuals. Increased bone resorption due to renal insufficiency with consecutive secondary hyperparathyroidism is a main reason for BMD loss in CHF. Calcium supplementation alone cannot sufficiently prevent the decrease in BMD.

Mycophenolate acid inhibits endothelial NAD(P)H oxidase activity and superoxide formation by a Rac1-dependent mechanism.

Endothelial dysfunction precedes hypertension and atherosclerosis and predicts cardiac allograft vasculopathy and death in heart transplant recipients. Endothelial overproduction of reactive oxygen species, such as superoxide anions produced by NAD(P)H oxidase, induces endothelial dysfunction. Because immunosuppressive drugs have been associated with increased reactive oxygen species production and endothelial dysfunction, we sought to elucidate the underlying mechanisms. Reactive oxygen species, release of superoxide anions, and NAD(P)H oxidase activity were studied in human umbilical vein endothelial cells and in polymorphonuclear neutrophils. Gp91ds-tat was used to specifically block NAD(P)H oxidase. Transcriptional activation of different subunits of NAD(P)H oxidase was assessed by real-time RT-PCR. Rac1 subunit translocation and activation were studied by membrane fractionation and pull-down assays. Calcineurin inhibitors significantly increased endothelial superoxide anions production because of NAD(P)H oxidase, whereas mycophenolate acid (MPA) blocked it. MPA also attenuated the respiratory burst induced by neutrophil NAD(P)H oxidase. Because transcriptional activation of NAD(P)H oxidase was not affected, but addition of guanosine restored endothelial superoxide anions formation after MPA treatment, we speculate that the inhibitory effect of MPA was mediated by depletion of cellular guanosine triphosphate content. This prevented activation of Rac1 and, thus, of endothelial NAD(P)H oxidase. Because all heart transplant recipients are at risk for cardiac allograft vasculopathy development, these differential effects of immunosuppressants on endothelial oxidative stress should be considered in the choice of immunosuppressive drugs.

Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is relevant to prognosis of congestive heart failure and heart transplantation. Proof of reversibility by pharmacologic testing in potential transplantation candidates is important because it indicates a reduced probability of right ventricular failure or death in the early post-transplant period. This study aimed to clarify the possible extent of acute reversibility of elevated PVR in a large, consecutive cohort of heart transplant candidates. METHODS: This study included 208 consecutive patients (age 52 +/- 10 years, 89% men and 11% women, ejection fraction 21 +/- 9%, Vo2max 12.6 +/- 4.2 ml/kg/min) being evaluated for heart transplantation in 7 transplant centers in Germany and Switzerland. Testing was performed with increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173 +/- 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline PVR of > 2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of > 12 mm Hg. RESULTS: PGE1 testing lowered PVR from 4.1 +/- 2.0 to 2.1 +/- 1.1 WU (p < 0.01), increased cardiac output from 3.8 +/- 1.0 to 5.0 +/- 1.5 liters/min (p < 0.01), and decreased TPG from 14 +/- 4 to 10 +/- 3 mm Hg (p < 0.01), mean pulmonary artery pressure (PAM) from 39 +/- 9 to 29 +/- 9 mm Hg (p < 0.01) and mean pulmonary capillary wedge pressure (PCWP) from 24 +/- 7 to 19 +/- 9 mm Hg (p < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic hypotension was not observed. For the whole population the percentage of patients with PVR > 2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in each patient; only 2 patients (1%) remained ineligible for listing because of a final PVR of > 4.0 WU. TPG, ejection fraction and male gender were independent predictors of reversibility of PVR. CONCLUSIONS: Elevated PVR in heart transplant candidates is highly reversible and can be normalized during acute pharmacologic testing with PGE1.

Clinical validation of the gated blood pool SPECT QBS processing software in congestive heart failure patients: correlation with MUGA, first-pass RNV and 2D-echocardiography.

INTRODUCTION: Left (LVEF) and right ventricular ejection fraction (RVEF) as well as LV regional wall motion at rest are valuable tools to monitor and tailor treatment of congestive heart failure (CHF) patients. Gated blood pool SPECT (GBPS) is under evaluation as an "all-in-one" technique, providing information on LVEF, RVEF, and wall motion derived from a single examination. Aim of the study was to evaluate a commercially available automated GBPS processing software for EF measurements and wall motion analysis in heart failure patients. METHODS: Thirty-two patients (12 female; mean age+/-SD: 53+/-13 years), suffering from dilated (63%), ischemic (25%) or hypertrophic (13%) cardiomyopathy, were studied. First-pass radionuclide ventriculography (FP-RNV), planar multigated radionuclide angiography (MUGA), and GBPS were performed at rest after in vivo labeling of red blood cells, and LVEF and RVEF was calculated with each method. Later on the same day LVEF was calculated by echocardiography. LV wall motion (summed motion score and wall motion index) was derived from GBPS and echocardiography using the standard 16-segment model. RESULTS: Mean LVEF measured by GBPS, echocardiography, MUGA and FP-RNV was 33+/-13%, 37+/-15%, 41+/-14% and 45+/-13%, respectively. LVEF values calculated from GBPS showed moderate to good correlation with FP-RNV (r=0.61), MUGA (r=0.65) and ECHO (r=0.74; all p<0.01). Mean RVEF calculated by GBPS, FP-RNV and MUGA was 45+/-14%, 46+/-9% and 38+/-9%, respectively. RVEF values calculated from GBPS showed weak correlation with FP-RNV (r=0.33) and MUGA (r=0.26; all p=n.s.). Assessment of GBPS wall motion was qualitatively possible in all patients. The agreement between GBPS and ECHO was 82% (kappa=0.73). The wall motion index showed good correlation between both methods (r=0.88; p<0.001). CONCLUSION: An automated algorithm for LVEF calculation and wall motion analysis using GBPS is feasible for clinical routine diagnostic in CHF patients. The RVEF calculation method needs to be improved before routine clinical application can be recommended.

