Association between the severity of newly diagnosed obstructive sleep apnea and subclinical carotid atherosclerosis in patients without overt cardiovascular disease.

OBJECTIVE: Obstructive Sleep Apnea (OSA) has been associated with both subclinical and accelerated atherosclerosis; however, it still remains unknown whether this association is unique or is mediated by the higher burden of co-existing cardio-metabolic disorders frequently seen in patients with OSA. PATIENTS AND METHODS: A total of 40 subjects without clinically diagnosed cardiovascular disease (CVD) referred for polysomnography test were included in the study. Subjects with apnea/hypopnea index (AHI > 15/h) were classified as moderate/severe OSA. Subclinical changes in carotid atherosclerosis were assessed using mean carotid intima-media thickness (cIMT) and presence of atheromatic plaques on both carotid arteries. The measurement was performed using B-mode ultrasonogram. Framingham risk score was used in the approximation of cardiovascular risk. RESULTS: The mean age of our cohort was 56.8 years, 70% (n = 28) of whom were males. Moderate/severe OSA was diagnosed in 21 subjects. Both groups were well matched in terms of clinical and demographic characteristics, and cardiovascular risk profile, as shown in their respective Framingham risk scores (10.4 ± 6.6 vs. 11.8 ± 8.8, p = NS). Patients with moderate/severe OSA had a higher mean AHI, 3% oxygen desaturation index, and lower minimum nocturnal oxygen saturation than controls. No significant differences were detected in terms of C-reactive protein levels. The two groups had similar cIMT (0.66 ± 0.17 vs. 0.75 ± 0.20 p = 0.33) and presence of atheromatic plaque (50% vs. 45%, p = 1.00). CONCLUSIONS: Our study suggests that among patients with similar cardiovascular risk profile and free of overt CVD, the severity of newly diagnosed OSA was not correlated with increased inflammation or subclinical carotid atherosclerosis.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Prognostic value of post-procedural aPTT in patients with ST-elevation myocardial infarction treated with primary PCI.

Unfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defined. A mean aPTT was calculated of all aPTT measurements in the first 24 hours after pPCI in a total of 1,876 STEMI patients. Mean aPTT measurements were stratified into four categories; < 1.5 times the upper limit of normal (ULN), 1.5 - 2.0 times ULN (the therapeutic group), 2.01 - 3.99 times ULN, and ≥ 4 times ULN. Compared to patients with a therapeutic aPTT, patients with aPTTs < 1.5 times ULN had no increase in recurrent ischaemic events and had similar rates of bleeding complications. Patients with a mean aPTT ≥ 4 times ULN had higher rates recurrent ischaemic and haemorrhagic complications. After multivariable analyses, aPTT ratios ≥ 4 times ULN were no longer associated with recurrent ischaemic events, but remained a strong predictor of severe and moderate bleeding (hazard ratio [HR] 4.64, p = 0.016 and HR 2.27, p = 0.052). In conclusion, in 1,876 STEMI patients treated with pPCI, low aPTTs in the first 24 hours after PCI were not associated with an increase in ischaemic events, whereas high aPTT values were associated with more frequent bleeding complications. These results indicate no clear benefit as well as a safety concern with heparin treatment after primary PCI.

Future stent drug delivery systems.

Drug-eluting stents (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced in-stent restenosis and repeat revascularization compared with bare metal stent (BMS) across nearly all lesion and patient subsets. However, the small number of patients with in-stent restenosis after DES treatment still exists. Furthermore, concerns about long-term safety of DES are raised, particularly regarding the higher-than-expected late-event thrombosis. There is no doubt that the DES will continue to play a pivotal role in the treatment of coronary artery disease, yet future designs need to incorporate features that reduce thrombosis and promote endothelialization along with maintaining the efficacy. This review focuses on novel generation of DES, discussing new programs, including new antiproliferative agents, novel polymeric and non polymeric stents.

Cardiac biomarkers for the prediction and diagnosis of atherosclerotic disease and its complications.

Inflammation has been implicated in all stages of cardiovascular disease. This has driven a very fruitful search for new biomarkers, which potentially can be used as tools in the diagnosis and prognosis of atherothrombotic disease. While these new markers might prove useful in predicting the onset of atherosclerosis in healthy individuals, the utility of biomarkers in risk assessment for events in those patients with established disease and/or those with acute coronary syndrome requires further work. Effective biomarkers must be standardized, logistically simple to analyze, and clinically useful. Understanding what impact sex, age, ethnicity, and comorbid conditions may have on biomarkers is also of importance. Unfortunately, many of the candidate markers have yet to satisfy these requirements.

Common pathways for primary hypertrophic and dilated cardiomyopathy.

