Epicardial Flow Research Articles

Microvascular Obstruction in Acute Myocardial Infarction

Abstract Introduction: The no-reflow phenomenon has been described in 20–40% of patients with acute ST-segment elevation myocardial infarction, despite restoration of TIMI 3 myocardial flow. It is associated with adverse left ventricular remodeling and an unfavorable long-term prognosis. Case presentation: A 45-year-old gentleman was admitted one hour after the onset of an acute anterior ST-segment elevation myocardial infarction. Emergency coronary angiography was performed, and a severe stenosis of the left anterior descending artery was identified. The lesion was crossed with a pressure-wire, and a drug-eluting stent was directly implanted, with restoration of TIMI 3 epicardial flow. Predilatation was not performed. Coronary wedge pressure was measured during stent deployment. The mean pressure value was 27 mmHg. However, a tall systolic wave was identified in the morphology of the pressure curve. Myocardial blush grade and ST-segment resolution were concordant with early micro-vascular obstruction. Similarly, at transthoracic Doppler echocardiography, the flow in the left anterior descending artery revealed the same pattern. An apical left ventricular aneurysm was echocardiographically detected. The MRI described extensive interstitial edema that affected the anterior, septal, and apical regions of the left ventricle. Areas of intramyocardial hemorrhage and microvascular obstruction were also detected. According to recent literature data, the morphology of the coronary wedge pressure wave suggested at least the presence of pre-procedural distal embolization. Conclusions: In the setting of acute myocardial infarction, the integrity of coronary microvasculature is an important issue. The distal coronary pressure wave pattern before primary percutaneous revascularization can be a deciding factor for an early therapeutic approach.

TCT-723 Clinical and Angiographic Predictors of No-Reflow Phenomenon in ST Segment Elevation Myocardial Infarction Treated with Successful Primary Percutaneous Intervention

In ST segment elevation myocardial infarction (STEMI) primary percutaneous coronary intervention remains the optimal treatment modality to restore normal epicardial coronary artery blood flow. However, despite successful PCI a small, but still significant proportion of patients continue to present

Usefulness of coronary flow reserve measured by transthoracic coronary Doppler ultrasound in the elderly.

The left anterior descending (LAD) coronary artery is the main vessel of human coronary circulation, and life-threatening consequences are seen when flow in this area is impaired.[1] Noninvasive measurement of coronary flow reserve (CFR), defined as the ratio of maximal to baseline coronary blood flow, has been repeatedly shown to be a feasible technique by ultrasound transthoracic Doppler (TTD) both in the LAD and, with some limitations, in the posterior descending (PD) coronary artery.[2]–[7] CFR by TTD offers two important pieces of information: information about patency and flow through the large epicardial coronary artery proximal to the site of CFR assessment and information about the functional integrity of coronary microcirculation distal to the site of CFR assessment.[4] CFR by TTD is a valuable research tool for investigating the pathophysiology of coronary circulation. However, CFR by TTD is also an important clinical decision-making instrument, enabling functional assessment of epicardial coronary stenosis, particularly in cases of anatomically borderline stenosis, i.e., 50%–70% of cases.[8] CFR by TTD enables insight downstream into coronary microvascular function that might be impaired due to primary coronary microvascular disease, as a consequence of myocardial diseases with extramural compression and microvascular remodeling and rarefaction (in left ventricular hypertrophy, dilated or hypertrophic cardiomyopathy, or aortic stenosis), or as a consequence of microvascular obstruction due to micro-embolization by plaque and thrombus debris during percutaneous coronary interventions.[9] Epicardial coronary artery patency and flow may be particularly jeopardized in the elderly as a result of advanced atherosclerosis (a disease of aging). Coronary microcirculatory function might also be impaired in the elderly even in the absence of obstructive epicardial atherosclerosis due to accumulated risk factors (e.g., hypertension, diabetes, obesity) and co-morbidities (e.g., chronic kidney, aortic stenosis).[10],[11] As a technique that is noninvasive, inexpensive, easily repeatable, and that does not require radiation, TTD CFR may be very useful in the fragile population of the elderly, offering a better understanding of coronary vascular aging as well as clinically important information regarding the diagnosis and prognosis of coronary artery disease.

