Stent-Only Versus Adjunctive Balloon Angioplasty Approach for Saphenous Vein Graft Percutaneous Coronary Intervention: Insights From DIVA Trial.

BACKGROUND: Direct stenting without pre-dilation or post-dilation has been advocated for saphenous vein graft percutaneous coronary intervention to decrease the incidence of distal embolization, periprocedural myocardial infarction, and target lesion revascularization. METHODS: We performed a post hoc analysis of patients enrolled in the DIVA (Drug-Eluting Stents Versus Bare Metal Stents in Saphenous Vein Graft Angioplasty; NCT01121224) prospective, double-blind, randomized controlled trial. Patients were stratified into stent-only and balloon-stent groups. Primary end point was 12-month incidence of target vessel failure (defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization). Secondary end points included all-cause death, stent thrombosis, myocardial infarction, and target lesion revascularization during follow-up. RESULTS: Of the 575 patients included in this substudy, 185 (32%) patients underwent stent-only percutaneous coronary intervention. Patients in the stent-only versus balloon-stent group had similar baseline characteristics and similar incidence of target vessel failure at 12-months (15% versus 19%; hazard ratio, 1.34 [95% CI, 0.86-2.08]; P=0.19). During long-term follow-up (median of 2.7 years), the incidence of definite stent thrombosis (1% versus 5%; hazard ratio, 9.20 [95% CI, 1.23-68.92]; P=0.0085), the composite of definite or probable stent thrombosis (5% versus 11%; hazard ratio, 2.52 [95% CI, 1.23-5.18]; P=0.009), and target vessel myocardial infarction (8% versus 14%; hazard ratio, 1.92 [95% CI, 1.08-3.40]; P=0.023) was lower in the stent-only group. Multivariable analysis showed that a higher number of years since coronary artery bypass grafting and >1 target saphenous vein graft lesions were associated with increased target vessel failure during entire follow-up, while preintervention Thrombolysis in Myocardial Infarction-3 flow was protective. CONCLUSIONS: In patients undergoing percutaneous coronary intervention of de novo saphenous vein graft lesions, there was no difference in target vessel failure at 12 months and long-term follow-up in the stent-only versus the balloon-stent group; however, the incidence of stent thrombosis was lower in the stent-only group, as was target vessel myocardial infarction. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01121224.

Comparative Quantification of Arterial Lipid by Intravascular Photoacoustic-Ultrasound Imaging and Near-Infrared Spectroscopy-Intravascular Ultrasound.

Intravascular photoacoustic-ultrasound (IVPA-US) imaging and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) are two hybrid modalities that detect arterial lipid, with comparison necessary to understand the relative advantages of each. We performed in vivo and ex vivo IVPA-US imaging of the iliac arteries of Ossabaw swine with metabolic syndrome (MetS) and lean swine to investigate sensitivity for early-stage atherosclerosis. We repeated imaging ex vivo with NIRS-IVUS for comparison to IVPA-US and histology. Both modalities showed significantly greater lipid in MetS vs. lean swine, but only IVPA-US localized the lipid as perivascular. To investigate late-stage atherosclerosis, we performed ex vivo IVPA-US imaging of a human coronary artery with comparison to NIRS-IVUS and histology. Two advanced fibroatheromas were identified, with agreement between IVPA-measured lipid area and NIRS-derived lipid content. As confirmed histologically, IVPA-US has sensitivity to detect lipid content similar to NIRS-IVUS and provides additional depth resolution, enabling quantification and localization of lipid cores within plaques.

Poor agreement between pulmonary capillary wedge pressure and left ventricular end-diastolic pressure in a veteran population.

