Wednesday, October 27, 2010

Diuretics: Sequential blockade (Diuril-Lasix) "misconception"

JACC 2010;56:1527-34


Combination of Loop Diuretics With Thiazide-Type Diuretics in Heart Failure

Jacob C. Jentzer, MD,Tracy A. DeWald, RD, PharmD, BCPS andAdrian F. Hernandez, MD

Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-typediuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. We summarize the existing literature evaluating the combination of loop and thiazide diuretics in patients with heart failure in order to describe the possible benefits and hazards associated with this therapy. Combinationdiuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution, at the risk of inducing severe hypokalemia in addition to hyponatremia, hypotension, and worsening renal function. We provide considerations about prudent use of this therapy and review potential misconceptions about this long-used diuretic approach. Finally, we seek to highlight the need for pragmatic clinical trials for this commonly used therapy.

Saturday, October 23, 2010

Implantable Pressure Transducer: Cardiomems.com

Cardiomems.com

Dabigatran - Alternative for Warfarin (RE-LY trial)

Dabigatran versus Warfarin in Patients with Atrial Fibrillation

Connolly SJ. et al.

NEJM 2009;361:1139-51



BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.
METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism.
RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 p="0.003)" p="0.31)." p="0.13)" p="0.051).">

(ClinicalTrials.gov number, NCT00262600.)2009 Massachusetts Medical Society PMID: 19717844 [PubMed - indexed for MEDLINE]

Thursday, October 21, 2010

INR - Home testing does not improve outcome measures.

Effect of Home Testing of International Normalized Ratio on Clinical Events
David B. Matchar, M.D., Alan Jacobson, M.D., Rowena Dolor, M.D., M.H.S., Robert Edson, M.A., Lauren Uyeda, M.A., Ciaran S. Phibbs, Ph.D., Julia E. Vertrees, Pharm.D., Mei-Chiung Shih, Ph.D., Mark Holodniy, M.D., and Philip Lavori, Ph.D. for the THINRS Executive Committee and Site Investigators
N Engl J Med 2010; 363:1608-1620
October 21, 2010

Background
Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.
Methods
We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).
Results
The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).
Conclusions
As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.)

Tuesday, October 19, 2010

Stent Malposition - Predictors

J Am Coll Cardiol Intv, 2010; 3:1080-1086

Anatomic and Technical Predictors of Stent Malposition During Implantation for Vascular Obstruction in Patients With Congenital and Acquired Heart Disease

Jeffery Meadows, MD*, David Teitel, MD, Phillip Moore, MD

Objectives: We evaluated the anatomic and technical factors predicting stent malposition and embolization in patients undergoing endovascular stent implantation for relief of noncoronary vascular obstruction.

Background: Endovascular stent implantation provides a highly effective, minimally invasive solution to vascular obstruction in patients with structural heart disease. However, stent implantation is technically challenging and stent embolization occurs in up to 5.5% of cases.
Methods: We reviewed patient and procedural characteristics of all endovascular stent implantations performed for relieving noncoronary vascular obstruction from January 1, 1999, through December 31, 2009. Univariate and multivariate predictors of stent malposition or embolization were explored through logistic regression methods.

Results: During the 10-year study period, 429 stents were implanted. Of these, 399 were placed for relief of vascular obstruction in 267 patients during 322 procedures. Initial implantation failure occurred in 33 patients (8.3%), including stent malposition in 18 (4.5%) and stent embolization in 15 (3.8%). Patient size and vascular obstruction caused by external compression or a vascular fold were independent predictors of stent malposition or embolization. All malpositioned and embolized stents were successfully managed without surgery, and none resulted in death, sustained hemodynamic instability, or important vascular injury.

Conclusions: Endovascular stent implantation is a highly effective and safe means of relieving noncoronary vascular obstruction in patients with congenital and acquired structural heart disease. Stent embolization occurs in approximately 3.8% of implantation procedures but can be managed successfully without surgical intervention. Anatomic and technical factors predict stent malposition, and consideration of these factors may improve procedural results.

