Congestive heart failure and thrombosis: Difference between revisions
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| bgcolor="CornFlowerBlue" |'''Year''' | | bgcolor="CornFlowerBlue" |'''Year''' | ||
| bgcolor="CornFlowerBlue" |'''Event''' | | bgcolor="CornFlowerBlue" |'''Event''' | ||
|- | |||
| 1628 | |||
| William Harvey describes the [[circulation]]. | |||
|- | |||
| 1785 | |||
| William Withering publishes an account of medical use of [[digitalis]]. | |||
|- | |||
| 1920 | |||
| Organomercurial [[diuretics]] are first used. | |||
|- | |- | ||
| 1950s | | 1950s | ||
| Line 20: | Line 29: | ||
|- | |- | ||
| 1980s - 1990s | | 1980s - 1990s | ||
| Better understanding of hypercoaugubilty in Heart failure patients. | | Better understanding of hypercoaugubilty in Heart failure patients. In 1987, the landmark CONSENSUS-I study showed the unequivocal survival benefits of [[enalapril]] in patients with severe heart failure. | ||
|- | |- | ||
| 2000- | | 2000- | ||
| Line 27: | Line 36: | ||
==Pathophysiology== | ==Pathophysiology== | ||
Stagnation of blood flow, disorder in vascular wall, and blood coagulation system are known factors that participate in the thrombosis formation | 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<ref name="pmid9200399">{{cite journal| author=Massie BM, Shah NB| title=Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. | journal=Am Heart J | year= 1997 | volume= 133 | issue= 6 | pages= 703-12 | pmid=9200399 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9200399 }} </ref> <ref name="pmid7539015">{{cite journal| author=Yamamoto K, Ikeda U, Furuhashi K, Irokawa M, Nakayama T, Shimada K| title=The coagulation system is activated in idiopathic cardiomyopathy. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 7 | pages= 1634-40 | pmid=7539015 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7539015 }} </ref> <ref name="pmid8122609">{{cite journal| author=Sbarouni E, Bradshaw A, Andreotti F, Tuddenham E, Oakley CM, Cleland JG| title=Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. | journal=Am Heart J | year= 1994 | volume= 127 | issue= 3 | pages= 607-12 | pmid=8122609 | doi= | pmc= | url= }} </ref>. | ||
{{familytree/start |summary=Thrombus formation:Pathophysiology}} | {{familytree/start |summary=Thrombus formation:Pathophysiology}} | ||
| Line 34: | Line 43: | ||
{{familytree |JOE| |ME| |SIS| | JOE=Abnormal blood flow (Blood [[Stasis (medicine)|Stasis]])|ME=[[Thrombophilia|Abnormal blood constituents]]|SIS=Abnormal blood vessel wall}} | {{familytree |JOE| |ME| |SIS| | JOE=Abnormal blood flow (Blood [[Stasis (medicine)|Stasis]])|ME=[[Thrombophilia|Abnormal blood constituents]]|SIS=Abnormal blood vessel wall}} | ||
{{familytree/end}} | {{familytree/end}} | ||
In Heart failure, several factors come into play, | |||
*Firstly | |||
**Akinetic ventricular segments | |||
**Dilated ventricular chambers, | |||
**Dilated atria | |||
with stagnant flow may increase thrombus formation<ref name="pmid19739040">{{cite journal| author=de Peuter OR, Kok WE, Torp-Pedersen C, Büller HR, Kamphuisen PW| title=Systolic heart failure: a prothrombotic state. | journal=Semin Thromb Hemost | year= 2009 | volume= 35 | issue= 5 | pages= 497-504 | pmid=19739040 | doi=10.1055/s-0029-1234145 | pmc= | url= }} </ref>. | |||
*Secondly endothelial dysfunction which occur in heart failure, may impair the antithrombotic function of the endothelium<ref name="pmid10193748">{{cite journal| author=Lip GY, Gibbs CR| title=Does heart failure confer a hypercoagulable state? Virchow's triad revisited. | journal=J Am Coll Cardiol | year= 1999 | volume= 33 | issue= 5 | pages= 1424-6 | pmid=10193748 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10193748 }} </ref>. | |||
*Thirdly, elevated levels of | |||
**[[d-dimer]], | |||
**[[Beta-thromboglobulin]], | |||
**[[von Willebrand factor]] have been observed<ref name="pmid8122609">{{cite journal| author=Sbarouni E, Bradshaw A, Andreotti F, Tuddenham E, Oakley CM, Cleland JG| title=Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. | journal=Am Heart J | year= 1994 | volume= 127 | issue= 3 | pages= 607-12 | pmid=8122609 | doi= | pmc= | url= }} </ref>. | |||
The prothrombotic stage<ref name="pmid10359409">{{cite journal| author=Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M et al.| title=Endotoxin and immune activation in chronic heart failure: a prospective cohort study. | journal=Lancet | year= 1999 | volume= 353 | issue= 9167 | pages= 1838-42 | pmid=10359409 | doi=10.1016/S0140-6736(98)09286-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10359409 }} </ref> is further enhanced by | |||
