Time elapsed after contrast injection is crucial to determine infarct transmurality and myocardial functional recovery after an acute myocardial infarction.

BACKGROUND: In acute myocardial infarction (MI), late Gadolinium enhancement (LGE) has been proposed to include the infarcted myocardium and area at risk. However, little information is available on the optimal timing after contrast injection to differentiate these 2 areas. Our aim was to determine in acute and chronic MI whether imaging time after contrast injection influences the LGE size that better predicts infarct size and functional recovery. METHODS: Subjects were evaluated by cardiovascular magnetic resonance (CMR) the first week (n = 60) and 3 months (n = 47) after a percutaneously revascularized STEMI. Inversion-recovery single-shot (ss-IR) imaging was acquired at multiple time points following contrast administration and compared to segmented inversion-recovery (seg-IR) sequences. Inversion time was properly adjusted and images were blinded, randomized and measured for LGE volumes. RESULTS: In acute MI, LGE volume decreased over several minutes (p = 0.005) with the greatest volume occurring at 3 minutes and the smallest at 25 minutes post-contrast injection; however, LGE volume remained constant over time in chronic MI (p = 0.886). Depending on the imaging time, in acute phase, a change in the transmurality index was also observed. A transmural infarction (>75%) at 25 minutes better predicted the absence of improvement in the wall motion score index (WMSI), a higher increase in left ventricular volumes and a lower ejection fraction compared to 10 minutes. CONCLUSIONS: A change was observed in LGE volume in the minutes following contrast administration in acute but not in chronic MI. Infarct transmurality 25 minutes post-contrast injection better predicted infarct size and functional recovery at follow-up.

Prevalence of regional myocardial thinning and relationship with myocardial scarring in patients with coronary artery disease.

IMPORTANCE: Regional left ventricular (LV) wall thinning is believed to represent chronic transmural myocardial infarction and scar tissue. However, recent case reports using delayed-enhancement cardiovascular magnetic resonance (CMR) imaging raise the possibility that thinning may occur with little or no scarring. OBJECTIVE: To evaluate patients with regional myocardial wall thinning and to determine scar burden and potential for functional improvement. DESIGN, SETTING, AND PATIENTS: Investigator-initiated, prospective, 3-center study conducted from August 2000 through January 2008 in 3 parts to determine (1) in patients with known coronary artery disease (CAD) undergoing CMR viability assessment, the prevalence of regional wall thinning (end-diastolic wall thickness ≤5.5 mm), (2) in patients with thinning, the presence and extent of scar burden, and (3) in patients with thinning undergoing coronary revascularization, any changes in myocardial morphology and contractility. MAIN OUTCOMES AND MEASURES: Scar burden in thinned regions assessed using delayed-enhancement CMR and changes in myocardial morphology and function assessed using cine-CMR after revascularization. RESULTS: Of 1055 consecutive patients with CAD screened, 201 (19% [95% CI, 17% to 21%]) had regional wall thinning. Wall thinning spanned a mean of 34% (95% CI, 32% to 37% [SD, 15%]) of LV surface area. Within these regions, the extent of scarring was 72% (95% CI, 69% to 76% [SD, 25%]); however, 18% (95% CI, 13% to 24%) of thinned regions had limited scar burden (≤50% of total extent). Among patients with thinning undergoing revascularization and follow-up cine-CMR (n = 42), scar extent within the thinned region was inversely related to regional (r = -0.72, P < .001) and global (r = -0.53, P < .001) contractile improvement. End-diastolic wall thickness in thinned regions with limited scar burden increased from 4.4 mm (95% CI, 4.1 to 4.7) to 7.5 mm (95% CI, 6.9 to 8.1) after revascularization (P < .001), resulting in resolution of wall thinning. On multivariable analysis, scar extent had the strongest association with contractile improvement (slope coefficient, -0.03 [95% CI, -0.04 to -0.02]; P < .001) and reversal of thinning (slope coefficient, -0.05 [95% CI, -0.06 to -0.04]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CAD referred for CMR and found to have regional wall thinning, limited scar burden was present in 18% and was associated with improved contractility and resolution of wall thinning after revascularization. These findings, which are not consistent with common assumptions, warrant further investigation.

Infarct healing is a dynamic process following acute myocardial infarction.

