An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan hemostat with a tortuous spherical microporous design that enables rapid blood absorption and concentrated platelets and fibrin microthrombi in localized regions, a phenomenon less observed with other classical hemostats without structural optimization. The interaction between blood components and the porous hemostat was further amplified based on the charged surface of chitosan. Contrary to the dogma that chitosan does not directly affect physiological clotting mechanism, the hemostat induced coagulation via a direct activation of platelet Toll-like receptor 2. Our engineered porous hemostat effectively stopped the bleeding from murine liver wounds, swine liver and carotid artery injuries, and the human radial artery puncture site within a few minutes with significantly reduced blood loss, even under the anticoagulant treatment. The integration of engineering design principles with an understanding of the molecular mechanisms can lead to hemostats with improved functions to address emerging medical needs.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Expanding treatment horizons: transcatheter mitral valve-in-valve replacement in bridging to heart transplant.

Transcatheter mitral valve (MV) replacement is an option in complex MV disease with potentially more predictable treatment outcomes and less invasiveness that increases the treatment spectrum to high-risk or non-surgical patients. We present an interesting case of failed MV bioprosthesis who presented with progressively worsening heart failure for heart transplant evaluation, but was successfully managed with transcatheter mitral valve-in-valve replacement (TMViVR). This case illustrates the pivotal role of TMViVR utilization in addressing complex cardiac scenarios, particularly when re-operative surgical MV replacement poses a high risk and also bridging the gap between the present and future heart transplantation preparations by paving the way for a well-prepared patient in the subsequent phase. The lifetime disease management and patient-centric approach with meticulous risk assessment reinforces the importance of shared decision-making in complex cases.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Novel use of intravascular lithotripsy for coral reef aorta: a case report.

BACKGROUND: The coral reef aorta (CRA) is a rare disease of extreme calcification in the juxtarenal aorta. These heavily calcified exophytic plaques grow into the lumen and can cause significant stenoses, leading to visceral ischaemia, renovascular hypertension, and claudication. Surgery or percutaneous intervention with stenting carries a high risk of complications and mortality. CASE SUMMARY: A 67-year-old female had presented with severe hypertension and exercise limiting claudication for 18 months. On evaluation, she was found to have severe bilateral renal artery stenoses with juxtarenal CRA causing subtotal occlusion. Both renal arteries were stented. For CRA, we used intravascular lithotripsy (IVL) assisted plain balloon angioplasty to minimize possibilities of major dissection and perforation and avoided chimney stent-grafts required to protect visceral and renal arteries. We used a double-balloon technique using a 6 × 60 mm IVL Shockwave M5 catheter and a 9 × 30 mm simple peripheral balloon catheter, inflated simultaneously at the site of CRA as parallel, hugging balloons to have an effective delivery of IVL. Shockwaves were given in juxta/infrarenal aorta to have satisfactory dilatation without any complication. The gradient across aortic narrowing reduced from 80 to 4 mmHg. She had an uneventful recovery and has remained asymptomatic at 6-month follow-up. DISCUSSION: When CRA is juxtarenal with no safe landing zones for stent-grafts, IVL may be a safe, less complex and effective alternative to the use of juxtarenal aortic stent-graft with multiple chimney or snorkel stent-grafts. This is the first report of a novel use of IVL to treat CRA.

Transradial interventions: our experience.

Traditional coronary angiography and angioplasty are usually performed via femoral approach. Though this route provides an easier vascular access, it is associated with a smaller but potentially serious incidence of vascular complications at the puncture site that may result in significant groin haematoma, blood transfusion or require surgical repair. A useful and safe alternative approach is through the transradial access. This route has a very low rate of vascular complications and also allows early mobilization of patients. Though this approach is less commonly used all over the world, recently the usage of this technique has improved. Currently we as a team of Heart Care Clinic are performing more than 90% of the procedure via transradial route. We have performed thousands of angiographies and angioplasties by this route in past several years. Here we performed an analysis of our experience with transradial angiography and angioplasty, demonstrating this to be a safe and effective technique suitable for most of the patients.

