Faculty Bibliography

Background: Coronary artery disease (CAD) and left ventricular hypertrophy (LVH) are prevalent in the chronic kidney disease (CKD) and renal transplant population. We hypothesised that the myocardial oxygenation response to stress would be impaired in CKD Methods: Fifty-three subjects: twenty-three subjects with CKD, ten renal transplant (RT) recipients, ten hypertensive (HT) controls, and ten normal controls without known heart disease underwent CMR scanning at 3T. The RT and HT groups also had late gadolinium CMR to assess infarction/ replacement fibrosis. The CKD group underwent 2D echocardiography strain to assess fibrosis. Results: A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT, 480 segments in HT, and 666 segments in normal controls) were compared using linear mixed modelling. Diabetes mellitus (p= 0.47) and hypertension (p= 0.57) were similar between CKD, RT, and HT groups. The mean BOLD SI change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (-0.89 +/- 10.63 in CKD versus 5.66 +/- 7.87 in RT versus 15.54 +/- 9.58 in HT controls, p< 0.0001). BOLD SI Change was associated with eGFR (beta= 0.16, 95% CI= 0.10 to 0.22, p<0.0001). Left ventricular mass index and left ventricular septal wall diameter was similar between the CKD pre-dialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain (GLS) and none of the RT group had late gadolinium hyperenhancement. Conclusion: Myocardial oxygenation response to stress is impaired in CKD and RT patients, and unlikely to be solely accounted for by the presence of diabetes mellitus

BACKGROUND: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. METHODS: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. RESULTS: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). CONCLUSIONS: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).

BACKGROUND: Transradial access for cardiac catheterisation results in lower bleeding and vascular complications than the traditional transfemoral access route. However, the increased radiation exposure potentially associated with transradial access is a possible drawback of this method. Whether transradial access is associated with a clinically significant increase in radiation exposure that outweighs its benefits is unclear. Our aim was therefore to compare radiation exposure between transradial access and transfemoral access for diagnostic coronary angiograms and percutaneous coronary interventions (PCI). METHODS: We did a systematic review and meta-analysis of the scientific literature by searching the PubMed, Embase, and Cochrane Library databases with relevant terms, and cross-referencing relevant articles for randomised controlled trials (RCTs) that compared radiation parameters in relation to access site, published from Jan 1, 1989, to June 3, 2014. Three investigators independently sorted the potentially relevant studies, and two others extracted data. We focused on the primary radiation outcomes of fluoroscopy time and kerma-area product, and used meta-regression to assess the changes over time. Secondary outcomes were operator radiation exposure and procedural time. We used both fixed-effects and random-effects models with inverse variance weighting for the main analyses, and we did confirmatory analyses for observational studies. FINDINGS: Of 1252 records identified, we obtained data from 24 published RCTs for 19 328 patients. Our primary analyses showed that transradial access was associated with a small but significant increase in fluoroscopy time for diagnostic coronary angiograms (weighted mean difference [WMD], fixed effect: 1.04 min, 95% CI 0.84-1.24; p<0.0001) and PCI (1.15 min, 95% CI 0.96-1.33; p<0.0001), compared with transfemoral access. Transradial access was also associated with higher kerma-area product for diagnostic coronary angiograms (WMD, fixed effect: 1.72 Gy.cm2, 95% CI -0.10 to 3.55; p=0.06), and significantly higher kerma-area product for PCI (0.55 Gy.cm2, 95% CI 0.08-1.02; p=0.02). Mean operator radiation doses for PCI with basic protection were 107 muSv (SD 110) with transradial access and 74 muSv (68) with transfemoral access; with supplementary protection, the doses decreased to 21 muSv (17) with transradial access and 46 muSv (9) with transfemoral. Meta-regression analysis showed that the overall difference in fluoroscopy time between the two procedures has decreased significantly by 75% over the past 20 years from 2 min in 1996 to about 30 s in 2014 (p<0.0001). In observational studies, differences and effect sizes remained consistent with RCTs. INTERPRETATION: Transradial access was associated with a small but significant increase in radiation exposure in both diagnostic and interventional procedures compared with transfemoral access. Since differences in radiation exposure narrow over time, the clinical significance of this small increase is uncertain and is unlikely to outweigh the clinical benefits of transradial access. FUNDING: None.

