Survival and cardiac remodeling benefits in patients undergoing late percutaneous coronary intervention of the infarct-related artery: evidence from a meta-analysis of randomized controlled trials

Our purpose was to perform a systematic review and meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) with medical therapy in patients randomized >12 h after acute myocardial infarction (AMI).

Relation of morning serum cortisol to prothrombotic activity in women with stable coronary artery disease

BACKGROUND: Increased circulating cortisol levels have been associated with severity of atherosclerosis. Low-grade systemic thrombogenicity plays a major role in the initiation and progression of coronary disease. We hypothesized a direct relationship between cortisol and hemostasis factors related to a prothrombotic state in coronary artery disease. METHODS: We measured morning serum cortisol and activated clotting factor VII, fibrinogen, von Willebrand factor antigen, and plasminogen activator inhibitor-1 activity in 285 women (56 +/- 7 years) between 3 and 6 months after an acute coronary event. To test whether the relationship between cortisol and hemostasis factors would be independent, statistical adjustment was made for demographic, biomedical, life style, and psychosocial variables. RESULTS: Higher serum cortisol levels predicted higher fibrinogen (beta = .17, P = .001) and higher von Willebrand factor (beta = .16, P = .008), all independently of covariates, including C-reactive protein, which was also an independent predictor of fibrinogen (beta = .20, P = .001) and von Willebrand factor (beta = .16, P = .004). Higher levels of vital exhaustion were associated with higher levels of activated clotting factor VII independently of covariates and depression (beta = .18, P = .045). Cortisol showed crude correlations with vital exhaustion (r = .14, P = .022) and with depression (r = .13, P = .043) but did not mediate the relationship between psychosocial variables and hemostatic factors. CONCLUSIONS: Morning serum cortisol showed a modest but independent association with prothrombotic activity in women with coronary artery disease suggesting that increased cortisol levels might contribute to atherosclerosis via eliciting a hypercoagulable state.

Autonomic function and prothrombotic activity in women after an acute coronary event

BACKGROUND: The link between decreased heart rate variability (HRV) and atherosclerosis progression is elusive. We hypothesized that reduced HRV relates to increased levels of prothrombotic factors previously shown to predict coronary risk. METHODS: We studied 257 women (aged 56 +/- 7 years) between 3 and 6 months after an acute coronary event and obtained very low frequency (VLF), low frequency (LF), and high frequency (HF) power, and LF/HF ratio from 24-hour ambulatory ECG recordings. Plasma levels of activated clotting factor VII (FVIIa), fibrinogen, von Willebrand factor antigen (VWF:Ag), and plasminogen activator inhibitor-1 (PAI-1) activity were determined, and their levels were aggregated into a standardized composite index of prothrombotic activity. RESULTS: In bivariate analyses, all HRV indices were inversely correlated with the prothrombotic index explaining between 6% and 14% of the variance (p < 0.001). After controlling for sociodemographic factors, index event, menopausal status, cardiac medication, lifestyle factors, self-rated health, metabolic variables, and heart rate, VLF power, LF power, and HF power explained 2%, 5%, and 3%, respectively, of the variance in the prothrombotic index (p < 0.012). There were also independent relationships between VLF power and PAI-1 activity, between LF power and fibrinogen, VWF:Ag, and PAI-1 activity, between HF power and FVIIa and fibrinogen, and between the LF/HF power ratio and PAI-1 activity, explaining between 2% and 3% of the respective variances (p < 0.05). CONCLUSIONS: Decreased HRV was associated with prothrombotic changes partially independent of covariates. Alteration in autonomic function might contribute to prothrombotic activity in women with coronary artery disease (CAD).