Reperfusion ventricular arrhythmia bursts identify larger infarct size in spite of optimal epicardial and microvascular reperfusion using cardiac magnetic resonance imaging.

Ventricular arrhythmia (VA) bursts following recanalisation in acute ST-elevation myocardial infarction (STEMI) are related to larger infarct size (IS). Inadequate microvascular reperfusion, as determined by microvascular obstruction (MVO) using cardiac magnetic resonance imaging (CMR), is also known to be associated with larger IS. This study aimed to test the hypothesis that VA bursts identify larger infarct size in spite of optimal microvascular reperfusion. All 65 STEMI patients from the Maastricht ST elevation (MAST) study with brisk epicardial flow (TIMI 3), complete ST recovery post-percutaneous coronary intervention and early CMR were included. Using 24-hour Holter registrations from the time of admission, VA bursts were identified against subject-specific Holter background VA rates using a statistical outlier method. MVO and final IS were determined using delayed enhancement CMR. MVO was present in 37/65 (57%) of patients. IS was significantly smaller in the group without MVO (median 9.4% vs. 20.5%; p < 0.001). IS in the group with MVO did not differ depending on VA burst ( n = 28/37; median 20.8% vs. 19.7%; p = 0.64). However, in the group without MVO, VA burst was associated with significantly larger IS ( n = 17/28; median 10.5% vs. 4.1%; p = 0.037). In multivariable analyses, VA burst as well as anterior infarct location remained independent predictors of larger infarct size. In the presence of suboptimal reperfusion with MVO by CMR, VA burst does not further define MI size. However, with optimal TIMI 3 reperfusion and optimal microvascular perfusion (i.e. no MVO), VA burst is associated with larger IS, indicating that VA burst is a marker of additional cell death.

The Role of Nitrates in the Management of Stable Ischemic Heart Disease: A Review of the Current Evidence and Guidelines.

Coronary artery disease is the leading cause of mortality in the United States and can result in significant morbidity. In particular, stable ischemic heart disease (SIHD) is a condition that affects nearly 9 million individuals in the United States alone, with substantial annual health care costs related to recurrent medical visits and chronic disease management. Nitrates form a cornerstone of SIHD management by reducing myocardial oxygen consumption and increasing exercise capacity by several mechanisms, including increasing epicardial blood flow through vasodilation and decreased vascular resistance, blunting coronary steal, and reducing preload. Yet the role of nitrates may be underappreciated in clinical practice and their utilization may be limited due to concerns of tolerance to treatment, a lack of randomized data validating their ability to prevent adverse cardiovascular events, and the pervasive use of percutaneous interventions without robust attempts at implementing optimal medical therapy. In this review, we discuss both the recent ACC/AHA/ACP/AATS/PCNA/SCAI/STS and European Society of Cardiology guidelines, with a particular focus on indications, contraindications, and future directions of nitrate therapy in SIHD.

Abstract 12861: Assessment of Both Coronary Microvascular Damage and Epicardial Flow Velocity Measurement Immediately After Successful Percutaneous Coronary Intervention Predicts In-Hospital Complications and Survival in ST-Segment Elevation Myocardial Infarction

