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.

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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]

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.)

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.

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?

Kanter et al. Ann Thorac Surgery 2010;89:858-63

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

Kolcz J & Pizarro, C. Eur J Cardio-thorac Surg 2005;394-99

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.