Absence Of Revascularization Research Articles

Guest Editorial: are diabetes‐related wounds and amputations worse than cancer?

Certainly one of the most feared complications of diabetes is the lower extremity amputation 1. This fear is not unwarranted. Diabetes-related ulcer and amputation may be associated with surprisingly high 5-year mortality. Moulik et al.2 reported a 5-year mortality of 45%, 18% and 55% for neuropathic, neuroischaemic and ischaemic ulcers, respectively. As expected, mortality was higher in ischaemic ulcers than neuropathic ulcers. However, it is fairly evident based on these data that all types of diabetic foot ulcers are associated with high morbidity and mortality. Similarly, approximately half the persons receiving a diabetes-related amputation will not be alive in 5 years. Certainly, peripheral vascular disease may be implicated as a significant factor associated with shorter life span. Criqui reported the 10-year mortality in patients with peripheral arterial disease and found a substantially higher risk of mortality among patients with large vessel peripheral arterial disease – a factor that may be even more profound today than when it was reported in the early 1990s 3, 4. Faglia et al. related this high mortality with the absence of revascularisation, citing a 1.7-fold greater risk for death in ischaemic subjects who might have benefited from intervention 5. How do these data compare with other serious medical conditions, such as cancer? If one reviews Figure 1, one might conclude that persons with lower extremity complications of diabetes have 5-year mortality rates similar or worse than many common types of cancer 6-10. In fact, some high-risk subgroups such as persons with renal disease requiring distal bypass may have 5-year mortality rates approaching 95% 10. Five-year mortality (%). Perhaps now is the time to change our discussion with health-care administrators, policy makers and especially ourselves. The disease state that many of us treat routinely is, quite literally, killing our patients at a rate comparable to cancer. Addressing this issue aggressively may alter this and make a difference for millions of people worldwide.

Early and Five-year Amputation and Survival Rate of Diabetic Patients with Critical Limb Ischemia: Data of a Cohort Study of 564 Patients

Objective To evaluate the early and late major amputation and survival rates and related risk factors in diabetic patients with critical limb ischemia (CLI). Design Retrospective study. Methods Revascularization feasibility, major amputation, survival rate and related risk factors were recorded in 564 diabetic patients consecutively hospitalized for CLI from 1999 to 2003 and followed until June 2005. Results Peripheral angioplasty (PTA) was carried out in 420 (74.5%), bypass graft (BPG) in 117 (20.7%) patients. In 27 (4.8%) patients both PTA and BPG were not possible. Twenty-three above-the-ankle amputations (4.1%) were performed at 30 days: 6 in PTA patients, 3 in BPG patients, 14 in non revascularized patients. In the follow-up of 558 patients (98.9%), 62 repeated PTAs and 9 new BPGs, 32 new major amputations (16 in PTA patients, 14 in BPG patients and 2 in non-revascularized patients) were performed. Major amputation was associated with absence of revascularization (OR 35.9, p<0.001, CI 12.9–99.7), occlusion of each of the three crural arteries (OR 8.20, p=0.022, CI 1.35–49.6), wound infection (OR 2.1, p=0.004 CI 1.3–3.6), dialysis (OR 4.7, p=0.001 CI 1.9–11.7) increase in TcPO2 after revascularization (OR 0.80, p<0.001 CI 0.74–0.87). One hundred seventy three patients died during follow-up and this was associated with age (HR 1.05, p<0.001 CI 1.03–1.07), history of cardiac disease (HR 2.16, p<0.001 CI 1.53–3.06), dialysis (HR 3.52, p<0.001 CI 2.08–5.97), absence of revascularization (HR 1.68, p<0.001, CI 1.29–2.19) and impaired ejection fraction (HR 1.08, p<0.001, CI 1.05–1.09). Conclusions In diabetic patients with CLI the revascularization is feasible in most cases and allows a low rate of early major amputation. This rate is higher in the follow-up period. Major amputation is very high in patients where revascularization is not feasible while the high mortality rate is due to the serious comorbidities observed in these patients.

