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Background: The prognostic significance of impaired left ventricular (LV) relaxation and increased LV stiffness as precursor of heart failure with preserved ejection fraction and death is still largely unknown in apparently healthy subjects. Methods: We constituted a cohort of 353 patients with normal ejection fraction (>45%) and no significant heart disease, based on a total of 3,575 consecutive left-sided heart catheterizations performed. We measured peak negative first derivative of LV pressure (-dP/dt) and operating chamber stiffness (Κ) using a validated equation. Patients were categorized as having: 1) normal diastolic function, 2) isolated relaxation abnormalities (-dP/dt > 1860mm Hg/sec and K <0.025mm Hg/ml), or 3) predominant stiff heart (K ≥0.025mm Hg/ml). Results: During a follow-up of at least 5 years, the incidence of the primary composite endpoint (death, major arterial event, heart failure, and arrhythmia) was 23.2% (82 patients). Compared to isolated relaxation abnormalities, predominant stiff heart showed stronger prognostic significance for all events (p=0.002), namely heart failure (HR, 2.9; p=0.0499), cardiac death (HR, 5.8; p=0.03), and heart failure and cardiac death combined (HR, 3.7; p=0.003). Conclusion: In this apparently healthy population referred to our center for cardiac catheterization, the prevalence of diastolic dysfunction was very high. Moreover, predominant stiff heart was a better predictor of cardiovascular outcomes than isolated relaxation abnormalities.

Background: Current guidelines for diagnosis and management of heart failure (HF) rely on clinical findings and natriuretic peptide values, but evidence suggests that recently identified cardiac biomarkers may aid in early detection of HF and improve risk stratification. The aim of this study was to assess the diagnostic and prognostic utility of multiple biomarkers in patients with HF and left ventricular systolic dysfunction (LVSD). Methods: High-sensitivity cardiac troponin I (cTnI), N-terminal pro b-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), endothelin-1 (ET-1), pro-matrix metalloproteinase-9 (pMMP-9), and tumor necrosis factor-alpha (TNF-α) were measured using single-molecule counting technology in 200 patients with varying stages of HF. Plasma detection with cross-sectional associations of biomarkers across all HF stages, and advanced-therapy and transplant-free survival were assessed using multivariate analysis and Cox regression analyses, respectively. Results: NTproBNP, pMMP-9, IL-6 were elevated in early, asymptomatic stages of HF, and increased with HF severity. Higher circulating levels of combined IL-6, NTproBNP, and cTnI predicted significantly worse survival at 1500-day follow-up. Cox regression analysis adjusted for ACC/AHA HF stages demonstrated that a higher concentration of IL-6 and cTnI conferred greater risks in terms of time to death, implantation of left ventricular assist device (LVAD), or heart transplantation. Conclusion: Biomarkers of inflammation, LV remodeling, and myocardial injury were elevated in HF and increased with HF severity. Patients had a significantly higher risk of serious cardiac events if multiple biomarkers were elevated. These findings support measuring NTproBNP, cTnI and IL-6 among patients with HF and LVSD for diagnostic and prognostic purposes.

Anomalies of coronary artery origin are congenital malformations characterized by the abnormal birth of a coronary artery from the controlateral coronary aortic sinus (birth of the left coronary artery from the right sinus or birth of the right coronary artery from the left sinus). The artery concerned has an abnormal initial path between the aorta and the pulmonary artery; this segment is most often intramural, in the aortic wall. They are rare with a prevalence (0.1% to 0.3% of the population). They pose a high risk of sudden stress death related to exercise myocardial ischemia. The most common mode of discovery is aborted sudden death, but sometimes fortuitously. The contribution of multi-round CT is described for the positive diagnosis of these anatomical variations, sometimes delicate in coronary angiography, but also for the distinction between “benign” and “malignant” forms, potentially responsible for myocardial ischemia. Treatment is usually surgical in symptomatic forms. We report the cases of two patients with coronary connection abnormalities discovered in adulthood.