BACKGROUND: The role of infarct size on left ventricular (LV) remodeling in heart failure after an acute ST-segment elevation myocardial infarction (STEMI) is well recognized. Infarct size, as determined by cardiovascular magnetic resonance (CMR), decreases over time. The amount, rate, and duration of infarct healing are unknown. METHODS: A total of 66 patients were prospectively enrolled after reperfusion for an acute STEMI. Patients underwent a CMR evaluation within 1 week, 4 months, and 14 months after STEMI. RESULTS: Mean infarct sizes for the 66 patients at baseline (acute necrosis), early follow-up (early scar), and late follow-up (late scar) were 25 ± 17 g, 17 ± 12 g, and 15 ± 11 g, respectively. Patients were stratified in tertiles, based on infarct size, with the largest infarcts having the greatest absolute decrease in mass at early and late scar. The percent reduction of infarct mass was independent of initial infarct size. There was an 8 g or 32% decrease in infarct mass between acute necrosis and early scar (p < 0.01) with a 2 g or 12% additional decrease in infarct mass between early and late scar (p < 0.01). CONCLUSIONS: Infarct healing is a continuous process after reperfusion for STEMI, with greatest reduction in infarct size in the first few months. The dynamic nature of infarct healing through the first year after STEMI indicates that decisions based on infarct size, and interventions to reduce infarct size, must take into consideration the time frame of measurement.

Recovery of the lumbopelvic movement and muscle recruitment patterns using motor control exercise program in people with chronic nonspecific low back pain: A prospective study.

This study aims to investigate the dysfunction and recovery of the lumbopelvic movement and motor control of people with chronic nonspecific low back pain after a structured rehabilitation which emphasizes on re-education and training of movement and motor control. The lumbopelvic movement and motor control pattern of 30 adults (15 with chronic low back pain, 15 healthy controls) were assessed using 3D motion and electromyographic analysis during the repeated forward bending test, in additional to the clinical outcome measures. Regional kinematics and muscle recruitment pattern of the symptomatic group was analysed before and after the 6-week rehabilitation, and compared to healthy controls. Significant improvement in back pain, functional capacity and self-efficacy of the symptomatic group was found after the rehabilitation. Patients with chronic nonspecific low back pain were capable to recover to a comparable level of the healthy controls in terms of their lumbopelvic movement and motor control pattern upon completion of a 6-week rehabilitation program, despite their dysfunction displayed at baseline. Phase specific motor control reorganization in which more profound and positive changes shown during the flexion phase. Our findings indicate that the recovery of the movement and motor control pattern in patients with chronic low back pain achieved to a comparable level of the healthy able-bodies. The improvement of both the physical outcome measures suggest that specific rehabilitation program which emphasizes on optimizing motor control during movements would help promoting the functional recovery of this specific low back pain subgroup.

Estimating Myocardial Infarction Size With a Simple Electrocardiographic Marker Score.

Background Myocardial infarction (MI) size is a key predictor of prognosis in post-MI patients. Cardiovascular magnetic resonance (CMR) is the gold standard test for MI quantification, but the ECG is less expensive and more widely available. We sought to quantify the relationship between ECG markers and cardiovascular magnetic resonance infarct size. Methods and Results Patients with prior MI enrolled in the DETERMINE (Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation) and PRE-DETERMINE Trial and Registry were included. ECG leads were analyzed for markers of MI: Q waves, fragmented QRS, and T wave inversion. DETERMINE Score=number of leads with [Q waves×2]+[fragmented QRS]+[T wave inversion]. Left ventricular ejection fraction (LVEF) and infarct size as a percentage of left ventricular mass (MI%) were quantified by cardiovascular magnetic resonance. The Modified Selvester Score estimates MI size from 37 ECG criteria. In 551 patients (aged 62.1±10.9 years, 79% men, and LVEF=40.3±11.0%), MI% increased as the number of ECG markers increased (P<0.001). By univariable linear regression, the DETERMINE Score (range 0-26) estimated MI% (R2=0.18, P<0.001) with an accuracy approaching that of LVEF (R2=0.22, P<0.001) and higher than the Modified Selvester Score (R2=0.09, P<0.001). By multivariable linear regression, addition of the DETERMINE Score improved estimation of MI% over LVEF alone (P<0.001) and over Modified Selvester Score alone (P<0.001). Conclusions In patients with prior MI, a simple ECG score estimates infarct size and improves infarct size estimation over LVEF alone. Because infarct size is a powerful prognostic indicator, the DETERMINE Score holds promise as a simple and inexpensive risk assessment tool.