Early and Five-year Amputation and Survival Rate of Diabetic Patients with Critical Limb Ischemia: Data of a Cohort Study of 564 Patients

To evaluate the early and late major amputation and survival rates and related risk factors in diabetic patients with critical limb ischemia (CLI). Retrospective study. Revascularization feasibility, major amputation, survival rate and related risk factors were recorded in 564 diabetic patients consecutively hospitalized for CLI from 1999 to 2003 and followed until June 2005. Peripheral angioplasty (PTA) was carried out in 420 (74.5%), bypass graft (BPG) in 117 (20.7%) patients. In 27 (4.8%) patients both PTA and BPG were not possible. Twenty-three above-the-ankle amputations (4.1%) were performed at 30 days: 6 in PTA patients, 3 in BPG patients, 14 in non revascularized patients. In the follow-up of 558 patients (98.9%), 62 repeated PTAs and 9 new BPGs, 32 new major amputations (16 in PTA patients, 14 in BPG patients and 2 in non-revascularized patients) were performed. Major amputation was associated with absence of revascularization (OR 35.9, p < 0.001, CI 12.9-99.7), occlusion of each of the three crural arteries (OR 8.20, p = 0.022, CI 1.35-49.6), wound infection (OR 2.1, p = 0.004 CI 1.3-3.6), dialysis (OR 4.7, p = 0.001 CI 1.9-11.7) increase in TcPO2 after revascularization (OR 0.80, p < 0.001 CI 0.74-0.87). One hundred seventy three patients died during follow-up and this was associated with age (HR 1.05, p < 0.001 CI 1.03-1.07), history of cardiac disease (HR 2.16, p < 0.001 CI 1.53-3.06), dialysis (HR 3.52, p < 0.001 CI 2.08-5.97), absence of revascularization (HR 1.68, p < 0.001, CI 1.29-2.19) and impaired ejection fraction (HR 1.08, p < 0.001, CI 1.05-1.09). In diabetic patients with CLI the revascularization is feasible in most cases and allows a low rate of early major amputation. This rate is higher in the follow-up period. Major amputation is very high in patients where revascularization is not feasible while the high mortality rate is due to the serious comorbidities observed in these patients.

Revascularization and cardioprotective drug treatment in myocardial infarction patients: how do they impact on patients' survival when delivered as usual care

BackgroundRandomized clinical trials showed the benefit of pharmacological and revascularization treatments in secondary prevention of myocardial infarction (MI), in selected population with highly controlled interventions. The objective of this study is to measure these treatments' impact on the cardiovascular (CV) mortality rate among patients receiving usual care in the province of Quebec.MethodsThe study population consisted of a "naturalistic" cohort of all patients ≥ 65 years old living in the Quebec province, who survived a MI (ICD-9: 410) in 1998. The studied dependant variable was time to death from a CV disease. Independent variables were revascularization procedure and cardioprotective drugs. Death from a non CV disease was also studied for comparison. Revascularization procedure was defined as percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG). The exposure to cardioprotective drugs was defined as the number of cardioprotective drug classes (Acetylsalicylic Acid (ASA), Beta-Blockers, Angiotensin-Converting Enzyme (ACE) Inhibitors, Statins) claimed within the index period (first 30 days after the index hospitalization). Age, gender and a comorbidity index were used as covariates. Kaplan-Meier survival curves, Cox proportional hazard models, logistic regressions and regression trees were used.ResultsThe study population totaled 5596 patients (3206 men; 2390 women). We observed 1128 deaths (20%) within two years following index hospitalization, of them 603 from CV disease. The CV survival rate at two years is much greater for patients with revascularization, regardless of pharmacological treatments. For patients without revascularization, the CV survival rate increases with the number of cardioprotective drug classes claimed. Finally, Cox proportional hazard models, regression tree and logistic regression analyses all revealed that the absence of revascularization and, to a lower extent, absence of cardioprotective drugs were major predictors for CV death, even after adjusting for age, gender and comorbidity.ConclusionConsidering usual care management of MI in the province of Quebec in 1998, CV survival is positively correlated to the presence of a revascularization procedure and to the intensity of cardioprotective pharmacological treatment. These results are coherent with data from randomized control trials.