BACKGROUND: Accurate determination of left ventricular filling pressure is essential for differentiation of pre-capillary pulmonary hypertension (PH) from pulmonary venous hypertension (PVH). Previous data suggest only a poor correlation between left ventricular end-diastolic pressure (LVEDP) and its commonly used surrogate, the pulmonary capillary wedge pressure (PCWP). However, no data exist on the diagnostic accuracy of PCWP in veterans. Furthermore, the effects of age and comorbidities on the PCWP-LVEDP relationship remain unknown. METHODS: We investigated the PCWP-LVEDP relationship in 101 patients undergoing simultaneous right and left heart catherization at a large VA hospital. PCWP performance was evaluated using correlation and Bland-Altman analyses. Area under Receiver Operating Characteristics curves (AUROC) for PCWP were determined. RESULTS: PCWP-LVEDP correlation was moderate (r = 0.57). PCWP-LVEDP calibration was poor (Bland-Altman limits of agreement -17.2 to 11.4 mmHg; mean bias -2.87 mmHg). 59 patients (58.4%) had pulmonary hypertension; 15 (25.4%) of those met pre-capillary PH criteria based on PCWP. However, if LVEDP was used instead of PCWP, 7/15 patients (46.6%) met criteria for PVH rather than pre-capillary PH. When restricting analysis to patients with a mean pulmonary artery pressure of ≥25 mmHg and pulmonary vascular resistance of >3 Wood units (n = 22), 10 patients (45.4%) were classified as pre-capillary PH based on PCWP ≤15 mmHg. However, if LVEDP was used, 4/10 patients (40%) were reclassified as PVH. Among patients with any type of pulmonary hypertension, PCWP discriminated moderately between high and normal LVEDP (AUROC, 0.81; 95%CI 0.69-0.94). PCWP-LVEDP correlation was particularly poor in patients with COPD or obesity. CONCLUSION: Reliance on PCWP rather than LVEDP results in misclassification of veterans as having pre-capillary PH rather than PVH in almost 50% of cases. This is clinically relevant, as misclassification may lead to inappropriate therapies and adverse events.

C-reactive protein and fibrin clot strength measured by thrombelastography after coronary stenting.

Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16-24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P = 0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ±â€Š623 vs. 2184 ±â€Š576 dyn/cm, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P = 0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration.

Protease activated receptor-1 (PAR-1) mediated platelet aggregation is dependent on clopidogrel response.

INTRODUCTION: Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response. MATERIAL AND METHODS: Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance aggregometry using ADP 20 µM and thrombin receptor agonist peptide (TRAP) at 15 µM and 25 µM as agonists. Genomic DNA was genotyped for common CYP2C19 variants. RESULTS: Increasing quartiles of 20 µM ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 µM: 79.6 ± 5% vs. 69.5 ± 8%, p<0.001]. CONCLUSIONS: Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation.

Cardiac events after non-cardiac surgery in patients with previous coronary intervention in the drug-eluting stent era.

The peri-operative risk for patients with coronary drug-eluting stents (DES) who subsequently have non-cardiac surgery (NCS) is unclear. We performed this retrospective study of all patients in our institution who had coronary intervention and subsequent NCS from 2003 through December 2008 to evaluate the incidence of major adverse cardiac events (MACE) in patients who received DES compared to those who received bare-metal stents (BMS) or had percutaneous transluminal coronary angioplasty (PTCA) during the same time period. The main outcome measures were 30-day post-operative myocardial infarction, stent thrombosis, target vessel revascularization (TVR) and cardiac death. During the 6-year study period, 1,770 coronary interventions were performed and 238 patients subsequently had NCS in 8 days to 49 months. Eighteen patients had PTCA, 79 BMS and 141 DES. Acute myocardial infarction occurred in 1 patient who had PTCA, 2 who had BMS and 14 who had DES (p = 0.10). Stent thrombosis occurred in 6 patients who had DES and none who had BMS (p = 0.09). Seven patients who had DES had TVR compared to 1 patient who had BMS and none who had PTCA (p = 0.41). Cardiac mortality occurred in 2 patients who had DES and none who had PTCA or BMS (p = 0.35). In conclusion, the 30-day MACE in patients who received coronary DES and undergone NCS were not significantly different compared to those who received BMS or had PTCA only, with a trend toward higher stent thrombosis in the DES group.

Spontaneous closure of an iatrogenic circumflex coronary artery-to-coronary vein fistula.

Coronary artery fistulae are rare and usually discovered as incidentally during coronary angiography. They may be congenital or acquired secondary to trauma or cardiac intervention, and usually involve the left anterior descending or right coronary artery, with the circumflex artery much less often affected. They have been reported in transplanted hearts, usually as a secondary complication to right ventricular biopsies, and typically drain into the right ventricle. We hereby report a case of circumflex coronary artery to the great cardiac vein fistula that we believe occurred after transplantation and spontaneously closed while we were assessing the patient for percutaneous closure of the fistula.

Have all the ICD primary prevention trials excluded an important group of patients?

Primary prevention trials of implantable cardioverter defibrillator (ICD) therapy have generally excluded patients early after revascularization. Clinicians are commonly faced with patients who have ventricular dysfunction and nonsustained ventricular tachyarrhythmia developing shortly after revascularization. Since there are no evidence-based guidelines, management is currently at the discretion of the treating clinician. Recently, evidence has emerged that this patient population is at increased risk of development of life-threatening ventricular tachyarrhythmia and, pending prospective trials, we suggest that ICD therapy should be used in appropriately selected patients with perioperative ventricular arrhythmia.

Endothelial dysfunction: its role in hypertensive coronary disease.