BACKGROUND: Randomized trials of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) routinely exclude patients with chronic kidney disease (CKD). OBJECTIVES: This study evaluated outcomes of PCI versus CABG in patients with CKD. METHODS: Patients with CKD who underwent PCI using everolimus-eluting stents were propensity-score matched to patients who underwent isolated CABG for multivessel coronary disease in New York. The primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction (MI), stroke, and repeat revascularization. RESULTS: Of 11,305 patients with CKD, 5,920 patients were propensity-score matched. In the short term, PCI was associated with a lower risk of death (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.35 to 0.87), stroke (HR: 0.22; 95% CI: 0.12 to 0.42), and repeat revascularization (HR: 0.48; 95% CI: 0.23 to 0.98) compared with CABG. In the longer term, PCI was associated with a similar risk of death (HR: 1.07; 95% CI: 0.92 to 1.24), higher risk of MI (HR: 1.76; 95% CI: 1.40 to 2.23), a lower risk of stroke (HR: 0.56; 95% CI: 0.41 to 0.76), and a higher risk of repeat revascularization (HR: 2.42; 95% CI: 2.05 to 2.85). In the subgroup with complete revascularization with PCI, the increased risk of MI was no longer statistically significant (HR: 1.18; 95% CI: 0.67 to 2.09). In the 243 matched pairs of patients with end-stage renal disease on hemodialysis, PCI was associated with significantly higher risk of death (HR: 2.02; 95% CI: 1.40 to 2.93) and repeat revascularization (HR: 2.44; 95% CI: 1.50 to 3.96) compared with CABG. CONCLUSIONS: In patients with CKD, CABG is associated with higher short-term risk of death, stroke, and repeat revascularization, whereas PCI with everolimus-eluting stents is associated with a higher long-term risk of repeat revascularization and perhaps MI, with no long-term mortality difference. In the subgroup on dialysis, the results favored CABG over PCI.

BACKGROUND: Clinical trial evidence suggests poorer outcomes in blacks compared with whites when treated with an angiotensin-converting enzyme (ACE) inhibitor-based regimen, but this has not been evaluated in clinical practice. OBJECTIVES: This study evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared with whites. METHODS: We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. RESULTS: Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05), and congestive heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. CONCLUSIONS: ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen.

Treatment-resistant hypertension (TRH) affects between 3 and 30% of hypertensive patients, and its presence is associated with increased cardiovascular morbidity and mortality. Until recently, the interest on these patients has been limited, because providing care for them is difficult and often frustrating. However, the arrival of new treatment options [i.e. catheter-based renal denervation (RDN) and baroreceptor stimulation] has revitalized the interest in this topic. The very promising results of the initial uncontrolled studies on the blood pressure (BP)-lowering effect of RDN in TRH seemed to suggest that this intervention might represent an easy solution for a complex problem. However, subsequently, data from controlled studies have tempered the enthusiasm of the medical community (and the industry). Conversely, these new studies emphasized some seminal aspects on this topic: (i) the key role of 24 h ambulatory BP and arterial stiffness measurement to identify 'true' resistant patients; (ii) the high prevalence of secondary hypertension among this population; and (iii) the difficulty to identify those patients who may profit from device-based interventions. Accordingly, for those patients with documented TRH, the guidelines suggest to refer them to a hypertension specialist/centre in order to perform adequate work-up and treatment strategies. The aim of this review is to provide guidance for the cardiologist on how to identify patients with TRH and elucidate the prevailing underlying pathophysiological mechanism(s), to define a strategy for the identification of patients with TRH who may benefit from device-based interventions and discuss results and limitations of these interventions, and finally to briefly summarize the different drug-based treatment strategies.