Congestive heart failure and thrombosis

Editors-in-Chief: C. Michael Gibson, M.S., M.D. Associate Editor-In-Chief: Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
CHF results when heart is not able to meet the demands of circulation causing insufficient blood flow. These patients are at higher risk of arterial and venous thrombosis.

Historical Perspective
Throughout history many renowned researchers and health care professionals have contributed to the understanding, definition, and recognition of thrombosis in Heart Failure patients.

Pathophysiology
Stagnation of blood flow, disorder in vascular wall, and blood coagulation system are known factors that participate in the thrombosis formation, and its evident that Heart failure is often accompanied by hypercoaguble state.

In Heart failure, several factors come into play,
 * Firstly
 * Akinetic ventricular segments
 * Dilated ventricular chambers,
 * Dilated atria

with stagnant flow may increase thrombus formation.
 * Secondly endothelial dysfunction which occur in heart failure, may impair the antithrombotic function of the endothelium.


 * Thirdly, elevated levels of
 * d-dimer,
 * Beta-thromboglobulin,
 * von Willebrand factor have been observed.

The prothrombotic stage is further enhanced by
 * Activated renin-angiotensin-aldosterone system (RAAS)
 * Sympathetic nervous system,
 * Systemic inflammation.

Epidemiology
Heart failure is the most frequent cause of hospitalization in patient aged 65 and above. Heart failure is one of the most important public health problems, affecting an approximate half million patients in United States, with more than 550,000 new cases each year, and many more worldwide.

The incidence is expected to increase further in the next two decade as more number of people are surviving after myocardial infarction.

Natural History, Complications & Prognosis
Death is the ultimate complication that can happen in heart failure patients having thrombosis. In the ATLAS (Assessment of Treatment with Lisinopril and Survival) trial, there were many Heart failure patients who underwent autopsy, providing an unique opportunity and answering many questions about the cause of death.

Various trials have been conducted to suggest surrogate markers of heart failure.

Rationale for Antithrombotic therapy in Heart failure

 * Prevention of Stroke ,
 * Prevention of Systemic or Pulmonary embolism,
 * Prevention of coronary thrombosis,
 * Retarding progression of Heart failure.
 * Increase survival.

Supportive Trial Data
The following Table shows the comparative data from various studies, each showing the probability of a thromboembolic events in Heart Failure patients.

Figures mentioned under CVA, MI, PE, TTE represents per 100 patient-years. Abbreviations Used: TTE, Total Thromboembolic event rate; NR, not reported; V-HeFT I and II Vasodilator-Heart Failure Trials; SAVE, Survival and Ventricular Enlargement; SOLVD, Studies of Left Ventricular Dysfunction; WASH, Warfarin/Aspirin Study of Heart Failure;HELAS,Heart Failure Long-Term Antithrombotic Study;IHD, Ischemic Heart Disease;DCM, Dilated Cardiomyopathy SCD-HeFT, Sudden Cardiac Death in Heart Failure Study.

Other Trials

 * The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH ) trial was the first modern RCT to study warfarin in patients with heart failure. The trial showed a reduction of nonfatal stroke events with warfarin over aspirin or clopidogrel.


 * In the ARixtra for ThromboEMbolISm prevention in a medical indications study (ARTEMIS ) trial in acutely ill medical patients, fondaparinux signiﬁcantly reduced the risk of total venous thromboembolism, without increasing bleeding risk compared with placebo.


 * In the Survival and Ventricular Enlargement (SAVE ) Trial,which enrolled patients with left ventricular dysfunction after MI, the VTE annual rate (fatal and nofatal stroke) was 1.5%.


 * The Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial is a randomized study evaluating the efficacy of warfarin versus aspirin in reducing the risk of death or stroke in patients with congestive heart failure and a left ventricular ejection fraction < 35%. Read more about WARCEF Trial by clicking here.

Current Guidelines
====European Society of Cardiology ====
 * Anticoagulants have shown to be more effective than antiplatelet agents in reducing the risk of stroke; thus they are preferred agents in
 * patients with more than one risk factors, like
 * Left ventricular ejection fraction ≤ 35%
 * Age≥75
 * Hypertension
 * Diabetes mellitus
 * In patients with Heart failure and Atrial fibrillation lacking any other additional risk factors., to prevent primary VTE event.


 * With respect to Antiplatelet agents,
 * They are found to be less efficacious than anticougulants, in preventing a VTE event in patients with Atrial fibrillation,.
 * Hospitalization for heart failure was significantly greater in aspirin-treated patients than in warfarin-treated patients.

====ACC/AHA ====
 * Anticoagulants should be considered in
 * Patients with heart failure having prior history of VTE.
 * Patients having paroxysmal or persistant Atrial fibrillation.
 * Patients with other co-morbidity, which increases the risk for VTE.
 * Patients with familial dilated cardiomyopathy and a history of VTE in first-degree relatives.


 * With respect to Antiplatelet agents, it should be used in:
 * Myocardial infarction.
 * Heart failure patients with known history of coronary artery disease.


 * However, ACC/AHA has stated that
 * Role of aspirin in heart failure is still not established.
 * Aspirin may attenuate the hemodynamic and survival benefits of ACE inhibitors.