Testing the hypothesis that hypertrophic and dilated cardiomyopathy as well as viral myocarditis share a common mitogenic growth response pathway with mitotically competent cell types are the aims of this study. The expression of the c-fos, H-ras and c-myc genes was immunohistochemically determined in biopsies from 12 patients with dilated cardiomyopathy, 24 patients with hypertrophic cardiomyopathy, and 4 patients with myocarditis. Normal myocardium from 9 subjects was used as the control group. Staining results were correlated with patient's demographic data. C-fos, H-ras and c-myc protein overexpression was seen in 15 patients (62.5%) with primary hypertrophic and 4 patients (33.3%) with dilated cardiomyopathy. The majority of hypertrophic and dilated cardiomyopathy patients expressed at least one of the genes studied compared with the control group (p = 0.006). Primary cardiomyopathy patients also showed a statistically significant difference in the gene co-expression compared with the control group (p = 0.042). C-fos, H-ras, and C-myc protein expression did not differ substantially between patients with hypertrophic and dilated cardiomyopathy. Patients with myocarditis expressed only the C-fos protein (n = 2, 50%). C-fos, h-ras and c-myc genes are overexpressed in patients with cardiac hypertrophy and cardiac dilation. Cardiac myocytes respond to biomechanical stress by initiating several different processes. One of them is oncogene expression. This results in a hypertrophy of the myocytes proportional in length and width (hypertrophic cardiomyopathy or with a relatively greater increase in length than in the width (dilated cardiomyopathy).

Effect of short pulsed nonablative infrared laser irradiation on vascular cells in vitro and neointimal hyperplasia in a rabbit balloon injury model.

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Vascular complications after percutaneous coronary interventions following hemostasis with manual compression versus arteriotomy closure devices.

OBJECTIVES: We evaluated the vascular complications after hemostasis with arteriotomy closure devices (ACD) versus manual compression after percutaneous coronary interventions (PCI). BACKGROUND: Previous clinical studies have indicated that ACD can be used for achievement of hemostasis and early ambulation after PCI. This study investigated the safety of ACD in achieving hemostasis after PCI compared with manual compression in a large cohort of consecutive patients. METHODS: A total of 5,093 patients were followed after PCI was performed with the transfemoral approach. Univariate and multivariate analysis were used to identify the predictors of vascular complications with ACD (n = 516) or with manual compression (n = 5,892) as a hemostasis option after sheath removal. RESULTS: The use of ACD was associated with a more frequent occurrence of hematoma compared with manual compression (9.3 vs. 5.1%, p < 0.001). There was also a higher rate of significant hematocrit drop (>15%) with ACD versus manual compression (5.2% vs. 2.5%, p < 0.001). Similar rates of pseudoaneurysm and arteriovenous fistulae were noted with either hemostasis technique. Vascular surgical repair at the access site was required more often with ACD versus manual compression (2.5 vs. 1.5%, p = 0.03). CONCLUSIONS: In this early experience with ACD after PCI, their use was associated with higher vascular complication rates than hemostasis with manual compression.

Differential impact on survival of electrocardiographic Q-wave versus enzymatic myocardial infarction after percutaneous intervention: a device-specific analysis of 7147 patients.

BACKGROUND: The relative prognostic importance of ECG myocardial infarction (MI) after intervention compared with varying degrees of enzymatic elevation has not been characterized, and the device-specific implications of periprocedural MI are also unknown. METHODS AND RESULTS: Serial creatine phosphokinase (CPK)-MB levels were determined after elective percutaneous intervention of 12 098 lesions in 7147 consecutive patients at a tertiary referral center. Procedural, in-hospital, and follow-up data were collected by independent research nurses, and clinical and ECG events were adjudicated by a separate committee. Stents were implanted in 50.6% of lesions, atheroablation was performed in 54.8%, and PTCA alone was performed in 9.8%. The peak periprocedural CPK-MB level was >3x the upper limit of normal (ULN) in 17.9% of patients, and Q-wave MI developed in 0.6%. By multivariate analysis, the periprocedural development of new Q waves was the most powerful independent determinant of death (2-year mortality rate, 38.3%; hazard ratio, 9.9; P<0.0001). Non-Q-wave MI with CPK-MB >8x ULN was also a strong predictor of death (2-year mortality rate, 16.3%; hazard ratio, 2.2; P<0.0001); survival was unaffected by lesser degrees of CPK-MB elevation. Though CPK-MB elevation was more common after atheroablation and stenting than PTCA, the rates of Q-wave MI and survival were device-independent. CONCLUSIONS: Myonecrosis after percutaneous intervention is common in a high-risk referral population dominated by atheroablation and stent use. Large periprocedural infarctions (signified by new Q waves and CPK-MB >8xULN) are powerful determinants of death, whereas lesser degrees of CPK-MB release and specific device use do not adversely affect survival.