Nature Decides Survival: Primary Angioplasty in Congenitally Corrected Transposition of Great Arteries at 76 Years of Age.

A 76-year-old man with congenitally corrected transposition of great arteries (CCTGA) presented with acute inferior wall myocardial infarction and underwent primary angioplasty. Coronary anatomic variations and challenges are discussed. (Level of Difficulty: Advanced.).

Late coronary stent infection: a difficult to diagnose rare complication after percutaneous coronary intervention.

Percutaneous transluminal coronary angioplasty (PTCA) with drug-eluting stent placement is a well-established treatment modality for coronary stenotic lesions. Although infection involving implanted stent is rare, it can occur at any point of time, leading to high morbidity and mortality. We describe a rare case of infected coronary stents complicated with recurrent stent thrombosis, sepsis, and myocardial abscess formation after 2 years of percutaneous cornary intervention (PCI). Using multi-modality imaging final diagnoses to evaluate the precise location, extent and morphology of myocardial abscess (MA) was done. "On pump" coronary artery bypass graft (CABG) was performed, left anterior descending (LAD) artery intramyocardially was opened up, about 7-10 ml of pus was evacuated, and two drug-eluting stents (DES) were removed. The isolated identified organism was Pseudomonas aeruginosa which had remained dormant and restricted to the stent area for almost 2 years thinning the myocardium; an unusual trait of a very virulent bacterium which otherwise spreads fast to cause septicemia. The present case exemplifies the high index of clinical sensitivity with early multi-modality diagnosis, aggressive medical therapy, multidisciplinary care, and timely surgical intervention saving the patient's life in otherwise fatal condition.

Efficacy of PercuSurge in acute myocardial infarction patients undergoing revascularization with a special emphasis on procedural time.

AIM: To evaluate the efficacy of the PercuSurge Guardwire(R) Plus Temporary Occlusion and Aspiration System, the actual procedural time involved and long-term follow-up in acute MI patients undergoing primary/rescue percutaneous coronary intervention (PCI). METHODS & RESULTS: It was a single centred, prospective study in 67 prospective AMI patients undergoing PCI. They were divided randomly into two groups depending on whether PercuSurge was used (n=30) or not used (control n=37) during PCI. Final TIMI flow, TMP grade and the time involved in or necessary for various steps of the PCI were recorded. PercuSurge showed significantly greater achievement of TIMI III flow and TMP III grade (p<0.01). Its use was associated with less total procedural time (p<0.05). The time required from guidewire crossing to stent placement; from guidewire crossing to TIMI III flow and from predilatation/stent placement to optimal TIMI flow was significantly reduced with its use (p<0.05 for all). Slow/no-reflow was significantly reduced (p<0.001), thus reducing intracoronary vasodilators and GP IIb/IIIa antagonists requirements. A 2 years' follow-up revealed four deaths in control and one death in PercuSurge group. CONCLUSION: PercuSurge reduced the total procedural time with better and faster optimal TIMI flow and TMP grade in primary/rescue PCI and was associated with less long term events.

Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions.

OBJECTIVE: To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors, especially plasma fibrinogen, in patients with acute coronary syndrome (ACS) requiring percutaneous coronary interventions. METHODS: A randomized, non-blinded, prospective study with parallel group design. One hundred two ACS patients who underwent angioplasty were randomly assigned to atorvastatin (20 mg/day, n=25), simvastatin (40 mg/day, n=27), atorvastatin-fenofibrate (10 mg/day-200 mg/day) combination (n=25) or simvastatin-fenofibrate (20 mg/day-200 mg/day) combination (n=25). The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments. RESULTS: All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines. The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels, and caused an increase in high-density lipoprotein levels. All the treatment groups showed a significant decrease in the plasma fibrinogen levels. Plasma fibrinogen did not correlate with study parameters such as age, body weight, hemo-dynamic characteristics and lipoprotein levels. Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels. CONCLUSIONS: The addition of fenofibrate to statins seems to be beneficial in patients with ACS. Statins decreased plasma fibrinogen significantly, contrary to results from various reports, and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen.

