A toolbox of machine learning software to support microbiome analysis.

The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.

Statistical and Machine Learning Techniques in Human Microbiome Studies: Contemporary Challenges and Solutions.

The human microbiome has emerged as a central research topic in human biology and biomedicine. Current microbiome studies generate high-throughput omics data across different body sites, populations, and life stages. Many of the challenges in microbiome research are similar to other high-throughput studies, the quantitative analyses need to address the heterogeneity of data, specific statistical properties, and the remarkable variation in microbiome composition across individuals and body sites. This has led to a broad spectrum of statistical and machine learning challenges that range from study design, data processing, and standardization to analysis, modeling, cross-study comparison, prediction, data science ecosystems, and reproducible reporting. Nevertheless, although many statistics and machine learning approaches and tools have been developed, new techniques are needed to deal with emerging applications and the vast heterogeneity of microbiome data. We review and discuss emerging applications of statistical and machine learning techniques in human microbiome studies and introduce the COST Action CA18131 "ML4Microbiome" that brings together microbiome researchers and machine learning experts to address current challenges such as standardization of analysis pipelines for reproducibility of data analysis results, benchmarking, improvement, or development of existing and new tools and ontologies.

Angiotensin-converting enzyme gene polymorphism in arrhythmogenic right ventricular dysplasia: is DD genotype helpful in predicting syncope risk?

INTRODUCTION: Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterised by fibrofatty replacement of right ventricular myocytes and increased risk of ventricular arrhythmias and sudden cardiac death. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects myocardial ACE levels. DD genotype favours myocardial fibrosis and is associated with malignant ventricular tachycardia. The aim of this study was to explore ACE gene polymorphism in ARVD patients. METHODS: Twenty-nine patients with ARVD and 24 controls were included. All ARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death. ACE gene polymorphism was identified by polymerase chain reaction technique. RESULTS: There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750, 95% confidence interval: 1.318-34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36). CONCLUSION: High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.

Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease.

We investigated the oxidative modifications of lipids, proteins and DNA, three potential molecular targets of oxidative stress, in 30 patients with angiographically defined coronary artery disease (CAD) and 30 healthy control subjects. In addition, we examined relationships between these oxidative modifications and the severity of vascular lesions in patients with CAD. Malondialdehyde (MDA) and protein carbonyl (PC) levels, as well as ferric reducing antioxidant power (FRAP), were measured in the plasma. DNA damage was evaluated as single strand breaks (SSBs), formamidopyrimidine glycosylase (Fpg) and endonuclease III (E-III)-sensitive sites by the comet assay in DNA isolated from lymphocytes. MDA and PC levels increased, but FRAP values decreased, in patients as compared to controls. However, these values did not vary with the number of affected coronary vessels and were not correlated with Duke score, a parameter of the severity of vascular lesions in patients with CAD. We also found that lymphocyte DNA damage (SSBs, Fpg and E-III sites) were increased in patients. Although there were no significant differences in SSBs values in patients grouped according to affected vessel number, Fpg and E-III sites increased. We also detected significant correlations between Duke scores and SSBs and Fpg sites. Serum cholesterol, triglyceride and LDL-cholesterol levels were found to increase, but HDL-cholesterol levels decreased in CAD patients, but these lipids were not correlated with Duke scores. The results of this study reinforce the presence of increased combined oxidative modifications in lipid, protein and DNA in patients with CAD. However, lymphocyte DNA damage seems to be a more reliable assay than MDA and PC determinations to detect the severity of vascular lesions in patients.

Effects of percutaneous coronary thrombectomy with the X-sizer catheter on epicardial flow and microvascular function in acute coronary syndromes.

