Applications

PeriPort® Applications
As a standalone product

Pericardial Effusion

Web MD, 2008:
A higher incidence of pericardial effusion is associated with many diseases. Twenty-one percent of cancer patients have metastases to the pericardium. The most common are lung (37% of malignant effusions), breast (22%), and leukemia/lymphoma (17%). Patients with HIV, with or without AIDS, are found to have increased prevalence, with 41-87% having asymptomatic effusion and 13% having moderate-to-severe effusion.

Cardiovascular Applications

  • Anti-Thrombotic: Nitric Oxide Donor (1996)
  • Heart Repair: IGF-I For Ischemic DCM (2005), Ac-SDKP Prevents Gal-3 Remodeling – IPC Drugs Used To Produce AND Treat Heart Failure (2009)
  • Anti-Arrhythmic: Procainamide – Chronic IPC Catheter Data (2005), Amiodarone (1996), L-Arginine (1997), Esmolol (2000), Nitroglycerin (2003), 3-Omega FA (2008)
  • Cell Transplant: Endothelial Progenitor Cells For I/R Injury (2003)
  • Anti-Restenosis: Nitric Oxide Donor(s) (1998, 1999, 2002), Apo A-I Milano (1999), Paclitaxel (2000), Ethanol (2003)
  • Angiogenesis: bFGF (1997, 1998, 2000)
  • Gene Transfer: Adenovirus (1997, 1999)
  • Electrophysiology: Ablation (2000, 2003, 2004, 2008), Anti-Inflammatory IPC Drug (2007), Mapping (2003, 2007), EpicardialLead Placement (2005)
  • Echocardiography: Cardiac Imaging (2004, 2006)

As a delivery vehicle for electrophysiology devices:

Atrial Fibrillation

National Heart, Lung, and Blood Institute, 2005:
Atrial fibrillation (AF) is a major public health burden with a lifetime risk of 1 in 4 for its development (1 in 6, even if no heart failure or Myocardial Infarction is present) and costs of $6.4 billion per year. The prevalence of AF in the U.S. is 2.2 million and will double by 2020. AF prevalence increases with age, and AF doubles the risk for death and accounts for 15-20 percent of all strokes. In 2007, hospitalizations for arrhythmias increased 28% between 1997 and 2007. In 2007 731,000 individuals were hospitalized for irregular heart rhythms including atrial fibrillation and tachycardia. Hospitalizations for congestive heart failure in 2007 were just over one million.

Introduction of Electrophysiology Devices, Avila, et al:
“The development of novel techniques for percutaneous access to the pericardial space is changing our view of the usefulness of this space to treat cardiovascular disease. However, the idea of nonsurgically entering the normal pericardial sac for diagnostic or therapeutic purposes was unrealistic until recently. This was largely due to the perception that access to the pericardial space by a pericardial puncture approach was only safely possible in the presence of a sizeable pericardial effusion.” The paper concludes: “An understanding of this pericardial anatomy…is important as more cardiologists and electrophysiologists begin to exploit this novel approach to the heart. This is true not just for catheter ablation of arrhythmias but also for a number of other potential cardiovascular applications ranging from cardiovascular drug delivery to cardiac pacing.”

Hsia, et al:
Additionally, as recently as 2009, studies are showing that implantation of a cardioverter defibrillator inserted subxiphoid via a pericardial window in children. They concluded that: “Intrapericardial placement of an ICD coil system can be safely and successfully carried out through a minimally invasive subxiphoid approach in small infants and children. This novel ICD configuration demonstrates excellent performance, and provides a particularly efficacious approach to ventricular tachyarrhythmia therapy in pediatric patients.”

Conclusion:
The use of electrophysiology equipment for pacing, cardioverters and arrthymia treatments are beginning to be focused on the outside of the heart rather than the inside of the heart. PeriPort™ is an ideal candidate to provide delivery of these devices as it can provide access to the normal pericardial space.

For drug delivery

Cardiac Rhythm and Disease Management division of Medtronic, Xiao, et al:
The interest is spreading from the research environment to commercial enterprises. For example, the lead four of the six authors of the Xiao, et al paper concludes, “Worldwide, millions of patients die annually from sudden cardiac death. More than half of such deaths occur within one hour following an acute myocardial infarction, and this is typically associated with sustained ventricular arrhythmias.” “Therefore, pericardial infusion of n-3 PUFAs was considered to be an effective way to build up a high concentration around the heart. It was also considered that high concentrations of n-3 PUFAs should rapidly enhance their protective effects on myocardium, since they are highly lipid-soluble.

Furthermore, previous studies with the pericardial administration of amiodarone and procainamide have shown that the active motion of the heart within the pericardium mixes and distributes the drugs throughout the epicardium and that deep penetrations can occur.” Further, “Here, we report that a novel delivery approach with dosed DHA directly to the pericardial space had a dramatic cardioprotective effect.”

Cardiovascular Week:
“Intrapericardial (IPC) delivery of drugs to the heart may allow higher drug efficiencies with lesser side effects, researchers say. “Targeting drugs to the heart by intrapericardial (IPC) delivery may be a promising strategy to obtain higher drug efficiencies with lesser side effects.”

Kumar, et al:
“Interest is increasing in the direct delivery of agents into the pericardial space for local treatment of cardiovascular disorders to achieve maximum therapeutic effects and to minimize side effects of systemic administration.

The intrapericardial approach to local cardiac drug delivery possesses several intrinsic advantages: 1) Delivery into a low-turnover reservoir, which maximizes contact with tissue and minimizes loss of agent into circulation; 2) Access to coronary vessels and to the sympathetic and parasympathetic efferent fibers, both of which have significant segments of epicardial exposure, particularly at the base of the heart. Perfusion of atrial and ventricular epicardial tissue to affect ionic currents; 4) Reduced exposure to degradative enzymes, notably those contained in erythrocytes; and 5) Avoidance of systemic effects. Safe, rapid, reliable access without thoracotomy to the normal pericardial space has been demonstrated.”

It continued, “The well-established vascular effects of nitric oxide (NO) donors are augmented when administered intrapericardially. The NO donor sodium nitroprusside more effectively protected against platelet aggregation in stenosed and injured coronary arteries when administered intrapericardially than intravenously. Intrapericardial nitroglycerin (NTG) produced persistent coronary vasodilation without systemic hypotension or reflex elevations in heart rate (HR). The vasodilatory effect, measured by intravascular ultrasound, was more pronounced and enduring (3 to 15 min) than an equal intracoronary dose (200 µg bolus). Baek, et al, demonstrated a prolonged vasodilatory effect and positive remodeling by the NO donor diazeniumdiolated bovine serum albumin, which has 22-h intrapericardial residence time, and suggested a clinical application in protecting against restenosis after angioplasty.” The paper concluded, “Intrapericardial nitroglycerine exerts a robust antifibrillatory action.”

Baek, et al:
The paper concludes, “The data suggest that intrapericardial delivery of NO (nitric oxide) donors for which NO release rates and pericardial residence times are matched and optimized might be a beneficial adjunct to coronary angioplasty.”

Laham, et al:
The paper concludes, “A single intrapericardial bolus of basic fibroblast growth factor may be a useful therapeutic strategy for the treatment of myocardial ischemia in patients with coronary artery disease.”

Conclusion:
The pericardial space is unique and region-specific to give effective cardio active drug therapy without many of the systemic side effects of conventional drug delivery methods. The PeriPort™ provides a minimally invasive and safe method of delivery of drug therapy to the heart via the pericardial space.