|Year : 2009 | Volume
| Issue : 1 | Page : 2-5
|Date of Web Publication||17-Jun-2010|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Cardiovascular News. Heart Views 2009;10:2-5
Thirty-Year Trends (1975 to 2005) in the Magnitude of, Management of, and Hospital Death Rates Associated with Cardiogenic Shock in Patients with Acute Myocardial Infarction
Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. Investigators examined 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers.
The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized with acute myocardial infarction at all greater Worcester medical centers during 15 annual periods between 1975 and 2005. Overall, 6.6% of patients developed cardiogenic shock during their index hospitalization. The incidence rates of cardiogenic shock remained stable between 1975 and the late 1990s but declined in an inconsistent manner thereafter. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (65.4%) than those who did not develop cardiogenic shock (10.6%) (P < 0.001). Encouraging increases in hospital survival in patients with cardiogenic shock, however, were observed from the mid-1990s. Several patient demographic and clinical characteristics were associated with an increased risk for developing cardiogenic shock.
The findings indicate improving trends in the hospital prognosis associated with cardiogenic shock. Given the high death rates associated with this clinical complication, monitoring future trends in the incidence and death rates and the factors associated with an increased risk for developing cardiogenic shock remains warranted.
Adjunctive Thrombectomy and Distal Protection in Primary Percutaneous Coronary Intervention: Impact on Microvascular Perfusion and Outcomes
A significant proportion of patients with ST-elevation myocardial infarction have persistent impairment of microvascular blood flow despite successful reperfusion of epicardial vessels. Microvascular dysfunction has been associated with larger infarct size, increased predisposition to ventricular arrhythmias, heart failure, cardiogenic shock, recurrent myocardial infarction, and death. It remains unclear whether this association is of direct mechanistic significance or whether the microcirculatory injury is an epiphenomenon and a manifestation of greater ischemic insult to the myocardium.
There has been increasing interest in the concept of adjunctive mechanical thrombectomy to improve outcomes in primary percutaneous coronary intervention. Until recently, randomized trials of thrombectomy and distal protection devices during primary percutaneous coronary intervention have provided conflicting results with no definitive evidence for efficacy. The recently published Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study has rekindled the interest in this area. This trial is the largest randomized study of a thrombectomy device published to date and demonstrates that adjunctive treatment with aspiration thrombectomy during primary percutaneous coronary intervention improves surrogate and clinical end points.
The evidence to date suggests that adjunctive thrombectomy with an aspiration catheter does offer microvascular protection during primary PCI, a conclusion supported by 2 recent meta-analyses, however, both studies reported no improvement in 30-day mortality. The data set continues to evolve. The recent TAPAS trial suggests that in a large study, it is possible to demonstrate that improved myocardial perfusion is associated with better clinical outcomes. The precise role of rheolytic thrombectomy in primary PCI remains to be established and is being investigated in an ongoing trial. Current embolic protection devices are not effective for microvascular protection in native coronary arteries and do not improve outcomes. Therefore, they should not be used routinely during primary PCI.
On the basis of current evidence, the authors recommend aspiration thrombectomy as the primary adjunctive mechanical strategy of choice for the majority of patients undergoing primary PCI. Rheolytic thrombectomy with the AngioJet system and distal protection devices may be appropriate in a few selected patients with a very large thrombotic burden. Large, multicenter, randomized trials are needed to definitively establish the efficacy of these devices in reducing myocardial infarct size, heart failure, and mortality.
Predictors of Initial Nontherapeutic Anticoagulation With Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction
Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging.
In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (< 1.25 times); and 16.3% were markedly high (3 2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RRadj], 1.14 per decade; P = 0.001), were female (RRadj, 1.46; P < 0.001), were of lower weight (RRadj, 1.19 per 10-kg decrease; P < 0.001) or had renal dysfunction (RRadj, 1.08 per 0.2-mg/dL increase in serum creatinine; P = 0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P = 0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P =0.057).
Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.
Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients with Chronic Heart Failure. The (WATCH) Trial
Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.
This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women 18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of 35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P = 0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P = 0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P = 0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P = 0.02 for warfarin versus aspirin).
The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.
Safety of Short-Term Discontinuation of Antiplatelet Therapy in Patients with Drug-Eluting Stents
Antiplatelet therapy is often discontinued in patients with drug-eluting stents who are undergoing surgical procedures. However, discontinuation of antiplatelet therapy is an important risk factor for late stent thrombosis. Our objective was to examine the safety of short-term discontinuation of antiplatelet therapy.
Investigators systematically searched Medline for reported cases of late stent thrombosis and very late stent thrombosis published between January 2001 and July 2008. We restricted our search to Academic Research Consortium-defined definite cases. We identified 161 cases of late stent thrombosis or very late stent thrombosis from 84 articles (79 from case reports, 61 from registries, and 21 from randomized clinical trials). Patients had a mean age of 58.4 ± 13.4 years, and 88% were male. A total of 19 cases occurred in patients who were receiving dual antiplatelet therapy at the time of the event. If patients stopped both antiplatelet agents simultaneously, the median time to event was 7 days. If patients had previously stopped a thienopyridine with no ill effect and subsequently stopped acetylsalicylic acid, the median time to event was also 7 days from the time of acetylsalicylic acid cessation. If the thienopyridine was stopped but acetylsalicylic acid was maintained, the median time to event was 122 days. Among the 48 patients who stopped both agents, 36 cases (75%) occurred within 10 days. Among the 94 patients who discontinued a thienopyridine but continued acetylsalicylic acid, only 6 cases (6%) occurred within 10 days.
If acetylsalicylic acid therapy is maintained, short-term discontinuation of a thienopyridine may be relatively safe in patients with drug-eluting stents.