Editorial on this article: By Audrey Marshall & James Lock
JACC Interv 2010;3:1087-8

Additional referece:
Law MA, Shamzad P, Nugent AW, et al. Pulmonary artery stents: Long-term follow-up. Catheter Cardiovasc Interv 2010;75:757-64.

Thursday, October 7, 2010

BT shunt: Sternotomy vs. Thoracotomy

Heart Lung Circ. 2010 Aug;19(8):460-4.
Surgical approaches to the blalock shunt: does the approach matter?
Shauq A, Agarwal V, Karunaratne A, Gladman G, Pozzi M, Kaarne M, Ladusans EJ.
Department of Paediatric Cardiology, Alder Hey Royal Children Hospital, Eaton Rd, Liverpool L12 2AP, United Kingdom. shauq7@yahoo.com
Abstract
OBJECTIVE: The Blalock-Taussig (BT) shunt is an excellent palliative procedure for cyanotic congenital heart defects. We reviewed two techniques of performing the BT shunt, median sternotomy and thoracotomy, in relation to morbidity and mortality.
METHODS: Forty-five modified BT shunts in 41 patients, mean age 93 days (1-1045 days), were performed between January 2002 and October 2004. Twenty-four (53.3%) shunts in 21 (51.2%) patients were performed through thoracotomy and 21 (46.7%) shunts in 20 (48.8%) patients through median sternotomy. One surgeon preferred thoracotomy and the other sternotomy approach irrespective of age/weight or elective/emergency. Thirty-eight (84.4%) cases underwent elective operation and 7 (15.6%) cases were operated as emergencies. In both groups the most frequent diagnosis was complex Tetralogy of Fallot.
RESULTS: Postoperative oxygen saturation was same in both groups and there were no significant complications in either group. Patients undergoing BT shunt via median sternotomy approach had longer duration of ventilation (mean 183 h vs. 53 h, P<0.001)>inotropic requirements (33.3% vs. 4.2%, P<0.05)>longer intensive care unit stay (mean 9.14 days vs. 3.3 days, P<0.05)>hospital stay (mean 14.59 days vs. 5 days P<0.005).
CONCLUSIONS: Median sternotomy approach to performing BT shunt seems to carry a higher morbidity than thoracotomy. We recommend a large case series study and longer follow up.
PMID: 20434951 [PubMed - in process]

Neonatal Repair of Tetralogy of Fallot

Symptomatic neonatal Tetralogy of Fallot: Repair or Shunt?

Neonatal repair of TOF results in improved pulmonary artery development without increased need for reintervention.

Long-term results in right ventricular outflow tract reconstruction in neonatal cardiac surgery: Options and outcomes.
Kaza AK, et al. 2009;138:911-16

Poor outcome was reported from Boston Children's Hospital in 1991: 14 symptomatic babies had complete repair of TOF at less than 30 days. 4/14 (28.6%) died (JTCVS 1991;101:126-37).

Better results from Michigan. (Hennein HA et al. JTCVS 1995:109:332-44). n-30, No hospital death. 25% reoperation rate in mean f-up of 15 months.
Updated data from Michigan in 2000 (Hirsch JC et al. 2000;232:508-14), report 61% freedom from reoperation at 5 yrs.

Melbourne BT shunt experience.
Twelve year experience with the modified Blalock-Taussig shunt in neonates. Eur J Thorac Cardiovasc Surg 1992;6:586-9. Nearly 100 neonates with 1 death in 10 years. Find the paper and read it.

Sunday, October 3, 2010

Gen. Cardiology: Innocent vs. Pathologic murmur in Neonates

Can cardiologists distinguish innocent from pathologic murmurs in neonates?
Mackie, AS. et al.
J Pediatr 2009;154:50-4.

n-201
5 cardiologists
After clinical exam, documented murmur as "likely innocent" or "likely pathologic".
After EKG, the documentation was repeated.
Echocardiogram was taken as gold-standard.