*Activated [[renin-angiotensin-aldosterone system]] (RAAS) | |||
*Sympathetic nervous system, | |||
*Systemic inflammation. | |||
==Epidemiology== | ==Epidemiology== | ||
[[Heart failure]] is the most frequent cause of hospitalization in patient aged 65 and above.<ref name="pmid17194875">{{cite journal| author=Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K et al.| title=Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. | journal=Circulation | year= 2007 | volume= 115 | issue= 5 | pages= e69-171 | pmid=17194875 | doi=10.1161/CIRCULATIONAHA.106.179918 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17194875 }} </ref> [[Congestive heart failure|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<ref name="pmid18799522">{{cite journal| author=Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P et al.| title=ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 19 | pages= 2388-442 | pmid=18799522 | doi=10.1093/eurheartj/ehn309 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18799522 }} </ref><ref name="pmid9200399">{{cite journal| author=Massie BM, Shah NB| title=Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. | journal=Am Heart J | year= 1997 | volume= 133 | issue= 6 | pages= 703-12 | pmid=9200399 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9200399 }} </ref>. | [[Heart failure]] is the most frequent cause of hospitalization in patient aged 65 and above.<ref name="pmid17194875">{{cite journal| author=Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K et al.| title=Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. | journal=Circulation | year= 2007 | volume= 115 | issue= 5 | pages= e69-171 | pmid=17194875 | doi=10.1161/CIRCULATIONAHA.106.179918 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17194875 }} </ref> [[Congestive heart failure|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<ref name="pmid18799522">{{cite journal| author=Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P et al.| title=ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 19 | pages= 2388-442 | pmid=18799522 | doi=10.1093/eurheartj/ehn309 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18799522 }} </ref><ref name="pmid9200399">{{cite journal| author=Massie BM, Shah NB| title=Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. | journal=Am Heart J | year= 1997 | volume= 133 | issue= 6 | pages= 703-12 | pmid=9200399 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9200399 }} </ref>. | ||
The incidence is expected to increase further in the next two decade as more number of people are surviving after myocardial infarction. | The incidence is expected to increase further in the next two decade as more number of people are surviving after myocardial infarction<ref name="pmid10617530">{{cite journal| author=Davis RC, Hobbs FD, Lip GY| title=ABC of heart failure. History and epidemiology. | journal=BMJ | year= 2000 | volume= 320 | issue= 7226 | pages= 39-42 | pmid=10617530 | doi= | pmc=PMC1117316 | url= }} </ref>. | ||
== | |||
==Natural History, Complications & Prognosis== | ==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<ref name="pmid10931799">{{cite journal| author=Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM et al.| title=Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. | journal=Circulation | year= 2000 | volume= 102 | issue= 6 | pages= 611-6 | pmid=10931799 | doi= | pmc= | url= }} </ref>, there were many Heart failure patients who underwent autopsy, providing an unique opportunity and answering many questions about the cause of death. | 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<ref name="pmid10931799">{{cite journal| author=Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM et al.| title=Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. | journal=Circulation | year= 2000 | volume= 102 | issue= 6 | pages= 611-6 | pmid=10931799 | doi= | pmc= | url= }} </ref>, 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 endpoint|surrogate markers]] of heart failure. | |||
===Cause of death in autopsied Heart failure patients: ATLAS Trial=== | ===Cause of death in autopsied Heart failure patients: ATLAS Trial=== | ||