Syncope and Risk of Sudden Death in Hypertrophic Cardiomyopathy
The prognostic significance of syncope has not been investigated systematically in hypertrophic cardiomyopathy, and treatment strategies have been based largely on intuition and experience. Investigators assessed the relationship between syncope and sudden death in 1511 consecutive patients with hypertrophic cardiomyopathy. Unexplained (n = 153) or neurally mediated (n = 52) syncope occurred in 205 patients (14%). Over a 5.6 ± 5.2-year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% confidence interval 0.88 to 3.51, P = 0.08) in patients with unexplained syncope and 0.91 (95% confidence interval 0.00 to 3.83, P = 1.0) in those with neurally mediated syncope compared with patients without syncope.
In multivariable analysis, the temporal proximity of unexplained syncope to initial patient evaluation was independently associated with risk of sudden death (P = 0.006). Patients with unexplained syncope within 6 months before the initial evaluation showed a 5-fold increase in risk compared with patients without syncope (adjusted hazard ratio 4.89, 95% confidence interval 2.19 to 10.94), a relationship that was maintained throughout all age groups (<18, 18 to 39, and 40 years). Older patients (≥ 40 years of age) with remote episodes of syncope (>5 years before initial evaluation) did not show an increased risk of sudden death (adjusted hazard ratio 0.38, 95% confidence interval 0.05 to 2.74).
In the present large cohort of patients with hypertrophic cardiomyopathy, unexplained syncope was a risk factor for sudden death. Patients with syncopal events that occurred in close temporal proximity to the initial evaluation showed a substantially higher risk of sudden death than patients without syncope. Older patients with remote syncopal events did not show an increased risk.
Trends in All-Cause and Cardiovascular Disease Mortality Among Women and Men with and without Diabetes Mellitus in the Framingham Heart Study, 1950 to 2005
Despite population declines in all-cause mortality, women with diabetes mellitus may have experienced an increase in mortality rates compared with men.
Investigators examined change in all-cause, cardiovascular, and non-cardiovascular disease mortality rates among Framingham Heart Study participants who attended examinations during an "earlier" (1950 to 1975; n = 930 deaths) and a "later" (1976 to 2001; n = 773 deaths) time period. Diabetes mellitus was defined as casual glucose 200 mg/dL, fasting plasma glucose 126 mg/dL, or treatment. Among women, the hazard ratios (HRs) for all-cause mortality in the later versus the earlier time period were 0.59 (95% confidence interval, 0.50 to 0.70; P < 0.0001) for those without diabetes mellitus and 0.48 (95% confidence interval, 0.32 to 0.71; P = 0.002) for those with diabetes mellitus. Similar results were observed in men. Among women and men, the HR of cardiovascular disease mortality declined among those with and without diabetes mellitus. Non-cardiovascular disease mortality declined among women without diabetes mellitus (HR, 0.76; P = 0.01), whereas no change was observed among women with diabetes mellitus or among men with or without diabetes mellitus. Individuals with versus those without diabetes mellitus were at increased risk of all-cause mortality in the earlier (HR, 2.44; P < 0.0001) and later (HR, 1.95; P < 0.0001) time periods.
Reductions in all-cause mortality among women and men with diabetes mellitus have occurred over time. However, mortality rates among individuals with diabetes mellitus remain 2-fold higher compared with individuals without diabetes mellitus.
Stress Doppler Echocardiography in Relatives of Patients with Idiopathic and Familial Pulmonary Arterial Hypertension: Pulmonary Artery Pressure Response to Exercise and Hypoxia
This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene.
TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO2 = 12%; ≈ 4500m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (P < 0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (P = 0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations.
Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a BMPR2 mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies.
Incidence and Prognostic Significance of Acquired Thrombocytopenia During Acute Coronary Syndrome in Contemporary Clinical Practice
Prior studies examining thrombocytopenia among patients with acute coronary syndromes (ACS) evaluated highly selected patients in a clinical trial setting using varying definitions of thrombocytopenia. The incidence, severity, and prognostic significance of acquired thrombocytopenia during ACS in community practice have not been well defined.
Investigators examined 36 182 patients with non-ST-segment elevation ACS enrolled at 379 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement initiative between June 2004 and December 2006.
Patients with baseline platelet counts < 150 x 109/L were excluded. Overall, 4697 patients (13%) developed new thrombocytopenia, defined as nadir platelet count < 150x10 9 /L (referenced lower limit of normal), during their ACS hospitalization.
Risks of in-hospital mortality and bleeding correlated directly with severity of thrombocytopenia; even mild thrombocytopenia (nadir 100 to 149x10 9 /L) was associated with increased risks of mortality (adjusted odds ratio [OR], 2.01; 95% CI, 1.69 to 2.38) and bleeding (adjusted OR, 3.76; 95% CI, 3.43 to 4.12). Each 10% drop in platelet count was associated with increased mortality and bleeding risks (adjusted ORs, 1.39 [95% CI, 1.33 to 1.46] and 1.89 [95% CI, 1.83 to 1.95], respectively). A 50% drop in platelet count was associated with higher risk of adverse outcomes regardless of the nadir count. A novel combined definition of acquired thrombocytopenia-nadir <150x109/L or platelet count drop ≥ 50%-identifies a population of ACS patients at higher risk of mortality and major bleeding (adjusted ORs, 2.58 [95% CI, 2.23 to 2.98] and 4.32 [95% CI, 3.97 to 4.70], respectively).
Thrombocytopenia, a common complication of ACS, is associated with increased mortality and bleeding risks. Even mild thrombocytopenia or a platelet count drop 50% in the setting of normal nadir values is clinically significant. Application of a combined definition for thrombocytopenia using both absolute and relative thresholds permits increased sensitivity for patients at high risk of adverse outcomes.
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