Age 2-31 days (median 12 day)
113/201 had heart defect (56%)
Clinical assessment: Senstivity 80.5%, Specificity 90.9%
Positive predictive value 91.9%
Negative predictive value 78.4%

Cannulation in PA-IVS with RV dependent Coronary Circulation

Veno-venous bypass to prevent myocardial ischemia during right heart bypass operation in PA, IVS and RV dependent coronary circulation.
Asou et al.
Ann Thoracic Surg 200;69:955-6



Outcome: LBW babies with CHD

Outcome Analysis of Major Cardiac Operations in Low Birthweight Neonates.
Bove et al. Ann Thoracic Surg 2004;78:181-7.

1995-2003; Belgium, Less than 2.5 kg.
n=49 (Corrective Surgery 31, Palliative Surgery 18)
Weight: 1.3 - 2.5 (mean = 2.19) kg
Age at operation: 1 - 90 (mean = 15.2) days
Lesions: VSD 10, TOF 8, CoA 8, TGA 7, Single V 4, PA-IVS 4, IAA 3, TAPVR 3, CAVSD 2.
Overall mortality: 18% (4/31 & 5/18)
Mean f-up: 2.8 yrs
Survival: 87% for corrective surgery gp. 54% for palliative surgery gp.

Saturday, October 2, 2010

Viewpoint: Live Case Demonstrations

J Am Coll Cardiol, 2010; 56:1283-1285

Interventional Cardiology Live Case Presentations

Regulatory Considerations

Andrew Farb, MD*, Sheila A. Brown, RN, CCRC,Deborah A. Wolf, JD and Bram Zuckerman, MD

Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland

Live case presentations are increasingly common at interventional cardiology conferences. Taking advantage of significant advances in communication technology, broadcasts of procedures can be viewed as an extension of traditional medical education targeted to large groups of practitioners. However, there are important ethical, commercial, and patient safety issues associated with live cases that deserve attention. Use of investigational devices in live case demonstrations is subject to review and approval by FDA's Center for Devices and Radiological Health (CDRH), and the outcomes of patients participating in live cases areconsidered in the overall clinical study results. This article discusses CDRH's regulatory view of live case presentations with a focus on patient safety, clinical trial integrity, and concerns regarding improper medical device promotion.

Introduction:

The past 2 decades have witnessed a proliferation of live casedemonstrations of interventional cardiology procedures to treat coronary artery disease, structural heart disease, peripheral vascular disease, and cardiac arrhythmias. These presentations have often become integral parts of the scientific sessions sponsored by cardiovascular professional societies, large research foundations, and some individual medical institutions.

Multiple ethical, promotional, and educational issues surround the issue of live case presentations. Sade et al. (1), on behalf of the American Association for Thoracic Surgery Ethics Committee and the Society of Thoracic Surgeons Standards and Ethics Committee strongly question the value of live case demonstrations. The authors highlight patient safety risks and questionable medical ethics associated with live cases. Although they recognize that the teaching of surgical techniques by direct observation of live surgery in the surgeon's home operating room is a time-honored acceptable practice, they conclude that the educational benefits of broadcast live cases are "meager" compared to the potential harms faced by the participating patient. Thus, they recommend that national and international cardiothoracic societies consider prohibiting live surgery broadcasts at their annual meetings.

In contrast, a writing group composed on behalf of several U.S. and international cardiovascular professional societies, in the current issue of the Catheterization and Cardiovascular Interventions, the HeartRhythm Journal, and the Journal of the American College of Cardiology, provide greater emphasis on the merits of live case demonstrations and view them as an evolutionary advance in physician teaching methods (2). The authors attest to the inherent (but difficult to measure) benefits of live cases for physician education, improved quality of medical care, increased enrollment in clinical trials, and fostering innovations in medical device development. Importantly, the writing group recognize that there are no objective measures of the educationalvalue derived from the observation of live cases, and there is a paucity of data on the potential safety risks to patients who are subjects of live cases. The authors rightfully acknowledge the critique of live case demonstrations presented by Sade et al. (1); in response, they offer a detailed program of measures aimed at mitigating patient risks and ethical concerns. Their suggestions provide mechanisms to standardize the performance of live cases to enhance patient safety and improve their educational value.