Background: Quantitative measurement of post-reperfusion epicardial flow velocity by a Doppler guidewire can predict clinical cardiac events in ST-segment elevation myocardial infarction (STEMI). It has also been reported that the coronary flow velocity pattern in patients with microvascular obstruction is characterized by the presence of early systolic retrograde flow and a rapid diastolic deceleration time (DDT). The purpose of this study was to examine the role of assessing both epicardial flow velocity and microvascular damage in the prediction of in-hospital complications and survival after percutaneous coronary intervention (PCI). Methods: Two hundred and fifty-one consecutive patients with first anterior STEMI who underwent successful PCI were subjected to coronary flow measurement with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: time-averaged peak velocity (cm/s, APV), systolic peak velocity (cm/s) and DDT (ms). We defined the presence of microvascular obstruction as DDT ≤600 ms and the presence of systolic flow reversal, and slow epicardial flow as resting APV ≤10cm/s. We classified the patients into three categories: without microvascular obstruction (group 1, n=140), with microvascular obstruction and normal epicardial flow (group 2, n= 51, with microvascular obstruction and slow epicardial flow (group 3, n=60). The clinical event rate was compared among the 3 groups. Results: The in-hospital event rates for congestive heart failure (15/140 [11%], 15/51 [29%] and 34/60 [57%], respectively; P &lt; 0.01), left ventricular thrombus (3/140 [2%], 9/51 [18%] and 14/60 [23%], respectively; P &lt; 0.01), and cardiac rupture (0/140 [0%], 5/51 [10%], and 16/60 [27%]; P &lt; 0.01) were highest in group 3 and lowest in group 1. Group 3 was at the highest risk of cardiac death, while group 1 was at the lowest (0/140 [0%], 3/51 [6%], and 12/60 [20%]; P &lt; 0.01). Conclusions: Assessment of both coronary microvascular damage and epicardial flow velocity can accurately predict in-hospital complications and survival in STEMI patients who underwent successful reperfusion of the infarct-related coronary artery, identifying a subset of high risk patients.

Mechanical strategies to enhance myocardial salvage during primary percutaneous coronary intervention in patients with STEMI.

Primary percutaneous coronary intervention (PPCI) has become the mainstay of reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI). Despite timely reperfusion by PPCI and restoration of epicardial blood flow in up to 95% of patients, tissue reperfusion remains suboptimal in a sizeable proportion of patients with STEMI. Over the years mechanical and pharmacological strategies to enhance myocardial salvage during PPCI have been developed and used in patients with STEMI. The most common mechanical strategies used in the setting of PPCI include: coronary stenting, direct stenting, mesh-covered stents, self-expanding stents, deferred stenting, thrombectomy, distal protection devices, intra-aortic balloon pumping, left ventricular assist devices and ischaemic conditioning. These strategies are thought to enhance myocardial salvage via improving acute procedural success, attenuation of distal embolisation, microvascular obstruction and reperfusion injury, and providing haemodynamic support. Coronary (direct) stenting is almost the default approach of reperfusion during PPCI procedures. Evidence on the use of mesh-covered stents, self-expanding stents, deferred stenting or left ventricular assist devices is scant and their use in the setting of PPCI remains limited. Mechanical thrombectomy, distal protection devices or routine intra-aortic balloon counterpulsation seem to offer no clinical benefit when used in the setting of PPCI. Although manual aspiration may improve indices of tissue reperfusion, recent research showed no clinical benefit of routine use of this strategy in patients with STEMI undergoing PPCI. Ischaemic conditioning, although promising, remains at an investigational stage and needs further research.

Diagnostic Ultrasound Impulses Improve Microvascular Flow in Patients With STEMI Receiving Intravenous Microbubbles