Increased Framingham Coronary Heart Disease Risk Score in dementia caregivers relative to non-caregiving controls

BACKGROUND: Elderly individuals who provide care to a spouse suffering from dementia bear an increased risk of coronary heart disease (CHD). OBJECTIVE: To test the hypothesis that the Framingham CHD Risk Score would be higher in dementia caregivers relative to non-caregiving controls. METHODS: We investigated 64 caregivers providing in-home care for their spouse with Alzheimer's disease and 41 gender-matched non-caregiving controls. All subjects (mean age 70 +/- 8 years, 75% women, 93% Caucasian) had a negative history of CHD and cerebrovascular disease. The original Framingham CHD Risk Score was computed adding up categorical scores for age, blood lipids, blood pressure, diabetes, and smoking with adjustment made for sex. RESULTS: The average CHD risk score was higher in caregivers than in controls even when co-varying for socioeconomic status, health habits, medication, and psychological distress (8.0 +/- 2.9 vs. 6.3 +/- 3.0 points, p = 0.013). The difference showed a medium effect size (Cohen's d = 0.57). A relatively higher blood pressure in caregivers than in controls made the greatest contribution to this difference. The probability (area under the receiver operator curve) that a randomly selected caregiver had a greater CHD risk score than a randomly selected non-caregiver was 65.5%. CONCLUSIONS: Based on the Framingham CHD Risk Score, the potential to develop overt CHD in the following 10 years was predicted to be greater in dementia caregivers than in non-caregiving controls. The magnitude of the difference in the CHD risk between caregivers and controls appears to be clinically relevant. Clinicians may want to monitor caregiving status as a routine part of standard evaluation of their elderly patients' cardiovascular risk.

Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.

Complete arterial revascularization in multivessel coronary artery disease with 2 conduits (skeletonized grafts and T grafts)

BACKGROUND: Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis. METHODS AND RESULTS: Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%). CONCLUSIONS: Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.

Intimal proliferation and restenosis in paclitaxel-eluting stents with aminoparylene as carrier substance in swines

BACKGROUND: Polymer as carrier substance for drugeluting stents (DES) has been accused of inducing inflammation and hypersensitivity reactions leading to restenosis and stent thrombosis. Thus, a new paclitaxel-eluting stent (PES) with aminoparylene as a carrier substance is tested in the present study. METHODS: In 10 pigs, stents were implanted in the epicardial coronary arteries: 1) bare-metal stents (BMS, control stent); 2) cobalt-chromium stents (CCS); and 3) PES. Stent length was 15 mm, and diameter was 3 mm. The animals were restudied after 6 weeks. Quantitative coronary angiography was performed at baseline and follow up. Minimum luminal diameter (MLD) and late loss were calculated in all animals. Histologic vessel lumen, intimal proliferation and restenosis were determined by morphometry. Disruption of the lamina elastica interna (LEI) and inflammatory reactions were assessed by histology. RESULTS: The MLD at baseline was 2.83 +/- 0.28 mm, and at follow up it was 2.29 +/- 0.44 (p < 0.05; n = 30). Late loss and angiographic restenosis were smallest in the CCS and largest in the PES (ns). Neointimal proliferation was similar for all 3 stents, ranging between 1.38 and 1.64 mm(2) (ns). There was a significant correlation between disruption of the LEI and inflammatory reactions. CONCLUSIONS: PTs with aminoparylene as a carrier substance show similar late loss and angiographic restenosis to that of BM and CCS. The incidence of inflammatory reactions (35% of all histologic sections) is similar in all stents, but highest in PES. The mechanism of this reaction is unclear, but may be either due to the drug itself, the disruption of the LEI or to a hypersensitivity reaction.

Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization

AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.

Haemodynamic and arrhythmic effects of moderately cold (22 degrees C) water immersion and swimming in patients with stable coronary artery disease and heart failure