Intravascular ultrasound-guided renal artery stenting.

PURPOSE: To evaluate the clinical outcomes of patients undergoing renal artery stenting with intravascular ultrasound (IVUS) guidance and compare measurements between IVUS and angiography. METHODS: One hundred thirty-one patients (71 women; mean age 71 +/- 8 years) underwent IVUS-guided Palmaz stent implantation in 153 stenotic renal arteries at a single center. The indications for stenting were uncontrolled hypertension (102, 77.9%), renal insufficiency (10, 7.6%), and both conditions (19, 14.5%). The majority of lesions were ostial (114, 74.5%); the remainder occupied the proximal renal artery (39, 25.5%). The mean lesion length and diameter stenosis were 6.5 +/- 3.0 mm and 74% +/- 10%, respectively, as measured by angiography. Data were recorded in a prespecified database; angiographic and IVUS images were analyzed at dedicated core laboratories and compared. RESULTS: Angiographic success was achieved in all patients, but IVUS indicated the need for additional intervention in 36 (23.5%) cases. There was strong correlation between the angiographic and IVUS measurements of lesion length (r = 0.60, p < 0.0001) and pre-/postprocedural minimal luminal diameter (r = 0.72 and 0.63, respectively; p < 0.0001). The mean contrast volume was 74 +/- 18 mL per case. In-hospital renal failure occurred in 8 (6.1%) patients; 2 (1.5%) required transient hemodialysis. At a mean 15-month follow-up, patients were treated with fewer antihypertensive medications (p = 0.05), and systolic and diastolic arterial blood pressures had decreased (p = 0.001); no significant change was noted in serum creatinine. CONCLUSIONS: IVUS-guided stenting facilitates safe renal artery revascularization. IVUS imaging may complement angiography in certain cases, which should be studied further in prospective studies with iodinated or noniodinated contrast agents.

Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.

BACKGROUND AND PURPOSE: Early postoperative stroke is a serious adverse event after coronary artery bypass grafting (CABG). This study sought to investigate risk factors, prevalence, and prognostic implications of postoperative stroke in patients undergoing CABG. METHODS: We investigated the predictors of postoperative stroke (n=333, 2%) in 16 528 consecutive patients who underwent CABG between September 1989 and June 1999 in our institution. Predictors of postoperative stroke were identified by logistic regression analysis. RESULTS: Among the preoperative and postoperative factors, significant correlates of stroke included (1) chronic renal insufficiency (P<0.001), (2) recent myocardial infarction (P=0.01), (3) previous cerebrovascular accident (P<0.001), (4) carotid artery disease (P<0.001), (5) hypertension (P<0.001), (6) diabetes (P=0.001), (7) age >75 years (P=0.008), (8) moderate/severe left ventricular dysfunction (P=0.01), (9) low cardiac output syndrome (P<0.001), and (10) atrial fibrillation (P<0.001). Postoperative stroke was associated with longer postoperative stay (11+/-4 versus 7+/-3 days for patients without stroke, P<0.001) and with higher in-hospital mortality (14% versus 2.7% for patients without stroke; P<0.001). CONCLUSIONS: Stroke after CABG is associated with high short-term morbidity and mortality. Increased stroke risk can be predicted by preoperative and postoperative clinical factors.

Are we making progress with percutaneous saphenous vein graft treatment? A comparison of 1990 to 1994 and 1995 to 1998 results.

OBJECTIVES: We sought to determine whether strategies to reduce procedural distal embolization and late repeat revascularization have resulted in more favorable outcomes after saphenous vein graft (SVG) angioplasty. BACKGROUND: Angioplasty of SVG lesions has been associated with frequent procedural and late cardiac events. Therefore, evolving strategies have been attempted to improve outcomes after SVG angioplasty. METHODS: We compared our earlier experience (1990 to 1994) of 1,055 patients with 1,412 SVG lesions with a recent group (1995 to 1998) of 964 patients with 1,315 lesions. RESULTS: Baseline characteristics were similar between the groups. However, there were significantly more unfavorable lesion characteristics (older, longer and significantly more degenerated SVGs) in the recent series. Between the two periods, there was decreased use ofatheroablative devices, whereas stent use increased. The procedural success rates (96.6% vs. 96.1%) were similar. However, one-year outcome (event-free survival) was significantly improved in the more recent experience (70.7% vs. 59.1%, p < 0.0001), especially late mortality (6.1% vs. 11.3%, p < 0.0001). Multivariate analysis showed stent use to be the only protective variable for both periods. CONCLUSIONS: This study shows that despite higher risk lesions, strategies to reduce distal embolization have maintained high procedural success. Late cardiac events, including mortality, have also been substantially reduced.

Creatine kinase-MB fraction elevation after percutaneous coronary intervention in patients with chronic renal failure.