Objectives: We report our results regarding the use of BioPath™ paclitaxel-coated balloon catheters for superficial or distal external iliac artery revascularization via single retrograde popliteal access. Methods: We included 105 prospective consecutive patients. Single retrograde popliteal access was achieved under ultrasound guidance with the patients laid prone. An over-the-wire atherectomy system was used if risk of distal embolization was high due to plaque intensity of the target lesion. A 4 to 7 mm-diameter BioPath™ 035 balloon catheter was used for all lesions. Follow-up at 6th month included doppler ultrasound examination for patency. Results: Seventy-two patients (68.6%) had total SFA occlusion and 41 patients (39%) had concomitant external iliac artery involvement, out of whom 31 (29.5%) had total occlusion. Procedural success 90.5% for superficial femoral artery and 85.3% for external iliac artery. One-year patency rates in SFA and EIA were 84.8% and 80.4%, respectively Conclusion: Single retrograde popliteal access and drug-coated balloon angioplasty may offer a useful alternative to known modalities in treatment of challenging superficial femoral artery and concomitant iliac artery lesions

Purpose: This study reports resource utilization during a Medicare Beneficiary’s (MBs) Transcatheter Aortic Valve Replacement (TAVR) index hospitalization and all subsequent encounters for 12 months and compares data between MBs who did or did not receive a pacemaker implantation (PPM) during their index hospitalization. Method: This retrospective study examined Medicare hospital claims from January 1, 2014 through June 30, 2015. 15,533 MBs who survived for 365 days were studied. Information from all encounters during the study period was combined to compare hospital resource utilization and outcomes. Results: 14.8% of MBs had a PPM during the index hospitalization. 46.0% of MBs had at least one readmission to a hospital during the 365-day follow-up period. 54.6% of MB’s first hospital readmission occurred within 90 days of their TAVR discharge date. Average total Medicare reimbursement for all hospitalizations was $60,638 ± $28,974 associated with average total hospital length of stay of 11.2 ± 11.7 days. After adjusting for demographics and 47 comorbid conditions, MBs receiving a PPM during the index TAVR had significantly higher estimated Medicare reimbursement ($5,132) and longer total length of stay (1.8 days) for the entire study period than MBs not receiving a PPM. Conclusion: Total Medicare reimbursement and hospital LOS were significantly higher among MBs that had a PPM implantation during their index admission; however, there were no significant differences in readmission rates, readmission length of stay, or days to first readmission during the follow-up period between the two study cohorts.

Chronic heart failure has been extensively characterized as a disorder arising from a complex interaction between impaired ventricular performance and neurohormonal activation. Since beta adrenoceptor blocking agents are currently considered an integral component of therapy for the management of patients with severe chronic heart failure; several well designed clinical trials have been conducted to determine the morbidity and mortality benefits of these agents these studies, however did not yield the same results in terms of morbidity and mortality benefits. Currently only Bisoprolol, Carvedilol and sustained release metoprolol succinate have clinically proven and convincing morbidity and mortality benefits the current list of approved medicines of the National Health Insurance Scheme (NHIS) of the republic of Ghana does not provide coverage for these lifesaving therapeutic agents. The objective of this review was to collate the relevant scientific evidence that will convince the authorities at the National Health Insurance Authority (NHIA) of the Republic of Ghana to include at least one of the evidence based beta adrenoceptor blocking agents in the list of approved medicines. A thorough search on the internet was conducted using Google scholar to obtain only the clinically relevant studies associated with the benefits of beta adrenoceptor blocking agents in patients with chronic heart failure published in the English language. The phrases beta adrenoceptor blocking agents and chronic heart failure were used as search engines. The search engine yielded several studies that met the predefined inclusion criteria. However, only the Cardiac Insufficiency BIsoprolol Studies (CIBIS-I and CIBIS-II), Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) and Metoprolol CR/XL Randomized Intervention Trial (MERIF-HF) because of the clinical relevance of their findings Beta adrenoceptor blocking agents such as atenolol and propranolol have been used in the management of patients with chronic heart failure. However, their efficacy and optimal dose in reducing mortality have not been scientifically established not all beta adrenoceptor blocking agents scientifically studied provide the same degree of clinically meaningful and convincing morbidity and mortality benefits in patients with chronic heart failure.