BackgroundPre-clinical trials have demonstrated that, during intravenous microbubble infusion, high mechanical index (HMI) impulses from a diagnostic ultrasound (DUS) transducer might restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). ObjectivesThe purpose of this study was to test the safety and efficacy of this adjunctive approach in humans. MethodsFrom May 2014 through September 2015, patients arriving with their first STEMI were randomized to either DUS intermittent HMI impulses (n = 20) just prior to emergent percutaneous coronary intervention (PCI) and for an additional 30 min post-PCI (HMI + PCI), or low mechanical index (LMI) imaging only (n = 10) for perfusion assessments before and after PCI (LMI + PCI). All studies were conducted during an intravenous perflutren lipid microsphere infusion. A control reference group (n = 70) arrived outside of the time window of ultrasound availability and received emergent PCI alone (PCI only). Initial epicardial recanalization rates prior to emergent PCI and improvements in microvascular flow were compared between ultrasound-treated groups. ResultsMedian door-to-dilation times were 82 ± 26 min in the LMI + PCI group, 72 ± 15 min in the HMI + PCI group, and 103 ± 42 min in the PCI-only group (p = NS). Angiographic recanalization prior to PCI was seen in 12 of 20 HMI + PCI patients (60%) compared with 10% of LMI + PCI and 23% of PCI-only patients (p = 0.002). There were no differences in microvascular obstructed segments prior to treatment, but there were significantly smaller proportions of obstructed segments in the HMI + PCI group at 1 month (p = 0.001) and significant improvements in left ventricular ejection fraction (p < 0.005). ConclusionsHMI impulses from a diagnostic transducer, combined with a commercial microbubble infusion, can prevent microvascular obstruction and improve functional outcome when added to the contemporary PCI management of acute STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330)

INDEX OF MICROCIRCULATORY RESISTANCE AND INFARCT SIZE IN ACUTE MYOCARDIAL INFARCTION: A VALIDATION STUDY USING CARDIAC MAGNETIC RESONANCE IMAGING

Microvascular dysfunction even after achieving normal epicardial flow is associated with an adverse prognosis in patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Several studies demonstrated that index of microcirculatory resistance (IMR)

Effect of Beam Hardening on Transmural Myocardial Perfusion Quantification in Myocardial CT Imaging.

The detection of subendocardial ischemia exhibiting an abnormal transmural perfusion gradient (TPG) may help identify ischemic conditions due to micro-vascular dysfunction. We evaluated the effect of beam hardening (BH) artifacts on TPG quantification using myocardial CT perfusion (CTP). We used a prototype spectral detector CT scanner (Philips Healthcare) to acquire dynamic myocardial CTP scans in a porcine ischemia model with partial occlusion of the left anterior descending (LAD) coronary artery guided by pressure wire-derived fractional flow reserve (FFR) measurements. Conventional 120 kVp and 70 keV projection-based mono-energetic images were reconstructed from the same projection data and used to compute myocardial blood flow (MBF) using the Johnson-Wilson model. Under moderate LAD occlusion (FFR~0.7), we used three 5 mm short axis slices and divided the myocardium into three LAD segments and three remote segments. For each slice and each segment, we characterized TPG as the mean "endo-to-epi" transmural flow ratio (TFR). BH-induced hypoenhancement on the ischemic anterior wall at 120 kVp resulted in significantly lower mean TFR value as compared to the 70 keV TFR value (0.29±0.01 vs. 0.55±0.01; p<1e-05). No significant difference was measured between 120 kVp and 70 keV mean TFR values on segments moderately affected or unaffected by BH. In the entire ischemic LAD territory, 120 kVp mean endocardial flow was significantly reduced as compared to mean epicardial flow (15.80±10.98 vs. 40.85±23.44 ml/min/100g; p<1e-04). At 70 keV, BH was effectively minimized resulting in mean endocardial MBF of 40.85±15.3407 ml/min/100g vs. 74.09±5.07 ml/min/100g (p=0.0054) in the epicardium. We also found that BH artifact in the conventional 120 kVp images resulted in falsely reduced MBF measurements even under non-ischemic conditions.

Comparison of Outcome of Patients With ST-Segment Elevation Myocardial Infarction and Complete Versus Incomplete ST-Resolution Before Primary Percutaneous Coronary Intervention