We evaluated the short- and long-term clinical outcomes of 326 consecutive patients with chronic renal failure, not on dialysis, who had creatine kinase (CK)-myocardial band (MB) fraction elevation after successful percutaneous coronary intervention in a native coronary artery. Based on peak CK-MB levels measured after intervention, patients were divided into 3 groups: no elevation (group 1, n = 184), 1 to 3 x upper normal levels (group 2, n = 72), and >3 x upper normal levels (group 3, n = 70). Baseline clinical and angiographic characteristics were similar among the 3 groups. Angiographic success was similar among the 3 groups, although there was a significantly higher use of intra-aortic balloon pump in patients who had postprocedural CK-MB >3 x normal values and a higher rate of in-hospital complications, i.e., repeat catheterization, repeat target lesion intervention, pulmonary edema, renal function deterioration, emergency dialysis, and major bleeding complications. At 1-year follow-up, mortality rates were significantly higher in these patients (35.4% vs 22.0% for patients with CK-MB 1 to 3 x normal values and 16.7% for patients without CK-MB elevation, p = 0.007). Multivariate analysis showed that CK-MB >3 x normal (odds ratio 3.04; 95% confidence interval 1.41 to 6.57, p = 0.005) and intra-aortic balloon pump (odds ratio 1.49; confidence interval 1.15 to 1.93, p = 0.002) were independent predictors of late mortality. Therefore, patients with chronic renal failure who had CK-MB elevation >3 x the upper normal limit after a successful percutaneous coronary intervention had a higher incidence of in-hospital complications and a significantly higher mortality rate at 1-year follow-up than patients without CK-MB elevation or with <3 x normal CK-MB elevation.

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Transient contrast encephalopathy after carotid artery stenting.

PURPOSE: To report an unusual case of transient contrast encephalopathy arising after carotid artery stenting. CASE REPORT: An 82-year-old right-handed man with a recent history of transient ischemic events was admitted to the hospital for evaluation of carotid artery disease. During cerebral angiography, which identified a 90% right internal carotid artery stenosis, the patient received 25 mL of an ionic, low-osmolar contrast agent (ioxaglate) in each carotid artery. The following day he underwent successful carotid stenting, during which 180 mL of ioxaglate were used. He developed rapidly worsening confusion and left hemiparesis on the table. Noncontrast computed tomography showed marked cortical enhancement and edema of the right cerebral hemisphere in the distribution of the right anterior and middle cerebral arteries. The patient improved rapidly and by day 2 was completely recovered; magnetic resonance imaging documented no cortical edema and normal sulci. One month after the procedure, he was well, with patent carotid arteries. CONCLUSIONS: Transient neurotoxicity after carotid interventions must be differentiated from massive cerebral infarction and hyperperfusion syndrome, but the prognosis is excellent. However, subsequent contrast studies in a patient with this complication should be undertaken with extreme caution.

Acute renal failure requiring dialysis after percutaneous coronary interventions.

Acute renal failure requiring dialysis is a rare but serious complication after percutaneous coronary interventions (PCI), associated with high in-hospital mortality and poor long-term survival. We have analyzed the incidence, resource utilization, short- and long-term outcomes, and predictors of dialysis after percutaneous coronary interventions. We studied 51 consecutive patients who were not on dialysis on admission and developed acute renal failure that required in-hospital dialysis after PCI in comparison to the 7,690 patients who did not require dialysis after PCI. Patients who required dialysis were older, with a higher incidence of hypertension, diabetes, prior bypass surgery, chronic renal failure, and a significantly lower left ventricular ejection fraction. Despite similar angiographic success, these patients had a higher incidence of in-hospital mortality (27.5% vs. 1.0%, P < 0.0001), non-Q-wave myocardial infarction (45.7% vs. 14.6%, P < 0.0001), vascular and bleeding complications, and longer hospitalization. At 1-year follow-up, mortality (54.5% vs. 6.4%, P < 0.0001), myocardial infarction (4.5% vs. 1.6%, P = 0.006), and event-free survival (38.6% vs. 72.0%, P < 0.0001) were significantly worse in patients who required dialysis compared to patients who did not. Multivariate analysis revealed in-hospital dialysis and an increase in baseline serum creatinine levels as the most important predictors of in-hospital and long-term mortality. Thus, acute renal failure that requires dialysis after percutaneous coronary interventions is associated with very high in-hospital and 1-year mortality rates and a dramatic increase in hospital resource utilization.

Prognostic importance of myonecrosis after percutaneous coronary interventions.

Occurrence of myonecrosis can be documented after percutaneous coronary interventions (PCI). Data have correlated this phenomenon with late mortality, and with diffuse atherosclerotic disease. While controversy still exists, the potential for improved mortality after PCI should be fully explored in a systematic way.