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What's new in cardiology

Last literature review version 17.3: September 2009  |  This topic last updated: October 16, 2009   (More)

The following represent additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

ARRHYTHMIAS

The RE-LY trial, which evaluated the efficacy and safety of two different doses of dabigatran relative to warfarin in over 18,000 patients with atrial fibrillation, is the first trial to demonstrate that an alternative oral anticoagulant may be superior to adjusted-dose warfarin [1]. Dabigatran 110 mg was non-inferior to warfarin for the primary efficacy endpoint of stroke or systemic embolization, while dabigatran 150 mg was significantly more effective than warfarin or dabigatran 110 mg. Major bleeding occurred significantly less often with dabigatran 110 mg than warfarin; dabigatran 150 mg had equal safety to warfarin. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", section on 'Dabigatran'.)

The decision to use antithrombotic therapy to prevent embolization in patients with nonvalvular atrial fibrillation (AF) is based upon an assessment of the absolute benefits and risks. The ATRIA study evaluated the net clinical benefit (NCB) of warfarin, measured as the difference between the annualized rate of thromboembolic events prevented by warfarin minus the annualized rate of intracranial hemorrhages induced by warfarin, in over 13,000 patients with nonvalvular AF [2]. After six years the NCB became statistically significant at a CHADS2 score of 2 and progressively increased at higher CHADS2 scores. This relationship reflects the greater reduction in embolic risk compared to increase in intracranial hemorrhage risk with higher CHADS2 scores. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", section on 'Net clinical benefit'.)

Many patients who are at significant risk for embolization in atrial fibrillation (AF) cannot take anticoagulation therapy. The WATCHMAN, a device placed percutaneously to occlude the left atrial appendage, was evaluated in a randomized non-inferiority trial in patients with non-valvular AF that compared the device and long-term warfarin [3]. The device was found to be non-inferior for the composite primary efficacy end point (stroke, cardiovascular death, and systemic embolism) but the primary safety end point (a composite of major bleeding, pericardial effusion, procedure related stroke, and device embolization) occurred significantly more often in the device group. (See "Left atrial appendage amputation, ligation, or occlusion in patients with atrial fibrillation", section on 'Percutaneous LAA occlusion'.)

A large prospective community-based cohort study of individuals from the Framingham Heart Study reviewed outcomes for individuals with first degree atrioventricular (AV) block [4]. Compared with those with a normal PR interval, individuals with first degree AV block were more likely to develop atrial fibrillation, had a greater risk of receiving a permanent pacemaker, and a higher all-cause mortality. These findings are not consistent with the benign prognosis for this condition suggested by earlier studies. (See "First degree atrioventricular block", section on 'Prognosis'.)

Although a retrospective study funded by the Food and Drug Administration (FDA) reported an association between stimulant attention deficit hyperactivity disorder (ADHD) medication and sudden unexpected death in youths [5], the FDA concluded that this study was not able to verify a relationship between the use of stimulant therapy and sudden unexpected death because of methodologic limitations [6].(See "Cardiac evaluation of children receiving pharmacotherapy for attention deficit hyperactivity disorder", section on 'FDA ongoing safety review'.)

CORONARY HEART DISEASE

In July 2009 the United States Food and Drug Administration (FDA) approved the oral antiplatelet agent prasugrel for use (along with aspirin) in patients with acute coronary syndromes (ACS) undergoing PCI. This was based upon the results of the TRITON-TIMI 38 trial in which over 13,000 patients with ACS who underwent PCI were randomly assigned to either prasugrel or clopidogrel [7]. Patients with non-ST elevation ACS received thienopyridine treatment after coronary angiography, while those with ST-elevation myocardial infarction generally received treatment before coronary angiography. At 15 months the primary endpoint (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) occurred significantly less often with prasugrel (9.9 versus 12.1 percent). (See "Antiplatelet agents in unstable angina and acute non-ST elevation myocardial infarction", section on 'Summary and recommendations' and "Antiplatelet agents in acute ST elevation myocardial infarction", section on 'Summary and recommendations'.)

A number of perioperative factors influence the rate of operative mortality after CABG and a variety of algorithms are available to predict risk. However, many of these algorithms are limited by their complexity, questionable validity, or derivation from patients having both elective and emergent surgery. The ACEF (Age, Creatinine, Ejection fraction) score, developed to address these issues, includes only three variables and is derived from a population that underwent elective open heart surgery [8]. ACEF was able to predict mortality as well as or better than five other more complex risk scores such as EUROSCORE or the Cleveland Clinic model. (See "Operative mortality after coronary artery bypass graft surgery", section on 'Predictors of risk'.)

An association between lipoprotein(a) and cardiovascular disease (CVD) has been suggested by relatively small cross-sectional and retrospective epidemiologic studies. Two recent publications have shed further light on this association [9,10]:

  • A 2009 meta-analysis found a continuous association between Lp(a) and CHD risk although the risk ratio was lower than that found in most prior studies (risk ratio 1.13, 95% CI 1.09-1.18) [10].
  • A causative role for Lp(a) in the increased risk for CVD is suggested by a Mendelian randomization study, in which Lp(a) levels, myocardial infarctions, and the frequency of the number of 5.6-kilobase repeats determined by a polymorphism in the Lp(a) gene (inversely related to Lp(a) levels in past studies) were correlated [9]. (See "Lipoprotein(a) and cardiovascular disease", section on 'CVD risk'.)