Some patients presenting with ST-segment elevation myocardial infarction (STEMI) have complete ST resolution in the electrocardiogram, which may be clinical useful in the triage of patients with STEMI. However, the importance of complete ST resolution in these patients remains uncertain. Thus, the purpose was to describe the prognosis of patients with complete ST resolution before primary percutaneous coronary intervention (PCI). Continuous ST monitoring from arrival until 90minutes after PCI was performed in 933 patients with STEMI. Complete ST resolution was defined as no residual significant ST elevations before intervention. The patients were followed clinically for 5.5years (range 0 to 6.8years). Infarct size and myocardial salvage were assessed in a subgroup of patients (n=221) by cardiovascular magnetic resonance. Complete ST resolution was observed in 24% of the patients, who had a higher incidence of Thrombolysis In Myocardial Infarction grade 2/3 flow before intervention (64% vs 24%), smaller infarct size (6% vs 11%), and higher myocardial salvage index (0.82 vs 0.69; all p <0.001) compared with patients with continuous ST elevations. Complete ST resolution was associated with a significantly lower rate of the composite end point of all-cause death and admission for heart failure (14% vs 22%; p= 0.006) although it only tended to be an independent predictor in a multivariate analysis (hazard ratio 0.69, 95% CI 0.49 to 1.06; p= 0.09). In conclusion, compared to patients without incomplete ST resolution, patients with STEMI and complete ST resolution before primary PCI have a higher incidence of normalized epicardial flow before PCI, a larger myocardial salvage and smaller infarct size after the procedure and presumably improved long-term outcome compared with incomplete ST resolution.

Impact of bivalirudin on post-procedural epicardial blood flow, risk of stent thrombosis and mortality after percutaneous coronary intervention

We aimed to assess the association of bivalirudin with post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow, acute (≤24 hours) and 30-day stent thrombosis (ST), and one-year mortality. The study included 11,623 patients undergoing percutaneous coronary intervention (PCI). The primary outcomes were post-procedural TIMI flow grade ≤2 and definite acute ST. In groups treated with bivalirudin (n=3,135), abciximab plus unfractionated heparin (UFH; n=3,539) and UFH alone (n=4,949), post-procedural TIMI was ≤2 in 5.2%, 3.2% and 3.2% of patients, respectively (adjusted odds ratio [OR]=1.96 [95% confidence interval] 1.47-2.56 for bivalirudin versus abciximab plus UFH and OR=1.56 [1.20-2.04] for bivalirudin versus UFH). Definite acute ST occurred in two patients (0.06%) treated with bivalirudin, two patients (0.06%) treated with abciximab plus UFH, and seven patients (0.14%) treated with UFH (p=0.47). Bivalirudin was not associated with increased risk of 30-day ST (hazard ratio [HR]=1.20 [0.59-2.43] versus abciximab plus UHF, and HR=0.93 [0.48-1.82] versus UFH) or one-year mortality (HR=0.95 [0.70-1.28] versus abciximab plus UHF, and HR=1.05 [0.78-1.41] versus UFH). Bivalirudin was associated with higher risk of suboptimal post-PCI TIMI flow but not with increased risk of acute or 30-day definite ST or one-year mortality compared with abciximab plus UFH or UFH alone.

Manual Thrombus Aspiration and the Improved Survival of Patients With Unstable Angina Pectoris Treated With Percutaneous Coronary Intervention (30 Months Follow-Up).

The clinical effect of intracoronary thrombus aspiration during percutaneous coronary intervention in patients with unstable angina pectoris is unknown. In this study, we aimed to assess how thrombus aspiration during percutaneous coronary intervention affects in-hospital and 30-month mortality and complications in patients with unstable angina pectoris.We undertook an observational cohort study of 645 consecutive unstable angina pectoris patients who had performed percutaneous coronary intervention from February 2011 to March 2013. Before intervention, 159 patients who had culprit lesion with thrombus were randomly assigned to group 1 (thrombus aspiration group) and group 2 (stand-alone percutaneous coronary intervention group). All patients were followed-up 30 months until August 2015.Thrombus aspiration was performed in 64 patients (46%) whose cardiac markers (ie, creatinine kinase [CK-MB] mass and troponin T) were significantly lower after percutaneous coronary intervention than in those of group 2 (CK-MB mass: 3.80 ± 1.11 vs 4.23 ± 0.89, P = 0.012; troponin T: 0.012 ± 0.014 vs 0.018 ± 0.008, P = 0.002). Left ventricular ejection fraction at 6, 12, and 24 months postintervention was significantly higher in the group 1. During a mean follow-up period of 28.87 ± 6.28 months, mortality rates were 6.3% in the group 1 versus 12.9% in the group 2. Thrombus aspiration was also associated with significantly less long-term mortality in unstable angina pectoris patients (adjusted HR: 4.61, 95% CI: 1.16–18.21, P = 0.029).Thrombus aspiration in the context of unstable angina pectoris is associated with a limited elevation in cardiac enzymes during intervention that minimises microembolization and significantly improves both of epicardial flow and myocardial perfusion, as shown by angiographic TIMI flow grade and frame count. Thrombus aspiration during percutaneous coronary intervention in unstable angina pectoris patients has better survival over a 30-month follow-up period.