PURPOSE OF REVIEW: Coronary artery disease is the major cause of death worldwide. Hypertension is a major risk factor for developing coronary disease. It is now recognized that endothelial dysfunction is an early marker of coronary artery disease before structural changes to the vessel wall are apparent on angiography or intravascular ultrasound and that it has a prognostic value in predicting cardiovascular events in hypertensive patients. This review addresses recent developments in hypertension-induced endothelial dysfunction. RECENT FINDINGS: Hyperaldosteronism causes endothelial dysfunction independent of high blood pressure. Exaggerated exercise blood pressure response has been related to endothelial dysfunction. Cyclosporin-A-induced endothelial dysfunction is related to reduced cholesterol content in caveolae. Chronic kidney disease induces changes in caveoli-1 and thus contributes to the reduced nitric oxide bioavailability, and causes oxidative stress independent of the high blood pressure. Asymmetric dimethylarginine plays a role in endothelial dysfunction in hypertensive patients independent of insulin resistance. 20-Hydroxyeicosatetraenoic acid is an independent predictor of hypertension in postmenopausal women. Endothelial dysfunction precedes and predicts the development of hypertension in postmenopausal women. Oral treatment with L-arginine improves endothelial dysfunction in hypertensives and lowers the blood pressure. SUMMARY: The pathophysiology of endothelial dysfunction in hypertension is multifactorial. Recent findings have contributed to our understanding of mechanisms of endothelial dysfunction and support a role for early intervention to prevent irreversible vascular and organ damage.

Percutaneous treatment of superior vena cava obstruction following transvenous device implantation.

The aim of this study is to assess the feasibility and safety of percutaneous treatment of superior vena cava (SVC) obstruction following transvenous device implantation. SVC obstruction is an uncommon but serious complication that can occur following permanent pacemaker or cardioverter defibrillator implantation utilizing transvenous endocardial leads. The treatment has traditionally been surgical but with the advent of stents, percutaneous approach is becoming popular. We report on the prevalence of SVC obstruction and the safety of its percutaneous catheter-based treatment. This is a retrospective study of SVC obstruction following device implantation in our institution from January 1993 through November 2003. A total of 1,850 permanent pacemaker and 1,200 implantable cardioverter defibrillator initial implants were performed during that period. Three patients developed SVC obstruction following implant (prevalence, 1/1,000 implant). Two patients were males and the mean age at implant was 57 +/- 13 years. Laser lead extraction and SVC angioplasty with or without stenting were performed in all patients. In two of them, this was followed by reimplantation of new systems. There were no procedural complications or mortality. The patients remain free of SVC obstruction symptoms 24 +/- 19 months after treatment. SVC obstruction prevalence after device implantation is low. Percutaneous treatment of SVC obstruction can be safely performed and appears to be effective in maintaining medium-term patency.

Effectiveness of early implantation of cardioverter defibrillator for postoperative ventricular tachyarrhythmia.

The effectiveness of implantable cardioverter defibrillators (ICDs) implanted in the early postoperative period after cardiac surgery for ventricular tachyarrhythmias is unknown, because all of the major trials excluded this patient population. Thus, a 10-year retrospective study was conducted of patients who had ICDs implanted for de novo postoperative ventricular tachyarrhythmias during the index admission for cardiac surgery. There was a high rate of early recurrence of ventricular tachyarrhythmia treated by defibrillators, and this finding questions the exclusion of this important patient population from large trials.

Use of proteomics to discover novel markers of cardiac allograft rejection.

Endomyocardial biopsy remains the most reliable method of detecting rejection following cardiac transplantation. Despite numerous attempts to detect rejection using a blood assay, none have proved reliable enough to replace the biopsy. Here, we have investigated the hypothesis that proteomics has the potential to reveal many molecules which are upregulated in the heart during rejection, some of which may serve as novel blood markers of rejection. Initially, sequential cardiac biopsies (33 in total) from 4 patients were analysed by two-dimensional gel electrophoresis according to whether they showed rejection (n = 16) or no rejection (n = 17); over 100 proteins were found to be upregulated by between 2- and 50-fold during rejection. Of these, 13 were identified and were found to be cardiac specific or heat shock proteins. Two of these (alphaB-crystallin, tropomyosin) were measured by ELISA in the sera of 17 patients followed for 3 months after their transplants. Mean levels of alphaB-crystallin and tropomyosin were significantly higher in sera associated with biopsies showing 1A (p = 0.007) or all grades of rejection (p = 0.022) compared to no rejection. These studies demonstrate that proteomics is a powerful method that can be used to identify novel serum markers of human cardiac allograft rejection.