Prognosis of hibernating myocardium is independent of recovery of function: evidence from a routine based follow-up study.

Revascularization of hibernating segments improves both ventricular function (VF) and survival. In this study, we determined whether this relation is true in a routine based patients population with mildly reduced VF. Two to 6 years after undergoing 201Tl scintigraphy to detect hibernation, 153 patients were interviewed in order to collect medical information. This population was divided into four groups, according to the presence or absence of myocardial hibernation and of revascularization. Age, gender and left ventricular ejection fraction (LVEF) were similar in the four groups. Hard cardiac events (HEs) were noted in 14/33 (41%) patients with uncorrected hibernation, while in the other three groups HEs were recorded in fewer than 3% of patients. Univariate analysis indicated that the presence of hibernation, regardless of its extension, was the highest significant predictor of HEs. Multivariate analysis indicated that hibernation, stress ischaemia, age and absence of revascularization were significant predictors of HEs. These findings were not related to changes in LVEF or to New York Heart Association (NYHA) class during follow-up. In this routine based patient population, with mildly reduced VF, the rate of HEs seems to be related to uncorrected hibernation regardless of its extension. In these patients revascularization of hibernating segments is effective in reducing the risk of HEs while its role in improving VF or NYHA class is negligible.

Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword?

Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of platelet aggregation that provide marked protection from ischemic events in patients undergoing percutaneous coronary intervention (PCI).1,2⇓ Abciximab, the prototypic GP IIb/IIIa inhibitor, has been studied in >8000 patients undergoing elective or high-risk PCI.2,3,4⇓⇓ In these patients, it produces a consistent 35% to 56% reduction in ischemic end points at 30 days, with a significant 22% reduction in the risk of death, as shown in a combined analysis of long-term (3-year minimum) follow-up of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG), and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials.5 Similar results, albeit of a smaller magnitude, have been seen with the small-molecule antagonists tirofiban and eptifibatide, with a 16% to 35% reduction in ischemic events in patients undergoing PCI.1,6⇓ Attempts to expand the therapeutic indication of GP IIb/IIIa antagonists to other conditions associated with platelet-mediated thrombosis, however, have been less fruitful than expected. Instead of reducing major ischemic events, long-term oral GP IIb/IIIa inhibitor therapy7 has uniformly increased the fatality rate. Furthermore, the overall efficacy of a number of the intravenous antagonists in non–ST-segment elevation acute coronary syndromes (ACS), or in combination with thrombolysis in ST-segment elevation myocardial infarction (MI), has been less than anticipated.8 Of particular concern is the fact that there has been a paradoxical increase in adverse events in 2 of the trials of intravenous therapy in ACS.9,10⇓ Platelets are known to play an important role in the pathogenesis of ACS, yet the high levels of platelet inhibition attainable with GP IIb/IIIa antagonists have failed to dramatically improve clinical outcomes outside of PCI. In this article, we discuss these …

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit

OBJECTIVESThe goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD).BACKGROUNDTreatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD.METHODSData for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated.RESULTSFactors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 ± 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 ± 0.07 (se) years (two-sided p = 0.05).CONCLUSIONSPatients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.

Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization.

The uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome. One hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 +/- 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG- segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG- findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG- groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death. Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.