Role of endothelial function in coronary slow-flow phenomenon with angiographically normal coronaries

Background: Coronary slow flow phenomenon (CSFP) is not a benign phenomenon and has been associated with recurrent angina and sudden cardiac death but its etiopathogenesis remains unclear. Aims and Objectives: To evaluate the role of endothelial function in patients with coronary slow flow (CSF) and to compare them with patients with normal coronary flow. Methods: Fifty (n = 50) patients >18 years of age who presented with history of angina and whose coronary angiogram revealed normal epicardial coronaries with slow flow were included in the study. Fifty patients who presented with chest pain with normal epicardial coronaries and normal flow were taken as controls. Results: There were no major differences in terms of mean age, sex distribution, prevalence of hypertension, diabetes, smoking status, lipid profile, haemoglobin, blood glucose, serum creatinine levels in between the two study groups ([Table 1]). A significant difference was found in the hs-CRP levels between the two groups (5.52 + 3.03 vs. 2.98 + 1.48 mg/L, P Conclusion: Coronary slow flow phenomenon is a marker of atherosclerosis (as documented by carotid intima media thickness) and our study has also shown that endothelial function is significantly impaired in patients with coronary slow flow (as documented by impaired endothelial dependent vasodilatation) than that of patients with normal epicardial coronaries with normal flow.

SAVEME (Myocardial Salvage After Rescue Angioplasty: Evaluation by Magnetic Resonance) Study: Rationale and Study Design

ABSTRACT Introduction Atherosclerotic disease accounts for one-third of deaths annually, as it often leads to complications such as ST-elevation myocardial infarction (STEMI). Rescue percutaneous coronary intervention (PCI) is indicated in case of thrombolytic therapy failure administered in this scenario. However, the benefits regarding mortality rate reduction and the amount of myocardium that is actually salvaged are not well established. The development of new tools, including cardiac magnetic resonance imaging, to identify the myocardium at risk and the infarcted area has increased diagnostic accuracy. Differently from the context of primary PCI, little is known about the association between epicardial and microvascular coronary flow following rescue PCI and the salvaged myocardial area. The aim of this study is to evaluate whether there is an association between coronary flow and the salvaged myocardial area identified by magnetic resonance imaging. Methods This will be a prospective, open, single-center, intervention study. A total of 72 patients with STEMI who underwent rescue PCI after documented failure of the fibrinolytic therapy, and were transferred to our institution, will be selected, observing a pharmacoinvasive strategy. Conclusions At the end of this study, the authors expect to contribute to the knowledge about coronary flow and its association with the amount of salvaged cardiac muscle after rescue PCI. This type of information that can help to understand which cases can benefit the most from rescue PCI.

Effect of Ischemia Duration and Door-to-Balloon Time on Myocardial Perfusion in ST-Segment Elevation Myocardial Infarction: An Analysis From HORIZONS-AMI Trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction).