The FDA's Role:

The FDA's broad public health mission is to provide assurance that drugs and devices are safe and effective for their intended uses. At the FDA, the Center for Devices and Radiological Health (CDRH) is responsible for establishing reasonable assurance of the safety and effectiveness of medical devices prior to marketing in the United States. Within CDRH, the Office of Device Evaluation's Division of Cardiovascular Devices evaluates the safety and effectiveness of devices used in interventional and electrophysiologic cardiovascular procedures. The agency appreciates the range of opinions offered by the authors representing thoracicsurgery and cardiology professional societies regarding the merits of live case demonstrations (1,2). Although there are clear individual patient welfare and public health implications associated with live cases, it is important to appreciate the FDA's oversight role and the scope of its regulatory review of these procedures.


Use of Investigational Devices in Live Case Demonstrations:

The FDA's most important role in the regulation of live cases occurs in the use of investigational non-FDA approved devices in patients enrolled in clinical trials in the U.S. It must be understood that the study of significant risk unapproved medical devices in any clinical study may only occur if a sponsor obtains approval of an Investigational Device Exemption (IDE, 21 CFR 812) from the FDA. An IDE allows the use of investigational devices in clinical trials of human subjects. Often, the objective of the clinical trial is to collect data on device safety and effectiveness to support a premarket approval application (PMA) or a premarket notification [510 (k)], which following FDA approval (PMA) or clearance [510 (k)], allows commercial marketing and use of the device. In other situations, an IDE is required if a sponsor is seeking a new indication for an approved deviceor the clinical research study involves off-label use of an approved device. An IDE provides protection to human subjects and ensures monitoring of the clinical study.

In the context of an unapproved device being used in an IDE study, FDA defines a live case presentation as:

"Treatment of a human subject under the auspices of an approved or conditionally approved IDE, conducted and broadcast in real time, or recorded and broadcast at a later time, to an audience at a widely attended professional scientific meeting."

Since investigational devices are not available for use outside of an IDE study (and might not ever become available in the U.S. if the device does not ultimately receive FDA approval or clearance), the Agency's view is that the use of an unapproved device in live case demonstrations should be limited to providing increased awareness of the IDE study for potential investigators and practicing physicians to augment the recruitment of study subjects.

The FDA approval of a live case presentation under the auspices of an IDE study requires a formal request from the sponsor and a detailed review by FDA staff; the application should be submitted at least 30 days prior to the live case demonstration to allow adequate time for a comprehensive evaluation. The applicationform for a live case demonstration requires that the sponsor address many of the concerns presented by the professional organizations (1,2). The sponsor should identify whether the case will be presented live in real time or videotaped for later broadcast. The FDA's primary focus regarding live cases is patient safety, and specific patient protection measures include:

• Institutional Review Board (IRB) approval. Approval of the live case presentation by an independent IRB is required.
• Risk analysis. A justification for a real time broadcast should include a rationale describing why a videotaped presentation would not serve as an adequate substitute. Procedural risks that may be increased by a live case setting include infections, prolonged procedure and anesthesia time, increased radiation exposure, increased intravenous contrast use, distraction of the operator, and patient privacy concerns. The application should discuss measures to minimize these risks. Although a case videotaped for later broadcast might be associated with reduced risk compared to a live case, the application process for FDA review and approval for a planned videotape is the same as that for a case to be shown live.
Informed consent. A signed informed consent that details potential additional risks posed by the live presentation must be obtained prior to subject participation. The consent document should outline confidentiality issues (e.g., broadcast of the procedure and possible recording for future viewing). A patient who agrees to be a subject in a live case should be informed that he or she should have no expectation of direct benefit as a result of his or her participation.

Live case demonstrations of investigational devices may be performed only at approved investigational sites by investigators who are currently participating in the study. Adherence to the study protocol, data collection, and reporting of adverse events apply equally to live cases as they do for all other patients enrolled in the IDE study. Any planned deviations from the approved IDE study protocol should be described and justified. Operators performing live cases must keep patient safety paramount and not compromise clinical decision-making or care for the sake of demonstrating a new device or technique. To reduce risks, we recommend that an on-site investigator (rather than the operator who is actively performing the procedure) primarily interacts with the off-site moderator and panel. Unanticipated adverse effects that occur during a live case presentation, or adverse effects that occur at increased frequency, should be separately reported to the FDA in an IDE supplement within 10 days.