During percutaneous coronary intervention, slow coronary flow and distal embolization are still important problems, especially in cases with intracoronary thrombus. The aim of this study was to learn the effectiveness and early term results of thrombectomy with the X-SIZER catheter system in acute coronary syndrome. Twenty-nine patients (22 [76%] men; 55.9 +/- 11.1 years) with acute coronary syndrome and intracoronary thrombus detected in coronary angiography were included into the study. X-sizer thrombectomy was applied to 14 of the patients, and conventional percutaneous transluminal coronary angioplasty (PTCA) was applied to the others. Baseline characteristics were similar in both groups. Mean thrombolysis in myocardial infarction (TIMI) flow increased from 0.8 +/- 0.9 to 2.4 +/- 0.6 in X-sizer-treated patients (p<0.001) and TIMI 3 flow was maintained in 71.4% of the patients. Similary, mean TIMI flow increased from 0.36 +/- 0.81 to 2.73 +/- 0.47 in conventional PTCA-treated patients (p<0.001) and TIMI 3 flow was maintained in 73% of the patients (NS). Mean myocardial blush grade (MBG) increased from 0.7 +/- 0.7 to 2.6 +/- 0.6 in X-sizer-treated patients (p<0.001) and from 0.27 +/- 0.65 to 2.36 +/- 0.67 in the conventional PTCA-treated patients (p<0.001). Postprocedural MBG 3 was obtained in 64.3% of X-Sizer-treated patients and in 45% of controls. Although microvascular function in the thrombectomy-applied patients was found better, there was no significant difference between the two groups. Furthermore it was detected that the use of tirofiban yielded no additional improvement in epicardial and microvascular flow. In acute coronary syndromes, use of X-sizer in addition to primary percutaneous coronary interventions is a safe and relatively effective method in the prevention of distal embolization.

Can thrombolytic therapy provide beneficial effects additional to epicardial coronary artery recanalization? A study based on coronary pressure measurement.

BACKGROUND: Collaterals provide significant blood supply to the myocardium at risk and the presence of a preserved and adequate collateral network may limit microvascular damage during the occlusion of an epicardial coronary artery. The aim of this study was to evaluate whether thrombolytic therapy (TT) may produce beneficial effects at the level of microvascular circulation in addition to epicardial coronary artery recanalization by using quantitative intracoronary pressure measurement techniques in patients with recent acute myocardial infarction (AMI). MATERIALS AND METHODS: Thirty-six patients who presented with AMI and had preinfarction angina pectoris, more than 60% stenosis and thrombolysis in myocardial infarction (TIMI) grade II flow in the infarct-related artery and who underwent a stent implantation procedure within 10 days of AMI were included in this study. Seventeen of 36 patients had received TT (group 1) and 19 had not received TT due to presence of contraindications or late admission (group 2). Quantitative coronary angiography, TIMI frame count (TFC) assessment and intracoronary pressure measurements were performed before and after stent implantation for all patients. Myocardial fractional flow reserve (FFRmyo) was calculated as the ratio of mean distal coronary pressure to mean aortic pressure. During total occlusion with balloon inflation, distal pressure was recorded as coronary wedge pressure (CWP). Collateral flow index (CFI) was determined by the ratio of simultaneously measured CWP to mean aortic pressure. RESULTS: There were no differences between the two groups with respect to mean per cent stenosis and mean FFRmyo both before and after stent implantation. The mean CWP (25.1 +/- 8.6 mmHg compared with 17.2 +/- 6.2 mmHg, P < 0.01) and CFI (0.24 +/- 0.10 compared with 0.16 +/- 0.11, P < 0.01) were significantly higher and mean post-stent corrected TFC (18.8 +/- 3.7 compared with 22.4 +/- 3.1, P < 0.01) was significantly faster in the group of patients who had received TT compared to those who had not. CONCLUSIONS: We concluded that destruction degree of collateral circulation and distal microvasculature is lower in patients who had received TT, compared to patients who could not be treated with TT. Besides protective effect on collateral vessels, TT provides even more reperfusion and less destruction of the microvasculature.

Relationship between pressure-derived collateral blood flow and diabetes mellitus in patients with stable angina pectoris: a study based on coronary pressure measurement.