This study sought to investigate the effect of treatment delay on microvascular reperfusion in ST-segment elevation myocardial infarction (STEMI) patients from the large, multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. Despite restoration of epicardial blood flow during primary percutaneous coronary intervention (PCI), one-third of patients do not obtain myocardial perfusion due to impairment in the microvascular circulation. We examined the effect of symptom onset-to-balloon time (SBT) and door-to-balloon time (DBT) on myocardial reperfusion during primary PCI in STEMI, utilizing resolution of ST-segment elevation (STR) and the myocardial blush grade (MBG). The primary analysis was the relationships between SBT ≤2, >2 to 4, and >4 h and DBT ≤1, >1 to 1.5, >1.5 to 2, and >2 h with MBG and STR. Clinical risk was assessed using a modified version of the Thrombolysis In Myocardial Infarction risk score for STEMI. In 2,056 patients, absent microvascular perfusion (MBG 0/1) and STR (STR <30%) after primary PCI was significantly more common in patients with longer SBT, in patients with both low and high clinical risk profiles. By multivariable analysis, SBT (p < 0.0001), anterior infarction (p < 0.0001), reference vessel diameter (p = 0.005), lesion minimum lumen diameter (p < 0.0001), hyperlipidemia (p = 0.03), and current smoking (p = 0.001) were independent predictors of MBG 0/1, whereas SBT (p = 0.007), anterior infarction (p < 0.0001), and history of renal insufficiency (p = 0.0002) were independent predictors of absent STR. DBT (p < 0.0001) was an independent predictor of MBG 0/1. MBG 0/1 and STR<30% identified patients with increased 3-year mortality. The present study suggests that delay in mechanical reperfusion therapy during STEMI is associated with greater injury to the microcirculation.

Effect of Elevated Reperfusion Pressure on "No Reflow" Area and Infarct Size in a Porcine Model of Ischemia-Reperfusion.

The "no reflow" phenomenon (microvascular obstruction despite restoration of epicardial blood flow) develops postreperfusion in acute myocardial infarction and is associated with poor prognosis. We hypothesized that increased reperfusion pressure may attenuate the no reflow phenomenon, as it could provide adequate flow to overcome the high resistance of the microvasculature within the no reflow zone. Thus, we investigated the effect of modestly elevated blood pressure during reperfusion on the extent of no reflow area and infarct size in a porcine model of ischemia-reperfusion. Eighteen farm pigs underwent acute myocardial infarction by occlusion of the anterior descending coronary artery for 1 hour, followed by 2 hours of reperfusion. Just prior to reperfusion, animals were randomized into 2 groups: in group 1 (control group, n = 9), no intervention was performed. In group 2 (n = 9), aortic pressure was increased by ∼20% (compared to ischemia) by partial clamping of the ascending aorta during reperfusion. Following 2 hours of reperfusion, animals were euthanized to measure area at risk, infarct size, and area of no reflow. Partial clamping of the ascending aorta resulted in modest elevation of blood pressure during reperfusion. The area at risk did not differ between the 2 groups. The no reflow area was significantly increased in group 2 compared to control animals (50% ± 13% vs 37% ± 9% of the area at risk; P = .04). The infarcted area was significantly increased in group 2 compared to control animals (75% ± 17% vs 52% ± 23% of the area at risk; P = .03). Significant positive correlations were observed between systolic aortic pressure and no reflow area, between systolic aortic pressure and infarcted area and between infarcted area and no reflow area during reperfusion. Modestly elevated blood pressure during reperfusion is associated with an increase in no reflow area and in infarct size in a clinically relevant porcine model of ischemia-reperfusion.

Prognostic utility of myocardial blush grade after PCI in patients with NSTE-ACS: Analysis from the ACUITY trial.