Patients who participate in a live case count toward the total approved enrollment in the clinical trial, and procedural and clinical outcomes in these patients have the potential to affect the overall results of the study. Further, it is understood that live case patients may be chosen for specific anatomic or clinical features of interest (introducing selection bias), and their participation may violate study randomization or blinding. In the analysis of the study results, clinical outcomes of live case subjects should be analyzed separately and compared with the outcomes for the rest of the study population to assess whether these subjects were exposed to additional risks.

The FDA is sensitive to any overt or implied commercial promotion of the investigational devices demonstrated in live cases. Sponsors should provide a rationale for why the live case presentation is not a form of product promotion or advertising, and unapproved devices should be clearly identified as investigational during the broadcast and discussion of the case. Extremely high risk procedures or interventions in highly complex patients or anatomies are generally not suitable for live case presentation involving devices under IDE investigation. In addition, invasive procedures in children may be more technically challenging than in adults, and a live case presentation involving pediatric subjects must present no more than minimal additional risks. Live case demonstrations in pediatric patients are associated with special safety concerns (technically challenging anatomic features and heightened attention to radiation exposure and blood loss) and patient protection considerations (including assent by the child and parental permission); the sponsor must comprehensively address these pediatric-specific concerns in the request to the FDA for live case approval. Finally, use of an investigational device for compassionate use or in a continued access study (that is initiated after IDE enrollment has been completed) is not appropriate for live case presentations.


Use of FDA-Approved Devices in Live Case Demonstrations:

When not part of an IDE study, medical devices may be used either 1) in accordance with their FDA-approved indications for use (on-label use), or 2) off-label. Off-label use refers to use of an approved medical product in diagnosis or treatments other than those explicitly included in labeling. Although off-label use of a medical product should not be interpreted as inappropriate or substandard clinical practice, in many cases, it does meanthat data from well-designed clinical trials have not been developed that establish a reasonable assurance of safety and effectiveness for FDA approval for the specific condition. The on-label or off-label use of an approved medical device used in a live case demonstration is subject to IRB approval and informed consent.However, use of a device beyond its labeled indication should be publicly disclosed during the presentation. Although the planned use of approved devices that are not part of an IDE study in live cases is not subjected to FDA review and approval, the agency maintains an active interest in all live cases and can initiate disciplinary action if the live case encourages or commercially promotes off-label use of a medical device.


The FDA's Reach:

With advances in communication technology, interventional cardiology live case demonstrations are increasingly global in nature and are transmitted from medical centers worldwide. However, the FDA only has regulatory authority over live case presentations of investigational medical devices that are broadcast from sites within the US. It is our hope that high standards of patient safety, privacy, and ethics are also applied to live case procedures performed outside the U.S.


Summary:

Live case presentations may be viewed as an extension of traditionalmethods of medical education in an era of unparalleled growth of communication and broadcast transmission technology. However, the objective educational benefits of live case presentations are difficult to measure, and potential patient safety and ethical concerns need to be recognized. As a public health regulatory agency, FDA has important oversight of many aspects of live case demonstrations with patient protection as its highest priority. FDA is considering developing further guidance on live case presentations during IDE clinical trials. Lastly, as there have been few studies of adverse events or outcomes related to live cases (3,4), more research on procedural safety outcomes during live case presentations is needed to better define patient risks, particularly at a time in which live case presentations have become a cornerstone of many interventional cardiology meetings.

