Post-mortem examination of fatal acute type A aortic dissection: what does it teach us?

OBJECTIVES: Acute type A aortic dissection (ATAAD) remains a highly life-threatening condition. This study investigates factors associated with fatal ATAAD prior to surgical treatment. METHODS: We reviewed autopsy reports of ATAAD decedents who died before surgical intervention and underwent postmortem examination at our clinic from 1994 to 2022. RESULTS: Among 94 eligible cases, 50 (53.2%) decedents had DeBakey type I dissection, and 44 (46.8%) had DeBakey type II dissection. Most were males, 63 (67%), and 72 (77%) had a history of hypertension. The median age was 70.5 years, and the type II group was a decade older than the type I group (P < 0.001). Decedents in the type II group predominantly died during the first hour after symptoms onset 16 (52%), while in the type I group, fatalities occurred between 1 h and 1 day, 27 (66%). The most common site of the intimal tear was the midportion of the ascending aorta, 45 (48%). The median ascending aorta size was 5 cm for the entire cohort, 5.2 cm for type I and 4.6 cm for type II (P < 0.045). CONCLUSIONS: In this autopsy study of fatal acute aortic dissection, the median aortic size was below the current guideline threshold for elective repair. Type II acute aortic dissections were found more frequently than expected and were characterized by older age, advanced aortic atherosclerosis, smaller aortic size, a shorter interval from symptom onset to death and a higher frequency of syncope compared to type I dissection.

Hyperactivity of the CD155 immune checkpoint suppresses anti-viral immunity in patients with coronary artery disease.

Pre-existent cardiovascular disease is a risk factor for weak anti-viral immunity, but underlying mechanisms remain undefined. Here, we report that patients with coronary artery disease (CAD) have macrophages (Mϕ) that actively suppress the induction of helper T cells reactive to two viral antigens: the SARS-CoV2 Spike protein and the Epstein-Barr virus (EBV) glycoprotein 350. CAD Mϕ overexpressed the methyltransferase METTL3, promoting the accumulation of N6-methyladenosine (m6A) in Poliovirus receptor (CD155) mRNA. m6A modifications of positions 1635 and 3103 in the 3'UTR of CD155 mRNA stabilized the transcript and enhanced CD155 surface expression. As a result, the patients' Mϕ abundantly expressed the immunoinhibitory ligand CD155 and delivered negative signals to CD4+ T cells expressing CD96 and/or TIGIT receptors. Compromised antigen-presenting function of METTL3hi CD155hi Mϕ diminished anti-viral T cell responses in vitro and in vivo. LDL and its oxidized form induced the immunosuppressive Mϕ phenotype. Undifferentiated CAD monocytes had hypermethylated CD155 mRNA, implicating post-transcriptional RNA modifications in the bone-marrow in shaping anti-viral immunity in CAD.

Early Right Ventricular Reverse Remodeling Predicts Survival After Isolated Tricuspid Valve Surgery.

BACKGROUND: There are limited data on the impact of isolated tricuspid valve (TV) surgery on recovery of right ventricular (RV) function and RV reverse remodeling. METHODS: Among 223 patients who had isolated TV procedures between 2001 and 2017, 60 (27%) underwent TV repair and 163 (73%) received TV replacement. Indication for surgery was functional tricuspid valve regurgitation in 64%, lead induced in 18%, and primary leaflet dysfunction in 18%. RV reverse remodeling was assessed by echocardiography at a median of 11.3 months (interquartile range [IQR] 5.9-13.5) post-dismissal. RESULTS: Mean age was 67.3 ± 13.7 years, and 57% were female. Overall 30-day mortality was 2.7%. After a median follow-up period of 9.5 years (IQR 3.6-12.9), adjusted Cox regression analysis revealed comparable survival for TV repair and replacement and identified older age, and presence of RV dysfunction (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.14-2.98; P = .01), as independent predictors of poor survival. Patients who exhibited RV reverse remodeling within 18 months postoperatively had significantly improved survival compared with those who did not (log-rank P = .005), and reverse remodeling was independently associated with improved survival (HR 0.42, 95% CI 0.24-0.74; P = .003). Lower preoperative right atrial pressure (odds ratio 0.83, 95% CI 0.73-0.94; P = .004) was predictive of early RV reverse remodeling. CONCLUSIONS: Isolated TV surgery can be performed with acceptable outcomes (early mortality 2.7%), and overall survival is best in patients who receive the operation before developing RV systolic dysfunction. Adjusted survival was similar for patients undergoing TV repair or replacement. Early reverse remodeling of RV after surgery is associated with survival benefit.