<ref name="pmid10931799">{{cite journal| author=Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM et al.| title=Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. | journal=Circulation | year= 2000 | volume= 102 | issue= 6 | pages= 611-6 | pmid=10931799 | doi= | pmc= | url= }} </ref> | <ref name="pmid10931799">{{cite journal| author=Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM et al.| title=Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. | journal=Circulation | year= 2000 | volume= 102 | issue= 6 | pages= 611-6 | pmid=10931799 | doi= | pmc= | url= }} </ref> | ||
| Line 88: | Line 115: | ||
| ''' 3*''' | | ''' 3*''' | ||
|} | |} | ||
==Treatment== | ==Treatment== | ||
| Line 99: | Line 125: | ||
===Supportive Trial Data=== | ===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. | |||
{| border="1" | |||
|+ | |||
! Study !! Year !! Patients (n) !! Follow-up (y) !! [[ NYHA classification|NYHA Class]] !! [[Ejection fraction|LVEF]] (%) !! [[Cerebrovascular accident|CVA]] !! [[MI]] !! [[PE]] !! TTE | |||
|- | |||
| V-Heft I<ref name="pmid8500246">{{cite journal| author=Dunkman WB, Johnson GR, Carson PE, Bhat G, Farrell L, Cohn JN| title=Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group. | journal=Circulation | year= 1993 | volume= 87 | issue= 6 Suppl | pages= VI94-101 | pmid=8500246 | doi= | pmc= | url= }} </ref> | |||
| 1993 | |||
| 642 | |||
| 2.3 | |||
| NR | |||
| 30 | |||
| NR | |||
| NR | |||
| NR | |||
| 2.7 | |||
|- | |||
| V-Heft II | |||
| 1993 | |||
| 804 | |||
| 2.6 | |||
| NR | |||
| 29 | |||
| NR | |||
| NR | |||
| NR | |||
| 2.1 | |||
|- | |||
| SAVE<ref name="pmid8995087">{{cite journal| author=Loh E, Sutton MS, Wun CC, Rouleau JL, Flaker GC, Gottlieb SS et al.| title=Ventricular dysfunction and the risk of stroke after myocardial infarction. | journal=N Engl J Med | year= 1997 | volume= 336 | issue= 4 | pages= 251-7 | pmid=8995087 | doi=10.1056/NEJM199701233360403 | pmc= | url= }} </ref> | |||
| 1997 | |||
| 2231 | |||
| 3.5 | |||
| NR | |||
| 31 | |||
| 1.5 | |||
| NR | |||
| NR | |||
| NR | |||
|- | |||
| SOLVD<ref name="pmid9120162">{{cite journal| author=Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ| title=Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials. | journal=J Am Coll Cardiol | year= 1997 | volume= 29 | issue= 5 | pages= 1074-80 | pmid=9120162 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9120162 }} </ref> | |||
| 1997 | |||
| 6796 | |||
| 3.3 | |||
| '''I-III''' | |||
| ≤35 | |||
| 1.1 | |||
| NR | |||
| NR | |||
| 1.6 | |||
|- | |||
| WASH<ref name="pmid15215806">{{cite journal| author=Cleland JG, Findlay I, Jafri S, Sutton G, Falk R, Bulpitt C et al.| title=The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. | journal=Am Heart J | year= 2004 | volume= 148 | issue= 1 | pages= 157-64 | pmid=15215806 | doi=10.1016/j.ahj.2004.03.010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15215806 }} </ref> | |||
| 2004 | |||
| 254 | |||
| 2.3 | |||
| '''I-IV''' | |||
| ≤35 | |||
| 0.6 | |||
| 2.7 | |||
| NR | |||
| 3.3 | |||
|- | |||
| HELAS IHD<ref name="pmid16737850">{{cite journal| author=Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK, HELAS investigators| title=Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. | journal=Eur J Heart Fail | year= 2006 | volume= 8 | issue= 4 | pages= 428-32 | pmid=16737850 | doi=10.1016/j.ejheart.2006.02.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16737850 }} </ref> | |||
| 2006 | |||
| 116 | |||
| 1.6 | |||
| '''II-IV''' | |||
| 29 | |||
| 2.3 | |||
| 0.6 | |||
| 0 | |||
| 2.8 | |||
|- | |||
| HELAS DCM<ref name="pmid16737850">{{cite journal| author=Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK, HELAS investigators| title=Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. | journal=Eur J Heart Fail | year= 2006 | volume= 8 | issue= 4 | pages= 428-32 | pmid=16737850 | doi=10.1016/j.ejheart.2006.02.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16737850 }} </ref> | |||
| 2006 | |||
| 82 | |||
| 1.7 | |||
| '''II-IV''' | |||
| 27 | |||
| 0.7 | |||
| 0.7 | |||
| 0 | |||
| 1.5 | |||
|- | |||
| SCD-HeFT<ref name="pmid17485579">{{cite journal| author=Freudenberger RS, Hellkamp AS, Halperin JL, Poole J, Anderson J, Johnson G et al.| title=Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). | journal=Circulation | year= 2007 | volume= 115 | issue= 20 | pages= 2637-41 | pmid=17485579 | doi=10.1161/CIRCULATIONAHA.106.661397 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17485579 }} </ref> | |||