UNLABELLED: Although the pressure gradient between the normal and stenotic vascular regions is known to be the most important factor for collateral vessel development, factors which are responsible for variations among patients with ischemic heart disease are not well known. Likewise, it is still not clear whether diabetes mellitus (DM) has any effect on coronary collateral development. Coronary angiography, the most commonly used technique for studying collateral circulation, may not be accurate in assessing collateral circulation because most collaterals are situated intramurally or are too small to visualize angiographically. Intracoronary pressure measurement is a new technique to provide accurate and quantitative information about the collateral circulation. Therefore, we sought the effects of DM on coronary collateral vessels in patients with coronary artery disease by using intracoronary pressure measurement technique. METHODS: Study material consisted of 40 patients (20 diabetic) with chronic ischemic heart disease referred to angiography laboratory due to their ischemic symptoms verified previously with at least one non-invasive test. All of the patients had single vessel disease with more than 70% narrowing and had undergone PTCA and/or stent implantation procedure for this vessel. Quantitative coronary angiographic analysis (QCA) and all of the coronary pressure measurements were performed both pre- and post-revascularization procedure. After angiography, a fiber-optic pressure monitoring guidewire (Pressure wire, RADI Medical Systems, Inc., Reading, Massachusetts) was advanced to the stenosis to be dilated. The same wire was used as a guidewire for the angioplasty catheter. During complete occlusion with balloon inflation, distal pressure was recorded as coronary wedge pressure (CWP). As a more valuable parameter, collateral flow index (CFI) was determined by the ratio of simultaneously measured CWP (mmHg) to mean aortic pressure (Pa, mmHg, obtained from the guiding catheter) (CFI: CWP/Pa). RESULTS: Pressure measurements were performed on 20 diabetic and 20 non-diabetic patients. The mean value of CWP was 18.1 8.6 mmHg in the diabetic group and 26.8 +/- 9.6 mmHg in the non-diabetic group; this difference was statistically significant (p < 0.01). Also, the mean value of CFI was significantly higher in the non-diabetic group (0.17 +/- 0.08 in the diabetic group and 0.25 0.09 in the non-diabetic group; p < 0.01). CONCLUSION: This study demonstrated that the coronary collateral vessel development is impaired in diabetic patients compared with non-diabetic patients.

The relationship between corrected TIMI frame count and myocardial fractional flow reserve.

UNLABELLED: Thrombolysis in myocardial infarction (TIMI) frame count (TFC) is a reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades. After myocardial infarction (MI), hyperemic and basal flows decrease in the infarct region due to residual stenosis and increased resistance in the microvasculature subtended by this infarct-related artery (IRA). Myocardial fractional flow reserve (FFRmyo) is a lesion-specific index for epicardial stenosis. FFRmyo can also be used as a criterion for assessing the success of revascularization therapy. The aim of this study was to investigate the relationship between improvement of the corrected TFC (CTFC) and change in FFRmyo, which were determined in the IRA in patients with recent MI who underwent mechanical revascularization. METHODS: Forty-one patients (28 male; age, 58.3 +/- 12.3 years) early after MI with > 60% narrowing in the IRA who underwent stent implantation for this residual stenosis were included in this study. After angiography, a fiber-optic pressure monitoring guidewire was positioned distal to the stenosis to be dilated. Means of aortic (Pa) and distal (Pd) pressures were recorded simultaneously under baseline and hyperemic conditions. FFRmyo (Pd/Pa) was determined under adenosine hyperemia before and after stent implantation, as was TFC. Percentage of the improvement in the CTFC and FFRmyo was calculated for each lesion. The first frame used for TFC was defined by a column of contrast extending across > 70% of the arterial lumen and last frame counted was that in which contrast first appeared in the distal, pre-defined landmark branches for each vessel. CTFC was calculated for the LAD by dividing TFC of the LAD by a factor of 1.7. RESULTS: Eighteen patients had LAD, 10 had CX and 13 had RCA lesions. After stent implantation, the CTFC improved by 41% (from 32.3 +/- 3.4 to 19.2 +/- 2.1; p < 0.0001) and FFRmyo improved by 69% (from 0.53 +/- 0.11 to 0.90 +/- 0.15; p < 0.0001). There was a statistically significant correlation between the change in FFRmyo and improvement in the TFC (r = 0.85). CONCLUSION: Improvement in CTFC is associated with change in FFRmyo in the IRA undergoing mechanical revascularization. After mechanical revascularization, CTFC decreases proportionally to improvement of the FFRmyo. These two parameters support each other in terms of successful revascularization and this relationship shows the recruitability of CTFC in terms of FFRmyo as well.

