Pinak B. Shah

Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina : A phase I/IIa double-blind, randomized controlled trial

Background— A growing population of patients with coronary artery disease experiences angina that is not amenable to revascularization and is refractory to medical therapy. Preclinical studies have indicated that human CD34+ stem cells induce neovascularization in ischemic myocardium, which enhances perfusion and function. Methods and Results— Twenty-four patients (19 men and 5 women aged 48 to 84 years) with Canadian Cardiovascular Society class 3 or 4 angina who were undergoing optimal medical treatment and who were not candidates for mechanical revascularization were enrolled in a double-blind, randomized (3:1), placebo-controlled dose-escalating study. Patients received granulocyte colony-stimulating factor 5 &mgr;g · kg−1 · d−1 for 5 days with leukapheresis on the fifth day. Selection of CD34+ cells was performed with a Food and Drug Administration–approved device. Electromechanical mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (versus saline). The total dose of cells was distributed in 10 intramyocardial, transendocardial injections. Patients were required to have an implantable cardioverter-defibrillator or to temporarily wear a LifeVest wearable defibrillator. No incidence was observed of myocardial infarction induced by mobilization or intramyocardial injection. The intramyocardial injection of cells or saline did not result in cardiac enzyme elevation, perforation, or pericardial effusion. No incidence of ventricular tachycardia or ventricular fibrillation occurred during the administration of granulocyte colony-stimulating factor or intramyocardial injections. One patient with a history of sudden cardiac death/ventricular tachycardia/ventricular fibrillation had catheter-induced ventricular tachycardia during mapping that required cardioversion. Serious adverse events were evenly distributed. Efficacy parameters including angina frequency, nitroglycerine usage, exercise time, and Canadian Cardiovascular Society class showed trends that favored CD34+ cell–treated patients versus control subjects given placebo. Conclusions— A randomized trial of intramyocardial injection of autologous CD34+ cells in patients with intractable angina was completed that provides evidence for feasibility, safety, and bioactivity. A larger phase IIb study is currently under way to further evaluate this therapy.

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association.

Background: Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. Methods and Results: To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. Conclusions: These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.

Best practices for transradial angiography and intervention: a consensus statement from the society for cardiovascular angiography and intervention's transradial working group.

Duke University Medical Center, Durham, North Carolina Stanford University Medical Center, Palo Alto, California Penn State Hershey Medical Center, Hershey, Pennsylvania Brigham and Women’s Hospital, Boston, Massachusetts Mayo Clinic, Rochester, Minnesota University of Illinois at Chicago/Jesse Brown VA Medical Center, Chicago, Illinois First Coast Heart and Vascular Center, Jacksonville, Florida G.V. (Sonny) Montgomery VA Medical CenterJackson, Mississippi. Stern Cardiovascular Foundation, Memphis, Tennessee Reid Heart Center at FirstHealth of the Carolinas, Pinehurst, North Carolina Deborah Heart & Lung Institute, Browns Mills, New Jersey Duke University Medical Center, Durham, North Carolina Lahey Clinic, Burlington, Massachusetts Geisinger Medical Center, Danville, Pennsylvania Apex Heart Institute, Seth N.H.L. Municipal Medical College, Ahmedabad, Gujarat, India The Wright Center for Graduate Medical Education, The Commonwealth Medical College, Scranton, Pennsylvania

Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: Initial clinical experience

BACKGROUND Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. METHODS We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent-anchored by the vessel walls and surrounding tissue-serves as the shunt. RESULTS TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. CONCLUSIONS TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted.

Management of Coronary Chronic Total Occlusion

A 67-year-old man with chronic stable angina presented with worsening angina to class III despite maximal medical therapy. He was referred for myocardial perfusion imaging, which showed a large area of inferior ischemia. Subsequent coronary angiography revealed a chronic total occlusion (CTO) of the right coronary artery with brisk collateral flow from the left anterior descending artery (Figure 1). There was minimal obstructive disease in the remainder of the coronary tree. An attempt at percutaneous coronary intervention (PCI) was unsuccessful. He was treated with continuation of his medical therapy, although he remained with lifestyle-limiting class II to III angina. Figure 1. Left, The totally occluded right coronary artery with the expected course of the distal vessel outlined in red and the total occlusion shown by the arrow. Right, Collateralization of the right coronary artery from the left anterior descending (LAD) artery with arrows pointing to the posterior descending artery (PDA) and posterolateral ventricular (PLV) branches of the right coronary artery. The septal collaterals from the LAD to RCA are highlighted. Coronary CTO is characterized by heavy atherosclerotic plaque burden within the artery, resulting in complete (or nearly complete) occlusion of the vessel. Although the duration of the occlusion is difficult to determine on clinical grounds, a total occlusion must be present for at least 3 months to be considered a true CTO.1 Patients with CTO typically have collateralization of the distal vessel on coronary angiography, but these collaterals may not provide sufficient blood flow to the myocardial bed, resulting in ischemia and anginal symptoms. CTO is clinically distinct from acute coronary occlusion, which occurs in the setting of ST-segment–elevation myocardial infarction, or subacute coronary occlusion, discovered with delayed presentation after ST-segment–elevation myocardial infarction. Clinical features and treatment considerations of these entities differ considerably from CTO. Among patients who have a clinical …

Non-viral vectors for gene therapy: clinical trials in cardiovascular disease.