Unrecognized non-Q-wave myocardial infarction: prevalence and prognostic significance in patients with suspected coronary disease.

BACKGROUND: Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR. METHODS AND FINDINGS: We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%+/-18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8-2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5-51.1) and cardiac mortality (HR 17.4, 95% CI 2.2-137.4). CONCLUSIONS: In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF. TRIAL REGISTRATION: Clinicaltrials.gov NCT00493168.

Prevalence and Prognosis of Unrecognized Myocardial Infarction in Asymptomatic Patients With Diabetes: A Two-Center Study With Up to 5 Years of Follow-up.

OBJECTIVE: To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes. RESEARCH DESIGN AND METHODS: In this prospective, two-center study of asymptomatic patients without known cardiac disease (n = 120), two prespecified cohorts underwent a research MRI: 1) a high-risk group with type 1 diabetes and chronic renal insufficiency (n = 50) and 2) an average-risk group with type 2 diabetes (n = 70). The primary end point was a composite of all-cause mortality and clinical MI. RESULTS: Overall, the prevalence of unrecognized MI was 19% by DE-MRI (28% high-risk group and 13% average-risk group) and 5% by electrocardiography. During up to 5 years of follow-up with a total of 460 patient-years of follow-up, the rate of death/MI was markedly higher in patients with diabetes with (vs. without) unrecognized MI (all 44% vs. 7%, high-risk group 43% vs. 6%, and average-risk group 44% vs. 8%; all P < 0.01). After adjustment for Framingham risk score, left ventricular ejection fraction, and diabetes type, the presence of unrecognized MI by DE-MRI conferred an eightfold increase in risk of death/MI (95% CI 3.0-21.1, P < 0.0001). Addition of unrecognized MI to clinical indices significantly improved model discrimination for adverse events (integrated discrimination improvement = 0.156, P = 0.001). CONCLUSIONS: Unrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.

The use of periinfarct contrast-enhanced cardiac magnetic resonance imaging for the prediction of late postmyocardial infarction ventricular dysfunction.

BACKGROUND: Although ejection fraction (EF) both perimyocardial infarction (MI) and late post-MI are important prognostic factors, only implantable cardioverter-defibrillator trials of post-MI patients with depressed late EF have shown improved survival. This may relate to imprecision of early EF because of post-MI stunning. We sought to determine if peri-MI infarct size, as measured by cardiac magnetic resonance (CMR), is superior to early EF to predict late post-MI EF. METHODS: Seventy-three patients with ST-elevation MI had infarct size and EF quantified using CMR early (<1 week) and late (>3 months) post-MI. RESULTS: Late EF was significantly correlated with early EF (R = 0.734, P < .001), and with infarct size (R = -0.661, P < .001), and both early EF and infarct size were significant predictors of late EF. Subgroup analyses showed that low late EF (35%. There was no difference in early EF between the subgroup with a late EF >35% compared to the subgroup with late EF

Assessment and key targets for therapy in the post-myocardial infarction patient with left ventricular dysfunction.

In the post-myocardial infarction (MI) patient with coronary artery disease (CAD) and left ventricular dysfunction (LVD), ischemia and adverse remodeling hinder myocardial performance and increase electrical instability. Collectively, the coronary arteries, myocardium, and conduction system represent the principal pathophysiologic targets in MI complicated by LVD. Consequently, an accurate assessment of disease severity in these targets is essential for the design of an effective therapeutic program. This review describes the current modalities for assessing the key pathophysiologic targets in post-MI patients with LVD and the effects of systemic factors on cardiac disease severity.

Anti-inflammatory effects of LK-3, on LPS-induced sepsis in rats.

Dextromethorphan (DM), an antitussive agent, has been shown to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of LK-3, an analog of DM, on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/ kg) in anesthetized Wistar rats. Results demonstrated that post-treatment with LK-3 (4 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and bradycardia) in rats treated with LPS. Meanwhile, LK-3 (4 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by post-treatment of LK-3. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by post-treatment with LK-3. In conclusion, the beneficial effects of LK-3 on LPS-induced sepsis resulted from its anti-inflammatory and antioxidant effects.

JKB-122 is effective, alone or in combination with prednisolone in Con A-induced hepatitis.