Objective: To investigate in an animal model of Pulmonary Hypertension (PH) by monocrotaline whether a lower exercise intensity, which has lower potential to provoke dyspnea symptoms, could prevent the increase the right ventricle pressure and the decrease in respiratory compliance. Setting: A research laboratory. ANIMALS: twenty-one Wistar rats were randomized to the groups: Control (CO; saline solution); PH-sedentary; PH-low and PH-moderate intensity of exercise training (ET). Interventions: They received a single saline or monocrotaline subcutaneous injection (50 mg/kg). The exercise program was performed during 3-weeks. Main Outcome Measures: Rats were evaluated by their morphometric and hemodynamic changes and by the respiratory mechanic responses induced by the exercise protocols. Results: Both protocols of ET significantly (p < 0.05) attenuated the increase in the right ventricular systolic pressure. However, the lower intensity was more effective to prevent the impairment in the respiratory and quasi-static compliance. Conclusion: Collectively, our results showed for the first time the benefits of ET to the respiratory system mechanics. We also demonstrated that intensity is crucial in PH, probably due to the difficulty to match VO2 capacity and O2 demand during exercise. The improvement in quasi-static compliance not only might improve the ability to breathe, and capture oxygen, but also welfare.

Objectives: Cardioembolic etiology is a frequent source of ischemic stroke. Echocardiogram is the mainstay of cardioembolic source detection with regard to plan secondary stroke management, however it remains unclear how often clinically actionable findings are provided hereby. In addition, it is uncertain whether echocardiography should be performed transthoracic or transesophageal (TEE). In a monocenter study, we evaluated the frequency of pathological findings from TEE evaluation in patients with ischemic stroke with suspected cardioembolic and cryptogenic source and determined whether there was an associated adjustment in the prescribed administration of antithrombotic therapy. Materials and Methods: Over a 21-month period (2012-2013), we enrolled 143 patients in a prospective monocenter study (mean age ± standard deviation, 70 ± 12 years; females, 44.1%) who were admitted to the Department of Neurology at the University of Lübeck due to ischemic stroke and who underwent TEE due to supposed cardiac embolism. We assessed the presence of atrial fibrillation; days from admission to TEE; and TEE findings, including atrial septal aneurysm, thrombogenic aortic arch, valve failure, presence of left atrial thrombus, and patent foramen ovale. Demografic information and medical history were drawn from patient records and the hospital information system. Results: On average, TEE was performed 4 days after admission to the hospital. Left atrial thrombus was detected in 3 patients (2.1%), patent foramen ovale (PFO) in 27 (18.9%), atrial septum aneurysm in 17 (11.9%), and thrombogenic aortic arch in 29 (20.3%). Findings from TEE were commonly associated with therapeutic adjustment; antiplatelet therapy increased from 30.1% to 80.4%, oral anticoagulation therapy increased from 2.8% to 27.3%. Conclusion: Findings from TEE for the evaluation of ischemic stroke lead to frequent adjustment of prior antithrombotic therapy, antiplatelet as well as anticoagulation.

Background: Adoption of the Lung Allocation Score (LAS) has led to increased listing of older patients and those with idiopathic pulmonary fibrosis (IPF) for lung transplantation (LTX). Older patients and those with IPF have higher prevalence of coronary artery disease (CAD), a relative contraindication for LTX. The impact of the LAS on CAD prevalence and cardiovascular morbidity in LTX recipients is unknown. Methods: Retrospective review of single institution database from January 2000 to December 2010. Patients with and without CAD were compared by age, gender, LAS, single vs double LTX, and transplant indication. Survival was calculated by Kaplan-Meier method, and statistical significance determined by log-rank method. Survival analysis was performed on all patients and by 3:1 propensity matching. Differences in CAD, gender, and indication were determined by Chi-squared test. Differences in LAS and age were calculated with a two-tailed t - test. Results: In the pre-LAS era, 6.2% (9/145) recipients had CAD vs. 9.2% (17/184) in the post-LAS era (p = 0.411). Among all patients, recipients with CAD had a worse long term survival as estimated by Kaplan-Meier method (p = 0.001), although there was no statistically significant difference after propensity matching ((p = 0.14). Although more recipients in the post-LAS era had a diagnosis of IPF [15/145 vs. 71/184 patients, (p < 0.001)], there was no difference in the prevalence of CAD in the IPF cohort compared to others. There were no differences in cardiovascular deaths among recipients with CAD, with IPF, or in the post-LAS era. Patients with a pre-transplant diagnosis of CAD had an descreased risk of new onset postoperative atrial fibrillation (AF) (p = 0.007; HR:0.133; CI:0.030-0.583). Conclusion: Adoption of the LAS was not associated with a significant change in proportion of recipients with CAD who underwent LTX at our institution, despite an increase in recipients with IPF. Recipients with CAD had a higher risk of developing new postoperative AF and worse survival than patients without CAD. Differences in survival, however, could not be attributed directly to CAD based on propensity matched analysis