AIMS: Data on moderately cold water immersion and occurrence of arrhythmias in chronic heart failure (CHF) patients are scarce. METHODS AND RESULTS: We examined 22 male patients, 12 with CHF [mean age 59 years, ejection fraction (EF) 32%, NYHA class II] and 10 patients with stable coronary artery disease (CAD) without CHF (mean age 65 years, EF 52%). Haemodynamic effects of water immersion and swimming in warm (32 degrees C) and moderately cold (22 degrees C) water were measured using an inert gas rebreathing method. The occurrence of arrhythmias during water activities was compared with those measured during a 24 h ECG recording. Rate pressure product during water immersion up to the chest was significantly higher in moderately cold (P = 0.043 in CHF, P = 0.028 in CAD patients) compared with warm water, but not during swimming. Rate pressure product reached 14200 in CAD and 12 400 in CHF patients during swimming. Changes in cardiac index (increase by 5-15%) and oxygen consumption (increase up to 20%) were of similar magnitude in moderately cold and warm water. Premature ventricular contractions (PVCs) increased significantly in moderately cold water from 15 +/- 41 to 76 +/- 163 beats per 30 min in CHF (P = 0.013) but not in CAD patients (20 +/- 33 vs. 42 +/- 125 beats per 30 min, P = 0.480). No ventricular tachycardia was noted. CONCLUSION: Patients with compensated CHF tolerate water immersion and swimming in moderately cold water well. However, the increase in PVCs raises concerns about the potential danger of high-grade ventricular arrhythmias.

Revascularisation of coronary artery disease in patients with diabetes mellitus

Diabetes mellitus is becoming increasingly prevalent and magnifies the risk of cardiovascular complications. Endothelial dysfunction caused by oxidative stress is a hallmark of diabetes and is responsible for the ubiquitous manifestations of vascular disease in diabetics. Compared with non-diabetic patients, coronary artery disease is more severe and the clinical outcome impaired in diabetic patients undergoing revascularisation. Despite these limitations the benefit of revascularisation therapy is particularly pronounced in diabetics. The optimal revascularisation strategy (coronary artery bypass graft surgery versus percutaneous coronary intervention) in diabetic patients with coronary artery disease depends on clinical and anatomical considerations.

Impact of vessel size on angiographic and clinical outcomes of revascularization with biolimus-eluting stent with biodegradable polymer and sirolimus-eluting stent with durable polymer the LEADERS trial substudy

OBJECTIVES: We assessed the impact of vessel size on outcomes of stenting with biolimus-eluting degradable polymer stent (BES) and sirolimus-eluting permanent polymer stent (SES) within a randomized multicenter trial (LEADERS). BACKGROUND: Stenting of small vessels might be associated with higher rates of adverse events. METHODS: "All-comer" patients (n = 1,707) were randomized to BES and SES. Post-hoc-stratified analysis of angiographic and clinical outcomes at 9 months and 1 year, respectively, was performed for vessels with reference diameter 2.75 mm. RESULTS: Of 1,707 patients, 429 patients in the BES group with 576 lesions and 434 patients in the SES group with 557 lesions had only small vessels treated (50.6% of the patient cohort). In patients with small vessels there was no significant difference in overall major adverse cardiac events (MACE) rate (12.1% vs. 11.8%; p = 0.89) or target lesion revascularization (TLR) rate (9.6% vs. 7.4%; p = 0.26) between BES and SES. The MACE and TLR rates in the small-vessel patient population were higher than in the large-vessel population. The TLR rate was 9.6% versus 2.6%, and MACE rate was 12.1% versus 7.1% for small versus large vessels in the BES arm (TLR: hazard ratio [HR] = 3.724, p = 0.0013; MACE: HR = 1.720, p = 0.0412). In the SES arm, TLR was 7.4% versus 5.1%, and MACE was 11.8% versus 10.3% in small versus large vessels (TLR: HR = 1.435, p = 0.2594; MACE: HR = 1.149, p = 0.5546). CONCLUSIONS: Prevalence of small vessel disease is high in an "all-comer" population with higher TLR and MACE rates. The BES and SES seem equivalent in treatment outcomes of small vessels in this "all-comer" patient population.

