Nadish Garg

Vascular Functions of the Plasminogen Activation System

The plasminogen activator (PA) system, which controls the formation and activity of plasmin, plays a key role in modulating hemostasis, thrombosis, and several other biological processes. While a great deal is known about the function of the PA system, it remains a focus of intensive investigation, and the list of biological pathways and human diseases that are modulated by normal and pathologic function of its components continues to lengthen. Because of remarkable advances in molecular genetics, the laboratory mouse has become the most useful animal system to study the normal and pathologic functions of the PA system. The purpose of this review is to summarize studies that have used genetically modified mice to examine the functions of the PA system in hemostasis and thrombosis, intimal hyperplasia after vascular injury, and atherosclerosis. Particular emphasis is placed on the vascular functions of PA inhibitor-1, a key regulator of the PA system, and the multiple variables that appear to account for the complex role of PA inhibitor-1 in regulating vascular remodeling. Lastly, the strengths and limitations of using mice to model human vascular disease processes are discussed.

Effectiveness of Percutaneous Coronary Intervention With Drug-Eluting Stents Compared With Bypass Surgery in Diabetics With Multivessel Coronary Disease: Comprehensive Systematic Review and Meta-analysis of Randomized Clinical Data

Background Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). Coronary artery bypass grafting (CABG) has been compared with percutaneous coronary intervention (PCI) using drug‐eluting stents (DES) in recent randomized controlled trials (RCTs). Methods and Results RCTs comparing PCI with DES versus CABG in diabetic patients with MVD who met inclusion criteria were analyzed (protocol registration No. CRD42013003693). Primary end point (major adverse cardiac events) was a composite of death, myocardial infarction, and stroke at a mean follow‐up of 4 years. Analyses were performed for each outcome by using risk ratio (RR) by fixed‐ and random‐effects models. Four RCTS with 3052 patients met inclusion criteria (1539 PCI versus 1513 CABG). Incidence of major adverse cardiac events was 22.5% for PCI and 16.8% for CABG (RR 1.34, 95% CI 1.16 to 1.54, P<0.0001). Similar results were obtained for death (14% versus 9.7%, RR 1.51, 95% CI 1.09 to 2.10, P=0.01), and MI (10.3% versus 5.9%, RR 1.44, 95% CI 0.79 to 2.6, P=0.23). Stroke risk was significantly lower with DES (2.3% versus 3.8%, RR 0.59, 95% CI 0.39 to 0.90, P=0.01) and subsequent revascularization was several‐fold higher (17.4% versus 8.0%, RR 1.85, 95% CI 1.0 to 3.40, P=0.05). Conclusions These data demonstrate that CABG in diabetic patients with MVD at low to intermediate surgical risk (defined as EUROSCORE <5) is superior to MVD PCI with DES. CABG decreased overall death, nonfatal myocardial infarction, and repeat revascularization at the expense of an increase in stroke risk.

Plasminogen activator inhibitor‐1 and vitronectin expression level and stoichiometry regulate vascular smooth muscle cell migration through physiological collagen matrices

Summary.  Background:  Vascular smooth muscle cell (VSMC) migration is a critical process in arterial remodeling. Purified plasminogen activator inhibitor‐1 (PAI‐1) is reported to both promote and inhibit VSMC migration on two‐dimensional (D) surfaces.

Heart Failure With a Normal Left Ventricular Ejection Fraction: Epidemiology Pathophysiology, Diagnosis and Management

Abstract:Heart failure (HF) with a normal left ventricular (LV) ejection fraction (HFNEF) occurs in 40-71% of patients with HF and carries a prognosis similar to that of HF with a reduced LV ejection fraction (LVEF). The pathophysiology of HFNEF is distinct from that of HF with a reduced LVEF and is characterized by impaired relaxation of myocardium, LV stiffness and, in many cases, increased arterial stiffness. Systemic hypertension accounts for most cases of HFNEF in the United States. Those with HFNEF tend to be older and obese. Diabetes mellitus and atrial fibrillation occur with disproportionately high frequency in HFNEF. The diagnosis of HFNEF requires the presence of symptoms or signs of HF, a normal or near-normal LVEF and evidence of LV diastolic dysfunction based on cardiac catheterization or Doppler echocardiographic techniques and/or elevation of plasma natriuretic peptide levels. Current guidelines for management of HFNEF include control of systolic and diastolic hypertension, control of the ventricular rate in patients with atrial fibrillation and judicious use of diuretics. In selected cases, coronary revascularization or restoration of sinus rhythm in those with atrial fibrillation may be indicated. To date, no drug or drug group has consistently improved survival in HFNEF. For this reason and because of the poor long-term prognosis, preventative measures and effective treatment of underlying causes and precipitating factors are particularly important in avoiding HF exacerbations in patients with HFNEF.