A 56-year-old man was admitted to our hospital because of sudden onset of right-sided thoracic pain. The ECG showed inferior ST segment elevations. He has been treated with aspirin, clopidogrel, unfractionated heparin and tenecteplase, and his symptoms resolved after 30 minutes. About half an hour later, the patient developed again left-sided thoracic pain and the signs of an anterior myocardial ST-segment elevation infarction. 90 minutes after receiving the initial medications, the performed coronary angiography revealed a long dissection of a large ramus circumflexus. Furthermore, the left anterior descending coronary artery was occluded at about the mid-level. The left ventriculography showed a reduced ventricular function and a Stanford type A aortic dissection. Immediate patient transfer for emergency surgical intervention was arranged. However, ventricular fibrillation occurred during transport and he required endotracheal intubation and prolonged cardiopulmonary resuscitation. Unfortunately, he died during further transport. In a patient with massive thoracic pain of initially uncommon localization in combination with fluctuation of ST-segment elevations, aortic dissection should be seriously taken into the differential diagnosis as well as into therapeutic management decisions (in particular antiplatelet and thrombolytic therapy).

Purpose: This was a prospective study conducted at Benha University hospital and National Heart Institute on one hundred patients undwent coronary artery bypass grafting (CABG) to evaluate the effect of CABG on the right ventricular (RV) function using speckle tracking echocardiography (STE). Methods: All cases were subjected to detailed medical history, full physical examination, 12 leads electrocardiogram (ECG), routine laboratory tests including (complete blood picture, liver functions, renal functions and lipid profile) and echocardiography either conventional echocardiography or STE, all parameters obtained before and within 2 weeks after surgery. Results: By conventional echocardiography there was statistically significant decrease in peak right ventricle systolic velociy (RVS) from (12.76 ± 1.72) to (7.33 ± 1.71) and tricuspid annular plane systolic excursion (TAPSE) from (22.8 ± 3.99) to (13.77 ± 4.63) among the studied patients after CABG. While there was significant increase in right ventricle fractional area change (RVFAC) from (44.69 ± 3.25) to (49.01 ± 3.36). On the other hand, there was non-significant change in right ventricle end diastolic diameter (RVEDD) at mid-cavity from (26.37 ± 2.72) to (26.53 ± 2.72) and basal segment from (36.05 ± 2.98) to (36.29 ± 3.04), right ventricle stroke volume (RVSV) from (65.44 ± 7.02) to (65.85 ± 6.86) and right myocardial performance index (RMPI) from (0.491 ± 0.088) to (0.498 ± 0.086). By STE There was statistically significant decrease in right ventricle global longitudinal strain (RVGLS) from (-20.63 to -14.1) after CABG. There was statistically significant decrease in right ventricle free wall longitudinal strain [apical decreased from (-23.73 to -13.7), mid-cavity decreased from (-25.76 to -11.53), basal decreased from (-20.39 to -10.13) and lateral wall declined from (-23.01 to -9.13)]. There was statistically significant decrease in interventricular septum longitudinal strain [apical decreased from (-19.77 to -10.06), mid-cavity decreased from (-17.81 to -10.87) and basal decreased from (-15.89 to -11.13)]. There was statistically significant increase in RV circumferential strain of lateral free wall from (-12.04 to -16.21), while there was non-significant change in RV circumferential strain of septum from (-19.77 ± 4.86) to (-20.37 ± 5.14). Conclusion: Distorted RV geometry after CABG can lead to altered deformation parameters, in other words longitudinal functional parameters may underestimate RV function and the decrease in RVGLS was compensated by increase in circumferential strain of lateral free wall of RV without change in RVSV or RMPI. Therefor changes in deformation parameters should always be interpreted in relation to change in geometry.