Con A-induced hepatitis in mice is an established model of autoimmune hepatitis (AIH). JKB-122, a toll-like receptor 4 (TLR4) antagonist, was tested for hepatotprotectant activity. Within several hours of Con A challenge (15mg/kg iv), increased production of proinflammatory cytokines with inflammatory infiltrate occurred in the liver. The severity of tissue necrosis and the amount of circulating liver enzymes peak at 24h post Con A challenge. JKB-122 was given 24 and 16h before, then concurrently, and 4 and 8h (× 5 doses) after challenge with Con A. Serum and liver were harvested at 3, 9 and 24h post Con A challenge. JKB-122 at 20 and 50mg/kg po prevented the increase of serum liver enzymes by 47% and 95% respectively vs vehicle control 24h post Con A. JKB-122 significantly inhibited Con A-induced pathological lesions in the liver and the amount of IFN-γ IL-1ß, IL-4, IL-5, IL-6, IL-17A and TNF-α starting as early as 3h post Con A. Moreover, JKB-122 given concurrently (× 3 doses) with Con A showed similar effect. Finally, JKB-122 enhanced the therapeutic effects of submaximal dose of prednisolone with improved lesion score. It is concluded that JKB-122 at 20 and 50mg/kg po caused dose-dependent inhibition of elevated liver enzymes in Con A-induced hepatitis in mice, indicating hepatoprotectant activity. The results suggest that JKB-122 as monotherapy or in combination with prednisolone may offer a viable approach to the treatment of AIH.

Ubiquitin orchestrates proteasome dynamics between proliferation and quiescence in yeast.

Proteasomes are essential for protein degradation in proliferating cells. Little is known about proteasome functions in quiescent cells. In nondividing yeast, a eukaryotic model of quiescence, proteasomes are depleted from the nucleus and accumulate in motile cytosolic granules termed proteasome storage granules (PSGs). PSGs enhance resistance to genotoxic stress and confer fitness during aging. Upon exit from quiescence PSGs dissolve, and proteasomes are rapidly delivered into the nucleus. To identify key players in PSG organization, we performed high-throughput imaging of green fluorescent protein (GFP)-labeled proteasomes in the yeast null-mutant collection. Mutants with reduced levels of ubiquitin are impaired in PSG formation. Colocalization studies of PSGs with proteins of the yeast GFP collection, mass spectrometry, and direct stochastic optical reconstitution microscopy of cross-linked PSGs revealed that PSGs are densely packed with proteasomes and contain ubiquitin but no polyubiquitin chains. Our results provide insight into proteasome dynamics between proliferating and quiescent yeast in response to cellular requirements for ubiquitin-dependent degradation.

Inflammation as a Driver of Adverse Left Ventricular Remodeling After Acute Myocardial Infarction.

Treatment of acute myocardial infarction (AMI) has improved significantly in recent years, but many patients have adverse left ventricular (LV) remodeling, a maladaptive change associated with progressive heart failure. Although this change is usually associated with large infarcts, some patients with relatively small infarcts have adverse remodeling, whereas other patients with larger infarcts (who survive the first several days after AMI) do not. This paper reviews the relevant data supporting the hypothesis that individual differences in the intensity of the post-AMI inflammatory response, involving 1 or more inflammatory-modulating pathways, may contribute to adverse LV remodeling. It concludes by outlining how individual variations in the inflammatory response could provide important novel therapeutic targets and strategies.

Magnetic resonance versus radionuclide pharmacological stress perfusion imaging for flow-limiting stenoses of varying severity.

BACKGROUND: Although magnetic resonance first-pass imaging (MRFP) has potential advantages in pharmacological stress perfusion imaging, direct comparisons of current MRFP and established radionuclide techniques are not available. METHODS AND RESULTS: Graded regional differences in coronary flow were produced during global coronary vasodilation in chronically instrumented dogs by partially occluding the left circumflex artery. Regional differences in full-thickness flow quantified using microspheres were compared with regional differences obtained with MRFP and radionuclide SPECT imaging (99mTc-sestamibi and 201Tl). Relative regional flows (RRFs) derived from the initial areas under MRFP signal intensity-time curves were linearly related to reference microsphere RRFs over the full range of vasodilation (y=0.93x+4.3; r2=0.77). Relationships between 99mTc-sestamibi and 201Tl RRFs and microsphere RRFs were curvilinear, plateauing as flows increased. The high spatial resolution of the MRI enabled transmural flow to be evaluated in 3 to 5 layers across the myocardial wall. Reductions in subendocardial flow were visually apparent in MRFP images for > or =50% reductions in full-thickness flow. Endocardial-to-epicardial gradients in MRFP flow increased progressively with stenosis severity, whereas transmural flow patterns in remote normally perfused myocardium remained normal. Flow reductions of > or =50% not identified by radionuclide imaging were apparent in MRFP full-thickness and transmural analyses. CONCLUSIONS: High-resolution MRFP can identify regional reductions in full-thickness myocardial blood flow during global coronary vasodilation over a wider range than current SPECT imaging. Transmural flow gradients can also be identified; their magnitude increases progressively as flow limitations become more severe and endocardial flow is compromised increasingly.