Intravascular ultrasound-guided percutaneous coronary intervention in a human immunodeficiency virus-positive patient with cocaine-associated acute myocardial infarction: case report and review.

Cocaine use is a major problem worldwide and there are numerous reports about cocaine-associated myocardial infarction. Nevertheless minimal data are available from randomised clinical trials to suggest evidence-based approaches to the management of cocaine-associated myocardial ischemia. Moreover, most reports have been limited to conservative management of cocaine-associated myocardial infarction. We report a case of a young male cocaine user with acute myocardial infarction, undergoing diagnostic coronary angiography and intravascular ultrasound revealing severe atherosclerosis, followed by successful stent implantation.

Discrepancy between morphologic and functional criteria of optimal stent deployment using intravascular ultrasound and pressure derived myocardial fractional flow reserve.

BACKGROUND: Pressure derived myocardial FFR, a functional index of epicardial stenosis has been proposed for the assessment of optimal stent deployment. The following study evaluated the potential of serial fractional flow reserve (FFR) measurements in comparison to the 'gold standard' intravascular ultrasound (IVUS) for optimal stent deployment and its long-term outcome. METHODS: 35 patients with a single de novo lesion underwent PTCA followed by stent implantation with an initial inflation pressure of 12 atm. If optimal stent expansion using IVUS-criteria were not fulfilled, re-dilatation at 16 atm as well as additional inflations with larger balloon sizes were performed to reach the procedural end-point. IVUS and FFR were performed after each dilatation (n = 136). Angiography was repeated after 6 months. RESULTS: In 30 pts who fulfilled IVUS criteria, mean lumen area (2.9+/-1.3 mm2) increased after PTCA and stent implantation to 10.0+/-3.0 mm2. In six pts, optimum stent deployment according to a value of FFR0.94 was not reached. Four of six pts reached the IVUS criteria at 12 atm and two pts at 16 atm, respectively. Positive and negative predictive values of FFR were 26 and 64%. Three of the 30 pts (10%) revealed a restenosis at three months follow-up. One of these restenosis was seen in a patient with a post-procedural FFR<0.94. CONCLUSIONS: FFR was not valid to predict optimal stent expansion according to IVUS criteria but could delineate under-expanded stents despite a reasonable angiographic appearance. Morphologic (IVUS) and functional criteria (FFR) for optimal stent deployment revealed a comparably low restenosis rate.

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

BACKGROUND: Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. METHODS: FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 microg as boli) and a standard intravenous infusion of 140 microg/kg/min were administered in a randomized fashion. RESULTS: Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-microg intracoronary bolus and 140-microg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-microg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-microg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. CONCLUSIONS: This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 microg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 microg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.

Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.

Comparison of pressure measurement, dobutamine contrast stress echocardiography and SPECT for the evaluation of intermediate coronary stenoses. The COMPRESS trial.

BACKGROUND: DSE and SPECT are two well-established methods to non-invasively investigate the functional significance of coronary artery stenoses in patients with coronary artery disease. The measurement of Fractional Flow Reserve has emerged a new invasive reference standard for lesion specific quantification of coronary artery stenoses. The objective of our prospective study was to compare sensitivity and specificity of Dobutamine Stress Echocardiography (DSE) and Single Photon Emission Computer tomography (SPECT) with the pressure derived Fractional Flow Reserve (FFR) for the identification of hemodynamic relevant coronary lesions in patients with predominately coronary multivessel disease and angiographically intermediate stenoses. METHODS: Inclusion criteria were a coronary lesion of 50-75% diameter stenosis by visual assessment in patients with known or suspected CAD. SPECT, DSE and FFR testing was performed within one week of coronary angiography. RESULTS: The study comprised 48 consecutive symptomatic patients. In 41 cases, a coronary multivessel disease was present. Mean FFR was 0.80 +/- 0.13 (0.41-1.0). Overall sensitivity of DSE and SPECT was 67% and 69% whereas specificity reached 77% and 87%. However, sensitivity was significantly reduced if the target lesion was located distally. DSE showed poor results if the lesions were located in the circumflex artery or if a history of prior myocardial infarctions was present. CONCLUSION: DSE and SPECT are both useful methods for the non-invasive assessment of coronary artery disease. DSE showed reasonable combination of sensitivity and specificity even in patients with multivessel disease. Although use of noninvasive stress tests is only limited in patients with prior myocardial infarctions and invasive stress testing should be preferred in these patients.