| 2007 | |||
| 2114 | |||
| 3.8 | |||
| '''II-III''' | |||
| ≤35 | |||
| 0.8 | |||
| NR | |||
| 0.1 | |||
| 1.7 | |||
|} | |||
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''', [[ischaemic heart disease|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'''<ref name="pmid15101020">{{cite journal| author=Massie BM, Krol WF, Ammon SE, Armstrong PW, Cleland JG, Collins JF et al.| title=The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics. | journal=J Card Fail | year= 2004 | volume= 10 | issue= 2 | pages= 101-12 | pmid=15101020 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15101020 }} </ref>) 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]]. | *The Warfarin and Antiplatelet Therapy in Chronic Heart Failure ('''WATCH'''<ref name="pmid15101020">{{cite journal| author=Massie BM, Krol WF, Ammon SE, Armstrong PW, Cleland JG, Collins JF et al.| title=The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics. | journal=J Card Fail | year= 2004 | volume= 10 | issue= 2 | pages= 101-12 | pmid=15101020 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15101020 }} </ref>) 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]]. | ||
| Line 104: | Line 227: | ||
* In the Survival and Ventricular Enlargement ('''SAVE'''<ref name="pmid9396419">{{cite journal| author=St John Sutton M, Pfeffer MA, Moye L, Plappert T, Rouleau JL, Lamas G et al.| title=Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. | journal=Circulation | year= 1997 | volume= 96 | issue= 10 | pages= 3294-9 | pmid=9396419 | doi= | pmc= | url= }} </ref>) Trial,which enrolled patients with left ventricular dysfunction after [[Myocardial infarction|MI]], the [[VTE]] annual rate (fatal and nofatal [[stroke]]) was 1.5%. | * In the Survival and Ventricular Enlargement ('''SAVE'''<ref name="pmid9396419">{{cite journal| author=St John Sutton M, Pfeffer MA, Moye L, Plappert T, Rouleau JL, Lamas G et al.| title=Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. | journal=Circulation | year= 1997 | volume= 96 | issue= 10 | pages= 3294-9 | pmid=9396419 | doi= | pmc= | url= }} </ref>) Trial,which enrolled patients with left ventricular dysfunction after [[Myocardial infarction|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 [[Congestive heart failure and thromboembolism|here]]. | |||
===Current Guidelines === | ===Current Guidelines === | ||
| Line 144: | Line 269: | ||
[[Category:Pulmonology]] | [[Category:Pulmonology]] | ||
[[Category:Cardiology]] | [[Category:Cardiology]] | ||
{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
Latest revision as of 15:03, 3 February 2012
Editors-in-Chief: C. Michael Gibson, M.S., M.D. Associate Editor-In-Chief: Ujjwal Rastogi, MBBS [1]
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Thrombosis Microchapters |
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Site of Thrombosis |
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Differentiating Thrombosis from other Diseases |
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Diagnosis |
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Treatment |
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Congestive heart failure and thrombosis On the Web |
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to Hospitals Treating Congestive heart failure and thrombosis |
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Risk calculators and risk factors for Congestive heart failure and thrombosis |
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.[1] [2] [3]
| Year | Event |
| 1628 | William Harvey describes the circulation. |
| 1785 | William Withering publishes an account of medical use of digitalis. |
| 1920 | Organomercurial diuretics are first used. |
| 1950s | Prognosis appeared better in Anticoagulated patient. |
| 1960s - 1970s | Retrospective analysis and Autopsy findings showed thromboembolism as an etiology. |
| 1980s - 1990s | Better understanding of hypercoaugubilty in Heart failure patients. In 1987, the landmark CONSENSUS-I study showed the unequivocal survival benefits of enalapril in patients with severe heart failure. |
| 2000- | Role of Aspirin in heart failure patients is studied. |
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[4] [5] [6].