The randomized PLATO trial compared ticagrelor, an investigational antiplatelet agent, with clopidogrel in over 18.000 patients with an acute coronary syndrome [11]. At 12 months, the composite primary end point (death from vascular causes, MI, or stroke) occurred significantly less often in patients receiving ticagrelor (9.8 percent versus 11.7 percent with clopidogrel); there was no significant difference in major bleeding. (See "Antiplatelet agents in unstable angina and acute non-ST elevation myocardial infarction", section on 'Ticagrelor therapy'.)

The optimal blood pressure goal in hypertensive patients at increased risk for cardiovascular disease is unknown. The Cardio-Sis trial randomly assigned over 1100 patients on therapy with a systolic BP above 150 mmHg to a target of less than 140 mmHg (usual-control) or less than 130 mmHg (tight-control) [12]. After two years, the primary outcome of the prevalence of electrocardiographic left ventricular hypertrophy (LVH) was significantly lower (11.4 versus 17.0 percent) in the tight-control compared to the usual-control group. (See "Choice of antihypertensive drug and blood pressure goal in patients at increased risk for a cardiovascular event", section on 'Trials comparing blood pressure goals'.)

Among patients undergoing major vascular surgery, we recommend continuing statin therapy in patients already being treated with a statin. Evidence for starting statin therapy in untreated patients with vascular disease comes from the DECREASE III trial that randomly assigned nearly 500 such patients to either 80 mg of extended release fluvastatin daily or placebo at least 30 days before elective non-cardiac vascular surgery [13]. The primary end point of myocardial ischemia, defined as release of troponin T and/or transient electrocardiographic abnormalities within 30 days of surgery, occurred significantly less often in the fluvastatin group (10.8 versus 19.0 percent). (See "Management of cardiac risk for noncardiac surgery", section on 'Statins'.)

A subgroup analysis of over 1500 patients in the ACUITY trial who had an acute coronary syndrome and received CABG found that those who received clopidogrel, compared to those who did not, had significantly fewer adverse events (death, myocardial infarction, or unplanned revascularization) at 30 days, while rates of bleeding were not significantly different [14]. Thus, clopidogrel should not be withheld prior to coronary angiography due to concerns of excess bleeding in this population. (See "Antiplatelet agents in unstable angina and acute non-ST elevation myocardial infarction", section on Concerns about early CABG.)

HEART FAILURE AND CARDIOMYOPATHY

First-degree relatives of patients with cardiomyopathy (including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and left ventricular noncompaction) are at increased risk for cardiomyopathy and affected relatives are frequently asymptomatic. Progressive disease may occur within a relatively short period of time in initially asymptomatic family members. The 2009 Heart Failure Society of America (HFSA) genetic evaluation of cardiomyopathy practice guideline recommends screening asymptomatic first-degree relatives of patients with cardiomyopathy by clinical evaluation including echocardiography [15]. (See "Evaluation of the patient with heart failure or cardiomyopathy".)

Cardiac resynchronization therapy (CRT) is indicated in patients in sinus rhythm with a left ventricular ejection fraction (LVEF) ≤35 percent and a QRS >120 msec, who have moderate to severe symptoms (NYHA class III or IV HF) (table 1) despite optimal medical therapy. Randomized trials suggests that CRT can also provide functional improvement and decrease HF events in patients with mild or no HF symptoms (class I or II HF), although no impact on mortality has been demonstrated. The MADIT-CRT trial randomly assigned 1820 patients with an LVEF ≤30 percent, QRS ≥130 msec, and NYHA class I or II HF to CRT-ICD or ICD alone [16]. CRT-ICD decreased HF events and induced reverse remodeling, with benefit observed primarily in patients with a QRS duration >150 msec. (See "Cardiac resynchronization therapy in heart failure", section on 'Efficacy in NYHA class I or II HF'.)

INTERVENTIONAL CARDIOLOGY

Drug-eluting stents (DES) significantly reduce the incidence of target vessel revascularization compared to bare-metal stents (BMS) and have become the stent of choice for the treatment of a majority of lesions. However, their utility has been somewhat limited by concerns about stent thrombosis. Currently, placement of a DES is the recommended treatment for bare metal stent restenosis, although other strategies are being investigated. In a study of 131 patients with BMS restenosis who were randomly assigned to either a paclitaxel-coated balloon or a paclitaxel-eluting stent (PES), the coated balloon was associated with a significantly lower rate of six month in-segment late lumen loss and a non-significant trend toward a lower rate of 12 month major adverse cardiac events [17]. (See "Intracoronary stent restenosis", section on 'Drug-coated balloon angioplasty'.)