Transcatheter closure of a ruptured ventricular septum following inferior myocardial infarction and cardiogenic shock.

Elective transcatheter closure of congenital septal defects has emerged as a valuable method, but the clinical experience on occlusion of ventricular septal rupture after myocardial infarction is very limited. We report a case of fatal outcome in a patient with inferior myocardial infarction and cardiogenic shock despite technically successful transcatheter closure of a large complex ventricular septal defect.

The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx). METHODS: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy. CONCLUSIONS: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.

Early detection of myocardial microcirculatory disturbances after primary PTCA in patients with acute myocardial infarction: coronary blood flow velocity versus sestamibi perfusion imaging.

BACKGROUND: The extent of myocardial salvage after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) is variable and can not be predicted on the basis of vessel patency. The aim of this study was to evaluate the tissue salvage and the microvascular integrity after successful intervention in AMI by coronary blood flow velocity and sestamibi perfusion imaging. METHODS: Twenty-two patients (17 m, 5f; mean age 57 +/- 14 yrs.) undergoing primary PTCA and stent implantation for AMI were studied. 99mTc Sestamibi was injected intravenously before intervention and single photon emission computed tomography (SPECT) was performed immediately after successful reperfusion to determine the area at risk before PTCA due to the minimal 99mTc Sestamibi redistribution. Sestamibi SPECT was repeated 3 days and 6 months after AMI. Area at risk (%) was determined automatically by myocardial perfusion tomography (PERFIT) with the use of a multistage, 3D iterative inter-subject registration of patient images to normal templates (2SD) and myocardial salvage was calculated. Coronary flow velocity was measured using a Doppler-tipped guidewire in the infarct-related artery after successful completion of primary PTCA and in an angiographically normal reference vessel. Absolute coronary flow reserve (CFR) and relative CFR (rCFR) were calculated using hyperemic to basal average peak velocity. RESULTS: Despite successful reperfusion of the target vessel (TIMI grade III flow) CFR and rCFR remained impaired (1.8 +/- 0.9 and 0.77 +/- 0.21). Area at risk decreased significantly from 21 +/- 9% to 9 +/- 10% (p < 0.05) corresponding to 11 +/- 8% myocardial salvage. Acute CFR and rCFR showed no correlation with the area at risk before and after primary PTCA. The increase of CFR within 6 months correlated with the myocardial salvage (p < 0.05). CONCLUSIONS: Despite successful primary PTCA in AMI, CFR and rCFR often remain impaired because of a significant loss of microvascular integrity. The long-term success of primary PTCA can be assessed by myocardial salvage and the change of CFR which might be a useful parameter for additional reperfusion strategies such as glycoprotein IIb/IIIA receptor inhibition.

Fractional flow reserve predicts major adverse cardiac events after coronary stent implantation.

OBJECTIVES: Determination of fractional flow reserve (FFR) allows the functional assessment of coronary stenoses before and after an intervention. Preliminary data suggest that a FFR > or = 0.94 is associated with an excellent clinical outcome after stent implantation. However, these results were limited both by the number of patients included and the use of non-contemporary stent designs. We sought to determine the prognostic value of FFR measurements in a large patient cohort undergoing coronary stent implantation. METHODS: Eighty-nine consecutive patients were enrolled in whom a stent implantation was performed and a pressure wire was used as a guide wire. Patients were followed for at least 6 months. Death, myocardial infarction (MI) and target vessel revascularization (TVR) were considered cardiac events. A FFR > or = 0.94 was regarded as an optimal functional result. RESULTS: A complete follow-up was available in all patents. Pre-interventional FFR increased from 0.66 +/- 0.16 to 0.95 +/- 0.05 (p < 0.0001) after stent implantation. Sixteen (18%) events occurred during follow-up including 10 (11.2%) TVR. Final FFR was significantly higher in patients without compared to patients with an event (0.92 +/- 0.06 vs. 0.96 +/- 0.05, p < 0.003). By univariate analysis, the presence of diabetes mellitus, left ventricular function, residual diameter stenosis and final FFR were associated with a worse clinical outcome. In the multivariate analysis, only the final FFR and left ventricular function remained as significant predictors for cardiac events (relative risk, 3.50; 95% CI: 1.29-9.52, P < 0.014, and 0.97; 95% CI: 0.93-1.00, p = 0.047). CONCLUSION: These results demonstrate in a nonselected patient cohort a strong correlation between FFR values after coronary stenting and subsequent cardiac events. Further studies have to investigate whether outcome after stenting might be improved by guiding the procedure with a pressure guide wire.