Effect of weight reduction on the severity of lower urinary tract symptoms in obese male patients with benign prostatic hyperplasia: a randomized controlled trial.

PURPOSE: We assessed whether weight reduction is an effective intervention for the management of lower urinary tract symptoms (LUTS) and investigated the relationship between obesity and LUTS. MATERIALS AND METHODS: This was a prospective randomized controlled trial that enrolled obese men older than 50 years with LUTS. The study period was 52 weeks. All patients received standardized alpha-adrenergic blocker therapy for the treatment of benign prostatic hyperplasia (BPH) during the run-in period. Patients were randomized to receive either a standardized prerecorded video program on the general principle of weight reduction or a comprehensive weight reduction program. Patients were assessed at different time points with symptom assessment, uroflowmetry, transrectal ultrasound, and metabolic assessment. RESULTS: Sixty-five patients were allocated to each study arm. After the study period, no significant difference in weight reduction was found between the two arms. When the pre- and postintervention parameters were compared, none were statistically different between the 2 arms, namely nocturia, International Prostate Symptom Score, quality of life assessment, and uroflowmetry parameters. When the whole study population was taken as a single cohort, these parameters were also not significantly different between the group with a body mass index of 25 to <30 kg/m(2) and the group with a BMI of 30 to 35 kg/m(2). CONCLUSIONS: We found no association between obesity and LUTS. This could have been due to the less marked weight difference in our cohort. Whereas weight reduction may be an effective measure to improve LUTS, the implementation of a successful program remains a challenge.

Effects of amino acid supplementation on left ventricular remodeling in patients with chronic heart failure with decreased systolic function and diabetes mellitus: rationale and design of a magnetic resonance imaging study.

A considerable number of patients with reduced systolic function caused by primary or ischemic cardiomyopathy have viable and noncontractile myocardium. This may be related to numerous and perhaps overlapping factors, such as chronic ischemia (stunning/hibernation), neurohormonal abnormalities, oxidative stress, metabolic imbalances, and/or nutritional depletion. Changes in myocardial substrate utilization have adverse effects on the metabolism of the viable but noncontractile myocardium. Shifting the energy substrate preference away from fatty acids and replenishing the tricarboxylic acid cycle components via amino acids rather than via fatty acids would increase adenosine triphosphate production, with positive effects on cellular metabolism. A proposed study design is described and will be piloted through the Effects of Diatrofen on Myocardial Function in Patients with Chronic Heart Failure trial (D-CHF), an evaluation of an oral amino acid supplementation treatment in outpatients with heart failure.

Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients.

The aim of this study was to evaluate the value of microvascular obstruction (MO) and infarct size as a percentage of left ventricular mass (IS%LV), as measured by contrast-enhanced cardiac magnetic resonance, in predicting major cardiovascular adverse events (MACE) at 2 years in patients with ST-segment elevation myocardial infarction reperfused by primary percutaneous coronary intervention. Individual data from 1,025 patients were entered into the pooled analysis. MO was associated with the occurrence of MACE, defined as a composite of cardiac death, congestive heart failure, and myocardial re-infarction (adjusted hazard ratio: 3.74; 95% confidence interval: 2.21 to 6.34). IS%LV ≥25% was not associated with MACE (adjusted hazard ratio: 0.90; 95% confidence interval: 0.59 to 1.37). The authors conclude that MO is an independent predictor of MACE and cardiac death, whereas IS%LV is not independently associated with MACE.

Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).

OBJECTIVES: This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. BACKGROUND: Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. METHODS: Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. RESULTS: In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. CONCLUSIONS: Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).