References:

1. Sade RM, American Association for Thoracic Surgery Ethics Committee and the Society of Thoracic Surgeons Standards and Ethics Committee Broadcast of surgical procedures as a teaching instrument in cardiothoracic surgery Ann Thorac Surg 2008;86:357-361.[Free Full Text]

Table I Potential Concerns Related to Live Surgical Cases
Adapted from Sade et al. (1).
• Increased infection risk associated with individuals who are unfamiliar with sterile technique and the placement of filming equipment in the procedure room
• Disruption of the operating theatre by audiovisual technicians and equipment, which may interfere with treatment
• Time delays to accommodate transmission schedules
• Hurried procedures due to transmission time constraints
• Performance of cases outside of regular working hours
• Changes in case strategies to accommodate the educational process or pre-specified case transmission schedules
• Distractions to the site operators associated with maintaining a dialogue with moderators or panelists, or as part of providing an educational experience
• Exposing visiting operators to an unfamiliar clinical environment and patient care team, without proper review of the planned case

2. Dehmer GJ, Douglas JS, Abizaid A, et al. SCAI/ACCF/HRS/ESC/SOLACI/APSIC statement on the use of live case demonstrations at cardiology meetings: assessments of the past and standards for the future J Am Coll Cardiol 2010;56:1267-1282.[Free Full Text]

Table II Goals for Case and Patient Selection for Live Demonstrations

• The rationale and indications for the procedure should be identified and explained to the audience before starting the case. These should fit within established guidelines or appropriate use criteria.
• The case strategy should be reviewed in advance of the broadcast and reflect the consensus of all available experts. Ideally, the case strategy should also be reviewed in advance with the case moderators, so that teaching objectives are understood.
• The case should have well-defined teaching objectives that have a high likelihood of being completed in the allotted time.
• Cases should be of medium to high complexity such that the educational lessons appeal to a broad audience with varying degrees of experience.
• Very high-risk scenarios should be avoided, as there is a greater chance of complications that may require the operators undistracted attention.
• The demonstration of new devices or evolving treatment strategies may be appropriate, but these procedures should be performed only by operators with the greatest amount of experience with the new device.
• Avoid non-standard techniques just for the sake of demonstrating a new device or treatment strategy. Avoid undue emphasis on performing cases simply to highlight a new device.
• Avoid sensational or "oddity" cases which will have little educational value to the practicing physician.

3. Wood S. Show and tell or just plain show?. Experts ponder the risks and benefits of live case demonstrations. http://www.theheart.org/article/309435.do 2010Accessed November 6, 2003.

4. Franke J, Reimers B, Scarpa M, et al. Complications of carotid stenting during live transmissions J Am Coll Cardiol Intv 2009;2:887-891.[Abstract/Free Full Text] - States that there was no increased risk (procedural and 30-day outcome)

when compared to published data.


Radiation Safety: Adult-oriented paper and Editorial.


Cumulative Exposure to Ionizing Radiation From Diagnostic and Therapeutic Cardiac Imaging Procedures: A Population-Based Analysis
Jersey Chen, Andrew J. Einstein, Reza Fazel, Harlan M. Krumholz, Yongfei Wang, Joseph S. Ross, Henry H. Ting, Nilay D. Shah, Khurram Nasir, and Brahmajee K. Nallamothu
J Am Coll Cardiol 2010;56 702-711

Editorial
Radiation Exposure From Cardiac Imaging Procedures: Do the Risks Outweigh the Benefits? Matthew J. Budoff and Mohit Gupta.
J Am Coll Cardiol 2010;56 712-714

Transcatheter Aortic Valve - Edwards CoreValve

J Am Coll Cardiol Intv, 2010; 3:859-866

Anatomic Suitability for Present and Next Generation Transcatheter Aortic Valve Prostheses

Evidence for a Complementary Multidevice Approach to Treatment

Hasan Jilaihawi, BSc (Hons), MBChB, Raoul Bonan, MD, Anita Asgar, MD, RĂ©da Ibrahim, MD, Tomasz Spyt, MD, Derek Chin, MBBS, Jan Kovac, MD.

Objectives: This study sought to assess the proportion of patients anatomically suitable for transcatheter aortic valve implantation by multiple access approaches.

Background: The devices currently in mainstream use for transcatheter treatment of severe aortic stenosis are those of Edwards (Edwards Lifesciences, Nyon, Switzerland) and Medtronic CoreValve (M-C) (Luxembourg City, Luxembourg). The range of patients that these can presently treat requires elucidation to guide the necessary evolution of these technologies and increase their scope of therapy.