[Reduced coronary collateral vessel recruitment capacity in diabetes mellitus: an evidence for defective ischaemic tolerance]. / Diyabetes mellitus'ta azalmis koroner kollateral damar açilma kapasitesi: defektif iskemik tolerans için bir kanit.

OBJECTIVE: Collateral channel opening is one of the components of the ischemic tolerance developing during subsequent coronary balloon occlusions. The effect of diabetes mellitus (DM) on coronary collateral recruitment (CR) is still not known. We therefore sought the effect of DM on CR in patients with stable angina pectoris (SAP) by using intracoronary pressure measurement technique. METHODS: Study material consisted of 44 patients (21 diabetic) with SAP. All of the patients had single vessel disease with more than 70% vessel narrowing and all of them underwent stent implantation to this vessel. After angiography, fiber-optic pressure monitoring guidewire was advanced distal to the stenosis to be dilated. Myocardial fractional flow reserve (FFRmyo) was determined under adenosine hyperemia by the ratio of simultaneously measured mean distal pressure to mean aortic pressure. During subsequent two 1 minute balloon occlusions, distal pressures were recorded as coronary wedge pressure (CWP). Collateral flow index was determined by the ratio of simultaneously measured CWP to mean aortic pressure. Percentage of the improvement in the coronary flow index (CFI) (first to second occlusion) between two occlusions was determined for each patient. RESULTS: There was no difference between two groups in terms of pre-intervention FFRmyo (0.54 +/- 0.12 in DM group and 0.50 +/- 0.11 in non-DM group). The baseline CFI was significantly higher in non-DM group (0.26 +/- 0.09 versus 0.17 +/- 0.08, p<0.03). Beyond this finding, mean CFI increased by 17% (from 0.17 +/- 0.08 to 0.20 +/- 0.09) in DM group and by 30% (from 0.26 +/- 0.09 to 0.34 +/- 0.10) in non- DM group. There was statistically significant difference between these two groups in terms of improvement in CFI during subsequent balloon occlusions (p<0.01). CONCLUSION: In addition to poor collateral vessels seen in patients with DM, CR is also impaired. This finding suggests that DM abolishes ischemic tolerance in terms of CR as well.

Relationship between the serum sCD40L level and aspirin-resistant platelet aggregation in patients with stable coronary artery disease.

BACKGROUND: Current evidence supports the central role of inflammation in all phases of the atherosclerotic process, including its thrombotic complications. Increased serum sCD40L may trigger platelet activation, so the aim of the present study was to determine the relation between sCD40L levels and aspirin-resistant platelet aggregation in patients with coronary atherosclerosis. METHODS AND RESULTS: A total of 167 consecutive patients (39-85 years old, 35.9% women) with stable coronary artery disease was enrolled in the study. Platelet function was evaluated by a Platelet Function Analyzer 100 device (PFA-100) with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (ADP) (Col/ADP) cartridges. Aspirin resistance was defined as a closure time (CT) <186 s with Col/Epi cartridges, despite regular aspirin therapy. Serum sCD40L level was determined quantitatively with an ELISA method. Fifty-seven (34.1%) patients had aspirin resistance according to the PFA-100. Mean CT measured with the Col/ADP cartridges was 83+/-18 s (65-101 s). Mean serum sCD40L was 157 pg/ml (6-700 pg/ml) in the entire cohort. Patients with aspirin resistance had a mean serum sCD40L level of 166 pg/ml and patients with aspirin-sensitive platelet aggregation had an sCD40L level of 152 pg/ml (p=0.582). CONCLUSION: The sCD40L level is similar in patients with aspirin-resistant and aspirin-sensitive platelet aggregation according to the PFA-100. There is still need for further studies to elucidate the relationship between aspirin-resistant platelet aggregation and sCD40L, which is now known to be prothrombotic, proinflammatory and to be a risk factor for cardiovascular events.