Long-term safety and performance of the orbital atherectomy system for treating calcified coronary artery lesions: 5-Year follow-up in the ORBIT I trial.

BACKGROUND/PURPOSE: The ORBIT I trial, a first-in-man study, was conducted to evaluate the safety and performance of the orbital atherectomy system (OAS) in treating de novo calcified coronary lesions. METHODS/MATERIALS: Fifty patients were enrolled between May and July 2008 based on several criteria, and were treated with the OAS followed by stent placement. The safety and performance of the OAS were evaluated by procedural success, device success, and overall major adverse cardiovascular event (MACE) rates, including cardiac death, myocardial infarction (MI) and need for target lesion revascularization (TLR). Our institution enrolled and treated 33 of the 50 patients and continued follow-up for 5 years. RESULTS: Average age was 54 years and 91% were males. Mean lesion length was 15.9 mm. Device success was 100%, and average number of orbital atherectomy devices (OAD) used per patient was 1.3. Stents were placed directly after OAS in 31/32 patients (96.9%). All stents (average stent per lesion 1.1) were successfully deployed with 0.3% residual stenosis. The overall cumulative MACE rate was 6.1% in-hospital, 9.1% at 30 days, 12.1% at 6 months, 15.2% at 2 years, 18.2% at 3 years and 21.2% at 5 years (4 total cardiac deaths). None of the patients had Q-wave MIs. Angiographic complications were observed in 5 patients. No flow/slow flow due to distal embolization was observed. CONCLUSIONS: The ORBIT I trial suggests that OAS treatment continues to offer a safe and effective method to change compliance of calcified coronary lesions to facilitate optimal stent placement in these difficult-to-treat patients.

Orbital atherectomy system in treating calcified coronary lesions: 3-Year follow-up in first human use study (ORBIT I trial).

BACKGROUND/PURPOSE: The ORBIT I trial evaluated the safety and performance of an orbital atherectomy system (OAS) in treating de novo calcified coronary lesions. Severely calcified coronary arteries pose ongoing treatment challenges. Stent placement in calcified lesions can result in stent under expansion, malapposition and procedural complications. OAS treatment may be recommended to facilitate coronary stent implantation in these difficult lesions. MATERIALS/METHODS: Fifty patients with de novo calcified coronary lesions were enrolled in the ORBIT I trial. Patients were treated with the OAS followed by stent placement. Our institution treated 33/50 patients and continued follow-up for 3 years. RESULTS: Average age was 54.4 years and 90.9% were males. Mean lesion length was 15.9mm. The average number of OAS devices used per patient was 1.3. Procedural success was achieved in 97% of patients. Angiographic complications were observed in five patients (two minor dissections, one major dissection and two perforations). The cumulative major adverse cardiac event (MACE) rate was 6.1% in-hospital, 9.1% at 30 days, 12.1% at 6 months, 15.2% at 2 years, and 18.2% at 3years. The MACE rate included two in-hospital non Q-wave myocardial infarctions (MI), one additional non Q-wave MI at 30 days leading to target lesion revascularization (TLR), and three cardiac deaths. CONCLUSIONS: The ORBIT I trial suggests that OAS treatment may offer an effective method to modify calcified coronary lesion compliance to facilitate optimal stent placement in these difficult-to-treat patients with acceptable levels of safety up to 3 years post-index procedure.

Deliverability of the Resolute Integrity stent and a post hoc comparison of radial and femoral access: the DELIVER study.