Methods: A consecutive series of patients were assessed with transthoracic or transesophageal echocardiography and invasive angiography to assess anatomical suitability by different approaches. The transfemoral access requirements for Edwards and M-C (Edwards currently 22- and 24-F, soon to be 18- and 19-F; M-C 18-F) as well as the aortic valve annular criteria (18 to 25 mm and 20 to 27 mm, respectively) were incorporated in this assessment. Patients unsuitable for the transfemoral approach were considered for Edwards transapical and M-C transaxillary and direct ascendingaortic access. Patients suitable for these devices and access approaches were identified.

Results: Data were analyzed for 100 consecutive patients. Edwards suitability was 28% for Edwards-Sapien transfemoral, 78% for Edwards Novaflextransfemoral, and 88% for Edwards-Sapien transapical. Medtronic CoreValve suitability was 84% for transfemoral and 89% using additional transaxillary and direct aortic approaches. Of the 12 patients unsuitable for Edwards-based procedures, 8 were suitable for M-C. Of the 11 patients unsuitable for M-C–based techniques, 8 were suitable for Edwards. Only 3% were anatomically unsuitable for all approaches.

Conclusions: In this series, 97% of patients were anatomically suitable for a complementary approach to treatment.

Figure 1 Case Selection:

Figure 1

Suggested case selection algorithm for contemporary 2-device approach to transcatheter aortic valve implantation: (blue) "Edwards track"; (red)"CoreValve track." Multiple approaches increase the number of patients anatomically suitable for at least 1 transcatheter aortic valve implantation approach. CT = computed tomography; LVOT = left ventricular outflow track.


Figure 5: Newer Devices Studied

Figure 5

(A) The Novaflex system. This new system facilitates reduction in profile for the Edwards XT device to 18- and 19-F for 23- and 26-mm prostheses, respectively. (A, Top) The stented valve is crimped ex vivo onto catheter shaft. (A, Middle) The delivery system facilitates advancement of stented valve onto balloon in vivo. (A, Bottom) The stented valve is deployed at the level of the aortic annulus. (B) The Medtronic Ventor system, a self-expanding transapical device.

Left Atrial Appendage Obliteration - Pathology review

J Am Coll Cardiol Intv, 2010; 3:870-877

Left Atrial Appendage Obliteration

Mechanisms of Healing and Intracardiac Integration

Robert S. Schwartz, MD, David R. Holmes, MD, Robert A. Van Tassel, MD, Robert Hauser, MD, Timothy D. Henry, MD, Michael Mooney, MD, Ray Matthews, MD, Shephal Doshi, MD, Russell M. Jones, BS, Renu Virmani, MD

Objectives: The objectives of this study were: 1) to delineate the temporal course of histopathologic healing as the left atrial appendage (LAA) is obliterated by a mechanical device; and 2) to compare this process with other intravascular and intracardiac implanted technologies.

Background: Intracardiac device healing is incompletely understood. We thus studied the histopathology of device-based LAA obliteration.

Methods: Nine dog hearts were examined over time after LAA device placement and results were compared with human hearts with prior LAA obliteration using the same device.

Results: At 3 days in dogs, atrial surfaces were covered by fibrin, which sealed gaps between the LA wall and the device and filled the LA appendage cavity. At 45 days, endothelial cells covered the endocardial surface with underlying smooth muscle cells that sealed the device-LA interface. Regions with prior thrombus were replaced by endocardium surrounding the device membrane. Disorganized thrombus remained in the LAA body and at the periphery near the appendage walls. Mild inflammation was observed as thrombus resorbed. By 90 days, a complete endocardial lining covered the former LAA ostium. Organizing thrombus had become connective tissue, with no residual inflammation. The human necropsy hearts had similar findings. In these 4 hearts (139, 200, 480, and 852 days after implant), the ostial fabric membrane was covered with endocardium. The appendage surface contained organizing thrombus with minimal inflammation. Organizing fibrous tissue was inside the LAA cavity, prominent near the atrial wall. The LAA interior contained organizing thrombus.

Conclusions: This intracardiac device integration study delineated healing stages of early thrombus deposition, thrombus organization, inflammation and granulation tissue, final healing by connective tissue, and endocardialization without inflammation. These observations may yield insight into cellular healing processes in other cardiac devices.