Implantation of a permanent pacemaker in a patient with severe Parkinson's disease and a preexisting bilateral deep brain stimulator.

Cardiac pacemakers and implantable defibrillators are commonly used therapeutic modalities in cardiac arrhythmias. Thalamic deep brain stimulation has also become an important modality in the treatment of drug-refractory tremors and other complications in advanced Parkinson's disease. Concerns exist about the potential electrical interaction and interference between these 2 devices in the same patient. There are only a limited number of reports that have investigated this issue. We describe a patient with advanced Parkinson's disease and a previously implanted deep brain stimulator, who subsequently needed a permanent cardiac pacemaker due to severe bradyarrhythmia. Despite the probability of interference between the devices, there were no problems during implantation of the cardiac pacemaker; both the deep brain stimulator and cardiac pacemaker functioned appropriately afterwards.

Depression and anxiety status of patients with implantable cardioverter defibrillator and precipitating factors.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are life-saving devices in treatment of life-threatening arrhythmia. We evaluate the emotional status of Turkish patients with ICD and try to explain factors that affect emotional status of the patients. METHODS: Ninety-one patients with previously implanted ICD were included in the study. Follow-up periods, presence of ICD shock, shock frequency, time of the recent shock, age, and gender were noted. Depression and anxiety scores were evaluated according to Hospital Anxiety and Depression (HAD) chart. RESULTS: Mean anxiety and depression scores were found as 9.1 +/- 5.3 and 7.2 +/- 5.1, respectively. According to HAD charts, 42 patients (46%) had anxiety and 37 patients (41%) had depression. Depression scores indicated significant difference between subgroups divided on the basis of follow-up periods (P = 0.026) and on the basis of time of recent shock (P = 0.028). There was significant difference in anxiety scores (P = 0.016) between patients with ICD shocks and patients with no shocks. When the patients were divided into subgroups according to shock frequency, both depression (P = 0.024) and anxiety (P = 0.016) scores presented significant difference. In female patients, depression and anxiety scores were found significantly higher compared to male patients (P = 0.046 and P = 0.016, respectively). In multivariate analysis, gender and shock frequency were found as predictors for anxiety scores (P = 0.019 and P = 0.044, respectively). However same analysis revealed no predictive factor for depression score. CONCLUSION: Our study indicates presence of depression and anxiety in nearly half of the patients with ICD. Consultation with psychiatry should be a part of the treatment for patients with ICD, especially for those who constitute high-risk groups.

The use of human heart-type fatty acid-binding protein as an early diagnostic biochemical marker of myocardial necrosis in patients with acute coronary syndrome, and its comparison with troponin-T and creatine kinase-myocardial band.