Influence of LDL-Cholesterol Lowering on Cardiovascular Outcomes in Patients With Diabetes Mellitus Undergoing Coronary Revascularization.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations. OBJECTIVES: This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM). METHODS: Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke). RESULTS: A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI. CONCLUSIONS: In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl.

Coronary Disease Surveillance in the Community: Angiography and Revascularization.

Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age- and sex-adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI, 25%-34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95% CI, 1.07-1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI, 27%-39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95% CI, 1.00-1.22]). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.

Left ventricular ejection hemodynamics before and after relief of outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy and valvular aortic stenosis.

OBJECTIVE: There has been debate on the importance and pathophysiologic effects of the dynamic subaortic pressure gradient in hypertrophic obstructive cardiomyopathy. The study was conducted to elucidate the hemodynamic abnormalities associated with the dynamic pressure gradient in hypertrophic obstructive cardiomyopathy. METHODS: Eight patients with hypertrophic obstructive cardiomyopathy and 7 patients with valvular aortic stenosis underwent a detailed hemodynamic study of pressure flow relationships before and after myectomy or aortic valve replacement during operation. RESULTS: In aortic stenosis, the increased gradient after premature ventricular contraction was associated with an increase in peak flow (325 ± 122 mL/s to 428 ± 147 mL/s, P = .002) and stroke volume (75.0 ± 27.3 mL to 88.0 ± 24.0 mL, P = .004), but in hypertrophic obstructive cardiomyopathy peak flow remained unchanged (289 ± 79 mL/s to 299 ± 85 mL/s, P = .334) and stroke volume decreased (45.9 ± 18.7 mL to 38.4 ± 14.4 mL, P = .04) on the postpremature ventricular contraction beat. After myectomy, the capacity to augment stroke volume on the postpremature ventricular contraction beats was restored in patients with hypertrophic obstructive cardiomyopathy (45.6 ± 14.4 mL to 54.4 ± 11.8 mL, P = .002). CONCLUSIONS: The pressure flow relationship in hypertrophic obstructive cardiomyopathy supports the concept of true obstruction to outflow, with a low but continued flow during late systole, when the ventricular-aortic pressure gradient is the highest. Septal myectomy can abolish obstruction and restore the ability to augment stroke volume, which may explain the mechanism of symptomatic improvement after operation.

BARI 2D: A Reanalysis Focusing on Cardiovascular Events.

OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease. PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events. RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization.

OBJECTIVE: To assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG. METHODS: From January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used. RESULTS: In multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65). CONCLUSION: RCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.

Impact of Chronic Kidney Disease on Outcomes of Myocardial Revascularization in Patients With Diabetes.

BACKGROUND: The optimal coronary revascularization strategy in patients with stable ischemic heart disease (SIHD) who have type 2 diabetes (T2DM) and chronic kidney disease (CKD) remains unclear. OBJECTIVES: This patient-level pooled analysis sought to compare outcomes of 3 large, federally-funded randomized trials in SIHD patients with T2DM and CKD (COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation], BARI 2D [Bypass Angioplasty Revascularization Investigation 2 Diabetes], and FREEDOM [Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-vessel Disease]). METHODS: The primary endpoint was the composite of major adverse cardiovascular or cerebrovascular events (MACCE) including all-cause death, myocardial infarction (MI), or stroke adjusted for trial and randomization strategy. RESULTS: Of the 4,953 patients with available estimated glomerular filtration rate (eGFR) at baseline, 1,058 had CKD (21.4%). CKD patients were more likely to be older, be female, and have a history of heart failure. CKD subjects were more likely to experience a MACCE (adjusted hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28 to 1.71; p = 0.0001) during a median 4.5-year follow-up. Both mild (eGFR 45 to 60 ml/min/1.73 m2) and moderate to severe (eGFR <45 ml/min/1.73 m2) CKD predicted MACCE (adjusted HRs: 1.25 and 2.26, respectively). For patients without CKD, coronary artery bypass graft (CABG) surgery combined with optimal medical therapy (OMT) was associated with lower MACCE rates compared with percutaneous coronary intervention (PCI) + OMT (adjusted HR: 0.69; 95% CI: 0.55 to 0.86; p = 0.001). For the comparison of CABG + OMT versus PCI + OMT in the CKD group, there was only a statistically significant difference in subsequent revascularization rates (HR: 0.25; 95% CI: 0.15 to 0.41; p = 0.0001) but not in MACCE rates. CONCLUSIONS: Among SIHD patients with T2DM and no CKD, CABG + OMT significantly reduced MACCE compared with PCI + OMT. In subjects with CKD, there was a nonsignificant trend toward a better MACCE outcome with CABG and a significant reduction in subsequent revascularization.