| Thrombus formation | |||||||||||||||||||||||||
| Abnormal blood flow (Blood Stasis) | Abnormal blood constituents | Abnormal blood vessel wall | |||||||||||||||||||||||
In Heart failure, several factors come into play,
- Firstly
- Akinetic ventricular segments
- Dilated ventricular chambers,
- Dilated atria
with stagnant flow may increase thrombus formation[7].
- Secondly endothelial dysfunction which occur in heart failure, may impair the antithrombotic function of the endothelium[8].
- Thirdly, elevated levels of
- d-dimer,
- Beta-thromboglobulin,
- von Willebrand factor have been observed[6].
The prothrombotic stage[9] 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.[10] 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[11][4].
The incidence is expected to increase further in the next two decade as more number of people are surviving after myocardial infarction[12].
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[13], 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.
Cause of death in autopsied Heart failure patients: ATLAS Trial
| Condition | Percentage (%) |
|---|---|
| No specific pathology (presumed arrhythmic death) | 50.6 |
| Myocardial infarction | 42.1 |
| Other Cardiovascular cause | 4.8 |
| Non-cardiac | 2.4 |
Cause of death in Heart failure: SOLVD Trial
| Condition | Percentage (%) |
|---|---|
| Pump failure | 49 |
| Sudden death | 23 |
| Myocardial infarction | 12 |
| Non-cardiac | 13 |
| Fatal stroke or Pulmonary embolism | 3* |
Treatment
Rationale for Antithrombotic therapy in Heart failure
- Prevention of Stroke[15],
- 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.
| Study | Year | Patients (n) | Follow-up (y) | NYHA Class | LVEF (%) | CVA | MI | PE | TTE |
|---|---|---|---|---|---|---|---|---|---|
| V-Heft I[16] | 1993 | 642 | 2.3 | NR | 30 | NR | NR | NR | 2.7 |
| V-Heft II | 1993 | 804 | 2.6 | NR | 29 | NR | NR | NR | 2.1 |
| SAVE[17] | 1997 | 2231 | 3.5 | NR | 31 | 1.5 | NR | NR | NR |
| SOLVD[18] | 1997 | 6796 | 3.3 | I-III | ≤35 | 1.1 | NR | NR | 1.6 |
| WASH[19] | 2004 | 254 | 2.3 | I-IV | ≤35 | 0.6 | 2.7 | NR | 3.3 |
| HELAS IHD[20] | 2006 | 116 | 1.6 | II-IV | 29 | 2.3 | 0.6 | 0 | 2.8 |
| HELAS DCM[20] | 2006 | 82 | 1.7 | II-IV | 27 | 0.7 | 0.7 | 0 | 1.5 |
| SCD-HeFT[21] | 2007 | 2114 | 3.8 | II-III | ≤35 | 0.8 | NR | 0.1 | 1.7 |
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[22]) 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[23]) 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[24]) 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[11]
- 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
- 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[25]
- 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.
See also
References
- ↑ WISHART JH, CHAPMAN CB (1948). "Dicumarol therapy in congestive heart failure". N Engl J Med. 239 (19): 701–4. doi:10.1056/NEJM194811042391902. PMID 18892580.
- ↑ HARVEY WP, FINCH CA (1950). "Dicumarol prophylaxis of thromboembolic disease in congestive heart failure". N Engl J Med. 242 (6): 208–11. doi:10.1056/NEJM195002092420603. PMID 15403339.
- ↑ GRIFFITH GC, STRAGNELL R, LEVINSON DC, MOORE FJ, WARE AG (1952). "A study of the beneficial effects of anticoagulant therapy in congestive heart failure". Ann Intern Med. 37 (5): 867–87. PMID 12986600.
- ↑ 4.0 4.1 Massie BM, Shah NB (1997). "Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management". Am Heart J. 133 (6): 703–12. PMID 9200399.
- ↑ Yamamoto K, Ikeda U, Furuhashi K, Irokawa M, Nakayama T, Shimada K (1995). "The coagulation system is activated in idiopathic cardiomyopathy". J Am Coll Cardiol. 25 (7): 1634–40. PMID 7539015.