Diabetes and acute coronary syndromes

Diabetic patients with acute coronary syndromes (ACSs) are at a high risk for subsequent cardiovascular events but derive, at the same time, greater benefit from evidence-based therapy than non-diabetic individuals. State-of-the-art anti-thrombotic therapy includes a triple anti-platelet combination - aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa receptor inhibitors - and unfractionated heparin or enoxaparin. For low- or medium-risk individuals, a treatment based on aspirin, clopidogrel and bivalirudin is a valuable alternative. Prasugrel, a new and more potent inhibitor of the platelet P2Y(12) receptor, has to be regarded as the most promising anti-thrombotic agent for diabetic patients with ACS. This agent may replace clopidogrel - and possibly GP IIb/IIIa inhibitors - in the future. In addition to aggressive anti-thrombotic therapy, diabetic patients should undergo systematic early invasive angiography if presenting with non-ST-segment elevation ACS, and immediate percutaneous coronary intervention if presenting with ST-segment elevation myocardial infarction. Indeed, the benefit derived from these strategies appears to be more pronounced in the diabetic population than in non-diabetic individuals. Despite the benefit, multiple surveys have demonstrated that, in the setting of ACS, diabetic patients receive evidence-based therapy less frequently than non-diabetic counterparts.

[The role of percutaneus coronary interventions in the treatment of coronary artery disease]

In industrial countries, cardiovascular diseases remain the primary cause of death. This review summarizes the role of percutaneous coronary interventions (PCI) in the treatment of coronary heart disease. Interventional therapy of coronary artery disease was initiated in 1977 with the introduction of balloon angioplasty by Andreas Grüntzig in Zurich. Technical progress since has been related to construction and materials of catheters, but also to digital processing of x-ray imaging. Additional methods - rotablation, atherectomy, laser, intravascular ultrasound, and most importantly stent implantation were developed. Only stents significantly changed the procedure. They are today an integral part of PCI.

Comparison of long versus short ("spot") drug-eluting stenting for long coronary stenoses

We compared spot drug-eluting stenting (DES) to full stent coverage for treatment of long coronary stenoses. Consecutive, consenting patients with a long (>20 mm) coronary lesion of nonuniform severity and indication for percutaneous coronary intervention were randomized to full stent coverage of the atherosclerotic lesion with multiple, overlapping stenting (full DES group, n = 90) or spot stenting of hemodynamically significant parts of the lesion only (defined as diameter stenosis >50%; spot DES group, n = 89). At 1-year follow-up, 14 patients with full DES (15.6%) and 5 patients (5.6%) with spot DES had a major adverse cardiac event (MACE; p = 0.031). At 3 years, MACEs occurred in 18 patients with full DES (20%) and 7 patients (7.8%) with spot DES (p = 0.019). Cox proportional hazard model showed that the risk for MACEs was almost 60% lower in patients with spot DES compared to those with full DES (hazard ratio 0.41, 95% confidence interval 0.17 to 0.98, p = 0.044). This association remained even after controlling for age, gender, lesion length, and type of stent used (hazard ratio 0.42, 95% confidence interval 0.17 to 1.00, p = 0.05). In conclusion, total lesion coverage with DES is not necessary in the presence of diffuse disease of nonuniform severity. Selective stenting of only the significantly stenosed parts of the lesion is an appropriate therapeutic alternative in this setting, offering a favorable clinical outcome.

Successful percutaneous coronary intervention after implantation of a CoreValve percutaneous aortic valve

BACKGROUND: The association between aortic valve disease and coronary atherosclerosis is common. In the recent era of percutaneous aortic valve replacement (PAVR), there is little experience with coronary artery intervention after valve implantation. CASE REPORT: To our knowledge, this is the first case of successful percutaneous coronary intervention after implantation of a CoreValve percutaneous aortic valve. We report a case of a 79-year-old female patient who underwent successful coronary artery intervention few months after a CoreValve's percutaneous implantation for severe aortic valve stenosis. Verifying the position of the used wires (crossing from inside the self expanding frame) is of utmost importance before proceeding to coronary intervention. In this case, crossing the aortic valve, coronary angiography, and multivessel stenting were successfully performed. CONCLUSION: Percutaneous coronary intervention in patients with previous CoreValve is feasible and safe.