Figure 1

Figure 1 Composite Images of the LAA and Obliteration

(A) Post-mortem dog heart (no device implanted), showing the exterior view of the left atrial appendage (LAA). (B) Diagrammatic view of the Watchman LAA obliteration method. Metal struts with anchoring hooks secure the device within the body of the appendage cavity. A fabric membrane filter covers the atrial surface of the device, preventing thrombi from escaping into the left atrial chamber. A center hub is used to connect the device to the catheter delivery system. (C) Dog autopsy specimen 28 days after Watchman implant showing a cross-sectional cutaway view of the Watchman device. The fabric membrane is covered with a fine layer of endocardium, and the metal struts are shown holding the device in place. Pectinate muscles internal to the LAA cavity are labeled. (D) Dog autopsy specimen showing a view of the former LAA ostium, now completely obliterated by the endocardium-covered fabric membrane. This view is from the left atrial cavity, where it is clear that thrombi potentially residing the left atrial appendage body could no longer escape into the left atrium and systemic circulation.

There are multiple other images of this device with pathologic specimens from Dog heart and Human heart at different times after implanation. Longest one, after 852 days after implantation.

Oxygen Therapy in Cardiac Patients (Acute Coronary Syndrome)

Viewpoint:
Revisiting the role of oxygen therapy in cardiac patients
JACC 2010;56:1013-6

Rationale for oxygen therapy in ACS:
1) Increasing oxygen tension decreases ischemic injury and the infarct size
2) Some patients have hypoxia due to ventilation-perfusion mismatch with pulmonary edema

Coronary vasoconstriction has been demonstrated in a Doppler-based study by measurement of coronary flow velocity (Am J Physiol Heart Circ Physiol 2009;296:H854-61). Potential mechanisms of this coronary vasoconstriction to Hyperoxia:
1) Hyperoxia -> Production of reactive oxygen species ->Decreases bioavailability of nitric oxide -> causes vasoconstriction
2) K ATP channels: Hypoxia → Depletion of ATP → Opening of KATP channel → Hyperpolarization of vacular smooth muscles → Vasodilation. The opposite happens with hyperoxia.
3) Oxygen-sensitive L-type Calcium channel in vascular smooth muscles. Hyperoxia causes vasoconstriction via these channels.
4) Hyperoxia → Angiotensin II → Endothelin-1 release → Vasoconstriction
5) Hyperoxia facilitates release of a potent vasoconstrictor 20-HETE (an archdonic acid metabolite).
6) High flow oxygen, despite increasing overall oxygen delivery, may not improve organ-specific oxygen delivery. In critically ill patients, high-flow oxygen causes a misdistribution of microcirculatory blood flow and reduce oxygen consumption by organs - heart (Reinhart et al. Reversible decrease of oxygen consumption by hyperoxia Chest 1991;99:690-4).

Conclusion:
Although use of oxygen is clearly appropriate and advisable to treat hypoxia, we - the authors - hypothesize that excessive use of supplemental oxygen in normoxic cardiac patients could potentially lead to worse outcomes. Further studies are needed to delineate the role of oxygen n these conditions.

My comment: Interesting view point. Not to be taken on its face value. Such, seemingly rational, claims have been made in the past - supported by seemingly adequate data. Many of them have proven wrong or disappeared without firm legs to stand on. Examples from the past that I have followed are (i) Vit K at birth causes cancer in later life, (ii) Milrinone will not work in neonates because the PDE isoform that is present in neonates is the kind that Milrinone does not work on (iii) Dopamine has no effect when given below 2 or 3 mcg/kg/min especially in newborn, etc.

Iron Overload Cardiomyopathy - Review

Iron Overload Cardiomyopathy. Better understanding of an increasing disorder.
Pradeep Gujja, Douglas Rosing, Dorothy Tripoli, Yukitaka Shizukuda.
JACC 2010;56(13):1001-12.

Adult oriented. But, summarizes the current state and future directions in dealing with this disease. Useful read.

Ethics: US apologizes to Guatemala over syphilis experiments in 1940s

NY Time article reports the news in Oct 1st 2010 edition.