Permanent pacemaker implantation is conventionally done via upper limb veins. But in 1% - 6% cases, usual sub clavicular approach is either not possible or contraindicated due to complete occlusion of superior vena cava (SVC) or bilateral subclavian vein and/or bilateral implant site infection or thin skin [1]. Alternative approaches are warranted, including leadless pacemaker or complex lead extraction techniques, before considering surgical epicardial lead placement as a last resort because it has own hazards. We report a patient with complete heart block, total SVC obstruction, and a previously implanted malfunctioning epicardial lead presenting with pacemaker end of life. In view of exhaustion of the surgical option and in a resource constrained situation for lead extraction or leadless pacemaker, transiliac endocardial pacemaker implantation was done and a repeat surgery was averted. Learning objective: Complete venous occlusion is not very often encountered after pacemaker/ICD implantation. Apart from the risk of general anesthesia and invasive surgery, epicardial leads increase battery drain, and have a shorter operating life compared to an endocardial lead. The sparingly utilized iliac venous approach for permanent pacemaker implantation is a valuable, safe and minimally invasive alternative, when the conventional percutaneous access is unavailable, and surgery is undesirable or not possible. 

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca2+/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca2+/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca2+] changes. I suggest here that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation, not involving G proteins. is by translocation of the β-arrestin from the sarcoplasm to the plasma membrane thus reducing its kinase inhibition action in the sarcoplasm. This reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

Biventricular (BiV) pacing revolutionized the heart failure management in patients with sinus rhythm and left bundle branch block; however, left ventricular-lead placement is not always technically possible. Also, BiV pacing does not fully normalize ventricular activation and, therefore, the ventricular resynchronization is imperfect. On the other hand, right ventricular pacing for bradycardia may cause or worsen heart failure in some patients by causing dyssynchronous ventricular activation. His bundle pacing comes as an alternative to current approaches as it activates the ventricles via the native His-Purkinje system, resulting in true physiological pacing, and, therefore, is a promising site for pacing in bradycardia and traditional CRT indications in cases where it can overcome left bundle branch block. Furthermore, it has the potential to open up new indications for pacing therapy in heart failure, such as targeting patients with PR prolongation, but a narrow QRS duration. In this article we explore the history, clinical evidence, proposed mechanisms, procedural characteristics, and the role in current therapy of His bundle pacing in the prevention and treatment of heart failure.

Background: Infants of diabetic mothers (IDMs) are at increased risk of developing congenital anomalies including cardiac defects. Pathological left ventricular hypertrophy, asymmetrical septal hypertrophy and outflow tract obstruction is a rare but known cardiac comorbidity in infants of diabetic mothers. The severity of this condition in IDMs can vary from an incidental finding on echocardiography to an infant with severe symptoms of congestive heart failure and specific management of the condition varies. Aim: The aim of this article is to report this clinical entity in a Nigerian infant born to a mother with poor glycaemic control in pregnancy and highlight management. Case report: We report a term neonate who was diagnosed as a case of pathological left ventricular hypertrophy, asymmetrical septal hypertrophy and outflow tract obstruction delivered to a mother with gestational diabetics with poor glycaemic control in pregnancy. Child was treated successfully with β-adrenergic blocker and showed resolution of hypertrophy in follow-up echocardiography. Conclusion: Infants of diabetic mothers are very high risk infants. Pathological left ventricular hypertrophy in IDM have good prognosis. Early recognition and prompt intervention is advocated.

Dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor has been consistently shown to reduce recurrent major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) compared with aspirin monotherapy but at the expense of an increased risk of significant bleeding. Among patients with stable CAD undergoing PCI with drug-eluting stents (DES), shorter duration of DAPT (3–6 months) were shown non-inferior to 12 or 24 months duration concerning MACE but reduced the rates of major bleeding? Contrariwise, prolonged DAPT durations (18–48 months) reduced the incidence of myocardial infarction and stent thrombosis, but at the cost of an increased risk of majör bleeding and all-cause mortality. Until more evidence becomes available, the choice of optimal DAPT regimen and duration for patients with CAD requires a tailored approach based on the patient clinical presentation, baseline risk profile and management strategy. Patients with acute coronary syndromes (ACS) and a history of atrial fibrillation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. This article provides a contemporary state-of-the-art review of the current evidence on DAPT for secondary prevention of patients with CAD and its future perspectives.