BACKGROUND/PURPOSE: DELIVER (DELiverability of the Resolute Integrity Stent in All-Comer Vessels and Cross-OvER stenting) was a prospective, multicenter, all-comers registry to assess the deliverability of the Resolute Integrity™ zotarolimus-eluting stent (R-ZES). METHODS/MATERIALS: Patients (n=7740 patients, 10449 lesions) undergoing percutaneous coronary intervention and deemed suitable for R-ZES implantation were enrolled and treated according to standard practice of the participating centers in 30 countries. Outcomes included delivery success and in-hospital target lesion failure (TLF), major adverse cardiac event (MACE), and Academic Research Consortium definite/probable stent thrombosis. We performed a post hoc analysis comparing deliverability, in-hospital clinical outcomes and resource utilization with radial vs. femoral access. RESULTS: A high proportion of the population had complex disease (71%): mean lesion length was 26.7±17.5 mm, 35% of lesions were moderately/severely calcified and 17% were bifurcated. Femoral and radial accesses were used in 53% and 46% of patients, respectively. Patients treated using femoral access had more complex coronary artery disease. Primary delivery success was 98.9% and did not differ by approach. Radial access was associated with lower stent and balloon utilization, but higher guide catheter utilization, lower procedure duration, and contrast administered compared with femoral access. In-hospital TLF and MACE occurred in 1.6% of patients; definite or probable stent thrombosis occurred in 0.2%. Clinical outcomes did not differ by vascular access. CONCLUSIONS: R-ZES was found to be highly deliverable in a complex, all-comers, international population, regardless of whether radial or femoral access was used. In-hospital outcomes were excellent with very low risk of complications.

Ovalum CiTop Expander: a novel guidewire for crossing coronary chronic total occlusions--first-in-man (FIM) experience.

AIMS: To evaluate the safety and efficacy of the CiTop Expander guidewire in attempting to cross through chronic total occlusion in CAD patients with various coronary dimensions and morphology. Although chronic total occlusions are encountered frequently in patients with coronary artery disease, an effective strategy to deal with them has yet to be devised. Various new guidewires have been designed in an attempt to negotiate chronic occlusions successfully. The aim of the CiTop Expander guidewire is to improve the success rate of chronic total occlusion (CTO) recanalisation. METHODS AND RESULTS: Ten consecutive male or female patients between 21 and 80 years of age, with no significant comorbidities and with angiographic documented chronic total occlusion (> 1 month) showing distal TIMI flow 0, or a prior failed guidewire attempted CTO were included in the study. The endpoints analysed were technical success (crossing of CTO by placement of CiTop Expander distal to occlusion with no device related major complications), angiographic success (<20% residual stenosis and TIMI flow grade 3), and clinical success. The basic features of the novel guidewire and its assessment of compatibility with other cathlab equipments were also recorded. The mean (+/- SD) age of the all male patient group was 53.6+/-9 years. The mean (+/-SD) lesion diameter and length was 3.1+/-0.4 mm and 20.4+/-7.9 mm, respectively, while the mean (+/-SD) age of occlusion was 25.5+/-26.8 months. Technical and angiographic successes were obtained in seven patients (70%). No events were recorded within seven days and 30-days follow-up after discharge. CONCLUSIONS: The CiTop Expander guidewire was found to be efficacious and safe for use in recanalisation of chronically occluded coronary arteries in this initial experience.

Effect of pioglitazone and its combination with statins in coronary artery disease patients with hyperinsulinemia.

The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.

Intracoronary boluses of adenosine and sodium nitroprusside in combination reverses slow/no-reflow during angioplasty: a clinical scenario of ischemic preconditioning.

No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 microg/bolus) or the combination of adenosine (12 microg/bolus) and sodium nitroprusside (50 microg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persistent in 70% patients receiving saline solution, 31% patients receiving adenosine, and 4% patient receiving the combination. IC injection with saline solution did not produce improvement in TIMI flow or TMP grade. IC injection with combination resulted in greater improvement of TIMI flow and TMP grade. The crossover of patients with no-reflow in saline solution group or adenosine with combination treatment was associated with reestablishment of TIMI II in 4 and TIMI III in 20 patients. Our data suggest that combination therapy of adenosine and nitroprusside is safe and provides better improvement in coronary flow and MACE as compared with IC adenosine alone in cases of impaired flow during coronary interventions.