The population of patients with end-stage symptomatic coronary and peripheral vascular disease is ever-expanding. Many of these patients no longer have options for mechanical revascularization, and despite maximal medical therapy, they remain physically limited due to angina or critical limb ischemia. The fundamental problem in these patients is insufficient blood supply to muscle due to severely diseased conduit vessels to the target tissue. Therefore, it seems logical that increasing the blood supply to ischemic tissue will relieve symptoms. One potential means to achieving this goal is via therapeutic angiogenesis. The molecular mechanisms behind vascular development are being elucidated, and animal models have shown that mediators of vascular development can be harnessed to produce new capillaries in ischemic tissue. These mediators include cytokines such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Angiogenic cytokines can be delivered in several forms including recombinant protein or via gene delivery as a naked plasmid or via viral vector. This chapter will describe the clinical trial experience to date with delivery of non-viral gene therapy for therapeutic angiogenesis in humans with disabling myocardial ischemia and peripheral vascular disease.

Bivalirudin Compared With Heparin During Coronary Angioplasty for Thrombus-Containing Lesions

OBJECTIVES We investigated whether bivalirudin is more effective than heparin in preventing ischemic complications in high risk patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. BACKGROUND Heparin is administered during coronary angioplasty to prevent closure of the dilated vessel. Bivalirudin (Hirulog) is a direct thrombin inhibitor that can be safely substituted for heparin during angioplasty. Bivalirudin has several theoretic advantages over heparin as an anticoagulant agent. METHODS We performed an observational analysis of the Hirulog Angioplasty Study in which 4,098 patients with unstable or postinfarction angina were randomized to receive either bivalirudin or heparin during coronary angioplasty. The study group for this analysis consisted of 567 patients who had thrombus-containing lesions on angiography. The primary end point was death, myocardial infarction, emergency coronary artery bypass graft surgery or abrupt vessel closure before hospital discharge. RESULTS Patients with thrombus-containing lesions had a higher incidence of myocardial infarction (5.1% vs. 3.2%, p = 0.03) and abrupt vessel closure (13.6% vs. 8.3%, p < 0.001) than those without thrombus. In patients with thrombus-containing lesions, however, the incidence of the primary end point was not different between the bivalirudin and heparin treatment groups. Furthermore, no difference in the incidence of ischemic events at 6 months was seen between the treatment groups. CONCLUSIONS Bivalirudin is not more effective than heparin in preventing ischemic complications in patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. Other approaches, perhaps involving potent anti-platelet agents, should be considered for patients with thrombus-containing lesions.

Radial Artery Catheterization

Cardiac catheterization is a minimally invasive procedure commonly used to diagnose and treat heart conditions. During catheterization, small tubes (catheters) are inserted into the circulatory system under x-ray guidance in order to obtain information about blood flow and pressures within the heart and to determine if there are obstructions within the blood vessels feeding the heart muscle (coronary arteries). Obstructions of the arteries are caused by plaque buildup, and when severe they can cause a variety of symptoms including chest pain and shortness of breath. A catheterization may be recommended on an elective basis if the symptoms are stable or on an emergency basis if the symptoms are sudden and the treating physician is concerned that they may represent an active or impending heart attack. On the basis of the location and number of obstructions, the treatment plan will include the use of specialized medications and possibly the placement of a stent or referral for bypass surgery to improve blood flow to the heart muscle and alleviate symptoms. The catheters necessary for cardiac catheterization can be inserted either into the femoral artery (in the groin), or into the radial artery (in the wrist). The femoral artery is a larger vessel and provides a more direct route to the heart. Because of these advantages, the femoral artery has become the standard entry site for catheterization procedures. However, there has been a recent increase in …

Incidence and predictors of late total occlusion following coronary stenting

To determine the incidence and predictors of total occlusion in‐stent restenosis, we reviewed three randomized stent vs. stent trials and one stent registry, which provided 955 coronary artery lesions with 6‐month angiographic follow‐up. Fifteen (1.6%) of the 955 stented lesions were totally occluded at 6‐month follow‐up. Most patients with total occlusion presented with recurrent angina at the time of repeat angiography (60.0%) while no patient presented with an acute ST segment elevation myocardial infarction. The univariate predictors of total occlusion following elective coronary stenting included stenting for restenosis after a previous percutaneous intervention (P = 0.001), longer stent length (P < 0.001), longer lesion length (P < 0.001), smaller reference vessel diameter (P = 0.022), smaller preprocedure minimum lumen diameter (MLD; P = 0.004), and smaller postprocedure MLD (P = 0.036). Stepwise multiple logistic regression analysis demonstrated that stenting for restenotic lesions (P = 0.004), longer stent length (P < 0.001), and smaller preprocedure MLD (P = 0.012) were independent predictors of total occlusion following coronary stenting. Catheter Cardiovasc Interv 2003;60:344‐351.

Cangrelor Use Since FDA Approval: A Single-Center, Real-World Experience at a Tertiary Care Hospital

Cangrelor, a rapidly acting, intravenous P2Y12 inhibitor, has been approved for use during percutaneous coronary intervention (PCI). The 3 phase 3 CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively provided robust randomized data in