The optimal management of ST-elevation myocardial infarction (STEMI) patients with failed fibrinolysis has been uncertain. The REACT trial randomly assigned 427 patients with STEMI and failed fibrinolysis to conservative medical therapy, repeat fibrinolysis, or rescue percutaneous coronary intervention (69 percent with stenting) [18,19]. At more than four years of follow-up, rescue PCI was associated with a lower rate of all-cause mortality (6.2 versus 12.7 and 12.8 percent compared to repeat fibrinolysis or conservative therapy. (See "Management of failed fibrinolysis (thrombolysis) or threatened reocclusion in acute ST elevation myocardial infarction", section on 'Rescue PCI'.)

The NORDISTEMI and TRANSFER AMI trials of patients with STEMI who were treated with fibrinolytic therapy randomly assigned patients to a strategy of either transfer for possible percutaneous coronary intervention or ischemia guided treatment in local hospitals [20,21]. Both studies confirmed the benefit of early intervention and are consistent with prior trials results. The results of these two trials have led to a change in our recommendations for the management of patients after fibrinolysis. (See "Percutaneous coronary intervention after fibrinolysis for acute ST elevation myocardial infarction", section on 'Adjunctive PCI'.)

VALVULAR DISEASE

Commonly used models for operative risk stratification are based on data that is a decade or more old. The 2008 Society of Thoracic Surgeons (STS) risk model for valve surgery, coronary artery bypass surgery, or both was developed and validated based on data from 2002 to 2006 from nearly 90 percent of cardiac surgery providers in the United States [22,23]. The model provides estimates of risk of mortality as well as nonfatal complications such as stroke, renal failure, and prolonged ventilation. A calculator is available online (http://www.sts.org/sections/stsnationaldatabase/riskcalculator/). (See "Estimating the mortality risk of valvular surgery", section on 'Risk stratification models'.)

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REFERENCES

  1. Connolly, SJ, Ezekowitz, MD, Yusuf, S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139.
  2. Singer, DE, Chang, Y, Fang, MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151:297.
  3. Holmes, DR, Reddy, VY, Turi, ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374:534.
  4. Cheng, S, Keyes, MJ, Larson, MG, et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 2009; 301:2571.
  5. Gould, MS, Walsh, BT, Munfakh, JL, et al. Sudden death and use of stimulant medications in youths. Am J Psychiatry 2009; 166:992.
  6. US Food and Drug Administration. Stimulant medications used in children with Attention-Deficit /Hyperactivity disorder-Communication about an Ongoing Safety Review. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166667.htm. (Accessed June 15, 2009).
  7. Wiviott, SD, Braunwald, E, McCabe, CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357:2001.
  8. Ranucci, M, Castelvecchio, S, Menicanti, L, et al. Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony. Circulation 2009; 119:3053.
  9. Kamstrup, PR, Tybjaerg-Hansen, A, Steffensen, R, Nordestgaard, BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301:2331.
  10. Erqou, S, Kaptoge, S, Perry, PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009; 302:412.
  11. Wallentin, L, Becker, RC, Budaj, A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361:1045.
  12. Verdecchia, P, Staessen, JA, Angeli, F, et al. Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial. Lancet 2009; 374:525.
  13. Schouten, O, Boersma, E, Hoeks, SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med 2009; 361:980.
  14. Ebrahimi, R, Dyke, C, Mehran, R, et al. Outcomes following pre-operative clopidogrel administration in patients with acute coronary syndromes undergoing coronary artery bypass surgery: the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. J Am Coll Cardiol 2009; 53:1965.
  15. Hershberger, RE, Lindenfeld, J, Mestroni, L, et al. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline. J Card Fail 2009; 15:83.
  16. Moss, AJ, Hall, WJ, Cannom, DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009; 361:1329.
  17. Unverdorben, M, Vallbracht, C, Cremers, B, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation 2009; 119:2986.
  18. Gershlick, AH, Stephens-Lloyd, A, Hughes, S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med 2005; 353:2758.
  19. Carver, A, Rafelt, S, Gershlick, AH, et al. Longer-term follow-up of patients recruited to the REACT (Rescue Angioplasty Versus Conservative Treatment or Repeat Thrombolysis) trial. J Am Coll Cardiol 2009; 54:118.
  20. Bohmer, E, Hoffmann, P, Abdelnoor, M, et al. Efficacy and Safety of Immediate Angioplasty Versus Ischemia-Guided Management After Thrombolysis in Acute Myocardial Infarction in Areas With Very Long Transfer Distances Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction). J Am Coll Cardiol 2009; :.
  21. Cantor, WJ, Fitchett, D, Borgundvaag, B, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med 2009; 360:2705.
  22. Shahian, DM, O'Brien, SM, Filardo, G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 1--coronary artery bypass grafting surgery. Ann Thorac Surg 2009; 88:S2.
  23. O'Brien, SM, Shahian, DM, Filardo, G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2--isolated valve surgery. Ann Thorac Surg 2009; 88:S23.
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UpToDate performs a continuous review of over 430 journals and other resources. Updates are added as important new information is published. The literature review for version 17.3 is current through September 2009; this topic was last changed on October 16, 2009. The next version of UpToDate (18.1) will be released in March 2010.

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