Cellular characterization of human epicardial adipose tissue: highly expressed PAPP-A regulates insulin-like growth factor I signaling in human cardiomyocytes.

Little is known about the cellular biology of fat surrounding the human heart. In this study, we obtained paired samples of epicardial fat, the visceral fat depot attached to the heart, and subcutaneous skin fat from patients undergoing open heart surgery to test the hypothesis that human epicardial fat cells differentially express bioactive molecules that have the potential to affect cardiac function. First, we characterized the free fatty acids (FFAs), adipocytokines, and growth factors secreted by isolated adipocytes and preadipocytes in cell culture. There was little to distinguish the fat cell secretory products in terms of FFAs and adipocytokines. The most striking finding was that preadipocytes from epicardial adipose tissue expressed high levels of pregnancy-associated plasma protein-A (PAPP-A), a novel metalloproteinase that enhances local insulin-like growth factor (IGF) action through cleavage of inhibitory IGF binding protein-4 (IGFBP-4). PAPP-A levels were 15-fold higher in conditioned medium from epicardial preadipocytes than from subcutaneous preadipocytes (P < 0.0001). PAPP-A was not expressed in mature adipocytes. Next we determined whether PAPP-A could affect IGF-I signaling in a human cardiomyocyte cell line. IGF-I activated receptor-mediated auto-phosphorylation, and this was blocked by wild-type and protease-resistant IGFBP-4. Addition of PAPP-A induced cleavage of wild-type, but not protease-resistant, IGFBP-4 thereby restoring IGF-I action. A proteolytically defective PAPP-A had no effect. IGF-I receptor-mediated signaling through the phosphatidylinositol 3-kinase pathway was similarly inhibited by IGFBP-4 and restored by PAPP-A. Thus, human epicardial fat cells differentially express PAPP-A, which has the potential to affect IGF signaling in the heart.

Hypoglycemia and Elevated Troponin in Patients With Diabetes and Coronary Artery Disease.

BACKGROUND: Diabetic medications can cause hypoglycemia, which may lead to myocardial damage. OBJECTIVES: This study sought to determine whether hypoglycemia is associated with higher levels of high-sensitivity cardiac troponin T (hsTnT). METHODS: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial randomized patients with type 2 diabetes mellitus and stable coronary artery disease, and closely followed them for hypoglycemia over the first year. Hypoglycemia was classified by maximum severity and frequency. hsTnT was measured at baseline and 1 year, and analyzed using multivariable regression. RESULTS: Of 1,984 patients, follow-up hypoglycemia was absent in 1,026 (52%) patients, mild in 875 (44%), and severe in 83 (4%), and occurred less than weekly in 561 (28%) and greater than or equal to weekly in 397 (20%). hsTnT levels were associated with hypoglycemia: a median of 11.4 ng/l (interquartile range [IQR]: 8.1 to 17.3 ng/l) for none, 12.5 ng/l (IQR: 8.3 to 19.3 ng/l) for mild, and 13.7 ng/l (IQR: 9.9 to 24.9 ng/l) for severe hypoglycemia (p = 0.0001); and 12.5 ng/l (IQR: 8.3 to 18.1 ng/l) for less than weekly and 13.0 ng/l (IQR: 8.8 to 21.1 ng/l) for greater than or equal to weekly hypoglycemia (p = 0.0013). Severe hypoglycemia was associated with 34% higher 1-year hsTnT levels (p < 0.0001) in unadjusted analysis, 17% higher (p = 0.006) after adjustment for baseline factors unrelated to diabetes, and 6% higher (p = 0.23) after further adjustment for the duration and severity of diabetes. Hypoglycemia greater than or equal to weekly was associated with 14% higher hsTnT (p = 0.0003) in unadjusted analysis, 12% higher (p = 0.0002) after adjustment for baseline factors unrelated to diabetes, and 4% higher (p = 0.16) after adjustment for diabetes related factors. CONCLUSIONS: Hypoglycemia was associated with elevated hsTnT levels, but this may be due to more severe diabetes in patients who developed hypoglycemia, rather than the direct result of hypoglycemia. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI2D]; NCT00006305).

Multiarterial grafts improve the rate of early major adverse cardiac and cerebrovascular events in patients undergoing coronary revascularization: analysis of 12 615 patients with multivessel disease.