Acute coronary syndrome caused by coronary artery mycotic aneurysm due to late stent infection localized with radiolabeled autologous leukocyte imaging.

Mycotic coronary artery aneurysm presenting as acute coronary syndrome is an uncommon but fatal condition. The diagnosis of mycotic aneurysm can be very challenging and difficult. Therefore, a high index of suspicion along with the use of multimodality imaging may help to diagnose this condition in patients with a prior history of coronary artery bypass grafting or percutaneous coronary intervention with persistent bacteremia with no identifiable source of infection. This case highlights a possibility of late stent infection and its association to drug eluting stents.

Plasminogen activator inhibitor-1 and restenosis

Despite the introduction of drug-eluting stents restenosis remains an important clinical problem. In this review we examine the role of plasminogen activator inhibitor-1 (PAI-1) in controlling restenosis after balloon angioplasty and stent implantation.

Outcomes of percutaneous coronary intervention of chronic total saphenous vein graft occlusions in the contemporary era

Percutaneous coronary intervention of a chronic total occlusion to a saphenous vein graft is currently not recommended because the benefit/risk ratio is considered unfavorable. However, there is a patient subset with clinical ischemia, and PCI of the native chronic total occlusion (CTO) is unfavorable. In this setting, PCI to the saphenous vein graft (SVG) may have utility. We reviewed our experience to determine its value in the modern era.

Giant left ventricular pseudoaneurysm

Left ventricular (LV) pseudoaneurysm (PS) is an uncommon, often fatal complication associated with myocardial infarction, cardiothoracic surgery, trauma, and, rarely, infective endocarditis. A 28-year-old man with prior history of bioprosthetic mitral valve replacement presented with congestive heart failure and bacteremia with Abiotrophia granulitica. Transesophageal echocardiogram showed bioprosthesis dysfunction, large vegetations, mitral regurgitation, and probable PS. Cardiac and chest CT confirmed a PS communicating with the left ventricle Patient had pulseless electrical activity and died. Autopsy showed a giant PS with layered thrombus and pseudo-endothelialized cavity. Our case highlights the importance of multimodality imaging as an important tool in management of PS.

Secondary Hyperparathyroidism in Heart Failure

ABSTRACT Secondary hyperparathyroidism (SHPT) is a well‐known pathophysiologic feature of chronic renal failure. In recent years, SHPT has become recognized as a complication of the aldosteronism associated with congestive heart failure and where excretory Ca2+ and Mg2+ wasting results in plasma‐ionized hypocalcemia and hypomagnesemia. Elevations in plasma parathyroid hormone have adverse systemic consequences, including intracellular Ca2+ overloading of myocytes and vascular smooth muscle with the induction of oxidative stress. Herein, we briefly review the presence and adverse outcomes of SHPT in persons with heart failure.

Comparison of left ventricular ejection fraction values obtained using invasive contrast left ventriculography, two-dimensional echocardiography, and gated single-photon emission computed tomography:

Objectives: Left ventricular ejection fraction can be measured by a variety of invasive and non-invasive cardiac techniques. This study assesses the relation of three diagnostic modalities to each other in the measurement of left ventricular ejection fraction: invasive contrast left ventriculography, two-dimensional echocardiography, and quantitative gated single-photon emission computed tomography. Methods: Retrospective chart review was conducted on 58 patients hospitalized with chest pain, who underwent left ventricular ejection fraction evaluation using each of the aforementioned modalities within a 3-month period not interrupted by myocardial infarction or revascularization. Results: The mean left ventricular ejection fraction values were as follows: invasive contrast left ventriculography (0.44±0.15), two-dimensional echocardiography (0.46±0.13), and gated single-photon emission computed tomography (0.37±0.10). Correlations coefficients and associated p values were as follows: invasive contrast left ventriculography versus two-dimensional echocardiography (r=0.69, p<0.001), invasive contrast left ventriculography versus gated single-photon emission computed tomography (r=0.80, p<0.0001), and gated single-photon emission computed tomography versus two-dimensional echocardiography (r=0.69, p<0.001). Conclusion: Our results indicate that strong positive correlations exist among the three techniques studied.