Effect of left ventricular aneurysm on risk of sudden and nonsudden cardiac death

Although left ventricular (LV) aneurysm is associated with increased mortality, its independent prognostic significance is controversial. To determine the effect of LV aneurysm on risk, 121 patients with healed myocardial infarction (MI), 55 manifesting akinesia on ventriculography (MI group) and 66 with LV aneurysm characterized by diastolic deformity (eccentricity) and systolic dyskinesia (LV aneurysm group) were studied. At a mean follow-up of 5.7 years, there were 32 cardiac deaths (12 MI vs 20 LV aneurysm), including 9 sudden deaths (1 MI vs 8 LV aneurysm). Multivariate analysis revealed decreasing ejection fraction to be the best predictor of total cardiac death, and revascularization to be protective. Nonsudden cardiac death was predicted by ejection fraction, absence of revascularization and right coronary artery disease, whereas sudden cardiac death was predicted by LV aneurysm and the frequency of ventricular ectopic complexes on Holter monitoring. In the MI group, ejection fraction was the only significant predictor of total cardiac death and nonsudden cardiac death. In the LV aneurysm group, total cardiac death, as well as nonsudden cardiac death, were predicted by ejection fraction, ventricular tachycardia and right coronary artery disease, whereas ventricular tachycardia predicted sudden cardiac death. It is concluded that the risk profile for total cardiac death differs between LV aneurysm and MI patients, and that LV aneurysm constitutes an independent predictor of late sudden cardiac death after MI. Moreover, on a substrate of LV aneurysm, the risk factors for sudden cardiac death and nonsudden cardiac death differ, with ventricular tachycardia being the sole predictor of sudden cardiac death. Furthermore, Holter monitoring is valuable in Identifying patients at persistent risk of sudden cardiac death.

Failure of adipose tissue to heal in the capsule preformed by a silicone implant

In experiments on rats 2 ml of adipose tissue obtained by resection of parauterine fat were introduced as free implants beneath the dorsal skin. In a first group, which served as control, implantation was made into a freshly made pocket. In a second group a silicone prosthesis was first implanted in the site. Two months later the prosthesis was removed, cutting through its connective tissue capsule, and replaced with the adipose tissue. In the first group the implants healed, though with the usual reduction in volume. In the second group transplantation failed completely, with absence of revascularization and resorption of the implant. This failure was ascribed to two causes: 1) delayed activation of the preformed capsule, and 2) compression of the implant due to exudate collecting in the intracapsular space.

Stress electrocardiography in the evaluation of surgical revascularization of the heart.

Electrocardiography was carried out during hypoxemia and graded exercise tests before and at intervals between 2 and 20 months after attempts to revascularize the heart by internal mammary artery implantation in 44 patients with angiographically documented coronary disease and angina pectoris. Eleven patients had single vessel disease; the right coronary was involved in seven of these patients. Thirteen patients had single vessel implants, employing the left internal mammary artery in 11 patients and a saphenous vein graft from the aorta in two. Thirty-one patients had double internal mammary artery implantation accompanied by gastroepiploic arterial implantation in four. Fifty per cent of the patients were symptomatically improved after surgery, the best results occurring in two patients with isolated anterior descending coronary disease. Of the 34 patients having postoperative coronary and mammary arteriography, 15% showed improvement which could be ascribed to mammary revascularization; 24% had limited myocardial revascularization and no symptomatic improvement; 29% had patent implants without development of collateral vessels, and the implanted vessels were occluded in 32%. Eleven of the 34 (32%) had fair or good symptomatic improvement in the absence of revascularization. The results of postoperative stress electrocardiography correlated closely with the findings on postoperative coronary and mammary angiography. The stress tests were persistently positive after operation in 83% of the patients having angiographically confirmed implant occlusion or nonrevascularization. The stress ECG response was reversed, becoming negative postoperatively, in five cases of angiographically proved significant revascularization. Thus, stress electrocardiography provided objective evidence of improvement in a small number of patients with limited coronary disease who developed good collateral circulation and correlated with the lack of revascularization in the majority even in those subjectively improved.