OBJECTIVES: Our goal was to compare the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) including death, stroke, myocardial infarction and repeat revascularization in patients with multivessel disease undergoing multiarterial (MultArt) coronary artery bypass grafting (CABG) with the left internal mammary artery/saphenous vein (LIMA/SV) CABG or percutaneous coronary intervention (PCI). METHODS: From 1 January 1993 to 31 December 2009, 12 615 consecutive patients underwent isolated primary CABG (n = 6667) with LIMA/SV (n = 5712) or MultArt (n = 955) or were treated by PCI (n = 5948) with balloon angioplasty (n = 1020), bare metal stent (n = 3242), and drug-eluting stent (n = 1686). We excluded patients with acute myocardial infarction. We matched the CABG group with the 3 PCI subgroups, and the PCI group with the 2 CABG subgroups. Multivariable analyses were used to evaluate the impact of CABG versus PCI and their subgroups on early MACCE. RESULTS: Unadjusted early MACCE were lower for MultArt (1.5%) than for LIMA/SV (4.5%, P < 0.001) and PCI (8.5%, P < 0.001). In matched analysis, CABG had lower early MACCE versus balloon angioplasty (4.7% vs 13.2%, P < 0.001), bare metal stent (4.3% vs 8.3%, P < 0.001), and drug-eluting stent (2.9% vs 5.5%, P = 0.008), as well as LIMA/SV versus PCI (4.6% vs 9.2%, P < 0.001) and MultArt versus PCI (1.8% vs 7.8%, P < 0.001). Stroke rate was similar in MultArt versus PCI (0.8% vs 0.3%, P = 0.18) but higher with LIMA/SV versus PCI (2.3% vs 0.4%, P < 0.001). In multivariable analysis, PCI (odds ratio 4.53, 95% confidence interval: 2.62-7.83; P < 0.001) and LIMA/SV (odds ratio 2.04, 95% confidence interval: 1.18-3.53; P < 0.011) were strong predictors of early MACCE compared with MultArt. CONCLUSIONS: MultArt confers the lowest rate of early MACCE.

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial.

BACKGROUND: The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. OBJECTIVES: This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. METHODS: Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. RESULTS: A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p < 0.001). Among patients with low SYNTAX scores (≤22), major cardiovascular events did not differ significantly between revascularization and medical therapy, either in the CABG stratum (26.1% vs. 29.9%, p = 0.41) or in the PCI stratum (17.8% vs. 19.2%, p = 0.84). Among patients with mid/high SYNTAX scores, however, major cardiovascular events were lower after revascularization than with medical therapy in the CABG stratum (15.3% vs. 30.3%, p = 0.02), but not in the PCI stratum (35.6% vs. 26.5%, p = 0.12). CONCLUSIONS: Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).

Prognostic Value of Adipokines in Predicting Cardiovascular Outcome: Explaining the Obesity Paradox.

OBJECTIVE: To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. PATIENTS AND METHODS: The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008). RESULTS: In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005). CONCLUSION: Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox." TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

Multiple arterial grafts improve survival with coronary artery bypass graft surgery versus conventional coronary artery bypass grafting compared with percutaneous coronary interventions.

OBJECTIVE: To compare long-term survival with multiple arterial coronary artery bypass grafting (CABG) (MultArt) versus percutaneous coronary intervention (PCI) in patients with multivessel disease (MVD). METHODS: We reviewed 12,615 patients with MVD with isolated primary CABG or PCI from 1993 to 2009. Patients with CABG (n = 6667) were grouped according to the number of arterial grafts into left internal thoracic artery (LITA)/saphenous vein (SV) (n = 5712) or MultArt (n = 955); patients with PCI (n = 5948) were grouped into balloon angioplasty (BA) (n = 1020), drug-eluting stent (DES) (n = 1686), and bare metal stent (BMS) (n = 3242). RESULTS: Unadjusted long-term survival was lower for CABG than PCI (15-year survival, 34% vs 46%; P < .001); however, in patients with MultArt, survival was greater than LITA/SV, BA, BMS (15-year survival, 65% vs 31%, 47%, 45%, respectively; P < .001), and DES (8-year survival, 87% vs 70%; P < .001). In matched analyses, 15-year survival of MultArt was higher than BA (66% vs 57%; P = .002), LITA/SV (64% vs 56%; P = .02), and BMS (5-year survival 94% vs 90%; P = .01), and similar to DES at 8 years. In multivariate analysis, compared with MultArt, LITA/SV had worse survival (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.52; P = .003). BMS (HR, 0.87; 95% CI, 0.80-0.94; P < .001) and DES (HR, 0.76; 95% CI, 0.66-0.88; P < .001) had improved survival versus LITA/SV but not versus MultArt (HR, 1.12; 95% CI, 0.94-1.34; P = .21, and HR, 0.98; 95% CI, 0.79-1.21; P = .83, respectively). Secondary analyses for treatment crossover indicated lower survival for LITA/SV versus MultArt and PCI. CONCLUSIONS: In patients with MVD undergoing primary revascularization, MultArt increased survival benefit versus LITA/SV compared with PCI. Use of MultArt must increase.