- ↑ 6.0 6.1 Sbarouni E, Bradshaw A, Andreotti F, Tuddenham E, Oakley CM, Cleland JG (1994). "Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure". Am Heart J. 127 (3): 607–12. PMID 8122609.
- ↑ de Peuter OR, Kok WE, Torp-Pedersen C, Büller HR, Kamphuisen PW (2009). "Systolic heart failure: a prothrombotic state". Semin Thromb Hemost. 35 (5): 497–504. doi:10.1055/s-0029-1234145. PMID 19739040.
- ↑ Lip GY, Gibbs CR (1999). "Does heart failure confer a hypercoagulable state? Virchow's triad revisited". J Am Coll Cardiol. 33 (5): 1424–6. PMID 10193748.
- ↑ Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M; et al. (1999). "Endotoxin and immune activation in chronic heart failure: a prospective cohort study". Lancet. 353 (9167): 1838–42. doi:10.1016/S0140-6736(98)09286-1. PMID 10359409.
- ↑ Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K; et al. (2007). "Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee". Circulation. 115 (5): e69–171. doi:10.1161/CIRCULATIONAHA.106.179918. PMID 17194875.
- ↑ 11.0 11.1 Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P; et al. (2008). "ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)". Eur Heart J. 29 (19): 2388–442. doi:10.1093/eurheartj/ehn309. PMID 18799522.
- ↑ Davis RC, Hobbs FD, Lip GY (2000). "ABC of heart failure. History and epidemiology". BMJ. 320 (7226): 39–42. PMC 1117316. PMID 10617530.
- ↑ 13.0 13.1 Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM; et al. (2000). "Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial". Circulation. 102 (6): 611–6. PMID 10931799.
- ↑ Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW (1998). "Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction". J Am Coll Cardiol. 32 (3): 695–703. PMID 9741514.
- ↑ Kannel WB, Wolf PA, Verter J (1983). "Manifestations of coronary disease predisposing to stroke. The Framingham study". JAMA. 250 (21): 2942–6. PMID 6227757.
- ↑ Dunkman WB, Johnson GR, Carson PE, Bhat G, Farrell L, Cohn JN (1993). "Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group". Circulation. 87 (6 Suppl): VI94–101. PMID 8500246.
- ↑ Loh E, Sutton MS, Wun CC, Rouleau JL, Flaker GC, Gottlieb SS; et al. (1997). "Ventricular dysfunction and the risk of stroke after myocardial infarction". N Engl J Med. 336 (4): 251–7. doi:10.1056/NEJM199701233360403. PMID 8995087.
- ↑ Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ (1997). "Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials". J Am Coll Cardiol. 29 (5): 1074–80. PMID 9120162.
- ↑ Cleland JG, Findlay I, Jafri S, Sutton G, Falk R, Bulpitt C; et al. (2004). "The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure". Am Heart J. 148 (1): 157–64. doi:10.1016/j.ahj.2004.03.010. PMID 15215806.
- ↑ 20.0 20.1 Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK, HELAS investigators (2006). "Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study". Eur J Heart Fail. 8 (4): 428–32. doi:10.1016/j.ejheart.2006.02.012. PMID 16737850.
- ↑ Freudenberger RS, Hellkamp AS, Halperin JL, Poole J, Anderson J, Johnson G; et al. (2007). "Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)". Circulation. 115 (20): 2637–41. doi:10.1161/CIRCULATIONAHA.106.661397. PMID 17485579.
- ↑ Massie BM, Krol WF, Ammon SE, Armstrong PW, Cleland JG, Collins JF; et al. (2004). "The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics". J Card Fail. 10 (2): 101–12. PMID 15101020.
- ↑ Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W; et al. (2006). "Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial". BMJ. 332 (7537): 325–9. doi:10.1136/bmj.38733.466748.7C. PMC 1363908. PMID 16439370.
- ↑ St John Sutton M, Pfeffer MA, Moye L, Plappert T, Rouleau JL, Lamas G; et al. (1997). "Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial". Circulation. 96 (10): 3294–9. PMID 9396419.
- ↑ Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG; et al. (2009). "2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation". J Am Coll Cardiol. 53 (15): e1–e90. doi:10.1016/j.jacc.2008.11.013. PMID 19358937.