We evaluated the ability of post-procedural myocardial blush grade (MBG) to stratify outcomes of patients undergoing percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndromes (NSTE-ACS). MBG strongly correlates with survival after reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI). Of 13,819 NSTE-ACS patients randomized in the ACUITY trial, 3,115 patients underwent PCI and had MBG analyzed by an independent angiographic core laboratory. We examined net adverse clinical events (NACE; composite ischemia or bleeding), composite ischemia (death, MI or ischemia-driven revascularization) and non-CABG major bleeding according to final MBG. At 30 days, patients with MBG-0/1 had higher rates of NACE (25.1% vs. 13.9%, P = 0.002) and composite ischemia (19.1% vs. 9.4%, P = 0.002) than patients with MBG-2/3. At 1-year follow-up, MBG-0/1 patients had significantly higher rates of composite ischemia compared to other patients (27.8% vs. 19.8%, P = 0.02). By multivariable analysis, MBG-0/1 was an independent predictor of 30-day ischemia-driven revascularization (OR 5.74 [2.63, 12.54], P < 0.0001) in the total population and among patients with normal post-PCI epicardial TIMI-3 flow (OR 6.39 [2.06, 19.78], P = 0.001). However, 1-year outcomes were similar between patients with and without normal myocardial perfusion. In conclusion, MBG is a predictor of 30-day revascularization in the overall population and in patients with normal epicardial flow but fails to stratify 1-year outcomes. Thus, unlike in STEMI patients, the prognostic value of MBG in NSTE-ACS patients appears to be limited to the short-term. © 2015 Wiley Periodicals, Inc.

Role of short-acting nitroglycerin in the management of ischemic heart disease.

Nitroglycerin is the oldest and most commonly prescribed short-acting anti-anginal agent; however, despite its long history of therapeutic usage, patient and health care provider education regarding the clinical benefits of the short-acting formulations in patients with angina remains under-appreciated. Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation. The potential for the prophylactic effect of short-acting nitrates remains an under-appreciated part of optimal medical therapy to reduce angina and decrease myocardial ischemia, thereby enhancing the quality of life. Short-acting nitroglycerin, administered either as a sublingual tablet or spray, can complement anti-anginal therapy as part of optimal medical therapy in patients with refractory and recurrent angina either with or without myocardial revascularization, and is most commonly used to provide rapid therapeutic relief of acute recurrent angina attacks. When administered prophylactically, both formulations increase angina-free walking time on treadmill testing, abolish or delay ST segment depression, and increase exercise tolerance. The sublingual spray formulation provides several clinical advantages compared to tablet formulations, including a lower incidence of headache and superiority to the sublingual tablet in terms of therapeutic action and time to onset, while the magnitude and duration of vasodilatory action appears to be comparable. Furthermore, the sublingual spray formulation may be advantageous to tablet preparations in patients with dry mouth. This review discusses the efficacy and utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for both preventing and aborting an acute angina attack, thereby leading to an improved quality of life.

Effect of Diltiazem on Coronary Artery Flow and Myocardial Perfusion in Patients With Isolated Coronary Artery Ectasia and Either Stable Angina Pectoris or Positive Myocardial Ischemic Stress Test

Isolated coronary artery ectasia (CAE) may be associated with stable or unstable coronary events despite the absence of epicardial coronary stenosis. Impaired coronary flow dynamics and myocardial perfusion have been demonstrated in stable patients with ectatic coronary arteries. We aimed to assess whether epicardial flow and tissue-level perfusion would be improved by diltiazem in myocardial regions subtended by the ectatic coronary arteries in patients with isolated CAE. A total of 60 patients with isolated CAE were identified of 9,780 patients who underwent elective coronary angiography. Patients were randomized to 5mg of intracoronary diltiazem or saline. Coronary blood flow of the microvascular network was assessed using myocardial blush grade (MBG) technique. The thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (TFC) were used to assess epicardial coronary flow. MBG (from 2.4 to 2.6, p= 0.02), TIMI flow grades (from 2.4 to 2.8, p <0.001), and TFC (from 35 to 26, p <0.001) were significantly improved after diltiazem, whereas no significant change was noticed after saline (from 2.4 to 2.4, p= 0.86 for MBG; from 2.3 to 2.3, p= 0.71 for TIMI flow grade; and from 35 to 33, p= 0.43 for TFC). Diltiazem provided amelioration of the altered coronary flow dynamics, which was suggested as the pathophysiological influence of CAE. In conclusion, the favorable effects of the diltiazem on myocardial perfusion were observed at both epicardial and tissue levels.