Heart-type fatty acid-binding protein (H-FABP), a new biochemical marker of sarcolemmal injury due to acute myocardial ischemia, can be used as a tool in early diagnosis and management of patients at high risk. The aim of this study was to determine the early diagnostic value of H-FABP in acute coronary syndrome (within 6-24 h of chest pain) and to compare it with troponin-T (TnT) and creatine kinase-myocardial band (CK-MB) for accuracy. The study consisted of 40 consecutive patients with chest pain admitted to the coronary care unit with the diagnosis of suspected acute coronary syndrome. The patient population consisted of two groups according to the time of admission; the first group (26 patients) included patients admitted within 6 h of chest pain, and the second group (14 patients) included patients admitted within 6-24 h of chest pain. The blood samples for H-FABP, TnT, and CK-MB were obtained at admittance, at the 6th, and at the 24th hours for the first group, and at admittance and at the 24th hours for the second. Statistical analysis was performed among the 26 patients for the first 6 h values, and among all 40 patients for the values obtained within 6-24 h and at the 24th hour. The patients were then divided into groups according to the changes in the electrocardiogram (ECG) and cardiac enzymes as unstable angina pectoris, non-ST elevation myocardial infarction (MI), and ST-elevation MI. Coronary angiography was performed in 38 (95%) patients. Sensitivity of TnT, CK-MB, and H-FABP in the first group (within 6 h of chest pain) were 38%, 76%, and 95% respectively. The sensitivity of H-FABP was significantly higher than TnT (P=0.014). Sensitivity of TnT, CK-MB, and H-FABP tests in the second time period (within 6-24 h of chest pain) were 100%, 90%, and 91% respectively. In this time period, the sensitivity of TnT was higher than H-FABP, but it was statistically insignificant. At the 24th hour, sensitivity of TnT was 100%, CK-MB 90%, and H-FABP 27.3%, and TnT and CK-MB were more sensitive than H-FABP for the whole group (P=0.002). In the first group (within 6 h of chest pain) H-FABP positivity was slightly but insignificantly higher in patients with two- and three-vessel disease compared with those with one-vessel disease (60.7% and 33.3%, P=0.19) and in the same group, patients who underwent primary coronary intervention had a significantly higher H-FABP positivity than others (80%, 32%, P=0.02). Within 6-24 h of chest pain, H-FABP positivity was 80% in patients with one-vessel disease and 71.4% in patients with two- and three-vessel disease (P=0.69). Within 6-24 h, positivity of H-FABP reached a peak value of 100% in patients who underwent primary coronary intervention, while H-FABP was positive in 60% of the others (P<0.001). We conclude that within the 6 h of acute coronary syndrome, H-FABP seems to be a more sensitive biochemical marker than TnT in the early detection of ischemic myocardial necrosis. But after the first 6 h of the onset of chest pain the sensitivity of H-FABP decreases, and this marker should not be used alone in patients admitted 24 h after the onset of chest pain.

Tricuspid endocarditis in an adult patient with Ebstein's anomaly who has a residual pacemaker lead.

Ebstein's anomaly is defined as an apical displacement of the attachment of the septal tricuspid valve leaflet from the right atrioventricular annulus that exceeded 1.2 cm in length. Patients with Ebstein's anomaly are known to have a high potential for developing arrhythmia, in the vast majority, of the tachycardia type. Infective endocarditis is characterized by ulcerovegetational lesions that result from the graft of a microorganism, usually bacterial, on the valvuler endocardium (native valve endocarditis) or on a prosthesis (prosthetic valve endocarditis). Ebstein's anomaly with tricuspid regurgitation is also thought to be a predisposing condition for infective endocarditis. In this case, we report a patient who presented with atrial flutter and infective endocarditis due to residual pacemaker lead and Ebstein's anomaly.

Relationship between collateral blood flow and microvascular perfusion after reperfused acute myocardial infarction.

During acute occlusion of an epicardial vessel collaterals preserve the microvascular perfusion and limit the extent of myocardial damage. Pressure-derived collateral flow index (CFIp) assessed by intracoronary pressure measurement allow us to quantify collateral vessel development. The angiographic myocardial blush (MB) scores, based on the contrast dye density and washout in the infarcted myocardium, provide important information about microvascular perfusion after acute myocardial infarction (AMI). In this study we assessed the microvascular perfusion with MB and studied the relation between CFIp in patients with AMI who treated with thrombolytic therapy and TIMI grade III flow restored in the infarct related artery (IRA). Forty-one patients with AMI who were treated with thrombolytic therapy and underwent stent implantation (mean of 3 days after AMI) to the IRA were included in this study. After angiography, CFIp was calculated as the ratio of simultaneously measured coronary wedge pressure--central venous pressure (Pv) to mean aortic pressure--Pv. Myocardial blush was graded densitometrically based on visual assessment of the relative contrast opacification of the myocardial territory subtended by the infarct vessel. There was a statistically significant correlation between CFIp and post-stent myocardial blush grades (P < 0.01, r = 0.70). There was a significant difference in mean CFIp among myocardial blush grades implying that higher CFIp is associated with better MB (0.39 +/- 0.11 in grade 3, 0.32 +/- 0.10 in grade 2, 0.24 +/- 0.09 in grade 1, and 0.16 +/- 0.08 in grade 0, P < 0.01). Well developed collaterals can limit microvascular damage by preserving microvascular perfusion. A higher pressure-derived collateral flow index is associated with better tissue level perfusion as evidenced by the higher myocardial blush score.