Myocardial infarction without ST segment elevation is one of the most common causes of hospitalization of the elderly patient [1]. Coronarography followed by revascularization, is performed in the vast majority of cases of myocardial infarction without ST segment elevation, in the regions with a well-developed health system. The decision to perform the procedure, the type of approach (early/late) and the selection of the type of myocardial revascularization depend on numerous factors such as: associated comorbidities, clinical presentation, the risk group in which the patient is framed, fragility, cognitive status, life expectancy etc. [2,3]. Older patients often present with various comorbidities, having a higher risk of complications and an unfavorable evolution. Thus, it was observed that invasively treatment is less commonly used in elderly patients with comorbidities, even if, the current guideline recommends that the invasive strategy should be considered in all patients with NSTEMI, regardless of age. At the same time, this subgroup of patients is not so well represented in the studies performed so far, the type of treatment chosen, being most often at the discretion of the attending physician [1,2]. Objective The present study aims to analyze the evolution of a subgroup of patients ≥ 70 years of age, with different comorbidities, with the diagnosis of myocardial infarction without ST segment elevation, according to the type of treatment applied: conservative versus invasive strategy (diagnostic coronarography ± revascularization, if appropriate).

Background: Various surgical methods have been utilized in the management of complete atrioventricular septal defects (CAVSD). Early intervention and achievement of a competent left atrioventricular valve are the key factors for successful treatment. Methods: A total of 66 patients with complete atrioventricular septal defect have been operated in a tertiary care center. Patient group consisted of 28 males and 38 females with an average age of 6.2 ± 3.3 months. Ventricular and atrial defects were repaired generally with single-patch technique using autogenous pericardium. Results: Preoperative catheterization and angiography was performed in 41 patients. Single patch and modified single patch techniques were preferred in 57 and 9 patients respectively. The average duration for respiratory support, intensive care unit stay and discharge from hospital were 36 ± 49.3 hours, 4.1 ± 1.9 days, and 10.1 ± 3.3 days respectively. In the left atrioventricular valve mild, moderate and severe regurgitation were detected in 44 (66.6%), 17 (25.7%) and 2 (3%) patients postoperatively. No regurgitation was determined in 3 patients (4.5%). Two cases ended up with mortality (3%). Conclusion: Single patch repair technique can provide satisfactory surgical outcomes in patients with complete atrioventricular septal defect.

Peripartum cardiomyopathy is one of the curable cardiomyopathy. It’s a severe and frequent disease arising among women of childbearing age. Its evolution in the long-term among some patients leads to chronic heart failure. Our study aims to determine from a prospective cohort, the factors associated with the non-recovery of myocardial function upon 12 months of diagnosis. Sociodemographic, clinical and echocardiographic data were collected at the time of diagnosis and then in months 3, 6 and 12. The outcome was the non-recovery of myocardial function at one year, defined by a left ventricular ejection fraction (LVEF) below 50%. 60 patients were analyzed after 12 months of follow-up. Mortality was about 13.3% and recovery rate of myocardial function reached 42.3%. After logistic regression, delay diagnosis and observance were the factors related to non- recovery of myocardial function.

Fibrinolytic therapy has become synonymous with tissue plasminogen activator (tPA) based on the belief that tPA alone was responsible for natural fibrinolysis. Although this assumption was belied from the outset by disappointing clinical results, it persisted, eventually causing fibrinolysis to be discredited and replaced by an endovascular procedure. Since time to reperfusion is the critical determinant of outcome, which in acute myocardial infarction (AMI) means within two hours, a time-consuming hospital procedure is ill-suited as first line treatment. For this purpose, fibrinolysis is more fitting. The assumption that tPA is responsible for fibrinolysis is contradicted by published findings. Instead, tPA ‘s function is limited to the initiation of fibrinolysis, which is continued by urokinase plasminogen activator (uPA) and that has the dominant effect. tPA and uPA gene deletion and clot lysis studies showed the activators have complementary functions, requiring both for a full effect at fibrin-specific doses. They are also synergistic in combination thereby requiring lower doses for efficacy. A clinical proof of concept study in 101 AMI patients who were treated with a 5 mg bolus of tPA followed by a 90 minute infusion of prouPA, the native form of uPA. A near doubling of the 24 h TIMI-3 infarct artery patency rate was obtained compared to that in the best of the tPA trials (GUSTO). In further contrast to tPA, there were no reocclusions and the mortality was only 1% [1]. A sequential combination of both activators, mimicking natural fibrinolysis, holds promise to significantly improve the efficacy and safety of therapeutic fibrinolysis.